Abstract Lipopolysaccharide (LPS) causes an inflammatory response, and α-mangostin (α-MG) is an ingredient of a Chinese herbal medicine with anti-inflammatory effects. We investigated the mechanism by which α-MG reduces LPS-stimulated IEC-6 cells inflammation. A genome-wide examination of control, LPS-stimulated, and α-MG-pretreated cells was performed with the Illumina Hiseq sequencing platform, and gene expression was verified with quantitative real-time PCR (qPCR). Among the 37,199 genes profiled, 2014 genes were regulated in the LPS group, and 475 genes were regulated in the α-MG group. GO enrichment and KEGG pathway analyses of the differentially expressed genes (DEGs) showed that they were mainly related to inflammation and oxidative stress. Based on the transcriptomic results, we constructed a rat model of inflammatory bowel disease (IBD) with LPS and investigated the effects of α-MG on NLRP3 inflammasomes. After LPS stimulation, the rat intestinal villi were significantly detached, with congestion and hemorrhage; the intestinal epithelial cell nuclei were deformed; and the mitochondria were swollen. However, after pretreatment with α-MG, the intestinal villus congestion and hemorrhage were reduced, the epithelial nuclei were rounded, and the mitochondrial morphology was intact. qPCR and western blotting were used to detect NLRP3, caspase 1, interleukin (IL)-18, and IL-1β expression at the gene and protein levels. Their expression increased at both the transcript and protein levels after LPS stimulation, whereas it decreased after pretreatment with α-MG. This study provides new methods and ideas for the treatment of inflammation. α-MG may have utility as a drug for intestinal inflammation.
Objective
To explore the clinical efficacy and safety of colorectal stents combined with laparoscopic radical surgery for left colon cancer with intestinal obstruction.
Methods
A retrospective analysis of ninety patients with radical resection of left colon cancer with intestinal obstruction from January 2012 to December 2016 in Jiangmen Central Hospital was carried out. Patients were divided into two groups according to the treatment method: combined treatment group (33 cases, received early enteric stent implantational sequence with first-stage laparocopic resection and anastomosis) and simple operation group (57 cases, underwent emergency operation). Clinical success rates, safety, and surgical outcomes were compared between two groups.
Results
In the combined treatment group, 3 cases failed to place the stent through the stenosis. No patient had stent implantation related perforation, stent displacement, bleeding or postoperative intestinal perforation. The technical success rate and clinical success rate were both 90.9% (30/33). Laparoscopic radical resection was performed in 30 cases 3-5 d after stenting without prophylactic intestinal stoma. The average operation time of the combined treatment group and the simple operation group was (274.6±58.4) min and (294.3±54.2) min, with no statistically significant difference (t=1.569, P=0.120). The amount of bleeding in the combined treatment group was significantly lower than that of the simple operation group [(35.4±20.4) ml vs (135.5±26.9) ml, t=17.84, P<0.001]. No patient died during the perioperative period. There were no significant differences in overall complications, infectious complications, and non-infectious complications between the two groups.
Conclusion
As a pre-operative bridge for laparoscopic radical surgery, the application of colorectal stents in left colon cancer with intestinal obstruction is safe and effective, with acceptable complication rate, similar clinical short-term outcome, and preventive enterostomy is avoided.
Key words:
Colonic neoplasms; Intestinal obstruction; Stents; Laparoscopes
Abstract Heat stress (HS) and secondary restricted blood flow to the intestines cause dysfunction of the intestinal epithelial barrier. Tight junctions (TJs) are essential to maintain intestinal integrity. l -Arginine has beneficial effects on gut functions. However, the underlying mechanisms remain largely unknown. This study tested the hypothesis that l -arginine regulates the TJ network by activating AMP-activated protein kinase (AMPK) signaling, which in turn improves intestinal barrier functions under HS. IEC-6 cells and rat small intestines were used as experiment models of heat stress. AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively. Cell proliferation, apoptosis, differential gene expression and KEGG pathway analysis, intestinal paracellular permeability, intestinal morphology, and expression of HSP and TJ proteins, and p-AMPK were determined. l -Arginine promoted cell proliferation and reduced apoptosis after heat exposure at an optimal concentration of 5 mmol. Transcriptome sequencing analysis revealed that differentially expressed genes associated with the HSP family and TJs were elevated by l -arginine. According to KEGG pathway analysis, l -arginine activated the AMPK signaling pathway. In vivo, intestinal damage resulted in obvious morphological changes as well as apoptosis with TUNEL and caspase-3 staining under HS and dorsomorphin treatments. Furthermore, HS and dorsomorphin increased the serum D-lactate concentration, diamine oxidase activity, and mRNA expression level of MLCK ( P < 0.05). In contrast, l -arginine and AICAR treatments reduced intestinal injury, maintained intestinal permeability, and increased the villus/crypt ratio under hyperthermia. l -Arginine had the same effect as AICAR both in vitro and in vivo, namely increasing p-AMPK protein expression. l -Arginine and AICAR also upregulated the mRNA expression level of HSP70 and HSP90, and downregulated mRNA expression of MLCK ( P < 0.05). The protein expression levels of TJ proteins ZO-1 and claudin-1 were suppressed by heat stroke and dorsomorphin, but enhanced by l -arginine and AICAR. Our findings indicate that activation of AMPK signaling by l -arginine is associated with improved intestinal mucosal barrier functions by enhancing the expression of TJs in rat small intestines and IEC-6 cells during HS.
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