Podcasts about tcf4

Gastroparesis, severe GI side effects, pancreatic cancer risk and more? Is Ozempic worth it? Tune in to hear us discuss recent updates on Ozempic including reports of stomach paralysis, blurred vision, kidney failure and beyond. We'll cover why keto is a safer alternative and how you can level up your keto with focused supplementation.    In this episode we talk about some of the recent news about Ozempic and new revelations about some scary side effects, cover why keto is superior to ozempic, and talk about why berberine has been touted as nature's Ozempic.    Also in this episode: LIVE Food-as-Medicine Ketosis Program What is OzempicNaturally Nourished 323 Ozempic, Wonder Drug or Too Good to be True Side Effects Gastroparesis Digestaid Naturally Nourished Episode 328 Childhood Obesity Fueling Pharma Profits Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial - The Lancet Naturally Nourished Episode 356 Low Fat Keto for Leptin Resistance Keto Vs. OzempicLong-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial Naturally Nourished Episode 262 The Keto-Immune Connection and Natural Immunity Updates | Ali Miller RD Improvement of Glucose Tolerance by Food Factors Having Glucagon-Like Peptide-1 Releasing Activity - PMC Berberine: Is it Nature's Ozempic?Beat the Bloat Bundle Berberine Boost Efficacy and Safety of Berberine Alone for Several Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Clinical Trials Recent updates on GLP-1 agonists: Current advancements & challenges - ScienceDirect Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion The Effect of Berberis Vulgaris Extract on Transaminase Activities in Non-Alcoholic Fatty Liver Disease Safety and efficacy of Berberis integerrima root extract in patients with type 2 diabetes. A parallel intervention based triple blind clinical trial Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway Berberine activates the β-catenin/TCF4 signaling pathway by down-regulating miR-106b to promote GLP-1 production by intestinal L cells Effects of Berberine on the Gastrointestinal Microbiota Probiotic Challenge Keto Essentials Bundle Boost and Burn   Sponsors for this episode:  This episode is sponsored by Peak State Coffee, makers of coffee with real health benefits! Are you a coffee drinker seeking a healthier option but don't want to quit your ritual? Enjoy whole bean coffee infused with adaptogenic mushrooms to boost your brain, support gut health, and balance stress, all while keeping the taste you love. With 500mg lion's mane, reishi, chaga, and more per serving, you'll love this delicious coffee that is also chemical free, mold free, non-GMO, and low acid. Go to www.PeakStateCoffee.com/ALIMILLERRD for 20% off and free shipping on two or more bags, use code ALIMILLERRD at checkout.  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.14.520376v1?rss=1 Authors: Zhao, H., Chen, J., Qi, C., Wang, T., Liang, T., Hao, X., Li, X., Yin, X., Yu, T., Zhang, Y. Abstract: Restoring the normal structure and function of injured tendons is one of the biggest challenges faced by the Department of Orthopedics and Sports Medicine. Tendon-derived stem cells (TDSCs), a new type of pluripotent stem cells with multidirectional differentiation potential, are expected to be promising cell seeds for the treatment of tendon injury and tendon-bone healing in the future. In this study, tendon stem cells were successfully isolated from human tissues, which were positive for markers CD44, CD90, and CD105, and exhibited clonality and multilineage differentiation ability. Analysis of single-cell sequencing results and mass spectrometry identification results showed that there were differences in protein expression during CTGF-induced TDSC tendon differentiation. Reverse Co-IP, qPCR, WB, and immunofluorescence detection all confirmed that CTGF directly interacts with KIT, thereby mediating the transcription factor HES1 to regulate the Wnt/{beta}-catenin signaling pathway (GSK3{beta}, {beta}-catenin, TCF4). ChIP-qPCR and dual-luciferase reporter gene assays indicated that HES1 regulates stem cell differentiation by directly regulating the expression of GSK3{beta} in the Wnt/{beta}-catenin pathway. Rats were treated with TDSCs overexpressing the KIT gene after repair surgery. This method had a more ideal recovery effect than other methods through animal behavioral scores, mechanical properties testing, and HE staining tissue observation. This study found that the use of modified human tendon stem cells (hTDSC) could promote graft ligamentization and tendon-bone healing after ACL reconstruction, which could provide an effective way for faster and better recovery from tendon injury. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Alysson Muotri discusses modeling Pitt-Hopkins syndrome (PTHS) using stem cells and brain organoids. He shares how rescuing TCF4 expression with CRISPR-mediated epigenetic induction of AAV vector delivery provides a gateway for targeted therapeutics for PTHS and related conditions. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38516]

Strategies to replace or compensate for mutated copies of the TCF4 gene could lead to treatments for this profound form of autism, a new study suggests. The post Organoids test gene therapies for Pitt-Hopkins syndrome appeared first on Spectrum | Autism Research News.

Strategies to replace or compensate for mutated copies of the TCF4 gene could lead to treatments for this profound form of autism, a new study suggests.

Strategies to replace or compensate for mutated copies of the TCF4 gene could lead to treatments for this profound form of autism, a new study suggests.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.27.175257v1?rss=1 Authors: Komorowski, A., Vidal, R., Singh, A., Murgas, M., Pena-Centeno, T., Gryglewski, G., Kasper, S., Wiltfang, J., Lanzenberger, R., Goya-Maldonado, R. Abstract: The exploration of the relationship between gene expression profiles and neural response patterns known to be altered in major depressive disorder provides a unique opportunity to identify novel targets for diagnosis and therapy. Here, we estimated the spatial association between genome-wide transcriptome maps and brain activation patterns from functional magnetic resonance imaging (fMRI) with two established paradigms of great relevance for mood disorders. While task-specific neural responses during emotion processing were primarily associated with expression patterns of genes involved in cellular transport, reward processing was related to neuronal development, synapse regulation, as well as gene transcription. Multimodal integration of single-site and meta-analytic imaging data with risk genes associated with depression revealed a regional susceptibility of functional activity, modulated by master regulators TCF4 and MEF2C. The identification of multiple subordinate genes correlated with fMRI maps and their corresponding regulators presumably will reshape the prospects for neuroimaging genetics. Copy rights belong to original authors. Visit the link for more info

This week on the On Your Mind Neuroscience Podcast: The hosts are taking the time to look at their respective big pictures this week, with Kat organizing and analyzing her onslaught of data and Liam working on an outline for his thesis. Fortunately, all this computer time has led to some pretty productive procrastination. While perusing Nature Jobs and Science, Kat’s come across an editorial piece highlighting the pervasiveness of “Imposter Syndrome” in science and a fresh perspective on the concept of “research parasites”.  On the other hand, Liam’s been catching up on his Netflix, and a documentary by David Thorpe has his mind tuned to the question of how our voice defines us.  Then it’s onto this week’s article. Published in Neuron, this week’s paper uses in utero gene transfection and electrophysiology to show that TCF4, a gene that’s been linked to neurodevelopmental disorders, regulates neuron excitability in the prefrontal cortex.  This paper, and it’s sometimes counter-intuitive data, raises more questions than it answers for us, but we’re refreshed by its earnestness.   

Markus Gerhard explains how the E3 ubiquitin ligase RNF43 inhibits a transcription factor that mediates Wnt-β-catenin signaling without ubiquitylating it.

Background: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects - for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD. Results: We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, P-empirical = 0.0004) and at chromosome 18 (18q21.2, P-empirical = 0.0005). Conclusions: In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD.

Tue, 18 Sep 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15766/ https://edoc.ub.uni-muenchen.de/15766/1/Daniel_Guillaume.pdf Daniel, Guillaume ddc:570, ddc:500, Fakultät für Biolo

In this work, we were able to take advantage of a deregulated wnt signaling pathway – a condition which is found in most gastrointestinal cancers, in particular in colorectal carcinomas. In order to restrict reporter gene expression to the desired cell type, we utilized the β-catenin dependent CTP4-promoter to restrict the expression of Firefly Luciferase and enhanced green fluorescent fusion protein (EGFPLuc) to cell lines with deregulated wnt signaling including SW480, LS174T, HepG2, Coga2 and Coga12. Stable cell lines containing this CTP4-driven EGFPLuc construct were established with the help of a lentiviral vector to monitor wnt activity by transgene expression. With these stably transduced cell lines, we performed a therapeutic target screen via siRNA-mediated knock-down of a number of potentially therapeutic targets within the wnt pathway – osteoprotegerin (OPG), Traf2 and Nck-interacting kinase (TNIK), SRY-related HMG-box (Sox2), protease-activated receptor 1 (PAR-1), β-catenin and transcription factor 4 (TCF4). The in vitro screening system was utilized as a prevalidation tool for therapeutically relevant targets. The degree of interference of our novel targets was determined and the search for a suitable siRNA target in colorectal cancer cells was narrowed down to β-catenin, PAR-1 and TNIK. As proof of principle the siRNA-mediated knock down of β-catenin was verified on mRNA and protein level in LS174T cells. After the initial read-out of various cell lines with different siRNAs has been established via the reduction of Luciferase expression levels, the biological effect of these targets were validated. For this purpose colony formation and cell motility/invasion assays were conducted for all relevant target cell lines. Furthermore in the in vitro experiments, the tumor-selectivtiy of the CTP4-promoter was employed in the delivery of the cytotoxic protein diphteria toxin A (DTA) in colorectal cancer target cells. Data evaluation of all in vitro assays pointed at reduced levels of proliferation, invasive behavior and aggressiveness, which yielded three candidates (PAR-1, TNIK and β-catenin) considered as viable for a treatment attempt in vivo. In the in vivo experiments, systemic delivery of siRNA against β-catenin, sticky siRNA targeting PAR-1 and plasmid DNA encoding for CTP4 controlled DTA were evaluated in a disseminated liver metastasis model of LS174T colorectal cancer. Specific knock-downs of β-catenin and PAR-1 were achieved which was confirmed via mRNA analysis. As for CTP4-DTA pDNA delivery the overall tumor load of the liver was reduced without any significant systemic toxicity, indicating specific DTA expression in tumor tissue. Also knock down of PAR1 using sticky siRNA significantly reduced tumor growth. All in all, the therapeutic effect of PAR-1 and β-catenin knock-down could be verified in various in vitro assays analyzing invasive behavior and anchorage independent growth and ultimately also in vivo. The tumor-specific expression of DTA pDNA could also be confirmed in vitro and was further investigated in an orthotopic liver dissemination model in NMRI nude mice.

Background: Recently, a role of the transcription factor 4 (TCF4) gene in schizophrenia has been reported in a large genome-wide association study. It has been hypothesized that TCF4 affects normal brain development and TCF4 has been related to different forms of neurodevelopmental disorders. Schizophrenia patients exhibit strong impairments of verbal declarative memory (VDM) functions. Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients. Method: The TCF4 variant was genotyped in 401 schizophrenia patients. VDM functioning was measured using the Rey Auditory Verbal Learning Test (RAVLT). Results: Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype (13.76 vs. 13.06; p = 0.049). Moreover, a trend toward higher scores in patients with the risk allele was found for delayed recall (10.24 vs. 9.41; p = 0.088). The TCF4 genotype did not influence intelligence or RAVLT immediate recall or total verbal learning. Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment. Copyright (C) 2011 S. Karger AG, Basel

Background: Most colorectal carcinomas are driven by an activation of the canonical Wnt signalling pathway, which promotes the expression of multiple target genes mediating proliferation inavasion and invasion. Upon activation of the Wnt signalling pathway its key player beta-catenin translocates from the cytoplasm to the nucleus and binds to members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF-1) family namely LEF-1 and TCF4 which are central mediators of transcription. In this study we investigated the expression of beta-Catenin, LEF1 and TCF4 in colorectal carcinomas and their prognostic significance. Methods: Immunohistochemical analyses of LEF-1, TCF4 and nuclear beta-Catenin were done using a tissue microarray with 214 colorectal cancer specimens. The expression patterns were compared with each other and the results were correlated with clinicopathologic variables and overall survival in univariate and multivariate analysis. Results: LEF-1 expression was found in 56 (26%) and TCF4 expression in 99 (46%) of colorectal carcinomas and both were heterogenously distributed throughout the tumours. Comparing LEF-1, TCF4 and b-catenin expression patterns we found no correlation. In univariate analysis, TCF4 expression turned out to be a negative prognostic factor being associated with shorter overall survival (p = 0.020), whereas LEF-1 expression as well as a LEF-1/TCF4 ratio were positive prognostic factors and correlated with longer overall survival (p = 0.015 respectively p = 0.001). In multivariate analysis, LEF-1 and TCF4 expression were confirmed to be independent predictors of longer respectively shorter overall survival, when considered together with tumour stage, gender and age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4: 2.18; p = 0.014). Conclusions: This study demonstrates different prognostic values of LEF-1 and TCF4 expression in colorectal cancer patients indicating different regulation of these transcription mediators during tumour progression. Moreover both factors may serve as new potential predictive markers in low stage colon cancer cases in advance.

Ziel der Arbeit war die Etablierung RNA Interferenz basierender Systeme zur Senkung der Proteinspiegel von b- und g-Catenin und die darauf aufbauende Evaluierung potentieller b-Catenin Zielgene mittels Microarray Technologie. Der Schwerpunkt sollte dabei auf die Untersuchung von im Wnt-Signalweg beteiligten Genen gelegt werden. Wir konnten in den kolorektalen Karzinomzelllinien SW-480, DLD-1 und HT-29 mehrere voneinander unabhängige siRNA sowohl gegen b- als auch g-Catenin etablieren. Dabei stand neben ausreichender Senkung der Protein- und mRNA-Spiegel auch die Vermeidung unerwünschter Effekte auf die Zellen im Mittelpunkt dieser Etablierungsarbeit. Im Rahmen der vorliegenden Arbeit konnten vier neue funktionale Zelllinien etabliert werden. Sowohl in HT-29 als auch in SW-480 konnte ein universell einsetzbarer TET-Repressor stabil integriert werden. Die Linien HT-29TR und SW-480TR können als Basis für induzierbare Expressionssysteme verwendet werden. Auf Grundlage der Linie SW-480TR konnten Zelllinien etabliert werden, die durch Doxycyclin vermittelte Induktion shRNA gegen b-Catenin exprimieren. Mittels dieser Linien können Effekte, die durch die Senkung der b-Catenin Proteinspiegel hervorgerufen werden, einfach, schnell und zuverlässig in einem breiten Spektrum an in vitro und in vivo Assays untersucht werden. Im Rahmen einer Microarray Analyse des Transkriptoms von SW-480 Zellen nach RNA Interferenz basierter Senkung der b-Catenin Proteinspiegel wurde DKK4 als sehr stark reguliertes Gen auffällig. Mittels RT-PCR konnten wir bestätigen, dass die Expression von DKK4 direkt von den vorliegenden b-Catenin Proteinspiegeln abhängig ist. Basierend auf einer in silico Analyse des DKK4 Promoters wurden mit Hilfe von Reportergen Konstrukten der für die Aktivierbarkeit durch b-Catenin verantwortliche Abschnitt des DKK4 Promoters bestimmt. Wir konnten darstellen, dass die Aktivierung des DKK4 Promotors sowohl von der Präsenz von b-Catenin als auch von TCF4 abhängt. Die Expression von DKK4 bedingt die Gegenwart des aus TCF4 und b-Catenin bestehenden Transaktivierungskomplexes, der für die Aktivierung Wnt-abhängiger Transkription verantwortlich zeichnet. Gleichzeitig stellt der DKK4 Promoter durch die Präsenz von TCF-Bindestellen eine Zielstruktur für diesen Transaktivierungskomplex dar. Unsere Daten belegen, dass DKK4 ein b-Catenin Zielgen darstellt. Wir konnten auflerdem zeigen, dass die Aktivierung Wnt-abhängiger Transkription durch Gabe von rekombinantem DKK4 gehemmt werden kann. Es konnte im Rahmen dieser Arbeit dargestellt werden, dass die Expression des Wnt-Antagonisten DKK4 in einen negativen Feedback Mechanismus, der durch b-Catenin autoreguliert wird, eingebunden ist. Der vermutete Feedback Mechanismus stellt sich wie folgt dar. Wnt-Faktoren aktivieren die Transkription b-Catenin abhangiger Zielgene, darunter auch DKK4. DKK4 initiiert durch Bindung an LRP und Kremen den Abbau von b-Catenin und verhindert somit die weiterführende Transkription von Wnt-b-Catenin Zielgenen. DKK4 übernimmt als autokriner Inhibitor des Wnt-Signalwegs feinregulatorische Aufgaben, um bei moglicher Bedarfsdeckung b-Catenin abhängiger Gentranskription die weitere Aktivierung durch Wnt-Faktoren zu verhindern. Fur den Fall, dass DKK4 als parakriner Inhibitor agiert, wäre es denkbar, dass DKK4 von Zellen im unteren Teil der Krypte, die in hohem Maße durch Wnt-Faktoren aktiviert, werden sezerniert wird, um die darüber liegenden Zellen durch Abschirmung von weiteren Wnt-Signalen vor überschieflender Expression Wnt-b-Catenin abhängiger Gene und Proliferation zu schutzen und die Differenzierung dieser Zellen einzuleiten. Die unkontrollierte Expression von Wnt-b-Catenin Zielgenen nimmt bei der Entstehung kolorektaler Karzinome eine entscheidende Schlüsselposition ein. Zur Etablierung neuer Diagnostik- und Therapieoptionen bedarf es daher auch der stetigen Erweiterung des Verständnisses des Wnt-Signalwegs. Diese Arbeit fügt ein weiteres Rädchen in die komplexe Mechanik dieses Signalwegs ein.