Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases.

AF6, a known polarity protein, contributes to the maintenance of homeostasis while ensuring tissue architecture, repair, and integrity. Mice that lack AF6 display embryonic lethality owing to cell-cell junction disruption. However, we show AF6 promotes necroptosis via regulating the ubiquitination of RIPK1 by directly interact with the intermediate domain of RIPK1, which was mediated by the deubiquitylase enzyme USP21. Consistently, while injection of mice with an adenovirus providing AF6 overexpression resulted in accelerated TNFα-induced necroptosis-mediated mortality in vivo, we observed that mice with hepatocyte-specific deletion of AF6 prevented hepatocytes from necroptosis and the subsequent inflammatory response in various liver diseases model, including non-alcoholic steatohepatitis (NASH) and the systemic inflammatory response syndrome (SIRS).Together, these data suggest that AF6 represents a novel regulator of RIPK1-RIPK3 dependent necroptotic pathway. Thus, the AF6-RIPK1-USP21 axis are potential therapeutic targets for treatment of various liver injuries and metabolic diseases.

Assessment of efficacy of pinaverium bromide in treatment of irritable bowel syndrome and its effect on visceral motility and sensitivity / 中华消化杂志

Objective To investigate the therapeutic effects of pinaverium bromide on irritable bowel syndrome (IBS), and to study its effect on rectal visceral perception and anorectal manometry. Methods Eighty four patients with IBS received pinaverium bromide 50 mg t.i.d for 2 weeks. The score of symptoms was assessed before, after one week and 2 weeks of threatment. Rectal visceral perception thresholds, rectal compliance and anorectal manometry were measured before and after administration of pinaverium bromide. Results Pinaverium bromide 150 mg/d significantly improved the score of abdominal pain, abdominal distension and mucus stool(2.13?0.36 vs 1.28?0.35,2.49?0.73 vs 1.35?0.17,1.03?0.27 vs 0.43?0.12, P

A study on colonic transit test and ano-manometry in functional constipation and constipation-predominant irritable bowel syndrome / 中华消化杂志

Objective To investigate rectal visceral perception、 anorectal manometry and colonic transit time in functional constipation and constipation-predominant irritable bowel syndrome (IBS) and to assess their variety of manometric abnormalities. Methods The cases with functional constipation and constipation-predominant IBS were studied in a colonic transit test by radiopaque markers. Rectal visceral perception thresholds, rectal compliance and anorectal manometry were examined in patients with functional constipation or constipation-predominant IBS by electric barastat. Results The colonic transit time in both groups of constipation patients was abnormal. A lot of radiopaque markers remined in right colon when patients with constipation-predominant IBS were examined, as the patients with functional constipation in anorectum. The anorectal resting pressure, squeeze pressure and relaxation pressure were similar in both groups. Rectal compliance and defecation thresholds were much higher than normal, and the rectal visceral perception of functional constipation was also abnormal. Conclusion The motility abnormalities between functional constipation and constipation-predominant IBS occure in the different colonic segments. The results suggested that colonic transit test and anorectal manometry might provide a method in differentiatial diagnosis.

Morphological and functional alteration of serotonin-producing intestinal enterochromaffin cells in patients with irritable bowel syndrome / 中华消化杂志

Objective To investigate morphological and synthetic alteration of enterochromaffin(EC) cells of intestinal mucosa in patients with irritable bowel syndrome(IBS). Methods Fifty cases of IBS were classified into diarrhea predominant and constipation predominant in accordance with RomeⅡ criteria. Colon biopsy tissues were stained through Envision immunohistochemistry. Morphological changes of EC cells in intestinal mucosa were also studied by electron microscopy. Results EC cells were seen in the crypt of intestinal mucosa. The shapes and the number of EC cells in diarrhea predominant IBS and constipation predominant IBS increased remarkably, compared with those in controls (15.90 ?5.09, 14.73?2.73 vs. 7.27?2.50). It was shown that EC cells synthesized excessive 5 hydroxytryptamine (5 HT) by immunohistochemistry. The function of EC cells in IBS was active under electron microscopy. Conclusions Active enteral EC cells noticed in IBS indicate that excessive 5 HT may play an important role in the pathogenesis of IBS.

APPLICATION OF DEFECOGRAPHY IN THE DIAGNOSIS OF IRRITABLE BOWEL SYNDROME / 解放军医学杂志

To evaluate the clinical application of defecography in irritable bowel syndrome, 14 cases of diarrhoea predominant IBS, 12 cases of constipation predominant IBS and 10 cases of mixed patterns underwent defecography. Thirteen cases showed abnormal IBS (36 11%). The abnormal X ray features of anorectal angle and pelvic floor descent included rectocele, rectal mucosal prolapse, splanchnoptosis, perineum descent and spastic pelvic floor syndrome. Defecography is valuable in the diagnosis and treatment of irritable bowel syndrome