Targeting mitochondrial proteases CLPP and LONP1 via disruption of mitochondrial redox homeostasis induces proteotoxic stress and suppresses tumor progression.

Background: Cancer cells, which rely heavily on mitochondria for their energy demands and oncometabolites, have a high mitochondrial load, often associated with an aggressive, invasive, and metastatic phenotype. Mitochondrial ROS (mtROS), which play a causal role in cancer, represent the Achilles' heel of cancer since excessive mtROS causes protein misfolding/aggregation, resulting in cell death via proteotoxic stress. Furthermore, the detailed underlying mechanism(s) of mitochondrial oxidative stress-induced cell death remain obscure.

Nephrology in Nepal: How it Started and Where We Are.

Nepal has made significant strides in nephrology, progressing from no dialysis services to offering comprehensive kidney care, including dialysis and transplantation. The journey began in the 1980s with the establishment of the first nephrology unit at Bir Hospital and has since grown to encompass over 60 dialysis centers and multiple transplant facilities. Government initiatives, such as financial subsidies and health insurance schemes, have increased accessibility, yet disparities persist due to workforce shortages, uneven infrastructure distribution, and inconsistent quality control in dialysis services.

Comprehensive biobanking to enhance precision medicine in head & neck cancer through systematic sample collection & data integration.

Background & objectives Head and neck carcinomas (HNCs), including oral cancers (OCs), represent a significant global health issue, especially in India, where they contribute to one-third of the global OC burden. Despite advances in treatment, survival rates remain poor, often due to limited treatment options and underlying research gaps. The Rajiv Gandhi Cancer Institute & Research Centre (RGCIRC) biorepository initiative undertook to address this gap by systematically collecting and storing biological specimens and their derivatives for HNC, fostering translational research and collaborations.

Indian Association of Conservative Dentistry and Endodontics consensus statement on deep caries management.

Dental caries remains one of the most ubiquitous chronic diseases worldwide, affecting people across geographic, socioeconomic, and demographic boundaries. In response to this pervasive burden, the consensus statement; developed by a panel of experts in cariology, restorative dentistry and endodontics during the Symposium on Deep Caries Management Symposium at the 39 Indian Association of Conservative Dentistry and Endodontics National Conference, Jio Convention Centre, Mumbai, November 29, to December 3, 2024, synthesises contemporary understanding of carious pathogenesis with evidence-based clinical strategies. It is intended for dental practitioners managing deep caries in vital permanent teeth of all age groups, from adolescents to older adults.

Computational discovery of novel SIRT4 inhibitors for cardiac hypertrophy treatment.

Cardiac hypertrophy is characterized by the enlargement of the heart muscle, often resulting from conditions such as hypertrophic cardiomyopathy (HCM) and physiological hypertrophy. SIRT4 plays a crucial role in cardiac hypertrophy, primarily through its regulation of oxidative stress and mitochondrial function. Therefore, downregulating SIRT4 could help slow the progression of cardiac hypertrophy.

Synthesis of ferrocenyl/phenyl isothiazole-3-thione and isoselenazole-3-selenone as new heterocycles.

A direct one-pot synthesis for novel heterocycles, isothiazole-3-thiones and isoselenazole-3-selenones the annulation of ferrocenyl/phenyl-β-chloro acrylaldehyde, amines and chalcogen powder (S and Se) has been established. The reaction was catalyzed by an environmentally benign iron cluster and Cu(OAc)·HO salt. The method is unique and rare as it consists of five consecutive bonds formation.

Agronomic improvement using gamma ray induced mutagenesis is associated with changes in phytochemical and phytohormonal profiles in functional rice variety 'Gathuwan'.

Background: Gamma ray induced mutation breeding has emerged as an excellent method for expedited development of improved varieties of rice, a staple food for more than half the world's population. However, the assessment of radiation induced variations are primarily phenotypic in nature. In this direction, evaluation of the metabolic signature of bio-active ingredients, which confer beneficial properties to rice, could be employed as a tool to select varieties which not only retain the health benefits of the parent variety but also exhibit better agronomic traits.

Machine learning driven identification of therapeutic phytochemicals targeting Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), being the most common liver cancer, remains a global health concern due to the high mortality rate. HCC is also attributed to severe alcohol abuse, further leading to liver cirrhosis and cytochrome expression. The known treatments for HCC are becoming less effective with high side effects, which highlights the need for promising phytochemicals, as antioxidants, anti-inflammatories, antitumor, and other pharmacological properties.

Skyrmionic Polarization Texture around the Phase Singularity of Optical Vortices.

We disclose the existence of a type of optical skyrmion, Gauss-Stokes (GS) skyrmions, that is naturally present in an optical vortex around its phase singularity. Contrary to previous research with optical skyrmions, we neither shape vector beams nor superpose different spatial modes and polarizations. In GS skyrmions, the phase singularity in the transversal field of a single monochromatic beam of uniform polarization (a scalar beam) is concealed by the axial field dictated by Gauss's divergence law, giving rise to a polarization singularity of undefined polarization plane.

Differentiating α-synuclein aggregates using charge-sensitive gold nanoclusters.

The accumulation of α-synuclein (α-syn) aggregates in the brain is associated with Parkinson's disease, making it a promising biomarker for understanding the disease's pathogenesis. Distinguishing between oligomeric forms of amyloidogenic proteins is crucial, as their toxicity depends on conformation. This study leverages surface charge differences to distinguish α-syn monomers from amyloids.

Boredom and self-control in adolescent athletes: preventing non-contact mechanical fatigue-related anterior cruciate ligament injuries, a commentary.

Introduction Or Background: Anterior cruciate ligament (ACL) injuries from the accumulated micro-trauma that precedes non-contact mechanical fatigue-related failure in adolescent athletes are increasing. This commentary aims to increase the understanding about how boredom may provide a self-control development stimulus which, in addition to modified sport training, may decrease non-contact ACL injuries.

Sources Of Data: PubMed, Google Scholar.

Gut dysbiosis influences the pathophysiology of multiple sclerosis: A case-control study from North India.

Background And Objectives: Alterations in gut microbiota have been linked to pathophysiology of immune-mediated diseases like multiple sclerosis (MS). This study was undertaken to characterise the gut microbiome profile in North Indian MS patients and to evaluate gut health using biomarkers like zonulin (intestinal permeability) and calprotectin (intestinal inflammation).

Methods: 84 Patients with relapsing-remitting MS patients (RRMS) of 18-75 years of age with an expanded disability status scale (EDSS) score less than or equal to 5.

Inhibition of cytochrome bd oxidase in Mycobacterium tuberculosis by benzothiazole amides.

Cytochrome bd (Cyt-bd) oxidase, a key enzyme in the Mtb respiratory chain, is particularly crucial for ATP synthesis when the primary cytochrome bc:aa (Cyt-bc:aa) complex is compromised. There are several reported inhibitors of the Cyt-bd oxidase, predominantly featuring quinoline and quinazoline scaffolds. This study explores benzothiazole amides as potential inhibitors of Cyt-bd oxidase for their ability to deplete ATP in the presence of the Cyt-bc:aa inhibitor Q203.

Optimization and characterization of collagenase KU665299 and its application in effective in-vitro clot digestion.

Objective: The study employed response surface methodology (RSM) to optimize physicochemical variables for extracellular collagenase production by gram negative bacterial strain Chryseobacterium contaminans KU665299 under submerged fermentation. It is also revealing the ability of collagenase to degrade collagen, main structural protein in human blood.

Result: The study successfully enhanced collagenase activity by 1.

Mitochondrial Oxidative Stress Alters the Phosphoproteome and Reverses Epithelial-Mesenchymal Transition in Human Breast Cancer Cells via the β-Catenin/c-Myc Axis.

Mitochondrial redox status plays a critical role in cancer progression, yet the effects of mitochondrial oxidative stress on the epithelial-mesenchymal transition (EMT), a key step in metastasis, remain elusive. We have investigated the phosphoproteomic landscape of breast cancer cells exposed to mitochondrial oxidative stress induced by mitochondria-targeted curcumin (mitocurcumin (MC)) and explored its potential as a druggable target. Mitocurcumin led to altered cell morphology, reduced migration, and shift to a cobblestone-like epithelial morphology, indicating EMT reversal.

Study of the Correlation Between Multi-parametric MRI (MP-MRI) Prostate Findings and Transrectal Ultrasound (TRUS)-Guided Prostate Biopsy Results in Patients With Raised Serum PSA.

Background Prostate cancer requires early and accurate diagnosis to improve outcomes of various treatment modalities. Multi-parametric MRI (MP-MRI) has emerged as a non-invasive imaging modality for detecting and evaluating prostate cancer for histological diagnosis; however, transrectal ultrasound (TRUS)-guided biopsy is still the gold standard. Aim To study the correlation between MP-MRI prostate findings using Prostate Imaging Reporting and Data System (PIRADS) scoring and TRUS-guided prostate biopsy results, including Gleason's score, in patients with raised serum PSA.

Evaluation of Antimicrobial Orthodontic Adhesives Incorporating Metal-Organic Frameworks.

Background: Orthodontic adhesives are prone to bacterial colonization, leading to demineralization and white spot lesions during orthodontic treatment. Incorporating antimicrobial agents such as metal-organic frameworks (MOFs) into adhesives offers a novel approach to mitigate bacterial growth.

Materials And Methods: A commercially available orthodontic adhesive was modified by incorporating 5% and 10% weight concentrations of a zirconium-based MOF.

Impact of Laser-Etched Titanium Plates on Osteoblast Attachment and Proliferation.

Background: Titanium plates are widely used in orthopedic and maxillofacial surgery due to their excellent biocompatibility and mechanical properties. Surface modifications, such as laser etching, aim to enhance osteoblast attachment and proliferation, which are critical for successful osseointegration. This study investigates the impact of laser-etched titanium plates on osteoblast attachment and proliferation compared to untreated plates.

Assessment of Peri-Implant Bone Loss in Smokers vs. Non-Smokers: A Prospective Study.

Background: One important aspect affecting dental implants' long-term success is peri-implant bone loss. Because smoking has a negative impact on osseointegration and healing, it has been recognized as a risk factor that might hasten peri-implant bone resorption.

Materials And Methods: One hundred patients in need of single dental implants were recruited, fifty of whom were smokers and fifty of whom were not.

Targeting drug-resistant tuberculosis: Thioacetamide-substituted benzothiazoles as bactericidal agents inhibiting type II NADH dehydrogenase.

The identification of novel anti-tubercular agents that inhibit the function of less-explored yet essential components of Mycobacterium tuberculosis is critically needed to address the increasing prevalence of drug-resistant tuberculosis. The type II NADH dehydrogenase, an indispensable component of the oxidative phosphorylation pathway, is the entry point of electrons into the electron transport chain, facilitating ATP production. This enzyme is a promising drug target because its inhibition leads to a bactericidal response through energy starvation.

3D printed gyroid scaffolds enabling strong and thermally insulating mycelium-bound composites for greener infrastructures.

Mycelium-bound composites (MBCs) grown from fungi onto solid lignocellulosic substrates offer a sustainable alternative to petroleum-based materials. However, their limited mechanical strength and durability are often insufficient for practical applications. In this work, we report a method for designing and developing strong and thermally insulating MBCs.

Evaluation of Erectile Dysfunction as a Consequence of Urethroplasty: A Prospective Observational Study.

Objective The objective of this study is to evaluate the change in erectile function in patients undergoing urethroplasty for anterior urethral strictures and pelvic fracture urethral injuries (PFUI) and to assess vascular insufficiency as the cause of erectile dysfunction after urethroplasty. Material & Methods For this study, 58 participants were enrolled. Eight patients had progressive perineal urethroplasty (PPU) for pelvic fracture urethral injury (PFUI), while five patients had urethroplasty for anterior urethral stricture (AUS).

Five-year Experience of Using Single Port Rigid Thoracoscopy in Patients of Undiagnosed Exudative Pleural Effusion at Tertiary Center in North India.

Background: Pleural effusion is one of the common pleural diseases encountered by pulmonologists worldwide. Malignancy and tuberculosis are the two most common etiologies in such patients, who have completely different prognoses. Pleural biopsy is the gold standard investigation to diagnose various causes of pleural effusion.

Systemic Inflammatory Response Syndrome Following High-Dose Intravenous Glutathione-Containing Revitalising Solution in a Patient on Tirzepatide: A Case Report.

Intravenous glutathione-based products are increasingly used for cosmetic purposes despite lacking regulatory approval in the United Kingdom and robust safety data. We report a case of systemic inflammatory response syndrome (SIRS) following administration of Glutax 75GX DCRP, a high-dose unregulated glutathione infusion, in a patient on tirzepatide with prolonged low nutritional intake. A previously healthy woman presented with shock, hyperpyrexia (>41°C), and collapsed within an hour of receiving the infusion for skin lightening.

Native Oxide MoOâ‚‚- MoSeâ‚‚ Heterostructure-Based Self-Powered Gas Sensor for Selective NOâ‚‚ and Hâ‚‚ Detection.

A single-step chemical vapor deposition method is reported to synthesize native oxide metal -semiconductor MoOâ‚‚-MoSeâ‚‚ heterostructure flakes for self-powered gas sensing. Two types of flakes, S1 and S2, with distinct compositions, are analyzed using Raman, photoluminescence spectroscopy, Atomic Force Microscopy, X-ray and UV Photoelectron Spectroscopy, and High-Resolution Transmission Electron Microscopy (HRTEM). TEM and Energy Dispersive Spectroscopy (EDS) mapping confirm a clear interface and compositional gradation in the heterostructures.