Anti-inflammatory effect of resveratrol in human coronary arterial endothelial cells via induction of autophagy: implication for the treatment of Kawasaki disease.

NOTE: Its not known if these effects would translate to beneficial effects in COVID-19 at all. Please don't think it's known if it would or would not, it's not. ------ Kawasaki disease (KD) is an acute febrile vasculitis in childhood, which is the leading cause of acquired heart disease in children. If untreated, KD can result in coronary aneurysms in 25% of patients, and even under intravenous immunoglobulin (IVIG) treatment, 10-20% of children will have IVIG resistance and increased risk of developing coronary arteritis complication. Additional therapies should be explored to decrease the incidence of coronary artery lesions and improve the prognosis in KD. Autophagy has been reported to play a critical role in a variety of heart diseases. Resveratrol (RSV) confers cardio protection during ischemia and reperfusion in rats via activation of autophagy. Serum TNF-alpha levels are elevated in KD, which might activate the endothelial cells to express intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1(VCAM-1), inducible nitric oxide synthase (iNOS) and IL-1β. METHODS: Human coronary arterial endothelial cells (HCAECs) were either untreated or treated by TNF-α 10 ng/ml for 2 h in the presence or absence of RSV or autophagy-related protein 16-like 1 (Atg16L1) siRNA. Total RNA was analyzed by real-time quantitative PCR for ICAM-1, VCAM-1, iNOS and IL-1β mRNA expressions. The involvement of autophagy proteins was investigated by Western blot. RESULTS: Pretreatment with resveratrol significantly inhibited TNF-α-induced ICAM-1, iNOS and IL-1β mRNA expression in HCAECs. Western blot revealed the enhanced autophagy proteins LC3B and Atg16L1 expression by RSV. The suppressive effects of RSV were obviously counteracted by Atg16L1 siRNA. CONCLUSIONS: We demonstrated RSV had anti-inflammatory effects on HCAECs via induction of autophagy. Our results suggest that resveratrol may modulate the inflammatory response of coronary artery in KD and explore the role of autophagy in the pathogenesis and alternative therapy of coronary arterial lesions in KD. KEYWORDS: Autophagy; Endothelial cells; Kawasaki disease; Resveratrol PMID: 28069066 PMCID: PMC5223384 DOI: 10.1186/s40360-016-0109-2

6000 Coronavirus dead unreported in Guayaquil: Corpses left on the sidewalk.

Ecuador has the highest per capita COVID-19 death toll in Latin America and the Caribbean. This story shows what will likely happen to the countries that have current infections if we abandon the social distancing too soon. The government should take care of people forced to stay at home, not give up on the poor and allow them to be evicted and forced to stand in line for aid. It should not be telling people to do things that will get them sick. This is why we should never have signed away the right to regulate. If we did not have GATS we could have public healthcare and housing, in particular. Not be trapped at a level set in the 90s. just before GATS (and perhaps soon TISA, TTIP, etc.) put us on their one way path to eventual "full unemployment" (due to it's massive offshoring, outsourcing, etc. jobs, a process which is only just beginning. Why? Its cheaper to offshore and outsource the jobs to temporary workers from developing countries than pay decent wages. That is "services liberalization": the Washington Consensus's real plan for everything. We should especially dump GATS before it dumps us.)

Antiviral properties of resveratrol against pseudorabies virus are associated with the inhibition of IκB kinase activation

Sci Rep. 2017; 7: 8782. Published online 2017 Aug 18. doi: 10.1038/s41598-017-09365-0 PMCID: PMC5562710 PMID: 28821840 Pseudorabies virus (PRV) is a pathogen of swine resulting in devastating disease and economic losses worldwide. Resveratrol (Res) exhibits inhibitory activity against a wide range of viruses. Despite these important advances, the molecular mechanism(s) by which Res exerts its broad biological effects have not yet been elucidated. In this paper, the antiviral activity of Res against PRV and its mechanism of action were investigated. The results showed that Res potently inhibited PRV replication in a dose-dependent manner, with a 50% inhibition concentration of 17.17 μM. The inhibition of virus multiplication in the presence of Res was not attributed to direct inactivation or inhibition of viral entry into the host cells but to the inhibition of viral multiplication in host cells. Further studies demonstrated that Res is a potent inhibitor of both NF-κB activation and NF-κB-dependent gene expression through its ability to inhibit IκB kinase activity, which is the key regulator in NF-κB activation. Thus, the inhibitory effect of Res on PRV-induced cell death and gene expression may be due to its ability to inhibit the degradation of IκB kinase. These results provided a new alternative control measure for PRV infection and new insights into the antiviral mechanism of Res.

Resveratrol inhibits rhinovirus replication and expression of inflammatory mediators in nasal epithelia.

Antiviral Res. 2015 Nov;123:15-21. doi: 10.1016/j.antiviral.2015.08.010. Epub 2015 Aug 19. Resveratrol inhibits rhinovirus replication and expression of inflammatory mediators in nasal epithelia. Mastromarino P1, Capobianco D2, Cannata F2, Nardis C2, Mattia E2, De Leo A2, Restignoli R3, Francioso A4, Mosca L4. Author information Abstract Human rhinoviruses (HRV), the cause of common colds, are the most frequent precipitants of acute exacerbation of asthma and chronic obstructive pulmonary disease, as well as causes of other serious respiratory diseases. No vaccine or antiviral agents are available for the prevention or treatment of HRV infection. Resveratrol exerts antiviral effect against different DNA and RNA viruses. The antiviral effect of a new resveratrol formulation containing carboxymethylated glucan was analyzed in H1HeLa cell monolayers and ex vivo nasal epithelia infected with HRV-16. Virus yield was evaluated by plaque assay and expression of viral capsid proteins by Western blot. IL-10, IFN-β, IL-6, IL-8 and RANTES levels were evaluated by ELISA assay. ICAM-1 was assessed by Western blot and immunofluorescence. Resveratrol exerted a high, dose-dependent, antiviral activity against HRV-16 replication and reduced virus-induced secretion of IL-6, IL-8 and RANTES to levels similar to that of uninfected nasal epithelia. Basal levels of IL-6 and RANTES were also significantly reduced in uninfected epithelia confirming an anti-inflammatory effect of the compound. HRV-induced expression of ICAM-1 was reversed by resveratrol. Resveratrol may be useful for a therapeutic approach to reduce HRV replication and virus-induced cytokine/chemokine production. Copyright © 2015 Elsevier B.V. All rights reserved. KEYWORDS: Human rhinovirus; Inflammatory mediators; Nasal epithelia; Resveratrol PMID: 26296578 DOI: 10.1016/j.antiviral.2015.08.010

Antioxidant and anti-inflammatory effects of resveratrol in airway disease.

Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are a significant and increasing global health problem. These diseases are characterized by airway inflammation, which develops in response to various stimuli. In asthma, inflammation is driven by exposure to a variety of triggers, including allergens and viruses, which activate components of both the innate and acquired immune responses. In COPD, exposure to cigarette smoke is the primary stimulus of airway inflammation. Activation of airway inflammatory cells leads to the release of excessive quantities of reactive oxygen species (ROS), resulting in oxidative stress. Antioxidants provide protection against the damaging effects of oxidative stress and thus may be useful in the management of inflammatory airways disease. Resveratrol, a polyphenol that demonstrates both antioxidative and anti-inflammatory functions, has been shown to improve outcomes in a variety of diseases, in particular, in cancer. We review the evidence for a protective role of resveratrol in respiratory disease. Mechanisms of resveratrol action that may be relevant to respiratory disease are described. We conclude that resveratrol has potential as a therapeutic agent in respiratory disease, which should be further investigated.

Resveratrol as a potential therapeutic drug for respiratory system diseases

Respiratory system diseases are common and major ailments that seriously endanger human health. Resveratrol, a polyphenolic phytoalexin, is considered an anti-inflammatory, antioxidant, and anticancer agent. Thanks to its wide range of biological activities, resveratrol has become a hotspot in many fields, including respiratory system diseases. Indeed, research has demonstrated that resveratrol is helpful to relieve pulmonary function in the general population. Meanwhile, growing evidence indicates that resveratrol plays a protective role in respiratory system diseases. This review aimed to summarize the main protective effects of resveratrol in respiratory system diseases, including its anti-inflammatory, antiapoptotic, antioxidant, antifibrotic, antihypertensive, and anticancer activities. We found that resveratrol plays a protective role in the respiratory system through a variety of mechanisms, and so it may become a new drug for the treatment of respiratory system diseases. Keywords: respiratory system diseases, resveratrol, inflammation, apoptosis, oxidation

WebMD on COVID-19 CNS symptoms

It's mainstream recognition that this is a danger to people, and that brainstem involvement may be one of the reasons people stop breathing. Personally, I suspect from what I have read that its a significant cause of mortality in COVID-19. If we can protect the brain, prevent apoptosis, far fewer people may die.

Resveratrol was predicted to have possible activity against COVID-19 by a cutting edge medical informatics program looking for substances active against coronavirus induced heart damage.

Exploration of omics mechanism and drug prediction of coronavirus-induced heart failure based on clinical bioinformatics. --------------------- Journal: Zhonghua Xin Xue Guan Bing Za Zhi. -------------------- 2020 Mar 31;48(0):E013. ----------------- doi: 10.3760/cma.j.cn112148-20200308-00172. [Epub ahead of print] ------------------------------------------- [Article in Chinese; Abstract available in Chinese from the publisher] ----------------------- Author information Chen XM1, Cao F2, Zhang HM1, Chen HR3, Zhang JD4, Zhi P3, Li ZY3, Wang YX5, Lu XC1. ---------------------- Abstract in English, Chinese Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc . There are 5 KEGG pathways, mainly interacting with tumor necrosis factor signaling pathway, IL-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the SREING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis are mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis. KEYWORDS: Bioinformatics; Coronavirus infections; Drug prediction; Heart failure PMID: 32228827 DOI: 10.3760/cma.j.cn112148-20200308-00172

Synthesis of stilbene derivatives with inhibition of SARS coronavirus replication.

Eur J Med Chem. 2006 Sep;41(9):1084-9. Epub 2006 Jul 27. Synthesis of stilbene derivatives with inhibition of SARS coronavirus replication. Li YQ1, Li ZL, Zhao WJ, Wen RX, Meng QW, Zeng Y. Author information Abstract Stilbene derivatives have wide range of activities. In an effort to find other potential activities of this kind of compounds, 17 derivatives, including resveratrol, were synthesized. Twelve of them were evaluated for their antiviral potential against severe acute respiratory syndrome (SARS)-CoV-induced cytopathicity in Vero E6 cell culture. The result showed that SARS virus was totally inhibited by compounds 17 and 19 (<or=0.5 mg ml(-1)) and no significant cytotoxic effects were observed in vitro. PMID: 16875760 DOI: 10.1016/j.ejmech.2006.03.024 [Indexed for MEDLINE] Share on FacebookShare on TwitterShare on Google+

Covid-19 and the Digestive System.

J Gastroenterol Hepatol. 2020 Mar 25. doi: 10.1111/jgh.15047. [Epub ahead of print] Covid-19 and the Digestive System. Wong SH1,2, Lui RN1,2, Sung JJ1,2. Author information Abstract The novel coronavirus disease (Covid-19) is currently causing a major pandemic. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Betacoronavirus genus that also includes the SARS-CoV and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). While patients typically present with fever and a respiratory illness, some patients also report gastrointestinal symptoms such as diarrhoea, vomiting and abdominal pain. Studies have identified the SARS-CoV-2 RNA in stool specimens of infected patients, and its viral receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in gastrointestinal epithelial cells. These suggest that SARS-CoV-2 can actively infect and replicate in the gastrointestinal tract. This has important implications to the disease management, transmission, and infection control. In this article, we review the important gastrointestinal aspects of the disease. This article is protected by copyright. All rights reserved. KEYWORDS: Covid-19; coronavirus; diarrhoea; gastrointestinal infection; pneumonia PMID: 32215956 DOI: 10.1111/jgh.15047 Share on FacebookShare on TwitterShare on Google+