👤 Manoranjan Mahapatra

Dyslipidemia is the leading cause of cardiovascular disease (CVD) in Type 2 diabetes mellitus patients. As a result, it is critical to target and manage the level of atherogenic lipids. Angiopoietin-like proteins 3 and 4 (ANGPTL 3 and ANGPTL 4) play an important role in the intravascular lipolysis of triglyceride-rich lipoproteins by blocking the enzyme lipoprotein lipase. This study aimed to determine the amounts of these angiopoietin-like proteins in T2DM and find their association with dyslipidemia in T2DM. Sixty-one T2DM patients of age group 25-65 years and 27 healthy age-matched control participants were enrolled in the study. Glycemic status (FBS, PPBS, HbA1C), serum lipid parameters (cholesterol, TG, LDL, VLDL, HDL, Tc/HDL ratio), free fatty acid, serum insulin, and ANGPTL3, 4 were measured. A correlation was found between the ANGPTLs and the above parameters in T2DM patients. Serum ANGPTL3 ( This study shows that ANGPTL 3,4 may be associated with dyslipidemia in T2DM. ANGPTL4 is more correlated with glycemic status. Show less

Fibroblast growth factor receptor1 (FGFR1) kinase has a crucial role in cell proliferation, migration, and differentiation. Any imbalance in its level can cause cancer and many other illnesses. Despite the availability of numerous treatments, cytotoxicity, selectivity, and drug resistance issues demand the development of new FGFR1 inhibitors. Herein, we performed a high-throughput virtual screening of 54 624 compounds from NPASS and HMDB databases using the Schrodinger software suite. Compounds with a docking score cutoff of -11.0 kcal mol Show less

Fibroblast Growth Factor Receptor (FGFR) is connected to numerous downstream signalling cascades regulating cellular behavior. Any dysregulation leads to a plethora of illnesses, including cancer. Therapeutics are available, but drug resistance driven by gatekeeper mutation impedes the treatment. Ponatinib is an FDA-approved drug against BCR-ABL kinase and has shown effective results against FGFR-mediated carcinogenesis. Herein, we undertake molecular dynamics simulation-based analysis on ponatinib against all the FGFR isoforms having Val to Met gatekeeper mutations. The results suggest that ponatinib is a potent and selective inhibitor for FGFR1, FGFR2, and FGFR4 gatekeeper mutations. The extensive electrostatic and van der Waals interaction network accounts for its high potency. The FGFR3_VM mutation has shown resistance towards ponatinib, which is supported by their lesser binding affinity than wild-type complexes. The disengaged molecular brake and engaged hydrophobic spine were believed to be the driving factors for weak protein-ligand interaction. Taken together, the inhibitory and structural characteristics exhibited by ponatinib may aid in thwarting resistance based on Val-to-Met gatekeeper mutations at an earlier stage of treatment and advance the design and development of other inhibitors targeted at FGFRs harboring gatekeeper mutations. Show less

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that has been widely detected in the environment and is known to accumulate in organisms, including humans. The study investigated dose-dependent mortality, hatching rates, malformations, lipid accumulation, lipid metabolism alterations, and impacts on cholinergic neurotransmission. Increasing PFOS concentration led to higher mortality, hindered hatching, and caused concentration-dependent malformations, indicating severe abnormalities in developing zebrafish. The results also demonstrated that PFOS exposure led to a significant increase in total lipids, triglycerides, total cholesterol, and LDL in a concentration-dependent manner, while HDL cholesterol levels were significantly decreased. Additionally, PFOS exposure led to a significant decrease in glucose levels. The study identified TGs, TCHO, and glucose as the most sensitive biomarkers in assessing lipid metabolism alterations. The study also revealed altered expression of genes involved in lipid metabolism, including upregulation of fasn, acaca, and hmgcr and downregulation of ldlr, pparα, and abca1, as well as decreased lipoprotein lipase (LPL) and increased fatty acid synthase (FAS) activity,suggesting an impact on fatty acid synthesis, cholesterol uptake, and lipid transport. Additionally, PFOS exposure led to impaired cholinergic neurotransmission, evidenced by a concentration-dependent inhibition of acetylcholinesterase activity, altered gene expressions related to neural development and function, and reduced Na Show less

Immunophenotyping by flow cytometry (FCM) is a useful diagnostic tool for the evaluation of mature B-cell neoplasms (MBN). Here, CD200 expression may play a significant role and improve the distinction between various MBNs, but any potential as a prognostic marker is yet to be established. The present prospective study was conducted on all the suspected cases of MBNs. Immunophenotyping was done using a BD FACS Canto FCM using a panel of 4 to 6 color combinations of monoclonal antibodies; CD45, CD34, CD5, CD19, CD20, CD22, CD23, CD79b, FMC7, CD10, CD38, ZAP70, CD200, IgG, IgM, CD25, CD103, CD2, CD3, CD11c as well as κ and λ light chains. CD200 expression was compared in different subgroups. Of the total of 130 cases included in the study, CD200 was positive in 118 cases (90%). CD200 was expressed in 100% of the cases of CLL(86 cases), atypical CLL(06 cases), HCL(14 cases), FL(02 cases), SMZL(04 cases), LPL (01 case), and low-grade NHL (05 cases), with the highest intensity of fluorescence in HCL followed by CLL. All the cases of MCL and PLL were exclusively negative for CD200. In conclusion, the results of the present study support inclusion of this marker in the flow cytometric panels for the differential diagnosis of MBNs. Show less