Electroacupuncture Regulates TRPV1 through PAR2/PKC Pathway to Alleviate Visceral Hypersensitivity in FD Rats

Visceral hypersensitivity (VH) is the predominant pathogenesis of functional dyspepsia (FD). Duodenal hypersensitivity along with nausea further reduces the comfort level in gastric balloon dilatation and inhibits gastric receptive relaxation. The potential mechanism behind electroacupuncture- (EA-) mediated alleviation of VH has not been elucidated. In an FD rat model with tail clamping stress, iodine acetamide (IA) induced VH. The rats were treated with EA with or without PAR2 antagonist FSLLRY-NH2, and the body weight, gastric sensitivity, compliance, and gastrointestinal motility were determined. Mast cells and activated degranulation were stained with toluidine blue (TB) staining and visualized under a transmission electron microscope (TEM). Immunofluorescence was used to detect the expression of PAR2, PKC, and TRPV1 in the duodenum and dorsal root ganglion (DRG) and that of CGRP, SP in DRG, and c-fos in the spinal cord. EA alone and EA + antagonist enhanced the gastrointestinal motility but diminished the expression of TRPV1, CGRP, SP, and c-fos-downstream of PAR2/PKC pathway and alleviated VH in FD rats. However, there was no obvious superposition effect between the antagonists and EA + antagonists. The effect of EA alone was better than that of antagonists and EA + antagonists 2 alone. EA-induced amelioration of VH in FD rats was mediated by TRPV1 regulation through PAR2/PKC pathway. This protective mechanism involved several pathways and included several targets.

SPINK1-induced amelioration of impaired autophagy contributes to suppression of trypsinogen activation in a model of acute pancreatitis

SPINK1 has been regarded as a reversible trypsinogen inhibitor for the inappropriate activation of trypsin, a key step in the initiation of acute pancreatitis (AP). However, the mechanisms of its action remains largely unclear and controversial. Here, we reported an unexpected effects of SPINK1 on inhibiting trypsinogen activation through the regulation of impaired autophagy in cerulein-stimulated AR42J cells, a well-established in vitro model of acute pancreatitis. Firstly, we found that the impaired autophagic flux was induced and trypsinogen activity enhanced in the above setting. Then, we showed that SPINK1 overexpression could inhibit the level of increased autophagic activity, improving the hindered autophagy flux, and significantly decreased the trypsinogen activity, whereas shRNA-caused downregulation of SPINK1 exacerbated the impairment of autophagic flux and trypsin activity, in the same cerulein-processed cells. More importantly, the trypsinogen activation in this model could be ameliorated by 3-Methyladenine(3-MA), an autophagy inhibitor. Thus, this study revealed, possibly for the first time, that SPINK1 greatly blocked the trypsinogen activation possibly through the modulation of impaired autophagy in cerulein-induced in vitro model of acute pancreatitis.

Stillverhalten von Frauen mit rheumatoider Arthritis

Die Weltgesundheitsorganisation empfiehlt, dass Säuglinge bis zum Alter von 6 Monaten ausschließlich gestillt werden. Im Rahmen der prospektiven PARA-Studie (Pregnancy-induced Amelioration of Rheumatoid Arthritis) wurde die Häufigkeit des Stillens und der Zeitpunkt der Beendigung zwischen Frauen mit rheumatoider Arthritis (RA) und der Allgemeinbevölkerung verglichen und Gründen gesucht, warum RA-Patientinnen mit dem Stillen aufhören.