Immediate health risk: Concentration of heavy metals in contaminated freshwater fishes from the river channel of Turag-Tongi-Balu.

The consumption of contaminated finfish from the polluted river channel of Turag-Tongi-Balu, Kamarpara site, Dhaka poses significant health hazards to humans. We used mass spectrometry on chemically digested liquid samples from five fish species from Turag-Tongi-Balu to estimate the concentrations of 10 elements (Cr, Mn, Ni, Cu, Zn, As, Se, Cd, Fe, and Pb). Except M. vittatus, the mean concentrations of Cd, Mn, Pb, and Se exceeded the Food Safety Guideline (FSG) value in all fish species. Among the species studied, L. rohita, C. punctata, C. batrachus, H. fossilis, and M. vittatus exhibited higher Mn concentrations surpassing the FSG threshold, thus elevating the non-carcinogenic risk across all species. There were statistically significant differences (p < .05) in the mean concentrations of heavy metals among fish species. The Target Hazard Quotient (THQ) value of Mn poses a significant non-carcinogenic risk to human health, while the hazard of other metals is negligible. Except for M. vittus, the Hazard Index value (HI ≥ 1) revealed the risk that all metals exceed the limit and pose a threat to human health. Cd, As, and Ni metals pose a significant carcinogenic risk to human health from the consumption of fish samples, which is a particularly alarming target cancer risk (TCR). In conclusion, regular dietary consumption of fish from this polluted ecosystem of the Turag-Tongi-Balu River channel's Kamarpara site poses a significant health risk and is indicated as cancer. This study emphasizes the significance of monitoring heavy metal contamination in finfish and minimizing the risk to human health with effective measures.

Emergence of SARS-CoV-2 variant of interest B.1.525 (Eta) in Bangladesh.

In the present study, we report the complete genome of five Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) from Bangladesh harboring mutations at Spike protein (E484K, Q677H, D614G, A67V, Q52R, Y144del, H69del, V70del, F888L) assigned to the B.1.525 lineage (Variant of interest). Mutations are also found in viral structural proteins other than spike region (E_L21F, M_I82F, N_A12G and N_T208I) and other mutations (NSP3_T1189I, NSP6_S106del, NSP6_F108del, NSP6_G107del, NSP12_P323F) from all of five B.1.525 SARS-CoV-2 variants of Bangladesh. We have also found four unique mutations from two of SARS-CoV-2 B.1.525 variant of Bangladesh. Among the four unique mutations two mutations (NS7a_L96H, NS7a_Y97D) obtained from strain BCSIR-NILMRC-718, one (NSP3_A1430V) from BCSIR-NILMRC-738 and two mutation including one spike protein mutation (NSP2_L444I, Spike_I68 M) present in BCSIR-AFIP-10 strain. The identification of new mutations will contribute to characterizing SARS-CoV-2, to continue tracking its spread and better understanding its biological and clinical features to take medical countermeasures and vaccines.

Genomic characterization of the dominating Beta, V2 variant carrying vaccinated (Oxford-AstraZeneca) and nonvaccinated COVID-19 patient samples in Bangladesh: A metagenomics and whole-genome approach.

Bangladesh is experiencing a second wave of COVID-19 since March 2021, despite the nationwide vaccination drive with ChAdOx1 (Oxford-AstraZeneca) vaccine from early February 2021. Here, we characterized 19 nasopharyngeal swab (NPS) samples from COVID-19 suspect patients using genomic and metagenomic approaches. Screening for SARS-CoV-2 by reverse transcriptase polymerase chain reaction and metagenomic sequencing revealed 17 samples of COVID-19 positive (vaccinated = 10, nonvaccinated = 7) and 2 samples of COVID-19 negative. We did not find any significant correlation between associated factors including vaccination status, age or sex of the patients, diversity or abundance of the coinfected organisms/pathogens, and the abundance of SARS-CoV-2. Though the first wave of the pandemic was dominated by clade 20B, Beta, V2 (South African variant) dominated the second wave (January 2021 to May 2021), while the third wave (May 2021 to September 2021) was responsible for Delta variants of the epidemic in Bangladesh including both vaccinated and unvaccinated infections. Noteworthily, the receptor binding domain (RBD) region of S protein of all the isolates harbored similar substitutions including K417N, E484K, and N501Y that signify the Beta, while D614G, D215G, D80A, A67V, L18F, and A701V substitutions were commonly found in the non-RBD region of Spike proteins. ORF7b and ORF3a genes underwent a positive selection (dN/dS ratio 1.77 and 1.24, respectively), while the overall S protein of the Bangladeshi SARS-CoV-2 isolates underwent negative selection pressure (dN/dS = 0.621). Furthermore, we found different bacterial coinfections like Streptococcus agalactiae, Neisseria meningitidis, Elizabethkingia anophelis, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Pseudomonas plecoglossicida, expressing a number of antibiotic resistance genes such as tetA and tetM. Overall, this approach provides valuable insights on the SARS-CoV-2 genomes and microbiome composition from both vaccinated and nonvaccinated patients in Bangladesh.

Adhesivity-tuned bioactive gelatin/gellan hybrid gels drive efficient wound healing.

Gelatin-based hydrogels have been widely used for wound healing applications. However, increase in ligand density and reduction in pore size with increasing gelatin concentration may delay wound healing by limiting cell infiltration. In this study, we address this shortcoming by combining gelatin with gellan-which is super hydrophilic and non-adhesive to cells. We show that UV crosslinked hybrid gels composed of methacrylated gelatin (GelMA) and methacrylated gellan gum (mGG), possess considerably larger pores and improved mechanical properties compared to GelMA gels. Reduced spreading and reduced formation of focal adhesions on hybrid gels combined with lower contractility and faster detachment upon trypsin-induced de-adhesion suggests that hybrid gels are less adhesive than GelMA gels. Gradual release of fibroblast growth factor (FGF) and silver nanoparticles (AgNPs) incorporated in hybrid gels not only boosts cell migration, but also confers anti-bacterial activity against gram-positive and gram-negative bacteria at concentrations nontoxic to cells. Full thickness wound healing in Wistar rats revealed increased granulation tissue formation in hybrid gels, fastest epithelialization and highest collagen deposition in rats treated with FGF entrapped hybrid gels. Together, our results demonstrate how adhesive tuning and incorporation of bioactive factors can be synergistically combined for achieving complete wound healing.

Transcriptome analysis reveals increased abundance and diversity of opportunistic fungal pathogens in nasopharyngeal tract of COVID-19 patients.

We previously reported that SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiomes (bacteria, archaea and commensal respiratory viruses) with inclusion of pathobionts. This study aimed to assess the possible changes in the abundance and diversity of resident mycobiome in the nasopharyngeal tract (NT) of humans due to SARS-CoV-2 infections. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 = 8, Recovered = 7, and Healthy = 7) were collected for RNA-sequencing followed by taxonomic profiling of mycobiome. Our analyses indicate that SARS-CoV-2 infection significantly increased (p < 0.05, Wilcoxon test) the population and diversity of fungi in the NT with inclusion of a high proportion of opportunistic pathogens. We detected 863 fungal species including 533, 445, and 188 species in COVID-19, Recovered, and Healthy individuals, respectively that indicate a distinct mycobiome dysbiosis due to the SARS-CoV-2 infection. Remarkably, 37% of the fungal species were exclusively associated with SARS-CoV-2 infection, where S. cerevisiae (88.62%) and Phaffia rhodozyma (10.30%) were two top abundant species. Likewise, Recovered humans NT samples were predominated by Aspergillus penicillioides (36.64%), A. keveii (23.36%), A. oryzae (10.05%) and A. pseudoglaucus (4.42%). Conversely, Nannochloropsis oceanica (47.93%), Saccharomyces pastorianus (34.42%), and S. cerevisiae (2.80%) were the top abundant fungal species in Healthy controls nasal swabs. Importantly, 16% commensal fungal species found in the Healthy controls were not detected in either COVID-19 patients or when they were cured from COVID-19 (Recovered). We also detected several altered metabolic pathways correlated with the dysbiosis of fungal mycobiota in COVID-19 patients. Our results suggest that SARS-CoV-2 infection causes significant dysbiosis of mycobiome and related metabolic functions possibly play a determining role in the progression of SARS-CoV-2 pathogenesis. These findings might be helpful for developing mycobiome-based diagnostics, and also devising appropriate therapeutic regimens including antifungal drugs for prevention and control of concurrent fungal coinfections in COVID-19 patients.

A multicentre study reveals dysbiosis in the microbial co-infection and antimicrobial resistance gene profile in the nasopharynx of COVID-19 patients.

The impact of SARS-CoV-2 infection on the nasopharyngeal microbiome has not been well characterised. We sequenced genetic material extracted from nasopharyngeal swabs of SARS-CoV-2-positive individuals who were asymptomatic (n = 14), had mild (n = 64) or severe symptoms (n = 11), as well as from SARS-CoV-2-negative individuals who had never-been infected (n = 5) or had recovered from infection (n = 7). Using robust filters, we identified 1345 taxa with approximately 0.1% or greater read abundance. Overall, the severe cohort microbiome was least diverse. Bacterial pathogens were found in all cohorts, but fungal species identifications were rare. Few taxa were common between cohorts suggesting a limited human nasopharynx core microbiome. Genes encoding resistance mechanisms to 10 antimicrobial classes (> 25% sequence coverages, 315 genes, 63 non-redundant) were identified, with ß-lactam resistance genes near ubiquitous. Patients infected with SARS-CoV-2 (asymptomatic and mild) had a greater incidence of antibiotic resistance genes and a greater microbial burden than the SARS-CoV-2-negative individuals. This should be considered when deciding how to treat COVID-19 related bacterial infections.

M gene targeted qRT-PCR approach for SARS-CoV-2 virus detection.

Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) is the gold standard method for SARS-CoV-2 detection, and several qRT-PCR kits have been established targeting different genes of the virus. Due to the high mutation rate of these genes, false negative results arise thus complicating the interpretation of the diagnosis and increasing the need of alternative targets. In this study, an alternative approach for the detection of SARS-CoV-2 viral RNA targeting the membrane (M) gene of the virus using qRT-PCR was described. Performance evaluation of this newly developed in-house assay against commercial qRT-PCR kits was done using clinical oropharyngeal specimens of COVID-19 positive patients. The limit of detection was determined using successive dilutions of known copies of SARS-CoV-2 pseudovirus. The M gene based assay was able to detect a minimum of 100 copies of virus/mL indicating its capacity to detect low viral load. The assay showed comparable accuracy, sensitivity and specificity with commercially available kits while detecting all the variants efficiently. The study concluded that the in-house M gene based assay might be an effective alternative for the currently available commercial qRT-PCR kits.

Sacralization of Coccygeal Vertebra: A Descriptive Observational Study in Bangladesh.

BACKGROUND: In the sacrococcygeal region, anatomical variation is due to the sacralization of the coccygeal vertebra, which is the due union of/fusion of the fifth sacral with the first coccygeal vertebra of five couples of sacral foramina under-detected or asymptomatic beyond radiological assessment. That is why it is challenging to know the cause of coccydynia, caudal block failure, the difficult second stage of labor, and perineal tears. The present study aims to improve knowledge about the anatomical variation of sacralization of the coccygeal vertebra. Additionally, to find the prevalence of sacralization of coccygeal vertebra in Sylhet, Bangladesh. METHODS: This study was performed on 60 parched, totally calcified, typical sacra of mature-age individuals of undetermined sexes, fulfilling the inclusion criteria from the bone bank of the osteology museum of the Department of Anatomy, Sylhet MAG Osmani Medical College, Sylhet, Bangladesh, from July 2017 to June 2018. Sex determination of the collected unknown sacra was conducted using discriminant function analysis. It was found that 50% (30) were male and 50% (30%) were female. The unpaired t-tests and chi-square were utilized to determine the statistical significance. RESULTS: Out of 60 sacra, eight (13.33%) samples presented with sacralization. This study found that males had significantly higher straight (p=0.05) and curved (p=0.05) lengths of sacrococcygeal vertebrae. The sacrococcygeal curvature index (SCI) showed statistically significant (p=0.05) differences between the sexes. CONCLUSION: Sacralization may exert an impact on the caudal block. It could extend the second stage of the labor process with perineal tears. Therefore, knowledge about the anatomical variation of the coccygeal vertebra is essential.

Immunoinformatics approach to epitope-based vaccine design against the SARS-CoV-2 in Bangladeshi patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic which has brought a great challenge to public health. After the first emergence of novel coronavirus SARS-CoV-2 in the city of Wuhan, China, in December 2019. As of March 2020, SARS-CoV-2 was first reported in Bangladesh and since then the country has experienced a steady rise in infections, resulting in 13,355,191 cases and 29,024 deaths as of 27 February 2022. Bioinformatics techniques are used to predict B cell and T cell epitopes from the new SARS-CoV-2 spike glycoprotein in order to build a unique multiple epitope vaccine. The immunogenicity, antigenicity scores, and toxicity of these epitopes were evaluated and chosen based on their capacity to elicit an immune response. RESULT: The best multi-epitope of the possible immunogenic property was created by combining epitopes. EAAAK, AAY, and GPGPG linkers were used to connect the epitopes. In several computer-based immune response analyses, this vaccine design was found to be efficient, as well as having high population coverage. CONCLUSION: This research is entirely reliant on the development of epitope-based vaccines, and these in silico findings would represent a major step forward in the development of a vaccine that might eradicate SARS-CoV-2 in Bangladeshi patients.

Differential gene expression profiling reveals potential biomarkers and pharmacological compounds against SARS-CoV-2: Insights from machine learning and bioinformatics approaches.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created an urgent global situation. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability and disease comorbidities. The pandemic continues to spread worldwide, despite intense efforts to develop multiple vaccines and therapeutic options against COVID-19. However, the precise role of SARS-CoV-2 in the pathophysiology of the nasopharyngeal tract (NT) is still unfathomable. This study utilized machine learning approaches to analyze 22 RNA-seq data from COVID-19 patients (n = 8), recovered individuals (n = 7), and healthy individuals (n = 7) to find disease-related differentially expressed genes (DEGs). We compared dysregulated DEGs to detect critical pathways and gene ontology (GO) connected to COVID-19 comorbidities. We found 1960 and 153 DEG signatures in COVID-19 patients and recovered individuals compared to healthy controls. In COVID-19 patients, the DEG-miRNA, and DEG-transcription factors (TFs) interactions network analysis revealed that E2F1, MAX, EGR1, YY1, and SRF were the highly expressed TFs, whereas hsa-miR-19b, hsa-miR-495, hsa-miR-340, hsa-miR-101, and hsa-miR-19a were the overexpressed miRNAs. Three chemical agents (Valproic Acid, Alfatoxin B1, and Cyclosporine) were abundant in COVID-19 patients and recovered individuals. Mental retardation, mental deficit, intellectual disability, muscle hypotonia, micrognathism, and cleft palate were the significant diseases associated with COVID-19 by sharing DEGs. Finally, the detected DEGs mediated by TFs and miRNA expression indicated that SARS-CoV-2 infection might contribute to various comorbidities. Our results provide the common DEGs between COVID-19 patients and recovered humans, which suggests some crucial insights into the complex interplay between COVID-19 progression and the recovery stage, and offer some suggestions on therapeutic target identification in COVID-19 caused by the SARS-CoV-2.

Glycocalyx disruption enhances motility, proliferation and collagen synthesis in diabetic fibroblasts.

Impaired wound healing represents one of the most debilitating side effects of Diabetes mellitus. Though the role of fibroblasts in wound healing is well-known, the extent to which their function is altered in the context of diabetes remains incompletely understood. Here, we address this question by comparing the phenotypes of healthy dermal fibroblasts (HDFs) and diabetic dermal fibroblasts (DDFs). We show that DDFs are more elongated but less motile and less contractile than HDFs. Reduced motility of DDFs is attributed to formation of larger focal adhesions stabilized by a bulky glycocalyx, associated with increased expression of the cell surface glycoprotein mucin 16 (MUC 16). Disruption of the glycocalyx not only restored DDF motility to levels comparable to that of HDFs, but also led to increased proliferation and collagen synthesis. Collectively, our results illustrate the influence of glycocalyx disruption on mechanics of diabetic fibroblasts relevant to cell motility.

High ligand density drives extensive spreading and motility on soft GelMA gels.

In comparison to synthetic hydrogels where ligand density and stiffness can be independently tuned, cell responses are expected to deviate on native biopolymer networks where ligand density and stiffness are coupled. Here we probe the tensional homeostasis of fibroblasts on methacrylated gelatin (GelMA) gels, which are widely used in tissue engineering applications. On 5%-15% GelMA gels which are very soft (10-100's of Pa's in stiffness), fibroblasts were found to spread extensively and assemble prominent stress fibers and focal adhesions. Probing of contractile mechanics using trypsin-induced detachment revealed adhesive drag, but not contractility, was sensitive to GelMA concentration. Contractility-altering drugs blebbistatin and nocodazole, which exhibited opposite effects on focal adhesion size, both led to reduction in adhesive drag and cell rounding. However, cell motility was impacted only in nocodazole-treated cells. Collectively, our experiments suggest that on soft GelMA gels, contractility-independent adhesion clustering mediated by high ligand density can drive cell spreading and motility.

Current Therapeutic Strategies of Xeroderma Pigmentosum.

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disease caused by a defect in the DNA repair system, exhibiting skin cancer on sun exposure. As it is an incurable disease, therapeutic strategies of this disease are critical. This review article takes an attempt to explore the current therapeutic advancements in XP. Different approaches including sun avoidance; surgical removal of cancerous lesions; laser and photodynamic therapy; use of retinoid, 5-fluorouracil, imiquimod, photolyase, and antioxidant; interferon therapy and gene therapy are chosen by doctors and patients to lessen the adverse effects of this disease. Among these options, sun avoidance, use of 5-fluorouracil and imiquimod, and interferon therapy are effective. However, some approaches including laser and photodynamic therapy, and the use of retinoids are effective against skin cancer having severe side effects. Furthermore, surgical removal of cancerous lesions and use of antioxidants are considered to be effective against this disease; however, efficacies of these are not experimentally determined. In addition, some approaches including oral vismodegib, immunotherapy, nicotinamide, acetohexamide, glimepiride-restricted diet are found to be effective to minimize the complications secondary to defects in the nucleotide excision repair (NER) system and also enhance the NER, which are under experimental level yet. Besides these, gene therapy, including the introduction of missing genes and genome edition, may be a promising approach to combat this disease, which is also not well established now. In the near future, these approaches may be effective tools to manage XP.

Effects of alternate nostril breathing exercise on cardiorespiratory functions in healthy young adults.

Introduction: Alternate nostril breathing (ANB) is an effective breathing exercise with therapeutic benefits on cardiorespiratory functions for healthy and diseased individuals. This study was conducted to assess the effects of ANB exercise on cardiorespiratory tasks in healthy adults. Materials and Methods: This randomized experimental study was conducted in the Department of Physiology, Chittagong Medical College, Chattogram, from July 2017 to June 2018. A total of 100 1st-year students, aged between 18 and 20 years, were included by a random sampling method. Fifty participants (25 males and 25 females) were enrolled in the experimental group, while age- and body mass index-matched another 50 participants (25 males and 25 females) served as the control group. Experimental group participants performed ANB exercise for 4 weeks. Cardiorespiratory parameters (pulse rate, blood pressure, forced vital capacity, forced expiratory volume in 1st s [FEV1], and peak expiratory flow rate [PEFR] were measured. Data were taken at the start and after 4 weeks in both groups. Results: Independent t-test showed no significant differences in the cardiorespiratory functions between the experimental and control groups among the male and female participants, except for the females' PEFR which showed small differences. On the other hand, repeated measure ANOVA shows significant improvement in the experimental groups among males (P < 0.001-0.028) and females (P < 0.001-0.001) in all the cardiorespiratory functions measured, except for the FEV1 and PEFR among males. Conclusion: The results of this study suggest that cardiorespiratory functions were improved after breathing exercise, and therefore, ANB can be recommended for increasing cardiorespiratory efficiency.

RésuméIntroduction: La respiration nasale alternée (ANB) est un exercice de respiration efficace avec des avantages thérapeutiques sur les fonctions cardiorespiratoires pour les individus sains et malades. Cette étude a été menée pour évaluer les effets de l'exercice ANB sur les tâches cardiorespiratoires chez des adultes en bonne santé. Matériels et méthodes: Cette étude expérimentale randomisée a été menée au Département de physiologie, Chittagong Medical College, Chattogram, de juillet 2017 à juin 2018. Un total de 100 étudiants de 1ère année, âgés de 18 à 20 ans, ont été inclus par un échantillonnage aléatoire. méthode. Cinquante participants (25 hommes et 25 femmes) ont été inscrits dans le groupe expérimental, tandis que l'âge et l'indice de masse corporelle correspondaient à 50 autres participants (25 hommes et 25 femmes) servant de groupe témoin. Les participants du groupe expérimental ont effectué des exercices ANB pendant 4 semaines. Les paramètres cardiorespiratoires (fréquence du pouls, pression artérielle, capacité vitale forcée, volume expiratoire forcé en 1ère s [VEMS] et débit expiratoire de pointe [PEFR] ont été mesurés. Les données ont été recueillies au début et après 4 semaines dans les deux groupes. Résultats: Le test t indépendant n'a montré aucune différence significative dans les fonctions cardiorespiratoires entre les groupes expérimentaux et témoins parmi les participants masculins et féminins, à l'exception du PEFR des femmes qui présentait de petites différences.D'autre part, l'ANOVA à mesures répétées montre une amélioration significative dans les groupes expérimentaux chez les hommes (P < 0,001 à 0,028) et les femmes (P < 0,001 à 0,001) dans toutes les fonctions cardiorespiratoires mesurées, à l'exception du VEMS et du DEP chez les hommes Conclusion: Les résultats de cette étude suggèrent que les fonctions cardiorespiratoires ont été améliorées après un exercice respiratoire , et par conséquent, l'ANB peut être recommandé pour augmenter l'efficacité cardiorespiratoire.

The Implications of Zinc Therapy in Combating the COVID-19 Global Pandemic.

The global pandemic from COVID-19 infection has generated significant public health concerns, both health-wise and economically. There is no specific pharmacological antiviral therapeutic option to date available for COVID-19 management. Also, there is an urgent need to discover effective medicines, prevention, and control methods because of the harsh death toll from this novel coronavirus infection. Acute respiratory tract infections, significantly lower respiratory tract infections, and pneumonia are the primary cause of millions of deaths worldwide. The role of micronutrients, including trace elements, boosted the human immune system and was well established. Several vitamins such as vitamin A, B6, B12, C, D, E, and folate; microelement including zinc, iron, selenium, magnesium, and copper; omega-3 fatty acids as eicosapentaenoic acid and docosahexaenoic acid plays essential physiological roles in promoting the immune system. Furthermore, zinc is an indispensable microelement essential for a thorough enzymatic physiological process. It also helps regulate gene-transcription such as DNA replication, RNA transcription, cell division, and cell activation in the human biological system. Subsequently, zinc, together with natural scavenger cells and neutrophils, are also involved in developing cells responsible for regulating nonspecific immunity. The modern food habit often promotes zinc deficiency; as such, quite a few COVID-19 patients presented to hospitals were frequently diagnosed as zinc deficient. Earlier studies documented that zinc deficiency predisposes patients to a viral infection such as herpes simplex, common cold, hepatitis C, severe acute respiratory syndrome coronavirus (SARS-CoV-1), the human immunodeficiency virus (HIV) because of reducing antiviral immunity. This manuscript aimed to discuss the various roles played by zinc in the management of COVID-19 infection.

Progenitor-like characteristics in a subgroup of UCP1+ cells within white adipose tissue.

Thermogenic beige fat found in white adipose tissue is a potential therapeutic target to curb the global obesity and diabetes epidemic. However, these inducible thermogenic beige adipocytes have been thought to be short-lived and to rapidly convert to "white-like" adipocytes after discontinuing stimuli. In this study, using effective labeling techniques and genetic mouse tools, we demonstrate that a subset of UCP1+ cells that exist within white adipose tissue are able to self-divide and contribute to new beige adipocyte recruitment in response to ß3 stimuli. When these cells are depleted or their adipogenic capability is blocked, ß3-induced beige adipocyte formation is impaired. We also identify a cell-cycle machinery of p21 and CDKN2A as a molecular basis of beige adipocyte regulation. Collectively, our findings provide new insights into the cellular and molecular mechanisms of beige adipocyte regulation and potential therapeutic opportunities to induce the beige phenotype and treat metabolic disease.

Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database.

BACKGROUND: Elevated inflammatory cytokines in Coronavirus disease 2019 (COVID-19) affect the lungs leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database. RESEARCH DESIGN AND METHODS: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients' demographic and clinical variables, and severity of involvement of organ system. RESULTS: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18-64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. 'Injury, Poisoning, and Procedural Complications' remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas. CONCLUSION: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting.

Fat-Soluble Vitamins and the Current Global Pandemic of COVID-19: Evidence-Based Efficacy from Literature Review.

The outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), later named COVID-19 by the World Health Organization (WHO), was initiated at Wuhan, Hubei, China, and there was a rapid spread of novel SARS-CoV-2 and the disease COVID-19 in late 2019. The entire world is now experiencing the challenge of COVID-19 infection. However, still very few evidence-based treatment options are available for the prevention and treatment of COVID-19 disease. The present review aims to summarize the publicly available information to give a comprehensive yet balanced scientific overview of all the fat-soluble vitamins concerning their role in SARS-CoV-2 virus infection. The roles of different fat-soluble vitamins and micronutrients in combating SARS-CoV-2 infection have been recently explored in several studies. There are various hypotheses to suggest their use to minimize the severity of COVID-19 infection. These vitamins are pivotal in the maintenance and modulation of innate and cell-mediated, and antibody-mediated immune responses. The data reported in recent literature demonstrate that deficiency in one or more of these vitamins compromises the patients' immune response and makes them more vulnerable to viral infections and perhaps worse disease prognosis. Vitamins A, D, E, and K boost the body's defense mechanism against COVID-19 infection and specifically prevent its complications such as cytokine storm and other inflammatory processes, leading to increased morbidity and mortality overemphasis. However, more detailed randomized double-blind clinical pieces of evidence are required to define the use of these supplements in preventing or reducing the severity of the COVID-19 infection.