Pragasam Viswanathan

The threat of Mycobacterium tuberculosis necessitates exploration of novel therapeutics to combat the upsurge in drug‐resistant profiles. This study integrates computational approaches to evaluate garlic‐derived compounds against putative Mtb targets. Structure‐based virtual screening indicated favorable predicted binding affinities for ajoene against 3PTY and 5VRL. Density functional theory revealed favorable geometry, electron density distribution, and structural characteristics as supported by optimized energy profiles and density‐of‐states spectra. Analyses of frontier molecular orbitals, natural bond orbital, and electrostatic potential indicated a low energy gap, ionization potential, and chemical hardness of ajoene and revealed distinct reactive centers for intermolecular interactions. Topological analysis characterized electron localization and delocalization, while reduced density gradient plots identified intramolecular noncovalent interactions within the ligands. Molecular dynamics simulations revealed minimal residue‐level fluctuations and stable backbone dynamics supporting complex stability throughout the simulation timeframe. Free energy landscape analysis revealed low cluster energy basins whereas binding free energy analysis provided insights into energetic contributions. The current in silico findings identified ajoene as a computationally prioritized phytocompound for further investigation against putative targets involved in cell wall and mycolic acid biosynthesis. Further experimental validation including microbiological and biochemical assays are necessary to determine whether the predicted activity corresponds to measurable biological activity.

The gut microbiome constitutes a complex and metabolically active ecosystem that exerts profound effects on host physiology through the production of diverse small-molecule metabolites. Increasing evidence indicates that microbiome-derived metabolites function as a critical bridge linking microbial dysbiosis with tumor initiation, progression, immune modulation, and therapeutic responsiveness. Alterations in microbial metabolic outputs, including short-chain fatty acids, secondary bile acids, polyamines, indole derivatives, and other bioactive compounds, can influence epithelial barrier integrity, inflammatory signaling, epigenetic regulation, and genomic stability within the tumor microenvironment. These metabolites serve as functional intermediaries in host-microbe communication and may contribute to systemic metabolic and immunological changes that support tumorigenesis across multiple malignancies. Notably, many microbiome-associated metabolites are detectable in accessible biological matrices such as stool, blood, and urine, highlighting their potential utility as minimally invasive biomarkers for cancer risk screening, diagnosis, and prognosis. Recent advances in high-throughput sequencing, metabolomics, and multi-omics integration have enabled comprehensive characterization of microbial metabolic networks associated with cancer development. In this review, we synthesize current insights into the functional diversity of microbiome-derived metabolites and their mechanistic roles in tumor biology. We further examine analytical platforms used for metabolite profiling and discuss emerging strategies for microbiome-targeted therapeutic modulation. Finally, we outline current methodological challenges and research priorities necessary for translating microbiome-metabolite interactions into clinically actionable frameworks for precision oncology.

Dysregulated iron handling—including catalytic iron and ferroptosis, hepcidin–ferroportin signaling, ferritin dynamics, and neutrophil gelatinase-associated lipocalin (NGAL)-mediated siderophore transport—has been implicated in the initiation and propagation of acute kidney injury (AKI) across ischemia–reperfusion, sepsis, and nephrotoxic contexts. To provide a SANRA-aligned narrative synthesis of mechanistic and translational evidence on iron biology in AKI, clarifying biomarker readiness and therapeutic prospects while explicitly separating preclinical from human findings. PubMed, Scopus, and Web of Science (1 January 2000 to 30 September 2025), plus appraised grey literature (guidelines/registries) using predefined criteria (authority, update recency, and methodological transparency). Narrative review with comprehensive database searches, single-reviewer screening/extraction (acknowledged as a limitation), and qualitative synthesis. Evidence is organized by pathway (catalytic iron/ferroptosis, transferrin (Tf)/transferrin receptor (/TfR), ferritin/ferritin heavy chain (FtH), hepcidin–ferroportin and NGAL) and translational domain (biomarkers and therapeutics). Statements are tagged as [Preclinical] or [Human]. [Preclinical] Robust signals support roles for catalytic iron and ferroptosis, protection by iron chelation, hepcidin modulation, heme oxygenase 1 (HO-1)/FtH induction, and apotransferrin/NGAL-based strategies. [Human] Biomarkers such as NGAL show clinical utility for kidney injury detection, whereas catalytic iron assays (labile plasma iron [LPI]/bleomycin-detectable iron [BDI]) remain investigational with limited standardization. Observational links between iron-regulatory pathways and AKI risk exist, but interventional trials are sparse; dose, timing, and safety of iron-targeted strategies in defined AKI settings remain to be established. Iron-handling pathways are compelling targets for AKI prevention/mitigation, yet high-quality human trials are limited. Priorities include standardized catalytic-iron assays, biomarker-guided enrichment, and pragmatic trials of tractable interventions (e.g., peri-contrast or cardiopulmonary bypass settings). Until such evidence accumulates, recommendations beyond standard care should be avoided.

Renal cell carcinoma (RCC) is one of the primary drivers of cancer-related mortality worldwide. Despite advancements in cancer diagnosis and management, there is a lack of effective available treatment options for such patients. This is often attributed to late diagnosis, lack of biomarkers, and resistance against standard-of-care therapies. Thus, identifying novel targets in RCC is needed to improve disease outcomes. Cu is a trace element required for homeostasis, and its dysregulation is linked to cancer. Cuproptosis, a programmed cell death, occurs due to intracellular Cu overload, disrupting the TCA cycle, inducing oxidative stress, and impairing metabolism. In cancer, abnormal Cu levels drive Cu-dependent proliferation, termed cuproplasia. The role of cuproptosis and cuproplasia in RCC remains unclear; their comprehensive understanding will enable the discovery of novel targets for effective therapy. This review explores their molecular mechanisms, impact on RCC progression, and therapeutic potential.

Renal cell carcinoma (RCC) is a complex and highly heterogeneous malignancy marked by an immunosuppressive tumor microenvironment, which facilitates immune evasion and disease progression. Programmed death-ligand 1 (PD-L1), a key immune checkpoint molecule expressed on tumor and immune cells, whose activation allows tumors to evade immune surveillance, plays a central role in modulating antitumor immunity in RCC. While the transcriptional and cytokine-mediated regulation of PD-L1 is well documented, emerging evidence emphasizes the critical influence of post-translational modifications particularly ubiquitination and deubiquitination in controlling PD-L1 stability and function. This review provides a comprehensive analysis of the ubiquitin-proteasome system (UPS), highlighting the roles of specific E3 ubiquitin ligases and deubiquitinases (DUBs) in modulating PD-L1 expression and their broader implications in RCC tumor biology. We further discuss how these proteins influence immune cell infiltration, tumor progression, and response to immunotherapy. The therapeutic potential of targeting UPS components, including proteasome inhibitors and proteolysis-targeting chimeras, is also explored. Understanding the UPS-mediated regulation of PD-L1 offers promising avenues for enhancing immunotherapeutic efficacy in RCC.

Osteoarthritis is a prevalent degenerative joint disease characterized by cartilage degradation, synovial inflammation, and subchondral bone alterations, leading to chronic pain and joint dysfunction. Conventional treatments provide symptomatic relief but fail to halt disease progression. Recent advancements in biomaterials, molecular signaling modulation, and gene-editing technologies offer promising therapeutic strategies. This review explores key molecular pathways implicated in osteoarthritis, including fibroblast growth factor, phosphoinositide 3-kinase/Akt, and bone morphogenetic protein signaling, highlighting their roles in chondrocyte survival, extracellular matrix remodeling, and inflammation. Biomaterial-based interventions such as hydrogels, nanoparticles, and chitosan-based scaffolds have demonstrated potential in enhancing cartilage regeneration and targeted drug delivery. Furthermore, CRISPR/Cas9 gene editing holds promise in modifying osteoarthritis-related genes to restore cartilage integrity. The integration of regenerative biomaterials with precision medicine and molecular therapies represents a novel approach for mitigating osteoarthritis progression. Future research should focus on optimizing biomaterial properties, refining gene-editing efficiency, and developing personalized therapeutic strategies. The convergence of bioengineering and molecular science offers new hope for improving joint function and patient quality of life in osteoarthritis management.