Cardiovascular diseases that develop from hypercholesterolemia-induced atherosclerosis have emerged as a significant threat to human health.Recently,probiotics exhibiting cholesterol-lowering properties have emerged as a prominent area of research.Numerous studies have demonstrated that Lactobacillus reuteri can effectively reduce endogenous cholesterol synthesis,regulate cholesterol transport,and promote cholesterol degradation by modulating the expression of key genes,such as sterol-regulatory element binding protein 2,3-hydroxy-3-methyl-glutaryl coenzyme A reductase,and cholesterol 7 alpha-hydroxylase,in both the liver and intestinal epithelial cells of the host.This leads to a notable decrease in total cholesterol and low-density lipoprotein cholesterol levels in the host serum.The present paper offers a comprehensive overview of the underlying mechanisms responsible for the cholesterol-lowering effects exerted by L.reuteri,aiming to provide valuable insights into the treatment of hypercholesterolemia and the development of probiotics with cholesterol-lowering properties.

Cardiovascular diseases that develop from hypercholesterolemia-induced atherosclerosis have emerged as a significant threat to human health.Recently,probiotics exhibiting cholesterol-lowering properties have emerged as a prominent area of research.Numerous studies have demonstrated that Lactobacillus reuteri can effectively reduce endogenous cholesterol synthesis,regulate cholesterol transport,and promote cholesterol degradation by modulating the expression of key genes,such as sterol-regulatory element binding protein 2,3-hydroxy-3-methyl-glutaryl coenzyme A reductase,and cholesterol 7 alpha-hydroxylase,in both the liver and intestinal epithelial cells of the host.This leads to a notable decrease in total cholesterol and low-density lipoprotein cholesterol levels in the host serum.The present paper offers a comprehensive overview of the underlying mechanisms responsible for the cholesterol-lowering effects exerted by L.reuteri,aiming to provide valuable insights into the treatment of hypercholesterolemia and the development of probiotics with cholesterol-lowering properties.

Our previous studies indicate that phosphatidylinositol 4-kinase IIα can promote the growth of multi-malignant tumors via HER-2/PI3K and MAPK pathways. However, the molecular mechanisms of this pathway and its potential for clinical application remain unknown. In this study, we found that PI4KIIα could be an ideal combinatorial target for EGFR treatment via regulating EGFR degradation. Results showed that PI4KIIα knockdown reduced EGFR protein level, and the expression of PI4KIIα shows a strong correlation with EGFR in human breast cancer tissues (r = 0.77, P < 0.01). PI4KIIα knockdown greatly prolonged the effects and decreased the effective dosage of AG-1478, a specific inhibitor of EGFR. In addition, it significantly enhanced AG1478-induced inhibition of tumor cell survival and strengthened the effect of the EGFR-targeting anti-cancer drug Iressa in xenograft tumor models. Mechanistically, we found that PI4KIIα suppression increased EGFR ligand-independent degradation. Quantitative proteomic analysis by stable isotope labeling with amino acids in cell culture (SILAC) and LC-MS/MS suggested that HSP90 mediated the effect of PI4KIIα on EGFR. Furthermore, we found that combined inhibition of PI4KIIα and EGFR suppressed both PI3K/AKT and MAPK/ERK pathways, and resulted in downregulation of multiple oncogenes like PRDX2, FASN, MTA2, ultimately leading to suppression of tumor growth. Therefore, we conclude that combined inhibition of PI4KIIα and EGFR exerts a multiple anti-tumor effect. Dual inhibition of EGFR at protein and activity level via combinatorial blocking of PI4KIIα presents a novel strategy to combat EGFR-dependent tumors.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Survival ; drug effects ; ErbB Receptors ; antagonists & inhibitors ; metabolism ; Female ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; MCF-7 Cells ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Minor Histocompatibility Antigens ; Mitogen-Activated Protein Kinases ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Quinazolines ; pharmacology ; Transplantation, Heterologous ; Tyrphostins ; pharmacology