MG53 ameliorates nerve injury induced neuropathic pain through the regulation of Nrf2/HO-1 signaling in rats.

Neuropathic pain is one of the most common types of chronic pain, and it arises as a direct consequence of a lesion or disease that affects the somatosensory system. Mitsugumin53 (MG53), which is a member of the TRIM family of proteins and is known as TRIM72, exerts protective effects on muscle, lung, kidney, brain, and other cells or tissues. Recently, increasing evidence has indicated that MG53 plays a vital role in regulating neuroinflammation and oxidative stress. However, the relationship between MG53 and neuropathic pain is unclear. In this study, we aimed to explore the role of MG3 in neuropathic pain after chronic constriction injury (CCI) to the sciatic nerve in rats. To explore the mechanism of MG53 regulating the development of neuropathic pain, the rats was injected (intrathecal injection) of recombinant human MG53 (rhMG53) protein and/or nuclear factor erythroid 2-related factor 2 (Nrf2) siRNA after CCI. Mechanical allodynia or thermal hyperalgesia was assessed by the 50% paw withdrawal threshold (PWT) or the paw withdrawal latency (PWL). The target molecules was detected using western blotting (WB), immunofluorescence (IF), quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), biochemical evaluations, and Dihydroethidium (DHE) staining. The results indicated that the expression level of MG53 in the spinal cord was increased after CCI in rats. Moreover, intrathecal injection with rhMG53 protein notably alleviated CCI-induced mechanical allodynia, thermal hyperalgesia, neuroinflammation，oxidative stress and the increased level of reactive oxygen species (ROS) via activation of the Nrf2/heme oxygenase-1 (HO-1) signaling pathway. However, administration of Nrf2 siRNA abrogated the analgesic, anti-inflammatory and antioxidant effects of rhMG53 in CCI model rats. Our study demonstrated that MG53 improved neuropathic pain, neuroinflammation, and oxidative stress via activation of the Nrf2/HO-1 signaling pathway in the spinal cord of CCI model rats, which suggested that MG53 may serve as a new target for the treatment of neuropathic pain.

Liver Transplantation Outcomes of HBV-, HCV-, and Alcohol-induced Hepatocellular Carcinoma in the United States: Analysis of National Inpatient Samples.

OBJECTIVE: Liver transplantation is a current treatment option for hepatocellular carcinoma (HCC). The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation, including locoregional recurrence, distant metastasis, and in-hospital mortality, in HCC patients with concurrent hepatitis B infection, hepatitis C infection, or alcoholic cirrhosis. METHODS: This retrospective cohort study included HCC patients (n=2391) from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection, co-infection with hepatitis B and C, or alcoholic cirrhosis of the liver between 2005 and 2014. Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models. RESULTS: Liver cirrhosis was due to alcohol in 10.5% of patients, hepatitis B in 6.6%, hepatitis C in 10.8%, and combined hepatitis B and C infection in 24.3%. Distant metastasis was found in 16.7% of patients infected with hepatitis B and 9% of hepatitis C patients. Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease. CONCLUSION: After liver transplantation, patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis. Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.

[Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats].

This paper was aimed to investigate the effect of voluntary wheel running exercise on depression-like behavior induced by chronic water immersion restraint stress (CWIRS) and the underlying mechanism. Sprague-Dawley (SD) rats received CWIRS to induce depression-like behavior and 4-week voluntary wheel running exercise. Meanwhile, the rats were treated with lipopolysaccharide (LPS) or STAT3 over-expression vector (pcDNA-STAT3) by intracerebroventricular injection. Behavioral tests were used to detect depression-like behavior. ELISA assay was used to detect levels of various inflammatory factors in the rat hippocampus. Western blot was used to detect protein expression levels of ionized calcium binding adaptor molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), phosphorylated STAT3 (p-STAT3) and total STAT3 (t-STAT3). The results showed that, compared with stress group, stress + exercise group exhibited improved depression-like behavior, decreased interleukin-1ß (IL-1ß) and IL-6 levels, increased IL-4 and IL-10 levels, down-regulated Iba-1 and iNOS protein expression levels, up-regulated Arg1 protein expression level, and decreased p-STAT3/t-STAT3 ratio in hippocampal tissue. LPS reversed the improving effect of voluntary wheel running exercise on depression-like behavior in rats, and the over-expression of STAT3 reversed the promoting effects of voluntary wheel running on M2 polarization of microglial cells in rat hippocampus and depression-like behavior. These results suggest that voluntary wheel running ameliorates the depression-like behavior induced by CWIRS in rats, and the mechanism may be related to regulating hippocampal microglia polarization via STAT3 signaling pathway.