Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is currently the surgical treatment of choice for medically refractory ulcerative colitis (UC), as well as for patients with familial adenomatous polyposis (FAP) . Although the ileal pouch serves as a reservoir for the stool and improves functional outcomes , pouchitis, an inflammation of this conduit, is a common complication in patients undergoing surgery for UC, and was reported to occur in approximately 50% of patients . Symptoms of pouchitis include diarrhea, increased stool frequency, abdominal cramping, fecal urgency, tenesmus, and incontinence . The pathogenesis of pouchitis remains incompletely understood but might be caused by altered mucosal metabolism , ischemia , bid acid cytotoxicity , recurrence of UC, and genetic susceptibility . IL-1 receptor antagonist (IL-1 RA) and TNF are involved in the regulation of epithelial physiology and defense, suggesting mucosal barrier function may have a pathogenic role in pouchitis .
TWP is a traditional Chinese medicine extracted from the roots of Tripterygium wilfordii Hook F. (TWhF), and was reported to be therapeutically efficacious in the treatment of autoimmune and inflammation-related diseases such as rheumatoid arthritis, ulcerative colitis, and Crohn's disease , . Triptolide is the major active component of TWP  and it is superior to placebo in inducing remission and preventing clinical postoperative recurrence in inflammatory bowel disease (IBD) patients . WU et al. reported that triptolide reduced intestinal permeability and protected the intestinal mucosal barrier function by inhibiting TNF-α–induced tight junction protein changes in epithelial cells . Therefore, TWP has attracted increasing attention and is widely used for clinical treatment both in China and worldwide .
However, the therapeutic effect of TWP on pouchitis remains rarely reported. The purpose of this study was to investigate whether TWP ameliorates pouchitis in a DSS-model of rats and to determine its potential mechanism of action.
Rabbit anti-occludin (bs-10011R) and rabbit anti-Zo-1 (PB0072) were purchased from BIOS (Beijing Bioengineering Company, China), and SABC kit (SA1022), and DAB kit (AR1022) were purchased from Boster (Wuhan Boster Bioengineering Company, China). Dextran sulfate sodium was purchased from MP Biomedicals (molecular weight 36,000–50,000 MP Biomedicals, Soho, OH, USA).
Male Sprague-Dawley (Laboratory Animal Center of Military Medical Science Academy of the PLA in Chinese people's Liberation Army,
General signs of pouchitis in rats
The pouchitis model in rats was successfully established. At day 35, there were no significant differences in the body weight of rats among the groups. As shown in Fig. 1, the weight of rats in the NI and NS groups continued to decline at 7days after the DSS intervention. The weight of rats in the TWP group was reduced initially, but at day 4 after TWP lavage, it began to increase (P<0.05) (Fig. 1). During the intervention of TWP and NS, weight loss in the TWP group (10.17±4.17) was
TWP, a Chinese herbal medicine derived from Tripterygium genus, has been widely used for the treatment of rheumatoid arthritis, skin disorders, CD, and other inflammatory diseases , , . The most important active component of TWP is triptolide (T10), which has anti-inflammatory effects in various experimental models by inhibiting the production of immune and inflammatory factors such as nitric oxide (NO) and nuclear factor kappa B (NFκB) . Wang reported a preventative effect of
Conflict of interest
This research was supported by the intestinal barrier research foundation of academician Jieshou Li (LJS_201008).
Recommended articles (6)
Simple fundoplication versus additional vagotomy and pyloroplasty in neurologically impaired children — a single centre experience
Journal of Pediatric Surgery, Volume 50, Issue 2, 2015, pp. 275-279
Gastrooesophageal reflux disease (GERD) is a significant problem in children with neurological impairment (NI) with high failure rates for fundoplication. Fundoplication with vagotomy and pyloroplasty (FVP) can improve the outcome by altering the sensory or motor dysfunction associated with the reflux. We report our comparative outcomes for simple fundoplication (SF) and FVP in NI children.
Case records of all patients having fundoplication under a single consultant at a tertiary UK paediatric surgical centre between January 1997 and December 2012 were retrospectively assessed for recurrent symptoms and redo surgery. The data were collected using a Microsoft Excel database and analysed on Graphpad prism software program. Data are median (range). P value <0.05 was considered significant.
Data were available for 244 out of 275 patients who underwent fundoplication during this period (157 SF and 87 FVP). Neurological disease or known syndromes were recorded in 158 patients. Thirty-five children had congenital anatomical abnormalities. Laparoscopic fundoplication was done in 37 cases. Revisional surgery for recurrent symptoms was performed in 22 patients. In the neurologically normal children, all of whom had SF, the revision rate was 6.5%. In the NI children the revision rates were 18.5% for SF and 3.9% for FVP, respectively (Fisher’s exact, P<0.05). The median time to redo surgery was 10 (1–63) months, and the median time to follow up was 19.5 (2–177) months.
There appears to be a significantly lower need for redo surgery following FVP than SF in children with NI.
Effect of donor STAT4 polymorphism rs7574865 on clinical outcomes of pediatric acute leukemia patients after hematopoietic stem cell transplant
International Immunopharmacology, Volume 43, 2017, pp. 62-69
STAT4 polymorphism, rs7574865 is linked to various autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Its T minor allele is associated with higher STAT4 mRNA and protein expression, indicating a stronger skewed immune response than the norm. Although widely studied in autoimmune disease patients and the general population, its effect on immunocompromised subjects is still unknown. Especially in situations, i.e. post-hematopoietic stem cell transplantation (post-HSCT), where control of the immune response is crucial. Hence, this study investigates if the presence of the T minor allele in donors would affect immunological response and clinical outcomes post-HSCT. Samples from 161 pediatric patients who underwent allogeneic HSCT for acute leukemia and showed complete chimerism by donor cells were obtained. Six clinical outcomes were investigated; hepatic veno-occlusive disease, acute graft-vs-host disease, chronic graft-vs-host disease, cytomegalovirus (CMV) infection, relapse and overall survival. The TT genotype was found to be significant in the occurrence of CMV infection (P=0.049), showing higher incidence of CMV infection compared to the others. Multivariate analysis confirmed that association of the TT genotype is independent from other variables in CMV infection occurrence (P=0.010). This is the first study on STAT4 polymorphism rs7574865 in allogeneic HSCT as well as immunocompromised patients. As the TT genotype is associated with autoimmune diseases, our results seem at a paradox with current evidence hinting at a different role of STAT4 in normal circumstances versus immunocompromised patients. Further investigation is needed to elicit the reason behind this and discover novel applications for better post-transplant outcomes.
CD14++ CD16− monocytes are the main source of 11β-HSD type 1 after IL-4 stimulation
International Immunopharmacology, Volume 43, 2017, pp. 156-163
The anti-inflammatory actions of IL-4 are well established through earlier findings. However, the exact mechanism it uses to downregulate the pro-inflammatory cytokine production through monocytes and macrophages is poorly understood. In this study, we examined the effect of IL-4 in the induction of 11β-HSD1 in the two main classes of monocytes, CD14++ CD16− (CD14) and CD14+ CD16+ (CD16). Peripheral Blood Mononuclear Cells (PBMCs) were isolated from 17 healthy donors and were sorted into CD14 and CD16 subpopulations using cell sorting. Effect of IL-4 on 11β-HSD1-enzyme activity was measured in sorted and unsorted monocytes using Homogeneous Time-Resolved Fluorescence (HTRF) and M1/M2 polarization analysis was performed by flow cytometry. Our results indicate that CD14 cells are the major source of 11β-HSD1 enzyme after IL-4 stimulation and that M2 phenotype is not a pre-requisite for its synthesis.
Phenylphenalenone glycosides: Occurrence, structure revision, and substituent effects on the steric orientation
Phytochemistry Letters, Volume 21, 2017, pp. 104-108
Glycosides and acyl glycosides of phenylphenalenones, phenylbenzoisochromenones, and structurally related natural products from plants are compiled. With the exception of one naphthalic anhydride glucoside from the Musaceae, all glycosides are chemotaxonomic markers of the Haemodoraceae, subfamily Haemodoroideae. NMR spectroscopic data indicate that in 6-O-glycosides of phenylphenalenones and phenylbenzoisochromenones, the substituents at C-5 and C-7 impede rotation of the interjacent sugar moiety at C-6. Furthermore, the structure of the acyl substituent at the C-6” hydroxyl group of some glucosides, previously reported as an allophanyl unit, in this review has been revised to a malonyl unit.
Evolutionary significance of exine ultrastructure in the subfamily Barnadesioideae (Asteraceae) in the light of molecular phylogenetics
Review of Palaeobotany and Palynology, Volume 221, 2015, pp. 32-46
Barnadesioideae (94 species) is the sister subfamily to the rest of the Asteraceae (23,000 species). Pollen grains in this subfamily are structurally and sculpturally distinctive and diverse. Although pollen morphology has contributed to the taxonomy of the subfamily, there is a gap of knowledge concerning the evolution of the exine structure. This study aims at exploring the systematic and phylogenetic significance of optimizing selected pollen characters of Barnadesioideae on the latest molecular phylogenetic tree. Transmission electron microscope (TEM) observations on pollen of selected species, some of them never explored so far, show that the exine probably evolved from a thin pattern (ca. 1–3μm), with a well-developed foot layer and solid and free columellae, present in sister family Calyceraceae, towards a thicker (>6–11μm) and a more complex columellate-granulate bilayered exine in Barnadesioideae (with very delicate columellae). The particular exine structure observed in the monotypic Schlechtendalia luzulaefolia, which combines compact and independent columellae (common in more derived Asteraceae) with a granular internal tectum as the inner ectexine layer (as in Barnadesioideae), reinforces its distant phylogenetic position within Barnadesioideae. More derived lineages within Asteraceae (e.g. Mutisioideae) retained some ancestral exine features although evolved an even thicker exine and a columellate trilayered exine (with robust columellae), rare in the angiosperm pollen grains.
Joint Bone Spine, Volume 81, Issue 1, 2014, p. 90
© 2016 Published by Elsevier B.V.