Detoxification II Prescription Suppresses the Th-17/IL-17 Inflammatory Axis to Improve the Liver Function of ACLF-Rats via Inactivating the P38MAPK Pathway

Hepatitis is a metabolic system disease which is a serious challenge to the medical and healthcare system of the world. This study attempted to investigate the therapeutic effect and illustrate the regulation pharmacological mechanism of Detoxification II Prescription on ACLF. In this study, the rats were injected with D-galactosamine to establish ACLF-rat models, and the levels of cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBiL) were measured with the related kits to reflect the liver functions of the rats. The levels of IL-17, IL-6, and IFN-γ in the serums of the rats were detected by qRT-PCR, and the percentages of Th-17 cells in CD4+ cells of the rats were measured by flow cytometry assay. In the results, the increased ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ and decreased ALB and CHE were found in the serums of the ACLF-rats, while Detoxification II Prescription could partly reverse those indexes of the ACLF-rats. Moreover, it was also found that Detoxification II Prescription could inhibit the expression of P38MAPK, and P38MAPK downregulation obviously improved the liver function indexes of the ACLF-rats including the levels of ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ cells. In conclusion, this study suggested that Detoxification II Prescription could suppress the Th-17/IL-17 inflammatory axis to improve the liver function of ACLF-rats via inhibiting the activity of the P38MAPK pathway.

Estrogen Promotes Pituitary Prolactinoma by Upregulating TLR4 / NF-κB/p38MAPK Pathway

Background: Prolactinomas have harmful effects on human health, and the pathogenesis is still unknown. Furthermore, the morbidity of women is much more than man, maybe related with estradiol level. Thus, it is important to reveal the pathogenesis and develop new therapeutic methods for prolactinomas.Methods: Immunofluorescence analysis or Immunohistochemistry analysis were performed on the ERβ, TLR4 and prolactin (PRL) expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of TLR4 in prolactinoma was determined using estradiol-induced mice models in C57BL/6 wild-type (WT) and TLR4−/− mice. MMQ cells were treated with estradiol, fulvestrant, LPS or transfected with different TLR4 small interfering RNA, which to study ERβ, TLR4 and PRL expression in MMQ cells. Co‑immunoprecipitates analysis was used to investigate the interaction between ERβ and TLR4.Results: Immunofluorescence analysis or Immunohistochemistry analysis showed that PRL and TLR4 expression were co-located and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and TLR4 expression was co-located and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of TLR4 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice through regulating TLR4/NF‑κB/p38MAPK pathway. Estradiol promoted PRL expression through regulating TLR4/NF‑κB/p38MAPK pathway in vitro study, and pre-Inhibiting ERβ or TLR4 reverse the effect, while simultaneously activating ERβ and TLR4 enhanced PRL expression than activating single ERβ or TLR4. Furthermore, ERβ co-immunoprecipitates with endogenous TLR4 was assessed by co-immunoprecipitation analysis.Conclusions: These results suggest that estradiol promoted prolactinoma development by activating the TLR4/NF‑κB/ p38MAPK pathway through Erβ and TLR4 knockout inhibited the proliferation and secretion of prolactin in prolactinoma.

Electroacupuncture Pretreatment Regulates Apoptosis of Myocardial Ischemia-Reperfusion Injury in Rats Through RhoA/p38MAPK Pathway Mediated by miR-133a-5p

The electroacupuncture (EA) pretreatment possesses a beneficial effect on myocardial ischemia/reperfusion (I/R) injury. However, the molecular mechanism of the EA effect is not fully understood. The study aimed to explore the protective effect of EA pretreatment on myocardial ischemia-reperfusion injury (MIRI) and apoptosis-related mechanisms in rats. Rats underwent in vivo myocardial ischemia-reperfusion, EA pretreatment, or intravenous injection of antagomirs. Cardiac function, infarct area, and myocardial cell apoptosis were measured. Meanwhile, the expressions of MKK3, MKK6, p38MAPK, Bax, Bcl-2, and Caspase-3 were also detected. We found that EA pretreatment significantly reduced infarct area and myocarpal cell apoptosis and enhanced cardiac function. EA pretreatment decreased the expression of Bax, Caspase-3, MKK3, MKK6, p38MAPK, Bax, and Caspase-3. In conclusion, The EA pretreatment down regulated the expression of MKK3, MKK6, and p38MAPK through the RhoA/p38MAPK pathway. EA pretreatment protect MIRI rats from apoptosis by down regulating the expression of MKK3, MKK6, and p38MAPK, thereby reducing the expression of Bax, Caspase-3 and up regulating the expression of Bcl-2, which mechanism is closely related to the RhoA/p38MAPK pathway mediated by miR-133a-5p.