Rashmi Chowdhary

With millions of deaths annually and a big impact on life expectancy reduction, cancer remains a serious global health concern. Colorectal cancer (CRC), which is the second most common cause of can...

Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer, posing challenges to modern oncology. Current treatments, including surgery, radiation, and chemotherapy (e.g., Temozolomide or TMZ), often fail due to the inevitable development of drug resistance. TMZ resistance remains a major therapeutic challenge for the reasons that it is the first-line treatment. Recent studies indicate a rising GBM tumour burden and a trend towards earlier age of onset. It highlights the urgent need for evidence-based policymaking and intensified research to address this most difficult-to-treat malignancy in clinical settings. Ferroptosis, a newly recognized type of controlled cell death induced by iron-dependent lipid peroxidation, has emerged as a potential approach to overcome apoptosis resistance and restore drug sensitivity in GBM. This mechanism is modulated by key molecules that can be specifically targeted to either enhance oxidative stress or inhibit antioxidant defences, ultimately leading to tumour cell death. This review conducts a meta-analysis of preclinical evidence to better understand the potential of activating ferroptosis as a key target for developing nanoparticles to resensitize TMZ-resistant GBM cells. Current evidence indicates that combining ferroptosis induction with strategically engineered nanocarrier systems can serve as a novel and effective therapeutic approach to overcome TMZ resistance and advance precision-based GBM treatment.

Objectives: Dengue virus (DENV), a single-stranded RNA virus from the Flaviviridae family, causes viral hemorrhagic fever and poses a global health threat due to limited diagnostics, treatments, and vaccines. The conserved NS5 protein, crucial for DENV replication, is a promising antiviral target. Antibody-dependent enhancement (ADE) complicates immunity, as serotype-specific antibodies may worsen infection. Moringa oleifera , rich in antiviral phytochemicals, shows potential as a DENV inhibitor by targeting proteomic, transcriptomic, and metabolomic pathways. Methods: This study employed molecular docking with 3D PubChem structures of bioactive compounds of M . oleifera to evaluate the binding affinity with DENV-2 NS5 proteins (PDB ID: 6KR2) using AutoDock Vina, and binding modes were analyzed using Discovery Studio. Further drug-likeness, oral bioavailability, ADME, and toxicity profiles were analyzed using SwissADME, ADMETSaR, and ADMETlab 3.0 web server. Complexes were subjected to molecular dynamics simulation (MDS) analysis using Desmond Schrodinger v2019. Results: Among the screened compounds, rhamnopyranosyl vincosamide (−9.0 kcal/mol), luteoxanthin (−8.6 kcal/mol), and luteolin (−8.3 kcal/mol) exhibited the most stable interactions and were further analyzed through molecular dynamics (MD) simulations. The results revealed that these phytochemicals interact with NS5 active-site residues, demonstrating significant inhibitory potential. Conclusions: The study suggests that M . oleifera phytochemicals hold promise as DENV-2 NS5 inhibitors with minimal toxicity and favorable pharmacokinetic properties. These findings provide a strong foundation for further clinical investigations, potentially contributing to developing novel anti-dengue therapeutics.

Background: Respiratory droplets are the main way in which the COVID-19 pandemic’s causal agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), spreads. Angiotensin-converting enzyme 2 (ACE2) receptors, especially in lung cells, allow the virus to enter host cells. However, ACE2 expression in intestinal cells has sparked worries about possible fecal transfer, particularly in poor-sanitation areas like India. Methods: Between July 2021 and July 2024, clinical (nasopharyngeal, saliva, and stool samples) and sewage samples were collected from outpatient departments and sewage treatment plants (STPs), respectively, from the high-population-density area under study in order to investigate SARS-CoV-2 transmission. Results: This proof-of-concept study analyzed clinical samples from n = 60 COVID-19-positive patients at a central Indian tertiary care hospital and n = 156 samples from hospital STPs. Variants of SARS-CoV-2 were found using qRT-PCR and Next-Generation Sequencing (NGS). Of the n = 37 qRT-PCR-positive patients who gave their assent, 30% had stool samples that tested positive for viral RNA. In 70% of positive NP and 65% of positive saliva samples, along with two stool samples from immunocompromised patients, the live virus was identified using Vero E6 cell lines. Although 18% of the tests reported qRT-PCR-positive results, no live virus was detected in sewage samples despite NGS validation. The detection of SARS-CoV-2 in the absence of confirmed clinical cases may indicate the silent circulation of the virus within the community, suggesting that sewage surveillance can serve as an early warning system before an outbreak occurs. Conclusions: These findings provide critical insights into the importance of continuous environmental surveillance, silent virus circulation, changes in viral epidemiology throughout the years, and strategies to mitigate coronavirus outbreaks.

Objectives: Restless Leg Syndrome (RLS) is a neurological disorder characterized by an uncontrollable urge to move the legs, often worsening at night, leading to insomnia and discomfort. RLS is linked to genetic factors, defects in iron metabolism, dopaminergic dysfunction, and disturbances in the central opiate system. Specific genetic variants, including MEIS1, BTBD9, PTPRD, and MAP2K5/SCOR1, affect dopamine synthesis, iron transport, and neuroprotection. Research on RLS prevalence and its underlying causes in India is limited, highlighting the need for more in-depth genetic and biochemical studies to improve diagnosis and treatment. Material and Methods: A hundred suspected RLS patients were screened at AIIMS Bhopal’s Pulmonary Medicine department. After obtaining consent, 36 confirmed RLS cases and age-matched healthy controls were enrolled. Blood samples were collected for fasting blood sugar (FBS), liver function tests (LFT), renal function tests (RFT), serum ferritin, and iron analysis using an auto-analyzer. Genotyping for single nucleotide polymorphisms (SNPs) was performed using ARMS-PCR. Results: RLS significantly impacts daily life, contributing to insomnia, irritability, and other comorbidities. The study revealed lower iron levels in RLS patients, suggesting a potential secondary form of the condition linked to iron deficiency. Variations in serum iron, total iron-binding capacity, iron saturation, and ferritin further underscore the relationship between iron metabolism and RLS. Genetic analysis identified SNPs in genes such as MEIS1, TOX3, and PTPRD, potentially contributing to RLS. Although no specific at-risk alleles were prevalent, heterozygous mutations, particularly at the T allele, suggested a possible genetic predisposition that may exacerbate RLS. Conclusion: This study supports the iron-dopamine hypothesis, linking RLS to brain iron deficiency that disrupts dopamine signaling. Genetic factors may further aggravate this disruption. Understanding the interplay between iron levels and dopaminergic function is crucial for effectively managing both primary and secondary RLS, aiding the development of better long-term treatment strategies.

Dengue fever remains a significant public health concern in tropical regions, including Central India, where outbreaks are frequent and associated with high morbidity and mortality. This study investigated the dynamics of dengue virus transmission and evolution in Central India from 2019 to 2023, focusing on the emergence of new strains and their impact on outbreak patterns. For this, 40 mosquito pools and 300 patient samples were recruited for the study. Phylogenetic and Bayesian evolutionary analyses performed on CPrM region and whole genome sequences generated by Sanger and Illumina sequencing, respectively, revealed the emergence and predominance of a novel DENV-2 genotype IV lineage III strain in the 2019 and 2023 outbreaks, which displaced the previously circulating DENV-1 genotype responsible for the 2016–2017 outbreak. Despite pre-existing DENV-1 neutralizing antibodies in the community (67 healthy volunteers), the novel DENV-2 strain exhibited higher viral loads and a greater reproduction number (R0), contributing to rapid disease spread. Molecular clock and Shannon entropy analyses suggest that DENV evolution occurred within the mosquito vector, driven by natural selection. Our findings highlight the importance of continuous DENV surveillance, including genetic characterization in both vectors and hosts, to understand viral evolution and predict future outbreaks. Rapid urbanization and inadequate sanitation in densely populated regions like India create ideal breeding grounds for mosquitoes, facilitating the introduction and establishment of novel DENV strains. Interrupting the vector–DENV–host cycle through targeted interventions is crucial for effective dengue control.

Background: Glioblastoma Multiforme (GBM) is a prevalent and deadly type of pri-mary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene ex-pression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM. Methods: The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- Rank-Aggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents. Results: The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs. Conclusion: These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alter-native to conventional GBM cancer chemotherapy.

MCAM-1 (CD146) is an endothelial cell adhesion molecule belonging to the immunoglobulin superfamily. Recent studies have identified CD146 expression as a critical marker for tumor progression, migration, and metastasis in various malignancies. This study aimed to evaluate CD146 immunohistochemical expression in various gynecological cancers. This study was conducted in a tertiary medical center in central India. A total of 49 gynecological cancer cases and 16 site-matched controls were included. The cases comprised 27 cervical, 10 endometrial, 10 ovarian, and two miscellaneous cancers. CD146 immunohistochemistry was performed and assessed for immunoreactivity score (IRS), microvascular density (MVD), and microvascular caliber (MVC). An IRS of 5 or more was considered CD146 positive. The p-values for CD146 positivity for cases vs. control were 0.0531, 0.0580, and 0.007 for cervical, endometrial, and ovarian sites, respectively. The mean MVD was found to be significantly higher in cases compared with benign tissues (p-value <0.00001), and the mean MVC of cases was found to be smaller when compared with the controls (p-value <0.0001). MVD by CD146 was found to be higher in gynecological malignancies, highlighting its role in cancer neo-angiogenesis and its potential therapeutic role. CD146 epithelial expression was also significantly higher in ovarian cancers. Further studies with a larger sample size are required to confirm that this protein may be a potential theognostic target in gynecological cancers.

Objectives: Worldwide, breast cancer is the most prevalent and common type of cancer. Physical examination and mammography with a range of sensitivities are currently used as screening methods. Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) gene expression. MicroRNAs (miRNA) as potential prognostic and diagnostic biomarkers, miRNA 125, 200c, 221, 21, and 34a were selected for study. Materials and Methods: Here, 25 consenting TNBC patients with negative ER/PR/HER-2 status and compatible history were accrued from the Department of Oncosurgery, All India Institutes of Medical Sciences (AIIMS) Bhopal. Serum from participants and 25 controls was collected for quantitative estimation of miRNA by quantitative real-time polymerase chain reaction. After being treated with epirubicin, capecitabine, and paclitaxel, the MDA-MB-231 cell line’s expression of these miRNA subtypes was also examined. Statistical Analysis: All statistical analyses, pie charts, dot plots, and box-whisker plots were performed using EZR (Easy R), R Commander version 2.7-1. Bar graphs were created using Microsoft Excel 2019 software. Heat map graphics were produced using Graph Prism Version 9. Results: miRNA125 (p< 0.0001) and miRNA21 (p< 0.05) were found to be statistically significant. miR125 (DCt [cycle threshold] 2.77) was seen to be upregulated and miR21 (DCt -1.61) was seen to be downregulated in TNBC patients. Epirubicin treatment caused miR125 to be downregulated, but capecitabine treatment caused miR125 to be upregulated. Paclitaxel was seen to downregulate miR21. All three chemotherapeutic agents were seen to downregulate miR34a. Conclusion: miRNAs can be developed into a reliable biomarker and prognostic tool with more research. They can also help develop and improve pharmaco-therapeutic strategies.