👤 P Chauhan

Psychedelic compounds such as psilocybin, Lysergic Acid Diethylamide (LSD), N,Ndimethyltryptamine (DMT), and 3,4-methylenedioxymethamphetamine (MDMA) are emerging as novel therapeutics for neuropsychiatric disorders, including depression, Post-Traumatic Stress Disorder (PTSD), and addiction. Acting primarily through serotonin 5-HT2A receptor agonism, they activate intracellular cascades involving Brain-Derived Neurotrophic Factor (BDNF), Tropomyosin receptor kinase B (TrkB), and the mammalian target of rapamycin (mTOR) pathway, leading to enhanced neuroplasticity and synaptogenesis. Recent evidence demonstrates direct TrkB binding and sustained cortical remodeling, underlying their rapid and durable antidepressant effects. Advanced Drug Delivery Systems (DDS)-including liposomes, Solid Lipid Nanoparticles (SLNs), and Poly(lactic-co-glycolic acid) (PLGA) carriers-are being engineered to achieve controlled, braintargeted, and stimuli-responsive release while minimizing systemic toxicity. Integration with microfluidic fabrication, Artificial Intelligence (AI)-based dosing, and non-invasive routes such as intranasal and transdermal delivery improves precision and patient adherence. By merging neuropharmacology with materials science, these innovations are redefining psychedelic-assisted therapy through enhanced safety, personalized dosing, and translational potential for central nervous system disorders. Show less

Lp(a) (lipoprotein[a]) is associated with cardiovascular disease, but neither the causal nature nor the underlying mechanisms are fully documented. This study investigated whether Lp(a) triggers atherogenesis by dysregulating vascular redox-sensitive inflammatory state. Plasma Lp(a) was measured in 1027 patients with advanced coronary artery disease undergoing cardiac surgery. These patients were genotyped, and a modified Increased plasma Lp(a) ( This study demonstrates for the first time that a genetically determined increase in plasma Lp(a) results in dysregulated vascular redox/nitrosative signaling in patients with atherosclerosis. Show less

Genetic polymorphisms in cardiovascular disease (CVD) susceptibility across different ethnic groups is highly imperetive. Therefore, it is of interest to investigate the role of genetic polymorphisms in cardiovascular disease (CVD) susceptibility across different ethnic groups. Participants were tested for variations in LDLR, APOE and LPL genes and their association with cardiovascular risk factors such as cholesterol levels and blood pressure was examined. Data shows ethnic differences in the prevalence of these polymorphisms, suggesting that genetic factors contribute to CVD risk in a population-specific manner. Thus, we show the need for personalized cardiovascular risk assessment strategies. The ethnic-specific distribution of genetic polymorphisms (LDLR, APOE and LPL) linked to cardiovascular disease susceptibility, highlighting the need for personalized cardiovascular risk assessment strategies based on genetic and ethnic factors is highlighted. Show less

Formalin-fixed paraffin-embedded (FFPE) tissue specimens represent precious resources for clinical genomic profiling studies, especially when coupled with comprehensive medical records. Even though next-generation sequencing (NGS) is an effective tool to detect somatic mutations and somatic copy number alterations (sCNA), the biggest challenges in unlocking clinically translatable genomic information from FFPE tissue are low DNA yields and degraded DNA, affected by variable formalin fixation. Another issue is that the proportion of carcinoma and other noncarcinoma cells is variable and can be confounded by intratumoral heterogeneity. To explore these challenges, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from nine primary and metastatic breast cancer and three primary ovarian high-grade serous carcinomas. This was followed by downstream shallow whole-genome sequencing (WGS) for copy number landscape profiling (10 samples) and/or a targeted panel for somatic mutation and sCNA analysis (seven samples), subject to cell availability. Seven out of 10 samples (even some with low tumour content or of old age) produced good-quality genomic data, detecting sCNA in all carcinoma population samples but not in the stromal populations. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them. Our workflow enabled the identification of clinically actionable targets, including PIK3CA, ERBB2, FGFR1/2, CDK6, CCNE1, KRAS amplifications and RB, BRCA1/2 losses in patients that would direct therapy. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. Show less

We recently demonstrated the utility of the 'TB Concentration & Transport' kit for bio-safe, ambient-temperature transport of dried sputum samples on Trans-Filter, along with the 'TB DNA Extraction' kit for efficient DNA extraction from Trans-Filter for use in the Line Probe Assay (LPA) for diagnosing drug-resistant tuberculosis (TB). The present study aimed to develop and evaluate a new 'Quick TB DNA Extraction' kit ('Quick DNA' kit) for rapid DNA isolation from Trans-Filter samples and assess its compatibility with LPA for the detection of multidrug-resistant TB (MDR-TB). Consecutive presumptive TB/MDR-TB/XDR-TB patients (n = 1823) were screened using LED-FM and/or TBDetect microscopy at 2 Designated Microscopy Centres associated with the National Institute of Tuberculosis and Respiratory Diseases (NITRD), New Delhi. Smear-positive samples (n = 235) were processed in duplicate using the 'TB Concentration and Transport' kit. Dried sputum on bio-safe Trans-Filters was transported at ambient temperature, along with sputum samples, in a 3-layer packing in cooling conditions to NITRD Hospital (a National Reference Laboratory). DNA was extracted from Trans-Filters using 'Quick DNA' kit and the 'TB DNA Extraction' kit, and from sputum using Hain's GenoLyse® DNA Extraction kit for first-line LPA for MDR-TB detection. Quick Kit-LPA and Kit-LPA (LPA with DNA extracted from Trans-Filter using 'Quick DNA' kit and 'TB DNA Extraction' kit, respectively) showed similar sensitivity of 88.9% (95% CI: 65.3-98.6) and 88.5% (95% CI: 69.9-97.5) and specificity of 100% (95% CI: 98.2-100) and 99.5% (95% CI: 97.3-99.9) for rifampicin and isoniazid resistance detection, respectively against Direct-LPA (LPA with DNA extracted from sputum samples using GenoLyse kit). User feedback obtained from laboratory technicians corroborated that the one-step 'Quick DNA' kit procedure was rapid (5 minutes), easy to perform, seamlessly integrated with LPA testing, and was suitable as a replacement for Kit-LPA or Direct-LPA. The gap between drug-resistant TB detection and treatment initiation can be narrowed through Universal-Drug Susceptibility Testing by implementing (i) bio-safe and ambient temperature transport of sputum from primary healthcare centres to central laboratories, and (ii) by using Quick Kit-LPA over Direct-LPA in patients residing in remote areas. Show less

Lipoprotein (a) [Lp (a)] may confer pro-thrombotic potential, and high concentrations may be an independent risk for MI. This systematic review sought to investigate the association of Lp (a) levels with post-revascularization Major Adverse Cardiac Events (MACE) in patients with CAD, ACS, and DM. A systematic literature search for original investigations was performed using PubMed/MEDLINE, Embase, Scopus, and Google Scholar, searching for articles (meeting inclusion criteria) focusing on the relationship between Lp(a), DM, and PCI in patients with ACS, MI, or IHD and the impact on cardiovascular outcomes. The data was abstracted and descriptively summarized. The systematic review selected four relevant articles: 3 prospective Konishi et al., (2016); Silverio et al., (2022); and Li et al., (2023) and one retrospective (Takahashi et al., 2020). Total population: 4624, total males: 3719. Konishi et al. (2016) concluded that an elevated Lp(a) is an independent risk factor for cardiac death and/or ACS recurrence in diabetics undergoing PCI. The adjusted OR for cardiac death and ACS in the high Lp(a) group vs. the low Lp(a) group was 1.20 (CI 1.00-1.42), p = 0.04. Takahashi et al. (2020) showed that after adjusting for clinical covariates, high Lp(a) was independently associated with a higher frequency of MACE and poorer long-term outcomes compared to low Lp(a). The adjusted OR for the risk of MACE in patients with high Lp (a) vs. low Lp (a) was 1.83 (CI 1.16-2.95), p = 0.009. Silverio et al. (2022) showed that while there was an increased risk of recurrent MI in this patient population without DM, it was not confirmed in patients with DM. Compared with the lowest Lp (a) category, non-DM patients with very high Lp (a) >70 mg/dl vs. low Lp (a) showed a higher risk of recurrent MI and all-cause death; adjusted OR 2.839 (CI 1.382-5.832), p = 0.005. In diabetics, high Lp (a) vs. low Lp (a) = 1.115 (CI 0.405-3.071), p = 0.833. There is some evidence that Lp (a) levels are an independent risk factor for MACE in patients who underwent PCI for CAD. There is also some evidence that elevated Lp (a) levels are associated with a worse prognosis in patients with DM after PCI, but this association is not consistent in the literature. Further prospective multicenter studies are required in order to elucidate this association. Show less

Adipocytokines, including leptin, adiponectin, and resistin, are key mediators linking adiposity, insulin resistance, and inflammation. We present the first genome-wide association study (GWAS; N = 5258) and exome-wide association study (ExWAS; N = 4578) on leptin, adiponectin, and resistin in South Asian population. We identified novel associations in genes ZNF467, and LEPREL2 for leptin; ZNF467, LEPREL2, CRLF3, ZNF732, SOX30, XIRP1, ATP8B3, SPATA2L, TMCO4, TLN2, ABCA12, and SHB for adiponectin; and D2HGDH for resistin. Additionally, we confirmed known associations of FTO, MC4R, and HOXB3 with leptin and ADIPOQ with adiponectin. Notably, ADIPOQ variants were consistently significant across GWAS, ExWAS, and gene-based analyses, reinforcing their central role in regulating adiponectin levels. Most of these novel associations identified were population-specific, highlighting the importance of studying diverse populations to uncover unique genetic signals. After adjusting for BMI, the associations with adiponectin and resistin remained significant, whereas most associations for leptin weakened in both effect size and significance. Functional annotation revealed that the identified variants were enriched for expression in adipose tissue, the brain (cerebellar hemisphere and cerebral cortex), and the pituitary gland. These variants act as eQTLs and splice-QTLs in adipose, brain, and pancreas, suggesting cross-tissue regulatory mechanisms. ExWAS further implicated rare variant burden in genes such as LONP1, ZNF335, and TTC16 for adiponectin and resistin. These findings enhance our understanding of adipocytokine biology, emphasises the need for population-specific genetic research, and lays foundation for future functional studies. Show less

Childhood obesity (OB) is influenced by complex gene-environmental interaction. While genetics of adult OB have been extensively studied, polygenic childhood OB in non-European populations is still underexplored. Furthermore, in a developing nation such as India, how the environmental component strongly modulated by the socioeconomic status (SES) shapes the genetic susceptibility is crucial to understand. A two-staged genome-wide association study (GWAS; N = 5673) and an independent exome-wide association study (ExWAS; N = 4963) were performed using a generalized linear model assuming additive effect to identify the common and rare genetic variants respectively associated with childhood OB. Rare-variant burden testing was also performed. We used the gene expression profiles and regulatory data from public databases to explain the novel associations. The implications of SES as a potential modifier of genetic susceptibility were evaluated. GWAS identified novel associations in TCF7L2, IMMP2L, IPMK, CDC5L, SNTG1, and MX1, whereas ExWAS uncovered CNTN4, COQ4, TNFRSF10D, FLG-AS1, and BMP3. Both GWAS and ExWAS validated known associations in FTO and MC4R. Furthermore, rare-variant testing highlighted the role of 101 genes. We also observed that SES can modulate the inherent susceptibility to OB. Our study identified genetic variants associated with childhood OB and highlighted the gene-environmental interaction in childhood OB. Show less

Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder. β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase-3β (GSK3β) contribute to Aβ plaque development, tau hyperphosphorylation, neurofibrillary tangles, and neuronal dysfunction in AD pathogenesis. This study aimed to investigate the neuroprotective potential of sabinene in an Aluminum chloride (AlCl Show less

Alzheimer's disease (AD) is the leading cause of dementia worldwide with therapeutic lacunae till date. The beta-amyloid (Aβ) accumulation triggers AD pathogenesis, though clinical trials lowering Aβ have not altered disease outcomes suggesting other interacting factors to be identified for drug design of AD. Therefore, it is of interest to identify potential hub proteins interlinked with disease-driving pathways using a network-based approach for AD therapeutic designing. Literature mining was done to identify proteins implicated in AD etiology. Protein-protein interactions (PPIs) were retrieved from the STRING database and merged into a single network using Cytoscape 3.10.1. The hub proteins involved in AD etiology were predicted based on the topological algorithms of CytoHubba. Six major proteins, with STRING database identifiers - APP, BACE1, PSEN1, MAPT, APOE4 and TREM2, were identified to be involved in AD pathogenesis. The merged network of PPIs of these proteins contained 51 nodes and 211 edges, as predicted by Analyzer module of Cytoscape. The Amyloid precursor protein (APP) emerged as the highest-scoring hub protein across multiple centrality measures and topological algorithms. Thus, current data provides evidence to support the ongoing investigation of APP's multifaceted functions and therapeutic potential for AD. Show less

Alzheimer's disease (AD), a debilitating neurodegenerative condition, is characterized by progressive cognitive decline brought about by the deposition of amyloid beta (Aβ) plaques in the brain initiates downstream neuronal dysfunction and death in AD pathogenesis. The β-secretase (BACE-1) enzyme plays a crucial role in generating Aβ from amyloid precursor protein (APP). Hence, we report the virtual screening of marine phytochemicals as BACE-1 inhibitors. 2583 compounds, retrieved from Comprehensive Marine Natural Product Database (CMNPD), were primarily screened for drug-likeliness and blood-brain barrier permeability using admetSAR 2.0 and Show less

Receptor tyrosine kinases (RTKs) serve as molecular targets for the development of novel personalized therapies in many malignancies. In the present study, expression pattern of receptor tyrosine kinases and its clinical significance in orbital RMS has been explored. Eighteen patients with histopathologically confirmed orbital RMS formed part of this study. Comprehensive q-PCR gene expression profiles of 19 RTKs were generated in the cases and controls. The patients were followed up for 59.53 ± 20.93 years. Clustering and statistical analysis tools were applied to identify the significant combination of RTKs associated with orbital rhabdomyosarcoma patients. mRNA overexpression of RTKs which included MET, AXL, EGFR was seen in 60-80% of cases; EGFR3, IGFR2, FGFR1, RET, PDGFR1, VEGFR2, PDGFR2 in 30-60% of cases; and EGFR4, FGFR3,VEGFR3 and ROS,IGFR1, EGFR1, FGFR2, VEGFR1 in 10-30% of cases. Immunoexpression of MET was seen in 89% of cases. A significant association was seen between MET mRNA and its protein expression. In all the cases MET gene expression was associated with worst overall survival (P = 0.03).There was a significant correlation of MET mRNA expression with RET, ROS, AXL, FGFR1, FGFR3, PDGFR1, IGFR1, VEGFR2, and EGFR3 genes. Association between MET gene and collective expression of RTKs was further evaluated by semi-supervised gene cluster analysis and Principal component analysis, which showed well-separated tumor clusters. MET gene overexpression could be a useful biomarker for identifying high risk orbital rhabdomyosarcoma patients. Well-separated tumor clusters confirmed the association between MET gene and collective expression of RTK genes. Therefore, the therapeutic potential of multi-kinase inhibitors targeting MET and the 9 other significant RTKs needs to be explored. Show less

Inducible defences allow prey to increase survival chances when predators are present while avoiding unnecessary costs in their absence. Many studies report considerable inter-individual variation in inducible defence expression, yet what underlies this variation is poorly understood. A classic vertebrate example of a predator-induced morphological defence is the increased body depth in crucian carp (Carassius carassius), which reduces the risk of predation from gape-size limited predators. Here, we report that among-individual variation in morphological defence expression can be linked to sex. We documented sexual dimorphism in lakes in which crucian carp coexisted with predators, where females showed shallower relative body depths than males, but not in a predator-free lake. When exposing crucian carp from a population without predators to perceived predation risk in a laboratory environment (presence/absence of pike, Esox lucius), we found that males expressed significantly greater morphological defence than females, causing sexual dimorphism only in the presence of predators. We uncovered a correlative link between the sex-specific inducible phenotypic response and gene expression patterns in major stress-related genes (POMC, MC3R, and MC4R). Together, our results highlight that sex-specific responses may be an important, yet underappreciated, component underlying inter-individual differences in the expression of inducible defences, even in species without pronounced sexual dimorphism. Show less

Clinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce. Measures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients ( The LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC ( Distinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery. Show less

The success of immune checkpoint therapy shows tumor-reactive T cells can eliminate cancer cells but are restrained by immunosuppression within the tumor micro-environment (TME). Cancer associated fibroblasts (CAFs) are the dominant stromal cell in the TME and co-localize with T cells in non-small cell lung cancer. We demonstrate the bidirectional nature of CAF/T cell interactions; T cells promote expression of co-inhibitory ligands, MHC molecules and CD73 on CAFs, increasing their production of IL-6 and eliciting production of IL-27. In turn CAFs upregulate co-inhibitory receptors on T cells including the ectonucleotidase CD39 promoting development of an exhausted but highly cytotoxic phenotype. Our results highlight the bidirectional interaction between T cells and CAFs in promoting components of the immunosuppressive CD39, CD73 adenosine pathway and demonstrate IL-27 production can be induced in CAF by activated T cells. Show less

Allergic airway disorders such as asthma and allergic rhinitis are mainly caused by inhaled allergen-induced improper activation and responses of immune and non-immune cells. One important response is the production of IL-27 by macrophages and dendritic cells (DCs) during the early stage of airway allergies. IL-27 exerts powerful modulatory influences on the cells of innate immunity [eg neutrophils, eosinophils, mast cells, monocytes, macrophages, dendritic cells (DCs), innate lymphoid cells (ILCs), natural killer (NK) cells and NKT cells)] and adaptive immunity (eg Th1, Th2, Th9, Th17, regulatory T, CD8 Show less

Protein ubiquitination is one of the most crucial posttranslational modifications responsible for regulating the stability and activity of proteins involved in homeostatic cellular function. Inconsistencies in the ubiquitination process may lead to tumorigenesis. Ubiquitin-specific peptidases are attractive therapeutic targets in different cancers and are being evaluated for clinical development. Ubiquitin-specific peptidase 37 (USP37) is one of the least studied members of the USP family. USP37 controls numerous aspects of oncogenesis, including stabilizing many different oncoproteins. Recent work highlights the role of USP37 in stimulating the epithelial-mesenchymal transition and metastasis in lung and breast cancer by stabilizing SNAI1 and stimulating the sonic hedgehog pathway, respectively. Several aspects of USP37 biology in cancer cells are yet unclear and are an active area of research. This review emphasizes the importance of USP37 in cancer and how identifying its molecular targets and signalling networks in various cancer types can help advance cancer therapeutics. Show less

Numerous studies have investigated the relationship between various candidate gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of common ABCG8 T400K, ABCG8 D19H, ABCG8 C54Y, ApoB100 EcoRI, ApoB100 XbaI, ApoE HhaI, CETP TaqI, CYP7A1 Bsa, LRPAP1 I/D and TNF-α A308G polymorphisms on the risk of gallbladder stone disease. 33 Full-text articles with 9250 cases and 12,029 healthy controls (total 21,279 subjects) were analyzed using the RevMan software (V5.1) and the Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) a Random-effects model was applied. Begg's funnel plots, Fail-safe number, Egger's regression intercept and Begg and Mazumdar rank correlation tests were performed for the potential publication bias and sensitivity analysis. The studies were also sub-grouped into European and non-European groups to find out role of ethnicity, if any, on GSD risk. Studies included in quantitative synthesis were ABCG8 T400K rs4148217 (cases/controls, n = 671/1416) (4 studies), ABCG8 D19H rs11887534 (n = 1633/2306) (8 studies), ABCG8 C54Y rs4148211 (n = 445/1194) (3 studies), ApoB100 EcoRI rs1042031 (n = 503/390) (4 studies), ApoB100 XbaI rs693 (n = 1214/1389) (9 studies), ApoE HhaI rs429358 (n = 1335/1482) (12 studies), CETP TaqI rs708272 (n = 1038/1025) (5 studies), CYP7A1 Bsa rs3808607 (n = 565/514) (3 studies), LRPAP1 I/D rs11267919 (n = 849/900) (3 studies), TNF-α A308G rs1800629 (n = 997/1413) (3 studies). The combined results displayed significant association of ABCG8 D19H (GC + CC) [OR with 95%CI = 2.2(1.7-2.8); Show less

IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy. Show less

Solid tumors elicit suppressive T cell responses which impair antigen-presenting cell (APC) functions. Such immune suppression results in uncontrolled tumor growth and mortality. Addressing APC dysfunction, dendritic cell (DC)-mediated anti-tumor vaccination was extensively investigated in both mice and humans. These studies never achieved full resistance to tumor relapse. Herein, we describe a repetitive RM-1 murine tumor rechallenge model for recurrence in humans. Using this newly developed model, we show that priming with tumor antigen-pulsed, Toll-like receptor (TLR)2 ligand-activated DCs elicits a host-protective anti-tumor immune response in C57BL/6 mice. Upon stimulation with the TLR2 ligand peptidoglycan (PGN), the tumor antigen-pulsed DCs induce complete resistance to repetitive tumor challenges. Intra-tumoral injection of PGN reduces tumor growth. The tumor resistance is accompanied by increased expression of interleukin (IL)-27, T-box transcription factor TBX21 (T-bet), IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, along with heightened cytotoxic T lymphocyte (CTL) functions. Mice primed four times with PGN-stimulated tumor antigen-pulsed DCs remain entirely resistant to repeat challenges with RM-1 tumor cells, suggesting complete prevention of relapse and recurrence of tumor. Adoptive transfer of T cells from these mice, which were fully protected from RM-1 rechallenge, confers anti-tumor immunity to syngeneic naive recipient mice upon RM-1 challenge. These observations indicate that PGN-activated DCs induce robust host-protective anti-tumor T cells that completely resist tumor growth and recurrence. Show less