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BACKGROUND AND PURPOSE Microglia-related inflammation is associated with the pathology of Parkinson's disease. Functional voltage-gated sodium channels (VGSCs) are involved in regulating microglial function. Here, we aim to investigate the effects of scorpion venom heat-resistant synthesized peptide (SVHRSP) on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease-like mouse model and reveal its underlying mechanism. EXPERIMENTAL APPROACH Unilateral brain injection of 6-OHDA was performed to establish Parkinson's disease mouse model. After behaviour test, brain tissues were collected for morphological analysis and protein/gene expression examination. Primary microglia culture was used to investigate the role of sodium channel Nav 1.6 in the regulation of microglia inflammation by SVHRSP. KEY RESULTS SVHRSP treatment attenuated motor deficits, dopamine neuron degeneration, activation of glial cells and expression of pro-inflammatory cytokines induced by 6-OHDA lesion. Primary microglia activation and the production of pro-inflammatory cytokines induced by lipopolysaccharide (LPS) were also suppressed by SVHRSP treatment. In addition, SVHRSP could inhibit mitogen-activated protein kinases (MAPKs) pathway, which plays pivotal roles in the pro-inflammatory response. Notably, SVHRSP treatment suppressed the overexpression of microglial Nav 1.6 induced by 6-OHDA and LPS. Finally, it was shown that the anti-inflammatory effect of SVHRSP in microglia was Nav 1.6 dependent and was related to suppression of sodium current and probably the consequent Na+ /Ca2+ exchange. CONCLUSIONS AND IMPLICATIONS SVHRSP might inhibit neuroinflammation and protect dopamine neurons via down-regulating microglial Nav 1.6 and subsequently suppressing intracellular Ca2+ accumulation to attenuate the activation of MAPKs signalling pathway in microglia.

In the paper, ZnO-deposited activated carbon composite (ZnO-AC) was firstly prepared in a simple two-step preparation process, and then covered with nano-graphene oxide to give the NGO-ZnOAC composite. The successful deposition of ZnO and NGO on the AC surface was demonstrated by various experiments, and the ZnO nanoparticles showed a mean diameter size mainly within about 10 nm. The specific surface area of the NGO-AC and NGO-ZnO-AC decreased from 67.74 m²/g of the parent AC to 32.54 and 11.43 m²/g, respectively. The fabricated NGO-ZnO-AC showed excellent adsorptive behaviors towards CrO2-₄ and Cu2+ ions, outperforming both ZnO-AC and AC.

Background: Intervention of neuroinflammation in central nervous system (CNS) represents a potential therapeutic strategy for a host of brain disorders. The scorpion Buthus martensii Karsch (BmK) and its venom have long been used in the Orient to treat inflammation-related diseases such as rhumatoid arthritis and chronic pain. Scorpion venom heat-resistant peptide (SVHRP), a component from BmK venom, has been shown to reduce seizure susceptibility in a rat epileptic model and protect against cerebral ischemia-reperfusion injury. As neuroinflammation has been implicated in chronic neuronal hyperexcitability, epileptogenesis and cerebral ischemia-reperfusion injury, the present study aimed to investigate whether SVHRP has anti-inflammatory property in brain.Methods: An animal model of neuroinflammation induced by lipopolysacchride (LPS) injection was employed to investigate the effect of SVHRP (125 µg/kg, intraperitoneal injection) on inflammagen-induced expression of pro-inflammatory factors and microglia activation. The effect of SVHRP (2–20 μg/ml) on neuroinflammation was further investigated in primary brain cell cultures containing microglia as well as the immortalized BV2 microglia culture stimulated with LPS. Real-time quantitative PCR were used to measure mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in hippocampus of animals. Protein levels of TNF-α, iNOS, P65 subunit of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were examined by ELISA or western blot. Microglia morphology in animal hippocampus or cell cultures and cellular distribution of p65 were shown by immunostaining.Results: Morphological study demonstrated that activation of microglia, the main component that mediates the neuroinflammatory process, was inhibited by SVHRP in both LPS mouse and cellular model. Our results also showed dramatic increases in the expression of iNOS and TNF-α in hippocampus of LPS-injected mice, which was significantly attenuated by SVHRP treatment. In vitro results showed that SVHRP attenuated LPS-elicited expression of iNOS and TNF-α in different cultures without cell toxicity, which might be attributed to suppression of NF-κB and MAPK pathways by SVHRP.Conclusion: Our study demonstrates that SVHRP is able to inhibit neuroinflammation and microglia activation, which may underlie the therapeutic effects of BmK-derived materials, suggesting that BmK venom could be a potential source for CNS drug development.

Gastric cancer (GC) is one of the major malignancies worldwide. This study was conducted to explore the mechanism by which GREM2 maintains biological properties of GC stem cells (GCSCs), and proved that GREM2 could potentially regulate the proliferation, apoptosis, invasion, migration and tumorigenic ability of GCSCs through the regulation of the JNK signaling pathway. In silico analysis was utilized to retrieve expression microarray related to GC, and differential analysis was conducted. The cell line with the highest GREM2 expression was overexpressed with GREM2 mimic, silencing GREM2 by siRNA, or treated with activator or inhibitor of the JNK signaling pathway. Subsequently, expression of GREM2, JNK signaling pathway-, apoptosis- or migration and invasion-associated factors were determined. Proliferation, migration, invasion, apoptosis of GCSCs in vitro and tumorigenic ability and lymph node metastasis of GCSCs in vivo were determined. Based on the in silico analysis of GSE49051, GREM2 was determined to be overexpressed in GC and its expression was the highest in the MKN-45 cell line, which was selected for the subsequent experiments. Silencing of GREM2 or inhibition of the JNK signaling pathway suppressed the proliferation, migration and invasion, while promoting apoptosis of GCSCs in vitro as well as inhibiting tumorigenesis and lymph node metastasis in vivo. In conclusion, the aforementioned findings suggest that the silencing of GREM2 suppresses the activation of the JNK signaling pathway, thereby inhibiting tumor progression. Therefore, GREM2-mediated JNK signaling pathway was expected to be a new therapeutic strategy for GC.

Background and Aims: Although autologous bone marrow stem cell (BMSC) transplantation is an effective treatment for liver cirrhosis, there are few reports describing the optimal delivery route and number of injected BMSCs. Methods: A literature search was conducted using PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, and EBSCO. A meta-analysis was performed to assess the effect of BMSCs on liver and coagulation function indices. Subgroup analysis was performed based on number of injected BMSCs, delivery route, and length of follow-up. Results: A total of 15 studies were selected from among 1903 potential studies for analysis. Autologous BMSC transplantation significantly improved aspartate aminotransferase, total bilirubin, albumin, prothrombin time, prothrombin activity, prothrombin concentration, Child-Pugh score, and model for end-stage liver disease. In the subgroup analysis of cell numbers, all four of the indices were significantly improved when the number of BMSCs was >4 × 108. The subgroup analysis referring to the delivery route showed that arterial infusion increased the therapeutic effect over venous infusion. Finally, in the subgroup analysis of follow-up length, the results showed that BMSC therapy significantly improved liver function at 2 weeks after transplantation. In addition, this therapy improved coagulation 4 weeks after the transplant, with a maintenance of efficacy for up to 24 weeks. Conclusions: Autologous BMSC therapy is beneficial for liver improvement and coagulation in patients with liver cirrhosis. The therapeutic effect was generated at 2–4 weeks after transplantation. The effect lasted for 24 weeks but no more than 48 weeks. The greatest benefit to patients was observed with a 4 × 108 autologous BMSC transplant via the hepatic artery.

Paeonol is one of main medicinal ingredients of Cortex Moutan. Paeonol has the functions of sedative, hypnosis, anti-bacterial, antibiosis, anti-inflammation, antioxidation, reducing blood pressure and so on. Paeonol has extensive biological activities and has broad prospects of exploitation and utilization. This paper reviews the latest progress of its pharmacology.

Hawthorn is a traditional Chinese medicine and has the effect of improving digestion and activating circulation to remove blood stasis. The present study indicates that extract of hawthorn leaf has the effects of lipid regulation, anti-myocardial ischemia, anti-atherosclerosis, cardiotonic and so on. Because of comprehensive treatment effects and less side effects, hawthorn leaves is becoming the research hotspot.

Supplemental Digital Content is available in the text, Background: Osteoporotic vertebral compression fractures (OVCFs) constitute an age-related health problem that affects approximately 200 million people worldwide. Currently, various treatments are performed with the goal of reducing pain, stabilizing the vertebrate, and restoring mobility. In this study, we aimed to assess the efficacy and safety of vertebroplasty (VP), kyphoplasty (KP), and conservative treatment (CT) for the treatment of OVCFs. Methods: We performed a network meta-analysis. PubMed and Embase databases were searched to identify randomized controlled trials (RCTs) that contained at least one of the following outcomes: visual analog scale (VAS), Roland–Morris Disability Questionnaire (RDQ), European Quality of Life-5 Dimensions (EQ-5D), and new fractures. Odds ratios with 95% confidence intervals (CIs) were used to calculate the risk of new fractures, and mean differences (MDs) with 95% CIs were utilized to express RDQ, EQ-5D, and VAS outcomes. Results: Sixteen RCTs with 2046 participants were included in this meta-analysis. Compared with CT, patients treated with VP had improved pain relief, daily function, and quality of life; however, no significant differences were found between VP and KP for these 3 outcomes. All treatment options were associated with comparable risk of new fractures. When the rank probability was assessed to distinguish subtle differences between the treatments, VP was the most effective treatment for pain relief, followed by KP and CT; conversely, KP was the most effective in improving daily function and quality of life and decreasing the incidence of new fractures, followed by VP and CT. Conclusion: VP might be the best option when pain relief is the principle aim of therapy, but KP was associated with the lowest risk of new fractures and might offer better outcomes in terms of daily function and quality of life.