The National Library of Medicine.

Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics. Purpose: To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia. Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched. Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group. Data Extraction: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality. Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% Cl, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after ≥4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41 % [Cl, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients. Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed. Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.

Meta-analysis: Convalescent blood products for spanish influenza pneumonia : A future H5N1 treatment? Commentary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2, is a positive-sense single-stranded RNA virus with epithelial cell and respiratory system proclivity. Like its predecessor, SARS-CoV, COVID-19 can lead to life-threatening disease. Due to wide geographic impact affecting an extremely high proportion of the world population it was defined by the World Health Organization as a global public health pandemic. The infection is known to readily spread from person-to-person. This occurs through liquid droplets by cough, sneeze, hand-to-mouth-to-eye contact and through contaminated hard surfaces. Close human proximity accelerates SARS-CoV-2 spread. COVID-19 is a systemic disease that can move beyond the lungs by blood-based dissemination to affect multiple organs. These organs include the kidney, liver, muscles, nervous system, and spleen. The primary cause of SARS-CoV-2 mortality is acute respiratory distress syndrome initiated by epithelial infection and alveolar macrophage activation in the lungs. The early cell-based portal for viral entry is through the angiotensin-converting enzyme 2 receptor. Viral origins are zoonotic with genomic linkages to the bat coronaviruses but without an identifiable intermediate animal reservoir. There are currently few therapeutic options, and while many are being tested, although none are effective in curtailing the death rates. There is no available vaccine yet. Intense global efforts have targeted research into a better understanding of the epidemiology, molecular biology, pharmacology, and pathobiology of SARS-CoV-2. These fields of study will provide the insights directed to curtailing this disease outbreak with intense international impact. Graphical Abstract.

/pdf/the-natural-history-pathobiology-and-clinical-manifestations-99m1qozpet.pdf

The Natural History, Pathobiology, and Clinical Manifestations of SARS-CoV-2 Infections.

Iconographies supplémentaires de l'article : New insights into the antiviral effects of chloroquine

In December 2019, a novel coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or (2019-nCoV) with unknown origin spread in Hubei province of China. The epidemic disease caused by SARS-CoV-2 called coronavirus disease-19 (COVID-19). The presence of COVID-19 was manifested by several symptoms, ranging from asymptomatic/mild symptoms to severe illness and death. The viral infection expanded internationally and WHO announced a Public Health Emergency of International Concern. To quickly diagnose and control such a highly infectious disease, suspicious individuals were isolated and diagnostic/treatment procedures were developed through patients’ epidemiological and clinical data. Early in the COVID-19 outbreak, WHO invited hundreds of researchers from around the world to develop a rapid quality diagnosis, treatment and vaccines, but so far no specific antiviral treatment or vaccine has been approved by the FDA. At present, COVID-19 is managed by available antiviral drugs to improve the symptoms, and in severe cases, supportive care including oxygen and mechanical ventilation is used for infected patients. However, due to the worldwide spread of the virus, COVID-19 has become a serious concern in the medical community. According to the current data of WHO, the number of infected and dead cases has increased to 8,708,008 and 461,715, respectively (Dec 2019 –June 2020). Given the high mortality rate and economic damage to various communities to date, great efforts must be made to produce successful drugs and vaccines against 2019-nCoV infection. For this reason, first of all, the characteristics of the virus, its pathogenicity, and its infectious pathways must be well known. Thus, the main purpose of this review is to provide an overview of this epidemic disease based on the current evidence.

/pdf/a-comprehensive-review-of-covid-19-characteristics-qmao3dcgeu.pdf

A comprehensive review of COVID-19 characteristics

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented unprecedented challenges to the healthcare systems in almost every country around the world. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes infection prevention and control measures and supportive care including supplemental oxygen and mechanical ventilatory support. Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. In this review, we will update and summarize the most common and plausible drugs for the treatment of COVID-19 patients. These drugs and therapeutic agents include antiviral agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir), and supporting agents (Ascorbic acid, Azithromycin, Corticosteroids, Nitric oxide, IL-6 antagonists), among others. We hope that this review will provide useful and most updated therapeutic drugs to prevent, control, and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2.

/pdf/an-update-on-current-therapeutic-drugs-treating-covid-19-4wibu0bl0n.pdf

An Update on Current Therapeutic Drugs Treating COVID-19.

Cancer is a complex disease and cancer development takes 10–50 years involving epigenetics. Evidence suggests that approximately 80% of human cancers are linked to environmental factors impinging upon genetics/epigenetics. Because advanced metastasized cancers are resistant to radiotherapy/chemotherapeutic drugs, cancer prevention by relatively nontoxic chemopreventive “epigenetic modifiers” involving epigenetics/epigenomics is logical. Isothiocyanates are relatively nontoxic at low nutritional and even higher pharmacologic doses, with good oral bioavailability, potent antioxidative stress/antiinflammatory activities, possess epigenetic-modifying properties, great anticancer efficacy in many in vitro cell culture and in vivo animal models. This review summarizes the latest advances on the role of epigenetics/epigenomics by isothiocyanates in prevention of skin, colon, lung, breast, and prostate cancers. The exact molecular mechanism how isothiocyanates modify the epigenetic/epigenomic machinery is unclear. We postulate “redox” processes would play important roles. In addition, isothiocyanates sulforaphane and phenethyl isothiocyanate, possess multifaceted molecular mechanisms would be considered as “general” cancer preventive agents not unlike chemotherapeutic agents like platinum-based or taxane-based drugs. Analogous to chemotherapeutic agents, the isothiocyanates would need to be used in combination with other nontoxic chemopreventive phytochemicals or drugs such as NSAIDs, 5-α-reductase/aromatase inhibitors targeting different signaling pathways would be logical for the prevention of progression of tumors to late advanced metastatic states.

/pdf/epigenetics-epigenomics-and-prevention-of-early-stages-of-4z0w74wv6w.pdf

Epigenetics/Epigenomics and Prevention of Early Stages of Cancer by Isothiocyanates.

Redox signaling, mitochondrial metabolism, epigenetics and redox active phytochemicals.

SCOPE
Butyrate (B) is a short-chain fatty acid produced by dietary fiber, known to inhibit histone deacetylases (HDACs) and possess cancer-preventive/anticancer effects. However, the role of B in metabolic rewiring, epigenomic reprogramming, transcriptomic network, NRF2 signaling and eliciting cancer-preventive effects in colorectal cancer (CRC) HCT116 cell remains unclear.


METHODS AND RESULTS
Sodium butyrate (NaB) dose-dependently inhibited the growth of CRC HCT116 cells. NaB inhibited NRF2/NRF2-target genes and blocked NRF2-ARE signaling. NaB increased NRF2 negative regulator KEAP1 expression through inhibiting its promoter methylation. Associative analysis of DEGs (differentially expressed genes) from RNA-seq and DMRs (differentially methylated regions) from CpG methyl-seq identified the tumor suppressor gene ABCA1 and tumor promote gene EGR3 were correlated with their promoters' CpG methylation indicating NaB regulates cancer markers through modulating their promoter methylation. NaB activated the mitochondrial tricarboxylic acid (TCA) cycle while inhibited the methionine metabolism which are both tightly coupled to the epigenetic machinery. NaB regulated the epigenetic enzymes/genes including DNMT1, HAT1, KDM1A, KDM1B and TET1. Altogether, B's regulation of metabolites coupled to the epigenetic enzymes illustrates the potential underlying biological connectivity between metabolomics and epigenomics.


CONCLUSION
B regulates KEAP1/NRF2 signaling, drives metabolic rewiring, CpG methylomic and transcriptomic reprogramming contributing to the overall cancer-prevention/anticancer effect in the CRC cell model. This article is protected by copyright. All rights reserved.

Butyrate Drives Metabolic Rewiring and Epigenetic Reprogramming in Human Colon Cancer Cells.

Metabolic rewiring and epigenetic reprogramming are closely inter-related, and mutually regulate each other to control cell growth in cancer initiation, promotion, progression, and metastasis. Epigenetics plays a crucial role in regulating normal cellular functions as well as pathological conditions in many diseases, including cancer. Conversely, certain mitochondrial metabolites are considered as essential cofactors and regulators of epigenetic mechanisms. Furthermore, dysregulation of metabolism promotes tumor cell growth and reprograms the cells to produce metabolites and bioenergy needed to support cancer cell proliferation. Hence, metabolic reprogramming which alters the metabolites/epigenetic cofactors, would drive the epigenetic landscape, including DNA methylation and histone modification, that could lead to cancer initiation, promotion, and progression. Recognizing the diverse array of benefits of phytochemicals, they are gaining increasing interest in cancer interception and treatment. One of the significant mechanisms of cancer interception and treatment by phytochemicals is reprogramming of the key metabolic pathways and remodeling of cancer epigenetics. This review focuses on the metabolic remodeling and epigenetics reprogramming in cancer and investigates the potential mechanisms by which phytochemicals can mitigate cancer.

https://www.pnfs.or.kr/journal/download_pdf.php?doi=10.3746/pnf.2022.27.4.335

Ahmad Shannar

Papers

An Update on Current Therapeutic Drugs Treating COVID-19.

Epigenetics/Epigenomics and Prevention of Early Stages of Cancer by Isothiocyanates.

Redox signaling, mitochondrial metabolism, epigenetics and redox active phytochemicals.

Butyrate Drives Metabolic Rewiring and Epigenetic Reprogramming in Human Colon Cancer Cells.

A New Frontier in Studying Dietary Phytochemicals in Cancer and in Health: Metabolic and Epigenetic Reprogramming