Proteins made and released by host cells in response to the presence of pathogens
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3 episodes with interferons
2 episodes with interferons
2 episodes with interferons
2 episodes with interferons
The Daily Quiz - Science and Nature Today's Questions: Question 1: Interferons are proteins produced by the human body to interfere with the spread of what? Question 2: Which of these marine mammals has 2 tusks? Question 3: From which type of tree do we get hardwood? Question 4: What Is The Worlds Largest Mammal? Question 5: What is the name of the physical law that states that energy is neither created or destroyed? Question 6: What is the word for a group of swans? Question 7: Heroin is the brand name of morphine once marketed by which pharmaceutical company? Question 8: What is a female rabbit known as? Question 9: What is the name of the bird whose scientific name is Phoenicopterus ruber roseus? This podcast is produced by Klassic Studios Learn more about your ad choices. Visit megaphone.fm/adchoices
Bats use proteins to offensively fight disease, keeping these creatures of the night healthy.
On this special episode of the BloodStream Podcast, we explore interferons in the treatment of polycythemia vera (or PV). This episode is brought to you by PharmaEssentia. If you'd like to learn more about polycythemia vera, check out our sister show PV Pod: Stories from the Marrow (brought to you by BloodStream Media and PharmaEssentia). Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook BloodStream on Twitter
Over 100 years ago, an Austrian psychiatrist cured patients of neurosyphilis by infecting them with malaria. The malaria caused a fever that triggered the patients' immune responses against their neurosyphilis. Patients don't necessarily need to suffer fever, though, to stimulate their immune response. The elevation of their body temperature alone can achieve this effect. Which key antiviral protein is mobilized when body temperature is raised? How can this be safely done to combat infections like COVID-19? On Vital Signs with Brendon Fallon, Dr. Roger Seheult highlights past and present methods used to escalate "virus-blocker" interferon proteins in the body. Dr. Seheult worked as a critical care physician in an intensive care setting during the pandemic. He oversaw the use of hydrotherapy to stimulate patients' interferon response against Coronavirus infection. Interferon is “effective against multiple variants, in fact, all the variants of COVID-19 … It's a very broad tool that our body has … to battle foreign invaders, especially viruses,” says Dr. Seheult. Although lacking modern medical technology, American sanitariums still effectively treated patients during the 1918–1920 flu pandemic. What do their methods tell us about how to counter viral infection today? Dr. Seheult is quadruple board-certified in internal medicine, pulmonary diseases, critical care medicine, and sleep medicine. He is an associate clinical professor of medicine at the University of California. ⭕️ Watch in-depth videos based on Truth & Tradition at Epoch TV
Fighting COVID-19 with Heat- Dr. Roger Seheult's Insights on Interferons and Hydrotherapy - EpochTV
TWiV notes the passing of Harald zur Hausen, dengue breaking records in the Americas, inhibition of SARS-CoV-2 infection and inflammation by modulation of type I IFN, and an armed nanobody that protects mice against influenza A and B disease. Hosts: Vincent Racaniello, Kathy Spindler, and Angela Mingarelli Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode MicrobeTV Discord Server MicrobeTV store at Cafepress Position in Rosenfeld Laboratory (pdf) Paul and the Mosquitos (pdf, English) Other childrens books (SMVIROLOGIA) Dengue breaking records in Americas (Nature) Harald zur Hausen, 1936-2023 (Nature) Vincent interviews zur Hausen (ASM) COVID-19 and modulation of IFN (Sci Immunol) Burning down the mouse (TWiV 900) Armed nanobody protects against influenza (Sci Immunol) Click chemistry Nobel prizes (The Nobel Prize) Letters read on TWiV 1033 Timestamps by Jolene. Thanks! Weekly Picks Angela – The Deepest Breath Kathy – Pink snow Vincent – Scientist vs PowerPoint Listener Picks Fernando – The Enigma of Reason by Hugo Mercier and Dan Sperber and Language vs. Reality by Nick Enfield Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv
In this episode, we review the high-yield topic of Interferons from the Microbiology section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message
In this episode of Behind the Breakthrough, Dr. Eleanor Fish dives into her groundbreaking research of treating viruses by harnessing a naturally occurring antiviral protein in our body called Interferons. Dr. Fish, an Emerita Scientist at Toronto General Hospital Research Institute, is a world leading immunology researcher and a passionate about the importance of Interferons in fighting pandemics and virus outbreaks such as COVID-19, SARS, and Ebola.
Interferons are innate immune agents of inflammation and recovery. Mutations or epigenetic modifications associated with advanced aging may corrupt interferon pathway fidelity involving mitophagy leading to autoimmune disease and morbidity later in life. References Nat Immunol. 2021 Mar; 22(3): 312–321 J Neuroinflammation. 2019; 16: 236. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
Many clinical trials are currently investigating the potential benefits of interferons in the treatment of myeloproliferative neoplasms (MPNs), in particular... The post Texas MPN Workshop 2021: updates on interferons for MPNs appeared first on VJHemOnc.
Many clinical trials are currently investigating the potential benefits of interferons in the treatment of myeloproliferative neoplasms (MPNs), in particular... The post Texas MPN Workshop 2021: updates on interferons for MPNs appeared first on VJHemOnc.
In this Buddisode, Dara & Jatin sit down with Adam Fike from Ziaur Rahman's lab at Penn State University. The discussion entails their 2020 publication that teased apart the contribution of Type I and Type II interferons in TLR7-mediated systemic autoimmunity. Check out our memes on Facebook (@antibuddies), Twitter (@antibuddiesP), and Instagram (@AntibuddiesPodcast). Website: Antibuddies – Science Communication & Immunology (Antibuddies.org) Join us on our monthly journal club at our YouTube channel: https://www.youtube.com/channel/UCxyrHotyyY3sSwcp1zigeCw Send us your queries/questions/suggestions at antibuddies1@gmail.com. Article of discussion: Type II but Not Type I IFN Signaling Is Indispensable for TLR7-Promoted Development of Autoreactive B Cells and Systemic Autoimmunity | The Journal of Immunology (jimmunol.org)
As infecções causadas por vírus estão entre as principais causas de mortalidade no mundo. Atualmente, com o aumento dos casos de doentes com covid-19, muito tem se falado sobre a busca de um medicamento antiviral para tratar a doença. No Pílula Farmacêutica desta semana, a acadêmica Kimberly Fuzel fala sobre a classificação dos medicamentos antivirais e como eles atuam. Segundo Kimberly, os medicamentos antivirais são uma classe de medicamentos voltada para tratar doenças causadas por vírus. Ela explica que os vírus são formados por ácidos nucleicos conhecidos por DNA ou RNA, apresentando características diferentes, mas, de modo geral, o material genético deles está envolvido sobre um núcleo composto de proteínas coberto por um capsídeo que também é composto de proteínas. “Os vírus são parasitas intracelulares obrigatórios, ou seja, eles precisam entrar no núcleo das células para aproveitar as vias metabólicas delas e então se reproduzir. Alguns vírus conseguem até mesmo integrar seu DNA ao do hospedeiro, fazendo com que, mesmo depois de tratado, o paciente possa apresentar sintomas da infecção novamente quando é exposto ao vírus, como no caso do herpes, por exemplo.” Classificações dos medicamentos antivirais Dentro da classe de antivirais existem algumas classificações, já que para cada tipo de vírus existe um medicamento antiviral com princípio ativo específico para conseguir eliminar e bloquear suas funções. Os principais fármacos ativos dos medicamentos antivirais são: os inibidores não nucleosídeos da transcriptase reversa, que agem inibindo a enzima transcriptase ao se incorporarem no DNA do vírus e, dessa forma, a tornam defeituosa para a multiplicação. Alguns exemplos são o Efavirenz, a Etravirina e a Nevirapina. Os inibidores nucleosídeos da transcriptase reversa também agem da mesma forma, ou seja, inibindo a enzima transcriptase no DNA do vírus para que ela se torne defeituosa e não se multiplique; alguns exemplos são o Tenofovir, a Estavudina e a Lamivudina, entre outros. “Os inibidores da protease bloqueiam a síntese de proteína do vírus, o que impede que eles amadureçam e se reproduzam em outras células.” Inibidores da DNA-polimerase atuam bloqueando a síntese de DNA do vírus, impedindo o alongamento da sua cadeia, como é o exemplo do Aciclovir, entre outros medicamentos. Os inibidores de fusão do HIV, como o nome já diz, são responsáveis por impedir o vírus HIV de entrar nas células de defesa do organismos e se reproduzir. Outra classe são os fármacos imunomoduladores, que atuam direto no sistema imunológico, ativando a cascata de sinalização que leva à produção de proteínas antivirais, como, por exemplo, a proteinocinase R, interrompendo o mecanismo de tradução nas células infectadas pelo vírus. Os medicamentos mais conhecidos dessa classe são os Interferons e a Imunoglobulina. E, por fim, temos ainda os inibidores da liberação e desmontagem viral, que inibem a ação da enzima neuraminidase do vírus, como, por exemplo, no vírus influenza. Essa enzima é importante para a replicação viral, porque atua no processo de liberação de partículas virais formadas nas células infectadas para depois se reproduzirem em outra célula e, ao bloquear a ação dessa enzima, os vírus não conseguem deixar a célula hospedeira, evitando uma maior disseminação do vírus no organismo. Alguns medicamentos dessa classe são o Zanamivir, a Amantadina, entre outros. Medicamento antiviral e covid-19 Recentemente foi aprovado pela Agência Nacional de Vigilância Sanitária (Anvisa) o uso do medicamento antiviral Remdesivir, sendo este o primeiro medicamento recomendado para o tratamento da covid-19 no Brasil. Após ter seu uso analisado durante meses pela Anvisa, o Remdesivir mostrou potencial para ser um grande aliado no combate ao coronavírus, mas, apesar disso, o medicamento mostrou algumas ressalvas, não podendo ser utilizado por todos. O Remdesivir foi desenvolvido para tratar o ebola e, assim como outros medicamentos antivirais, passou a ser testado para o tratamento da covid-19. Esse medicamento atua diminuindo ou interrompendo a replicação do vírus no organismo. Segundo uma das pesquisas publicadas no New England Journal of Medicine, a recuperação dos pacientes se mostrou mais rápida com o uso do Remdesivir, reduzindo o tempo de uso de suporte de oxigênio e também de hospitalização. Duas semanas depois dessa publicação, a Organização Mundial da Saúde divulgou uma atualização em suas diretrizes contraindicando o uso do medicamento, considerando que ainda não existia uma comprovação científica forte sobre sua eficácia. Mas a indicação do medicamento não se resume à forma leve, moderada ou grave da doença, ela está mais ligada à apresentação de alguns sintomas específicos, como a pneumonia, combinada com a necessidade de oxigênio suplementar, mas sem fazer uso de ventilação mecânica. Ainda segundo a Anvisa, diz Kimberly, esse antiviral só pode ser utilizado em ambiente hospitalar, ou seja, em casos em que o paciente está internado, já que é necessário ter o acompanhamento da equipe médica durante todo o tratamento, que geralmente dura de cinco a dez dias, e por isso a comercialização do mesmo foi restringida. “O Remdesivir é apenas uma forma de auxílio no tratamento para a covid-19, ele pode diminuir a chance do paciente com um caso grave precisar usar o respirador, mas ainda existem muitas incertezas no seu uso e, por isso, está longe de ser uma cura, sendo necessário que a pessoa seja vacinada mesmo depois de ter sido tratada com o medicamento.” Pílula Farmacêutica Apresentação: Kimberly Fuzel e Giovanna Bingre Produção: Professora Regina Célia Garcia de Andrade e Rita Stella Co-produção: Rita Stella Edição geral: Cinderela Caldeira E-mail: ouvinte@usp.br Horário: segunda e quarta, às 10h40 Você pode sintonizar a Rádio USP em São Paulo FM 107,9; ou Ribeirão Preto FM 107.9, ou pela internet em www.jornal.usp.br ou pelo aplicativo no celular para Android e iOS . Veja todos os episódios de Pílula Farmacêutica .
We're back with another apolitical science episode! Dr. Preeyam Patel (PhD in immunology) and Eric follow up their initial episode (8 of this podcast) and the supplemental vaccine talk (of episode 12) to update listeners on how much of the information previously discussed is still accurate (spoiler: it's 100%!) and talk about the latest questions emerging from COVID-19 across the globe. Such as: - We've updated the original sources cited document to include all-new research for today's episode! - What's the difference between a COVID variant, a mutation, and a strain? - has COVID been acknowledged as having aerosol status? - What is the Swiss Cheese Diagram? - How long do antibodies last? - Will COVID variants increasinly get more deadly and worse as time goes on? - What if COVID mutated as fast as influenza / the common flu? - from beach balls to proton packs, Dr. Patel has no trouble explaining heavy concepts to a captive Eric. - We discuss variants B117 and 501.v2, what gives them an edge, and whether they're actually more deadly or infectuous than other COVID. - ONCE you are vaccinated, can you still transmit the virus to others? - What's the deal with COVID reinfection? - We deep dive into the 5 major vaccines getting approval and trials across the globe - a summary of what went wrong with AstraZeneca's trials in the UK - Have scientists found a correlation among severe covid patients. - Why do more MEN die from severe COVID than women? - What are INTERFERONS and who has antibodies to them? - Do we know any more about the long-term effects of COVID? - Final advice It was thrilling having Dr. Patel back on the show. Please let us know if you still have questions about COVID after listening! e-mail the show at thankyouforspieling@gmail.com or @TYFSpiels on Twitter.
Dr. Helen Su, Chief of the Human Immunological Diseases Section at the National Institute of Allergy and Infectious Diseases (part of the NIH) and co-leader of the COVID Human Genetic Effort, joins host Lauren Richardson to discuss the results and implications of the articles "Inborn errors of type I IFN immunity in patients with life-threatening COVID-19" and "Autoantibodies against type I IFNs in patients with life-threatening COVID-19", both published in Science.
This “king of bitters” (so-called because of its flavor) has been used for centuries in Asia to treat gut and upper respiratory infections, fever, herpes, sore throat, and other chronic and infectious disease conditions. However, modern research is demonstrating Andrographis paniculata’s benefits include aiding with joint conditions such as arthritis. ParActin®: A Potent Form of Andrographis Paniculata for Pain Support & More The medicinal herb Andrographis paniculata has been traditionally used for its powerful anti-inflammatory properties and its ability to boost immune system activity. This “king of bitters” (so-called because of its flavor) has been used for centuries in Asia to treat gut and upper respiratory infections, fever, herpes, sore throat, and other chronic and infectious disease conditions [1]. However, modern research is demonstrating Andrographis paniculata’s benefits include aiding with joint conditions such as arthritis and it may even have anti-cancer benefits. Andrographis Goes by Many Names Andrographis is cultivated in many tropical Asian countries including India, China, Malaysia, Indonesia, and Sri Lanka, as well as in the West Indies, Brazil, parts of Africa, and Central America. Known as “chuan-xin-lian” in China, “kalmegh” in India, “senshinren” in Japan, “hempedu bumi” in Malaysia, “fah talai” in Thailand, and “green chiretta” in the Scandinavian countries, Andrographis is listed in the Indian Pharmacopoeia (a publication that lists standards for all drugs that are manufactured, sold, and consumed in India) and in a couple of dozen Ayurvedic formulas [2]. In traditional Chinese medicine (TCM), Andrographis is believed to rid the body of heat (e.g., fevers) and to dispel toxins [3]. Phytochemistry of Andrographis Paniculata Andrographis leaves are mainly responsible for its biological actions. They contain many bioactive compounds, including diterpene lactones – especially Andrographolide, the main bioactive ingredient that imparts the typical bitter taste. Andrographolide is an antioxidant that has been shown to be responsible for the herb’s anti-viral and anti-bacterial properties. Andrographolide is also reported in scientific literature to reduce blood clot formation, help protect the liver, have anti-cancer properties, and manage inflammation within safe levels [4]. What Is ParActin®? ParActin® is a patented extract of A. Paniculata, standardized to a fixed concentration of Andrographolide and other related compounds including 14-deoxyandrographolides and neoandrographolides [5]. Preliminary research shows that ParActin® promotes a healthy inflammatory response by blocking a powerful chemical known as NF-kappa B, which is known to be a key regulator of the inflammatory response system. As a result, ParActin® helps support a healthy and appropriate inflammatory response by reducing the levels of pro-inflammatory compounds that trigger the familiar pain and redness associated with inflammation. The safety and efficacy of ParActin® has been assessed in more than 30 studies, including laboratory experiments on cultured cells and animal models – and even a human clinical trial. Let’s take a closer look at some of these studies and what they tell us about Andrographis and ParActin®. Inflammation Is Linked to Many Disease Conditions Long-term, chronic inflammation that occurs when the immune system goes into overdrive may lie at the root of many otherwise unrelated diseases, including: asthma inflammatory bowel disease (IBD) rheumatoid arthritis (RA) autoimmune diseases depression cancer Alzheimer’s disease Inflammation – which manifests as swelling, redness, heat, and pain – is a normal response of our immune system and our body’s way of defending us from infections and disease. However, if it’s not managed properly, inflammation can harm the body. Chronic inflammation is the result of an overactive immune system that is constantly turned on – or cannot be turned off – so that it attacks parts of the very body it is supposed to protect. So-called oxygenated chemical species – including free radicals, oxygen ions, and peroxides – are continuously made in our body’s cells in response to UV radiation and as byproducts of ongoing metabolic activity. They are highly reactive and dangerous, because they can attack cellular DNA and proteins, damaging them. When oxygenated chemical species are generated in excess, they can overwhelm cellular defense systems, leading to a condition known as oxidative stress along with high levels of inflammation – which, as we discussed earlier, is known to contribute to the development of many diseases. Andrographolide, the best-known bioactive ingredient in Andrographis, has been shown to directly inactivate free radicals. It also protects mitochondria, blocks pro-oxidant enzymes, and activates other antioxidant enzymes in the body [6]. Andrographis Boosts the Immune System Andrographolide has been shown to enhance the immune system. For example, it boosts production of white blood cells known as lymphocytes, which scavenge and destroy bacteria and other foreign matter. It also triggers the release of signaling proteins known as interferons, along with enhancing activity of the lymphatic system [7]. Interferons are made and released by our body’s cells when they get infected with viruses, causing nearby cells to strengthen their anti-viral defenses. Interferons are potent antiviral agents that stop viruses from multiplying. The lymphatic system is another circulatory system in our body that carries a fluid known as lymph, which removes the waste products of cellular metabolism. The lymphatic system also transports invading bacteria and viruses to lymph nodes where the white blood cells (lymphocytes) destroy them. Andrographis has been shown to trigger our immune system in two ways: Antigen-specific response – specific proteins known as antibodies are made to counteract invading bacteria and viruses. Nonspecific immune response – immune cells known as macrophages are produced, which scavenge and destroy invaders. Andrographis activates both responses, meaning it is very effective against a variety of infectious and cancer-causing agents [8]. Benefits for Upper Respiratory Tract Infections & Cough Andrographis has been used for many hundreds of years in traditional medicinal systems to treat upper respiratory infections. Modern research supports this. For example, a 2004 meta-analysis of the results of seven double-blind, controlled trials (with a total of 896 participants) showed that Andrographis offers significant relief from the symptoms of upper respiratory tract infections and may even prevent them from taking hold in the first place. [Note: A meta-analysis is a quantitative epidemiological study used to systematically assess the results of previous research – typically randomized, controlled clinical trials – to derive overall conclusions about that body of research.] All the participants in these seven clinical trials reported reduced fever, runny nose, cough, and sore throat on taking Andrographis relative to control patients. Side effects were described as “generally mild and infrequent” [9]. Similarly, another meta-analysis published in 2015 reviewed six randomized controlled clinical trials, which assessed the effects of Andrographis in the treatment of cough. Combined, these six studies compared 333 patients who took various Andrographis preparations relative to 348 patients in control groups. All of these studies showed that Andrographis preparations reduced cough severity [10]. Andrographis Heals the Gut As mentioned above, Andrographis has long been used in traditional medicinal systems such as Ayurveda and traditional Chinese medicine (TCM) for treating gut infections. In a 2013 study published in the American Journal of Gastroenterology, 224 patients with mild to moderate ulcerative colitis were either given 1200 or 1800 milligrams of Andrographis for 8 weeks. Ulcerative colitis is an inflammatory bowel disease that causes long-lasting inflammation and ulcers in the gut, affecting the innermost lining of the large intestine (colon) and rectum. A colonoscopy was performed before the study started and after it ended. Stool frequency and the presence of blood in the stool were also assessed every two weeks. At the end of the study, 60% of patients who received 1800 mg of Andrographis – relative to 40% of patients in the control group – showed clinical symptoms of healing. Not only that, 50% of the patients who received the 1800 mg of Andrographis also showed mucosal healing, relative to 33% in the control group [11]. Andrographis & Joint Pain from Arthritis Arthritis affects more than 70 million Americans, leading to inflammation, pain, and stiffness in the joints and connective tissues. Over time, cartilage breaks down, bones erode, and joints become misshapen [12]. Our modern understanding is that rheumatoid arthritis (RA) happens because of the uncontrolled inflammation that is typical of an autoimmune disease. In such situations, the body’s defense mechanism malfunctions and attacks its own tissues (e.g., healthy joints) for a prolonged period of time. An immune-signaling protein known as cachexin or tumor necrosis factor-alpha is one of the key drivers of inflammation. Andrographolide has been shown to lower levels of cachexin. ParActin® and Mild Knee Osteoarthritis In a randomized, double-blind, placebo-controlled study the efficacy of ParActin® (300 and 600 mg daily) was assessed on pain reduction in 103 patients with mild to moderate knee osteoarthritis [13]. Patients treated with ParActin® showed a significant reduction in pain relative to the control group. Stiffness, physical function, and fatigue all showed a significant improvement with ParActin® treatment. At the end of the study, quality of life and Functional Assessment of Chronic Illness Therapy (FACIT) scores were significantly better in the ParActin®-treated groups compared to the control group. ParActin® and Rheumatoid Arthritis Similarly, in a randomized, double-blind and placebo-controlled study published in the journal Clinical Rheumatology in 2009, 60 individuals with compromised joints were given 100 mg of ParActin® or placebo in conjunction with methotrexate, three times a day for 14 weeks [14]. Methotrexate is proven to improve RA symptoms, but long-term use can cause serious infection and liver damage. In this study, ParActin® was effective in reducing the number and total grade of swollen joints, the number and total grade of tender joints, as well as improving scores on HAQ-52 (52-week Health Assessment Questionnaire), and SF-36 (36-item short form survey) health questionnaires. ParActin® treatment was associated with a reduction of various proteins, including enzymes, associated with cartilage damage. Currently, a human clinical trial testing the safety and efficacy of ParActin® in patients with mild to moderate osteoarthritis is ongoing. In other laboratory experiments, ParActin® and Andrographolide have also been shown to support bone [15]12, cartilage [16]13, and muscle [17]14 health and recovery. Can Andrographis Help Fight Cancer? Cancer results when our body’s cells grow uncontrollably. When cells develop normally, they become more and more specialized in their function at each stage of development. For example, immature pancreatic cells that will eventually go on to make insulin will develop the cellular machinery to do so as they become mature pancreatic cells. When cancer happens, it interferes with normal cellular development and cells do not mature. In fact, cancer cells resemble immature body cells – and the more they resemble immature cells, the more likely it is that they will spread to other locations – known as metastasis, often with fatal consequences. So, it logically follows that if cancer cells can be made to forcibly undergo maturation or differentiation, they will lose the ability to grow uncontrollably. Indeed, in one laboratory study in mice, researchers showed that Andrographis could induce differentiation in leukemia cells [18]. [Note: Leukemia is a cancer of the white blood cells, which are part of the immune system.] Andrographis can induce differentiation in laboratory conditions – but does this mean it can fight cancer? Indeed, it can – at least under laboratory conditions. A systematic review of no less than 139 pre-clinical and clinical studies shows that Andrographolide has anticancer effects on almost all types of cell lines in laboratory experiments [19]. Specifically, a 2019 study showed that Andrographolide prevented human colon cancer cells in culture from multiplying by inducing a process known as “programmed cell death” or apoptosis. Further, Andrographolide also displayed a combinatorial effect with chemotherapeutic anticancer drugs in these cells under laboratory conditions [20]. Similarly, the results of a 2019 study showed that a hot water extract of Andrographis could stimulate the production of specific components of the immune system and restore others to a more normal state. Furthermore, the Andrographis extract prevented tumor growth and metastasis in these mice, once again by inducing apoptosis, but without causing severe body weight loss as many anticancer chemotherapy drugs tend to do. Blood tests detected multiple bioactive Andrographis-derived diterpene compounds, suggesting that more than one might have contributed towards the beneficial effects seen in this study [21]. Andrographis extracts – especially bioactive lactone and diterpene compounds such as Andrographolide in them – have been shown to be very potent in suppressing the growth of various types of cancer cells in laboratory studies. In particular, Andrographolide has been shown to block the growth of human breast, prostate, and hepatoma tumors. It has even successfully been used in cancer chemotherapy [22]. Can Andrographis Help Prevent Alzheimer’s Disease? As a closing note, Andrographis is even showing promise in helping to combat Alzheimer’s disease. In a 2019 study published in the journal Plants – Basel, researchers reported that three compounds isolated from Andrographis may help stop the formation of structures known as beta-amyloid plaques, which underlie neurotoxicity and dementia, including Alzheimer’s disease [23]. As noted by the researchers “Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties.” Deeper Dive Resources Organixx’s Turmeric T3D https://shop.organixx.com/a/secure/checkout/OobbS9ROAoETfnAGmGDF?ch-tn-box=first-box&gl=5d8908c502e26b5f0c38083c Organixx Save & Subscribe Program https://organixx.com/subscribe-and-save/?gl=5eeaa19c8ebf588562f75d8f [1] Andrographis: In-depth review [2] Andrographolide, a Natural Antioxidant: An Update [3] Andrographis: In-depth review [4] Andrographolide, a Natural Antioxidant: An Update [5] ParActin® [6] Andrographolide, a Natural Antioxidant: An Update [7] Andrographis: In-depth review [8] Immunostimulant agents from Andrographis paniculata. [9] Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. [10] Herbal Medicine for Cough: A Systematic Review and Meta-Analysis. [11] Andrographis paniculata extract (HMPL-004) for active ulcerative colitis. [12] HP Ingredients: ParActin Joint Health. [13] A double-blind, randomized, placebo-controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis. [14] Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. [15] Assessment of the Efficacy of ParActin® in Subjects With Mild to Moderate Osteoarthritis (ParActin) [16] ParActin: Healthy Bone Support [17] ParActin: Healthy Cartilage Support [18] ParActin: Muscle Health and Recovery [19] Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. [20] Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer. [21] Antiproliferative and Apoptotic Properties of Andrographolide Against Human Colon Cancer DLD1 Cell Line [22] Multiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models. [23] Andrographolide and analogues in cancer prevention. [24] Multi-Target β-Protease Inhibitors from Andrographis paniculata: In Silico and In Vitro Studies. Study builds scientific support for HP Ingredients’ ParActin for joint health https://www.nutraingredients-usa.com/Article/2019/05/08/Study-builds-scientific-support-for-HP-Ingredients-ParActin-for-joint-health A double-blind, randomized, placebo-controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis. https://www.ncbi.nlm.nih.gov/pubmed/30968986 Subscribe to Empowering You Organically Never miss an episode! APPLE PODCASTS SPOTIFY GOOGLE PODCASTS
This “king of bitters” (so-called because of its flavor) has been used for centuries in Asia to treat gut and upper respiratory infections, fever, herpes, sore throat, and other chronic and infectious disease conditions. However, modern research is demonstrating Andrographis paniculata’s benefits include aiding with joint conditions such as arthritis. ParActin®: A Potent Form of Andrographis Paniculata for Pain Support & More The medicinal herb Andrographis paniculata has been traditionally used for its powerful anti-inflammatory properties and its ability to boost immune system activity. This “king of bitters” (so-called because of its flavor) has been used for centuries in Asia to treat gut and upper respiratory infections, fever, herpes, sore throat, and other chronic and infectious disease conditions [1]. However, modern research is demonstrating Andrographis paniculata’s benefits include aiding with joint conditions such as arthritis and it may even have anti-cancer benefits. Andrographis Goes by Many Names Andrographis is cultivated in many tropical Asian countries including India, China, Malaysia, Indonesia, and Sri Lanka, as well as in the West Indies, Brazil, parts of Africa, and Central America. Known as “chuan-xin-lian” in China, “kalmegh” in India, “senshinren” in Japan, “hempedu bumi” in Malaysia, “fah talai” in Thailand, and “green chiretta” in the Scandinavian countries, Andrographis is listed in the Indian Pharmacopoeia (a publication that lists standards for all drugs that are manufactured, sold, and consumed in India) and in a couple of dozen Ayurvedic formulas [2]. In traditional Chinese medicine (TCM), Andrographis is believed to rid the body of heat (e.g., fevers) and to dispel toxins [3]. Phytochemistry of Andrographis Paniculata Andrographis leaves are mainly responsible for its biological actions. They contain many bioactive compounds, including diterpene lactones – especially Andrographolide, the main bioactive ingredient that imparts the typical bitter taste. Andrographolide is an antioxidant that has been shown to be responsible for the herb’s anti-viral and anti-bacterial properties. Andrographolide is also reported in scientific literature to reduce blood clot formation, help protect the liver, have anti-cancer properties, and manage inflammation within safe levels [4]. What Is ParActin®? ParActin® is a patented extract of A. Paniculata, standardized to a fixed concentration of Andrographolide and other related compounds including 14-deoxyandrographolides and neoandrographolides [5]. Preliminary research shows that ParActin® promotes a healthy inflammatory response by blocking a powerful chemical known as NF-kappa B, which is known to be a key regulator of the inflammatory response system. As a result, ParActin® helps support a healthy and appropriate inflammatory response by reducing the levels of pro-inflammatory compounds that trigger the familiar pain and redness associated with inflammation. The safety and efficacy of ParActin® has been assessed in more than 30 studies, including laboratory experiments on cultured cells and animal models – and even a human clinical trial. Let’s take a closer look at some of these studies and what they tell us about Andrographis and ParActin®. Inflammation Is Linked to Many Disease Conditions Long-term, chronic inflammation that occurs when the immune system goes into overdrive may lie at the root of many otherwise unrelated diseases, including: asthma inflammatory bowel disease (IBD) rheumatoid arthritis (RA) autoimmune diseases depression cancer Alzheimer’s disease Inflammation – which manifests as swelling, redness, heat, and pain – is a normal response of our immune system and our body’s way of defending us from infections and disease. However, if it’s not managed properly, inflammation can harm the body. Chronic inflammation is the result of an overactive immune system that is constantly turned on – or cannot be turned off – so that it attacks parts of the very body it is supposed to protect. So-called oxygenated chemical species – including free radicals, oxygen ions, and peroxides – are continuously made in our body’s cells in response to UV radiation and as byproducts of ongoing metabolic activity. They are highly reactive and dangerous, because they can attack cellular DNA and proteins, damaging them. When oxygenated chemical species are generated in excess, they can overwhelm cellular defense systems, leading to a condition known as oxidative stress along with high levels of inflammation – which, as we discussed earlier, is known to contribute to the development of many diseases. Andrographolide, the best-known bioactive ingredient in Andrographis, has been shown to directly inactivate free radicals. It also protects mitochondria, blocks pro-oxidant enzymes, and activates other antioxidant enzymes in the body [6]. Andrographis Boosts the Immune System Andrographolide has been shown to enhance the immune system. For example, it boosts production of white blood cells known as lymphocytes, which scavenge and destroy bacteria and other foreign matter. It also triggers the release of signaling proteins known as interferons, along with enhancing activity of the lymphatic system [7]. Interferons are made and released by our body’s cells when they get infected with viruses, causing nearby cells to strengthen their anti-viral defenses. Interferons are potent antiviral agents that stop viruses from multiplying. The lymphatic system is another circulatory system in our body that carries a fluid known as lymph, which removes the waste products of cellular metabolism. The lymphatic system also transports invading bacteria and viruses to lymph nodes where the white blood cells (lymphocytes) destroy them. Andrographis has been shown to trigger our immune system in two ways: Antigen-specific response – specific proteins known as antibodies are made to counteract invading bacteria and viruses. Nonspecific immune response – immune cells known as macrophages are produced, which scavenge and destroy invaders. Andrographis activates both responses, meaning it is very effective against a variety of infectious and cancer-causing agents [8]. Benefits for Upper Respiratory Tract Infections & Cough Andrographis has been used for many hundreds of years in traditional medicinal systems to treat upper respiratory infections. Modern research supports this. For example, a 2004 meta-analysis of the results of seven double-blind, controlled trials (with a total of 896 participants) showed that Andrographis offers significant relief from the symptoms of upper respiratory tract infections and may even prevent them from taking hold in the first place. [Note: A meta-analysis is a quantitative epidemiological study used to systematically assess the results of previous research – typically randomized, controlled clinical trials – to derive overall conclusions about that body of research.] All the participants in these seven clinical trials reported reduced fever, runny nose, cough, and sore throat on taking Andrographis relative to control patients. Side effects were described as “generally mild and infrequent” [9]. Similarly, another meta-analysis published in 2015 reviewed six randomized controlled clinical trials, which assessed the effects of Andrographis in the treatment of cough. Combined, these six studies compared 333 patients who took various Andrographis preparations relative to 348 patients in control groups. All of these studies showed that Andrographis preparations reduced cough severity [10]. Andrographis Heals the Gut As mentioned above, Andrographis has long been used in traditional medicinal systems such as Ayurveda and traditional Chinese medicine (TCM) for treating gut infections. In a 2013 study published in the American Journal of Gastroenterology, 224 patients with mild to moderate ulcerative colitis were either given 1200 or 1800 milligrams of Andrographis for 8 weeks. Ulcerative colitis is an inflammatory bowel disease that causes long-lasting inflammation and ulcers in the gut, affecting the innermost lining of the large intestine (colon) and rectum. A colonoscopy was performed before the study started and after it ended. Stool frequency and the presence of blood in the stool were also assessed every two weeks. At the end of the study, 60% of patients who received 1800 mg of Andrographis – relative to 40% of patients in the control group – showed clinical symptoms of healing. Not only that, 50% of the patients who received the 1800 mg of Andrographis also showed mucosal healing, relative to 33% in the control group [11]. Andrographis & Joint Pain from Arthritis Arthritis affects more than 70 million Americans, leading to inflammation, pain, and stiffness in the joints and connective tissues. Over time, cartilage breaks down, bones erode, and joints become misshapen [12]. Our modern understanding is that rheumatoid arthritis (RA) happens because of the uncontrolled inflammation that is typical of an autoimmune disease. In such situations, the body’s defense mechanism malfunctions and attacks its own tissues (e.g., healthy joints) for a prolonged period of time. An immune-signaling protein known as cachexin or tumor necrosis factor-alpha is one of the key drivers of inflammation. Andrographolide has been shown to lower levels of cachexin. ParActin® and Mild Knee Osteoarthritis In a randomized, double-blind, placebo-controlled study the efficacy of ParActin® (300 and 600 mg daily) was assessed on pain reduction in 103 patients with mild to moderate knee osteoarthritis [13]. Patients treated with ParActin® showed a significant reduction in pain relative to the control group. Stiffness, physical function, and fatigue all showed a significant improvement with ParActin® treatment. At the end of the study, quality of life and Functional Assessment of Chronic Illness Therapy (FACIT) scores were significantly better in the ParActin®-treated groups compared to the control group. ParActin® and Rheumatoid Arthritis Similarly, in a randomized, double-blind and placebo-controlled study published in the journal Clinical Rheumatology in 2009, 60 individuals with compromised joints were given 100 mg of ParActin® or placebo in conjunction with methotrexate, three times a day for 14 weeks [14]. Methotrexate is proven to improve RA symptoms, but long-term use can cause serious infection and liver damage. In this study, ParActin® was effective in reducing the number and total grade of swollen joints, the number and total grade of tender joints, as well as improving scores on HAQ-52 (52-week Health Assessment Questionnaire), and SF-36 (36-item short form survey) health questionnaires. ParActin® treatment was associated with a reduction of various proteins, including enzymes, associated with cartilage damage. Currently, a human clinical trial testing the safety and efficacy of ParActin® in patients with mild to moderate osteoarthritis is ongoing. In other laboratory experiments, ParActin® and Andrographolide have also been shown to support bone [15]12, cartilage [16]13, and muscle [17]14 health and recovery. Can Andrographis Help Fight Cancer? Cancer results when our body’s cells grow uncontrollably. When cells develop normally, they become more and more specialized in their function at each stage of development. For example, immature pancreatic cells that will eventually go on to make insulin will develop the cellular machinery to do so as they become mature pancreatic cells. When cancer happens, it interferes with normal cellular development and cells do not mature. In fact, cancer cells resemble immature body cells – and the more they resemble immature cells, the more likely it is that they will spread to other locations – known as metastasis, often with fatal consequences. So, it logically follows that if cancer cells can be made to forcibly undergo maturation or differentiation, they will lose the ability to grow uncontrollably. Indeed, in one laboratory study in mice, researchers showed that Andrographis could induce differentiation in leukemia cells [18]. [Note: Leukemia is a cancer of the white blood cells, which are part of the immune system.] Andrographis can induce differentiation in laboratory conditions – but does this mean it can fight cancer? Indeed, it can – at least under laboratory conditions. A systematic review of no less than 139 pre-clinical and clinical studies shows that Andrographolide has anticancer effects on almost all types of cell lines in laboratory experiments [19]. Specifically, a 2019 study showed that Andrographolide prevented human colon cancer cells in culture from multiplying by inducing a process known as “programmed cell death” or apoptosis. Further, Andrographolide also displayed a combinatorial effect with chemotherapeutic anticancer drugs in these cells under laboratory conditions [20]. Similarly, the results of a 2019 study showed that a hot water extract of Andrographis could stimulate the production of specific components of the immune system and restore others to a more normal state. Furthermore, the Andrographis extract prevented tumor growth and metastasis in these mice, once again by inducing apoptosis, but without causing severe body weight loss as many anticancer chemotherapy drugs tend to do. Blood tests detected multiple bioactive Andrographis-derived diterpene compounds, suggesting that more than one might have contributed towards the beneficial effects seen in this study [21]. Andrographis extracts – especially bioactive lactone and diterpene compounds such as Andrographolide in them – have been shown to be very potent in suppressing the growth of various types of cancer cells in laboratory studies. In particular, Andrographolide has been shown to block the growth of human breast, prostate, and hepatoma tumors. It has even successfully been used in cancer chemotherapy [22]. Can Andrographis Help Prevent Alzheimer’s Disease? As a closing note, Andrographis is even showing promise in helping to combat Alzheimer’s disease. In a 2019 study published in the journal Plants – Basel, researchers reported that three compounds isolated from Andrographis may help stop the formation of structures known as beta-amyloid plaques, which underlie neurotoxicity and dementia, including Alzheimer’s disease [23]. As noted by the researchers “Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties.” Deeper Dive Resources Organixx’s Turmeric T3D https://shop.organixx.com/a/secure/checkout/OobbS9ROAoETfnAGmGDF?ch-tn-box=first-box&gl=5d8908c502e26b5f0c38083c Organixx Save & Subscribe Program https://organixx.com/subscribe-and-save/?gl=5eeaa19c8ebf588562f75d8f [1] Andrographis: In-depth review [2] Andrographolide, a Natural Antioxidant: An Update [3] Andrographis: In-depth review [4] Andrographolide, a Natural Antioxidant: An Update [5] ParActin® [6] Andrographolide, a Natural Antioxidant: An Update [7] Andrographis: In-depth review [8] Immunostimulant agents from Andrographis paniculata. [9] Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. [10] Herbal Medicine for Cough: A Systematic Review and Meta-Analysis. [11] Andrographis paniculata extract (HMPL-004) for active ulcerative colitis. [12] HP Ingredients: ParActin Joint Health. [13] A double-blind, randomized, placebo-controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis. [14] Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. [15] Assessment of the Efficacy of ParActin® in Subjects With Mild to Moderate Osteoarthritis (ParActin) [16] ParActin: Healthy Bone Support [17] ParActin: Healthy Cartilage Support [18] ParActin: Muscle Health and Recovery [19] Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. [20] Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer. [21] Antiproliferative and Apoptotic Properties of Andrographolide Against Human Colon Cancer DLD1 Cell Line [22] Multiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models. [23] Andrographolide and analogues in cancer prevention. [24] Multi-Target β-Protease Inhibitors from Andrographis paniculata: In Silico and In Vitro Studies. Study builds scientific support for HP Ingredients’ ParActin for joint health https://www.nutraingredients-usa.com/Article/2019/05/08/Study-builds-scientific-support-for-HP-Ingredients-ParActin-for-joint-health A double-blind, randomized, placebo-controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis. https://www.ncbi.nlm.nih.gov/pubmed/30968986 Subscribe to Empowering You Organically Never miss an episode! APPLE PODCASTS SPOTIFY GOOGLE PODCASTS
Outbreaks of severe virus infections with the potential to cause global pandemics are increasing. In many instances these outbreaks have been newly emerging (SARS coronavirus), re-emerging (Ebola virus, Zika virus) or zoonotic (avian influenza H5N1) virus infections. In the absence of a targeted vaccine or a pathogen-specific antiviral, broad-spectrum antivirals would function to limit virus spread.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.19.210955v1?rss=1 Authors: Onabajo, O. O., Banday, A. R., Yan, W., Obajemu, A., Stanifer, M. L., Santer, D. M., Florez-Vargas, O., Piontkivska, H., Vargas, J., Kee, C., Tyrrell, D. L., Mendoza, J. L., Boulant, S., Prokunina-Olsson, L. Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge on ACE2 expression and suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection. Copy rights belong to original authors. Visit the link for more info
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ParActin®: A Potent Form of Andrographis Paniculata for Pain Support & More The medicinal herb Andrographis paniculata has been traditionally used for its powerful anti-inflammatory properties and its ability to boost immune system activity. This “king of bitters” (so-called because of its flavor) has been used for centuries in Asia to treat gut and upper respiratory infections, fever, herpes, sore throat, and other chronic and infectious disease conditions [1]. However, modern research is demonstrating Andrographis paniculata’s benefits include aiding with joint conditions such as arthritis and it may even have anti-cancer benefits. Andrographis Goes by Many Names Andrographis is cultivated in many tropical Asian countries including India, China, Malaysia, Indonesia, and Sri Lanka, as well as in the West Indies, Brazil, parts of Africa, and Central America. Known as “chuan-xin-lian” in China, “kalmegh” in India, “senshinren” in Japan, “hempedu bumi” in Malaysia, “fah talai” in Thailand, and “green chiretta” in the Scandinavian countries, Andrographis is listed in the Indian Pharmacopoeia (a publication that lists standards for all drugs that are manufactured, sold, and consumed in India) and in a couple of dozen Ayurvedic formulas [2]. In traditional Chinese medicine (TCM), Andrographis is believed to rid the body of heat (e.g., fevers) and to dispel toxins [3]. Phytochemistry of Andrographis Paniculata Andrographis leaves are mainly responsible for its biological actions. They contain many bioactive compounds, including diterpene lactones – especially Andrographolide, the main bioactive ingredient that imparts the typical bitter taste. Andrographolide is an antioxidant that has been shown to be responsible for the herb’s anti-viral and anti-bacterial properties. Andrographolide is also reported in scientific literature to reduce blood clot formation, help protect the liver, have anti-cancer properties, and manage inflammation within safe levels [4]. What Is ParActin®? ParActin® is a patented extract of A. Paniculata, standardized to a fixed concentration of Andrographolide and other related compounds including 14-deoxyandrographolides and neoandrographolides [5]. Preliminary research shows that ParActin® promotes a healthy inflammatory response by blocking a powerful chemical known as NF-kappa B, which is known to be a key regulator of the inflammatory response system. As a result, ParActin® helps support a healthy and appropriate inflammatory response by reducing the levels of pro-inflammatory compounds that trigger the familiar pain and redness associated with inflammation. The safety and efficacy of ParActin® has been assessed in more than 30 studies, including laboratory experiments on cultured cells and animal models – and even a human clinical trial. Let’s take a closer look at some of these studies and what they tell us about Andrographis and ParActin®. Inflammation Is Linked to Many Disease Conditions Long-term, chronic inflammation that occurs when the immune system goes into overdrive may lie at the root of many otherwise unrelated diseases, including: asthma inflammatory bowel disease (IBD) rheumatoid arthritis (RA) autoimmune diseases depression cancer Alzheimer’s disease Inflammation – which manifests as swelling, redness, heat, and pain – is a normal response of our immune system and our body’s way of defending us from infections and disease. However, if it’s not managed properly, inflammation can harm the body. Chronic inflammation is the result of an overactive immune system that is constantly turned on – or cannot be turned off – so that it attacks parts of the very body it is supposed to protect. So-called oxygenated chemical species – including free radicals, oxygen ions, and peroxides – are continuously made in our body’s cells in response to UV radiation and as byproducts of ongoing metabolic activity. They are highly reactive and dangerous, because they can attack cellular DNA and proteins, damaging them. When oxygenated chemical species are generated in excess, they can overwhelm cellular defense systems, leading to a condition known as oxidative stress along with high levels of inflammation – which, as we discussed earlier, is known to contribute to the development of many diseases. Andrographolide, the best-known bioactive ingredient in Andrographis, has been shown to directly inactivate free radicals. It also protects mitochondria, blocks pro-oxidant enzymes, and activates other antioxidant enzymes in the body [6]. Andrographis Boosts the Immune System Andrographolide has been shown to enhance the immune system. For example, it boosts production of white blood cells known as lymphocytes, which scavenge and destroy bacteria and other foreign matter. It also triggers the release of signaling proteins known as interferons, along with enhancing activity of the lymphatic system [7]. Interferons are made and released by our body’s cells when they get infected with viruses, causing nearby cells to strengthen their anti-viral defenses. Interferons are potent antiviral agents that stop viruses from multiplying. The lymphatic system is another circulatory system in our body that carries a fluid known as lymph, which removes the waste products of cellular metabolism. The lymphatic system also transports invading bacteria and viruses to lymph nodes where the white blood cells (lymphocytes) destroy them. Andrographis has been shown to trigger our immune system in two ways: Antigen-specific response – specific proteins known as antibodies are made to counteract invading bacteria and viruses. Nonspecific immune response – immune cells known as macrophages are produced, which scavenge and destroy invaders. Andrographis activates both responses, meaning it is very effective against a variety of infectious and cancer-causing agents [8]. Benefits for Upper Respiratory Tract Infections & Cough Andrographis has been used for many hundreds of years in traditional medicinal systems to treat upper respiratory infections. Modern research supports this. For example, a 2004 meta-analysis of the results of seven double-blind, controlled trials (with a total of 896 participants) showed that Andrographis offers significant relief from the symptoms of upper respiratory tract infections and may even prevent them from taking hold in the first place. [Note: A meta-analysis is a quantitative epidemiological study used to systematically assess the results of previous research – typically randomized, controlled clinical trials – to derive overall conclusions about that body of research.] All the participants in these seven clinical trials reported reduced fever, runny nose, cough, and sore throat on taking Andrographis relative to control patients. Side effects were described as “generally mild and infrequent” [9]. Similarly, another meta-analysis published in 2015 reviewed six randomized controlled clinical trials, which assessed the effects of Andrographis in the treatment of cough. Combined, these six studies compared 333 patients who took various Andrographis preparations relative to 348 patients in control groups. All of these studies showed that Andrographis preparations reduced cough severity [10]. Andrographis Heals the Gut As mentioned above, Andrographis has long been used in traditional medicinal systems such as Ayurveda and traditional Chinese medicine (TCM) for treating gut infections. In a 2013 study published in the American Journal of Gastroenterology, 224 patients with mild to moderate ulcerative colitis were either given 1200 or 1800 milligrams of Andrographis for 8 weeks. Ulcerative colitis is an inflammatory bowel disease that causes long-lasting inflammation and ulcers in the gut, affecting the innermost lining of the large intestine (colon) and rectum. A colonoscopy was performed before the study started and after it ended. Stool frequency and the presence of blood in the stool were also assessed every two weeks. At the end of the study, 60% of patients who received 1800 mg of Andrographis – relative to 40% of patients in the control group – showed clinical symptoms of healing. Not only that, 50% of the patients who received the 1800 mg of Andrographis also showed mucosal healing, relative to 33% in the control group [11]. Andrographis & Joint Pain from Arthritis Arthritis affects more than 70 million Americans, leading to inflammation, pain, and stiffness in the joints and connective tissues. Over time, cartilage breaks down, bones erode, and joints become misshapen [12]. Our modern understanding is that rheumatoid arthritis (RA) happens because of the uncontrolled inflammation that is typical of an autoimmune disease. In such situations, the body’s defense mechanism malfunctions and attacks its own tissues (e.g., healthy joints) for a prolonged period of time. An immune-signaling protein known as cachexin or tumor necrosis factor-alpha is one of the key drivers of inflammation. Andrographolide has been shown to lower levels of cachexin. ParActin® and Mild Knee Osteoarthritis In a randomized, double-blind, placebo-controlled study the efficacy of ParActin® (300 and 600 mg daily) was assessed on pain reduction in 103 patients with mild to moderate knee osteoarthritis [13]. Patients treated with ParActin® showed a significant reduction in pain relative to the control group. Stiffness, physical function, and fatigue all showed a significant improvement with ParActin® treatment. At the end of the study, quality of life and Functional Assessment of Chronic Illness Therapy (FACIT) scores were significantly better in the ParActin®-treated groups compared to the control group. ParActin® and Rheumatoid Arthritis Similarly, in a randomized, double-blind and placebo-controlled study published in the journal Clinical Rheumatology in 2009, 60 individuals with compromised joints were given 100 mg of ParActin® or placebo in conjunction with methotrexate, three times a day for 14 weeks [14]. Methotrexate is proven to improve RA symptoms, but long-term use can cause serious infection and liver damage. In this study, ParActin® was effective in reducing the number and total grade of swollen joints, the number and total grade of tender joints, as well as improving scores on HAQ-52 (52-week Health Assessment Questionnaire), and SF-36 (36-item short form survey) health questionnaires. ParActin® treatment was associated with a reduction of various proteins, including enzymes, associated with cartilage damage. Currently, a human clinical trial testing the safety and efficacy of ParActin® in patients with mild to moderate osteoarthritis is ongoing. In other laboratory experiments, ParActin® and Andrographolide have also been shown to support bone [15]12, cartilage [16]13, and muscle [17]14 health and recovery. Can Andrographis Help Fight Cancer? Cancer results when our body’s cells grow uncontrollably. When cells develop normally, they become more and more specialized in their function at each stage of development. For example, immature pancreatic cells that will eventually go on to make insulin will develop the cellular machinery to do so as they become mature pancreatic cells. When cancer happens, it interferes with normal cellular development and cells do not mature. In fact, cancer cells resemble immature body cells – and the more they resemble immature cells, the more likely it is that they will spread to other locations – known as metastasis, often with fatal consequences. So, it logically follows that if cancer cells can be made to forcibly undergo maturation or differentiation, they will lose the ability to grow uncontrollably. Indeed, in one laboratory study in mice, researchers showed that Andrographis could induce differentiation in leukemia cells [18]. [Note: Leukemia is a cancer of the white blood cells, which are part of the immune system.] Andrographis can induce differentiation in laboratory conditions – but does this mean it can fight cancer? Indeed, it can – at least under laboratory conditions. A systematic review of no less than 139 pre-clinical and clinical studies shows that Andrographolide has anticancer effects on almost all types of cell lines in laboratory experiments [19]. Specifically, a 2019 study showed that Andrographolide prevented human colon cancer cells in culture from multiplying by inducing a process known as “programmed cell death” or apoptosis. Further, Andrographolide also displayed a combinatorial effect with chemotherapeutic anticancer drugs in these cells under laboratory conditions [20]. Similarly, the results of a 2019 study showed that a hot water extract of Andrographis could stimulate the production of specific components of the immune system and restore others to a more normal state. Furthermore, the Andrographis extract prevented tumor growth and metastasis in these mice, once again by inducing apoptosis, but without causing severe body weight loss as many anticancer chemotherapy drugs tend to do. Blood tests detected multiple bioactive Andrographis-derived diterpene compounds, suggesting that more than one might have contributed towards the beneficial effects seen in this study [21]. Andrographis extracts – especially bioactive lactone and diterpene compounds such as Andrographolide in them – have been shown to be very potent in suppressing the growth of various types of cancer cells in laboratory studies. In particular, Andrographolide has been shown to block the growth of human breast, prostate, and hepatoma tumors. It has even successfully been used in cancer chemotherapy [22]. Can Andrographis Help Prevent Alzheimer’s Disease? As a closing note, Andrographis is even showing promise in helping to combat Alzheimer’s disease. In a 2019 study published in the journal Plants – Basel, researchers reported that three compounds isolated from Andrographis may help stop the formation of structures known as beta-amyloid plaques, which underlie neurotoxicity and dementia, including Alzheimer’s disease [23]. As noted by the researchers “Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties.”
ParActin®: A Potent Form of Andrographis Paniculata for Pain Support & More The medicinal herb Andrographis paniculata has been traditionally used for its powerful anti-inflammatory properties and its ability to boost immune system activity. This “king of bitters” (so-called because of its flavor) has been used for centuries in Asia to treat gut and upper respiratory infections, fever, herpes, sore throat, and other chronic and infectious disease conditions [1]. However, modern research is demonstrating Andrographis paniculata’s benefits include aiding with joint conditions such as arthritis and it may even have anti-cancer benefits. Andrographis Goes by Many Names Andrographis is cultivated in many tropical Asian countries including India, China, Malaysia, Indonesia, and Sri Lanka, as well as in the West Indies, Brazil, parts of Africa, and Central America. Known as “chuan-xin-lian” in China, “kalmegh” in India, “senshinren” in Japan, “hempedu bumi” in Malaysia, “fah talai” in Thailand, and “green chiretta” in the Scandinavian countries, Andrographis is listed in the Indian Pharmacopoeia (a publication that lists standards for all drugs that are manufactured, sold, and consumed in India) and in a couple of dozen Ayurvedic formulas [2]. In traditional Chinese medicine (TCM), Andrographis is believed to rid the body of heat (e.g., fevers) and to dispel toxins [3]. Phytochemistry of Andrographis Paniculata Andrographis leaves are mainly responsible for its biological actions. They contain many bioactive compounds, including diterpene lactones – especially Andrographolide, the main bioactive ingredient that imparts the typical bitter taste. Andrographolide is an antioxidant that has been shown to be responsible for the herb’s anti-viral and anti-bacterial properties. Andrographolide is also reported in scientific literature to reduce blood clot formation, help protect the liver, have anti-cancer properties, and manage inflammation within safe levels [4]. What Is ParActin®? ParActin® is a patented extract of A. Paniculata, standardized to a fixed concentration of Andrographolide and other related compounds including 14-deoxyandrographolides and neoandrographolides [5]. Preliminary research shows that ParActin® promotes a healthy inflammatory response by blocking a powerful chemical known as NF-kappa B, which is known to be a key regulator of the inflammatory response system. As a result, ParActin® helps support a healthy and appropriate inflammatory response by reducing the levels of pro-inflammatory compounds that trigger the familiar pain and redness associated with inflammation. The safety and efficacy of ParActin® has been assessed in more than 30 studies, including laboratory experiments on cultured cells and animal models – and even a human clinical trial. Let’s take a closer look at some of these studies and what they tell us about Andrographis and ParActin®. Inflammation Is Linked to Many Disease Conditions Long-term, chronic inflammation that occurs when the immune system goes into overdrive may lie at the root of many otherwise unrelated diseases, including: asthma inflammatory bowel disease (IBD) rheumatoid arthritis (RA) autoimmune diseases depression cancer Alzheimer’s disease Inflammation – which manifests as swelling, redness, heat, and pain – is a normal response of our immune system and our body’s way of defending us from infections and disease. However, if it’s not managed properly, inflammation can harm the body. Chronic inflammation is the result of an overactive immune system that is constantly turned on – or cannot be turned off – so that it attacks parts of the very body it is supposed to protect. So-called oxygenated chemical species – including free radicals, oxygen ions, and peroxides – are continuously made in our body’s cells in response to UV radiation and as byproducts of ongoing metabolic activity. They are highly reactive and dangerous, because they can attack cellular DNA and proteins, damaging them. When oxygenated chemical species are generated in excess, they can overwhelm cellular defense systems, leading to a condition known as oxidative stress along with high levels of inflammation – which, as we discussed earlier, is known to contribute to the development of many diseases. Andrographolide, the best-known bioactive ingredient in Andrographis, has been shown to directly inactivate free radicals. It also protects mitochondria, blocks pro-oxidant enzymes, and activates other antioxidant enzymes in the body [6]. Andrographis Boosts the Immune System Andrographolide has been shown to enhance the immune system. For example, it boosts production of white blood cells known as lymphocytes, which scavenge and destroy bacteria and other foreign matter. It also triggers the release of signaling proteins known as interferons, along with enhancing activity of the lymphatic system [7]. Interferons are made and released by our body’s cells when they get infected with viruses, causing nearby cells to strengthen their anti-viral defenses. Interferons are potent antiviral agents that stop viruses from multiplying. The lymphatic system is another circulatory system in our body that carries a fluid known as lymph, which removes the waste products of cellular metabolism. The lymphatic system also transports invading bacteria and viruses to lymph nodes where the white blood cells (lymphocytes) destroy them. Andrographis has been shown to trigger our immune system in two ways: Antigen-specific response – specific proteins known as antibodies are made to counteract invading bacteria and viruses. Nonspecific immune response – immune cells known as macrophages are produced, which scavenge and destroy invaders. Andrographis activates both responses, meaning it is very effective against a variety of infectious and cancer-causing agents [8]. Benefits for Upper Respiratory Tract Infections & Cough Andrographis has been used for many hundreds of years in traditional medicinal systems to treat upper respiratory infections. Modern research supports this. For example, a 2004 meta-analysis of the results of seven double-blind, controlled trials (with a total of 896 participants) showed that Andrographis offers significant relief from the symptoms of upper respiratory tract infections and may even prevent them from taking hold in the first place. [Note: A meta-analysis is a quantitative epidemiological study used to systematically assess the results of previous research – typically randomized, controlled clinical trials – to derive overall conclusions about that body of research.] All the participants in these seven clinical trials reported reduced fever, runny nose, cough, and sore throat on taking Andrographis relative to control patients. Side effects were described as “generally mild and infrequent” [9]. Similarly, another meta-analysis published in 2015 reviewed six randomized controlled clinical trials, which assessed the effects of Andrographis in the treatment of cough. Combined, these six studies compared 333 patients who took various Andrographis preparations relative to 348 patients in control groups. All of these studies showed that Andrographis preparations reduced cough severity [10]. Andrographis Heals the Gut As mentioned above, Andrographis has long been used in traditional medicinal systems such as Ayurveda and traditional Chinese medicine (TCM) for treating gut infections. In a 2013 study published in the American Journal of Gastroenterology, 224 patients with mild to moderate ulcerative colitis were either given 1200 or 1800 milligrams of Andrographis for 8 weeks. Ulcerative colitis is an inflammatory bowel disease that causes long-lasting inflammation and ulcers in the gut, affecting the innermost lining of the large intestine (colon) and rectum. A colonoscopy was performed before the study started and after it ended. Stool frequency and the presence of blood in the stool were also assessed every two weeks. At the end of the study, 60% of patients who received 1800 mg of Andrographis – relative to 40% of patients in the control group – showed clinical symptoms of healing. Not only that, 50% of the patients who received the 1800 mg of Andrographis also showed mucosal healing, relative to 33% in the control group [11]. Andrographis & Joint Pain from Arthritis Arthritis affects more than 70 million Americans, leading to inflammation, pain, and stiffness in the joints and connective tissues. Over time, cartilage breaks down, bones erode, and joints become misshapen [12]. Our modern understanding is that rheumatoid arthritis (RA) happens because of the uncontrolled inflammation that is typical of an autoimmune disease. In such situations, the body’s defense mechanism malfunctions and attacks its own tissues (e.g., healthy joints) for a prolonged period of time. An immune-signaling protein known as cachexin or tumor necrosis factor-alpha is one of the key drivers of inflammation. Andrographolide has been shown to lower levels of cachexin. ParActin® and Mild Knee Osteoarthritis In a randomized, double-blind, placebo-controlled study the efficacy of ParActin® (300 and 600 mg daily) was assessed on pain reduction in 103 patients with mild to moderate knee osteoarthritis [13]. Patients treated with ParActin® showed a significant reduction in pain relative to the control group. Stiffness, physical function, and fatigue all showed a significant improvement with ParActin® treatment. At the end of the study, quality of life and Functional Assessment of Chronic Illness Therapy (FACIT) scores were significantly better in the ParActin®-treated groups compared to the control group. ParActin® and Rheumatoid Arthritis Similarly, in a randomized, double-blind and placebo-controlled study published in the journal Clinical Rheumatology in 2009, 60 individuals with compromised joints were given 100 mg of ParActin® or placebo in conjunction with methotrexate, three times a day for 14 weeks [14]. Methotrexate is proven to improve RA symptoms, but long-term use can cause serious infection and liver damage. In this study, ParActin® was effective in reducing the number and total grade of swollen joints, the number and total grade of tender joints, as well as improving scores on HAQ-52 (52-week Health Assessment Questionnaire), and SF-36 (36-item short form survey) health questionnaires. ParActin® treatment was associated with a reduction of various proteins, including enzymes, associated with cartilage damage. Currently, a human clinical trial testing the safety and efficacy of ParActin® in patients with mild to moderate osteoarthritis is ongoing. In other laboratory experiments, ParActin® and Andrographolide have also been shown to support bone [15]12, cartilage [16]13, and muscle [17]14 health and recovery. Can Andrographis Help Fight Cancer? Cancer results when our body’s cells grow uncontrollably. When cells develop normally, they become more and more specialized in their function at each stage of development. For example, immature pancreatic cells that will eventually go on to make insulin will develop the cellular machinery to do so as they become mature pancreatic cells. When cancer happens, it interferes with normal cellular development and cells do not mature. In fact, cancer cells resemble immature body cells – and the more they resemble immature cells, the more likely it is that they will spread to other locations – known as metastasis, often with fatal consequences. So, it logically follows that if cancer cells can be made to forcibly undergo maturation or differentiation, they will lose the ability to grow uncontrollably. Indeed, in one laboratory study in mice, researchers showed that Andrographis could induce differentiation in leukemia cells [18]. [Note: Leukemia is a cancer of the white blood cells, which are part of the immune system.] Andrographis can induce differentiation in laboratory conditions – but does this mean it can fight cancer? Indeed, it can – at least under laboratory conditions. A systematic review of no less than 139 pre-clinical and clinical studies shows that Andrographolide has anticancer effects on almost all types of cell lines in laboratory experiments [19]. Specifically, a 2019 study showed that Andrographolide prevented human colon cancer cells in culture from multiplying by inducing a process known as “programmed cell death” or apoptosis. Further, Andrographolide also displayed a combinatorial effect with chemotherapeutic anticancer drugs in these cells under laboratory conditions [20]. Similarly, the results of a 2019 study showed that a hot water extract of Andrographis could stimulate the production of specific components of the immune system and restore others to a more normal state. Furthermore, the Andrographis extract prevented tumor growth and metastasis in these mice, once again by inducing apoptosis, but without causing severe body weight loss as many anticancer chemotherapy drugs tend to do. Blood tests detected multiple bioactive Andrographis-derived diterpene compounds, suggesting that more than one might have contributed towards the beneficial effects seen in this study [21]. Andrographis extracts – especially bioactive lactone and diterpene compounds such as Andrographolide in them – have been shown to be very potent in suppressing the growth of various types of cancer cells in laboratory studies. In particular, Andrographolide has been shown to block the growth of human breast, prostate, and hepatoma tumors. It has even successfully been used in cancer chemotherapy [22]. Can Andrographis Help Prevent Alzheimer’s Disease? As a closing note, Andrographis is even showing promise in helping to combat Alzheimer’s disease. In a 2019 study published in the journal Plants – Basel, researchers reported that three compounds isolated from Andrographis may help stop the formation of structures known as beta-amyloid plaques, which underlie neurotoxicity and dementia, including Alzheimer’s disease [23]. As noted by the researchers “Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties.”
Our bodies need energy and we get that from the food we eat. No surprise, right? But, what is the gatekeeper between food consumption and the energy needed for athletic performance? It’s your gut – especially the gut flora. EPISODE SCRIPT There are millions and millions of bacteria in your gut – in fact, there are ten times more bacteria than cells in your gut. Ten times! What are these flora doing in addition to processing food? They can identify pathogens (dangerous compounds) Bolster and improve the health of the intestines Promote the growth of new cells What happens to athletes when the gut isn’t working well? It gets in the way of performance, recovery and long-term health and sustainability of athletic performance at a high level like competition. To be more specific, there’s a cascading effect that starts very small but ends up degrading your abilities to do what you want to do in the gym, at a race or in any competitive setting. It starts with: Too few interferons in your gut. Interferons (a type on immune cell in your body) are they’re released from cells in your gut and are important in helping to fight viruses. A healthy gut microbiome supports interferons. An unhealthy gut means fewer interferons and that can hurt your immune system. With that, the possibility of catching cold and suffering from other viruses increases. If your immune system is stressed, your body’s ability to repair the kind of inflammation that often comes with strenuous exercise is impaired. This can lead to an increased possibility of increasing the injuries sustained during training. Your digestion is also compromised, thus reducing the efficiency of processing nutrients for energy. If this continues, you’ll probably not be able to improve and sustain the kind of athletic performance we Spartans are aiming for. Luckily, it’s relatively easy to keep your gut healthy. First, eat healthy. We all know this, but don’t cut corners if you’re exercising at a high level. The difference between good performance and great performance can sometimes be very small – so you need to be disciplined if you’ve set ambitious goals for yourself. Give your gut what it wants. Probiotic supplements are very helpful. Yogurt is a common source of friendly bacteria. Many specialized probiotic supplements are very helpful, too. Some other options might be fermented foods, like sauerkraut. As we’re exercising, our gut normally performs silently and behind the scenes. That’s how you want to keep it because it usually draws our attention after something has gone wrong. Support you gut with good eating habits and you’ll keep your performance at a high level. KEY TERMS & IDEAS Gut health is key to thwarting viruses, processing food for energy and repairing the damage of inflammation. Keeping the gut healthy is relatively simple. It’s worth it because the gut and especially gut flora provide a necessary foundation for your health. Gut flora. “Bacteria and other organisms that live inside the intestines. They help digest food. Vitamins such as biotin and vitamin K are made by gut flora. Also called gut microflora, intestinal flora, intestinal microflora, and microflora.” (National Cancer Institute) Probiotics. “Probiotics are living microorganisms that, when ingested, provide numerous health benefits.” (Healthline) LINKS & RESOURCES: Follow Dr. Nada on: Linkedin https://www.linkedin.com/in/nada-milo... Sage Tonic www.sagetonic.com Sage Tonic on Instagram https://www.instagram.com/sagetonic/ “Microflora,” in NCI Dictionary of Cancer Terms, National Cancer Institute, https://www.cancer.gov/publications/dictionaries/cancer-terms/def/microflora, accessed January 2019. “Probiotics 101: A Simple Beginner’s Guide,” Healthline, https://www.healthline.com/nutrition/probiotics-101, accessed January 2019. Morgan Bickenbach-Davies, “Here’s How Your Gut Plays a Major Role in Your Athletic Performance,” Braveheart Coaching, February 22, 2017, http://www.braveheartcoach.com/2017/02/22/healthy-gut-healthy-athlete/, accessed January 2019. SUBSCRIBE: Apple Podcasts: http://bit.ly/SpartanUpShow YouTube: http://bit.ly/SpartanUpYT Google Play: http://bit.ly/SpartanUpPlay FOLLOW SPARTAN UP: Spartan Up on Instagram https://www.instagram.com/spartanuppo... Spartan Up on Twitter https://twitter.com/SpartanUpPod CREDITS: Producer: Marion Abrams, Madmotion, llc. Writer and Host: Nada Milosavljevic MD, JD © 2019 Spartan
The interferon defense for bats is switched on all the time, creating an upfront attack against disease without causing a toxic reaction.
Before we learned to make antimicrobial medicines and vaccines, before we had disinfectants and chemotherapies, we had interferons to thank for protection from viral infections. UC Santa Barbara Distinguished Professor Charles Samuel, an internationally recognized pioneer and leader in the study of interferons, explores why they remain a critical and significant field of research, especially in an age of powerful and constantly evolving viruses that spread rapidly. Series: "Scientific Horizons" [Science] [Show ID: 33097]
Before we learned to make antimicrobial medicines and vaccines, before we had disinfectants and chemotherapies, we had interferons to thank for protection from viral infections. UC Santa Barbara Distinguished Professor Charles Samuel, an internationally recognized pioneer and leader in the study of interferons, explores why they remain a critical and significant field of research, especially in an age of powerful and constantly evolving viruses that spread rapidly. Series: "Scientific Horizons" [Science] [Show ID: 33097]
In spite of being hosts for a multitude of different viruses, bats don’t display any signs of the resulting diseases. What is it that keeps these creatures of the night so healthy?
Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV.
Christine Biron is the chair of the Department of Molecular Microbiology and Immunology at Brown University in Providence, and she focuses her research program on the mechanisms of the innate immune system – the body’s system of non-specific munitions for fighting off pathogens. Dr. Biron is also a newly elected fellow of the American Academy of Microbiology. When a pathogen gets on or in your body, your innate immune system is on the front lines, working against the pathogen is a non-specific manner. In research, the innate immune system got short shrift for a long time, and only in the last 10 or 20 years has the field picked up momentum. Dr. Biron says back when she was in graduate school “the innate immune system wasn’t thought to be very cool”, but she says the field is fast-moving today, in part because of some major discoveries involving Type-1 interferons, natural killer cells, and an increased appreciation of a wider range of antigen processing cells that link the innate and adaptive immune responses. In this interview, I talked with Dr. Biron about our increasing awareness of the innate immune system, why it’s important to bring microbiologists and immunologists together under one big tent, and why it’s best that a battle between a virus and a host ends not in victory for one and defeat for the other, but in détente.
Helen Frankish discusses research on childhood stroke, and add-on drug therapy for MS.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 02/06
Interferons are the key cytokines of innate immunity and represent the first line of defense against invading viruses. By activating immediate antiviral mechanisms and stimulating the adaptive immune response, interferon signaling is decisive for the outcome of disease and virus clearance. The work presented in this thesis reveals a central role of the phosphoprotein P of rabies virus (Rhabdoviridae family), known as a polymerase cofactor, as an inhibitor of the host interferon system. Counter-mechanism to escape form recognition by the immune system were previously unknown for the neurotropic rabies virus, which is characterized by the highest case-fatality ratio. In my work I have shown that rabies virus (strain SAD L16) is able to prevent both the production IFN-alpha/beta and the effector functions of IFN-alpha/beta and IFN-gamma. The factor responsible is the viral phosphoprotein P. P interferes with transcriptional activation of IFN-alpha/beta by preventing phosphorylation of the essential transcription factors IRF3 and IRF7 by their kinases TBK1 and IKKepsilon. Unphosphorylated IRFs are unable to dimerize and fail to enter the nucleus. In addition, rabies virus P prevents IFN-mediated JAK/STAT signaling and the expression of IFN-stimulated genes which include a broad spectrum of antiviral and immune regulatory genes. The inhibition of JAK/STAT signaling by P involves a unique mechanism, namely, specific binding of the tyrosine-phosphorylated STAT1 and STAT2 isoforms and their retention in the cytoplasm. The inhibitory activities of RV P on IFN induction and signaling are independent functions, as shown by site-directed mutagenesis of P and identification of different short amino acid stretches required for either function. Importantly, the inhibitory activities of P were demonstrated in the context of recombinant viruses. Using reverse genetics, a rabies virus was constructed, in which P expression was “knocked down” by moving the P gene to a promoter-distal position of the genome (SAD deltaPLP). This virus caused efficient IFN-alpha/beta production in infected cells and upregulation of interferon stimulated genes. The IFN sensitivity of SAD deltaPLP was confirmed in cell culture and is now being studied in animal experiments including IFN receptor knock of mice, to verify the relevance of P functions in vivo. The described work contributes to the understanding of host responses to virus infections in general and of rabies virus pathogenicity in particular. In addition, viruses with modified IFN antagonists provide interesting opportunities for development of attenuated vaccines and vectors.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 02/07
Feline herpesvirus-1 (FHV-1)-infection, also known as feline viral rhinotracheitis (FVR) is distributed world wide in the cat population, with a high incidence in colony cats (>70%). FHV-1 typically infects and replicates in epithelial tissue of the upper respiratory tract and conjunctiva causing cytopathic lesions. The virus is recognized as one of the most important pathogens of feline upper respiratory tract infections, conjunctivitis and keratitis in cats. Following primary infection over 80% of cats are unable to eliminate the virus and develop a carrier state, with intermittent episodes of virus shedding. During latency, the virus persists most often in the trigeminal ganglion and the disease can be reactivated following stress and corticosteroid therapy. Successful treatment, particularly of ocular manifestations associated with recrudescent infection such as dendritic ulcers remains difficult. Available antiviral drugs are virostatic and in particular, the systemic application is associated with severe toxic side effects. Human natural and recombinant interferons and feline interferons have been described in their use against a selection of feline and canine viruses (JAMESON and ESSEX, 1983; FULTON and BURGE, 1985; WEISS and TOIVIO-KINNUCAN, 1988; WEISS, 1989; WEISS and OOSTROM-RAM, 1990; TRUYEN et al., 2001). To date, only two in vitro studies indicate a potent antiviral activity of the recombinant FeIFN-ω against FHV-1 (MOCHIZUKI et al., 1994, TRUYEN et al., 2001). The purpose of this study was to evaluate the antiviral efficacy of the recently available rFeIFN-ω (Virbagen®-ω) and the human rHuIFN-α2b (Intron®-A) on the replication of FHV-1 in vitro. A wider range of concentrations (100 U/ml – 500,000 U/ml) was studied than used in the previous studies (WEISS , 1989; MOCHIZUKI et al., 1994, TRUYEN et al., 2001) in order to repeat previously tested concentration and further, to determine whether the drugs have a dose-dependant response of antiviral activity and which concentration would be the most effective treatment. The species-specificity of type I interferons is well known and therefore, it was suggested that rFeIFN-ω would result in a more profound effect compared to the rHuIFN-α2b due to its homologous nature. In addition to cell and virus culture techniques, a methodology for the plaque reduction assay was established. Furthermore, for the first time antiviral efficacy for interferon was additionally measured by plaque size reductions and is reported in this study. An in vitro MTT-Assay was integrated in the experiment to exclude possible cytotoxic effects that could, in principle, contribute to the antiviral effects observed with either of the interferon treatments. For the plaque reduction assay, confluent monolayers of Crandell feline kidney (CRFK)-cells were grown in 24-well cell culture plates. Cells were treated with either rFeIFN-ω (Virbagen® Omega) or rHuIFN-α2b (Intron®-A) across a set of serial dilutions (100 U/ml - 500,000 U/ml). Cells were treated six hours before addition of FHV-1, concurrent with addition of FHV-1 and each drug concentration was added to the overlay medium (2X DMEM 1:1 with 1.6% Agarose). The treatments were performed in duplicates including virus controls, which received PBS instead of either one of the interferons and assays were performed on six occasions. Following incubation of 72 hrs, the cells were fixed with formalin, overlay plugs were discarded and the remaining cell layers were stained with crystal violet. Plaque numbers were counted under an inverted microscope and Plaque diameters were measured using a reticule. For the MTT-assay, 96-well culture plates were seeded with CRFK-cells. In each of the test wells (n=16) growth medium was supplemented with either rHuIFN-α2b or with rFeIFN-ω. Control wells (n=72) received growth medium with PBS instead of either one of the Interferons. Cell-death controls were treated with ethanol to obtain 100% cell death. After incubation, the medium was aspirated and replaced with medium containing the MTT-solution. Following another incubation period, the medium of each well was removed and replaced with a solubilization solution (0.1N HCL/Isopropanol). The plates were incubated for an additional five minutes to dissolve the crystals and the plates were read using a plate reader. The average optical densities were calculated for each dilution and compared with that of the positive control wells. A one-way ANOVA and Dunnett’s test were used for the statistical analysis of all experiments. A significant reduction of plaque numbers was observed for rFeIFN-ω at 100,000 U/ml with a plaque reduction of 54.7 % and at 500,000 U/ml with a plaque reduction of 59.8 %. Plaque sizes were significantly reduced by 47.5 % at 100,000 U/ml and by 81 % at 250,000 U/ml and 70.5% at 500,000 U/ml. Recombinant HuIFN-α2b treatment did not succeed to produce any significant plaque number reduction. However, significant plaque size reductions were observed following treatment with 100,000 U/ml, 250,000 U/ml and 500,000 U/ml with reductions of 56 %, 75.7% and 69% respectively. None of the high-dose treatments of either rHuIFN-α2b or rFeIFN-ω caused significant cellular toxicity in the MTT-Assay. Therefore, the antiviral activity demonstrated by both interferons is not attributable to an in vitro effect on the cellular viability of CRFK-cells. In agreement with previous authors, this study was able to demonstrated that rFeIFN-ω and rHuIFN-α2b have inhibitory effects on the replication of FHV-1. For rFeIFN-ω the antiviral effect is dose-dependent and could be reliably detected at high concentrations (> 50,000 U/ml) using both the plaque number and plaque size measurements. Treatment with high concentrations of rHuIFN-α2b also resulted in an antiviral effect, which was only detected at using the plaque size measure; there was no statistical evidence for a reduction in the plaque number measurement. The significantly smaller plaque sizes in drug–treated cell cultures indicate that high-dose treatment with rFeIFN-ω or rHuIFN-α2b may have potential efficacy on reducing the dimensions of FHV-1 induced cytopathic lesions. Treatment with rFeIFN-ω has shown more profound effects in antiviral activity compared to rHuIFN-α2b and, in contrast to rHuIFN-α2b, it also offers the advantage of a homologous compound. This is consistent with recently published results obtained on in vivo activity, which have demonstrated that high-dose treatment of rFeIFN-ω shows good antiviral efficacy and clinical improvement (VERNEUIL, 2004; BRAECKLEIN et al., 2003). Therefore, there are indications that rFeIFN-ω may provide effective prophylactic and therapeutic treatment for FHV-1 infected cats.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07
Marek´s disease virus (MDV) is a herpesvirus causing a lymphoproliferative disorder of domestic chickens worldwide. The early signs of disease like apathy, anorexy and the transient paralysis as well as the symptoms at the later stages (Neoplasia and death) causes large economical problems in the chicken industry. With the development of an effetive Vaccine, the first practical vaccine against an oncogenic disease of any type in any spieces, most of the serious problems were solved. However recent reports describing an increased virulence resulting in vaccine breaks, indicates a demand for better vaccines. To be able to enhance the prophylaxis against Marek´s disease virus, the understanding of the interaction between host and virus needs to be expanded. Interferons are cytokines with antiviral activity. On the basis of their structural and functional features they can be divided into type I (IFN-alpha and IFN-beta) and type II (IFN-gamma) interferons. Type I plays an important role during the early phase of viral infections, while IFN-gamma has a prominent role later during the infection through its immunmodulatory functions. In this study it was shown that chicken embryocellcultures responds to the infection with either an apathogenic strain of MDV (CVI 988) or a highly pathogenic strain (RB1B), with the secretion of an antiviral factor. Neutralisation with cytokine specific antibodies revealed that this activity could only be attributed to IFN-alpha but not IFN-beta. In addition, synthesis of IFN-gamma was not observed in any of the experiments. Treatment of MDV infected embryocellcultures with either recombinant chicken IFN-alpha (rChIFN-alpha) or recombinant chicken IFN-gamma (rChIFN-gamma) led to a significant reduction in plaque numbers. This antiviral effect was still observed when cultures were treated 48 hours after infection. In order to understand the functional role of the IFNs in vivo, leghorn birds were repeatedly treated with rChIFN-alpha or rChIFN-gamma for ten weeks starting on the day of hatch. The birds were then challanged on the second day of life with a highly virulent MDV-strain (vv+, EU-1). Treatment with IFN-gamma delayed the mortality to a very small degree. In contrast, IFN-alpha treatment delayed the mortality for 3 weeks. However, prevention of the disease was not achieved regardless of the used IFN-alpha dose. The functional relevance of IFN-alpha was further underscored by experiments where birds were treated with a neutralizing monoclonal antibody to ChIFN-alpha and thereafter infected with the EU-1 strain at the second day of life. Birds in this group died 3 weeks earlier than those in the untreated control group. These data shows that Interferons play a role in the progression of Mareks disease, however, regardless the IFN-dose applicated, the disease could not be prevented by the cytokines on their own.
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