Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 10

Published: March 27, 2024

Adenanthera pavonina is a medicinal plant with numerous potential secondary metabolites showing significant level of antidiabetic activity. The objective the current study was to identify phytochemicals from methanolic leaf extract as therapeutic agents against diabetes mellitus using GC-MS and in silico methods. analysis revealed total 17 phytochemicals. Molecular docking performed these phytochemicals, targeting mutated insulin receptor tyrosine kinase (5hhw), which inhibits glucose uptake by cells. Diazoprogesterone (−9.2 kcal/mol), 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid (−6.9 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] (−6.6 kcal/mol) exhibited better binding target protein. ADMET for top three compounds best scores, showed positive results no observed toxicity AMES test. Furthermore, molecular dynamics confirmed favorable Diazoprogesterone, throughout 100 ns simulation period.

Language: Английский

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Sensitive and label-free SPR biosensing platforms for high-throughput screening of plasma membrane receptors interactions with insulin-like targets of hypoglycaemic activity

Talanta, Journal Year: 2024, Volume and Issue: 274, P. 125914 - 125914

Published: March 27, 2024

Language: Английский

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Signaling pathways and targeted therapies in Ewing sarcoma

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 266, P. 108765 - 108765

Published: Nov. 30, 2024

Language: Английский

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Pre-existing cancer cells and induced fibroblasts are key cells for early chemoresistance in ovarian cancer

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 6, 2024

Abstract Chemoresistance has long been a significant but unresolved issue in the treatment of various cancers, including most deadly gynecological cancer, high-grade serous ovary cancer (HGSOC). In this study, single nuclei transcriptome analyses were utilized to identify key cells and core networks for chemoresistance HGSOC patients with different early responses platinum-based chemotherapy at single-cell level. Biomarkers also screened using bulk data from independent cohorts larger sample sizes. A total 62,482 six samples analyzed, revealing that chemoresistant (Epithelial cells_0) pre-existed within individual patient before treatment. Two network modules formed hub genes such as hormone-related (ESR1 AR), insulin-related (INSR IGF1R), CTNNB1, significantly overexpressed these patient. BMP1 TPM2 could be promise biomarkers identifying data. Additionally, chemotherapy-induced fibroblasts (Fibroblasts_01_after) emerged stromal chemoresistance. One module containing one subnetwork by cholesterol biosynthesis-related cancer-related STAT3 MYC, was Notably, NAMPT-INSR prioritized ligand-receptor pair interacting Fibroblasts_01_after Epithelial cells_0 drive up-regulation their genes, IL1R1, MYC INSR itself. Our findings deepen understandings about mechanisms patients.

Language: Английский

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Identification and Characterization of a Novel Insulin-like Receptor (LvRTK2) Involved in Regulating Growth and Glucose Metabolism of the Pacific White Shrimp Litopenaeus vannamei

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1300 - 1300

Published: Oct. 14, 2024

The insulin receptor (IR) plays a crucial role in the growth and metabolism of animals. However, there are still many questions regarding IR crustaceans, particularly their shrimp glucose metabolism. In this study, we identified novel insulin-like gene Litopenaeus vannamei cloned its full length 6439 bp. This exhibited highly conserved sequence structural characteristics. Phylogenetic analysis confirmed it as an unreported RTK2-type IR, namely, LvRTK2. Expression pattern showed that LvRTK2 is primarily expressed female reproductive digestive organs. Through series vivo vitro experiments, including treatment, exogenous starvation was to be involved endogenous metabolic pathway under different variations. Moreover, long-term short-term interference experiments with revealed significantly reduced rate serum clearance rate. Further studies indicated may regulate by modulating downstream PI3K/AKT signaling events, such glycolysis, gluconeogenesis, glycogen synthesis, glycogenolysis. report on characteristics functions confirms important IRs regulating

Language: Английский

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Diet influence on male sexual maturation through interplay between insulin signaling and juvenile hormone in insects

Insect Biochemistry and Molecular Biology, Journal Year: 2024, Volume and Issue: 177, P. 104252 - 104252

Published: Dec. 17, 2024

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français étrangers, laboratoires publics privés.

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Associations of Clusters of Cardiovascular Risk Factors with Insulin Resistance and Β-Cell Functioning in a Working-Age Diabetic-Free Population in Kazakhstan

International Journal of Environmental Research and Public Health, Journal Year: 2023, Volume and Issue: 20(5), P. 3918 - 3918

Published: Feb. 22, 2023

Cardiovascular risk factors aggregate in determined individuals. Patients with Type 2 diabetes mellitus (T2DM) have higher cardiovascular This study aimed to investigate insulinresistance (IR) and β-cell function using the homeostasis model assessment (HOMA) indexes a general Kazakh population determine effect he that may on those indexes. We conducted cross-sectional among employees of Khoja Akhmet Yassawi International Kazakh-Turkish University (Turkistan, Kazakhstan) aged between 27 69 years. Sociodemographic variables, anthropometric measurements (body mass, height, waist circumference, hip circumference), blood pressure were obtained. Fasting samples collected measure insulin, glucose, total cholesterol (TC), triglycerides (TG), high- (HDL) andlow-density lipoprotein (LDL) levels. Oral glucose tolerance tests performed. Hierarchical K-means cluster analyses The final sample was composed 427 participants. Spearmen correlation analysis showed parameters statistically associated HOMA-β (p < 0.001) not HOMA IR. Participants aggregated into three clusters where age revealed deficient functioning, but IR 0.000 p = 0.982). Common easy obtain biochemical capturing relevant been demonstrated be significant deficiency insulin secretion. Although further longitudinal studies incidence T2DM are needed, this highlights profiling has role just for stratification patients prevention also targeted vigilant monitoring.

Language: Английский

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Long-range repression by ecdysone receptor on complex enhancers of the insulin receptor gene

Fly, Journal Year: 2023, Volume and Issue: 17(1)

Published: Aug. 24, 2023

The insulin signalling pathway is evolutionarily conserved throughout metazoans, playing key roles in development, growth, and metabolism. Misregulation of this associated with a multitude disease states including diabetes, cancer, neurodegeneration. human receptor gene (INSR) widely expressed development was previously described as 'housekeeping' gene. Yet, there abundant evidence that cell-type specific manner, dynamic regulation response to environmental signals. Drosophila insulin-like (InR) homologous the INSR shown be regulated by multiple transcriptional elements located primarily within introns These were roughly defined ~1.5 kbp segments, but we lack an understanding potential detailed mechanisms their regulation. We characterized substructure these cis-regulatory S2 cells, focusing on through ecdysone (EcR) dFOXO transcription factor. By identifying locations activators repressors 300 bp subelements, show some identified enhancers consist relatively compact clusters activators, while others have distributed architecture not amenable further reduction. In addition, assays uncovered long-range repressive action unliganded EcR. complex circuitry likely endows InR highly flexible tissue-specific tune signalling. Further studies will provide insights demonstrate impact natural variation gene's regulation, applicable genetic studies.

Language: Английский

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Long-range repression by ecdysone receptor on complex enhancers of the insulin receptor gene

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 23, 2023

The insulin signaling pathway is evolutionarily conserved throughout metazoans, playing key roles in development, growth, and metabolism. Misregulation of this associated with a multitude disease states including diabetes, cancer, neurodegeneration. Genome-wide association studies indicate that natural variants putative intronic regulatory elements the human receptor gene ( INSR) are metabolic conditions, however, gene's transcriptional regulation remains incompletely studied. INSR widely expressed development was previously described as 'housekeeping' gene. Yet, there abundant evidence cell-type specific manner, dynamic response to environmental signals. Drosophila insulin-like InR ) homologous shown be regulated by multiple located primarily within introns These were roughly defined ∼1.5 kbp segments, but we lack an understanding potential detailed mechanisms their regulation, well integrative output battery enhancers entire locus. Using luciferase assays, characterized substructure these cis-regulatory S2 cells, focusing on through ecdysone (EcR) dFOXO transcription factor. direct action EcR Enhancer 2 reveals bimodal form active repression absence ligand, positive activation presence 20E. By identifying location activators enhancer, long-range acting over at least 475 bp, similar repressors found embryo. 20E have contrasting effects some individual elements, for adjacent 3, influence was/was not additive, indicating enhancer locus can/cannot part additive models. Other from exhibited "distributed" or "localized" modes action, suggesting predicting joint functional regions will require deeper experimental characterization. noncoding demonstrated expression cell type specificity. This complex circuitry goes beyond simple conception Further aimed how work together vivo generate finely tuned tissue- temporal-specific manners, provide guide impact variation applicable genetic studies.

Language: Английский

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Computational Screening and Experimental Validation of Inhibitor Targeting the Complex Formation of Grb14 and Insulin Receptor

Published: Dec. 8, 2023

The expedited development of drugs targeting gene products associated with insulin resistance holds the potential to enhance our comprehension type 2 diabetes mellitus (T2DM). virtual screening based on a three-dimensional (3D) protein structure has been expected as technique accelerate molecular target drugs. Among targets implicated in resistance, genetic characterization and function Grb14 have clarified without contradiction. displays notable variations T2DM, its product known inhibit receptor (IR) by directly binding tyrosine kinase domain. In present study, screening, 3D IR domain (IRβ) complex part Grb14, was conducted find compounds that can disrupt formation between IRβ. First, ten were selected from 154,118 via hierarchical silico structure-based drug composed grid docking-based algorithm-based programs. experimental validations suggested one compound affect blood glucose level. dynamics simulations co-immunoprecipitation analysis showed did not completely suppress protein–protein interaction IR, though competitively bound pseudosubstrate region Grb14.

Language: Английский

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