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.

Targeted Nanotherapy by Vinblastine-Loaded Chitosan-Coated PLA Nanoparticles to Improve the Chemotherapy via Reactive Oxygen Species to Hamper Hepatocellular Carcinoma.

Liver cancer is a prevalent and significant cause of death in humans. The use of novel biodegradable materials for various biomedical applications is being recently recommended as complementary as well as alternative solution for traditional chemotherapy. This study focuses on the synthesis of biodegradable nanocarriers [chitosan-coated poly(lactic acid) NPs (Cht-PLA NPs)] for the delivery of an anticancer drug vinblastine (Vbx) and to evaluate its therapeutic potential in human hepatocellular carcinoma (HepG2) cells.

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.

Dicer inhibition delays wound closure by increasing SUZ12 levels and regulating ITGAV levels in keratinocytes.

Delayed wound closure is a significant hallmark associated with diabetes. A previous study from our laboratory identified decreased levels of Dicer and miRNAs together with altered levels of wound healing genes in the wounded tissues of diabetic rats. Comprehensive regulators of these wound healing genes mapped onto the PRC2 (polycomb repressive complex 2) complex.

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.

Anaemia and iron deficiency in India: a venous blood-based survey of adolescents, adults, and the elderly in eight states.

Background: Surveys based on capillary blood show that anaemia is rampant in India, but capillary blood haemoglobin (Hb) may not accurately reflect venous blood Hb concentrations. Further, iron deficiency (ID) is thought to be the main cause of anaemia, there are no venous blood-based surveys to confirm this.

Methods: A community-based (urban, slum and rural) cross-sectional, venous blood survey was conducted in eight Indian states to estimate anaemia and ID prevalences from Hb and inflammation-corrected plasma ferritin concentrations in adolescents, adults, and elderly.

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.

NSD3 protein methylation and stabilization transforms human ES cells into variant state.

Cultured human embryonic stem cells (hESCs) can develop genetic anomalies that increase their susceptibility to transformation. In this study, we characterized a variant hESC (vhESC) line and investigated the molecular mechanisms leading to the drift towards a transformed state. Our findings revealed that vhESCs up-regulate EMT-specific markers, accelerate wound healing, exhibit compromised lineage differentiation, and retain pluripotency gene expression in teratomas.

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.

Functional genomics of primary congenital glaucoma by pathway analysis and functional characterization of CYP1B1 mutations.

CYP1B1 is the most common gene implicated in primary congenital glaucoma (PCG) - the most common form of childhood glaucoma. How CYP1B1 mutations cause PCG is not known. Understanding the mechanism of PCG caused by CYP1B1 mutations is crucial for disease management, therapeutics development, and potential prevention.

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.

Effect of antiepileptic drug monotherapy on endogenous sex hormonal profile in men and women with epilepsy.

Objective: To assess the alterations of endogenous sex hormone profiles in patients with epilepsy (PWE) on different antiepileptic drug (AED) monotherapies compared to healthy controls and drug naïve PWE (DNPWE).

Methods: Four databases MEDLINE, EMBASE, SCOPUS, and CENTRAL were searched for analytical observational/intervention studies on the assessment of endogenous sex hormones in PWE compared to healthy controls and DNPWE. Two researchers reviewed the title/abstract, and full-text articles for the selection of the studies independently.

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.

Development of an In Silico Platform (TRIPinRNA) for the Identification of Novel RNA Intramolecular Triple Helices and Their Validation Using Biophysical Techniques.

There are surprisingly few RNA intramolecular triple helices known in the human transcriptome. The structure has been most well-studied as a stability-element at the 3' end of lncRNAs such as and , but the intrigue remains whether it is indeed as rare as it is understood to be or just waiting for a closer look from a new vantage point. TRIPinRNA, our Python-based in silico platform, allows for a comprehensive sequence-pattern search for potential triplex formation in the human transcriptome─noncoding as well as coding.

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.

c-MET tyrosine kinase inhibitors reverse drug resistance mediated by the ATP-binding cassette transporter B1 (ABCB1) in cancer cells.

This study investigated the potential of MET kinase inhibitors, cabozantinib, crizotinib, and PHA665752, in reversing multidrug resistance (MDR) mediated by ABCB1 in cancer cells. The accumulation of the fluorescent probe, Rhodamine 123, was assessed using flow cytometry and fluorescence microscopy in MDR MES-SA/DX5 and parental cells. The growth inhibitory activity of MET inhibitors as monotherapies and in combination with chemotherapeutic drugs was evaluated by MTT assay.