👤 Bhoomi Prajapati

The statins remain the foundation of lipid management because they lower low-density lipoprotein cholesterol (LDL-C) and prevent cardiovascular events, and guidelines recommend stepwise intensification, often with ezetimibe first, when targets are not met or when intolerance limits dosing. This review introduces a mechanism-first, phenotype-guided framework that links add-on therapies to the dominant driver of residual risk, LDL-C, triglyceride-rich lipoproteins, elevated lipoprotein(a), or inherited dyslipidemia while integrating trial evidence with clinical practicality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies remain the best-validated add-on for very high-risk patients. FOURIER and ODYSSEY OUTCOMES demonstrated event reduction with evolocumab or alirocumab on background statin therapy. For patients who cannot tolerate adequate statin doses, bempedoic acid provides liver-selective inhibition of adenosine triphosphate (ATP)-citrate lyase, and CLEAR Outcomes showed fewer major cardiovascular events in statin-intolerant populations. Inclisiran extends PCSK9 pathway suppression through hepatic small interfering RNA (siRNA) and enables durable LDL-C reduction with twice-yearly maintenance dosing, offering an adherence-oriented alternative while outcomes data mature. Angiopoietin-like protein 3 (ANGPTL3)-directed therapies (evinacumab and investigational RNAi agents such as zodasiran) lower atherogenic lipoproteins through largely LDL receptor independent biology. They expand options for refractory disease, including homozygous familial hypercholesterolemia. Apolipoprotein C-III (ApoC-III) inhibitors (olezarsen and plozasiran) drive large triglyceride reductions that can be decisive in severe hypertriglyceridemia and pancreatitis-prone syndromes. Next-generation cholesteryl ester transfer protein (CETP) inhibition (notably obicetrapib) has re-emerged as an oral strategy with substantial lipid effects as outcomes programs progress. High-dose eicosapentaenoic acid (EPA) (icosapent ethyl) has the clearest triglyceride-focused outcomes signal; REDUCE-IT showed significant ischemic event reduction in statin-treated patients with persistent hypertriglyceridemia. Early Show less

Alzheimer's disease (AD), the leading cause of dementia worldwide, is characterized by progressive neuronal loss, amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, cholinergic dysfunction, and gut-brain axis dysregulation. Despite advances in anti-amyloid therapeutics, current interventions provide only modest symptomatic relief and face limitations in accessibility, cost, and long-term efficacy. Plant-derived bioactive compounds, rooted in traditional medicine systems such as Ayurveda and Traditional Chinese Medicine, have gained increasing attention as multi-target therapeutic agents due to their pleiotropic actions, relative safety, and ability to cross the blood-brain barrier. This review synthesizes mechanistic and translational evidence on major phytochemicals, including withanolides ( Show less

The melanocortin receptors are a class of centrally and peripherally expressed G protein-coupled receptors, of which the MC3R and MC4R subtypes are implicated in the regulation of appetite and energy homeostasis and can serve as potential therapeutic targets for disorders such as obesity and cachexia. An unbiased high-throughput mixture-based library screen was implemented to identify novel ligands with an emphasis on the identification of nanomolar-potent agonists of the mouse melanocortin-3 receptor. This screen yielded the discovery of an N-branched tricyclic guanidine scaffold (TPI2408) that contained three nanomolar potent mMC3R agonists and additional compounds that possessed antagonism for the mMC4R. The antagonist character of this scaffold library at the mMC4R was confirmed by a follow-up positional scanning antagonist screen. Additionally, molecular dynamics simulations herein provide mechanistic insight into the polypharmacological characteristics of melanocortin receptors. The disclosed materials have the potential to serve as important tools and SAR scaffolds in the study of melanocortin receptor function. Show less

The emergence of Candida albicans as a life-threatening pathogen and its resistance to available antifungal drugs is a significant global health concern. Previous findings have established that the ubiquitin mutations UbEP42, UbL50P and UbI61T interfere with morphogenesis of C. albicans from commensal yeasts to pathogenic hyphae. The main objective of this study is to investigate the influence of ubiquitin mutations on the molecular markers of morphogenesis and virulence of C. albicans to identify potential targets for therapeutic intervention. The auxotrophic strain BWP17 of C. albicans was transformed by the wild-type ubiquitin gene (UbWT) and its mutants UbEP42, UbS20F, UbA46S, UbL50P and UbI61T cloned under the doxycycline-inducible promoter in the integrative plasmid pTET25-MNC. Induced expression of the mutant forms UbEP42, UbL50P, and UbI61T while inhibiting morphogenesis, reduced chitin deposition, increased β-glucan exposure on the cell wall, decreased the secretion of aspartyl protease, caused the differential expression of cyclins Cln3, Ccn1, Clb2 and certain key transcription factors compared to UbWT. However, UbS20F and UbA46S did not have any influence. These findings demonstrating the disruptive influence of UbEP42, UbL50P, and UbI61T on the levels of molecular markers of morphology and pathogenesis of C. albicans, highlight the importance of a functional ubiquitination system. Show less

The study aimed to develop a nano-based drug delivery system for the treatment of hepatocellular carcinoma (HCC), a type of liver cancer that accounts for 90% of all liver malignancies. The study focused on the use of cabozantinib (CNB), a potent multikinase inhibitor that targets the VEGF receptor 2, as the chemotherapeutic drug. We developed CNB-loaded nanoparticles made from Poly D, L-lactic-co-glycolic acid, and Polysarcosine (CNB-PLGA-PSar-NPs) for use in human HepG2 cell lines. By O/W solvent evaporation method, the polymeric nanoparticles were prepared. The various techniques, such as photon correlation spectroscopy, scanning electron microscopy, and transmission electron microscopy were used, to determine the formulation's particle size, zeta potential, and morphology. SYBR Green/ROX qPCR Master Mix and RT-PCR equipment used to measure liver cancer cell line and tissue mRNA expression and MTT assay to test HepG2 cell cytotoxicity. Cell cycle arrest analysis, annexin V assay, and ZE5 Cell Analyzer apoptosis assay were also performed. The results of the study showed that the particle diameters were 192.0 ± 3.67 nm with 0.128 PDI and -24.18 ± 3.34 mV zeta potential. The antiproliferative and proapoptotic effects of CNB-PLGA-PSar-NPs were evaluated using MTT and flow cytometry (FCM). The IC50 value of CNB-PLGA-PSar-NPs was 45.67 µg/mL, 34.73 µg/mL, and 21.56 µg/mL for 24, 48, and 72 h, respectively. The study also found that 11.20% and 36.77% of CNB-PLGA-PSar-NPs-treated cells were apoptotic at 60 µg/mL and 80 µg/mL, respectively, suggesting that the nanoparticles were effective in inducing apoptosis in the cancer cells. It can also conclude that, CNB-PLGA-PSar-NPs inhibit human HepG2 hepatocellular carcinoma cells and kill them by upregulating the tumour suppressor genes MT1F, MT1X, and downregulating MTTP, APOA4. Further in vivo antitumor activity was well reported in SCID female mice. Overall, this study suggests that the CNB-PLGA-PSar-NPs are a promising drug delivery system for the treatment of HCC, and further research is needed to investigate their potential in clinical treatment. Show less

Genetic variations resulting in the loss of function of the discs large homologs (DLG2)/postsynaptic density protein-93 (PSD-93) gene have been implicated in the increased risk for schizophrenia, intellectual disability, and autism spectrum disorders (ASDs). Previously, we have reported that mice lacking exon 14 of the Show less

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD) during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients carrying either the Show less

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease, which affects the structure of heart muscle tissue. The clinical symptoms include arrhythmias, progressive heart failure, and even sudden cardiac death but the mutation carrier can also be totally asymptomatic. To date, over 1400 mutations have been linked to HCM, mostly in genes encoding for sarcomeric proteins. However, the pathophysiological mechanisms of the disease are still largely unknown. Two founder mutations for HCM in Finland are located in myosin-binding protein C (MYBPC3-Gln1061X) and α-tropomyosin (TPM1-Asp175Asn) genes. We studied the properties of HCM cardiomyocytes (CMs) derived from patient-specific human induced pluripotent stem cells (hiPSCs) carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. Both types of HCM-CMs displayed pathological phenotype of HCM but, more importantly, we found differences between CMs carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation in their cellular size, Ca(2+) handling, and electrophysiological properties, as well as their gene expression profiles. These findings suggest that even though the clinical phenotypes of the patients carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation are similar, the genetic background as well as the functional properties on the cellular level might be different, indicating that the pathophysiological mechanisms behind the two mutations would be divergent as well. Show less