Brain-derived neurotrophic factor (BDNF), a critical modulator in the neurodevelopment and maintenance of both central and peripheral nervous systems, is regarded as a potential therapeutic target of Parkinson's disease (PD). However, its association with PD remains unclear and the data are inconsistent. To explore the correlation, studies reporting BDNF levels in PD patients and healthy controls are searched and a sample of 1496 participants are pooled in the meta-analysis, demonstrating significantly decreased serum levels of BDNF in PD patients when compared with the healthy controls (SMD = -1.03; 95% CI [-1.83, -0.23]; P = .012). Meta-regression analysis indicates gender is an important confounding factor (Adj R2 = 69.20%, p = .004, I2 res = 90.64%), whereas age (Adj R2 = 11.91%, P = .95, I2 res = 96.86%), H-Y stages of PD progression (Adj R2 = -30.18%, P = .612, I2 res = 96.62%) and MoCA score assessed cognitive impairment (Adj R2 = 2.18%, P = .517, I2 res = 64.41%) show few moderating effects. The research provides evidence of moderate quality that blood levels of BDNF are decreased in PD patients despite various influencing factors, supporting an association between decreased level of peripheral BDNF and PD.

Na_v1. 9 voltage-gated sodium channel is preferentially expressed in peripheral nociceptive neurons. Recent progresses have proved its role in pain sensation, but our understanding of Na_v1.9, in general, has lagged behind because of limitations in heterologous expression in mammal cells. In this work, functional expression of human Na_v1.9 (hNa_v1.9) was achieved by fusing GFP to the C-terminal of hNa_v1.9 in ND7/23 cells, which has been proved to be a reliable method to the electrophysiological and pharmacological studies of hNa_v1.9. By using the hNa_v1.9 expression system, we investigated the electrophysiological properties of four mutations of hNa_v1.9 (K419N, A582T, A842P, and F1689L), whose electrophysiological functions have not been determined yet. The four mutations significantly caused positive shift of the steady-state fast inactivation and therefore increased hNa_v1.9 activity, consistent with the phenotype of painful peripheral neuropathy. Meanwhile, the effects of inflammatory mediators on hNa_v1.9 were also investigated. Impressively, histamine was found for the first time to enhance hNa_v1.9 activity, indicating its vital role in hNa_v1.9 modulating inflammatory pain. Taken together, our research provided a useful platform for hNa_v1.9 studies and new insight into mechanism of hNa_v1.9 linking to pain.

To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

μ-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.