Ganaxolone Reverses the Effect of Amyloid β-Induced Neurotoxicity by Regulating the Liver X Receptor Expression in APP Transfected SH-SY5Y Cells and Murine Model of Alzheimer's Disease.

Inhibiting β-amyloid aggregation and enhancing its clearance are the key strategies in Alzheimer's disease (AD) treatment. Liver X receptors (LXRs) plays a crucial role in cholesterol homeostasis and inflammation, and their activation can clear Aβ aggregates in AD. Allopregnanolone, a neurosteroid, positively influences AD through LXR regulation, while ganaxolone, its synthetic analog, is known for its neuroprotective properties.

An exploratory SWATH plasma proteomics analysis of phyllodes tumor- a type of female breast tumor.

Objective: Phyllodes tumors (PT) are rare fibroepithelial breast tumors with poorly understood molecular pathology. This study intent to identify the potential plasma markers of phyllodes tumors compared to controls using Sequential window acquisition of all theoretical fragment ion spectra-mass spectrometry (SWATH-LC-MS) based proteomics approach.

Method: Plasma samples from phyllodes tumor cases and controls underwent SWATH-LC-MS/MS based untargeted proteomics analysis.

RNA G-quadruplexes regulate mammalian mirtron biogenesis.

Mirtrons are a predominant class of noncanonical microRNAs derived from introns through a Drosha-independent, splicing-dependent pathway. Unregulated splicing of introns containing hairpins may adversely impact Dicer/Ago-mediated canonical microRNA biogenesis. However, the mechanism regulating mirtron biogenesis remains poorly understood.

In silico design of an epitope-based vaccine ensemble for fasliolopsiasis.

Introduction: Fasciolopsiasis, a food-borne intestinal disease is most common in Asia and the Indian subcontinent. Pigs are the reservoir host, and fasciolopsiasis is most widespread in locations where pigs are reared and aquatic plants are widely consumed. Human infection has been most commonly documented in China, Bangladesh, Southeast Asia, and parts of India.

Genome-Wide Association Study Reveals Genetic Architecture of Common Epilepsies.

Epilepsy, affecting approximately 50 million individuals worldwide, exhibits a genetic heritability of 32%. While several genes/loci associated with epilepsy have been identified through candidate and genome-wide association studies (GWAS), exploration of population-specific markers remains underexplored. We conducted the first GWAS in north Indian population (~1500 samples) to identify genetic variants/loci associated with epilepsy risk, validated using targeted next-generation sequencing (NGS).

Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway.

Pyridinyl-imidazole class p38 MAPKα/β (MAPK14/MAPK11) inhibitors including SB202190 have been shown to induce cell-type specific defective autophagy resulting in micron-scale vacuole formation, cell death, and tumor suppression. We had earlier shown that this is an off-target effect of SB202190. Here we provide evidence that this vacuole formation is independent of ATG5-mediated canonical autophagosome initiation.

First report of the chloroplast and mitochondrial genomes of the Indian pitcher plant, Nepenthes khasiana Hook.f.

Objectives: Nepenthes, sometimes known as tropical pitcher plants or monkey cups, is a carnivorous plant genus that contains more than 160 species. Nepenthes khasiana, India's sole representative of the genus, is a rare and endangered dioecious plant endemic to North-east India. Despite the fact that it is a prominent insectivorous plant in the Nepenthaceae family, genomic resources for the species are limited, making genomic breeding and understanding the genetic basis of botanical carnivory difficult.

Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension.

Hypoxia is a major cause of pulmonary hypertension (PH) worldwide, and it is likely that interstitial pulmonary macrophages contribute to this vascular pathology. We observed in hypoxia-exposed mice an increase in resident interstitial macrophages, which expanded through proliferation and expressed the monocyte recruitment ligand CCL2. We also observed an increase in CCR2+ macrophages through recruitment, which express the protein thrombospondin-1, which functionally activates TGF-β to cause vascular disease.

Genetic insights into CRP levels in Indian adolescents: confirming adult genetic associations.

CRP is a biomarker of acute inflammation linked to metabolic complications. Given the rising prevalence of these conditions in India, we investigated the genetic basis of CRP levels in Indian adolescents, an underrepresented group in genetic studies, to identify early markers of metabolic risk. We performed a two-phased genome-wide association study (GWAS; N = 5052) and an independent Exome-wide association study (ExWAS; N = 4547), to identify both common and rare genetic variants associated with CRP levels.

Novel 327bp Alu element insertion in LDLR exon 17 causes alternative splicing and familial hypercholesterolemia.

Background: Homozygous familial hypercholesterolemia (HoFH) is a severe form of familial hypercholesterolemia (FH) characterized by high low-density lipoprotein cholesterol (LDL-C) levels and increased coronary artery disease risk. This study reports a novel Alu insertion in the LDLR gene in a consanguineous Indian family, causing FH.

Objective: To identify and characterize the mutation causing HoFH in a proband and their family members.

Unprecedented Co-occurrence: Identification of a Pathogenic Genetic Variant in the KMT2B Gene in a Wilson Disease Patient with a Pathogenic ATP7B Mutation.

The pathophysiology of dystonia in Wilson disease (WD) is complex and poorly understood. Copper accumulation in the basal ganglia, disrupts dopaminergic pathways, contributing to dystonia's development via neurotransmitter imbalance. Despite advances in diagnosis and management, WD with dystonia remains a challenging condition to treat.

Integrative genomics would strengthen AMR understanding through ONE health approach.

Emergence of drug-induced antimicrobial resistance (AMR) forms a crippling health and economic crisis worldwide, causing high mortality from otherwise treatable diseases and infections. Next Generation Sequencing (NGS) has significantly augmented detection of culture independent microbes, potential AMR in pathogens and elucidation of mechanisms underlying it. Here, we review recent findings of AMR evolution in pathogens aided by integrated genomic investigation strategies inclusive of bacteria, virus, fungi and AMR alleles.

Citrus maxima extract-coated versatile gold nanoparticles display ROS-mediated inhibition of MDR-Pseudomonas aeruginosa and cancer cells.

The expanding prevalence of microbial resistance to conventional treatments has triggered a race to develop alternative/improved strategies to combat drug-resistant microorganisms in an efficient manner. Here, the lethal impact of the biosynthesized gold nanoparticles (AuNPs) against multi-drug resistant (MDR) bacteria has been elucidated. AuNPs, synthesized from the extracts of the fruit, leaf and peel of the Citrus maxima plant, were physicochemically characterized by UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), electron microscopy and spectroscopic techniques not only confirmed the production of AuNPs of size below 100 nm but also identified the phytochemicals adsorbed onto the surface of NPs.

Protocol for investigating intracellular microbial diversity using single-cell RNA-seq in immune cells of SARS-CoV-2-positive and recovered patients.

Intracellular microorganisms like viruses and bacteria impact immune cell function. However, detection of these microbes is challenging as the majority exist in a non-culturable state. This protocol presents detailed steps to investigate intracellular microbial diversity using single-cell RNA sequencing (scRNA-seq) in immune-cells of SARS-CoV-2-positive and recovered patients.

Nanoscale Prussian Blue and Its Analogues: Design and Applications in Infection Control, Wound Healing and Beyond.

Prussian blue nanoparticles (PBNPs) have gained significant attraction in the field of nanomedicine due to their excellent biocompatibility, potential for nanoscale production, exceptional photothermal conversion ability, and multi-enzyme mimicking capabilities. PBNPs have made considerable advancements in their application to biomedical fields. This review embarks with a comprehensive understanding of the physicochemical properties and chemical profiling of PB-based nanoparticles, discussing systematic approaches to tune their dimensions, shapes, and sizes, as well as their biomedical properties.

Exploring the influence of age and diet on gut microbiota development in children during the first 5 years: a study from Yaoundé, Cameroon.

Introduction: The development of the human gut microbiota is shaped by factors like delivery mode, infant feeding practices, maternal diet, and environmental conditions. Diet plays a pivotal role in determining the diversity and composition of the gut microbiome, which in turn impacts immune development and overall health during this critical period. The early years, which are vital for microbial shaping, highlight a gap in understanding how the shift from milk-based diets to solid foods influences gut microbiota development in infants and young children, particularly in Yaoundé, Cameroon.

Telomere length sensitive regulation of interleukin receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment.

Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood.

Physiological, biochemical, and genome-wide expression patterns during graded normobaric hypoxia in healthy individuals.

The regulation of oxygen homeostasis is critical in physiology and disease pathogenesis. High-altitude environment or hypoxia (lack of oxygen) can lead to adverse health conditions such as high-altitude pulmonary edema (HAPE) despite initial adaptive physiological responses. Studying genetic, hematological and biochemical, and the physiological outcomes of hypoxia together could yield a comprehensive understanding and potentially uncover valuable biomarkers for predicting responses.

Integrative metabolomic-proteomic analysis uncovers a new therapeutic approach in targeting rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory condition that, despite available approaches to manage the disease, lacks an efficient treatment and timely diagnosis. Using the most advanced omics technique, metabolomics and proteomics approach, we explored varied metabolites and proteins to identify unique metabolite-protein signatures involved in the disease pathogenesis of RA.

Methods: Untargeted metabolomics (n = 20) and proteomics (n = 60) of RA patients' plasma were carried out by HPLC/LC-MS/MS and SWATH, respectively and analyzed by Metaboanalyst.

SARS-CoV-2 pathophysiology and post-vaccination severity: a systematic review.

Currently, COVID-19 is still striking after 4 years of prevalence, with millions of cases and thousands of fatalities being recorded every month. The virus can impact other major organ systems, including the gastrointestinal tract (GIT), cardiovascular, central nervous system, renal, and hepatobiliary systems. The resulting organ dysfunction from SARS-CoV-2 may be attributed to one or a combination of mechanisms, such as direct viral toxicity, disruptions in the renin-angiotensin-aldosterone system (RAAS), thrombosis, immune dysregulation, and ischemic injury due to vasculitis.

Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.

NOTCH, a single-pass transmembrane protein, plays a crucial role in cell fate determination through cell-to-cell communication. It interacts with two canonical ligands, Delta-like (DLL) and Jagged (JAG), located on neighboring cells to regulate diverse cellular processes. Despite extensive studies on the functional roles of NOTCH and its ligands in cellular growth, the structural details of full-length NOTCH and its ligands remain poorly understood.

Subtyping strokes using blood-based protein biomarkers: A high-throughput proteomics and machine learning approach.

Background: Rapid diagnosis of stroke and its subtypes is critical in early stages. We aimed to discover and validate blood-based protein biomarkers to differentiate ischemic stroke (IS) from intracerebral haemorrhage (ICH) using high-throughput proteomics.

Methods: We collected serum samples within 24 h from acute stroke (IS & ICH) and mimics patients.