Salvianolic Acid B Inhibits Activation of Human Primary Hepatic Stellate Cells Through Downregulation of the Myocyte Enhancer Factor 2 Signaling Pathway

Various isoforms of myocyte enhancer factor 2 (MEF2) have been shown to play a role in the activation of rat hepatic stellate cells (HSCs) in culture. The signals that regulate MEF2 in HSCs are unknown. In addition, whether MEF2s regulate the activation of human HSCs (H-HSCs) is unclear. Here, we studied the expression and function of MEF2s in H-HSCs. Our data showed that the levels of MEF2A, C, and D proteins were high in liver tissues from patients with cirrhosis and increased during culture-induced activation of primary H-HSCs. Exposure of H-HSCs to transforming growth factor beta 1 (TGF-β1) led to a significant increase in MEF2A and C protein levels and enhanced MEF2 activity. Interestingly, TGF-β1 did not further enhance MEF2D levels. Furthermore, TGF-β1 activated p38 mitogen-activated protein kinase (MAPK) and led to increased phosphorylation of MEF2C at its p38 recognition site. Inhibition of p38 MAPK inhibited both TGF-β1- and culture-induced activation of MEF2. The activity of collagen I reporter in H-HSCs was significantly reduced when MEF2A and MEF2C were blocked with overexpression of dominant negative MEF2 mutants. Salvianolic-acid B (SA-B), a water-soluble element of Salvia miltiorrhiza known to have anti-fibrosis effects, attenuated both basal and TGF-β1-induced increased levels of MEF2A and C mRNA and protein. In addition, SA-B inhibited MEF2 activity, which correlated with reduced expression of the HSC activation markers, α-smooth muscle actin (α-SMA), and collagen I. Administration of SA-B reduced MEF2A in vivo, which was accompanied by reduced levels of α-SMA in a model of dimethylnitrosamine-induced rat liver fibrosis. We concluded that the MEF2 transcription factor was stimulated by TGF-β1 in H-HSCs. Antagonizing TGF-β1-induced activation of the MEF2 signaling pathway may account in part for the anti-fibrosis effects of SA-B

Effect of Fuzheng Huayu formula and its actions against liver fibrosis

Liver fibrosis is a common histological process to develop into cirrhosis in various chronic liver diseases including chronic hepatitis and fatty liver. Therefore anti-liver fibrosis is very important strategy to treat chronic liver diseases. Fuzheng Huayu (FZHY), a preparation containing herbs such as Radix Salvia Miltiorrhizae, Cordyceps, Semen Persicae, was formulated on the basis of Chinese medicine theory in treating liver fibrosis and was approved. Pharmacological studies and clinical trials demonstrate that FZHY has a significant effect against liver fibrosis and that many of the pharmacological actions are attributable to the effect. This article reviews the effects and actions of FZHY, in particular the effects observed from clinical trials in treating liver fibrosis caused by chronic hepatitis B and the actions on inhibition of hepatic stellate cell activation, protection of hepatocytes and inhibition of hepatic sinusoidal capillarization. This article also reviews the coordinated effects of the constituent herbs of FZHY and the actions of their active compounds such as salvianonic acid B (SA-B) on liver fibrosis

OsPIE1, the Rice Ortholog of Arabidopsis PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1, Is Essential for Embryo Development

orthologs in monocots remains unknown., respectively).Taken together, our results suggest that OsPIE1 is the rice ortholog of Arabidopsis PIE1 and plays an essential role in rice embryo development

Resolving blood stasis to improve liver microcirculation and treat chronic liver diseases

Chronic liver diseases are frequently accompanied by changes in the organ′s microcirculatory system. Changes in the vascular architecture can affect the rate of blood flow, which in turn may promote the underlying pathogenic etiology; for example, recent studies have indicated that decreased blood flow in the liver can suppress the clearance rate of pathogenic agents (such as hepatitis virus), enhance localized inflammation and or fibrosis-related injury, or increase pressure in the portal vein. The phenomenon of obstructed liver microcirculation in modern medicine is similar to the pathogenic concept of blood stasis in traditional Chinese medicine (TCM). Thus, TCM decoctions or methods that promote blood circulation, and have been historically applied to remove blood stasis, may prove useful for treating liver diseases. In this review of the promising TCM agents and treatment modalities, we discuss not only the reported outcomes of pharmacological applications in both humans and animal models but also the molecular mechanisms related to the beneficial effects. Future studies should continue to investigate the clinical efficacy of resolving blood stasis to treat portal hypertension, liver fibrosis, and cirrhosis

Salvianolic Acid B Inhibits ERK and p38 MAPK Signaling in TGF-β1-Stimulated Human Hepatic Stellate Cell Line (LX-2) via Distinct Pathways

Salvianolic acid B (SA-B) is water-soluble component of Radix Salvia miltiorrhiza. The previous work indicated that SA-B can inhibit MAPK and Smad signaling in activated hepatic stellate cells (HSCs) to perform anti-fibrotic activity Lv et al. 2010. However, some studies have shown that there is cross-talk between MAPK and Smad in certain cell types. Thus, the anti-fibrotic action of SA-B may be through the cross-talk. In order to clarify the mechanism of SA-B further, we knocked down Smad in LX-2 cells (SRV4) via RNAi, and then added TGF-β1, and PD98059 or SB203580 and SA-B. The levels of p-MEK and p-p38 were inhibited by SA-B in SRV4 independent of TGF-β1. The expression of Col I and α-SMA in SRV4 could be reduced by SA-B independent TGF-β1. SB203580 had not significant effect on p-MEK in SRV4 stimulated by TGF-β1. The levels of p-MEK in SRV4 were not increased significantly after TGF-β1 stimulation. PD98059 had no effect on the levels of p-p38 in SRV4 irrespective of TGF-β1. In conclusion, SA-B inhibits the synthesis of Col I in LX-2 cells independent of TGF-β1 stimulation, and the anti-fibrotic effect of SA-B is due to direct inhibition of p38 signaling and inhibition the cross-talk of Smad to ERK signaling

Role of vitamin D and vitamin D receptor in evaluation and treatment of liver cirrhosis

Vitamin D is mainly produced in the liver, and chronic liver injury caused by various reasons will affect the metabolism of vitamin D, lead to vitamin D deficiency, and accelerate disease progression. Recent studies have confirmed that in patients with liver cirrhosis, the degree of vitamin D deficiency is closely associated with the severity and complications of liver cirrhosis. This article introduces the role of vitamin D and vitamin D receptor in the evaluation and treatment of liver cirrhosis and points out that vitamin D helps to evaluate the severity of liver cirrhosis and may become a new point and an important drug for the treatment of liver cirrhosis

Role of the nuclear factor-kappa B signaling pathway on the progress of hepatic fibrosis and the anti-fibrotic mechanism of traditional Chinese medicine

Nuclear factor-kappa B (NF-κB) plays an important role in various physiological and pathological processes by regulating gene expression, such as cell survival, growth, proliferation, activation, and apoptosis. In particular, the NF-κB signaling pathway has an important regulatory effect on the progression of hepatic fibrosis. This article reviews the structure and function of NF-κB, the regulatory effect of NF-κB on hepatocytes, Kupffer cells, and hepatic stellate cells in the progression of hepatic fibrosis, and the anti-fibrotic mechanism of traditional Chinese medicine by regulating the activity of the NF-κB signaling pathway. We also point out the complex interaction between NF-κB and various types of cells in certain diseases and emphasize the clinical significance of traditional Chinese medicine in inhibiting the activity of NF-κB and alleviating hepatic fibrosis

Comparison of the diagnostic efficiency between the O-RADS US risk stratification system and doctors’ subjective judgment

Abstract Background This study aimed to compare the diagnostic efficiency of Ovarian-Adnexal Reporting and Data System (O-RADS) and doctors’ subjective judgment in diagnosing the malignancy risk of adnexal masses. Methods This was an analysis of 616 adnexal masses between 2017 and 2020. The clinical findings, preoperative ultrasound images, and pathological diagnosis were recorded. Each adnexal mass was evaluated by doctors’ subjective judgment and O-RADS by two senior doctors and two junior doctors. A mass with an O-RADS grade of 1 to 3 was a benign tumor, and a mass with an O-RADS grade of 4–5 was a malignant tumor. All outcomes were compared with the pathological diagnosis. Results Of the 616 adnexal masses, 469 (76.1%) were benign, and 147 (23.9%) were malignant. There was no difference between the area under the curve of O-RADS and the subjective judgment for junior doctors (0.83 (95% CI: 0.79–0.87) vs. 0.79 (95% CI: 0.76–0.83), p = 0.0888). The areas under the curve of O-RADS and subjective judgment were equal for senior doctors (0.86 (95% CI: 0.83–0.89) vs. 0.86 (95% CI: 0.83–0.90), p = 0.8904). O-RADS had much higher sensitivity than the subjective judgment in detecting malignant tumors for junior doctors (84.4% vs. 70.1%) and senior doctors (91.2% vs. 81.0%). In the subgroup analysis for detecting the main benign lesions of the mature cystic teratoma and ovarian endometriosic cyst, the junior doctors’ diagnostic accuracy was obviously worse than the senior doctors’ on using O-RADS. Conclusions O-RADS had excellent performance in predicting malignant adnexal masses. It could compensate for the lack of experience of junior doctors to a certain extent. Better performance in discriminating various benign lesions should be expected with some complement