Unraveling the protective mechanisms of Chuanfangyihao against acute lung injury: Insights from experimental validation.

Chuanfangyihao (CFYH) is an effective treatment for acute lung injury (ALI) in clinical practice; however, its underlying mechanism of action remains unclear. Therefore, the aim of the present study was to elucidate the pharmacological mechanism of action of CFYH in ALI through experimental validation. First, a rat model of ALI was established using lipopolysaccharide (LPS). Next, the pathological changes in the lungs of the rats and the pathological damage were scored. The wet/dry weight ratios were measured, and ROS content was detected using flow cytometry. ELISA was used to examine IL-6, TNF-α, IL-1ß, IL-18, and LDH levels. Immunohistochemistry was used to detect Beclin-1 and NLRP3 expression. Western blotting was performed to analyze the expression of HMGB1, RAGE, TLR4, NF-κB p65, AMPK, p-AMPK, mTOR, p-mTOR, Beclin-1, LC3-II/I, p62, Bcl-2, Bax, Caspase-3, Caspase-1, and GSDMD-NT. The mRNA levels of HMGB1, RAGE, AMPK, mTOR, and HIF-1α were determined using reverse transcription quantitative PCR. CFYH alleviated pulmonary edema and decreased the expression of IL-6, TNF-α, TLR4, NF-κB p65, HMGB1/RAGE, ROS, and HIF-1α. In addition, pretreatment with CFYH reversed ALI-induced programmed cell death. In conclusion, CFYH alleviates LPS-induced ALI, and these findings provide a preliminary clarification of the predominant mechanism of action of CFYH in ALI.

Research progress in traditional Chinese medicine in the treatment of Alzheimer's disease and related dementias.

Alzheimer's disease (AD) is the world's leading cause of dementia and has become a huge economic burden on nations and families. However, the exact etiology of AD is still unknown, and there are no efficient medicines or methods to prevent the deterioration of cognition. Traditional Chinese medicine (TCM) has made important contributions in the battle against AD based on the characteristics of multiple targets of TCM. This study reviewed the treatment strategies and new discoveries of traditional Chinese medicine in current research, which may be beneficial to new drug researchers.

Disrupted eNOS activity and expression account for vasodilator dysfunction in different stage of sepsis.

AIMS: Sepsis is a severe endothelial dysfunction syndrome. The role of endothelial nitric oxide synthase (eNOS) in endothelial dysfunction induced by sepsis is controversial. To explore the role of eNOS in vascular dysfunction. MAIN METHODS: The effect of sepsis on vasodilation and eNOS levels was examined in septic mouse arteries and in cell models. KEY FINDINGS: In early sepsis mouse arteries, endothelium-dependent relaxation decreased and phosphorylation of the inhibitory Thr495 site in endothelial nitric oxide synthase increased. Mechanically, the phosphorylation of endothelial nitric oxide synthase at Thr497 in bovine aortic endothelial cells occurred in a protein kinase C-α dependent manner. In late sepsis, both nitric oxide-dependent relaxation responses and endothelial nitric oxide synthase levels were decreased in septic mice arteries. Endothelial nitric oxide synthase levels expression levels decreased in tumor necrosis factor-α-treated human umbilical vein endothelial cells and this could be prevented by the ubiquitin proteasome inhibitor (MG-132). MG-132 could reverse the decrease in endothelial nitric oxide synthase expression and improve nitric oxide-dependent vasodilator dysfunction in septic mice arteries. SIGNIFICANCE: These data indicate that vasodilator dysfunction is induced by the increased phosphorylation of endothelial nitric oxide synthase in early sepsis and its degradation in late sepsis.

Progesterone promotes endothelial nitric oxide synthase expression through enhancing nuclear progesterone receptor-SP-1 formation.

Progesterone exerts antihypertensive actions partially by modulating endothelial nitric oxide synthase (eNOS) activity. Here, we aimed to investigate the effects and mechanisms of progesterone on eNOS expression. First, human umbilical vein endothelial cells (HUVECs) were exposed to progesterone and then the eNOS transcription factor specificity protein-1 (SP-1) and progesterone receptor (PRA/B) expression were assessed by Western blotting and qRT-PCR. The interaction between SP-1 and PRA/B was next determined through coimmunoprecipitation assay. The chromatin immunoprecipitation assay and luciferase assay were used to investigate the relationship of PRA/B, SP-1, and eNOS promoter. At last, rats were intraperitoneally injected with progesterone receptor antagonist RU-486, and then the expression of eNOS and vasodilation function in thoracic aorta and mesenteric artery were measured. The results showed that progesterone could increase eNOS expression in HUVECs. Further study showed that progesterone increased PRA-SP-1 complex formation and facilitated PRA/B and SP-1 binding to eNOS promoter. Mutating SP-1 or PR-binding motif on eNOS promoter abolished the effect of progesterone on eNOS gene transcription. We also observed that progesterone receptor antagonist RU-486 reduced eNOS expression and impaired vasodilation in rats. Those results suggest that progesterone modulates eNOS expression through promoting PRA-SP-1 complex formation, and progesterone antagonist attenuates eNOS expression, leading to the loss of vascular relaxation.NEW & NOTEWORTHY Progesterone directly upregulated endothelial nitric oxide synthase (eNOS) expression in human endothelial cells. Progesterone augmented eNOS promoter activity through a progesterone receptor A- and specificity protein-1-dependent manner. Antagonism of the progesterone receptor reduced eNOS expression and impaired vasodilation in rats.

Pyrazinamide alleviates rifampin-induced steatohepatitis in mice by regulating the activities of cholesterol-activated 7α-hydroxylase and lipoprotein lipase.

The combination of rifampin and pyrazinamide is commonly used in the clinical treatment of tuberculosis, but its safety needs to be further clarified. Mice were intragastric administration of rifampin 300 mg/kg, pyrazinamide 625 mg/kg, rifampin 300 mg/kg plus pyrazinamide 625 mg/kg. The results showed that rifampin significantly increased transaminases, TBIL and TBA levels in serum, increased TG, TC content, HMGCR and CYP7A1 protein, CYP7A1, FGFR4, PXR, FAS and FXR mRNA expression, but decreased the level of SREBP-1c mRNA and induced severe steatohepatitis and hepatocyte necrosis in liver in mice. While pyrazinamide can improve many abnormal indexes when it used with RFP, including liver histopathology, liver TG, TC level and serum biochemistry, GPHBP1, FAS and CYP7A1 mRNA, LPL protein expression and activity induced by rifampin. However, pyrazinamide alone significantly decreased liver TG levels and caused only slight inflammatory pathological changes in liver histopathology in mice. These data suggested that rifampin increases TG and TC levels in the liver may be related to activate HMGCR, CYP7A1, PXR and FXR, theses toxic actions of rifampin were alleviated by pyrazinamide may be due to inhibite the activity of CYP7A1, PXR and FAS, and increasing the LPL protein expression and activity.