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Non-small cell lung cancer (NSCLC) has been marked as the major cause of death in lung cancer patients. Due to tumor heterogeneity, mutation burden, and emerging resistance against the available therapies in NSCLC, it has been posing potential challenges in the therapy development. Hence, identification of cancer-driving mutations and their effective inhibition have been advocated as a potential approach in NSCLC treatment. Thereof, this study aims to employ the genomic and computational-aided integrative drug repositioning strategy to identify the potential mutations in the selected molecular targets and repurpose FDA-approved drugs against them. Accordingly, molecular targets and their mutations, i.e., EGFR (V843L, L858R, L861Q, and P1019L) and ROS1 (G1969E, F2046Y, Y2092C, and V2144I), were identified based on TCGA dataset analysis. Following, virtual screening and redocking analysis, Elbasvir, Ledipasvir, and Lomitapide drugs for EGFR mutants (>-10.8 kcal/mol) while Indinavir, Ledipasvir, Lomitapide, Monteleukast, and Isavuconazonium for ROS1 mutants (>-8.8 kcal/mol) were found as putative inhibitors. Furthermore, classical molecular dynamics simulation and endpoint binding energy calculation support the considerable stability of the selected docked complexes aided by substantial hydrogen bonding and hydrophobic interactions in comparison to the respective control complexes. Conclusively, the repositioned FDA-approved drugs might be beneficial alone or in synergy to overcome acquired resistance to EGFR and ROS1-positive lung cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The human gut microbiota is increasingly recognized as a pivotal factor in diabetes management, playing a significant role in the body's response to treatment. However, it is important to understand that long-term usage of medicines like metformin and other diabetic treatments can result in problems, gastrointestinal discomfort, and dysbiosis of the gut flora. Advanced sequencing technologies have improved our understanding of the gut microbiome's role in diabetes, uncovering complex interactions between microbial composition and metabolic health. We explore how the gut microbiota affects glucose metabolism and insulin sensitivity by examining a variety of -omics data, including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and metagenomics. Machine learning algorithms and genome-scale modeling are now being applied to find microbiological biomarkers associated with diabetes risk, predicted disease progression, and guide customized therapy. This study holds promise for specialized diabetic therapy. Despite significant advances, some concerns remain unanswered, including understanding the complex relationship between diabetes etiology and gut microbiota, as well as developing user-friendly technological innovations. This mini-review explores the relationship between multiomics, precision medicine, and machine learning to improve our understanding of the gut microbiome's function in diabetes. In the era of precision medicine, the ultimate goal is to improve patient outcomes through personalized treatments.

The normalization of RNA sequencing data is a primary step for downstream analysis. The most popular method used for the normalization is the trimmed mean of M values (TMM) and DESeq. The TMM tries to trim away extreme log fold changes of the data to normalize the raw read counts based on the remaining non-deferentially expressed genes. However, the major problem with the TMM is that the values of trimming factor M are heuristic. This paper tries to estimate the adaptive value of M in TMM based on Jaeckel's Estimator, and each sample acts as a reference to find the scale factor of each sample. The presented approach is validated on SEQC, MAQC2, MAQC3, PICKRELL and two simulated datasets with two-group and three-group conditions by varying the percentage of differential expression and the number of replicates. The performance of the present approach is compared with various state-of-the-art methods, and it is better in terms of area under the receiver operating characteristic curve and differential expression., (© The Author(s) 2024. Published by Oxford University Press.)

Caffeine, which shares consubstantial structural similarity with purine adenosine, has been demonstrated as a nonselective adenosine receptor antagonist for eliciting most of the biological functions at physiologically relevant dosages. Accumulating evidence supports caffeine's beneficial effects against different disorders, such as total cardiovascular diseases and type 2 diabetes. Conversely, paradoxical effects are also linked to caffeine ingestion in humans including hypertension-hypotension and tachycardia-bradycardia. These observations suggest the association of caffeine action with its ingested concentration and/or concurrent interaction with preferential molecular targets to direct explicit events in the human body. Thus, a coherent analysis of the functional targets of caffeine, relevant to normal physiology, and disease pathophysiology, is required to understand the pharmacology of caffeine. This review provides a broad overview of the experimentally validated targets of caffeine, particularly those of therapeutic interest, and the impacts of caffeine on organ-specific physiology and pathophysiology. Overall, the available empirical and epidemiological evidence supports the dose-dependent functional activities of caffeine and advocates for further studies to get insights into the caffeine-induced changes under specific conditions, such as asthma, DNA repair, and cancer, in view of its therapeutic applications., (© 2023 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

A new Coronaviridae strain, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), emerged from Wuhan city of China and caused one of the substantial global health calamities in December 2019. Even though several vaccines and drugs have been developed worldwide since COVID-19, a cost-effective drug with the least side effects is still unavailable. Currently, plant-derived compounds are mostly preferred to develop antiviral therapeutics due to its less toxicity, easy access, and cost-effective characteristics. Therefore, in this study, 124 phytochemical compounds from plants of Lauraceae family with medicinal properties were virtually screened against SARS-CoV-2 M pro . Identification of four phytomolecules, i.e., cassameridine, laetanine, litseferine and cassythicine, with docking scores -9.3, -8.8, -8.6, and -8.6 kcal/mol, respectively, were undertaken by virtual screening, and molecular docking. Furthermore, the molecular dynamic simulation and essential dynamics analysis have contributed in understanding the stability and inhibitory effect of these selected compounds. These phytomolecules can be considered for further in vitro and in vivo experimental study to develop anti-SARS-CoV-2 therapeutics targeting the main protease (M pro ).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accountable for causing the coronavirus diseases 2019 (COVID-19), is already declared as a pandemic disease globally. Like previously reported SARS-CoV strain, the novel SARS-CoV-2 also initiates the viral pathogenesis via docking viral spike-protein with the membranal angiotensin-converting enzyme 2 (ACE2) - a receptor on variety of cells in the human body. Therefore, COVID-19 is broadly characterized as a disease that targets multiple organs, particularly causing acute complications via organ-specific pathogenesis accompanied by destruction of ACE2 + cells, including alveolus, cardiac microvasculature, endothelium, and glomerulus. Under such circumstances, the high expression of ACE2 in predisposing individuals associated with anomalous production of the renin-angiotensin system (RAS) may promote enhanced viral load in COVID-19, which comparatively triggers excessive apoptosis. Furthermore, multi-organ injuries were found linked to altered ACE2 expression and inequality between the ACE2/angiotensin-(1-7)/mitochondrial Ang system (MAS) and renin-angiotensin-system (RAS) in COVID-19 patients. However, the exact pathogenesis of multi-organ damage in COVID-19 is still obscure, but several perspectives have been postulated, involving altered ACE2 expression linked with direct/indirect damages by the virus-induced immune responses, such as cytokinin storm. Thus, insights into the invasion of a virus with respect to ACE2 expression site can be helpful to simulate or understand the possible complications in the targeted organ during viral infection. Hence, this review summarizes the multiple organs invasion by SARS CoV-2 linked with ACE2 expression and their consequences, which can be helpful in the management of the COVID-19 pathogenesis under life-threatening conditions., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as coronavirus disease 2019 (COVID-19) pandemic, has killed more than a million people worldwide, and researchers are constantly working to develop therapeutics in the treatment and prevention of this new viral infection. To infect and induced pathogenesis as observed in other viral infections, we postulated that SARS-CoV-2 may also require an escalation in the anabolic metabolism, such as glucose and glutamine, to support its energy and biosynthetic requirements during the infection cycle. Recently, the requirement of altered glucose metabolism in SARS-CoV-2 pathogenesis was demonstrated, but the role of dysregulated glutamine metabolism is not yet mentioned for its infection. In this perspective, we have attempted to provide a summary of possible biochemical events on putative metabolic reprograming of glutamine in host cells upon SARS-CoV-2 infection by comparison to other viral infections/cancer metabolism and available clinical data or research on SARS-CoV-2 pathogenesis. This systematic hypothesis concluded the vital role of glutaminase-1 (GLS1), phosphoserine aminotransferase (PSAT1), hypoxia-inducible factor-1 alpha (HIF-1α), mammalian target of rapamycin complex 1 (mTORC1), glutamine-fructose amidotransferase 1/2 (GFAT1/2), and transcription factor Myc as key cellular factors to mediate and promote the glutamine metabolic reprogramming in SARS-CoV-2 infected cells. In absence of concrete data available for SARS-CoV-2 induced metabolic reprogramming of glutamine, this study efforts to connect the gaps with available clinical shreds of evidence in SARS-CoV-2 infection with altered glutamine metabolism and hopefully could be beneficial in the designing of strategic methods for therapeutic development with elucidation using in vitro or in vivo approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bharadwaj, Singh, Kirtipal and Kang.)

Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) - diseases termed as COVID-19. Current SARS-CoV-2 outbreak have fueled ongoing efforts to exploit various viral target proteins for therapy, but strategies aimed at blocking the viral proteins as in drug and vaccine development have largely failed. In fact, evidence has now shown that coronaviruses undergoes rapid recombination to generate new strains of altered virulence; additionally, escaped the host antiviral defense system and target humoral immune system which further results in severe deterioration of the body such as by cytokine storm. This demands the understanding of phenotypic and genotypic classification, and pathogenesis of SARS-CoV-2 for the production of potential therapy. In lack of clear clinical evidences for the pathogenesis of COVID-19, comparative analysis of previous pandemic HCoVs associated immunological responses can provide insights into COVID-19 pathogenesis. In this review, we summarize the possible origin and transmission mode of CoVs and the current understanding on the viral genome integrity of known pandemic virus against SARS-CoV-2. We also consider the host immune response and viral evasion based on available clinical evidences which would be helpful to remodel COVID-19 pathogenesis; and hence, development of therapeutics against broad spectrum of coronaviruses., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Interleukin-6 (IL6) is encoded by the IL6 gene in human and acts as pro-inflammatory cytokine and an anti-inflammatory cytokine. Recent studies established that IL6 substantially contribute in the diagnosed of systemic inflammation for the patients suffering from lung diseases such as chronic obstructive pulmonary disease (COPD). Thereof, this work aimed to investigate the protagonist of IL6 (-174 G/C) genotypes as an essential risk factor for COPD in north Indian population. In the study, a total of 200 clinically diagnosed patients with COPD were selected against 200 patients. Statistical analysis reveleaed that there was no significant association between the IL6 -174 G/C genetic polymorphism and the risk of COPD (P>0.05).

This research aimed to explore the ACE (insertion/deletion) gene association as key factor for chronic obstructive pulmonary disease (COPD) development in north Indian population. A total of 200 clinically diagnosed patients with COPD were selected against 200 healthy individuals. Genetic variations of ACE (insertion/deletion) were evaluated by using polymerase chain reaction techniques. Smoker showed higher risk of COPD (OR=1.67, 95% CI=1.12-2.48, P=0.012). Present results revealed the positive association between the DD genotype and the risk of COPD (OR= 2.14, 95% CI=1.22-3.78, P=0.006). Among smokers, DD genotype showed statistically significant association with increased risk of COPD (OR=3.10, 95% CI= 1.50-6.47, P=0.001)., Competing Interests: The authors have declared no conflict of interest.