Long noncoding RNAs have been implicated in neuropathy. Here, we identify and validate a long noncoding RNA, MRAK009713, as the primary regulator of neuropathic pain in chronic constriction injury (CCI) rats. MRAK009713 expression was markedly increased in CCI rats associated with enhanced pain behaviors, and small interfering RNA against MRAK009713 significantly reduced both mechanical and thermal hyperalgesia in the CCI rats. MRAK009713 is predicted to interact with the nociceptive P2X3 receptor by CatRAPID, a bioinformatics technology. Overexpression of MRAK009713 markedly increased expression of P2X3 in the dorsal root ganglia of the control rats, and MRAK009713 small interfering RNA significantly inhibited the P2X3 expression in the dorsal root ganglia of the CCI rats. MRAK009713 directly interacted with the P2X3 protein heterologously expressed in the human embryonic kidney (HEK) 293 cells and potentiated P2X3 receptor function. Thus, MRAK009713 is a novel positive regulator of neuropathic pain in rats through regulating the expression and function of the P2X3 receptor.

No abstract

Gastrectomy has been widely used for the treatment of gastric cancer, and the severity of physiological and microbial disorders has greatly harmed the health of patients. In the present study, a probiotic combination containing Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis and Bacillus cereus was used to reduce the physiological disorders induced by gastrectomy via monitoring the blood index and microbial diversity using high-throughput sequencing. Our results indicated that the probiotic combination had significantly reduced the inflammation indexes (leukocyte) (p<0.05), while it markedly enhanced the immunity indexes (lymphocyte) and nutrition indexes (albumin and total protein) (p<0.05). In addition, gastric cancer had a strong influence on the microbial diversity of the stomach via enhancing the number of pathogens of Streptococcus, Peptostreptococcus and Prevotella, and reducing the percentage of the probiotic Bifidobacterium. Although partial gastrectomy markedly changed intestinal microbial diversity, the taking of the probiotic combination greatly reduced the ratio of Firmicutes/Bacteroidetes compared with patients taking no probiotics at the phylum level. At the genus level, the probiotic combination significantly enhanced the numbers of the probiotic bacteria Bacteroides, Faecalibacterium and Akkermansia and lowered the richness of Streptococcus. Therefore, we concluded that the taking of the probiotic combination significantly enhances the immune response of patients and reduces the severity of inflammation through modification of gut microbiota.

P2X receptors participate in cardiovascular regulation and disease. After myocardial ischemic injury, sensorysympathetic coupling between rat cervical DRG nerves and superior cervical ganglia (SCG) facilitated sympathoexcitatory action via P2X 7 receptor. The results showed that after myocardial ischemic injury, the systolic blood pressure, heart rate, serum cardiac enzymes, IL-6, and TNF-α were increased, while the levels of P2X 7 mRNA and protein in SCG were also upregulated. However, these alterations diminished after treatment of myocardial ischemic (MI) rats with the P2X 7 antagonist oxATP. After siRNA P2X 7 in MI rats, the systolic blood pressure, heart rate, serum cardiac enzymes, the expression levels of the satellite glial cell (SGC) or P2X 7 were significantly lower than those in MI group. The phosphorylation of ERK 1/2 in SCG participated in the molecular mechanism of the sympathoexcitatory action induced by the myocardial ischemic injury. Retrograde tracing test revealed the sprouting of CGRP or SP sensory nerves (the markers of sensory afferent fibers) from DRG to SCG neurons. The upregulated P2X 7 receptor promoted the activation of SGCs in SCG, resulting in the formation of sensory-sympathetic coupling which facilitated the sympathoexcitatory action. P2X 7 antagonist oxATP could inhibit the activation of SGCs and interrupt the formation of sensory-sympathetic coupling in SCG after the myocardial ischemic injury. Our findings may benefit the treatment of coronary heart disease and other cardiovascular diseases.

No abstract