Mannich Base Derived from Lawsone Inhibits PKM2 and Induces Neoplastic Cell Death DOI Creative Commons
Lucas Rubini-Dias, Tácio Vinício Amorim Fernandes,

Michele Pereira de Souza

и другие.

Biomedicines, Год журнала: 2024, Номер 12(12), С. 2916 - 2916

Опубликована: Дек. 21, 2024

Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as promising target for disrupting the metabolic adaptability tumor cells. This study explores potential Mannich base derived from lawsone (MB-6a) to interfere with PKM2 enzymatic activity both in vitro and silico. Methods: The antiproliferative MB-6a was tested using MTT assay various lines, including SCC-9, Hep-G2, HT-29, B16-F10, normal human gingival fibroblast (HGF). inhibition mediated by assessed an LDH-coupled measuring ATP production. Docking studies molecular dynamics calculations were performed Autodock 4 GROMACS, respectively, on tetrameric crystallographic structure. Results: 6a demonstrated selective cytotoxicity against all lines without affecting migration, highest selectivity index (SI) 4.63 followed B16-F10 (SI = 3.9), Hep-G2 3.4), HT-29 2.03). compound effectively inhibited glycolytic activity, leading reduction production reaction cells treated this naphthoquinone derivative. showed favorable binding ATP-bound monomers through docking (PDB ID: 4FXF; affinity scores ranging −6.94 −9.79 kcal/mol) MD simulations, revealing affinities stabilized key interactions hydrogen bonds, halogen hydrophobic contacts. Conclusions: findings suggest that exerts its glucose consequently reducing triggering energetic collapse highlights lead targeting warrants further investigation into mechanism action clinical applications.

Язык: Английский

Berberine Inhibits Migration and Apoptosis of Rat Podocytes in Diabetic Nephropathy via the Novel lncRNA LOC102549726 Related Pathway DOI

Chen Wang,

Hao Wu,

Yongsheng Xie

и другие.

Phytotherapy Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

ABSTRACT Background Diabetic nephropathy (DN) stands as one of the most severe complications diabetes. Podocytes injury, particularly its attachment to lateral glomerular basement membrane, serves a crucial indicator DN. Growing evidence suggests that berberine (BBR) can mitigate onset and progression However, molecular mechanisms through which BBR exerts beneficial effects in treatment DN remain incompletely elucidated. Purpose To explore underlying by therapeutic Methods High‐throughput lncRNA sequencing on renal cortex both model group normal SD was performed dig for differentially expressed lncRNAs. The expression LOC102549726 evaluated using qPCR. biological functions were analyzed podocyets rats. bioinformatics techniques, qPCR WB used potential mechanisms. Results We found highly rats podocytes subjected high glucose conditions. Silencing inhibited migration apoptosis podocytes. Mechanistically, identified facilitator EGF forkhead box O1 (FOXO1). BBR, known agent DN, exhibited ability diminish level LOC102549726, FOXO1 Conclusion Our findings suggested suppresses targeting LOC102549726/EGF/FOXO1 axis. This sheds light avenue mitigating impact podocyte function.

Язык: Английский

Процитировано

0
Novel benzofuran-conjugated indolin-2-ones as anticancer agents; design, synthesis, biological assessments, and molecular modeling insights DOI
Wagdy M. Eldehna, Haytham O. Tawfik, Mohamed S. Nafie

и другие.

Bioorganic Chemistry, Год журнала: 2025, Номер unknown, С. 108494 - 108494

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
DNA methylation expression patterns predict outcome of clear cell renal cell carcinoma DOI
Xu‐Wen Li, Huanmin Wang, Yajian Li

и другие.

Опубликована: Апрель 21, 2025

Abstract Objective To identify DNA methylation markers related to clear cell renal carcinoma (ccRCC) prognosis and construct a prognostic model. Methods Methylation data from TCGA GSE113501 dataset were analyzed. Differential analysis, univariate Cox regression, LASSO regression used find survival - CpG sites build risk score The model was evaluated by the area under curve, multivariate analysis determined factors. Results We 13 CpGs that are significantly associated with through series of analyses established based on them. Patients divided into high-risk group low-risk according median score. results showed there significant difference in overall rate between two groups (p < 0.001), curve (AUC) greater than 0.8. Verified dataset, performed well distinguishing ccRCC different progression states. In addition, combining gene expression five methylation-related differentially expressed genes (LINC02541, SLAMF8, LPXN, LGALS12, EGFR) identified, their levels upregulated tumor tissues. Multivariate indicated age, clinical stage, independent Conclusion This study confirmed can effectively predict (ccRCC), providing highly efficient minimally invasive assessment tool for practice.

Язык: Английский

Процитировано

0
The role of neutrophils in osteosarcoma: insights from laboratory to clinic DOI Creative Commons
Ming Xia, Yu Han,

Lihui Sun

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 8, 2024

Osteosarcoma, a highly aggressive malignant bone tumor, is significantly influenced by the intricate interactions within its tumor microenvironment (TME), particularly involving neutrophils. This review delineates multifaceted roles of neutrophils, including tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs), in osteosarcoma’s pathogenesis. TANs exhibit both pro- anti-tumor phenotypes, modulating growth immune evasion, while NETs facilitate cell adhesion, migration, immunosuppression. Clinically, neutrophil-related markers such as neutrophil-to-lymphocyte ratio (NLR) predict patient outcomes, highlighting potential for neutrophil-targeted therapies. Unraveling these complex crucial developing novel treatment strategies that harness TME to improve osteosarcoma management.

Язык: Английский

Процитировано

0
Mannich Base Derived from Lawsone Inhibits PKM2 and Induces Neoplastic Cell Death DOI Creative Commons
Lucas Rubini-Dias, Tácio Vinício Amorim Fernandes,

Michele Pereira de Souza

и другие.

Biomedicines, Год журнала: 2024, Номер 12(12), С. 2916 - 2916

Опубликована: Дек. 21, 2024

Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as promising target for disrupting the metabolic adaptability tumor cells. This study explores potential Mannich base derived from lawsone (MB-6a) to interfere with PKM2 enzymatic activity both in vitro and silico. Methods: The antiproliferative MB-6a was tested using MTT assay various lines, including SCC-9, Hep-G2, HT-29, B16-F10, normal human gingival fibroblast (HGF). inhibition mediated by assessed an LDH-coupled measuring ATP production. Docking studies molecular dynamics calculations were performed Autodock 4 GROMACS, respectively, on tetrameric crystallographic structure. Results: 6a demonstrated selective cytotoxicity against all lines without affecting migration, highest selectivity index (SI) 4.63 followed B16-F10 (SI = 3.9), Hep-G2 3.4), HT-29 2.03). compound effectively inhibited glycolytic activity, leading reduction production reaction cells treated this naphthoquinone derivative. showed favorable binding ATP-bound monomers through docking (PDB ID: 4FXF; affinity scores ranging −6.94 −9.79 kcal/mol) MD simulations, revealing affinities stabilized key interactions hydrogen bonds, halogen hydrophobic contacts. Conclusions: findings suggest that exerts its glucose consequently reducing triggering energetic collapse highlights lead targeting warrants further investigation into mechanism action clinical applications.

Язык: Английский

Процитировано

0