Yixin-Fumai granules modulate autophagy through the PI3K/AKT/FOXO pathway and lead to amelioration of aging mice with sick sinus syndrome

Immunity & Ageing, Journal Year: 2024, Volume and Issue: 21(1)

Published: July 6, 2024

Abstract Objective By employing network pharmacology alongside molecular docking techniques, we can delve into the intricate workings of Yixin-Fumai granules (YXFMs) and their impact on sick sinus syndrome (SSS) within wrinkles mice. Specifically, aim to understand how YXFMs enhance autophagy through PI3K/AKT/FOXO path. Methods The active ingredients medicinal uses Ginseng, ligusticum wallichii , Ophiopogon, Schisandra, salvia, astragalus were compiled using BATMAN-TCM database. We also used Genecards, OMIM, Disgenet files identify disease goals. A hierarchical diagram “disease-drug-key targets” was generated Cytoscape programs. In addition, established a target protein interaction (PPI) STRING Then, Cluster Profiler R package conduct GO functional enrichment evaluation KEGG pathway analyses targets. Based PPI system, chose top communicating targets substances over docking. vivo studies performed validate these selections further. mouse model induced study damaged sinoatrial node (SAN) in mice with lower heart rates due age-related changes. Electrocardiogram Masson staining assessments obtain results. transmission electron microscope assess level SAN cells. Western blot employed analyze expression signaling process throughout SSS therapy aging Results One hundred forty-two ingredients, 1858 targets, 1226 266 intersection obtained. key encompassed TP53, AKT1, CTNNB1, INS, TNF, among others. According analysis, mechanism underlying treatment may primarily be associated control ion transport across membranes, cardiac contraction, regulation blood circulation, other biological processes. results it determined that they mainly enriched multiple pathways such as PI3K-Akt route, MAPK process, AGE-RAGE path, FOXO HIF-1 several paths. Molecular demonstrated five compounds had excellent binding candidate proteins AKT1 INS. Through studies, noticed notable effects when administering YXFMs. These included suppression aging-induced SSS, decrease R-R interval, rise rate, reduction fibrosis, boost level, spike levels molecules Conclusion This research has made preliminary predictions about potential treating SSS. It suggests have ability critical paths condition. Further testing been conducted discover new findings evidence ideas for tackling triggered by aging.

Language: Английский

---

Identification of a prognostic model based on cuproptosis and ferroptosis-related genes in patients with head and neck squamous cell carcinoma

Current Research in Biotechnology, Journal Year: 2024, Volume and Issue: 8, P. 100253 - 100253

Published: Jan. 1, 2024

Language: Английский

---

Using Bioinformatics and Machine Learning to Predict the Genetic Characteristics of Ferroptosis-Cuproptosis-Related Genes Associated with Sleep Deprivation

Nature and Science of Sleep, Journal Year: 2024, Volume and Issue: Volume 16, P. 1497 - 1513

Published: Sept. 1, 2024

Sleep deprivation (SD), a common sleep disease in clinic, has certain risks, and its pathogenesis is still unclear. This study aimed to identify ferroptosis-cuproptosis-related genes (FCRGs) associated with SD through bioinformatics machine learning, thus elucidating their biological significance clinical value.

Language: Английский

---

Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury

Neurotrauma Reports, Journal Year: 2024, Volume and Issue: 5(1), P. 1016 - 1026

Published: May 1, 2024

Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is multifunctional cytokine crucial development. Aberrant TGF-β signaling implicated in pathologies associated various neurological conditions. We recently developed novel small molecule drug, C381, activator ability restore lysosomal function. Here we used mouse model repetitive mild (mTBI) examine whether C381 would attenuate injury. first employed RNA-seq analysis investigate gene expression patterns mTBI and evaluated potential mitigating these changes. Our results demonstrate distinct mTBI-related signatures, prominently implicating pathways related integrity endothelial Notably, treatment reversed mTBI-induced Immunohistochemical further corroborated findings, revealing that attenuated damage mTBI-affected tissue. These findings strongly support clinical usefulness as intervention mTBI.

Language: Английский

---

Swertiamarin and sweroside are potential inhibitors of COVID-19 based on the silico analysis

Medicine, Journal Year: 2024, Volume and Issue: 103(45), P. e40425 - e40425

Published: Nov. 8, 2024

The severity of the respiratory disease caused by severe acute syndrome coronavirus 2 has escalated rapidly in recent years, posing a significant threat to global health. Sweroside and swertiamarin are bioactive iridoid glycosides extracted mainly from Swertia davidii Franch. It remains unclear how Specifically affects COVID-19 its underlying mechanisms. We first employed network pharmacology molecular docking techniques investigate sweroside affect order explore potential mechanism. found that 35 target genes can be used for treatment COVID-19, with androgen receptor (AR), HSP90AA1, RAC-alpha serine/threonine-protein kinase, cyclin-dependent kinase 1, epidermal growth factor receptor, glycogen synthase kinase-3 beta emerging as particularly promising candidates. Additionally, demonstrated unambiguous interactions 3CL protease AR through research. At active site, bind (1T65), main (5R82), (6M2N), showing therapeutic potential.

Language: Английский

---