The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

The JAK/STAT signaling pathway: from bench to clinic.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recognised by the WHO as a pandemic in 2020. Host preparation to combat the virus is an important strategy to avoid COVID-19 severity. Thus, the relationship between eating habits, nutritional status and their effects on the immune response and further implications in viral respiratory infections is an important topic discussed in this review. Malnutrition causes the most diverse alterations in the immune system, suppressing of the immune response and increasing the susceptibility to infections such as SARS-CoV-2. On the other hand, obesity induces low-grade chronic inflammation caused by excess adiposity, which increases angiotensin-converting enzyme 2. It decreases the immune response favouring SARS-CoV-2 virulence and promoting respiratory distress syndrome. The present review highlights the importance of food choices considering their inflammatory effects, consequently increasing the viral susceptibility observed in malnutrition and obesity. Healthy eating habits, micronutrients, bioactive compounds and probiotics are strategies for COVID-19 prevention. Therefore, a diversified and balanced diet can contribute to the improvement of the immune response to viral infections such as COVID-19.

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Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2.

The world is now experiencing its third major epidemic of coronavirus (CoV) infections began in Wuhan, Hubei, China, in late 2019 and named COVID-19. After an initial explosive outbreak of pneumonia of unknown etiology in China, the disease spread first to neighboring Asian countries and then worldwide. Patients with COVID-19 presented with a constellation of symptoms such as fever, dry cough, dyspnea, sore throat, and nasal congestion and radiological findings showed bilateral lung glassy opacities. Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death, including physical barrier, cellular natural immunity, and adaptive immunity. Vitamin D supplementation has shown favorable effects in viral infections including influenza and HIV. The effects of vitamin D supplementation during covid 19 infection remain controversial. Looking ahead, clinical studies are needed to define better cut offs for vitamin D levels and, finally, which dosage is the best.

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Vitamin D and Covid-19: an update on evidence and potential therapeutic implications.

The COVID-19 pandemic is a global health emergency, and therefore the prevention and treatment of this disease is an important priority of world health In the present study, some risk factors, including unhealthy nutrition, obesity, and physical inactivity, were assessed in patients infected with SARS-CoV-2, and their effects on the severity and duration of disease were evaluated The present study was a cross-sectional study Data was collected from all patients who visited the respiratory emergency department from March 20, 2020 to April 24, 2020 in the University Hospital The outcome measures were body mass index, diet quality that was evaluated with a 16-item food intake questionnaire, and physical activity level that was assessed by the global physical activity questionnaire Two hundred and six patients’ data was analyzed The results investigated that patients with lower levels of physical activity or lower METmin/week were affected by a more severe form of the disease (p = 005 and p = 003, respectively) We found that patients with a healthier dietary pattern were affected by lower severity of illness (p < 005) It seems that increasing levels of physical activity may partly reduce the severity of COVID-19 disease Some dietary patterns such as increasing fruit and poultry consumption as well as drinking less tea were correlated significantly with a less severe form of the disease The results did not confirm previous concerns regarding a potentially harmful effect of smoking on the severity or duration of symptoms

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Relationship between physical activity, healthy lifestyle and COVID-19 disease severity; a cross-sectional study.

Background As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Results We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. Conclusions These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

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Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor.

Catechins, phytochemicals contained mainly in green tea, exhibit antiviral activity against various acute infectious diseases experimentally. Clinical evidence supporting these effects, however, is not conclusive. We performed a placebo-controlled, single-blind, randomized control trial to evaluate the clinical effectiveness of consumption of catechins-containing beverage for preventing acute upper respiratory tract infections (URTIs). Two hundred and seventy healthcare workers were randomly allocated to high-catechin (three daily doses of 57 mg catechins and 100 mg xanthan gum), low-catechin (one daily dose of 57 mg catechins and 100 mg xanthan gum), or placebo (0 mg catechins and 100 mg xanthan gum) group. Subjects consumed a beverage with or without catechins for 12 weeks from December 2017 through February 2018. The primary endpoint was incidence of URTIs compared among groups using a time-to-event analysis. A total of 255 subjects were analyzed (placebo group n = 86, low-catechin group n = 85, high catechin group n = 84). The URTI incidence rate was 26.7% in the placebo group, 28.2% in the low-catechin group, and 13.1% in the high-catechin group (log rank test, p = 0.042). The hazard ratio (95% confidence interval (CI)) with reference to the placebo group was 1.09 (0.61–1.92) in the low-catechin group and 0.46 (0.23–0.95) in the high-catechin group. These findings suggest that catechins combined with xanthan gum protect against URTIs.

https://www.mdpi.com/2072-6643/12/1/4/pdf

Shinji Yamamoto

Papers

Prevention of Acute Upper Respiratory Infections by Consumption of Catechins in Healthcare Workers: A Randomized, Placebo-Controlled Trial