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N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions.
Izquierdo-Alonso, JL, Pérez-Rial, S, Rivera, CG, Peces-Barba, G
Journal of infection and public health. 2022;(12):1477-1483
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19) and can be associated with serious complications, including acute respiratory distress syndrome. This condition is accompanied by a massive release of cytokines, also denominated cytokine storm, development of systemic oxidative stress and a prothrombotic state. In this context, it has been proposed a role for acetylcysteine (NAC) in the management of patients with COVID-19. NAC is a molecule classically known for its mucolytic effect, but it also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Other effects of NAC have also been described, such as modulating the immune and inflammatory response, counteracting the thrombotic state, and having an antiviral effect. The pharmacological activities of NAC and its effects on the mechanisms of disease progression make it a potential therapeutic agent for COVID-19. NAC is safe, tolerable, affordable, and easily available. Moreover, the antioxidant effects of the molecule may even prevent infection and play an important role as a complement to vaccination. Although the clinical efficacy and dosing regimens of NAC have been evaluated in the clinical setting with small series of patients, the results are promising. In this article, we review the pathogenesis of SARS-CoV-2 infection and the current knowledge of the mechanisms of action of NAC across disease stages. We also propose NAC posology strategies to manage COVID-19 patients in different clinical scenarios.
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COVID-19 and One-Carbon Metabolism.
Perła-Kaján, J, Jakubowski, H
International journal of molecular sciences. 2022;(8)
Abstract
Dysregulation of one-carbon metabolism affects a wide range of biological processes and is associated with a number of diseases, including cardiovascular disease, dementia, neural tube defects, and cancer. Accumulating evidence suggests that one-carbon metabolism plays an important role in COVID-19. The symptoms of long COVID-19 are similar to those presented by subjects suffering from vitamin B12 deficiency (pernicious anemia). The metabolism of a cell infected by the SARS-CoV-2 virus is reshaped to fulfill the need for massive viral RNA synthesis, which requires de novo purine biosynthesis involving folate and one-carbon metabolism. Many aspects of host sulfur amino acid metabolism, particularly glutathione metabolism underlying antioxidant defenses, are also taken over by the SARS-CoV-2 virus. The purpose of this review is to summarize recent findings related to one-carbon metabolism and sulfur metabolites in COVID-19 and discuss how they inform strategies to combat the disease.
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Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.
Bisht, D, Rashid, M, Arya, RKK, Kumar, D, Chaudhary, SK, Rana, VS, Sethiya, NK
Phytomedicine plus : international journal of phytotherapy and phytopharmacology. 2022;(1):100206
Abstract
BACKGROUND Glycyrrhiza glabra L. (G. glabra) commonly known as liquorice is one of the highly exploited and utilized medicinal plant of the world. Since ancient times liquorice is considered as an auspicious and valuable traditional medicine across the world for treatment of various ailments. METHOD Several electronic online scientific databases such as Science Direct, PubMed, Scopus, Scifinder, Google Scholar, online books and reports were assessed for collecting information. All the collected information was classified into different sections to meet the objective of the paper. RESULTS The electronic database search yielded 3908 articles from different countries. Out of them one ninety-eight articles published between 1956 and 2021 were included, corresponding to all detailed review on G. glabra and research on anti-inflammatories, antivirals and immunomodulatory through pre-clinical and clinical models. From all selective area of studies on G. glabra and its bioactive components it was established (including molecular mechanisms) as a suitable remedy as per the current requirement of pandemic situation arise through respiratory tract infection. CONCLUSION Different relevant studies have been thoroughly reviewed to gain an insight on utility of liquorice and its bioactive constituents for anti-inflammatories, antivirals and immunomodulatory effects with special emphasized for prevention and treatment of COVID-19 infection with possible mechanism of action at molecular level. Proposed directions for future research are also outlined to encourage researchers to find out various mechanistic targets and useful value added products of liquorice in future investigations.
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Antiviral and anti-inflammatory drugs to combat COVID-19: Effects on cardiac ion channels and risk of ventricular arrhythmias.
Cubeddu, LX, de la Rosa, D, Ameruoso, M
BioImpacts : BI. 2022;(1):9-20
Abstract
Introduction: Drugs with no indication for the treatment of cardiovascular diseases (e.g., drugs employed to treat COVID-19) can increase the risk of arrhythmias. Of interest, a six-fold increase in the number of arrhythmic events was reported in patients with severe COVID-19. In this study, we reviewed (i) the pro-arrhythmic action of drugs given to patients with COVID-19 infection, and (ii) the effects of inflammatory cytokines on cardiac ion channels and possible generation of arrhythmias. Methods: We conducted a literature search on the drugs with purported or demonstrated efficacy against COVID-19 disease, emphasizing the mechanisms by which anti-COVID-19 drugs and inflammatory cytokines interfere with cardiac ion channels. Results: Antibiotics (azithromycin), antimalarials (hydroxychloroquine, chloroquine), antivirals (ritonavir/lopinavir, atazanavir), and some of the tyrosine kinase inhibitors (vandetanib) could induce long QT and increase risk for ventricular arrhythmias. The pro-arrhythmic action results from drug-induced inhibition of Kv11.1 (hERG) channels interfering with the repolarizing potassium IKr currents, leading to long QT and increased risk of triggered arrhythmias. At higher concentrations, these drugs may interfere with IKs, IK1, and/or Ito potassium currents, and even inhibit sodium (INa) and calcium (ICa) currents, inducing additional cardiac toxicity. Ibrutinib, an inhibitor of Bruton's TK, increased the incidence of atrial fibrillation and ventricular tachycardia associated with a short QT interval. Inflammatory cytokines IL-6 and TNF-α inhibit IKr and Ito repolarizing potassium currents. High levels of inflammatory cytokines could contribute to the arrhythmic events. For remdesivir, favipiravir, dexamethasone, tocilizumab, anakinra, baricitinib, and monoclonal antibodies (bamlanivimab, etesevimab, and casirivimab), no evidence supports significant effects on cardiac ion channels, changes in the QT interval, and increased risk for ventricular arrhythmias. Conclusion: This study supports the concept of hERG channel promiscuity. Different drug classes given to COVID-19 patients might delay repolarization, and increase the risk of ventricular arrhythmias. The presence of comorbid pro-arrhythmic disease states, and elevated levels of pro-arrhythmic cytokines, could increase the risk of ventricular arrhythmias. Discontinuation of nonessential drugs and correction of electrolyte abnormalities could prevent severe ventricular arrhythmias. Altogether, the most effective therapies against COVID-19 (remdesivir, dexamethasone, monoclonal antibodies) lack pro-arrhythmic activity.
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Reshaping Food Policy and Governance to Incentivize and Empower Disadvantaged Groups for Improving Nutrition.
Wang, J, Ding, X, Gao, H, Fan, S
Nutrients. 2022;(3)
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has exacerbated global malnutrition challenges, disrupted food supply chains, and left poor and vulnerable people unable to produce and access safe and affordable food, especially in developing countries. Food policy and governance are currently malfunctioning, despite their recognized roles in improving food security and public nutrition in many local and national contexts. This article reviews existing food policies and governance with implications for disadvantaged groups in the food systems, particularly smallholder farmers, women, and small- and medium-sized enterprises (SMEs), highlighting the importance of reshaping food policies and governance. To end malnutrition in the post-COVID era, multiple sectors, including health, agriculture, social protection, education, and infrastructure, must make greater collaborative efforts to develop and implement food and nutrition policies. Several recommendations for reshaping food policy interventions and governance are summarized.
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Work Stress, Dysbiosis, and Immune Dysregulation: The Interconnected Triad in COVID-19 Infection in the Medical Team Staff - A Mini-Review.
Yousof, SM, Tanvir, I, Kolieb, E, Atta, R
Journal of microscopy and ultrastructure. 2022;(4):147-153
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Abstract
The COVID-19 pandemic has hit most of the communities around the globe. Earlier researches have reported the psychological effects of pandemics either on the general populations or on specific communities such as students and health professionals. A scanty number of papers have focused on the interaction among complex factors underlying the pathogenesis of the disease. In this review, we aimed to integrate the accessible data about the possible mechanistic processes predisposing to COVID-19 infection in the health professions. We summarized these factors as "stress, microbiota, and immunity triad." We utilized the PubMed database, Google, and Google Scholar search engines to search the literature related to combinations of these keywords: "pandemics, COVID-19, coronavirus, SARS-CoV2;" "gut microbiota, gut-lung axis, dysbiosis, nutrition;" "work stress, workload, health workers, health professions, and medical team;" and "immunity, cytokine storm, and viral load." We detected no discussions combining the suggested triad concerning the medical team personnel. We cast light, for the first time to our knowledge, on the potential pathogenic role of "stress, microbiota, and immunity triad" in COVID-19-infected health workers.
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Traditional Chinese medicine for promoting mental health of patients with COVID-19: a scoping review.
Ji, Z, Hu, H, Wang, D, Di Nitto, M, Fauci, AJ, Okada, M, Li, K, Wang, H
Acupuncture and herbal medicine. 2022;(3):184-195
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Abstract
UNLABELLED This study aimed to systematically review and depict the current studies of traditional Chinese medicine for the mental health of patients with coronavirus disease 2019 (COVID-19). METHODS A scoping review was conducted by searching PubMed, Web of Science, CNKI, Wanfang database, VIP database, and SinoMed, with the retrieval time being from the establishment of the database to April 18, 2022. The basic information of the included studies, objective, design, types of patients, interventions, outcomes, etc., was reviewed and summarized narratively. Methodological quality was assessed using the Cochrane Risk of Bias assessment tool, the methodological index for non-randomized studies or the Newcastle-Ottawa scale. RESULTS We identified 30 traditional Chinese medicine (TCM) studies from six databases. Among them, finished randomized controlled trials (n = 16) accounted for most of the studies, followed by single-arm studies (n = 9). In terms of study theme, 20 studies defined the mental health of patients with COVID-19 as the research theme. Psychological assessment was included in the inclusion criteria (performed before participation) of nine studies, whereas the other studies only mentioned the mental outcomes. TCM interventions included TCM exercises (Yijinjing, Baduanjin, Liuzijue, Taichi), acupoint stimulation (auricular and body points), moxibustion, decoction, or granules based on TCM syndrome differentiation, decoction, or granules with fixed formulae (Baidu Jieduan granules, Xuanfei Baidu decoction, and Qingfei Paidu decoction), Chinese patent medicine (Jinhua Qinggan granules), TCM psychological therapy (TCM ideological therapy, TCM five-tone therapy, and TCM psychological sand table), and TCM nursing (dialectical care, dialectical diet, and psychological counseling). Anxiety and depression were the main outcomes evaluated in regard to mental health in patients with COVID-19. The limitations of methodological quality were predominantly from follow-up, blinding, and registration. Positive results were reported by 27 studies (90%, n = 30). CONCLUSION We summarized the existing literature about the impact of TCM on mental health in patients with COVID-19. The number of studies evaluating the impact of TCM on mental health is encouraging, but overall methodological quality was low. Several TCM interventions warrant further evaluation, particularly among populations outside of China, for the purpose of establishing supporting evidence. More importantly, research with stronger methodological quality needs to be developed. GRAPHICAL ABSTRACT http://links.lww.com/AHM/A36.
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An updated review on environmental occurrence, scientific assessment and removal of brominated flame retardants by engineered nanomaterials.
Rani, M, Keshu, , Meenu, , Sillanpää, M, Shanker, U
Journal of environmental management. 2022;:115998
Abstract
Due to the extensive manufacturing and use of brominated flame retardants (BFRs), they are known to be hazardous, bioaccumulative, and recalcitrant pollutants in various environmental matrices. BFRs make flame-resistant items for industrial purposes (textiles, electronics, and plastics equipment) that are disposed of in massive amounts and leak off in various environmental matrices. The consumption of plastic items has expanded tremendously during the COVID-19 pandemic which has resulted into the increasing load of solid waste on land and water. Some BFRs, such as polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDs), are no longer utilized or manufactured owing to their negative impacts, which promotes the utilization of new BFRs as alternatives. BFRs have been discovered worldwide in soil, sludge, water, and other contamination sources. Various approaches such as photocatalysis-based oxidation/reduction, adsorption, and heat treatment have been found to eradicate BFRs from the environment. Nanomaterials with unique properties are one of the most successful methodologies for removing BFRs via photocatalysis. These methods have been praised for being low-cost, quick, and highly efficient. Engineered nanoparticles degraded BFRs when exposed to light and either convert them into safer metabolites or completely mineralize. Scientific assessment of research taking place in this area during the past five years has been discussed. This review offers comprehensive details on environmental occurrence, toxicity, and removal of BFRs from various sources. Degradation pathways and different removal strategies related to data have also been presented. An attempt has also been made to highlight the research gaps prevailing in the current research area.
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The emerging multifunctional roles of ERAP1, ERAP2 and IRAP between antigen processing and renin-angiotensin system modulation.
Mattorre, B, Tedeschi, V, Paldino, G, Fiorillo, MT, Paladini, F, Sorrentino, R
Frontiers in immunology. 2022;:1002375
Abstract
The Endoplasmic Reticulum Aminopeptidase 1 and 2 (ERAP1 and ERAP2) and Insulin Regulated Aminopeptidase (IRAP) are three M1 zinc metalloproteases whose role in antigen processing is the refining of peptidome either in the Endoplasmic reticulum (ERAP1 and ERAP2), or in the endosomes (IRAP). However, other novel and distinct functions are emerging. Here, we focus specifically on ERAP2. This gene has a peculiar evolutionary history, being absent in rodents and undergoing in humans to a balanced selection of two haplotypes, one of which not expressing the full length ERAP2. These observations suggest that its role in antigen presentation is not essential. An additional, less investigated role is in the regulation of the Renin Angiotensin System (RAS). ERAP1 and ERAP2 cleave Angiotensin II (Ang II) into Ang III and IV, which counteract the action of Ang II whereas IRAP is itself the receptor for Ang IV. We have recently reported that macrophages, independently from the haplotype, express and release a N-terminus ERAP2 "short" form which directly binds IRAP and the two molecules are co-expressed in the endosomes and on the cell membrane. This new evidence suggests that the maintenance of the ERAP2 gene in humans could be due to its activity in the regulation of the RAS system, possibly as an Ang IV agonist. Its role in the immune-mediated diseases as well as in disorders more specifically related to an imbalance of the RAS system, including hypertension, pre-eclampsia but also viral infections such as COVID-19, is discussed here.
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Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable.
Jia, FJ, Han, J
World journal of clinical cases. 2022;(36):13148-13156
Abstract
Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.