Potential mechanisms of action of celastrol against rheumatoid arthritis: Transcriptomic and proteomic analysis.

The clinical efficacy for treating of celastrol rheumatoid arthritis (RA) has been well-documented, but its mechanism of action remains unclear. Here we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking. In this paper, expression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

Molecular mechanism of celastrol in the treatment of systemic lupus erythematosus based on network pharmacology and molecular docking technology.

BACKGROUND: Network pharmacology uses bioinformatics to broaden our understanding of drug actions and thereby advance drug discovery. Here we apply network pharmacology to generate testable hypotheses about the multi-target mechanism of celastrol against systemic lupus erythematosus (SLE). METHODS: We reconstructed drug-target pathways and networks to predict the likely protein targets of celastrol and the main interactions between those targets and the drug. Then we validated our predictions of candidate targets by performing docking studies with celastrol. RESULTS: The results suggest that celastrol acts against SLE by regulating the function of several signaling proteins, such as interleukin 10, tumor necrosis factor, and matrix metalloprotein 9, which regulate signaling pathways involving mitogen-activated protein kinase and tumor necrosis factor as well as apoptosis pathways. Celastrol is predicted to affect networks involved mainly in cytokine activity, cytokine receptor binding, receptor ligand activity, receptor regulator activity, and cofactor binding. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of interaction. CONCLUSIONS: This network pharmacology strategy may be useful for discovery of multi-target drugs against complex diseases, specifically, it provides protein targets associated with SLE that may be further tested for therapeutic potential by celastrol.

Treatment of Intestinal Paralysis Using Revised Major Purgative Decoction Combined with Nasointestinal Decompression: Experience with 31 Patients.

To investigate the feasibility of using a revised major purgative decoction in combination with nasointestinal decompression for the treatment of intestinal paralysis. 31 patients with intestinal paralysis underwent gastrointestinal decompression. A fluoroscopic guided tri-lumen nasointestinal decompression tube was placed, and the patients were randomly divided into two groups: patients in the study group (n = 16) received 100 ml of a revised major purgative decoction infused through the decompression tube, three times daily; and patients in the control group (n = 15) were given neostigmine 0.5 mg by muscle injection, twice daily. The clinical presentations and imaging findings both before and after the treatment were recorded and compared. A significant increase in decompression volumes and a rapid reduction in intra-abdominal pressure (IAP) were observed in all patients undergoing nasointestinal decompression (p < 0.05). Patients in the study group achieved significantly earlier restoration of intestinal function by presenting with earlier restoration of bowel sound, earlier passage of flatus and stools (p < 0.05). The deployment of gastrointestinal decompression using a long tri-lumen nasointestinal decompression tube is effective in reducing IAP and relieve abdominal distension, whereas revised major purgative decoction can enhance the recovery of intestinal function. The joint application of these two strategies is effective and safe in the management of intestinal paralysis and is worthy of adoption in clinical settings.

Clinical value of emergent perspective stent implantation for left-side obstructive colonic cancer / 中华消化外科杂志

Objective To investigate the clinical value of emergent perspective stent implantation for leftside obstructive colonic cancer.Methods The clinical data of 26 patients with obstructive colonic cancer who received emergent perspective stent implantation at the Affiliated Xuzhou Hospital of Southeast University from October 2011 to February 2014 were retrospectively analyzed.A soft and a hard guidewire and a catheter were applied in the operation.The guidewires were put through the hole of the intestinal tumor,and then the metal stent and the conveyor were guided by the guidewires and were pulled through the hole of the intestinal tumor,finally the stent was released and the conveyor was adjusted to ensure that the stent was at the right position.Patients were followed-up through outpatient examination till 4 weeks after tumor resection.Results Of the 26 patients,9 were with rectal cancer,10 with sigmoid colonic cancer,6 with descending colonic cancer,1 with splenic flexure cancer.The median length of stenosis was 4.6 cm (range,2.0-8.0 cm).The surgery of the 26 patients was successful.The mean operation time was 35.2 minutes (range,15.2-72.0 minutes),and the mean time of stent implantation was 5.6 minutes (range,2.6-26.9 minutes).Patients had watery or loose stool for 4-8 times after stent implantation.Ten hours after the operation,all the patients were given liquid diet.The remission rate of clinical symptoms was 100.0％ (26/26).No colonic perforation was detected during the operation.Two patients were complicated with slight bleeding,and was alleviated by medication.Twenty-six patients received stage Ⅰ tumor resection procedure within 7-10 days after the symptoms of intestinal obstruction were remised.The success rate of surgery was 100.0％ (26/26).No infection and other drainage were detected after tumor resection through follow-up.Conclusion Emergent perspective stent implantation for left-side obstructive colonic cancer is safe and effective.