Comprehensive structural and functional analysis of hVEGFR1: Insights into phosphorylation, molecular interactions, and potential inhibitors through docking and dynamics simulations.

Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), is an enzyme with tyrosine kinase activity that plays a pivotal role in angiogenesis, the process of new blood vessel formation. This receptor is of significant clinical importance as it is implicated in various cancers, particularly non-small cell lung cancer (NSCLC), where its dysregulation leads to uncontrolled cell growth through ligand-induced phosphorylation. While commercially available drugs target VEGFR1, their prolonged use often leads to drug resistance and the emergence of mutations in cancer patients. To address these challenges, researchers have identified the human tyrosine kinase (hTK) domain of VEGFR1 as a potential therapeutic marker for lung malignancies. The 3D crystal structure of the hTK domain, obtained from Protein Data Bank (PDB ID: 3HNG), has provided vital structural insights of hVEGFR1. This study has revealed variations within the hVEGFR1 tyrosine kinase domain, distinguishing between regions associated with phosphorylase kinase and transferase activities. We identified numerous potential phosphorylation sites within the TK domain, shedding light on the protein's regulation and signaling possible. Detailed molecular interaction analyses have elucidated the binding forces between lead molecules and hVEGFR1, including hydrogen bonds, electrostatic, hydrophobic, and π-sigma interactions. The stability observed during molecular dynamics simulations further underscores the biological relevance of these interactions. Furthermore, docked complexes has highlighted localized structural fluctuations, offering insight into potential allosteric effects and dynamic conformational changes induced by lead molecules. These findings not only provide a comprehensive characterization of hVEGFR1 but also pave the way for the development of targeted therapies. Eventually, this study has the potential in identifying drug to combat diseases associated with hVEGFR1 dysregulation, including cancer and angiogenesis-related disorders, contributing to effective treatment strategies.

Quantum dots based in-vitro co-culture cancer model for identification of rare cancer cell heterogeneity.

Cancer cell heterogeneity (CCH) is crucial in understanding cancer progression and metastasis. The CCH is one of the stumbling blocks in modern medicine's therapeutics and diagnostics . An in-vitro model of co-culture systems of MCF-7, HeLa, HEK-293, with THP-1 cells showed the occurrence of EpCAM positive (EpCAM+) and EpCAM negative (EpCAM-) heterogenetic cancer cell types labeled with the Quantum Dot antibody conjugates (QDAb). This in-vitro model study could provide insights into the role of rare cancer cells manifestation and their heterogeneity in metastatic progression and risk for severe infections in these patients. We successfully report the presence of CCH based on the fluorescence ratios of the co-cultured cancer cells when treated with the QDAb. These short-term mimic co-cultures give a compelling and quite associated model for assessing early treatment responses in various cancers.

Biocompatible Ni-doped CdSe/ZnS semiconductor nanocrystals for cellular imaging and sorting.

Quantum dots (QD) with chemical composition QD CdSe / ZnS _ Ni 650 were successfully synthesized using a hydrothermal method and chemical precipitation. The nanocrystalline phase of the nanostructures was isolated and characterized using X-ray diffraction (XRD). The mean crystalline size doped core/shell Ni-dopant range was 9.0 ± 2.0 nm. The ferromagnetic data revealed the magnetic behaviour of QD CdSe / ZnS _ Ni 650 . The optical absorption measurements of these QDs were in the UV-visible light range 200-800 nm for a band gap value of 2.11 eV for QD CdSe / ZnS _ Ni 650 . This means that pure QD CdSe 650 and QD CdSe / ZnS _ Ni 650 underwent a redshift when compared with bulk CdSe. For QD CdSe / ZnS _ Ni 650 there was successful uptake by cell lines including HeLa and MCF-7 for bioimaging and sorting applications.

The genetic susceptibility profile of type 2 diabetes and reflection of its possible role related to reproductive dysfunctions in the southern Indian population of Hyderabad.

BACKGROUND: The genetic association studies of type 2 diabetes mellitus (T2DM) hitherto undertaken among the Indian populations are grossly inadequate representation of the ethnic and geographic heterogeneity of the country. In view of this and due to the inconsistent nature of the results of genetic association studies, it would be prudent to undertake large scale studies in different regions of India considering wide spectrum of variants from the relevant pathophysiological pathways. Given the reproductive dysfunctions associated with T2DM, it would be also interesting to explore if some of the reproductive pathway genes are associated with T2DM. The present study is an attempt to examine these aspects in the southern Indian population of Hyderabad. METHODS: A prioritized panel of 92 SNPs from a large number of metabolic and reproductive pathway genes was genotyped on 500 cases and 500 controls, matched for ethnicity, age and BMI, using AGENA MassARRAYiPLEX™ platform. RESULTS: The allelic association results suggested 14 SNPs to be significantly associated with T2DM at P ≤ 0.05 and seven of those-rs2241766-G (ADIPOQ), rs6494730-T (FEM1B), rs1799817-A and rs2059806-T (INSR), rs11745088-C (FST), rs9939609-A and rs9940128-A (FTO)-remained highly significant even after correction for multiple testing. A great majority of the significant SNPs were risk in nature. The ROC analysis of the risk scores of the significant SNPs yielded an area under curve of 0.787, suggesting substantial power of our study to confer these genetic variants as predictors of risk for T2DM. CONCLUSIONS: The associated SNPs of this study are known to be specifically related to insulin signaling, fatty acid metabolism and reproductive pathway genes and possibly suggesting the role of overlapping phenotypic features of insulin resistance, obesity and reproductive dysfunctions inherent in the development of diabetes. Large scale studies involving gender specific approach may be required in order to identify the precise nature of population and gender specific risk profiles for different populations, which might be somewhat distinct.