Biology subjects

Chakrapani, L. N.

Publications and source records attributed to Chakrapani, L. N..

3 recordsLinked to original sources

bioRxiv2025

Oxidative stress and Atherosclerotic Plaque Progression: A plausible insight into the role of paraxonases and Ox-LDL

The atherosclerotic heart disease is a complex disease associated with a plethora of dynamics contributing to its initiation and progression. Despite, diabetes and hypertension provide favorable conditions that provoke and aggravate atherosclerosis, it is undeniable that all of them do not have the tendency to develop plaques. This study was devised to identify the attributes that discriminate the diabetic and/or hypertensive ischemic patients from their corresponding non-ischemic population. Serum total antioxidant status, ox-LDL levels, Paraoxonase levels and its activity were assessed in the study groups. In order to evaluate the extent of the atherosclerotic disease progression, the aortic punch tissue samples from patients undergoing CABG were analyzed for the expression of ox-LDL and PON-2. Our results showed that their serum levels correlated well with the tissue expression. To ascertain the same with the progression of the disease, animal studies with rats fed with High Cholesterol Diet were carried out. Our findings suggests that ox-LDL and HDL-PON activity reflects the atherogenic events taking place in the arteries and further assessment of atherosclerotic risk in terms of ox-LDL and PON might be recommended after further validation.

biochemistry↗

bioRxiv2025

HO-3867 mediated modulation of Extracellular vesicles and Tumor microenvironment: A novel immunotherapeutic strategy for ovarian cancer

IntroductionOvarian cancer (OC) remains the most lethal gynecologic malignancy, with poor long-term survival, largely due to its diagnosis at advanced stages and its high rate of recurrence with resistance to platinum therapies. This study evaluates the therapeutic efficacy of HO-3867, a STAT3 inhibitor, and bevacizumab, an anti-VEGF antibody, alone and in combination in an immunocompetent (IC) syngeneic ovarian cancer progression model. MethodsThe ability of HO-3867 to induce macrophage polarization was assessed in RAW264.7 cells, while its impact on anti-tumor immunity was evaluated in splenocytes co-cultured with ID8 and OC ascites cells. Immune modulation, including cytokine induction, extracellular vesicle (EV) release, and endosomal sorting complex required for transport (ESCRT) protein expression, was analyzed in-vitro and using in-vivo OC model. The therapeutic effects of HO-3867 and bevacizumab were examined in vivo by measuring ascites volume, EV secretion levels, and immune cell populations via flow cytometry. ResultsOur results demonstrate that combination therapy significantly reduced ascites accumulation, and limited peritoneal disease spread in ovarian cancer mouse models. EV analysis revealed a decrease in total EVs and CD9+ subpopulations, which correlated with the associated ESCRT proteins involved in EV formation and secretion implicating EVs in tumor progression and immune modulation. Flow cytometry analysis of ascites immune cell populations showed that combination therapy reduced myeloid-derived suppressor cells (MDSCs) and their PD-L1 expression, while enhancing CD8+ T cell cytotoxicity via granzyme B secretion. Cytokine profiling revealed upregulation of IFN-{gamma} and downregulation of IL-6, IL-10 and CXCL-2 suggesting enhanced anti-tumor immune response. Furthermore, HO-3867 promoted macrophage polarization toward tumoricidal M1 phenotype and reduced MDSC expansion in-vitro, enhancing anti-tumor immunity. ConclusionHO-3867 and bevacizumab synergistically reprogram the tumor microenvironment, inhibit EV-mediated progression, and enhance antitumor immunity. These findings support its immunomodulatory potential in ovarian cancer ascites, offering a promising therapeutic strategy.

cancer biology↗

bioRxiv2019

CHOLESTEROL MYTH AND THE IMPERATIVE ROLE OF FUNCTIONAL EVALUATION OF LIPOPROTEINS IN ATHEROSCLEROTIC RISK PREDICTION STRATEGIES

ObjectiveTo arrive at apposite risk prediction strategies in identifying markers that could delineate patients susceptible for atherosclerotic progression from other diabetic patient population thus circumventing undesirable drug exposure or conversely inadequate treatment. Research Design and MethodsThe study was designed to assess and compare the biochemical parameters along with lipoprotein ratios assessed in structural and functional aspects between the probable risk factor groups for CAD(diabetics with no symptoms for CAD) and untreated CAD patients (on admission for CAD) in a total of 593 participants. Anthropometric measurements were made and serum fasting glucose, lipid peroxide levels, lipid and lipoprotein ratio assessments were carried out. In addition to these basic parameters, oxidized LDL (Ox-LDL) and serum paraoxonase (PON) activity were also measured in this study. To ascertain the diagnostic accuracy of the individual markers, receiver operating characteristic curve analysis was carried out. ResultsSerum levels of blood lipids, lipid peroxides were higher in the diabetic and the cardiovascular patients with a concomitant decrease in the levels of HDL. Increased median levels of Ox-LDL and decreased PON activity was observed in the cardiovascular patients both with and without diabetes. ConclusionThis study proposes Ox-LDL/PON assessment would be more functional than the traditional LDL-c/HDL-c to categorize the risk group of patients into prospective atherosclerotic predisposed and non-predisposed population, thus enabling the former to get treated with appropriate medication.

biochemistry↗