Podcasts about sh sy5y

In this enlightening episode we welcome back the highly esteemed Rebecca Edwards, Director of Education at Activated Probiotics, to dive into the emerging and critical topic of the oral microbiome. The conversation covers the fundamental aspects of the oral microbiome, its significant links to brain health, Alzheimer's disease, cardiovascular issues, pregnancy outcomes, immune health, and even COVID-19 predispositions. Rebecca reveals the frightening realities of oral bacteria, including the pathways through which oral health can influence systemic conditions like Alzheimer's and rheumatoid arthritis. The podcast also emphasises practical actions for maintaining oral hygiene, the role of diet and hydration, and the groundbreaking potential of oral probiotics. Additionally, the episode provides a sneak peek into the upcoming Activated Probiotics Symposium, featuring a stellar lineup of speakers and groundbreaking topics aimed at shifting paradigms in healthcare.EPISODE HIGHLIGHTS:03:19 The importance of oral hygiene03:51 Understanding the oral microbiome06:45 The oral microbiome and public health09:05 The rise of microbiome interest post-COVID16:25 The oral microbiome's impact on brain health24:43 The role of dental plaque and gum disease29:49 Oral health and systemic diseases35:34 Call to action for practitioners38:19 The impact of COVID on healthcare39:28 Oral health and genetic predispositions41:29 The importance of dental care accessibility42:48 Rethinking mouthwash and bacteria45:26 Diet and oral microbiome48:02 Cardiovascular health and oral hygiene53:19 Probiotics for oral health59:13 Practical tips for oral hygiene01:03:04 Upcoming probiotic symposiumTickets to Activated Probiotics Symposium here:https://events.humanitix.com/activated-probiotics-symposium-2025Activated Probiotics instagram:https://www.instagram.com/activatedprobiotics/References to the oral microbiome:Kanagasingam S, von Ruhland C, Welbury R, Singhrao S K. Antimicrobial, polarizing light, and paired helical filament properties of fragmented tau peptides of selected putative gingipains. J Alzheimers Dis 2022; doi: 10.3233/JAD-220486.Kanagasingam S, von Ruhland C, Welbury R, Chukkapalli S S, Singhrao S K. Porphyromonas gingivalis conditioned medium induces amyloidogenic processing of the amyloid-β Protein precursor upon in vitro infection of SH-SY5Y cells. J Alzheimers Dis Rep 2022; doi: 10.3233/ADR-220029.Haditsch U, Roth T, Rodriguez L, Hancock S, Cecere T, Nguyen M, Arastu-Kapur S, Broce S, Raha D, Lynch CC, Holsinger LJ, Dominy SS, Ermini F. Alzheimer's Disease-Like Neurodegeneration in Porphyromonas gingivalis Infected Neurons with Persistent Expression of Active Gingipains. J Alzheimers Dis. 2020;75(4):1361-1376. doi: 10.3233/JAD-200393. PMID: 32390638; PMCID: PMC7369049.Stephen S. Dominy et al. ,Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.Sci. Adv.5,eaau3333(2019).DOI:10.1126/sciadv.aau3333The Oral-Gut-Brain AXIS: The Influence of Microbes in Alzheimer's DiseaseNarengaowa1, Wei Kong1, Fei Lan1, Umer Farooq Awan2, Hong Qing1* and Junjun Ni1*References to all 11 studies on Biome BreatheRanjith, A., Nazimudeen, N. Bin, & Baiju, K. V. (2022). Probiotic mouthwash as an adjunct to mechanical therapy in the treatment of stage II periodontitis: A randomized controlled clinical trial. International Journal of Dental Hygiene, 20(2), 415–421. https://doi.org/10.1111/idh.12589Doppalapudi, R., Vundavalli, S., & Prabhat, M. (2020). Effect of probiotic bacteria on oral Candida in head‑ and neck‑radiotherapy patients: A randomized clinical trial. Journal of Cancer Research and Therapeutics, 6(3), 470–477. https://doi.org/10.4103/jcrt.JCRTThakkar, P. K., Imranulla, M., Kumar, P. G. N., Prashant, G. M., Sakeenabi, B., & Sushanth, V. H. (2013). Effect of probiotic mouthrinse on dental plaque accumulation: A randomized controlled trial. Dentistry and Medical Research|, 1(1), 7–12.Purunaik, S., Thippeswamy, H. M., & Chavan, S. S. (2014). To Evaluate the Effect of Probiotic Mouthrinse on Plaque and Gingivitis among 15-16 Year Old School Children of Mysore City, India- Randomized Controlled Trial. Global Journal of Medical Research, 14(4), 9–14.Jothika, M., Vanajassun, Pp., & Someshwar, B. (2015). Effectiveness of probiotic, chlorhexidine and fluoride mouthwash against Streptococcus mutans - randomised, single-blind, in-vivo study. Journal of International Society of Preventive and Community Dentistry, 5(7), 44. https://doi.org/10.4103/2231-0762.156153Jindal, G., Pandey, R. K., Agarwal, J., & Singh, M. (2011). A comparative evaluation of probiotics on salivary mutans streptococci counts in Indian children. European Archives of Paediatric Dentistry, 12(4), 211–215. https://doi.org/10.1007/BF03262809Manikandan, S., Behera, S., Karthikeyan, R., Niranjana, A., Bharathan, R., & Mohammed, O. B. (2020). Effect of green tea extract mouthrinse and probiotic mouthrinse on salivary pH in a group of schoolchildren: An in vivo study. Journal of Pharmacy And Bioallied Sciences, 12(5), 404. https://doi.org/10.4103/jpbs.JPBS_119_20Jindal, V., Mahajan, N., Goel, A., Kaur, R., Mahajan, A., & Malhotra, P. (2017). Clinical efficacy of probiotic mouthwash in the treatment of gingivitis patients in Himachal population. Journal of the International Clinical Dental Research Organization, 9(1), 41. https://doi.org/10.4103/2231-0754.207386Deshmukh, M. A., Dodamani, A. S., Karibasappa, G., Khairnar, M. R., Naik, R. G., & Jadhav, H. C. (2017). Comparative evaluation of the efficacy of probiotic, herbal and chlorhexidine mouthwash on gingival health: A randomized clinical trial. Journal of Clinical and Diagnostic Research, 11(3), ZC13–ZC16. https://doi.org/10.7860/JCDR/2017/23891.9462Sharma, P., Datta, G., Gandhi, K., & Kumar, D. (2019). A comparative evaluation of efficacy of probiotic and chlorhexidine mouthrinses on gingival health and plaque accumulation in 6-9 year old children. International Journal of Applied Dental Sciences, 5(1), 156–162. http://www.oraljournal.com/archives/2019/5/1/C/5-1-43Doppalapudi, R., Vundavalli, S., & Prabhat, M. P. V. (2020). Effect of probiotic bacteria on oral Candida in head‑ and neck‑radiotherapy patients: A randomized clinical trial. Journal of Cancer Research and Therapeutics, 16, 470–477. https://doi.org/10.4103/jcrt.JCRT

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.24.538048v1?rss=1 Authors: Babylon, L., Meissner, J., Eckert, G. P. Abstract: Alzheimer's disease (AD) is characterized by mitochondrial dysfunction, increased A{beta} levels and altered glycolysis. So far, there is no cure for AD, therefore it is important to take preventive or supportive action against AD. The cocktail (SC) tested in this study consists of the substances hesperetin (HstP), magnesium-orotate (MgOr) and folic acid (Fol), as well as the combination (KCC) of caffeine (Cof), kahweol (KW) and cafestol (CF). All the compounds showed positive results in the above mentioned fields of AD. The question arose whether a combination of all of them would also positively affect all three fields of AD. In this regard, SH-SY5Y-APP695 cells were incubated with SC and ATP levels, complex respiration, A{beta} levels, ROS levels, lactate and pyruvate levels were examined. The SC increased the endogenous respiration of the cells while significantly decreasing the A{beta}1-40 levels. SC has no significant effects on the other parameters. In summary, the combination of all compounds did not show the desired success that we hoped for, but the cocktail has potential to be further investigated. It is possible that the results will improve by changing the combinations or by adjusting the concentrations. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.13.536725v1?rss=1 Authors: Tarutani, A., Lövestam, S., Zhang, X., Kotecha, A., Robinson, A. C., Mann, D. M. A., Saito, Y., Murayama, S., Tomita, T., Goedert, M., Scheres, S., Hasegawa, M. Abstract: The formation of amyloid filaments through templated seeding is believed to underlie the propagation of pathology in most human neurodegenerative diseases. A widely used model system to study this process is to seed amyloid filament formation in cultured cells using human brain extracts. Here, we report the electron cryo-microscopy (cryo-EM) structures of tau filaments from undifferentiated seeded SH-SY5Y cells, that transiently expressed N-terminally HA-tagged 1N3R or 1N4R human tau, using brain extracts from individuals with AD or CBD. Although the resulting filament structures differed from those of the brain seeds, some degree of structural templating was observed. Studying templated seeding in cultured cells, and determining the structures of the resulting filaments, can thus provide insights into the cellular aspects underlying neurodegenerative diseases. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.07.536081v1?rss=1 Authors: Graur, A., Kabbani, N. Abstract: Acetylcholinesterase (AChE) is a highly conserved enzyme responsible for the regulation of acetylcholine signaling within the brain and periphery. AChE has also been shown to participate in non-enzymatic activity and contributing to development and aging. In particular, enzymatic cleavage of the carboxy terminal region of the synaptic AChE isoform, AChE-T, is shown to generate a bioactive T30 peptide that binds to the 7 nicotinic acetylcholine receptor (nAChR) at synapses. Here, we explore intracellular mechanisms of T30 signaling within the human cholinergic neural cell line SH-SY5Y using high performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). Proteomic analysis of cells exposed to (100nM) T30 for 3-days reveals significant changes within proteins important for cell growth. Specifically, bioinformatic analysis identifies proteins that converge onto the mammalian target of rapamycin (mTOR) pathway signaling. Functional experiments confirm that T30 regulates neural cell growth via mTOR signaling and 7 nAChR activation. In addition, T30 was found promote mTORC1 pro-growth signaling through an increase in phosphorylated elF4E, and a decrease in autophagy LC3B-II level. Taken together, our findings define mTOR as a novel pathway activated by the T30 cleavage peptide of AChE and suggest a role for mTOR signaling in cholinergic aspects of brain development, as well as disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.22.529417v1?rss=1 Authors: Hino, C., Chan, G., Jordaan, G., Chang, S. S., Saunders, J., Bashir, M. T., Hansen, J. E., Gera, J., Weisbart, R. H., Nishimura, R. N. Abstract: Heat shock proteins (HSPs), especially Hsp70 (HSPA1), have been associated with cellular protection from various cellular stresses including heat, hypoxia-ischemia, neurodegeneration, toxins, and trauma. Endogenous HSPs are often synthesized in direct response to these stresses but in many situations are inadequate in protecting cells. The present study addresses the transduction of Hsp70 into cells providing protection from acute oxidative stress by H2O2. The recombinant Fv-Hsp70 protein and two mutant Fv-Hsp70 proteins minus the ATPase domain, and minus the ATPase and terminal lid domains were tested at 0.5 and 1.0 uM concentrations after two different concentrations of H2O2 treatment. All three recombinant proteins protected SH-SY5Y cells from acute H2O2 toxicity. This data indicated that the protein binding domain was responsible for cellular protection. In addition, experiments pretreating cells with inhibitors of antioxidant proteins catalase and gamma-glutamylcysteine synthase (GGCS) before H2O2 resulted in cell death despite treatment with Fv-Hsp70, implying that both enzymes were protected from acute oxidative stress after treatment with Fv-Hsp70. This study demonstrates that Fv-Hsp70 is protective in our experiments primarily by the protein-binding domain. The Hsp70 terminal lid domain was also not necessary for protection. Cellular protection was protective via the antioxidant proteins catalase and GGCS. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.12.523781v1?rss=1 Authors: Wang, L., Tang, Z., Deng, Y., Peng, Y., Xiao, Y., Xu, J., Ni, R., Qi, X. Abstract: Alzheimers disease is characterized by abnormal {beta}-amyloid (A{beta}) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to have neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in myricetin protective effect on the toxicity induced by the A{beta}42 oligomer. Neuronal SH-SY5Y cells were pretreated with myricetin before incubation with A{beta}42 oligomer. The levels of pre- and post-synaptic proteins, mitochondrial division and fusion proteins, glycogen synthase kinase-3{beta} (GSK-{beta}) and extracellular regulated kinase (ERK) 1/2 were assessed by Western blotting. Flow cytometry assays for mitochondrial membrane potential (JC1) and reactive oxidative stress, as well immunofluorescence staining for lipid peroxidation (4-HNE) and DNA oxidation (8-OHdG), were performed. We found that myricetin prevented A{beta}42 oligomer-induced tau phosphorylation and the reduction in pre/postsynaptic proteins. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation induced by the A{beta}42 oligomer. Moreover, myricetin prevented the A{beta}42 oligomer-induced reduction in mitochondrial fusion proteins (mitofusin-1, mitofusin-2), fission protein (dynamin-related protein 1) phosphorylation, and mitochondrial membrane potential via the associated GSK-3{beta} and ERK 1/2 signaling pathways. In conclusion, this study provides new insight into the neuroprotective mechanism of myricetin against A{beta}42 oligomer-induced toxicity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.07.523095v1?rss=1 Authors: Tripathi, M. K., Ojha, S. K., Kartawy, M., Hamoudi, W., Aran, A., Amal, H. Abstract: Autism spectrum disorders (ASDs) include a range of developmental disorders that share a core of neurobehavioral deficits manifested by abnormalities in social interactions, deficits in communication, restricted interests, and repetitive behaviors. Several reports showed that mutations in different high-risk ASD genes, including SHANK3 and CNTNAP2, lead to ASD. However, to date, the underlying molecular mechanisms have not been deciphered, and no effective pharmacological treatment has been established for ASD. Recently, we reported a dramatic increase of nitric oxide (NO) in ASD mouse models. NO is a multifunctional neurotransmitter that plays a key role in different neurological disorders. However, its role in ASD has not yet been investigated. To reveal the novel molecular, cellular, and behavioral role of NO in ASD, we conducted multidisciplinary experiments using cellular and mouse models as well as clinical samples. First, we treated WT mice with an NO donor, which led to an autism-like phenotype. Next, we measured and found high levels of nitrosative stress biomarkers in both the Shank3 and Cntnap2 ASD mouse models. Treating both mouse models with a selective neuronal NO synthase (nNOS) inhibitor led to a reversal in the molecular, synaptic, and behavioral ASD phenotypes. Using a primary neuronal cell culture, we confirmed that NO is specifically involved in neurons in ASD pathology. Next, using genetic manipulations in the human SH-SY5Y cell line, we found that nNOS plays a key role in the pathology. Finally, we examined human plasma samples from 19 low-functioning ASD patients, compared to 20 typically developed volunteers, and found a significant elevation in the NO levels in the ASD patients. Furthermore, using the SNOTRAP technology, which is an innovative mass spectrometric method to identify the SNO-proteome (SNO: NO-mediated post-translational modification), we revealed that the complement systems in the synaptic and neuronal development processes are enriched in the ASD group. This work indicates, for the first time, that NO plays a pathological role in ASD development. Our findings will open future and novel directions to examine NO in diverse mutations on the autism spectrum as well as other neurodevelopmental disorders and psychiatric diseases. Most importantly, it suggests a novel treatment strategy for ASD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.28.522104v1?rss=1 Authors: Sanz, F. J., Solana-Manrique, C., Paricio, N. Abstract: Parkinsons disease (PD) is an incurable neurodegenerative disorder caused by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Current therapies are only symptomatic, and are not able to stop or delay its progression. In order to search new and more effective therapies, our group carried out a high-throughput screening assay, identifying several candidate compounds able to suppress motor defects in DJ-1{beta} mutant flies (a Drosophila model of familial PD) and to reduce oxidative stress (OS)-induced lethality in DJ-1-deficient SH-SY5Y human cells. One of them was vincamine (VIN), a natural alkaloid obtained from the leaves of Vinca minor. Our results showed that VIN is able to suppress PD-related phenotypes in both Drosophila and human cell PD models. Specifically, VIN reduced OS levels in PD model flies. Besides, VIN diminished OS-induced lethality by decreasing apoptosis, increased mitochondrial viability and reduced OS levels in DJ-1-deficient human cells. In addition, we have demonstrated that VIN is able to exert its beneficial role, at least partially, by the inhibition of voltage-gated Na+ channels. Therefore, we propose that these channels might be a promising target in the search for new compounds to treat PD, and that VIN constitutes a potential therapeutic treatment for the disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Ya-Jen Chiu from the Department of Life Science at National Taiwan Normal University in Taipei, discusses a research paper she co-authored that was published by Aging (Aging-US) in Volume 14, Issue 18, entitled, “Novel TRKB agonists activate TRKB and downstream ERK and AKT signaling to protect Aβ-GFP SH-SY5Y cells against Aβ toxicity.” DOI - https://doi.org/10.18632/aging.204306 Corresponding authors - Chiung-Mei Chen - cmchen@cgmh.org.tw, Ying-Chieh Sun - sun@ntnu.edu.tw, Guey-Jen Lee-Chen - t43019@ntnu.edu.tw Video - https://www.youtube.com/watch?v=1rT96K9VeZw Transcript - https://aging-us.net/2022/11/01/behind-the-study-novel-trkb-agonists-activate-trkb-and-downstream-erk-and-akt-signaling/ Abstract Decreased BDNF and impaired TRKB signaling contribute to neurodegeneration in Alzheimer's disease (AD). We have shown previously that coumarin derivative LM-031 enhanced CREB/BDNF/BCL2 pathway. In this study we explored if LM-031 analogs LMDS-1 to -4 may act as TRKB agonists to protect SH-SY5Y cells against Aβ toxicity. By docking computation for binding with TRKB using 7,8-DHF as a control, all four LMDS compounds displayed potential of binding to domain d5 of TRKB. In addition, all four LMDS compounds exhibited anti-aggregation and neuroprotective efficacy on SH-SY5Y cells with induced Aβ-GFP expression. Knock-down of TRKB significantly attenuated TRKB downstream signaling and the neurite outgrowth-promoting effects of these LMDS compounds. Among them, LMDS-1 and -2 were further examined for TRKB signaling. Treatment of ERK inhibitor U0126 or PI3K inhibitor wortmannin decreased p-CREB, BDNF and BCL2 in Aβ-GFP cells, implicating the neuroprotective effects are via activating TRKB downstream ERK, PI3K-AKT and CREB signaling. LMDS-1 and -2 are blood-brain barrier permeable as shown by parallel artificial membrane permeability assay. Our results demonstrate how LMDS-1 and -2 are likely to work as TRKB agonists to exert neuroprotection in Aβ cells, which may shed light on the potential application in therapeutics of AD. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204306 Keywords - aging, Alzheimer's disease, TRKB agonists, Aβ, neuroprotection, therapeutics About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514622v1?rss=1 Authors: Tombesi, G., Chen, C., Favetta, G., Plotegher, N., Sevegnani, M., Marte, A., Battisti, I., Civiero, L., Onofri, F., Piccoli, G., Arrigoni, G., Manzoni, C., Parisiadou, L., Greggio, E. Abstract: Dendritic spines, small protrusions of the dendrites, constitute the postsynaptic compartment of excitatory synapses. Filamentous actin is the major cytoskeletal constituent of dendritic spines, whose dynamic nature allows them to plastically remodel their shape and volume in response to stimuli. Notably, dendritic spine abnormalities are linked to a number of neurological and neurodegenerative disorders. Here, we show that the Parkinson disease (PD)-associated kinase LRRK2 participates in spine remodeling processing by binding a panel of actin-related proteins enriched in postsynaptic compartments. Phosphorylation of LRRK2 Ser935, which controls LRRK2 subcellular localization, rapidly increases upon brain-derived neurotrophic factor (BDNF) stimulation of differentiated SH-SY5Y cells and primary mouse neurons. Affinity-purification coupled with mass spectrometry (AP-MS/MS) analysis revealed that LRRK2 interactome is significantly reshaped upon BDNF stimulation, with an interconnected network of actin cytoskeleton-associated proteins increasing their binding to LRRK2. Accordingly, Lrrk2 knockout primary neurons exhibit impaired response to BDNF-induced spinogenesis and TrkB signaling. In vivo, one-month old Lrrk2 knockout mice exhibit defects in spine maturation, a phenotype that disappears with age. Finally, by comparing the phosphoproteomes of Lrrk2 wild-type versus Lrrk2 G2019S PD mutant synaptosomes, we found that the differentially phosphorylated proteins are enriched in categories related to postsynaptic structural organization. Taken together, our study discloses a critical function of LRRK2 in shaping dendritic spine morphology during development and defines a mechanistic role of the kinase in postsynaptic actin-cytoskeletal dynamics. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.20.512990v1?rss=1 Authors: Kang, S., Choi, L. S., Im, S., Lee, K. W., Kim, D. H., Park, J. H., Park, M.-H., Lee, J., Park, S. K., Kim, K. P., Lee, H. M., Jeon, H. J., Park, H. S., Yoo, S.-K., Kim Pak, Y. Abstract: Parkinsons disease (PD), characterized by degeneration of dopaminergic neurons, share pathogenic features with obesity, including mitochondrial dysfunction and oxidative stress. Paraoxonase 2 (PON2) is an inner mitochondrial membrane protein that is highly expressed in dopaminergic neurons and is involved in the regulation of mitochondrial oxidative stress. However, no drug targeting PON2 has ever been developed for the treatment of PD. Here, we show that vutiglabridin, a clinical phase 2-stage drug for the treatment of obesity, has therapeutic effects in PD models, targeting mitochondrial PON2. Vutiglabridin penetrates into the brain, binds to PON2, and restores 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction in SH-SY5Y neuroblastoma cells. Knockdown of PON2 by lentiviral shRNA infection abolished the effects of vutiglabridin on mitochondria. In mice, vutiglabridin significantly alleviated motor impairments and damage to dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and these effects were also abolished in PON2-knockdown mice, suggesting that vutiglabridin is neuroprotective via PON2. Extensive in vitro and in vivo assessment of potential neurotoxicity showed vutiglabridin to be safe. Overall, these findings provide support for the clinical development of vutiglabridin as a novel PON2 modulator for the treatment of PD. One Sentence SummaryTargeting paraoxonase-2 by a clinical-stage compound vutiglabridin provides neuroprotective effects in preclinical models of Parkinsons disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.13.512083v1?rss=1 Authors: Lanteri, M. L., Silveyra, M. X., Moran, M. M., Boutet, S., Solis-Gozar, D.-D., Perreau, F., Andreu, A. B. Abstract: Andean potatoes (Solanum tuberosum L. ssp. andigena) are a good source of dietary antioxidant polyphenols. We have previously demonstrated that polyphenol extracts from Andean potato tubers exerted a dose-dependent cytotoxic effect in human neuroblastoma SH-SY5Y cells, being skin extracts more potent than flesh ones. In order to gain insight into the bioactivities of potato phenolics, we investigated the composition and the in vitro cytotoxic activity of total extracts and fractions of skin and flesh tubers of three Andean potato cultivars (Santa Maria, Waicha, and Moradita). Potato total extracts were subjected to liquid-liquid fractionation using ethyl acetate solvent in organic and aqueous fractions. We analyzed both fractions by HPLC-DAD, HPLC-ESI-MS/MS, and HPLC-HRMS. Results corroborated the expected composition of each fraction. Organic fractions were rich in hydroxycinnamic acids (principally chlorogenic acid isomers), whereas aqueous fractions contained mainly polyamines conjugated with phenolic acids, glycoalkaloids, and flavonoids. Organic fractions were not cytotoxic against SH-SY5Y cells, and indeed, some increased cellular metabolism compared to controls. Aqueous fractions were cytotoxic and even more potent than their respective total extracts. Treatment with a combination of both fractions showed a similar cytotoxic response to the corresponding extract. According to correlation studies, it is tempting to speculate that polyamines and glycoalkaloids are crucial in inducing cell death. Our findings indicate that the activity of Andean potato extracts is a combination of various compounds and contribute to the revalorization of potato as a functional food. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.06.511163v1?rss=1 Authors: Alves, A. C. d. B., Speck, A. E., Farias, H. R., dos Santos, N. S., Pannata, G. d. S., Tavares, A. P., Martins, L. M., de Oliveira, J., Tome, A. R., Cunha, R., Aguiar, A. S. Abstract: Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we presented the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We demonstrate here that the striatum rules the ergogenic effects of caffeine through neuroplasticity changes. Thirty-four Swiss (8-10 weeks, 47 {+/-} 1.5 g) and twenty-four C57BL6 (8-10 weeks, 23.9 {+/-} 0.4 g) adult male mice were challenged in behavior and electrophysiology experiments using caffeine and SH-SY5Y cells for energetic metabolism. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 g) caffeine was psychostimulant in the open field (p less than 0.05) and increased gripping muscle power (p less than 0.05). Caffeine also induced long-term potentiation (LTP) in striatal slices (p less than 0.05) and increased mitochondrial mass (p less than 0.05) and membrane potential p less than 0.05) in SH-SY5Y dopaminergic cells. In summary, our results demonstrate that caffeine stimulation in the striatum produces ergogenic effects accompanied by an LTP, possibly associated with acute increased mitochondrial metabolism observed in dopaminergic cell lines. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.24.505074v1?rss=1 Authors: Nagel, M., Noss, M., Xu, J., Horn, N., Ueffing, M., Boldt, K., Schuele, R. Abstract: Neurons critically depend on regulated RNA localization and tight control of spatio-temporal gene expression to maintain their morphological and functional integrity. Mutations in the kinesin motor protein gene KIF1C cause Hereditary Spastic Paraplegia, an autosomal recessive disease leading to predominant degeneration of the long axons of central motoneurons. In this study we aimed to gain insight into the molecular function of KIF1C and understand how KIF1C dysfunction contributes to motoneuron degeneration. We used affinity proteomics in neuronally differentiated neuroblastoma cells (SH-SY5Y) to identify the protein complex associated with KIF1C in neuronal cells; candidate interactions were then validated by immunoprecipitation and mislocalization of putative KIF1C cargoes was studied by immunostainings. We found KIF1C to interact with all core components of the exon junction complex (EJC); expression of mutant KIF1C in neuronal cells leads to loss of the typical localization distally in neurites. Instead, EJC core components accumulate in the pericentrosomal region, here co-localizing with mutant KIF1C. These findings suggest KIF1C as a neuronal transporter of the EJC. Interestingly, the binding of KIF1C to the EJC is RNA-mediated, as treatment with RNAse prior to immunoprecipitation almost completely abolishes the interaction. Silica-based solid-phase extraction of UV-crosslinked RNA-protein complexes furthermore supports direct interaction of KIF1C with RNA, as recently also demonstrated for kinesin heavy chain. Taken together, our findings are consistent with a model where KIF1C transports mRNA in an EJC-bound and therefore transcriptionally silenced state along neurites, thus providing the missing link between the EJC and mRNA localization in neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Videos :  2. Fake Cases: The Fraudulent PCR Test Is at the Heart of This Entire Plandemic – Dr. Reiner Fuellmich With Judy Mikovits & More   3.  Over 17,000 Physicians and Scientists Agree: “There Is No Medical Emergency” – Dr. Robert Malone   4. Honest Government Ad | Julian Assange   Cranberry juice may slash cardiometabolic risk factors: RCT study USDA Agriculture Research Center, April 30, 2022 Daily consumption of a low-calorie cranberry juice may improve certain risk factors of heart disease, including blood pressure and triglycerides, says a new study from the Agricultural Research Service at the USDA. Eight weeks of supplementing the diet with a cranberry juice containing 173 mg of phenolic compounds per serving was associated with significant reductions in C-reactive protein (CRP), diastolic blood pressure, and blood sugar levels, according to findings published in the Journal of Nutrition . While the majority of the science supporting the health benefits of cranberries is for urinary tract health, a growing body of data supports the cardiovascular potential of the berries. For example, a study by scientists at the Mayo Clinic and College of Medicine found that two glasses of cranberry juice a day may protect against the development of hardening of the arteries. Writing in the European Journal of Nutrition (Vol. 52, pp 289-296), the Mayo Clinic researchers reported that no effect was observed on the function of the cells lining the arteries (endothelial cells), but cranberry juice may reduce the number of endothelial cells that produce a compound called osteocalcin, which has been linked to hardening of the arteries.     Vitamin D toxicity rare in people who take supplements, researchers report Mayo Clinic, April 30, 2022   Over the last decade, numerous studies have shown that many Americans have low vitamin D levels and as a result, vitamin D supplement use has climbed in recent years. In light of the increased use of vitamin D supplements, Mayo Clinic researchers set out to learn more about the health of those with high vitamin D levels. They found that toxic levels are actually rare. A vitamin D level greater than 50 nanograms per milliliter is considered high. Vitamin D levels are determined by a blood test called a serum 25-hydroxyvitamin D blood test. A normal level is 20-50 ng/mL, and deficiency is considered anything less than 20 ng/mL, according the Institute of Medicine (IOM). The researchers analyzed data collected over 10 years from patients in the Rochester Epidemiology Project, a National Institutes of Health-funded medical records pool , one of the few places worldwide where scientists can study virtually an entire geographic population to identify health trends. Of 20,308 measurements, 8 percent of the people who had their vitamin D measured had levels greater than 50 ng/mL, and less than 1 percent had levels over 100 ng/mL. "We found that even in those with high levels of vitamin D over 50 ng/mL, there was not an increased risk of hypercalcemia, or elevated serum calcium, with increasing levels of vitamin D," says study co-author Thomas D. Thacher, M.D., a family medicine expert at Mayo Clinic. Only one case over the 10-year study period was identified as true acute vitamin D toxicity; the person's vitamin D level was 364 ng/mL. The individual had been taking 50,000 international units (IU) of vitamin D supplements every day for more than three months, as well as calcium supplements. The IOM-recommended upper limit of vitamin D supplementation for people with low or deficient levels is 4,000 IU a day.     Reducing sedentary time mitigates the risk of type 2 diabetes and cardiovascular diseases University of Turku (Finland), May 2, 2022 A new study suggests that reducing daily sedentary time can have a positive effect on the risk factors of lifestyle diseases already in three months. Spending just one hour less sitting daily and increasing light physical activity can help in the prevention of these diseases. In an intervention study of the Turku PET Centre and the UKK Institute in Finland, the researchers investigated whether health benefits can be achieved by reducing daily sedentary time during a three-month intervention period. The research participants were sedentary and physically inactive working-age adults with an increased risk of type 2 diabetes and cardiovascular diseases. The intervention group managed to reduce sedentary time by 50 minutes per day on average, mainly by increasing the amount of light- and moderate-intensity physical activity. In the three-month period, the researchers observed benefits in health outcomes related to blood sugar regulation, insulin sensitivity and liver health in the intervention group.     Study Finds Cannabis May Be A “Miracle” Treatment For Autistic Kids Shaare Zedek Medical Center (Israel), April 26, 2022 Autism could now be added to the lengthy and perpetually-expanding list of afflictions and symptoms treatable with the one product of nature shamefully prohibited by the federal government — the “miracle” palliative, cannabis. In a recent article titled, “Marijuana may be a miracle treatment for children with autism,” Israeli researchers began a new study comprised of 120 children ranging in age from five to 29 years, who have been diagnosed with mild to severe autism. Study participants are given one of two cannabis oil treatments or a placebo, drops of which can be mixed into a meal — none contain high levels of THC, the ingredient which gives users a ‘high.' Myriad scientific studies and innumerable anecdotal cases have proven cannabis to treat everything from PTSD to ADHD, various cancers to the painful pressure of glaucoma — but the plant's miraculous quality has been most apparent in treating severe seizures of childhood epilepsy. Now, it appears, cannabis — specifically, the non-psychoactive compound, cannabidiol or CBD — may offer improved quality of life for children with autism, and the families providing their care. In an observational study, the doctor found 70 patients with autism experienced positive results from cannabis — so the clinical trial was launched for in-depth study.     Resveratrol and pinostilbene provide neuroprotectoin against age-related deficits. Duquesne University, April 27, 2022 According to news, research stated, "Age-related declines in motor function may be due, in part, to an increase in oxidative stress in the aging brain leading to dopamine (DA) neuronal cell death. In this study, we examined the neuroprotective effects of natural antioxidants resveratrol and pinostilbene against age-related DAergic cell death and motor dysfunction using SH-SY5Y neuroblastoma cells and young, middle-aged, and old male C57BL/6 mice." The news reporters obtained a quote from the research from Duquesne University, "Resveratrol and pinostilbene protected SH-SY5Y cells from a DA-induced decrease in cell viability. Dietary supplementation with resveratrol and pinostilbene inhibited the decline of motor function observed with age. While DA and its metabolites (DOPAC and HVA), dopamine transporter, and tyrosine hydroxylase levels remain unchanged during aging or treatment, resveratrol and pinostilbene increased ERK1/2 activation in vitro and in vivo in an age-dependent manner. Inhibition of ERK1/2 in SH-SY5Y cells decreased the protective effects of both compounds." "These data suggest that resveratrol and pinostilbene alleviate age-related motor decline via the promotion of DA neuronal survival and activation of the ERK1/2 pathways." Study sheds light on the benefits of exercise in fatty liver disease University of Eastern Finland, May 3, 2022 Exercise supports the treatment of non-alcoholic fatty liver (NAFLD) disease by impacting on several metabolic pathways in the body, a new study from the University of Eastern Finland shows Regular high-intensity interval training (HIIT) exercise over a period of 12 weeks significantly decreased the study participants' fasting glucose and waist circumference, and improved their maximum oxygen consumption rate and maximum achieved workload. These positive effects were associated with alterations in the abundance of a number of metabolites. In particular, exercise altered amino acid metabolism in adipose tissue. The study was published in Scientific Reports. Exercise had a beneficial effect on fasting glucose concentrations, waist circumference, maximum oxygen consumption rate, and maximum achieved workload. These factors were also associated with many of the observed alterations in the abundance of various metabolites in the exercise intervention group. The most significant alterations were observed in amino acids and their derivatives, lipids, and bile acids. In particular, exercise increased the levels of amino acids, which are the building blocks of proteins, in adipose tissue. According to the researchers, their higher accumulations in adipose tissue may be associated with improved lipid and glucose metabolism, as well as with reduced insulin resistance. The levels of various gut microbial metabolites were altered as a result of exercise, which is suggestive of changes in the composition of gut microbes, or in their function. Among these metabolites, increased amount of indolelactic acid, for example, can strengthen the intestinal mucosa, immune defense, and glucose balance.    

Dietary propolis supplementation reduced proinflammatory cytokines associated with air pollution exposure, without impacting on immune cell infiltration or lung function New Zealand Institute for Plant and Food Research, September 10, 2021 Air pollution is estimated to cause 7 million annual deaths globally. Our aim was to determine if dietary propolis consumption could prevent the immune and functional damage in a mouse model of acute urban dust exposure. Female C57BL/6J mice were challenged three times with intranasal urban dust over seven days which significantly increased proinflammatory cytokines and immune cells in the lung 24 h post final challenge. Dietary New Zealand propolis (2%) with gamma cyclodextrin supplementation reduced urban dust-induced lung TNFα, IL-4, and IL-6 cytokine production; but did not alter immune cell infiltration into the lung, or lung function outcomes. This suggests that daily consumption of 8% propolis with gamma cyclodextrin supplemented food was sufficient to reduce urban dust pollution-induced proinflammatory cytokine production but was not sufficient to prevent immune cell recruitment into the lung or lung function decline in a murine model of lung inflammation. In this study we found that daily consumption of a New Zealand propolis reduced proinflammatory cytokines within the lung in response to acute urban dust exposure but this inhibition was not sufficient to reduce immune cell infiltration or prevent increased airways tissue constriction. These results suggest that dietary supplementation of 8% propolis with gamma cyclodextrin (equivalent to 2% propolis resin) does not result in sufficient bioavailable concentrations of the bioactive polyphenolics to fully overcome urban dust pollution-induced acute immune cell infiltration into the lung. Other studies have shown that acute gavage consumption or intraperitoneal injection of specific propolis bioactive components can protect against a number of different immune challenges within the lung. These effects appear to be both concentration and administration route dependent, and may not be achievable using unenriched propolis as a dietary intervention.   20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment Comprehensive Pain Management Institute (Ohio), August 6, 2021 New research published in the Journal of Evidence-Based Integrative Medicine shows that early intervention against a Wuhan coronavirus (Covid-19) infection using natural, over-the-counter remedies is a safe and effective way to avoid complications. Researchers from Ohio looked at modalities that are readily available for the Chinese Virus, including zinc, zinc ionophores, vitamins C, D3, and E, and l-lysine. These items were categorized in the study as “preventive measures” and “early-stage treatments” that can help to avoid the need for more “advanced” anti-covid measures such as pharmaceutical drugs and vaccines. Each of these tested remedies is natural, by the way, and the results of what they can do are impressive. Once again, nature wins out as our most abundant medicine cabinet, far exceeding anything cooked up in a lab. The clinical study found that this “multi-component OTC (over-the-counter) ‘core formulation' regimen” successfully protected test subjects against getting sick from the Chinese Virus, even as others got sick. “While both groups were moderate in size, the difference between them in outcomes over the 20-week study period was large and stark: Just under 4% of the compliant test group presented flu-like symptoms, but none of the test group was COVID-positive,” the paper reveals. “[W]hereas 20% of the non-compliant control group presented flu-like symptoms, three-quarters of whom (15% overall of the control group) were COVID-positive.” For 20 weeks, test subjects took these natural supplements. Adjustments were made for those with pre-existing health conditions and other health factors that may have influenced the outcome. Since all of the remedies utilized fall into the “low cost” category, anyone can access them. They are all dubbed as “anti-viral” as well, meaning they are safe and effective for use against viruses. By taking advantage of these remedies early, the paper explains, people can help to protect themselves against the types of adverse events that are causing some people to have to be hospitalized and put on a ventilator. “From early March through the end of July 2020, one of us (LM) monitored approximately 600 patients in Columbus and Cleveland, Ohio cities heavily affected by the COVID-19 pandemic, and did consultations with several colleagues (including JL) in the New York City metropolitan area, also heavily hit,” the paper explains. “Over that 5-month period, we dealt with dozens of clinical and/or test-confirmed cases of COVID-19. Much of the monitoring was performed via telemedicine; approximately 20% was performed in-office. It is from in-office monitored patients and staff that the study groups emerged.” We have been covering some of these same remedies along with others that have been scientifically shown to help protect against spike protein-induced illness. Hydroxychloroquine (HCQ), as one example, is a zinc ionophore that helps to deliver more zinc into cells for improved immune function. Epigallocatechin gallate (EGCG), a polyphenol component of green tea, is a natural zinc ionophore that improves zinc absorption. For this latest study, the research team used quina (cinchona) plant bark extract and quercetin as zinc ionophores, as these, too, help to deliver more healing nutrients like zinc to the cells. “The core supplementation formulation components have been demonstrated … to have beneficial effects both outside of and within clinical settings in the prevention of viral infections and also in the treatment of early stages of such diseases,” the study reveals. “Zinc ionophores can … be utilized to gain the anti-viral benefit of enhanced intracellular Zn+2 concentrations while limiting tolerance / side-effect / toxicity issues associated with elevated serum levels of zinc supplementation.” You can review the full paper at this link.     Neuroprotective effect of L-carnitine against glyceraldehyde-induced metabolic impairment University Politecnica delle Marche (Italy), September 7, 2021 According to news reporting originating from Ancona, Italy, research stated, “Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive regression and memory loss. Dysfunctions of both glucose metabolism and mitochondrial dynamics have been recognized as the main upstream events of the degenerative processes leading to AD.” Our news editors obtained a quote from the research from the School of Medicine, “It has been recently found that correcting cell metabolism by providing alternative substrates can prevent neuronal injury by retaining mitochondrial function and reducing AD marker levels. Here, we induced an AD-like phenotype by using the glycolysis inhibitor glyceraldehyde (GA) and explored whether L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid, LC) could mitigate neuronal damage, both in SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. We have already reported that GA significantly modified AD marker levels; here we demonstrated that GA dramatically compromised cellular bioenergetic status, as revealed by glycolysis and oxygen consumption rate (OCR) evaluation. We found that LC ameliorated cell survival, improved OCR and ATP synthesis, prevented the loss of the mitochondrial membrane potential (Dps) and reduced the formation of reactive oxygen species (ROS). Of note, the beneficial effect of LC did not rely on the glycolytic pathway rescue. Finally, we noticed that LC significantly reduced the increase in pTau levels induced by GA. Overall, these findings suggest that the use of LC can promote cell survival in the setting of the metabolic impairments commonly observed in AD.” According to the news editors, the research concluded: “Our data suggest that LC may act by maintaining mitochondrial function and by reducing the pTau level.”     Hyperbaric oxygen study shows reversal of biologic hallmarks responsible for development of Alzheimer disease Tel Aviv University  & Shamir Medical Center (Israel), September 10, 2021 A new study, published today in peer-review medical journal Aging, marks the first time non-pharmaceutical clinical exploration proves efficacy in reversing the main activators of Alzheimer's disease.    Using a specific protocol of hyperbaric oxygen therapy (HBOT), cerebral blood flow (CBF) improved/increased in elderly patients by 16-23%, alleviating vascular dysfunction and amyloid burden. The study, part of a comprehensive research program directed toward aging and accompanying ailments as a reversible disease, holds promise for a new strategic approach to the prevention of Alzheimer's by addressing not only the symptoms or targeting biomarkers, but rather the core pathology and biology responsible for the advancement of the disease.  Vascular dysfunction is a crucial element in the development of Alzheimer's and cognitive decline: Amyloid beta deposits in the brain blood vessel walls are the most common vascular pathology in Alzheimer's.  Reduced blood flow to the brain and its related decrease in oxygen supply (hypoxia) can precede the clinical onset of dementia and correlates with the degree of cognitive impairment in Alzheimer's. The comprehensive research, conducted at the Sagol School of Neuroscience at Tel Aviv University and the Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center, was led by study co-authors, Professor Shai Efrati, M.D.; Professor Uri Ashery, Ph.D.; Ronit Shapira, Ph.D.; Pablo Blinder, Ph.D.; Amir Hadanny, M.D. Using combined data from an animal model of Alzheimer's, where effects were evaluated directly on brain tissue (Sagol School of Neuroscience at Tel Aviv University); humans, assessed with the use of high-resolution MRI and computerized cognitive test (Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center); correlating results displayed beneficial effects of HBOT on patients suffering from mild cognitive impairment (MCI), the stage before dementia. Each patient received 60 HBOT sessions over a 90-day period, showcasing substantial improvement in cognitive functions – with memory, attention and information processing speed exhibiting the strongest results.  "After dedicating our HBOT research to exploring its impact on the areas of brain functionality and age-related cognitive decline, we have discovered for the first time HBOT induces degradation and clearance of pre-existing amyloid plaques – treatment, and the appearance of newly formed plaques- prevention," explains Professor Uri Ashery. "Elderly patients suffering from significant memory loss at baseline revealed an increase in brain blood flow and improvement in cognitive performance, demonstrating HBOT potency to reverse core elements responsible for the development of Alzheimer's disease." "By treating vascular dysfunction, we're mapping out the path toward Alzheimer's prevention. More research is underway to further demonstrate how HBOT can improve cognitive function and become an influential tool in the imperative fight against the disease," affirms Professor Efrati, research group leader and medical advisor to Aviv Scientific.  Aviv has developed a unique medical treatment protocol that includes HBOT, cognitive and physical training, and nutritional coaching, to enhance brain and body performance of aging adults at Aviv Clinics, currently available in Central Florida and Dubai.  HBOT is already used in patients with other pathologies and is known to be a relatively safe treatment modality, illustrating its potential to be easily implanted in clinical practice. In recent years, there is growing scientific evidence that certain protocols of HBOT can improve brain oxygen supply, induce proliferation of neuronal stem cells and induce generation of new blood vessels and neurons in the brain.       Increased flatulence from eating plant-based diet found to indicate healthier gut microbiome Center for Biomedical Research Network for Liver and Digestive Diseases (Spain), September 10, 2021 A team of researchers affiliated with a host of institutions across Spain has found that the increase in flatulence experienced by people switching to a plant-based diet is an indication of a healthier gut microbiome. In their paper published in the journal Nutrients, the group describes experiments they conducted with healthy, male volunteers regarding diet, fecal sample size and flatulence. It is widely known that switching from a fat or carbohydrate-based diet to one that features more vegetables results in more flatulence—particularly if the switch is to cruciferous vegetables. But as the researchers with this new effort have noted, little research has been done to learn more about the association between diet and flatulence. To learn more about the impact of switching to a plant-based diet on digestion and the gut biome, the researchers enlisted the assistance of 18 healthy, adult male volunteers. Each was asked to eat a western-style diet and then to switch to the plant-based Mediterranean diet for two weeks. Over the study period, the volunteers were asked to count the number of times they defecated each day and to capture and weigh each stool sample. Each of the volunteers was also asked to count the number of times they passed gas. The volunteers were also asked to submit to randomized testing that involved measuring the amount of gas that was emitted during episodes of flatulence, using balloons. The researchers found that the change in diet did not change the number of times the volunteers defecated each day—but it did change the amount of material discharged. The researchers found the plant-based diet doubled the stool size on average. The researchers note this was due to a huge increase in the mass of bacterial growth and excretion. The data also showed that the number of flatulence episodes increased by seven times per day on the plant-based diet—and each discharge had approximately 50% more gas. The researchers note this was due to fermenting of plant material in the gut. The researchers suggest their experiments show that a plant-based diet promotes more healthy types of gut bacteria which leads to better overall gut health.   Physical exercise can relieve tumor-associated anemia University of Basel (Switzerland), September 10, 2021 Many cancer patients suffer from anemia leaving them fatigued, weak, and an impaired ability to perform physical activity. Drugs only rarely alleviate this type of anemia. Researchers at the University of Basel have now been able to show what causes the anemia, and that physical exercise can improve this condition. The two major symptoms of cancer are loss of muscle mass and a reduced hemoglobin level, leading to weight loss, fatigue, lethargy and reduced physical performance. Moreover, both symptoms—atrophy and anemia—prompt many patients to schedule a doctor's appointment, then resulting in the diagnosis of a tumor. Why cancer causes muscle atrophy and anemia is not yet understood, and treatment is currently difficult. The fact that anemia leads to a decline of the overall state of health and can negatively affect the course of cancer therapy highlights the urgency to obtain insights into causes and potential remedies. In collaboration with the Department of Biomedicine at the University of Basel, the research group of Professor Christoph Handschin at the Biozentrum has now been able to show in a mouse model that cancer not only triggers a systemic inflammatory reaction, but also massively changes the handling of lipids and other metabolites in the body. The body's fight is unsuccessful These changes result in a tumor-related enhanced destruction of red blood cells. The study published in Science Advances shows that exercise normalizes these metabolic abnormalities and thereby reduces the anemia caused by cancer. The body tries to counteract the degradation by increasing red blood cell productionin the bone marrow and the spleen—without success. However, the increased production of blood cells is insufficient to prevent tumor-associated anemia. "We have now been able to clarify how cancer causes the degradation of red blood cells," says Christoph Handschin. "Cancer massively alters the metabolism of lipids and other compounds. This alters not only the red blood cells but also the macrophages, causing a sharp increase in red blood cells destruction by the macrophages." Macrophages are a type of white blood cells and part of the immune system. Exercise normalizes metabolism and alleviates anemia The research group attempted to normalize the metabolism by pharmacological means. However, none of the drugs could significantly improve the anemia. In contrast, however, the metabolism was regulated to such an extent by exercise that the anemia also decreased. Even the abnormal increase in red blood cell production could be reduced to a lower level. "Training was able to restore tumor-induced metabolic remodeling and inflammation sufficiently to blunt the excessive blood cell formation and destruction," explained Handschin. This study provides novel insights into the development of tumor-associated anemia. The findings suggest that exercise is a useful therapy for cancer patients, in order to counteract anemia and associated fatigue and lethargy and in turn to improve their general well-being and quality of life. This also leads to improved tolerance of radio- and chemotherapy, as has previously been established.   Mango could help maintain gut bacteria at risk from high-fat diets Oklahoma State University, September 13, 2021 Mango consumption could help prevent the loss of beneficial gut bacteria caused by a high fat diet, according to research on mice. The findings, published in the Journal of Nutrition , appears to reveal for the first time the positive impact of mango on gut microbiota. In the study, 60 male mice were assigned to one of four dietary treatment groups for 12 weeks - control (with 10% of calories from fat), high fat (with 60% calories from fat), or high fat with 1% or 10% mango. All high-fat diets had similar macronutrient, calcium, phosphorus, and fiber content. “We investigated the effects of freeze-dried mango pulp combined with an high-fat diet on the cecal microbial population and its relation to body composition, lipids, glucose parameters, short-chain fatty acid (SCFA) production, and gut inflammatory markers in a mouse model of diet-induced obesity,” the study reports. The high-fat dietary treatment with 10% mango (equivalent to 1½ cups of fresh mango pieces) was found to be the most effective in preventing the loss of beneficial bacteria from a high-fat diet without decreasing body weight or fat accumulation. Specifically, mango supplementation regulated gut bacteria in favor of Bifidobacteria and Akkermansia and enhanced short-chain fatty acid (SFCA) production. SCFAs have been shown to possess a wide range of beneficial effects, such as anti-inflammatory properties. Fibre benefits In previous studies, Bifidobacteria, for example, has been found to be lower in both obese individuals and those with type-2 diabetes. Similar results have been observed withAkkermansia in animal studies. High-fat diets, meanwhile, have been linked to gut dysbiosis, or bacterial imbalances within the intestinal tract. "Fibre and other bioactive compounds in plant-based foods are suggested to prevent gut dysbiosis caused by a high-fat diet," said Edralin A. Lucas, professor of nutritional sciences at Oklahoma State University and lead researcher of the study. "Mango is a good source of fibre and has been reported in previous studies to have anti-obesogenic, hypoglycemic and immunomodulatory properties. The results of this animal study showed that adding mango to the diet may help maintain and regulate gut health and levels of beneficial bacteria levels.” India, China, Indonesia and Thailand are the top four Mango growing countries, accounting for well over half the total global production. Although more research is needed on the effects of mango on human health, this study suggests that mango consumption may be important in improving gut health particularly for those consuming a high-fat diet, the researchers concluded.

Traditional Japanese food may hold building blocks of COVID-19 treatments Tokyo University of Agriculture and Technology, July 21, 2021 Natto, a fermented soybean dish often served for breakfast in Japan, originated at the turn of the last millennium but may hold an answer to a modern problem: COVID-19, according to a new study based on cell cultures.  Long thought to contribute to longer, healthier lives across Japan -- the country with the longest life expectancy on Earth and home to more than a quarter of the world's population aged 65 years or older -- natto was previously found to be a diet staple in those who were least likely to die from stroke or cardiac disease. Now, researchers have found that extract made from the sticky, strong smelling natto may inhibit the ability of the virus that causes COVID-19 to infect cells.  The team published its results on July 13th in Biochemical and Biophysical Research Communications.  "Traditionally, Japanese people have assumed that natto is beneficial for their health," said paper author Tetsuya Mizutani, director of the Center for Infectious Disease Epidemiology and Prevention Research at the Tokyo University of Agriculture and Technology (CEPiR-TUAT). "In recent years, research studies have revealed scientific evidence for this belief. In this study, we investigated natto's antiviral effects on SARS-CoV-2, the virus that causes COVID-19, and bovine herpesvirus 1 (BHV-1), which causes respiratory disease in cattle." Natto is made by fermenting soybeans with Bacillus subtilis, a bacteria found in plant and in soil. The researchers prepared two natto extracts from the food, one with heat and one without. They applied the extracts to sets of lab-cultured cells from cattle and from humans. One set was infected with SARS-CoV-2, while the other set was infected with BHV-1.  When treated with the natto extract made without heat, both SARS-CoV-2 and BHV-1 lost the ability to infect cells. However, neither virus appeared to be affected by the heat-treated natto extract.  "We found what appears to be a protease or proteases -- proteins that metabolize other proteins -- in the natto extract directly digests the receptor binding domain on the spike protein in SARS-CoV-2," Mizutani said, noting that the protease appears to break down in heat, losing the ability to digest proteins and letting the virus remain infectious.  The spike protein sits on the virus's surface and binds to a receptor on host cells. With an inactive spike protein, SARS-CoV-2 cannot infect healthy cells. The researchers found a similar effect on BHV-1.  "We also confirmed that the natto extract has the same digestive effects on the receptor binding domain proteins of the SARS-CoV-2 mutated strains, such as the Alpha variant," Mizutani said.  While the results are promising, Mizutani said, he also cautioned that further studies are needed to identify the exact molecular mechanisms at work. He also stressed that the research does not provide any evidence of reduced viral infection simply by eating natto. Once the components are identified and their functions verified, the researchers plan to advance their work to clinical studies in animal models.  "Although there are vaccines for COVID-19, we do not know how they effective they may be against every variant," Mizutani said. "It will also take time to vaccinate everyone, and there are still reports of breakthrough cases, so we need to make treatments for those who develop COVID-19. This work may offer a big hint for such pharmaceutical design."       Excess caffeine intake may be linked to an increased risk of osteoporosis   University of South Australia, July 19, 2021 University of South Australia researchers have a bone to pick when it comes to drinking too much coffee as new research finds that excess caffeine may be linked to an increased risk of osteoporosis. Investigating the effects of coffee on how the kidneys regulate calcium in the body, researchers found that high doses of caffeine (800 mg) consumed over a six-hour period almost doubled the amount of calcium lost in the urine. This is the first study to report the impact of high-dose, short-term caffeine intake on renal clearance of calcium, sodium, and creatinine in healthy adults. UniSA's Dr. Hayley Schultz says with the emergence of an increasing "coffee culture" it's important for people to understand the impacts of what they are putting into their bodies. "Caffeine is one of the most widely used recreational drugs in the world, with 80 percent of adults consuming at least one caffeinated beverage per day," Dr. Schultz says. "It's a common stimulant, consumed by professionals, parents, shift workers, and teenagers alike to start their day and stay alert—even the military use caffeine to help combat sleepiness.  "But while coffee has its perks, it's also important to acknowledge its fallbacks—one of them being how our kidneys handle calcium. "Our research found that people who consume 800 mg of caffeine over a typical working day will have a 77 percent increase in calcium in their urine, creating a potential deficiency that could impact their bones." Osteoporosis is a chronic, painful, and debilitating disease which makes your bones less dense and more susceptible to fracture. More common in women, it occurs when bones lose calcium and other minerals faster than the body can replace them. In Australia, an estimated 924,000 people have osteoporosis. The double-blind clinical study saw participants chew caffeine or a placebo gum for five minutes at two-hour intervals over a six-hour treatment period (total caffeine 800 mg). While the primary research objective was to examine the impact of caffeine consumption on wakefulness and other factors, this sub-study aimed to evaluate the impact of caffeine consumption on the renal clearance of calcium. Co-researcher, UniSA's Dr. Stephanie Reuter Lange says understanding the long-term impacts of high caffeine consumption is especially important for higher risk groups. "The average daily intake of caffeine is about 200 mg—roughly two cups of coffee. While drinking eight cups of coffee may seem a lot (800 mg of caffeine), there are groups who would fall into this category," Dr. Reuter Lange says. "People at risk could include teenagers who binge-consume energy drinks are at are at risk because their bones are still developing; professional athletes who use caffeine for performance enhancement; as well as post-menopausal women who often have low blood calcium levels due to hormonal changes and lack sufficient daily dietary calcium intake. "Increasingly, we are also seeing high levels of caffeine among shiftworkers who need to stay alert over the night-time hours, as well as those in the military who use caffeine to combat sleep deprivation in operational settings. "Caffeine in moderation certainly has its pros. But understanding how excess consumption could increase the risks of a highly preventable disease such as osteoporosis, is important." From here, researchers will explore and predict the impact of different levels of caffeine intake on short- and long-term bone health, with the aim to inform dietary guidelines in Australia.     From heart to diabetes, these are the health benefits of strawberries University of Nevada, July 16, 2021 Dietary berries, such as strawberries, are rich in bioactive compounds and have been shown to lower cardiometabolic risk. We examined the effects of two dietary achievable doses of strawberries on glycemic control and lipid profiles in obese adults with elevated serum LDL cholesterol (LDL-C).  Methods: In this 14-week randomized controlled crossover study, participants were assigned to one of the three arms for four weeks separated by a one-week washout period: control powder, one serving (low dose: 13 g strawberry powder/day), or two-and-a -half servings (high dose: 32 g strawberry powder/day). Participants were instructed to follow their usual diet and lifestyle while refraining from consuming other berries and related products throughout the study interval. Blood samples, anthropometric measures, blood pressure, and dietary and physical activity data were collected at baseline and at the end of each four-week phase of intervention.  Results: In total, 33 participants completed all three phases of the trial [(mean ± SD): Age: 53 ± 13 y; BMI: 33 ± 3.0 kg/m2). Findings revealed significant reductions in fasting insulin (p = 0.0002) and homeostatic model of assessment of insulin resistance (p = 0.0003) following the high dose strawberry phase when compared to the low dose strawberry and control phases. Glucose and conventional lipid profiles did not differ among the phases. Nuclear magnetic resonance-determined particle concentrations of total VLDL and chylomicrons, small VLDL, and total and small LDL were significantly decreased after the high dose strawberry phase, compared to control and low dose phases (all p < 0.0001). Among the biomarkers of inflammation and adipokines measured, only serum PAI-1 showed a decrease after the high dose strawberry phase (p = 0.002). Conclusions: These data suggest that consuming strawberries at two-and-a-half servings for four weeks significantly improves insulin resistance, lipid particle profiles, and serum PAI-1 in obese adults with elevated serum LDL-C.     Omega 3 has beneficial effects on reducing relapse rate, inflammatory markers in MS patients Imam Abdulrahman Bin Faisal University (Saudi Arabia), July 14, 2021 According to news originating from Dammam, Saudi Arabia, research stated, “Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system, resulting in the degradation of the myelin sheath. Diet especially fish oils and omega-3 has been found to play an important role in MS.” Our news journalists obtained a quote from the research from Imam Abdulrahman Bin Faisal University, “This work aimed to review the literature systematically for evidence on the effect of omega-3 fatty acids (EPA, DPA and DHA) on MS progression in adults. The literature search was conducted in PubMed, Oxford, Cochrane, Embase, International pharmaceutical abstract, PsychINFO, and clinical trials government. The inclusions were studies performed on humans both male and female, aged 18 years at minimum, diagnosed with MS according to McDonald 2010 criteria. Otherwise, all studies were excluded. A total of 5554 studies were screened and seven were thoroughly focused on as they typically met the inclusion criteria. These studies showed the beneficial roles of fish oil supplementation and omega-3 fatty acids in improving the quality of life of MS patients. These roles were attributed to their beneficial effects on inflammatory markers, glutathione reductase, reducing the relapsing rate, and achieving balanced omega-6 to omega-3 ratios.” According to the news editors, the research concluded: “Omega-3 and fish oils supplementations have beneficial effects on reducing the relapsing rate, inflammatory markers, and improving the quality of life for MS patients.” This research has been peer-reviewed.           Championing chrononutrition with protein, the morning elixir for muscle growth Waseda University (Japan), July 20, 2021 Proteins constitute an essential dietary component that help in the growth and repair of the body. Composed of long chains of amino acids, proteins promote the growth of skeletal muscles, the group of muscles that help us move. Humans have been aware of the benefits of proteins for long. However, recent studies have shown that having the right amount of protein at the right time of the day is essential for proper growth. This is called 'Chrononutrition,' in which when you eat is as important as what and how you eat. The reason behind this is the body's internal biological clock, called the 'circadian rhythm'. This rhythm is followed by all cells and controls life functions like metabolism and growth. Interestingly, protein digestion and absorption have been found to fluctuate across day and night according to this clock. Moreover, earlier studies have reported that intake of protein at breakfast and lunch promotes skeletal muscle growth in adults. However, details on the effect of the time of protein intake on muscle growth and function have remained elusive till date. Fortunately, researchers from Waseda University, led by Professor Shigenobu Shibata, recently endeavored to understand the effect of the distribution of protein intake through the day on muscles. They fed laboratory mice two meals per day containing either high (11.5% by proportion) or low (8.5% by proportion) protein concentrations. The researchers noted that protein intake at breakfast induced an increase in muscle growth, determined by assessing induced hypertrophy of the plantaris muscle in the leg, when compared with the effects of protein intake at dinner. Specifically, the ratio of muscle hypertrophy determined against the growth of the control muscle was 17% higher in mice fed 8.5% protein at breakfast, than that in mice fed 11.5% protein at dinner, despite the former group consuming a low proportion of protein overall. They also found that intake of a type of protein called the BCCA, short for branched-chain amino acids, early in the day increased the size of skeletal muscles specifically. To confirm the association of these effects with the workings of the circadian rhythm, the researchers next engineered whole-body mutant ClockΔ19 or muscle-specific Bmal1 knockout mice lacking the genes that control the biological clock. They repeated diet distribution experiments on these mice but did not observe similar muscle change, which confirmed the involvement of the circadian rhythm in muscle growth in the context of protein intake. Excited about the findings of their study published in a recent issue of the Cell Reports, Prof. Shibata emphasizes, "Protein-rich diet at an early phase of the daily active period, that is at breakfast, is important to maintain skeletal muscle health and enhance muscle volume and grip strength." To check if their findings were applicable to humans, the team recruited women in their study and tested if their muscle function, determined by measuring skeletal muscle index (SMI) and grip strength, varied with the timing of the protein-rich diet consumed. Sixty women aged 65 years and above who took protein at breakfast rather than at dinner showed better muscle functions, suggesting the possibility of the findings to be true across species. Additionally, the researchers also found a strong association between SMI and the proportion of protein intake at breakfast relative to total protein intake through the day. Prof. Shibata is hopeful that the findings of their study will lead to a widespread modification in the current diet regime of most people across the Western and Asian countries, who traditionally consume low amounts of protein at breakfast. He therefore stresses, "For humans, in general, the protein intake at breakfast averages about 15 grams, which is less than what we consume at dinner, which is roughly 28 grams. Our findings strongly support changing this norm and consuming more protein at breakfast or morning snacking time."   Ginseng compound exerts neuroprotective effects Gachon University (South Korea), July 16, 2021 According to news reporting from Gyeonggi Do, South Korea, research stated, “Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of b-amyloid plaques and hyperphosphorylated tau proteins in the brain.” The news correspondents obtained a quote from the research from Gachon University: “Cell signaling pathways such as PI3K/Akt are known to play an essential role in regulating cell survival, motility, transcription, metabolism, and progression of the cell cycle. Recent studies demonstrated that the disruption of these signaling pathways in neurodegenerative disorders leads to oxidative stress and cell death. Targeting these altered signaling pathways could be considered as the therapeutic approach for neurodegenerative disorders. Ginsenoside Rh1 is known to provide beneficial effects in various diseases such as cancer, diabetes, and inflammation. In this study, human neuroblastoma SH-SY5Y cells were treated with the b-amyloid oligomers alone or in combination with ginsenoside Rh1. We observed that ginsenoside Rh1 was able to attenuate b-amyloid induced oxidative stress and cell death by activating the PI3K/Akt signaling pathway.” According to the news reporters, the research concluded: “Based on these findings, we suggest that ginsenoside Rh1 might be an efficacious therapeutic agent for AD.”     Many kinds of happiness promote better health, study finds Weill Cornell University of Medicine, July 21, 2021  A new study links the capacity to feel a variety of upbeat emotions to better health. The research suggests people who experience a range of positive emotions in their daily lives – from enthusiasm to cheerfulness and calm – have lower levels of inflammation, compared to those who experience a narrower range of emotions. Lower levels of inflammation are linked to a lower risk of premature death and chronic diseases like diabetes. The researchers drew on analytic approaches used to measure the biodiversity of ecosystems. Their study was published June 22 in the journal Emotion. "There are many kinds of happiness, and experiencing a diversity of emotional states might reduce a person's vulnerability to psychopathology by preventing any one emotion from dominating their emotional life," said lead author Anthony Ong, professor of human development in the College of Human Ecology and professor of geriatrics and palliative medicine at Weill Cornell Medicine. Little is known about the biological processes through which emotional experiences influence health outcomes. This study sought to fill a bit of that gap. Specifically, the study sheds light on one potential biological pathway – systemic inflammation – through which diversity in everyday positive emotional experiences might "get under the skin" to influence long-term health. Ong and his colleagues analyzed the connection between "emodiversity" – the breadth and abundance of different emotions people experience – and markers of inflammation in the body. A person with low emodiversity feels about the same through most of the day, with emotions concentrated in just a few categories. In contrast, a person with high emodiversity feels a range of emotions throughout the day, distributed evenly across the spectrum of feelings. The researchers analyzed data from 175 people ages 40 to 65 who reported on their negative and positive emotions for 30 days. Each evening, they rated the extent to which they had experienced 16 positive emotions that day, from interested and determined to happy, excited, amused, inspired, alert, active and strong. They were also asked to rate their experience of 16 negative emotions, including scared, afraid, upset, distressed, jittery, nervous and ashamed. Their blood was drawn six months later and was tested for three inflammation markers that circulate in the blood. Their range of negative emotions – regardless of whether it was narrow or wide – had no effect on inflammation. But people in the study who reported a wide range of positive emotions had lower levels of inflammation than those who said they felt a narrower range. "Emotions serve functional roles for individuals, helping them prioritize and regulate behavior in ways that optimize adjustment to situational demands," Ong said. "Our findings suggest that depletion or overabundance of positive emotions, in particular, has consequences for the functioning and health of one's emotional ecosystem." Growing evidence from other research has linked emotional processes with systemic inflammation, which has been shown to contribute to poor health, such as atherosclerosis, diabetes, rheumatoid disease and osteoporosis, and leads to a number of processes that play a major role in premature death. How can these findings help one achieve better health? Label your good feelings as you experience them, Ong said. "The simple daily practice of labeling and categorizing good feelings in specific terms may help us experience more differentiated emotions in different contexts," Ong said.

Study presents evidence supporting the use of curcumin as alternative treatment for kidney fibrosis Zhejiang University (China), May 7, 2021 In a recent study, Chinese researchers explored the anti-fibrotic effects of curcumin, the active component of turmeric. Specifically, they looked at how curcumin affects epithelial-mesenchymal transition (EMT) and the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. EMT refers to epithelial cells undergoing molecular changes and gaining new characteristics, such as an enhanced ability to produce ECM components. Meanwhile, the PI3K/Akt pathway is one of the major cell signaling pathways that regulate fibrosis. The researchers reported their findings in an article published in the journal Biological and Pharmaceutical Bulletin. Curcumin is an effective alternative treatment for renal fibrosis According to several animal studies, curcumin can protect the kidneys by preventing the development of renal fibrosis. However, the mechanisms underlying this activity are still unknown. To explore these mechanisms and the anti-fibrotic activities of curcumin, the researchers treated human kidney tubular epithelial cells (HKCs) with transforming growth factor-B1 (TGF-B1), curcumin and a combination of both. TGF-B1 is a protein that’s involved in many cellular functions, including cell growth, proliferation, differentiation and death, as well as the induction of EMT. The researchers used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess the effect of curcumin on cell proliferation. They also used immunocytochemistry, real-time PCR and Western blot to analyze the expression of epithelial cell markers (E-cadherin and cytokeratin), mesenchymal cell markers (vimentin, alpha smooth muscle actin (a-SMA) and fibroblast-specific protein 1 (FSP1)) and key proteins involved in the Akt/mammalian target of rapamycin (mTOR) pathway. The researchers found that low-dose curcumin (3.125 and 25?micromol/L) effectively promoted HKC proliferation. After 72 hours of incubating HKCs with TGF-B1 and curcumin, curcumin caused the cells to maintain epithelial morphology in a dose-dependent manner. It also decreased the expression of EMT-related proteins, such as vimentin, a-SMA and FSP1, and increased the expression of E-cadherin and cytokeratin. In addition, the researchers noted that curcumin reduced Akt, mTOR and P70S6K phosphorylation, which effectively suppressed the activation of the Akt/mTOR pathway in HKCs. Based on these findings, the researchers concluded that curcumin is an effective alternative treatment for renal fibrosis because it can promote HKC proliferation and stop EMT by inhibiting the activation of the Akt/mTOR pathway activity.     Research reveals new approach to understanding our wellbeing Swansea University, May 12, 2021 The ability to connect and feel a sense of belonging are basic human needs but new Swansea University research has examined how these are determined by more than just our personal relationships. Research led by psychologist Professor Andrew Kemp, of the College of Human and Health Sciences, highlights the importance of taking a wider approach to wellbeing and how it can be influenced by issues such as inequality and anthropogenic climate change. Professor Kemp worked with Ph.D. student Jess Mead and consultant clinical psychologist Dr. Zoe Fisher, of the University's Health and Wellbeing Academy, on the study which presents a transdisciplinary framework to help understand and improve wellbeing. Professor Kemp said: "We define wellbeing as positive psychological experience, promoted by connections to self, community and environment, supported by healthy vagal function, all of which are impacted by socio-contextual factors that lie beyond the control of the individual." The researchers say their latest findings, which have just been published in Frontiers in Psychology, are particularly topical as society looks to recover and learn from COVID-19. He said: "Our framework has already contributed to a better understanding of how to protect wellbeing during the pandemic and has led to the development of an innovative wellbeing science intervention, targeting university students and people living with acquired brain injury." Professor Kemp added: "We feel our invited paper is timely as it not only aligns with a post-pandemic future that requires societal transformation, but it also picks up on global efforts to promote planetary wellbeing. "Globalization, urbanization and technological advancements have meant that humans have become increasingly disconnected from nature. This continues despite research showing that contact with nature improves wellbeing." The research reveals the advantages to health and wellbeing derived from connecting to oneself, others and nature and emphasizes a need for focused efforts to tackle major societal issues that affect our capacity for connection. He added: "The poorest are disproportionally impacted by major societal challenges including increasing burden of chronic disease, societal loneliness and anthropogenic climate change. "Economic inequality has adverse impacts on the entire population, not just the poor, so improving economic inequality is fundamental to improving population wellbeing." Taking a transdisciplinary approach to the topic of wellbeing is something currently reflected across Swansea University, particularly since the opening of the Morgan Advanced Studies Institute (MASI) which is dedicated to supporting transformative interdisciplinary research.   Taurine’s neuroprotective effect on cells under oxidative stress   University of Vale do Paraiba (Brazil), May 10, 2021 According to news reporting based on a preprint abstract, our journalists obtained the following quote sourced from biorxiv.org: “Alzheimer’s disease (AD) is a type of dementia that affects millions of people. Although there is no cure, several study strategies seek to elucidate the mechanisms of the disease. Recent studies address the benefits of taurine. Thus, the present study aims to analyze the neuroprotective effect of taurine on human neuroblastoma, using an in vitro experimental model of oxidative stress induced by hydrocortisone in the SH-SY5Y cell line as a characteristic model of AD. “The violet crystal assay was used for cell viability and the evaluation of cell morphology was performed by scanning electron microscopy (SEM). After pretreatment with taurine, the SH-SY5Y cell showed an improvement in cell viability in the face of oxidative stress and improved cell morphology. Thus, the treatment presented a neuroprotective effect.” This preprint has not been peer-reviewed.     Efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study Mazandaran University of Medical Sciences (Iran), May 4, 2021 According to news originating from Sari, Iran, by NewsRx correspondents, research stated, “Migraine is a disabling disorder that affects the quality of life of patients. Different medications have been used in prevention of migraine headache.” Our news journalists obtained a quote from the research from the Mazandaran University of Medical Sciences, “In this study, we evaluated the effectiveness of magnesium oxide in comparison with valproate sodium in preventing migraine headache attacks. This is a single-center, randomized, controlled, crossover trial which is double-blind, 24-week, 2-sequence, 2-period, 2-treatment. After patient randomization into two sequences, the intervention group received magnesium oxide 500 mg and the control group received valproate sodium 400 mg two tablets each day (every 12 h) for 8 weeks. The primary efficacy variable was reduction in the number of migraine attacks and number of days with moderate or severe headache and hours with headache (duration) per month in the final of 8 weeks in comparison with baseline. Seventy patients were randomized and seven dropped out, leaving 63 for analysis. In an intention-to-treat analysis, 31 patients were in group 1 (magnesium oxide-valproate) and 32 patients were in group 2 (valproate-magnesium oxide). The mean number of migraine attacks and days per month was 1.72 +/- 1.18 and 2.09 +/- 1.70, with a mean duration of 15.50 +/- 21.80 h in magnesium group and 1.27 +/- 1.27 and 2.22 +/- 1.96, with a mean duration 13.38 +/- 14.10 in valproate group.” According to the news editors, the research concluded: “This study has shown that 500 mg magnesium oxide appears to be effective in migraine prophylaxis similar to valproate sodium without significant adverse effect.” This research has been peer-reviewed       Vitamin D and calcium from food is associated with lower risk of early menopause University of Massachusetts, May 10, 2021 A new study led by epidemiologists at the University of Massachusetts Amherst's School of Public Health and Health Sciences suggests that high intake of dietary vitamin D and calcium may be modestly associated with lower risk of early menopause, the cessation of ovarian function before age 45. Early menopause affects about 10 percent of women and is associated with higher risk of cardiovascular disease, osteoporosis and early cognitive decline. Epidemiology doctoral candidate Alexandra Purdue-Smithe and her advisor Elizabeth Bertone-Johnson, with colleagues at Brigham and Women's Hospital, Boston, and Harvard Medical School, evaluated how vitamin D and calcium intake is associated with incidence of early menopause in the prospective Nurses' Health Study II. The study population includes 116,430 female U.S. registered nurses who were 25-42 years old when they responded to a baseline questionnaire. Diet was assessed five times over the 20-year study, allowing the researchers to capture changes in food and nutrient intake over time, Purdue-Smithe notes. Participants in the study contributed more than 1 million person-years of follow-up, during which 2,041 women experienced early menopause. The authors report the hazard ratio for early menopause comparing the highest vs. lowest dietary vitamin D intake groups was 0.83 (95% confidence interval = 0.72-0.95) and for dietary calcium 0.87 (95% CI=0.76-1.00). Details of the study, supported by the National Institutes of Health, appear in the current early online edition of the American Journal of Clinical Nutrition. Purdue-Smithe says, "Laboratory evidence relating vitamin D to some of the hormonal mechanisms involved in ovarian aging provided the foundation for our hypothesis. However, to our knowledge, no prior epidemiologic studies have explicitly evaluated how vitamin D and calcium intake may be related to risk of early menopause. We found that after adjusting for a variety of different factors, vitamin D from food sources, such as fortified dairy and fatty fish, was associated with a 17 percent lower risk of early menopause when comparing the highest intake group to the lowest intake group." Because higher intake of vitamin D and calcium from foods may simply act as a marker for better nutrition and overall health, Purdue-Smithe says, the researchers took into account other factors such as intake of vegetable protein and alcohol, as well as body mass index and smoking. She adds, "The large size of this study allowed us to consider a variety of potential correlates of a healthy lifestyle that might explain our findings; however, adjusting for these factors made almost no difference in our estimates." The nutritional and reproductive epidemiologist notes that "in addition to placing women at higher risk of adverse future health outcomes, early menopause is also problematic as women are increasingly delaying childbearing into their later reproductive years. Fertility declines drastically during the 10 years leading up to menopause, so early menopause can have profound psychological and financial implications for couples who are unable to conceive as they wish. As such, it is important to identify modifiable risk factors for early menopause, such as diet." Because associations were stronger for vitamin D and calcium from dairy sources than from non-dairy food sources in the study, and Purdue-Smithe plans further analyses investigating individual dairy foods and other components of dairy and how they may be associated with early menopause.     High levels of exercise linked to 9 years of less aging at the cellular level Brigham Young University, May 10, 2021 Despite their best efforts, no scientist has ever come close to stopping humans from aging. Even anti-aging creams can't stop Old Father Time. But new research from Brigham Young University reveals you may be able to slow one type of aging--the kind that happens inside your cells. As long as you're willing to sweat. "Just because you're 40, doesn't mean you're 40 years old biologically," Tucker said. "We all know people that seem younger than their actual age. The more physically active we are, the less biological aging takes place in our bodies." The study, published in the medical journal Preventive Medicine, finds that people who have consistently high levels of physical activity have significantly longer telomeres than those who have sedentary lifestyles, as well as those who are moderately active. Telomeres are the protein endcaps of our chromosomes. They're like our biological clock and they're extremely correlated with age; each time a cell replicates, we lose a tiny bit of the endcaps. Therefore, the older we get, the shorter our telomeres. Exercise science professor Larry Tucker found adults with high physical activity levels have telomeres with a biological aging advantage of nine years over those who are sedentary, and a seven-year advantage compared to those who are moderately active. To be highly active, women had to engage in 30 minutes of jogging per day (40 minutes for men), five days a week. "If you want to see a real difference in slowing your biological aging, it appears that a little exercise won't cut it," Tucker said. "You have to work out regularly at high levels." Tucker analyzed data from 5,823 adults who participated in the CDC's National Health and Nutrition Examination Survey, one of the few indexes that includes telomere length values for study subjects. The index also includes data for 62 activities participants might have engaged in over a 30-day window, which Tucker analyzed to calculate levels of physical activity. His study found the shortest telomeres came from sedentary people--they had 140 base pairs of DNA less at the end of their telomeres than highly active folks. Surprisingly, he also found there was no significant difference in telomere length between those with low or moderate physical activity and the sedentary people. Although the exact mechanism for how exercise preserves telomeres is unknown, Tucker said it may be tied to inflammation and oxidative stress. Previous studies have shown telomere length is closely related to those two factors and it is known that exercise can suppress inflammation and oxidative stress over time. "We know that regular physical activity helps to reduce mortality and prolong life, and now we know part of that advantage may be due to the preservation of telomeres," Tucker said.       How isolation affects memory and thinking skills Harvard University, May 2021 We've all been isolated from many family members and friends during the pandemic. If you've been having a harder time remembering things or processing information since the pandemic began, it could be an isolation side effect. "It's something I'm seeing clinically. Some people were okay before the pandemic and now they're having faster cognitive decline," says Dr. Joel Salinas, a behavioral neurologist and faculty member of the Harvard Center for Population and Development Studies. Dr. Salinas says we don't have a lot of evidence yet to back up a clear association between pandemic lockdowns and a change in memory or thinking skills. One small 2020 study found that 60% of people with mild cognitive impairment or Alzheimer's disease experienced worsening cognition and delirium during the lockdown. But the link between isolation and cognitive decline is more than speculation. Isolation risks Isolation (being cut off from social contact) was a problem for older adults long before the pandemic began. Life circumstances — such as living far from friends and family, losing a partner, or being unable to drive — often create unanticipated situations in which we find ourselves isolated. That sometimes puts health in jeopardy. "In studies of people, isolation is associated with an increased risk for dementia, although it's unclear how high the risk is," Dr. Salinas says. "In lab animals, isolation has been shown to cause brain shrinkage and the kind of brain changes you'd see in Alzheimer's disease — reduced brain cell connections and reduced levels of brain-derived neurotrophic factor, which is important for the formation, connection, and repair of brain cells." Isolation is also associated with elevated risks for heart attack, stroke, chronic inflammation, depression, anxiety, perceived stress, and loneliness. People who feel lonely (disconnected from others) have been shown to have faster rates of cognitive decline than people who don't feel lonely. Loneliness is also tied to risks of losing the ability to take care of yourself and early death. What's the link? We don't exactly know why being isolated sometimes leads to cognitive decline. Possibilities include a lack of access to crucial resources or help with daily needs a decrease in stimulating mental activity that can come from social interaction a reduction in social support. "Having access to others for emotional support or listening to you seems to have a protective brain health effect — increased levels of brain-derived neurotrophic factor, and reduced risks for dementia or stroke," Dr. Salinas says. In the pandemic, you may also be experiencing high stress levels, which can affect your brain's processing skills. "We're not good at being focused when there's danger," Dr. Salinas says. "It's the 'fight or flight' mode all the time." If family members are noticing that you seem to be experiencing cognitive changes, Dr. Salinas says it could be a new problem — or it could be that you're spending more time together and they're picking up on changes that were already occurring before the pandemic.

Treatment with Rhodiola mimics exercise to resist high-fat diet-induced muscle dysfunction Central South University (China), April 30, 2021   According to news reporting out of Changsha, People’s Republic of China, research stated, “Muscle dysfunction is a complication of high-fat diet (HFD)-induced obesity that could be prevented by exercise, but patients did not get enough therapeutic efficacy from exercise due to multiple reasons.” The news reporters obtained a quote from the research from Xiangya Hospital of Central South University: “To explore alternative or supplementary approaches to prevent or treat muscle dysfunction in individuals with obesity, we investigated the effects of Rhodiola on muscle dysfunction as exercise pills. SIRT1 might suppress atrogenes expression and improve mitochondrial quality control, which could be a therapeutic target stimulated by exercise and Rhodiola, but further mechanisms remain unclear. We verified the lipid metabolism disorders and skeletal muscle dysfunction in HFD feeding mice. Moreover, exercise and Rhodiola were used to intervene mice with a HFD. Our results showed that exercise and Rhodiola prevented muscle atrophy and dysfunction in obese mice and activating the SIRT1 pathway, while atrogenes were suppressed and mitochondrial quality control was improved. EX-527, SIRT1 inhibitor, was used to validate the essential role of SIRT1 in salidroside benefit.” According to the news editors, the research concluded: “Results of cell culture experiment showed that salidroside alleviated high palmitate-induced atrophy and mitochondrial quality control impairments, but these improvements of salidroside were inhibited by EX-527 in C2C12 myotubes. Overall, Rhodiola mimics exercise that activates SIRT1 signaling leading to improvement of HFD-induced muscle dysfunction.”     Prenatal exposure to pesticides increases the risk of obesity in adolescence First study to analyse the long-term effects of persistent organic pollutants on cardiometabolic risk in adolescents Barcelona Institute for Global Health (Spain), May 3, 2021 Exposure before birth to persistent organic pollutants (POPs)-- organochlorine pesticides, industrial chemicals, etc.--may increase the risk in adolescence of metabolic disorders, such as obesity and high blood pressure. This was the main conclusion of a study by the Barcelona Institute for Global Health (ISGlobal), a research centre supported by the "la Caixa" Foundation. The study was based on data from nearly 400 children living in Menorca, who were followed from before birth until they reached 18 years of age.  POPs are toxic, degradation-resistant chemicals that persist in the environment. Examples of such compounds are pesticides and organochlorine insecticides (DDT, etc.). POPs have adverse effects on both human health and the environment and their use is regulated globally. Prenatal exposure to these substances has been associated with cardiometabolic risk factors in childhood, but there were previously no studies assessing whether such associations continue into adolescence, a developmental stage characterised by significant changes in the endocrine system and rapid increases in body mass. The aim of this investigation, carried out within the framework of the INMA Project-Environment and Childhood, was to study the associations between prenatal exposure to POPs and body mass index (BMI) as well as other markers of cardiovascular risk in adolescence. Data from 379 children in Menorca was analysed. POP levels were measured in umbilical cord blood samples and the children were then seen periodically between the ages of 4 and 18 years. At these visits, BMI, body fat percentage and blood pressure were recorded as they grew. When the child reached 14 years of age, the scientists measured blood biomarkers of cardiometabolic risk (cholesterol, triglycerides, glucose, etc.). The results of this study, published in the journal Environment International, suggest an association between prenatal POP exposure and a higher BMI in adolescence, particularly in the case of the fungicide hexachlorobenzene (HCB) and the insecticide compound dichloro-diphenyl-trichloroethane (DDT).  Exposure to these two organochlorides--HCB and DDT¬--was also associated with higher blood pressure in childhood and adolescence and increased cardiometabolic risk at 14 years of age.  ISGlobal researcher Núria Güil-Oumrait, the first author of the study, explains that "this is the first longitudinal study to analyse the relationship between persistent organic pollutants and cardiometabolic risk throughout childhood and adolescence. Our findings show that the association between these substances and infant BMI does persist into adolescence and that prenatal exposures are associated with the main risk factors for metabolic syndrome in adults, a condition that today affects one in four people worldwide. With respect to the mechanisms that might explain this association, Güil-Oumrait points out that "it is thought that POPs may interact with hormone receptors or with the generation of free radicals, and the chief problem is that these pollutants accumulate in the fatty tissues of living organisms, where they can persist for years, even decades".  Martine Vrijheid, study coordinator and head of the Childhood and Environment Programme at ISGlobal, highlights the fact that "some of these substances could be considered endocrine disruptors, that is, chemicals that interfere with hormonal regulation". In her view "more studies are needed in this field, especially focussing on childhood and adolescence, which are critical developmental stages characterised by particular vulnerability".     One cup of leafy green vegetables a day lowers risk of heart disease Research has found that by eating just one cup of nitrate-rich vegetables each day people can significantly reduce their risk of heart disease. Edith Cowan University (Australia), May 4, 2021 New Edith Cowan University (ECU) research has found that by eating just one cup of nitrate-rich vegetables each day people can significantly reduce their risk of heart disease. The study investigated whether people who regularly ate higher quantities of nitrate-rich vegetables, such as leafy greens and beetroot, had lower blood pressure, and it also examined whether these same people were less likely to be diagnosed with heart disease many years later. Cardiovascular diseases are the number one cause of death globally, taking around 17.9 million lives each year. Researchers examined data from over 50,000 people residing in Denmark taking part in the Danish Diet, Cancer, and Health Study over a 23-year period. They found that people who consumed the most nitrate-rich vegetables had about a 2.5 mmHg lower systolic blood pressure and between 12 to 26 percent lower risk of heart disease. Lead researcher Dr Catherine Bondonno from ECU's Institute for Nutrition Research said identifying diets to prevent heart disease was a priority. "Our results have shown that by simply eating one cup of raw (or half a cup of cooked) nitrate-rich vegetables each day, people may be able to significantly reduce their risk of cardiovascular disease," Dr Bondonno said. "The greatest reduction in risk was for peripheral artery disease (26 percent), a type of heart disease characterised by the narrowing of blood vessels of the legs, however we also found people had a lower risk of heart attacks, strokes and heart failure."  Forget the supplements The study found that the optimum amount of nitrate-rich vegetables was one cup a day and eating more than that didn't seem to give any additional benefits. "People don't need to be taking supplements to boost their nitrate levels because the study showed that one cup of leafy green vegetables each day is enough to reap the benefits for heart disease," Dr Bondonno said. "We did not see further benefits in people who ate higher levels of nitrate rich vegetables." Smoothies are ok Dr Bondonno said hacks such as including a cup of spinach in a banana or berry smoothie might be an easy way to top up our daily leafy greens. "Blending leafy greens is fine, but don't juice them. Juicing vegetables removes the pulp and fibre," Dr Bondonno said. The paper "Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study" is published in the European Journal of Epidemiology. It is a collaboration between Edith Cowan University, the Danish Cancer Society and The University of Western Australia. The research adds to growing evidence linking vegetables generally and leafy greens specifically with improved cardiovascular health and muscle strength. This evidence includes two recent ECU studies exploring cruciferous vegetables and blood vessel health and green leafy vegetables and muscle strength.     Mindfulness programs can boost children's mental health   University of Derby (UK), May 4, 2021 Mindfulness programs can improve the mental health of school-age children and help them to feel more optimistic, according to new research from the University of Derby and Derbyshire Educational Psychology Service. More than 1,000 pupils aged between 9-12 years old across 25 schools in Derbyshire, received one 45-minute mindfulness session per week for nine weeks during the year-long project, which involved a collaboration between Dr. William Van Gordon, Associate Professor in Contemplative Psychology at the University, and Derbyshire Educational Psychology Service. Mindfulness is an ancient meditation technique that involves focussing awareness on the present moment, as a means of fostering calm, wellbeing and insight. The weekly sessions involved activities such as practicing mindful breathing and paying attention to bodily sensations, as well as exercises intended to help cultivate attention skills and a greater awareness of emotions. The impact of the sessions, which were delivered by teachers in a traditional classroom environment, was evaluated by comparing psychological assessments that the children completed before the classes began, with assessments undertaken after the program had concluded. Part of the evaluation measured children's emotional resiliency using The Resiliency Scale for Children, while wellbeing was rated using the Stirling Children's Wellbeing Scale. Overall, the study found a significant improvement in positive emotional state, outlook and resiliency. There was also an increase in the different dimensions of resilience: optimism increased by 10%, tolerance was improved by 8% and self-efficacy, how a child feels they can cope with a situation based on the skills they have and the circumstances they face, improved by 11%. Professor Van Gordon said: "Findings from the study indicate that mindfulness delivered by school teachers can improve wellbeing and resiliency in children and young people. "This is consistent with wider evidence demonstrating the positive impact of mindfulness on school children's levels of emotional resiliency, emotional stability, wellbeing and stress. "These findings are also in line with the view that preventative interventions given at a young age can help to reduce the incidence of mental health problems in young people."   Vitamin D levels higher in exercisers Johns Hopkins University, May 01 2021  The issue of the Journal of Clinical Endocrinology & Metabolism published the finding of researchers at Johns Hopkins University of a correlation between increased physical activity and higher levels of vitamin D. Higher levels of vitamin D and exercise was also associated with a lower risk of cardiovascular disease. The study included 10,342 men and women who were free of coronary heart disease and heart failure upon enrollment in the Atherosclerosis Risk in Communities study. Physical activity levels were assessed during follow-up visits that took place over a 19.3-year period. Stored serum samples obtained at the second visit were analyzed for 25-hydroxyvitamin D3. Subjects who achieved American Heart Association recommended physical activity levels had average levels of vitamin D that were higher than those who had intermediate and poor levels of activity. Following adjustment for lifestyle and other factors, those who met the recommended levels had a 31% lower risk of being deficient in vitamin D than those with poor activity levels. Subjects in the recommended activity group with levels of vitamin D of 30 ng/mL or more had a 24% lower risk of cardiovascular disease. The association between exercise and vitamin D was stronger in subjects of European ethnicity than among African Americans. The authors noted that European-Americans as well as those who engage in exercise are likelier to be supplement users. “We did find that vitamin D supplement use was higher among those with increased physical activity,” they observed. "In our study, both failure to meet the recommended physical activity levels and having vitamin D deficiency were very common" stated coauthor Erin Michos, MD, MS, of Johns Hopkins University School of Medicine. "The bottom line is we need to encourage people to move more in the name of heart health."     One teaspoon daily of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial  Hayashibara Co. Ltd (Japan), April 24, 2021 Background Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. Methods This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. Results There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. Conclusions Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal.     Coffee compound enhances autophagy to protect against cell injury Chengdu University of Traditional Chinese Medicine (China), April 30, 2021 According to news reporting originating from Sichuan, People’s Republic of China, research stated, “Autophagy serves an important role in amyloid-beta (A beta) metabolism and tau processing and clearance in Alzheimer’s disease. The progression of A beta plaque accumulation and hyperphosphorylation of tau proteins are enhanced by oxidative stress.” Our news editors obtained a quote from the research from the Chengdu University of Traditional Chinese Medicine, “A hydrogen peroxide (H2O2) injury cell model was established using SH-SY5Y cells. Cells were randomly divided into normal, H2O2 and chlorogenic acid (5-caffeoylquinic acid; CGA) groups. The influence of CGA on cell viability was evaluated using a Cell Counting Kit-8 assay and cell death was assessed using Hoechst 33342 nuclear staining. Autophagy induction and fusion of autophagic vacuoles assays were performed using monodansylcadaverine staining. Additionally, SH-SY5Y cells expressing Ad-mCherry-green fluorescent protein-LC3B were established to detect autophagic flow. LysoTracker Red staining was used to evaluate lysosome function and LysoSensor ™ Green staining assays were used to assess lysosomal acidification. The results demonstrated that CGA decreased the apoptosis rate, increased cell viability and improved cell morphology in H2O2-treated SH-SY5Y cells. Furthermore, CGA alleviated the accumulation of autophagic vacuoles, reduced the LC3BII/I ratio and decreased P62 levels, resulting in increased autophagic flux. Additionally, CGA upregulated lysosome acidity and increased the expression levels of cathepsin D. Importantly, these effects of CGA on H2O2-treated SH-SY5Y cells were mediated via the mTOR-transcription factor EB signaling pathway.” According to the news editors, the research concluded: “These results indicated that CGA protected cells against H2O2-induced oxidative damage via the upregulation of autophagosomes, which promoted autophagocytic degradation and increased autophagic flux.” This research has been peer-reviewed.

Sufficient vitamin D during gestation and early life can lower susceptibility to allergy in infants Wageningen University (Netherlands), April 5, 2021   According to news originating from Wageningen, Netherlands, the research stated, “Worldwide, the prevalence of allergies in young children, but also vitamin D deficiency during pregnancy and in newborns is rising. Vitamin D modulates the development and activity of the immune system and a low vitamin D status during pregnancy and in early life might be associated with an increased risk to develop an allergy during early childhood.” Our news editors obtained a quote from the research from Wageningen University and Research: “This review studies the effects of vitamin D during gestation and early life, on allergy susceptibility in infants. The bioactive form of vitamin D, 1,25(OH)2D, inhibits maturation and results in immature dendritic cells that cause a decreased differentiation of naive T cells into effector T cells. Nevertheless, the development of regulatory T cells and the production of interleukin-10 was increased. Consequently, a more tolerogenic immune response developed against antigens. Secondly, binding of 1,25(OH)2D to epithelial cells induces the expression of tight junction proteins resulting in enhanced epithelial barrier function. Thirdly, 1,25(OH)2D increased the expression of anti-microbial peptides by epithelial cells that also promoted the defense mechanism against pathogens, by preventing an invasive penetration of pathogens.” According to the news editors, the research concluded: “Immune intervention by vitamin D supplementation can mitigate the disease burden from asthma and allergy. In conclusion, our review indicates that a sufficient vitamin D status during gestation and early life can lower the susceptibility to develop an allergy in infants although there remains a need for more causal evidence.”   Training in compassion improves the well-being of relatives to people with mental illness Aarhus University (Denmark), April 7, 2021 If relatives of people with mental illness become better at accepting the difficult emotions and life events they experience - which is what training in compassion is about - their anxiety, depression and stress is reduced. These are the results of a new study from the Danish Center for Mindfulness at Aarhus University. Being a relative of a person with a mental illness can be very burdensome. It can feel like a great responsibility, and many people struggle with feelings of fear, guilt, shame and anger. A new study from the Danish Center for Mindfulness shows that eight weeks of training in compassion can significantly improve the well-being of relatives.  Compassion is a human quality that is anchored in the recognition of and desire to relieve suffering. In other words, compassion occurs when we come into contact with our own or others' suffering and feel motivated to relieve our own or others pain. "After completing the course, the relatives had increased their well-being on several parameters. They could deal with the illness in a new and more skillful way, and we saw that the training reduced their symptoms of depression, anxiety and stress," says psychologist and PhD student Nanja Holland Hansen, who is behind the study. And the positive results were maintained after a six month follow-up.  Trying to fix what is difficult "The relatives learned that the more they turn towards what is difficult, the more skillful they may act. For example, relatives often try to 'fix' the problem or the challenge - so as to relieve their loved ones of what is difficult. That's a huge pressure to constantly deal with, and very few people can bear it," says Nanja Holland Hansen.  Living with chronic fear She goes on to explain that training in compassion helps people to find the strength and courage to bear pain and suffering when life is difficult. It may seem both sensible and intuitive to guard yourself from the confrontation or avoid what is difficult and unpleasant. But this is the paradox of the training, explains the researcher. Because it is precisely actions and thoughts like these that shut down our compassion and thereby maintain the suffering.  "Fear and grief are emotions that take up a lot space for relatives of people with mental illness. For example chronic fear, which is a real fear that parents of a child with schizophrenia have about whether their child is going to commit suicide, or whether a child with autism will ever enjoy a 'normal life'," explains Nanja Holland Hansen and continues: "Our suffering is maintained inside of us when we don't work with it. To avoid feeling pain, we may resort to behaviour such as working too much or buying things that we don't need. It's therefore in all these everyday actions that our compassion training becomes important and can be used to help alleviate what is difficult," she says. No one escapes The purpose of training in compassion is thus more than just feeling empathy or worrying about another person.  "Not a single person can completely avoid experiencing painful things in their life. In this way we're all the same. But what isn't the same for everyone is our ability to deal with the pain and suffering we experience. Training programmes in compassion have been developed because the research shows that we can train and strengthen our mental health. With systematic training of compassion, we generate more attention - and understanding of - our own thoughts, feelings and behaviour. And this helps us to develop the tools and skills to engage in healthier relations with ourselves and others," she explains.  A total of 161 relatives of people with mental illness participated in the study. This makes the study one of the largest of its kind in the world, and also the first scientific randomised clinical trial carried out with relatives in Denmark. The relatives were between 18 and 75 of age and were family members to people with various psychiatric disorders such as e.g. ADHD, schizophrenia and depression.  Meditation as homework The relatives met once a week in groups of twenty participants over an eight-week period. Each session lasted two hours and was structured with small group exercises, large group discussions, instruction in the theme of the week and meditation. The homework consisted of twenty minutes of daily meditation. "There is definitely a shortage of offers for these relatives. They're often told that they should remember to take care of themselves, but they haven't learned how to. We found that those who were involved in the study received the tools for precisely this," says Nanja Holland Hansen. The results have just been published in the scientific journal JAMA. "My hope is that local authorities and regions can offer this type of intervention for relatives. It should be an option and could easily be incorporated into our healthcare system. Economically and socially, a healthy person going on sick leave solely because he or she is a relative is a huge loss," says the researcher. [Billedtekst:]: "Up to fifty percent of relatives of people with mental illness risk becoming ill themselves. That's why it's important that we also keep them and their well-being in mind," says Nanja Holland Hansen.   Sesaminol prevents Parkinson's disease by activating the Nrf2-ARE signaling pathway Osaka City University (Japan), March 331, 2021   Parkinson's disease (PD) is a neurodegenerative disease caused by the degeneration of substantia nigra neurons due to oxidative stress. Sesaminol has strong antioxidant and anti-cancer effects. We investigated the preventive effect on PD as a new physiological action of sesaminol produced from sesaminol glycoside using in vitro and in vivo PD models. To prepare an in vitro PD model, 6-hydroxydopamine (6-OHDA) was added to human neuroblastoma (SH-SY5Y cells). The viability of SH-SY5Y cells decreased dose-dependently following 6-OHDA treatment, but the addition of sesaminol restored viability to the control level. 6-OHDA increased intracellular reactive oxygen species production, and the addition of sesaminol significantly suppressed this increase. No Nrf2 expression in the nucleus was observed in the control group, but a slight increase was observed in the 6-OHDA group. The sesaminol group showed strong expression of Nrf2 in the cytoplasm and nucleus. NAD(P)H: quinone oxidoreductase (NQO1) activity was enhanced in the 6-OHDA group and further enhanced in the sesaminol group. Furthermore, the neurotoxine rotenone was orally administrated to mice to prepare an in vivo PD model. The motor function of rotenone-treated mice was shorter than that of the control group, but a small amount of sesaminol restored it to the control level. The intestinal motility in the rotenone group was significantly lower than that in the control group, but it remained at the control level in the sesaminol group. The expression of α-synuclein in the substantia nigra increased in the rotenone group but decreased in the sesaminol group. The rotenone group exhibited shortening and damage to the colonic mucosa, but these abnormalities of the colonic mucosa were scarcely observed in the sesaminol group. These results suggest that sesaminol has a preventative effect on PD.     Study finds connection between lifestyle choices, Alzheimer disease Brigham Young University, April 8, 2021   A recent study out of BYU has linked lifestyle choice to Alzheimer's disease, at least to some degree, through findings that show a possible energy gap between the amount of glucose and ketones being used to power the brain. BYU professor Ben Bikman, who studies diabetes and insulin resistance, thought of a fundamental question surrounding Alzheimer's disease and insulin resistance in the brain. Bikman said there has been growing evidence that the brains in humans with Alzheimer's disease are deficient in the use of glucose. "The brain has a certain energy demand, let's say that is 100%," Bikman said. "In most instances, glucose is providing virtually all of that energy, nearly 100% all of the time. There is a secondary fuel known as ketones, so the average brain is consuming almost all of its energy from glucose with a little bit of energy coming from ketones at any moment. In some individuals, the brain starts to become deficient in its ability to use glucose. So now glucose can only provide about 60% of that energy, and then ketones would be expected to fill up the rest of that energy. The tragedy is that the average individual has almost undetectable levels of ketones and that's entirely a matter of lifestyle." This lack of ketones as well as the brain's resistance to insulin is linked to lifestyle. Insulin is expected to stimulate tissues or cells to take in the glucose and use it for energy. As the brain becomes more insulin resistant, it can't take in glucose anymore and this is something Bikman said has been shown in other research. The BYU research expanded on some of those findings. "We found that indeed the expression of genes involved in glucose metabolism was significantly down, very broad across every cell type we looked at in the brain," Bikman said. "All of the cell types we looked at had significant reductions in glucose-related genes, but the ketone-related genes were almost totally normal." This is key because it shows that if the brain can receive more ketones, there is a possibility that one could overcome that energy gap. While it may not be able to be filled in with glucose, it can be with ketones but ketones need to be produced by one's body. With many people having diets that are high in refined sugars and starches, insulin is elevated all of the time, and ketones are only produced when insulin levels are low. These conditions include fasting or low-carb diets, also known as keto diets. Ph.D. student Erin Saito is another one of the lead authors of the study and is doing this project as her dissertation. Another collaborator included Washington University of Saint Louis, which gave the BYU research team access to various brain banks. "BYU is a wonderfully collaborative environment, not only encouraging collaborations within the university but also outside of the university," Bikman said. "Thus communicating with our internal and external collaborators was very easy and very natural. There was very much a common interest to work on this project together, a common enthusiasm for answering a question that had not been asked yet. It would not have been possible without that mutual collaboration and enthusiasm." He added that managing the project with enthusiastic students was a delight, making it easy because of the enthusiasm surrounding the project. Bikman said it is gratifying for him to be able to contribute to what little is known about Alzheimer's disease, because traditional strategies and approaches have continued to fail. "Looking at Alzheimer's disease as a metabolic problem, I would say, is the greatest breakthrough in our understanding of the disease in decades," Bikman said. Looking at it through the metabolic side of things allows people to possibly detect the problem years in advance, looking at changes in brain glucose metabolism long before Alzheimer's sets in. Bikman believes that someday the metabolic approach to Alzheimer's will be the standard of care. Moving forward, Bikman said he hopes that people feel empowered when it comes to Alzheimer's disease. He wants people to not look at it as a passive process where they are the victim, but rather acknowledging that their lifestyle choices can either act as the culprit or the cure. "For too long we have viewed Alzheimer's disease as a disease that is no respecter of person, no respecter of choices and that is simply not true," Bikman said. "We have long known that people with metabolic disorders, like type 2 diabetes and insulin resistance, are at significantly greater risk of developing Alzheimer's disease and we have more evidence suggesting that dietary choices and changes do make significant improvements in someone's cognition." Even someone in the midst of Alzheimer's disease can see improvements in memory and learning with a lifestyle change, according to Bikman, and he added that he hopes this evidence will help to strengthen that view and empower individuals to take matters into their own hands.     New Study Shows Broad Benefits Of High-CBD Cannabis Health Canada Research Institute, April 6, 2021 With CBD exploding in popularity, new studies continue to reveal its potential benefits. A new study published in the journal Aging-US reported that high-CBD cannabis has anti-inflammatory and anti-cancer properties and may even help reduce COVID symptoms. Cannabidiol, or CBD, is a non-psychoactive compound in cannabis and is legal in all 50 states. “Cannabis sativa, especially those high in the anti-inflammatory cannabinoid cannabidiol, has been found to alter gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties,” the researchers at Health Canada concluded. As such, they say specific CBD extracts “may become a useful and safe addition to the prevention/treatment of COVID-19 as an adjunct therapy.” Researchers hypothesized that high-CBD C. sativa extracts may be used to down-regulate ACE2 expression in target COVID-19 tissues. Using artificial 3D human models of oral, airway and intestinal tissues, they identified 13 high-CBD C. sativa extracts that decrease ACE2 protein levels. Some C. sativa extracts down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV-2 entry into host cells. This is not the first study to suggest that CBD could combat respiratory illnesses like COVID. In April 2020, researchers at the University of Nebraska and the Texas Biomedical Research Institute published a peer-reviewed article suggesting that CBD could be included in the treatment regimen for the COVID-19 coronavirus as THC and CBD both appeared to reduce the severe lung inflammation associated with the virus. In July 2020, researchers at the Dental College of Georgia and Medical College of Georgia found early evidence that Cannabidiol, or CBD, may help reduce the cytokine storm and excessive lung inflammation that killed many patients with COVID-19. “Our laboratory studies indicate pure CBD can help the lungs recover from the overwhelming inflammation, or cytokine storm, caused by the COVID-19 virus, and restore healthier oxygen levels in the body,” says co-author Dr. Jack Yu, physician-scientist and chief of pediatric plastic surgery at MCG. In October 2020, the same research group published a follow-up peer-reviewed study identifying the mechanism they believe was responsible for the encouraging results of using CBD to reduce lung inflammation. “One way CBD appears to reduce the “cytokine storm” that damages the lungs and kills many patients with COVID-19 is by enabling an increase in levels of a natural peptide called apelin, which is known to reduce inflammation and whose levels are dramatically reduced in the face of this storm,” they concluded. While this is incredibly encouraging news for relief from COVID, businesses that sell CBD edibles and oils are not allowed to mention these benefits in advertising because the FDA has not officially approved it for any specific treatment. Apparently, experimental vaccines are okay to advertise but natural plant extracts aren’t. The new study above is just another to suggest cannabis and CBD can help fight cancer. There have been many studies as well as countless confirmed anecdotal accounts. In 2018, a 44-year-old UK mom refused chemo for her aggressive triple-negative breast cancer. She opted for CBD oil instead and was declared cancer-free five months later. In 2019, an 81-year-old diagnosed with lung cancer shrunk his tumors in half by taking CBD oil. The case study was published in the peer-reviewed journal Sage. More recently, a Colorado State University study showed that CBD extract can slow growth and kill cancer cells in aggressive brain cancer. “Our experiments showed that CBD slows cancer cell growth and is toxic to both canine and human glioblastoma cell lines,” said Chase Gross, a doctoral student participating in the study. “Importantly, the differences in anti-cancer affects between CBD isolate and extract appear to be negligible.” That’s not all, CBD has shown potential for treating a variety of other ailments such as arthritis, seizures, chronic pain, high blood pressure, Alzheimer’s and more – with little to no severe side effects that are common with leading pharmaceuticals. Big Pharma hopes more people don’t discover natural treatments to common health issues, like CBD, because it could severely impact their profits and influence.     Polyphenol pills counter inflammation in women on hormonal contraceptives: RCT Universidade Federal do Rio Grande do Sul (Brazil), April 7, 2021 Supplements containing a mixture of polyphenols may counter increases in pro-inflammatory markers in women of childbearing age using combined hormonal contraceptives, says a new study. The supplements, formulated with resveratrol, catechin, quercetin, chlorogenic acid and cyanidin, were also found to prevent the increases in markers of systemic oxidative stress like F2-isoprostane, according to findings published in Prostaglandins, Leukotrienes and Essential Fatty Acids . “The increase in biomarkers of inflammation and oxidative stress observed in the present study were possibly caused by the use of hormonal contraceptives, as verified in the [control group], and this change was not observed in the group that used polyphenols,” wrote researchers from the Institute of Cardiology and the Universidade Federal do Rio Grande do Sul in Brazil. “Therefore, the results of this polyphenol supplementation showed that the antioxidant and anti-inflammatory effects observed in the studied population is due to the reduction in plasma levels of PGE2, supporting the conceptual hypothesis, by its action on the inflammatory cascade, probably by COX inhibition.”   Study details The Brazil-based researchers recruited 40 women aged between 25 and 35 using contraceptives, and randomly assigned them to receive either placebo or polyphenols (3,000 mg per day) for 15 days. “A higher dosage was chosen in order to reduce the risk of food ingestion of control group to overcome the dosage of polyphenol supplementation in the [polyphenol group],” they explained. Data from the 28 women who completed the study indicated that, as expected, markers of inflammation (PGE2 and C-reactive protein) and oxidative stress (F2-isoprostane) increased significantly in women in the placebo group. However, no such increases were observed in the polyphenol group. “Among participants of the polyphenols group, an inverse correlation was observed between the consumption of polyphenols estimated by the [food frequency questionnaire] with PGE2 levels at the end of the study. This finding had not yet been previously described in the literature and reinforces the hypothesis of the present study regarding the action of polyphenols in reducing PGE2 levels,” wrote the researchers. “The liver is the main organ involved in the metabolism of polyphenols, and metabolites are secreted in bile and urine. Excretion of polyphenols in participants of the [polyphenol group] was significantly higher than in the [control group], confirming the effective ingestion of capsules and absorption of compounds, which can vary depending on the amount ingested, the chemical structure of the substance and the intestinal flora of the subjects.”   Childhood diet and exercise creates healthier, less anxious adults University of California Riverside, April 9, 2021 Exercise and a healthy diet in childhood leads to adults with bigger brains and lower levels of anxiety, according to new UC Riverside research in mice.  Though diet and exercise are consistently recommended as ways to promote health, this study is the first to examine the long-lasting, combined effects of both factors when they are experienced early in life. "Any time you go to the doctor with concerns about your weight, almost without fail, they recommend you exercise and eat less," said study lead and UCR physiology doctoral student Marcell Cadney. "That's why it's surprising most studies only look at diet or exercise separately. In this study, we wanted to include both." The researchers determined that early-life exercise generally reduced anxious behaviors in adults. It also led to an increase in adult muscle and brain mass. When fed "Western" style diets high in fat and sugar, the mice not only became fatter, but also grew into adults that preferred unhealthy foods. These findings have recently been published in the journal Physiology and Behavior. To obtain them, the researchers divided the young mice into four groups -- those with access to exercise, those without access, those fed a standard, healthy diet and those who ate a Western diet.  Mice started on their diets immediately after weaning, and continued on them for three weeks, until they reached sexual maturity. After an additional eight weeks of "washout," during which all mice were housed without wheels and on the healthy diet, the researchers did behavioral analysis, measured aerobic capacity, and levels of several different hormones. One of those they measured, leptin, is produced by fat cells. It helps control body weight by increasing energy expenditure and signaling that less food is required. Early-life exercise increased adult leptin levels as well as fat mass in adult mice, regardless of the diet they ate. Previously, the research team found that eating too much fat and sugar as a child can alter the microbiome for life, even if they later eat healthier. Going forward, the team plans to investigate whether fat or sugar is more responsible for the negative effects they measured in Western-diet-fed mice. Together, both studies offer critical opportunities for health interventions in childhood habits.  "Our findings may be relevant for understanding the potential effects of activity reductions and dietary changes associated with obesity," said UCR evolutionary physiologist Theodore Garland.  In other words, getting a jump start on health in the early years of life is extremely important, and interventions may be even more critical in the wake of the pandemic.  "During the COVID-19 lockdowns, particularly in the early months, kids got very little exercise. For many without access to a park or a backyard, school was their only source of physical activity," Cadney said. "It is important we find solutions for these kids, possibly including extra attention as they grow into adults."  Given that exercise was also shown to reduce adult anxiety, Cadney believes children who face these challenges may face unique physical and mental health issues as they become adults in the coming decade.

Lion’s mane mushroom helps reduce depression and anxiety Tohoku University (Japan), March 21, 2021 Several studies have shown the potential of lion’s mane mushroom to help address several health problems including those that are related to brain function. Lion’s mane mushroom (Hericium erinaceus), also known as hedgehog mushroom, is a mushroom native to North America, Asia and Europe. Its fruiting bodies are said to contain polysaccharides that are beneficial to the human body. This mushroom has a long history of medical uses, especially in Traditional Chinese Medicine (TCM) where it was used to help support brain health. In recent years, its value in supporting cognitive health has been supported by a number of studies. The mushroom helps Reduce depression and anxiety In a study published in the journal Biomedical Research, the mushroom was tested on female participants in order to tests its effects on mental health. After taking lion’s mane mushroom cookies for four weeks, the participants reported reduced depression and anxiety. According to the researchers, this was due to two chemical constituents isolated from lion’s mane’s fruiting body called hericenones and erinacines. These two chemicals stimulate nerve growth factor (NGF) biosynthesis. NGF takes part in a number of activities in the body that are essential in maintaining and organizing neurons. By stimulating NGF biosynthesis, lion’s mane is able to help improve mental health. Meanwhile, in a study on mice, researchers from Tohoku University  in Japan discovered that lion’s mane mushroom may be used to prevent cognitive dysfunction. The Japanese researchers administered 10 micrograms of amyloid-beta peptide to the mice on days seven and 14 in their 23-day experimental period. Also, the mice subjects were fed with food containing lion’s mane mushroom over the course of the experimental period. To measure the results of their study, the team used Y-maze and the novel object recognition tests on the subjects. They discovered that the mushroom prevented the negative effects of amyloid-beta peptide on the spatial short-term and visual recognition memory of the mice. The study suggests that the mushroom might reverse even the effects of amyloid-beta peptide – a protein believed to cause Alzheimer’s disease. Lion’s mane for cognitive impairment Moreover, in another study conducted by Japanese scientists, lion’s mane mushroom showed potential in improving symptoms of mild cognitive impairment. This is the stage between aging-related cognitive decline and the development of dementia. Its symptoms include problems with memory, language, thinking or judgment. The team took 30 patients with mild cognitive impairment and gave them 250mg tablets with 96 percent lion’s mane extract to be taken in four pieces for three times a day for 16 weeks. During weeks eight, 12 and 16, the patients underwent observation wherein they showed improvement in their cognitive function as displayed by the increase of their scores on the cognitive function scale. Moreover, the researchers conducted laboratory tests on the patients and saw that the intake of lion’s mane did not result in any side effect. In addition, the patients’ scores in the cognitive function scale decreased by the time their intake of lion’s mane mushroom tablets stopped.       Quercetin-3-o-glucuronide alleviates cognitive deficit in mouse model of Alzheimer disease Hua-zhong University of Science & Technology (China), March 22, 2021   According to news reporting from Wuhan, People’s Republic of China, research stated, “Scope Alzheimer’s disease (AD) is characterized by amyloid-beta (A beta) related imbalance, Tau-hyperphosphorylation, and neuroinflammation, in which A beta and neuroinflammation can induce brain insulin resistance (IR). Gut microbiome disorder is correlated with inflammation in AD.” The news correspondents obtained a quote from the research from the Huazhong University of Science and Technology, “As of yet, there are no effective treatments clinically. Thus, it is focused on the potential benefit of quercetin-3-O-glucuronide (Q3G), a pharmacologically active flavonol glucuronide, on AD treatment by regulating brain IR and the gut microbiome. AD mice model built through intracerebroventricular injection of A beta(1-42) and AD cell model developed through the SH-SY5Y cell line and A beta(1-42) are used to explore the protective effects of Q3G on AD. Neurobehavioral test, brain insulin signaling pathway, and high-throughput pyrosequencing of 16S rRNA are assessed. Data show that Q3G attenuates neuroinflammation and brain IR in A beta(1-42)-injected mice and relieves apoptosis in A beta(1-42)-treated SH-SY5Y cells by interrupting the downstream insulin signaling. Q3G ameliorates A beta accumulation and Tau phosphorylation, restores CREB and BDNF levels in the hippocampus , and reverses A beta(1-42)-induced cognitive impairment. Besides, Q3G restores A beta(1-42)-induced reduction of short-chain fatty acids (SCFAs) and gut microbiota dysbiosis.” According to the news reporters, the research concluded: “Q3G can alleviate brain IR through directly acting on the brain or modulating the gut-brain axis, ultimately to relieve A beta(1-42)-induced cognitive dysfunction.” This research has been peer-reviewed.     Research shows possible link between number of fast-food outlets and heart attacks Hunter Medical Research Institute & University of Newcastle (UK), March 17, 2021  Researchers from the Hunter Medical Research Institute (HMRI), the University of Newcastle and Hunter New England Health (HNE Health) have found that for each new fast-food outlet the number of heart attacks per 100,000 people went up by four. Published in the latest edition of the Internal Medicine Journal the study aimed to determine whether the number of fast-foodoutlets in an area could be considered an environmental risk factor for Myocardial Infarction (heart attack). The team led by Dr. Tarunpreet Saluja from the University of Newcastle, compared all cases of Myocardial Infarction within the Hunter-New England Health District with the Fast-Food Outlet Density (FFD) of each Local Government Area within the district.  "Heart attack is one of the leading causes of death worldwide" said Dr. Saluja, "However, recent data suggests that an increasing number of heart attacks cannot be explained by known risk factors." "There is a well-established link between fast food consumption and cardiovascular diseases such as heart attack. This highlights the need to explore the role of food availability in the probability of having a heart attack." The team found that FFD was positively correlated with an increase of myocardial infarction, even after accounting for other factors such as age, obesity, hyperlipidaemia (high cholesterol), hypertension (high blood pressure), smoking status, diabetes, and socioeconomic status.  Study co-author and cardiologist at John Hunter Hospital, Professor Andrew Boyle said that while it has been known for some time that consuming fast food was bad for the heart no one had determined whether the number of stores was itself a predicting factor.  "Until now there has been very little data on the link between fast-food outlet density and heart attacks, so these results should provide an important consideration for future public‐health policy and community development," said Professor Boyle.  Study co-author and Associate Director of HMRI's Data Science Group, Dr. Christopher Oldmeadow, said that developing a new metric to calculate fast-food outlet density was key to the study and there was scope to expand the data to look at more outlets in the future.  "For this study, we focused on the 10 most popular fast-food outlets in Australia and used census data to determine the density per 100,000 people in each local government area," Dr. Oldmeadow said. "This worked for the majority of the LGAs, but there is scope to investigate the relationship between smaller, locally operated fast‐food outlets and heart attacks."   Vitamin B6 may help calm cytokine storms in COVID-19 University of Hiroshima (Japan), March 14, 2021 Vitamin B6 may help calm cytokine storms and unclog blood clots linked to novel coronavirus (COVID-19) lethality, according to a new study published in the journal Frontiers in Nutrition. In the paper, researchers from Hiroshima University pointed out growing evidence showing that vitamin B6 exerts a protective effect against chronic illnesses such as cardiovascular diseases and diabetes by suppressing inflammation, inflammasomes, oxidative stress, and carbonyl stress. Coronaviruses and influenza are among the viruses that can cause lethal lung injuries and death from acute respiratory distress syndrome worldwide. Viral infections evoke a “cytokine storm,” leading to lung capillary endothelial cell inflammation, neutrophil infiltration, and increased oxidative stress, the researchers said. The researchers said thrombosis or blood clotting and cytokine storm or hyper-inflammation might be closely linked to the graveness of COVID-19. Cytokine storms happen when the immune system dangerously goes into overdrive and starts attacking even the healthy cells. Meanwhile, blood clots linked to COVID-19 can block capillaries, damaging vital organs like the heart, lungs, liver, and kidneys, according to the study. Vitamin B6 is a known anti-thrombosis and anti-inflammation nutrient. Deficiency in this vitamin is also associated with lower immune function and higher susceptibility to viral infections. Studies have so far explored the benefits of vitamins D and C and minerals like zinc and magnesium in fortifying immune response against COVID-19. Research on vitamin B6 has been limited, the researchers said. The researchers said they hope the paper will show vitamin B6's potential in lowering the odds of patients becoming seriously ill with the coronavirus, and prompt further research. "It is of great interest to examine if vitamin B6 exerts protection against novel types of virus infection and pneumonia which will be encountered in the future,” said Thanutchaporn Kumrungsee, PhD, lead author of the paper, in a statement. “At present, there is few information regarding the protective role of nutrients against pneumonia and lung diseases.” Vitamin B6 has a close relationship with the immune system, she said. Its levels always drop in people under chronic inflammation such as obesity, diabetes, and heart diseases. “We can see from the news that obese and diabetic people are at high risk for COVID-19, said Kumrungsee. “Thus, our attempt in this paper is to shed light on the possible involvement of vitamin B6 in decreasing the severity of COVID-19.     Green space or light at night: How we can improve health University of Adelaide (Australia), March 18, 2021 There is a growing body of evidence that exposure to green space is good for our health but a new study from the University of Adelaide has found that this may equally be due to how much light we are exposed to at night. Spending time in green space can improve depressive symptoms, obesity, and sleep problems, and reduce the risk of breast and prostate cancer. Conversely, exposure to light at night, particularly urban light pollution, increases the risk of breast and prostate cancer, and can worsen depression, obesity and sleep problems.  Researchers identified a negative correlation between green space diversity and outdoor artificial light at night for Australian major cities—in other words, the greener your environment, the less the light pollution, and vice versa.  This makes intuitive sense, because the more developed an area is, the fewer trees there will be and the more lights there will be.  Published in Environmental Research, the study questions whether the health benefits of green space exposure may in part be a result of avoiding light at night.  "There seems to be a pattern here—yet, amazingly, no one has put these two things together—until now,"' said lead author Dr. Jessica Stanhope from the University of Adelaide's School of Allied Health Science and Practice.  "It is possible that these factors have been confounding each other in epidemiological studies of the associations between residential green spaces and improved health, and urban outdoor artificial light at night exposure and poor health.  "We have shown that green space is inversely associated with outdoor artificial light at night, making it unclear whether health outcomes result from the green space, the light at night, or possibly in an interaction of the two."  Researchers recommend that epidemiological studies focus on resolving this problem as a priority, so that recommendations can be made for interventions that would improve the public health. For example, to improve population health, is it more important to plant green space in urban areas to give people in cities better green space exposure, or is it better to invest that effort in reducing urban light pollution, or both?  "Some great studies have been done on the association between green space and health, which is a rapidly growing research area; and there are also very neat epidemiological studies of the adverse health effects of exposure to light at night," said Dr. Stanhope.  "It is now really important that future studies include both factors so that we can better understand their association—only then can we make better public health recommendations about planning health-giving sustainable urban landscapes."   Supplements may protect those with low vitamin D levels from severe COVID-19 Albert Einstein College of Medicine, March 20, 2021 Patients with low vitamin D levels who are hospitalized for COVID-19 may have a lower risk of dying or requiring mechanical ventilation if they receive vitamin D supplementation of at least 1,000 units weekly, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting. "Given how common vitamin D deficiency is in the world and the United States, we believe that this research is highly relevant right now," said co-author Sweta Chekuri, M.D., of Montefiore Health System and Albert Einstein College of Medicine in the Bronx, New York.  Research has shown that vitamin D supplementation can prevent inflammation in other respiratory diseases, but there have been limited studies examining the role of vitamin D supplementation in COVID-19. The purpose of the study was to determine whether being supplemented with vitamin D before being admitted to the hospital with COVID-19 resulted in less severe COVID-19 disease in patients with a low vitamin D level. The researchers studied 124 adult patients with low vitamin D that was measured up to 90 days before their admission for COVID-19. They compared the patients who were supplemented with at least 1,000 units of vitamin D weekly to those who had not received vitamin D supplements in terms of whether they were mechanically ventilated or died during admission. They found that patients who were supplemented were less likely to be mechanically ventilated or to die following admission, though the finding wasn't statistically significant (37.5 percent of patients who were not supplemented vs. 33.3 percent of those who were) They also found that more than half of those who should have been supplemented were not.  "Though we weren't able to show a definitive link to severe COVID-19, it is clear that patients with low vitamin D should receive supplementation not only for bone health, but also for stronger protection against severe COVID-19," said co-author Corinne Levitus, D.O., of Montefiore Health System and Albert Einstein College of Medicine. "We hope this research will encourage clinicians to discuss adding this supplement with their patients who have low vitamin D, as this may reduce the odds of people developing severe COVID-19." A study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism last fall found over 80 percent of 200 COVID-19 patients in a hospital in Spain had vitamin D deficiency.     Study finds changes in gut microbiome connected to Alzheimer-like behavior Oregon Health & Science University, March 19, 2021 New research in mice published in the journal Scientific Reports strengthens the growing scientific consensus regarding the role of the gut microbiome in neurodegenerative disorders including Alzheimer’s disease. The study, led by researchers at Oregon Health & Science University, found a correlation between the composition of the gut microbiome and the behavioral and cognitive performance of mice carrying genes associated with Alzheimer’s. The mice carried the human amyloid precursor protein gene with dominant Alzheimer’s mutations generated by scientists in Japan. The study further suggests a relationship between microbes in the digestive tract and the expression of genes that trigger Alzheimer-like symptoms in mice. “You know the expression, ‘You are what you eat?’” said senior author Jacob Raber, Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. “This may be part of that. While all mice were fed the same diet, the gut microbiome is affected in a genotype-dependent fashion and this in turn might affect your brain.” The findings are the first to demonstrate a direct connection between the gut microbiome and cognitive and behavioral changes in an Alzheimer’s disease animal model, and they are consistent with a recently published observational study in people newly diagnosed with Alzheimer’s. In fact, a U.S. clinical trial for the treatment of mild to moderate Alzheimer’s disease is currently underway involving a compound that targets microbes in the gut. The research published breaks new ground. In addition to the cognitive and behavioral changes that were measured, the study is the first to demonstrate a relationship between changes in the gut microbiome and epigenetic changes in neural tissue in the hippocampus, an area of the brain affected in Alzheimer’s. This type of research is not possible in people. The microbiome is a complex assemblage of microorganisms such as bacteria that play a critical role in a wide range of functions in the body. In this case, researchers wanted to see if the gut microbiome affected cognitive and behavioral measures in specially bred mice at 6 months of age. So they compared wild-type mice with those genetically engineered to carry the human amyloid precursor protein gene with dominant Alzheimer’s mutations. They found changes in the gut microbiome - measured in fecal pellets - corresponded with epigenetic regulation of the apolipoprotein E and Tomm40 genes, both associated with Alzheimer’s. They found a clear correlation, but they still can’t say whether one causes the other. “Microbes may elicit an impact on behavioral and cognitive measures relevant to Alzheimer’s disease via epigenetic changes in the hippocampus,” Raber said. “Or, alternatively, it might be that the epigenetic changes in the hippocampus affect changes in the gut microbiome.” The next phase of research will determine whether it’s possible to reduce Alzheimer’s-like symptoms in genetically predisposed mice by altering their diet. “The exciting part of this is that you can manipulate the gut microbiome,” Raber said. “We can use probiotics and see what the effect is.”

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.19.389841v1?rss=1 Authors: Solana-Manrique, C., Sanz, F. J., Munoz-Soriano, V., Paricio, N. Abstract: DJ-1 is a causative gene for familial Parkinson's disease (PD) with different functions, standing out its role against oxidative stress (OS). Accordingly, PD model flies harboring a mutation in the DJ-[beta] gene (the Drosophila ortholog of human DJ-1) show high levels of OS markers like protein carbonylation, a common post-translational modification that may alter protein function. To increase our understanding of PD pathogenesis as well as to discover potential therapeutic targets for pharmacological intervention, we performed a redox proteomic assay in DJ-[beta] mutant flies. Among the proteins that showed increased carbonylation levels in PD model flies, we found SERCA, an endoplasmic reticulum Ca2+ channel that plays an important role in Ca2+ homeostasis. Several studies have supported the involvement of Ca2+ dyshomeostasis in PD. Interestingly, a functional link between DJ-1 and Ca2+ homeostasis maintenance was previously reported. Thus, we decided to study the relation between SERCA activity and PD physiopathology. Our results showed that SERCA enzymatic activity is significantly reduced in DJ-[beta] mutant flies, probably as a consequence of OS-induced carbonylation, as well as in a human cell PD model based on DJ-1-deficiency. Indeed, higher carbonylation levels of SERCA were also observed in DJ-1-deficient SH-SY5Y neuron-like cells compared to controls. In addition, we demonstrated that SERCA activity was increased in both PD models after treatment with a specific activator of this protein, CDN1163. Consistently, CDN1163 was also able to restore PD-related phenotypes in PD model flies and to increase viability in the human cell PD model. Taken together, our results indicate that impaired SERCA activity in both familial PD models may play a role in PD physiopathology. In addition, we demonstrate that therapeutic strategies addressing SERCA activation could be beneficial to treat this disease as shown for CDN1163. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.16.384248v1?rss=1 Authors: Ball, S. R., Adamson, J. S., Sullivan, M. A., Zimmermann, M. R., Lo, V., Sanz-Hernandez, M., Jiang, F., Kwan, A. H., Werry, E. L., Knowles, T. P., Kassiou, M., Meisl, G., Todd, M. H., Rutledge, P. R., Sunde, M. Abstract: The amyloid-{beta} peptide, the main protein component of amyloid plaques in Alzheimer's disease, plays a key role in the neurotoxicity associated with the condition through the formation of small toxic oligomer species which mediate the disruption of calcium and glutamate homeostasis. The lack of therapeutic benefit associated with removal of mature amyloid-{beta} fibrils has focused attention on the toxic oligomeric species formed during the process of fibril assembly. Here, we present the design and synthesis of a family of perphenazine-macrocyle conjugates. We find that two-armed perphenazine-cyclam conjugates divert the monomeric form of the amyloid-{beta} peptide away from the amyloidogenic pathway into amorphous aggregates that are not toxic to differentiated SH-SY5Y cells in vitro. This strategy prevents the formation of damaging amyloid oligomers. Kinetic analysis of the effects of these compounds on the assembly pathway, together with NMR spectroscopy, identifies rapid monomer sequestration as the underlying neuroprotective mechanism. The ability to specifically target the monomeric form of amyloid-{beta} allows for further understanding of the impact of the multiple species formed between peptide biogenesis and plaque deposition. The modular, three-dimensional structure of these compounds provides a starting point for the design of more potent modulators of this amyloid-forming peptide, and can be adapted to probe the protein self-assembly pathways associated with other proteinopathies. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.20.347146v1?rss=1 Authors: Shrestha, J., Santerre, M., Allen, C. N., Arjona, S. P., Mukerjee, R., Park, J., Bagashev, A., Wang, Y., Kaul, M., Chin, J., Sawaya, B. E. Abstract: HIV-associated neurocognitive disorders (HAND) remains an unsolved problem in the clinical management of HIV-1 carriers, because existing anti-retroviral therapy while suppressing viral replication, do not prevent neurocognitive impairment (e.g. spatial memory loss). HIV-1 gp120 protein has been proposed to contribute to HAND because it is shed by infected cells and the use of antibodies revealed its presence in cerebrospinal fluid (CSF) even in the combinatory antiretroviral therapy (cART) era. The cyclic AMP response element-binding protein (CREB) has long been known to be a star player in memory. CREB exerts its effect partially through regulating the genes for peroxisome proliferator-activated receptor gamma coactivator (PGC)-1a and brain-derived neurotrophic factor (BDNF). CREB, PGC-1a, and BDNF levels are low in the brains of patients with neurodegenerative diseases and a dearth of either protein is associated with cognitive decline. We have obtained data showing that gp120 contributes to neurodegeneration by altering CREB phosphorylation on serine residue 133 thus disrupting mitochondrial movement and synaptic plasticity leading to spatial memory loss. Inhibition of CREB function was also associated with a decrease of ATP levels and lower mitochondrial DNA copy numbers. Our data was validated in vitro (primary mouse neurons and neuronal cell line, SH-SY5Y) and in vivo (gp120-tg mice and mice injected with gp120). The negative effect of gp120 was alleviated in cells and animals in the presence of Rolipram. Hence, we conclude that HIV-1 gp120 protein contributes to spatial memory impairment via inhibition of CREB protein activity. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.24.265157v1?rss=1 Authors: Costa, R. T. d., Santos, M. B. d., Silva, I. C. S., Almeida, R. P. d., Teruel, M. S., Carrettiero, D. C., Ribeiro, C. A. J. Abstract: Methylmalonic acidemia is a rare metabolic disorder characterized by the accumulation of methylmalonic acid (MMA) and alternatives metabolites which is caused by the deficient activity of L-methylmalonyl-CoA mutase or its cofactor 5-deoxyadenosylcobalamin (AdoCbl). The brain is one of the affected tissues by the accumulation of this metabolite in patients. The neurologic symptoms commonly appear in newborns and are clinically characterized by seizures, mental retardation, psychomotor abnormalities, and coma. The molecular mechanisms of neuropathogenesis in methylmalonic acidemia are still poorly understood, specifically regarding the impairments in neuronal development and maturation. In this study, we firstly investigated the neurotoxicity of MMA in both undifferentiated and 7-day RA-differentiated phenotypes of SH-SY5Y human neuroblastoma cells and found alterations in energetic homeostasis after the exposition to MMA. We observed an increase in glucose consumption and reduced respiratory parameters of both undifferentiated and differentiated SH-SY5Y cells after 48 hours of exposition to MMA. RA-differentiated cells slightly indicated to be more prone to perturbations in respiratory parameters by MMA than undifferentiated cells. In order to understand whether the presence of MMA during neuronal maturation could compromise this process in neuronal cells, we performed high-resolution respirometry to evaluate the mitochondria function and qPCR assay to evaluate mRNA levels of mature neuronal-specific genes in early-stage (day 3), and late-stage (day 7) of differentiation in cells co-treated with MMA 1mM during RA mediated differentiation. Our results showed that MMA compromises the respiratory parameters of routine, ATP-linked, and maximal respiration only at the late stage of differentiation as well as downregulates the transcriptional gene profile of mature neuronal markers ENO2 and SYP. Altogether, our finds point to important alterations observed during neuronal maturation and energetic stress vulnerability that can play a role in the neurological clinical symptoms at the newborn period and reveal important molecular mechanisms that could help the screening of targets to new approaches in the therapies of this disease. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.19.257295v1?rss=1 Authors: Thomson, A. C., de Graaf, T. A., Schuhmann, T., Kenis, G., Sack, A. T., Rutten, B. P. F. Abstract: Repetitive Transcranial Magnetic Stimulation (rTMS) is an established neuromodulation technique, using electromagnetic pulses that, depending on the precise parameters, are assumed to lead to lasting neural excitability changes. rTMS has widespread applications in both research and therapy, where it has been FDA approved and is considered a first-line treatment for depression, according to recent North American and European guidelines. However, these assumed excitability effects are often difficult to replicate, and highly unreliable on the single subject/patient level. Given the increasing application of rTMS, especially in clinical practice, the absence of a method to unequivocally determine effects of rTMS on human neuronal excitability is problematic. We have taken a first step in addressing this bottleneck, by administering excitatory and inhibitory rTMS protocols, iTBS and cTBS, to a human in vitro neuron model; differentiated SH-SY5Y cells. We use live calcium imaging to assess changes in neural activity following stimulation, through quantifying fluorescence response to chemical depolarization. We found that iTBS and cTBS have opposite effects on fluorescence response; with iTBS increasing and cTBS decreasing response to chemical depolarization. Our results are promising, as they provide a clear demonstration of rTMS after-effects in a living human neuron model. We here present an in-vitro live calcium imaging setup that can be further applied to more complex human neuron models, for developing and evaluating subject/patient-specific brain stimulation protocols. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.16.206094v1?rss=1 Authors: Goksu Erol, A. Y., Akinci, E., Kocanci, F. G., Akcakale, F., Demir Dora, D., Uysal, H. Abstract: Introduction: Microglia secretome includes not only growth factors and cytokines which support neuronal survival, it includes neurotoxic cytokines/enzymes, as well. MPTP is a neurotoxin which has degenerative effects on SH-SY5Y neuroblastoma cells. Masitinib mesylate is a tyrosine kinase inhibitor which has been shown to have beneficial effects in neurodegenerative diseases. Aim : We first aimed to determine the most efficient microglial cell conditioned medium in terms of neurodegenerative effect. Next, we investigated the possible protective/therapeutic effects of masitinib against MPTP/microglia-induced degeneration of differentiated ( d )-SH-SY5Y cells, and the role of transforming growth factor (TGF)-b1 and nitric oxide (NO) in these events. Material-Methods : Non-stimulated/LPS-stimulated microglia cells were treated with masitinib or its solvent, DMSO. With or without MPTP- d -SH-SY5Y cell cultures were exposed to the conditioned media (CM) from microglia cell cultures, followed by cell survival analysis. Immunofluorescence staining of microglia and d -SH-SY5Y cells were performed with anti-CD-11b and anti-PGP9.5 antibody, respectively. TGF-b1/NO concentrations in CM of microglia/ d -SH-SY5Y cell culture were measured. Results: The initial 24 hrs CM of non-stimulated microglia cell culture was found to be the most detrimental microglial medium with lowest survival rates of treated d -SH-SY5Y cells. The toxicity of 48 and 72 hrs CM on d -SH-SY5Y cells were both lower than that of 24 hrs CM. Masitinib (0.5 {micro}M), significantly prevented MPTP-related cell degeneration of d -SH-SY5Y cells. It also decreased the degenerative effects of both non-induced/LPS-induced microglia CM on with or without MPTP- d -SH-SY5Y cells. Although NO levels in microglia CM showed a negative correlation with survival rates of treated d -SH-SY5Y cells, a positive correlation was seen between TGF-{beta}1 concentrations in microglial CM and rates of treated d -SH-SY5Y cell survival. Conclusion : Masitinib ameliorates viability of with/without MPTP- d -SH-SY5Y cells. It does not only reverse the degenerative effects of its solvent, DMSO, but also prevents the degenerative effects of microglial secretions and MPTP. We suggest that masitinib begins to act as a neuroprotective agent via mediating TGF-b1 and NO secretion, as neurons are exposed to over-activated microglia or neurotoxins. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.26.173526v1?rss=1 Authors: Bell, M., Bachmann, S., Klimek, J., Langerscheidt, F., Zempel, H. Abstract: Somatodendritic missorting of the axonal protein TAU is a hallmark of Alzheimer's disease and related tauopathies. Cultured rodent primary neurons and iPSC-derived neurons are often used for studying mechanisms of neuronal polarity, including TAU trafficking. However, these models are expensive, time-consuming and/or re-quire the sacrification of animals. In this study, we show that neurons derived from SH-SY5Y neuroblastoma cells, generated with a RA/BDNF-based differentiation procedure, are suitable for investigating axonal TAU sorting. These SH-SY5Y-derived neurons show pronounced neuronal polarity, axodendritic outgrowth, ex-pression of the neuronal maturation markers TAU and MAP2, and, importantly, effi-cient axonal sorting of endogenous and transfected human wild type TAU. By using SH-SY5Y-derived neurons and mouse primary neurons, we demonstrate that axon-al TAU enrichment requires the presence of the TAU C-terminal half, as a truncated C-terminus-lacking construct (N-term-TAUHA) is localized in the soma, where it ac-cumulates. Moreover, SH-SY5Y-derived neurons do not show classical axon initial segment (AIS) formation, indicated by the lack of Ankyrin G (ANKG) enrichment at the proximal axon, which suggests that successful axonal TAU sorting is independ-ent of complete AIS formation. Taken together, our results suggest i) that SH-SY5Y-derived neurons are a valuable human neuronal model for studying TAU sorting, which is readily accessible at low cost and without animal need, and that ii) the mechanisms of axonal TAU targeting require the TAU C-terminal half but no ANKG enrichment at the proximal axon. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.16.154757v1?rss=1 Authors: Bachmann, S., Bell, M., Klimek, J., Zempel, H. Abstract: In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3 and 10 of the MAPT gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick's Disease and Progressive Supranuclear Palsy, are characterized by the accumulation of specific TAU isoforms. Many studies focused on the role of TAU in these diseases, however only few addressed isoform-specific functions of TAU in healthy and under pathological conditions. In this report, we investigated the subcellular localization of the human-specific TAU isoforms in primary mouse neurons. Our results show that 2N-TAU isoforms are particularly retained from axonal sorting and that axonal enrichment is independent from the number of repeat domains. Furthermore, we analyzed TAU isoform-specific effects on cell area and microtubule dynamics in SH-SY5Y neuroblastoma cells and observed a general reduction of cell size and an increase of microtubule counts in cells expressing 4R-TAU isoforms. Our study points out TAU isoform-specific effects that will be addressed in follow-up studies to unravel if and how TAU isoforms contribute to cellular functions in health and disease. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.12.149062v1?rss=1 Authors: da Rocha, J. F., Bastos, L., Domingues, S. C., Bento, A. R., Konietzko, U., da Cruz e Silva, O. A. B., Vieira, S. I. Abstract: The amyloid precursor protein (APP) is a transmembrane glycoprotein central to Alzheimer's disease (AD) with functions in brain development and plasticity, including in neurogenesis and neurite outgrowth. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) are well described neurotrophic and neuromodulator EGFR ligands, both implicated in neurological disorders like Schizophrenia and AD. Here we show that APP interacts with these two EGFR ligands and characterize the effects of APP-EGF interaction in ERK activation and neuritogenesis. HB-EGF was identified as a novel APP interactor in a yeast two-hybrid screen of a human brain cDNA library. Yeast co-transformation and co-immunoprecipitation assays confirmed APP interaction with HB-EGF. Moreover, co-immunoprecipitation also revealed that APP binds to cellular pro-EGF. Overexpression of HB-EGF in HeLa cells, or exposure of SH-SY5Y cells to EGF, both resulted in increased APP protein levels. EGF and APP were also observed to synergistically activate the ERK signaling pathway, crucial for early neuronal differentiation. Immunofluorescence analysis of cellular neuritogenesis in conditions of APP overexpression and EGF exposure, confirmed a synergistic effect in promoting the number and the mean length of neurite-like processes per cell. Synergistic ERK activation and neuritogenic effects were completely blocked by the EGFR inhibitor PD 168393, implying EGF-induced activation of EGFR as part of the mechanism. This work shows novel APP protein interactors and provides a major insight into the APP-driven mechanisms underlying neurite outgrowth and neuronal differentiation, with potential relevance for AD and for adult neuroregeneration. Copy rights belong to original authors. Visit the link for more info

Cell line contamination, coffee Smarties, confirmation bias, and the Southampton Six.  Plus fire alarms, SH-SY5Y cells, cat woo, and hurling Caramacs.  Growing like stink, it’s Skeptics with a K.

The processing of APP occurs in two alternative ways: upon release of the ectodomain by α-secretase, the neuroprotective APPsα-fragment is produced. But if APP is cleaved by the β-secretase the Aβ-peptide can be produced. To be able to influence the production of Aβ-peptides, it is essential to understand how it is decided if cleavage occurs by α- or β-secretase. At present little is known about the control of the alternate processing. Until now, the molecular mechanisms and especially the responsible cellular modulators are not understood in detail or not yet identified. To get a better understanding of cellular regulatory processes and to identify novel cellular modulators of APP ectodomain shedding, the present work chose two approaches: on the one hand cellular mechanisms of TMEM59-mediated inhibition ectodomain shedding of APP were investigated. On the other hand a genome-wide RNAi screening in Drosophila cells was performed in order to identify novel cellular modulators of APP ectodomain shedding in human cells. TMEM59 was identified as a novel modulator of APP ectodomain shedding in a cDNA expression screening in the lab (Neumann et al., 2006; Schobel et al., 2008; Schobel et al., 2006). TMEM59 is a Golgi protein that inhibits on the one hand processing and maturation of APP and on the other hand Golgi glycosylation reactions (Fischer, 2008). My own work could verify these effects of TMEM59 and its homolog TMEM59L on processing and maturation of APP. In particular, it was shown that these effects are not only true for transiently expressed APP but also for endogenous levels of APP. In detailed immunofluorescence studies it was shown that TMEM59 colocalizes with different markers of the Golgi subcompartments and that therefore TMEM59 is present throughout the whole Golgi apparatus. This finding points to a more general modulation of Golgi glycosylation reactions by TMEM59. To test if TMEM59-dependet modulation of Golgi glycosylation reactions also affects APP secretases ADAM10 and BACE1, which are also glycosylated proteins, the activities of these proteases were investigated. It was shown that proteolytic activities were not changed, ruling out that impairment of secretase activities by TMEM59 could cause the observed inhibition of APP processing. But interestingly, studies of intracellular APP transport could show that TMEM59 caused retention of APP in the Golgi apparatus and blockage of transport towards the cell surface and into endosomal compartments. Since APP is cleaved by α-secretase at the plasma membrane and by β-secretase in endosomes it is likely that a TMEM59-dependent APP transport block causes the observed inhibition of APP ectodomain shedding. For further validation of TMEM59 and its homolog TMEM59L as modulators of APP ectodomain shedding, a double knockdown study was performed. In this approach effects on APP ectodomain shedding could also be established, affirming TMEM59 and its homolog TMEM59L as modulators of APP ectodomain shedding with novel cellular mechanisms. In order to identify novel cellular modulators of APP ectodomain shedding a genome wide RNAi screening in Drosophila cells was performed and candidate genes were investigated in human cells in present work. Initially a suitable Drosophila reporter cell line expressing a reporter construct of APP ectodomain shedding (HRP-APP) was established. Other constructs were used to monitor general secretion (GLuc) and transfection efficiency (FLuc). Using Kuzbanian, the α-secretase in Drosophila (Sapir et al., 2005), as a positive control guaranteed that transfection of cDNAs into Drosophila cells did not interfere with uptake of dsRNAs or efficiency of RNAi and that the reporter construct HRP-APP is normally produced and processed in reporter cells. After successful establishment of the reporter cell line the genome wide RNAi was performed in two steps: a primary screening revealed approx. 300 candidate genes out of which 43 could be confirmed in a secondary screening to be modulators of APP ectodomain shedding. The RNAi screening was verified by the several-fold appearance of Kuzbanian among the top modulators. For further investigation of the top candidates human ortholog genes were identified. The 30 human candidate genes were investigated in RNAi studies in human SH-SY5Y cells. In these cells, APP is processed by α-secretase ADAM10 as well as by β-secretase BACE1. Therefore effects on both shedding products (APPsα and APPsβ) were investigated upon depletion of candidate genes using siRNAs. It is known that siRNAs produce a high rate of off target effects, to this end a robust validation strategy was developed. Candidate genes were first depleted with two different siRNA pools and their effects on APP shedding were compared. Afterwards the remaining 12 candidate genes were depleted using single siRNA sequences and the effects were compared to those of the siRNA pool. Only when a reproduction of effects was obtained in a next step correlation of knockdown and phenotype were assessed. Using these steps of validation 5 candidate genes could be verified as modulators of APP shedding in human cells: next to genes coding for a histone protein (HIST1H4C), a ribosomal protein (RPL36AL), a protein of the minor spliceosom (ZMAT5), an unknown gene (METTL16) and the gene VPS24 („vacuolar protein sorting-associated protein 24“), coding for a protein of intracellular protein transport, were identified. VPS24 was chosen for further validation by a pathway analysis. VPS24 belongs to the ESCRT machinery („endosomal sorting complex required for transport“) and therefore participates in endosomal-lysosomal protein transport. In further RNAi studies other members of the ESCRT machinery were depleted in human cells and effects on APP shedding were compared to VPS24 depletion. For most of the ESCRT members a consistent reduction in APPsβ production could be observed. To engross these results VPS24 was depleted by using an alternative RNAi system. With this stable knockdown approach, the knockdown phenotype could be confirmed. This stepwise validation strategy for candidate genes of the initial Drosophila RNAi screening verified VPS24 as a modulator of APP ectodomain shedding in human cells.

Overexpression or mutation of alpha-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human A53T] alpha-Synuclein-induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from A53T] alpha-Synuclein expression. In addition, decreased TRAP1 expression in A53T] alpha-Synuclein-expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued A53T] alpha-Synuclein-induced sensitivity to rotenone treatment. In human (non) neuronal cell lines, small interfering RNA directed against TRAP1 enhanced A53T] alpha-Synuclein-induced sensitivity to oxidative stress treatment. A53T] alpha-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by A53T] alpha-Synuclein overexpression in human SH-SY5Y cells. These results indicate that A53T] alpha-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to alpha-Synuclein.

Regulated intramembrane proteolysis of the amyloid precursor protein (APP) by the protease activities α-, β- and γ-secretase controls the generation of the neurotoxic amyloid β peptide. APLP2, the amyloid precursor-like protein 2, is a homolog of APP, which shows functional overlap with APP, but lacks an amyloid β domain. Compared to APP, less is known about the proteolytic processing of APLP2, in particular in neurons, and the cleavage sites have not yet been determined. APLP2 is cleaved by the β-secretase BACE1 and additionally by an α-secretase activity. The two metalloproteases ADAM10 and ADAM17 have been suggested as candidate APLP2 α-secretases in cell lines. Here, we used RNA interference and found that ADAM10, but not ADAM17, is required for the constitutive α-secretase cleavage of APLP2 in HEK293 and SH-SY5Y cells. Likewise, in primary murine neurons knock-down of ADAM10 suppressed APLP2 α-secretase cleavage. Using mass spectrometry we determined the proteolytic cleavage sites in the APLP2 sequence. ADAM10 was found to cleave APLP2 after arginine 670, whereas BACE1 cleaves after leucine 659. Both cleavage sites are located in close proximity to the membrane. γ-secretase cleavage was found to occur at different peptide bonds between alanine 694 and valine 700, which is close to the N-terminus of the predicted APLP2 transmembrane domain. Determination of the APLP2 cleavage sites enables functional studies of the different APLP2 ectodomain fragments and the production of cleavage-site specific antibodies for APLP2, which may be used for biomarker development.

Background: Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). Several mechanisms have been proposed to explain these findings including increased shedding of the soluble ectodomain of the amyloid precursor protein (sAPP), which functions as a neurotrophic and neuroprotective factor in vitro and in vivo. Objective: To clarify whether NSAIDs consistently stimulate sAPP secretion. Methods: 293-EBNA cells with stable overexpression of an APP-alkaline phosphatase fusion protein (APP-AP), SH-SY5Y and PC12 cells or primary telencephalic chicken neurons were treated with ibuprofen or indomethacin. APP shedding was then determined by measuring AP activity in conditioned media, Western blot analysis with antibodies against total sAPP or specific for sAPP-alpha, or in a pulse-chase paradigm. Results: AP activity in conditioned media was not increased after NSAID treatment of 293-EBNA cells whereas it was elevated by phorbol ester. Surprisingly, ibuprofen or indomethacin treatment of SH-SY5Y and PC12 cells expressing endogenous APP did not cause changes in sAPP or sAPP-alpha secretion or downregulation of cellular APP. These findings were further corroborated in primary chicken neuronal cultures. Conclusions: Using various experimental settings, we were unable to confirm sAPP or sAPP-alpha stimulation with the NSAIDs ibuprofen and indomethacin in transfected and nontransfected cells of neuronal and nonneuronal origin. Importantly, these findings seem to rule out chronic sAPP stimulation as an alternative mechanism of NSAID action in AD. Copyright (C) 2008 S. Karger AG, Basel

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.22.055152v1?rss=1 Authors: Pan, C.-Y., Lin, F.-Y., Kao, L.-S., Huang, C.-C., Liu, P.-S. Abstract: Zinc ions (Zn 2+ ) are important messenger molecules involved in various physiological functions. To maintain the homeostasis of cytosolic Zn 2+ concentration ([Zn 2+ ] c ), Zrt/Irt-related proteins (ZIPs) and Zn 2+ transporters (ZnTs) are the two families of proteins responsible for decreasing and increasing the [Zn 2+ ] c , respectively, by fluxing Zn 2+ across the membranes of the cell and intracellular compartments in opposite directions. Most studies focus on the cytotoxicity incurred by a high concentration of [Zn 2+ ] c and less investigate the [Zn 2+ ] c at physiological levels. Zinc oxide-nanoparticle (ZnO-NP) is blood brain barrier-permeable and elevates the [Zn 2+ ] c to different levels according to the concentrations of ZnO-NP applied. In this study, we mildly elevated the [Zn 2+ ] c by zinc oxide-nanoparticles (ZnO-NP) at concentrations below 1 mg/ml, which had little cytotoxicity, in cultured human neuroblastoma SH-SY5Y cells and characterized the importance of Zn 2+ transporters in 6-hydroxy dopamine (6-OHDA)-induced cell death. The results show that ZnO-NP at low concentrations elevated the [Zn 2+ ] c transiently in 6 hr, then declined gradually to a basal level in 24 hr. Knocking down the expression levels of ZnT 1 (mostly at the plasma membrane) and ZIP 8 (present in endosomes and lysosomes) increased and decreased the ZnO-NP-induced elevation of [Zn 2+ ] c , respectively. ZnO-NP treatment reduced the basal levels of reactive oxygen species and Bax/Bcl-2 mRNA ratios; in addition, ZnO-NP decreased the 6-OHDA-induced ROS production, p53 expression, and cell death. Therefore, mild elevations in [Zn 2+ ] c induced by ZnO-NP activate beneficial effects in reducing the 6-OHDA-induced cytotoxic effects. Therefore, brain-delivery of ZnO-NP can be regarded as a potential therapy for neurological disease. Copy rights belong to original authors. Visit the link for more info