Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a severe respiratory illness and alters the gut microbiota, which dynamically interacts with the human immune system. Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens. Here, we describe critical factors affecting the microbiota in coronavirus disease 2019 (COVID-19) patients. These include, such as gut microbiota imbalance and gastrointestinal symptoms, the pattern of altered gut microbiota composition in COVID-19 patients, and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis. Moreover, we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration. The role of ACE2 in the digestive system, and control of its expression using the gut microbiota is discussed, highlighting the interactions between the lungs, the gut, and the brain during COVID-19 infection. Similarly, we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19. Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review. Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity. However, understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.     

A suspected case of carbimazole-associated torsades de pointes

Torsades de pointes (TdP) or polymorphic ventricular tachycardia owing to drug-induced QT prolongation is a common cause of withdrawal of marketed drugs and has caused increasing concern in the recent past. Carbimazole, the common antithyroid drug, is not a very well-known offender to cause QT prolongation and TdP. Only a few cases of carbimazole-induced TdP have been reported so far. We report a 53-year-old woman who was on tab. carbimazole (10 mg) twice daily for one month and who presented with respiratory distress, palpitation and syncope attack. Her surface electrocardiogram (ECG) was showing the evidence of TdP and subsequently hypokalemia was also detected. She received conservative management including potassium supplementation. However, QT prolongation persisted even after normalization of serum potassium level. Carbimazole was withdrawn and the patient was discharged as she remained stable and symptom free. This study highlights a possible association between carbimazole and TdP.     

miRNA‐Regulated Key Components of Cytokine Signaling Pathways and Inflammation in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an inflammatory disease that primarily affects joints. This autoimmune disease pathogenesis is related to cytokine signaling. In this review, we have described the existence of various microRNAs (miRNAs) involved in regulation of major protein cascades of cytokine signaling associated with RA. Moreover, we have tried to portray the role of various miRNAs in different cytokines such as TNF‐α, IL‐1, IL‐6, IL‐10, IL‐17, IL‐18, IL‐21, and granulocyte macrophage colony‐stimulating factor (GMCSF). Along with this, we have also discussed the miRNA regulation in T cells and synovial tissue. From the analyzed data, we suggest that miR‐146a and miR‐155 might be the potential therapeutic target for treating RA. The insight illustrated in this review will offer a better understanding of the role of miRNA in cytokine signaling pathways and inflammation during RA and could project them as diagnostic or therapeutic agents in near future.     

Ebola virus disease: Recent advances in diagnostics and therapeutics

Ebola virus disease(EVD)is associated with haemorrhagic fever in humans and nonhuman primates,with a high rate of fatality(up to 90%).Some outbreaks in human history have proven the lethality of EVD.The recent epidemic of 2014 and 2015 in West Africa was the deadliest of all time(11 284 deaths).To understand the transmission dynamics,we have reviewed the epidemiology of EVD to date.The absence of any licensed vaccines or approved drugs against Ebola virus(EBOV)further highlights the severity and crisis level of EVD.Some organizations(public and private)are making considerable efforts to develop novel therapeutic approaches or vaccines to contain the outbreak of EBOV shortly.Here,we summarized the various potential drugs and vaccines(undergoing multiple phases of clinical trials)that have arisen as an alternative against EBOV,and we highlighted the numerous issues and limitations hindering this process.Alternatively,an increasing focus on strengthening the medical and civic health structure could provide speedy benefits in containing the spread of EVD,as well as offer a resilient foundation for the deployment of novel drugs and vaccines to the affected countries,once such drugs and vaccines become available.     

A hypothetical relationship between the nuclear reprogramming factors for induced pluripotent stem (iPS) cells generation--bioinformatic and algorithmic approach

A hypothetical evolutionary relationship was generated between the nuclear reprogramming factors for induced pluripotent stem (iPS) cells generation. Utilizing bioinformatics techniques, sequence analyses and phylogenetic tree algorithms, a comparative study has been performed to understand the evolutionary relationship of human nuclear reprogramming factors of induced pluripotent stem cells (iPSCs) generation. Among the total six nuclear reprogramming factors, the four reprogramming factors (SOX2, C-MYC, KLF4, and LIN28) have significant evolutionary origin. Our study shows SOX2 and C-MYC have evolutionary relationship and common point of origin. Likewise, KLF4 and LIN28 are having evolutionary relationship and have common point of origin. Based on these evidences, we propose that our study may be a great help to the future researchers to understand the mechanism(s) as well as pathway of nuclear reprogramming process.     

CRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases

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Role of Acidic Residues in Helices TH8–TH9 in Membrane Interactions of the Diphtheria Toxin T Domain

The pH-triggered membrane insertion of the diphtheria toxin translocation domain (T domain) results in transferring the catalytic domain into the cytosol, which is relevant to potential biomedical applications as a cargo-delivery system. Protonation of residues is suggested to play a key role in the process, and residues E349, D352 and E362 are of particular interest because of their location within the membrane insertion unit TH8–TH9. We have used various spectroscopic, computational and functional assays to characterize the properties of the T domain carrying the double mutation E349Q/D352N or the single mutation E362Q. Vesicle leakage measurements indicate that both mutants interact with the membrane under less acidic conditions than the wild-type. Thermal unfolding and fluorescence measurements, complemented with molecular dynamics simulations, suggest that the mutant E362Q is more susceptible to acid destabilization because of disruption of native intramolecular contacts. Fluorescence experiments show that removal of the charge in E362Q, and not in E349Q/D352N, is important for insertion of TH8–TH9. Both mutants adopt a final functional state upon further acidification. We conclude that these acidic residues are involved in the pH-dependent action of the T domain, and their replacements can be used for fine tuning the pH range of membrane interactions.     

Combination Therapy with Indolylquinoline Derivative and Sodium Antimony Gluconate Cures Established Visceral Leishmaniasis in Hamsters

2-(2"-Dichloroacetamidobenzyl)-3-(3'-indolylquinoline), designated indolylquinoline derivative A, reduced the splenic and the liver parasite burdens by >93.0% in Leishmania donovani-infected hamsters, whereas sodium antimony gluconate (SAG) reduced the burdens approximately 80.0%. Complete clearance of parasitemia from the livers and spleens was noticed when infected animals received indolylquinoline derivative A plus SAG, suggesting that indolylquinoline derivative A has potential as a new agent for sole or conjunctive therapy for leishmaniasis.