Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 1 - 21
Опубликована: Янв. 1, 2024
Язык: Английский
Molecular Cancer, Год журнала: 2023, Номер 22(1)
Опубликована: Авг. 10, 2023
Abstract The reversible oxidation-reduction homeostasis mechanism functions as a specific signal transduction system, eliciting related physiological responses. Disruptions to redox can have negative consequences, including the potential for cancer development and progression, which are closely linked series of processes, such adjustment reactive oxygen species (ROS) levels species, changes in antioxidant capacity, differential effects ROS on downstream cell fate immune capacity. tumor microenvironment (TME) exhibits complex interplay between immunity regulatory death, especially autophagy apoptosis, is crucially regulated by ROS. present study aims investigate multi-source affects autophagy, anti-tumor response TME mutual crosstalk these three processes. Given intricate role controlling immunity, we will further examine relationship traditional therapy It worth noting that discuss some ROS-related treatment options future studies.
Язык: Английский
Процитировано
53
Coordination Chemistry Reviews, Год журнала: 2024, Номер 518, С. 216101 - 216101
Опубликована: Июль 27, 2024
Язык: Английский
Процитировано
8
BMC Chemistry, Год журнала: 2025, Номер 19(1)
Опубликована: Фев. 28, 2025
Head and neck squamous cell carcinoma (HNSCC) is the most common head cancer highly aggressive heterogeneous. Targeted therapy still main treatment method used in clinic due to lower side effect personalized medication. In order discover novel effective drugs with low against HNSCC, we analyzed genes related found that PIK3CA was expressed tumor tissues often experienced mutations, leading excessive activation of phosphoinositide 3-kinase alpha (PI3Kα), promoting development HNSCC. The allosteric PI3Kα inhibitor STX-478 inhibits growth hotspot mutations shows prominent efficacy on human HNSCC xenografts without displaying metabolic dysfunction observed Alpelisib. These open site more readily, increasing selectivity for mutant PI3Kα. cleverly avoids ATP competitive inhibitors. So, structure optimized based interaction mechanism between Then, virtual screening, binding mode research, target verification, physical chemical properties, pharmacokinetic properties stabilities ligand-PI3Kα complexes were evaluated by computer technologies (scaffold hopping, cdocker, SuperPred, SwissTarget prediction, Lipinski's rule five, ADMET MD simulation). Finally, J-53 (2-oxopropyl urea compound) excellent selected. not only formed H-bonds key amino acids, but its unique -C(O)CH3 could also form ILE1019, making it stably bound contributing activity. After SciFinder had value further study. This study suggested be as potential inhibitors PI3Kα, provides valuable information subsequent drug discovery
Язык: Английский
Процитировано
1
Frontiers in Endocrinology, Год журнала: 2023, Номер 14
Опубликована: Март 3, 2023
Diabetic kidney disease (DKD) is the main cause of end-stage renal worldwide, and there a lack effective treatment strategies. Autophagy highly conserved lysosomal degradation process that maintains homeostasis energy balance by removing protein aggregates damaged organelles. Increasing evidence suggests dysregulated autophagy may contribute to glomerular tubulointerstitial lesions in under diabetic conditions. Emerging studies have shown Chinese herbal medicine its active compounds ameliorate injury regulating autophagy. In this review, we summarize dysregulation or insufficiency cells, including podocytes, mesangial proximal tubular epithelial key mechanism for development DKD, focus on protective effects compounds. Moreover, systematically reviewed DKD regulated herb compound preparations, single compounds, so as provide new drug candidates clinical DKD. Finally, also candidate targets Therefore, further research with regulation their great significance realization targeted therapies
Язык: Английский
Процитировано
14
Pharmaceuticals, Год журнала: 2024, Номер 17(3), С. 374 - 374
Опубликована: Март 15, 2024
One of the possible candidates for treatment diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, impacts liraglutide on integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were examined. Twenty-four Wistar albino distributed four different groups, and high-fat diet used to induce two groups. Rats untreated control groups administered 0.9% NaCl solution over 6-week period, those 3 weeks, followed by subcutaneous injection (150 μg/kg) an additional weeks. liraglutide-treated group, heart-to-body weight ratio was significantly reduced, levels cardiac biomarkers, troponin I creatine-kinase-MB, improved; activities antioxidant enzymes, glutathione peroxidase superoxide dismutase, increased; malondialdehyde decreased. Western blotting immunohistochemical studies revealed increased ILK, P-PI3K, P-AKT, BCL2, as well caspase 3, BAX, P-PTEN, indicating mitigation cardiomyocyte apoptosis. Our results show that targeting GLP1Rs, enhances expression proteins ILK/PI3K/AKT/PTEN pathway thereby exerts its cardioprotective effects DCM.
Язык: Английский
Процитировано
5
Molecular Biomedicine, Год журнала: 2024, Номер 5(1)
Опубликована: Апрель 15, 2024
Abstract Compared with those in adenocarcinoma, PIK3CA mutations are more common squamous cell carcinoma (SCC), which arises from stratified epithelia that usually exposed to adverse environmental factors. Although hotspot exons 9 and 20 of PIK3CA, including E542K, E545K, H1047L H1047R, frequently encountered the clinic, their clinicopathological meaning remains be determined context SCC. Considering few reviews on SCC available literature, we undertook this review shed light clinical significance mutations, mainly regarding implications ramifications malignant behavior, prognosis, relapse or recurrence chemo- radioresistance It should noted only studies was mutated were cherry-picked, fell within scope review. However, role adenocarcinoma has not been discussed. In addition, occurring other main members PI3K-AKT-mTOR signaling pathway than also excluded.
Язык: Английский
Процитировано
5
Journal of Molecular Histology, Год журнала: 2025, Номер 56(2)
Опубликована: Март 17, 2025
Язык: Английский
Процитировано
0
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Июнь 4, 2024
Glioblastoma multiforme (GBM) is one of the most prevalent and lethal primary central nervous system malignancies. GBM notorious for its high rates recurrence therapy resistance PI3K/Akt pathway plays a pivotal role in malignant behavior. Crebanine (CB), an alkaloid capable penetrating blood–brain barrier (BBB), has been shown to have inhibitory effects on proinflammatory molecules multiple cancer cell lines via pathways such as PI3K/Akt. This study aims investigate efficacy mechanisms CB treatment GBM. It first elucidate anti-tumor GBM, providing new possibilities therapy. Through series experiments, we demonstrate significant anti-survival, anti-clonogenicity, proapoptotic lines. Next-generation sequencing (NGS) also conducted provides complete list changes gene expression after treatment, including genes related apoptosis, cycle, FoxO, autophagy. The subsequent protein expressions upregulation apoptosis downregulation are further proved. clinical applicability could be BBB-penetrating feature, induction blockage pathway. Future research needed using vivo experiments other therapeutic NGS or studies.
Язык: Английский
Процитировано
4
Pharmacognosy Magazine, Год журнала: 2025, Номер unknown
Опубликована: Янв. 13, 2025
Background Gliomas are the most aggressive and devastating brain tumors, with a poor prognosis due to their complex etiology, diverse clinical manifestations, limited efficacy of existing treatment methods. Purpose The present work was conducted understand anticancer activities farnesol against glioma C6 cells. Methods effects on in vitro free radical scavenging were evaluated at various dosages (1–100 µM). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test used assess influence growth cells nonmalignant Vero apoptotic levels investigated using 4′,6-diamidino-2-phenylindole (DAPI) dual staining assays. oxidative stress markers, inflammatory biomarkers, protein levels, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) pathway proteins assessed respective kits. Results results assays proved antioxidant properties farnesol. MTT assay findings demonstrated significant reduction cell viability following fluorescent onset apoptosis farnesol-treated Furthermore, effectively increased stress, reduced marker PI3K, AKT, mTOR expression also successfully downregulated by Conclusion current demonstrate that suppresses triggers Thus, it has capacity be an effective agent treat glioma. Nonetheless, additional is still necessary future determine specific molecular mechanisms involved farnesol-induced
Язык: Английский
Процитировано
0
Journal of Neuro-Oncology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 28, 2025
Язык: Английский
Процитировано
0