Type 2 diabetes is a medical condition involving elevated blood glucose levels resulting from impaired or improper insulin utilization. As the number of type 2 diabetes cases increases each year, there is an urgent need to develop novel drugs having new targets and/or complementing existing therapeutic protocols. In this regard, marine sponge-derived compounds hold great potential due to their potent biological activity and structural diversity. In this study, a small library of 50 marine sponge-derived compounds were examined for their activity towards type 2 diabetes targets, namely dipeptidyl peptidase-4 (DPP-4) and protein tyrosine phosphatase 1B (PTP1B). The compounds were first subjected to molecular docking on protein models based on their respective co-crystal structures to assess binding free energies (BFE) and conformations. Clustering analysis yielded BFE that ranged from 24.54 kcal/mol to -9.97 kcal/mol for DPP-4, and from -4.98 kcal/mol to -8.67 kcal/mol for PTP1B. Interaction analysis on the top ten compounds with the most negative BFE towards each protein target showed similar intermolecular interactions and key interacting residues as in the previously solved co-crystal structure. These compounds were subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling to characterize drug-likeness and combining the results from these analyses, ()-6'-debromohamacanthin B was identified as a potential multi-target inhibitor of DPP-4 and PTP1B, having favorable protein interaction, no Lipinski violations, good gastrointestinal (GI) tract absorption, blood-brain barrier (BBB) penetration, and no predicted toxicity. Finally, the interaction of ()-6'-debromohamacanthin B with the two proteins was validated using molecular dynamics simulations over 100 ns through RMSD, radius of gyration, PCA, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) confirming favorable interactions with the respective proteins.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2024.2301751 | DOI Listing |
Background: To investigate the effectiveness of different bariatric metabolic surgeries in improving metabolic syndrome indicators in patients.
Methods: A retrospective analysis was conducted on obese patients who underwent laparoscopic sleeve gastrectomy (LSG), laparoscopic sleeve gastrectomy + jejunojejunal bypass (LSG + JJB), and laparoscopic Roux-en-Y gastric bypass (LRYGB). Patients were categorized into groups based on their surgical procedure: LSG (N = 199), LSG + JJB (N = 242), and LRYGB (N = 288).
J Gerontol A Biol Sci Med Sci
January 2025
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
Background: Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used in manageing type 2 diabetes mellitus and weight control. Their potential in treating ageing-related diseases has been gaining attention in recent years. However, the long-term effects of GLP1RAs on these diseases have yet to be fully revealed.
View Article and Find Full Text PDFDiabetes Ther
January 2025
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical, University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, China.
Introduction: More than half of diabetes patients are Asians, and their tolerance to antidiabetic drugs may differ from that of non-Asians. Oral semaglutide has recently gained attention for its advantages in glycemic and body weight control. However, its effects across different ethnic groups remain unknown.
View Article and Find Full Text PDFArch Orthop Trauma Surg
January 2025
Department of Orthopaedics, The Royal Infirmary of Edinburgh, Little France, Edinburgh, EH16 4SA, UK.
Introduction: The combined effect of diabetes mellitus and obesity (Diabesity) on total knee replacement (TKR) outcomes is unclear. This study aimed to assess whether diabesity influenced functional outcomes and complication rate following primary TKR.
Materials And Methods: This case-controlled study compared the independent effects of obesity, diabetes, and diabesity on TKR outcomes.
Mayo Clin Proc
January 2025
Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea; Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address:
Objective: To assess the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i), thiazolidinediones (TZD), and dipeptidyl peptidase-4 inhibitors (DPP-4i) for the cardiorenal outcomes and mortality in individuals with type 2 diabetes and a prior stroke.
Patients And Methods: Using the Korean National Health Insurance Service database from 2014 to 2021, a new-user cohort was established through propensity score matching for SGLT2i, TZD, and DPP-4i. The primary outcomes were major adverse cardiovascular events (MACE), comprising myocardial infarction, ischemic stroke, and cardiovascular death.
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