BDNF Contributes to Spinal Long-Term Potentiation and Mechanical Hypersensitivity Via Fyn-Mediated Phosphorylation of NMDA Receptor GluN2B Subunit at Tyrosine 1472 in Rats Following Spinal Nerve Ligation.

Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) contributes to spinal long-term potentiation (LTP) and pain hypersensitivity through activation of GluN2B-containing N-methyl-D-aspartate (GluN2B-NMDA) receptors in rats following spinal nerve ligation (SNL). However, the molecular mechanisms by which BDNF impacts upon GluN2B-NMDA receptors and spinal LTP still remain unclear. In this study, we first documented that Fyn kinase-mediated phosphorylation of GluN2B subunit at tyrosine 1472 (pGluN2BY1472) was involved in BDNF-induced spinal LTP and pain hypersensitivity in intact rats. Second, we revealed a co-localization of Fyn and GluN2B-NMDA receptor in cultured dorsal horn neurons, implying that Fyn is a possible intermediate kinase linking BDNF/TrkB signaling with GluN2B-NMDA receptors in the spinal dorsal horn. Furthermore, we discovered that both SNL surgery and intrathecal active Fyn could induce an increased expression of dorsal horn pGluN2BY1472, as well as pain hypersensitivity in response to von Frey filaments stimuli; and more importantly, all these actions were effectively abrogated by pre-treatment with either PP2 or ifenprodil to respectively inhibit Fyn kinase and GluN2B-NMDA receptors activity. Moreover, we found that intrathecal administration of BDNF scavenger TrkB-Fc prior to SNL surgery, could prevent the nerve injury-induced increase of both pFynY420 and pGluN2BY1472 expression, and also inhibit the mechanical allodynia in neuropathic rats. Collectively, these results suggest that Fyn kinase-mediated pGluN2BY1472 is critical for BDNF-induced spinal LTP and pain hypersensitivity in SNL rats. Therefore, the BDNF-Fyn-GluN2B signaling cascade in the spinal dorsal horn may constitute a key mechanism underlying central sensitization and neuropathic pain development after peripheral nerve injury.

Palladium-catalyzed cyclocarbonylation of arynes with methyl allyl carbonates: selective synthesis of 1H-inden-1-ones.

A selective protocol for the synthesis of 2-methylene-3-substituted-2,3-dihydro-1H-inden-1-ones and 2-benzylidene-2,3-dihydro-1H-inden-1-ones has been developed via palladium-catalyzed cyclocarbonylation reactions of arynes with allyl carbonates and carbon monooxide (CO). It is noteworthy that the selectivity of this new route is depended on both substrates and ligands.

Study on the mechanisms of "Xiaoerhuashi Pill, XP" in intervening the health status of high-calorie diet animals.

ETHNOPHARMACOLOGICAL RELEVANCE: "Xiaoerhuashi Pill, XP", with a history of 30 years in China, was included in the first part of the 2015 edition of the Chinese Pharmacopoeia and is widely used in the treatment for pediatric diseases in clinical application. Its main indications include the accumulation of heat caused by food stagnation in children, which has the effect of digestive stagnation and purge heat to relax the bowels. AIM OF THE STUDY: High-calorie diet, closely related to the occurrence and development of multiple diseases, is an unhealthy status of life. However, there is no effective intervention in clinic. Thus, based on animal experiments and bioinformatics, this study aims to explore the potential mechanisms of action of Chinese patent medicine- "Xiaoerhuashi Pill, XP" in the intervention of high-calorie diet. MATERIALS AND METHODS: A high-calorie diet model was prepared by 3-week-old rats. The defecation and intestinal mucosal morphology were observed after intragastric administration of "Xiaoerhuashi Pill, XP". The components of "Xiaoerhuashi Pill, XP" were obtained by chromatography-mass spectrometry, with the corresponding targets obtained by database and target fishing. The key effects substances were obtained by molecular docking, with the obtaining of the ore pathway of "Xiaoerhuashi Pill, XP" in intervention of high-calorie diet based on the enrichment analysis. RESULTS: "Xiaoerhuashi Pill, XP" can actively interfere with defecation and intestinal mucosal structures in high-calorie diet animals. A total of 37 substances were identified in the pediatric digestion solution, and 356 target proteins were mapped, 25 of which were associated with a high-calorie diet. Overall, the analysis shows that the highest degree of integration was quercetin and PON1 protein, with the highest enrichment of insulin resistance pathway. CONCLUSION: "Xiaoerhuashi Pill, XP" can intervene in the health status of high-calorie diet animals. Integration of quercetin and PON1 protein can regulate lipid levels, which may be the key mechanisms of action in "Xiaoerhuashi Pill, XP". The mechanisms, more specifically, may be related to the regulation of pancreas islet function, thus providing a reference for the clinical application of "Xiaoerhuashi Pill, XP", clinical intervention of high-calorie diet and new drug development.

[Professor Dong Gui-rong's experiences in treatment of child cerebral palsy].

According to the characteristics of the etiology and pathogenesis of child cerebral palsy, on the basis of "regulating the mind in treatment of all kinds of diseases" and "regulating the functions of five zang organs with back-shu points", Professor DONG Gui-rong applied the penetrating needling technique on the scalp points and acupuncture at back-shu points of five zang organs in the treatment of child cerebral palsy. The valuable clinical experiences have been summarized as "regulating the mind with scalp needling technique, benefiting the brain and opening the orifice", "regulating five zang organs with back-shu points" and "integration of acupuncture and rehabilitation, and function reconstruction". Two effective cases were introduced.