Genomic hotspots in the DENV-2 serotype (E, NS4B, and NS5 genes) are associated with dengue disease severity in the endemic region of India.

Dengue virus (DENV) infection manifests a wide spectrum of clinical outcomes, ranging from mild fever to severe and potentially fatal disease, yet the factors driving this variability remain poorly understood. This study aims to unravel the relationship between clinical manifestations of dengue and the genetic diversity of the virus, providing insights into the genomic variability driving disease severity. To achieve this, serum samples were collected during a dengue outbreak in National Capital Region-Delhi, India, from June to November 2023.

Unlocking the potential of Bavachin in vitamin D receptor cascade modulation for rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by joint damage and disrupted vitamin D signaling, leading to calcium deposition in joints. This study explores the therapeutic potential of Bavachin (BVN), a phytoestrogen from Psoralea corylifolia, in modulating vitamin D signaling in RA.

Methods: Vitamin D receptor (VDR) structure was modeled using SWISS-MODEL, AlphaFold, and I-TASSER, followed by docking with BVN and Estradiol (E2) via AutoDock Vina.

Cockroach allergen exposure alters redox homeostasis and mediates airway inflammation.

Allergic diseases are orchestrated by complex interplay of allergens with components of immune system as well as structural cells. As airway epithelium lies at the interface of environment and host immune responses, therefore we sought to study role of cockroach allergen exposure in context of oxidative stress in epithelia and its functional role in allergic pathophysiology. In vitro studies on Beas2B cells indicated elevation of intracellular ROS levels upon cockroach allergen (CE) exposure and transcriptional regulation of epithelial activation markers (CXCL-8 and IL-1 α) and endogenous antioxidant SOD-2.

Targeting GSK3β and signaling pathways in breast cancer: role of individual members of miR- 23/24/27 cluster.

Background: The high mortality rate of breast cancer and the difficulties associated with therapeutic resistance, especially in cases where targeted treatments are unavailable, make it a serious threat to women's health. This study examines the relationship between three mature microRNAs (miRNAs) that are clustered together, namely miR- 23a, miR- 27a, and miR- 24-2, as well as their potential correlation with breast cancer.

Methods: We identified common gene targets of miR- 23a, miR- 27a, and miR- 24-2 using computational analysis.

MiR-718-mediated inhibition of prohibitin 1 influences mitochondrial dynamics, proliferation, and migration of keratinocytes.

Keratinocyte hyperproliferation is a key characteristic of psoriasis. Prohibitins (PHB) are known to be associated with keratinocyte proliferation and cell cycle regulation, influenced by mitochondrial processes. The objective of this study was to examine the impact of miR-718 overexpression and downregulation on the various PHB1-mitochondria-driven activities in HaCaT keratinocytes.

Glutathione attenuates diesel exhaust-induced lung epithelial injury via NF-κB/Nrf2/GPX4-mediated ferroptosis.

Diesel exhaust (DE) emissions pose a significant threat to public health. This study linked DE-mediated reactive oxygen species (ROS) and ferroptosis with lung epithelial disruption, also the protective potential of exogenous glutathione (GSH) administration was investigated. C57BL/6 mice were divided into three groups: filtered air (control), DE exposed, and DE+GSH (administered intranasally on alternate days).

In-Situ Synthesis of Silver Nanoparticle within Self-Assembling Ultrashort Peptide Hydrogel as Antibacterial with Wound Healing Properties.

Introduction/objectives: Silver nanoparticles [AgNPs] are promising antimicrobial agents, but their synthesis often involves toxic reducing agents. To address this, we developed a green synthesis methodology employing an in-situ approach for synthesizing AgNPs within self- -assembled ultrashort peptide hydrogels through photochemical synthesis, eliminating the need for toxic chemicals.

Methods: A novel tetrapeptide was designed and synthesized to form hydrogels in aqueous solutions.

A Cdk5 inhibitor restores cognitive function and alleviates type 2 diabetes in mice.

Type 2 diabetes (T2D) is a metabolic disorder commonly linked with cognitive decline, increasing patients' susceptibility to dementia. Alzheimer's disease (AD) has a strong connection with hyperglycemia and insulin dysregulation. Interestingly, certain anti-diabetic drugs have shown potential in reducing T2D-induced cognitive impairment.

Phytochemicals from Musa acuminata Colla peel exhibit cathepsin B inhibition and anti-inflammatory activity.

Rheumatoid arthritis (RA) is a chronic inflammatory illness in which inflammatory mediators and cathepsin B and other proteases play a role in disease progression. The existing treatments may have negative side effects. Therefore, an alternative natural therapy for RA has been considered safe and beneficial.

Design, synthesis, and evaluation of 1,4-benzodioxane-hydrazone derivatives as potential therapeutics for skin cancer: In silico, in vitro, and in vivo studies.

In the pursuit of novel chemotherapeutic agents for skin cancer, we synthesized a series of 1,4-benzodioxane-hydrazone derivatives (7a-l) using the Wolff-Kishner reaction. These compounds were initially screened against the NCI-60 oncological cell lines in a one-dose assay at 10 μM. Among them, compound 7e emerged as a potent inhibitor of cancer cell growth across 56 cell lines, with an average GI of 6.

T Cells Promote Distinct Transcriptional Programs of Cutaneous Inflammatory Disease in Keratinocytes and Dermal Fibroblasts.

T cells and structural cells coordinate appropriate inflammatory responses and restoration of barrier integrity following insult. Dysfunctional T cells precipitate skin pathology occurring alongside altered structural cell frequencies and transcriptional states, but to what extent different T cells promote disease-associated changes remains unclear. We show that functionally diverse circulating and skin-resident CD4CLA T-cell populations promote distinct transcriptional outcomes in human keratinocytes and fibroblasts associated with inflamed or healthy tissue.

Weak D testing might be discontinued for RhD-negative blood donors with C and E negative phenotypes in the Indian population.

Background: Although serological testing to determine weak D status using the antihuman globulin reagent has been phased out for RhD-negative donors in many countries after the availability of RHD genotyping, it is routinely performed in India. However, weak D testing is a resource-intensive and time-consuming process. We devised a new algorithm for weak D testing in RhD-negative blood donors by performing CcEe phenotyping followed by weak D testing in only C+ and/or E + samples and compared it with the existing protocol in terms of time and cost-effectiveness.

Novel genetic associations with childhood adipocytokines in Indian adolescents.

Adipocytokines, including leptin, adiponectin, and resistin, are key mediators linking adiposity, insulin resistance, and inflammation. We present the first genome-wide association study (GWAS; N = 5258) and exome-wide association study (ExWAS; N = 4578) on leptin, adiponectin, and resistin in South Asian population. We identified novel associations in genes ZNF467, and LEPREL2 for leptin; ZNF467, LEPREL2, CRLF3, ZNF732, SOX30, XIRP1, ATP8B3, SPATA2L, TMCO4, TLN2, ABCA12, and SHB for adiponectin; and D2HGDH for resistin.

Probing the multitargeted potency of Theodrenaline and its comparative evaluation with Crizotinib against transferase, hydrolase, signalling, and apoptosis-related proteins to overcome lung cancer drug resistance.

Cancer has become a prevalent disease that imposes a huge burden on society and the scientific community, and the worst-case scenario has evolved nowadays due to its resistance profiles. Lung cancer comes first in diagnosis and death and is gender-neutral, causing 1.8 million deaths yearly.

CD38-mediated metabolic reprogramming promotes the stability and suppressive function of regulatory T cells in tumor.

In the tumor microenvironment (TME), regulatory T cells (T) adapt their metabolism to thrive in low-glucose, high-lactate conditions, but the mechanisms remain unclear. Our study identifies CD38 as a key regulator of this adaptation by depleting nicotinamide adenine dinucleotide (oxidized form) (NAD), redirecting lactate-derived pyruvate toward phosphoenolpyruvate and bypassing the tricarboxylic acid (TCA) cycle. This prevents accumulation of α-ketoglutarate, which destabilizes T by inducing hypermethylation at the locus.

A combination of systemic mannitol and mannitol modified polyester nanoparticles for caveolae-mediated gene delivery to the brain.

Overcoming the blood-brain barrier (BBB) remains a significant challenge for nucleic acid delivery to the brain. We have explored a combination of mannitol-modified poly (β-amino ester) (PBAE) nanoparticles and systemic mannitol injection for crossing the BBB. We incorporated mannitol in the PBAE polymer for caveolae targeting and selected monomers that may help avoid delivery to the liver.

A global survey about undiagnosed rare diseases: perspectives, challenges, and solutions.

Background: Undiagnosed rare diseases (URDs) are a complex and multifaceted challenge, especially in low-and medium-income countries. They affect individuals with unique clinical features and lack a clear diagnostic label. Although the Undiagnosed Diseases Network International (UDNI) definition of URDs is not universally accepted, it is widely recognized.

SARS-CoV-2 Alchemy: Understanding the dynamics of age, vaccination, and geography in the evolution of SARS-CoV-2 in India.

Background: COVID-19 pandemic had unprecedented global impact on health and society, highlighting the need for a detailed understanding of SARS-CoV-2 evolution in response to host and environmental factors. This study investigates the evolution of SARS-CoV-2 via mutation dynamics, focusing on distinct age cohorts, geographical location, and vaccination status within the Indian population, one of the nations most affected by COVID-19.

Methodology: Comprehensive dataset, across diverse time points during the Alpha, Delta, and Omicron variant waves, captured essential phases of the pandemic's footprint in India.

Understanding the genetic epidemiology of hereditary breast cancer in India using whole genome data from 1029 healthy individuals.

Breast cancer is the most highly reported cancer in India. Genetic testing could help tackle the increasing cancer burden by enabling carriers obtain early diagnosis through increased surveillance, and help guide treatment. However, accurate interpretation of variant pathogenicity must be established in a population-specific manner to ensure effective use of genetic testing.

Microbial landscape of Indian homes: the microbial diversity, pathogens and antimicrobial resistome in urban residential spaces.

Background: Urban dwellings serve as complex and diverse microbial community niches. Interactions and impact of house microbiome on the health of the inhabitants need to be clearly defined. Therefore, it is critical to understand the diversity of the house microbiota, the presence and abundance of potential pathogens, and antimicrobial resistance.

Mapping the landscape of childhood obesity: genomic insights and socioeconomic status in Indian school-going children.

Objective: Childhood obesity (OB) is influenced by complex gene-environmental interaction. While genetics of adult OB have been extensively studied, polygenic childhood OB in non-European populations is still underexplored. Furthermore, in a developing nation such as India, how the environmental component strongly modulated by the socioeconomic status (SES) shapes the genetic susceptibility is crucial to understand.

getENRICH: a tool for the gene and pathway enrichment analysis of non-model organisms.

Motivation: The Gene Ontology system facilitates the functional annotation of genes by categorizing them into specific biological processes, cellular components, and molecular functions. Despite numerous tools like DAVID and Enrichr, analysing non-model organisms remains challenging due to a lack of genetic information and available tools.

Results: To address this, we present getENRICH, a comprehensive tool for gene enrichment analysis tailored for non-model organisms.

Nonstop mutations cause loss of renal tumor suppressor proteins and and affect multiple stages of protein translation.

Nonstop extension or stop-loss mutations lead to the extension of a protein at its carboxyl terminus. Recently, nonstop mutations in the tumor suppressor () have been discovered to lead to proteasomal SMAD4 degradation. However, this mutation type has not been studied in other cancer genes.