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Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism. CD animal models were created using Il-10−/− mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed. The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10−/− mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10−/− mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10−/− mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10−/- mice, and transplantation of feces from AA-treated mice improved CD-like colitis. The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: There are no appropriate variables for predicting postoperative morbidity in Crohn's disease (CD) patients with severe malnutrition. We examined a retrospective cohort to clarify these. Materials and Methods: Between 2005 and 2013, 138 CD patients with severe malnutrition underwent elective intestinal resection after preoperative management, consisting of nutritional support, abscess drainage, intravenous antibiotics, steroids tapering, and infliximab weaning, as appropriate. The severity of postoperative morbidity (within the first 30 days) was examined according to the Clavien-Dindo classification system. Results: After a median duration of 26 days of preoperative management, Crohn's disease activity index (CDAI) and C-reactive protein (CRP) significantly decreased, and body mass index (BMI), skeletal muscle percentage (SMP), body fat percentage (BFP), albumin, prealbumin, and hemoglobin significantly increased ( P < 0.001). Postoperative overall morbidities occurred in 28 (20.3 %) patients including 15 (10.8 %) major complications (Clavien-Dindo classification ≥ III). In the multivariate logistic regression analysis, preoperative CRP ( P = 0.044, OR 1.156, 95 % CI 1.004-1.331) was a significantly independent risk factor for overall complications, and preoperative SMP ( P = 0.002, OR 0.487, 95 % CI 0.307-0.772) and BFP ( P = 0.036, OR 0.691, 95 % CI 0.490-0.996) were significantly independent protective factors. Notably, only preoperative SMP ( P = 0.002, OR 0.588, 95 % CI 0.422-0.820) was a significantly independent protective factor for major complications, and our threshold of SMP was 24.3 % ( P < 0.001, sensitivity 83.7 %, specificity 95.9 %). Conclusions: Preoperative SMP is a protective factor for postoperative overall and major complications in CD patients with severe malnutrition and deserves further study. [ABSTRACT FROM AUTHOR]

Mesenteric adipose tissue hypertrophy is unique to Crohn's disease while the molecular basis of the crosstalk between MAT and the intestinal inflammation is largely unknown. Telmisartan is an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-receptor-γ agonist which has beneficial effects on fat distribution and pro-inflammatory adipokine expression. We evaluated the effect of telmisartan upon mesenteric adipose tissue alterations and inflammatory features in IL-10 − / − mice. We found that treatment with telmisartan significantly ameliorated the severity of colitis in IL-10 − / − mice. Additionally, administration of telmisartan was associated with restoration of mesenteric adipose tissue adipocyte morphology and the expression of adipokines. Furthermore, telmisartan treatment suppressed the neurotensin/microRNA-155 pathway in mesenteric adipose tissue from spontaneous colitis which was confirmed by an in vitro study using cultured mesenteric adipose tissue from Crohn's disease patients. Administration of telmisartan showed promising results in spontaneous colitis which was associated with the attenuated mesenteric adipose tissue alteration which at least in part, was associated with its activity in the regulation of the neurotensin/microRNA-155 pathway. These results support the hypothesis that regulating the abnormal immune response in adipose tissue is an important target for the treatment of Crohn's disease. [ABSTRACT FROM AUTHOR]

Background Tripterygium wilfordii Hook. f. (TwHF) has been used for many years to induce the remission of Crohn's disease in China. Aims To compare TwHF versus azathioprine for the prevention of postoperative recurrence in Crohn's disease. Methods 90 Crohn's disease patients who had undergone resection were treated with TwHF 1.5 mg/kg/day or azathioprine 2.0 mg/kg/day. The primary endpoint was clinical recurrence, and the secondary endpoint was endoscopic recurrence. Results 47 patients completed the trial. Clinical recurrence was observed in 6/45 patients in the TwHF group and 4/45 patients in the azathioprine group at week 26 ( P = 0.74). At week 52, 8/45 azathioprine patients and 12/45 TwHF patients had clinical recurrence ( P = 0.45). During the first 26 weeks, 56.8% of the patients in the TwHF group versus 47.7% in the azathioprine group experienced endoscopic recurrence ( P = 0.52). However, at week 52, 74.4% of patients in the TwHF group and 50% in the azathioprine group had endoscopic recurrence ( P = 0.03). Conclusions TwHF was less effective in maintaining endoscopic remission at week 52, even though TwHF was comparable to azathioprine for preventing postoperative clinical recurrence. [ABSTRACT FROM AUTHOR]

Background: Data on risk factors of postoperative recurrence in patients with Crohn's disease (CD) have shown conflicting results. The aim of this retrospective study is to identify predictors of early symptomatic recurrence of CD after surgical intestinal resection in the Chinese population. Materials and Methods: Patients diagnosed as CD who underwent intestinal resection in Jinling Hospital between May 2004 and December 2010 were included in our study. Clinical data of these patients were reviewed. Multivariable survival analysis was performed to elucidate risk factors of early postoperative symptomatic recurrence. Results: There were a total of 141 CD patients who had at least one previous curative resection for CD under regular follow-up in our unit. Our data indicated disease behavior (95 % CI 1.01-1.70, P = 0.044), smoking habits (95 % CI 1.32-2.84, P = 0.001), indication of perforation (95 % CI 1.09-4.02, P = 0.026), and location of anastomosis (95 % CI 1.09-3.39, P = 0.023) which are, as a result, strong independent predictors of symptomatic recurrence, while the anastomosis type as side-to-side anastomosis (SSA) was significantly associated with a decreased risk of symptomatic recurrence when compared with other anastomosis type (95 % CI 0.26-0.94, P = 0.038). Medical prophylaxes also played a role in the prevention of postoperative symptomatic recurrence. Conclusions: A smoking habits and perforation indication for surgery at the time of resection are associated with an increased risk of symptomatic recurrence. Anastomosis type with SSA is associated with a reduced risk of symptomatic recurrence. This population-based study supports the concept that environmental factors, disease character, and surgical technique influence the risk of postoperative symptomatic recurrence of CD. [ABSTRACT FROM AUTHOR]

Both mesenteric adipose tissue (MAT) and lymphatic vessels (LVs) play important roles in the pathogenesis of Crohn’s disease (CD), and adipokines have been implicated in the crosstalk between MAT and LVs. Apelin, a newly identified adipokine, has been demonstrated to be crucial in the development and stabilization of LVs. We aimed to identify the expression of apelin in MAT of CD patients and explore whether apelin influences the disease course in murine colitis and determine its contributions to LVs. Expression of apelin in MAT specimens from patients with CD (n = 24) and without CD (control, n = 12) was detected. Il-10 deficient ( Il-10 −/− ) mice with established colitis were administered apelin, and untreated and wild-type mice served as controls (n = 8 for each group). Disease activity and colonic inflammation was evaluated. The LV density, lymphatic drainage function and related signaling pathways were also analyzed. We found that MAT from CD patients expressed a higher level of apelin compared with that from controls. Systemic delivery of apelin significantly ameliorated chronic colitis in Il-10 −/− mice, demonstrated by decreased disease activity index and inflammatory scores, and lower levels of Tnf-α , Il-1β and Il-6 . Increased LV density and podoplanin levels indicated that apelin promoted lymphangiogenesis. Evans blue dye and fluorescent lymphangiography revealed an enhanced lymphatic drainage function in apelin-treated mice. The role of apelin was found to be related to the activation of the Akt and Erk signaling pathways. These results indicate that the adipokine apelin was highly expressed in MAT of CD patients and has a promising role in ameliorating experimental colitis by promoting intestinal lymphatic functions, suggesting the potential crosstalk between adipokines and LVs in MAT in CD status. Therapies with adipokines, such as apelin, may be a novel approach for the treatment of CD. [ABSTRACT FROM AUTHOR]

[Display omitted] Microchromosome maintenance protein 7 (MCM7), a DNA replication permitting factor, plays an essential role in initiating DNA replication. MCM7 is reported to be involved in tumor formation and progression, whereas the expression profile and molecular function of MCM7 in colorectal cancer (CRC) remain unknown. In this study, we aimed to evaluate the clinical significance and biological function of MCM7 in CRC and investigated whether MCM7 can be used for a differential diagnosis in CRC and whether it may serve as a more sensitive proliferation marker for CRC evaluation. Moreover, immunohistochemical analysis of MCM7 was performed in a total of 89 specimens, and high MCM7 expression levels were associated with worse overall survival (OS) in CRC patients. Furthermore, the cell functional test suggested that lentivirus-mediated silencing of MCM7 with shRNA in CRC cells significantly inhibited cellular proliferation and promoted apoptosis in vitro and inhibited tumor growth in vivo. Additionally, mechanistic studies further demonstrated that P21-activated protein kinase 2 (PAK2) was regulated by MCM7 via microarray analysis and cell functional recovery tests, and miR-107 played a role in regulating expression MCM7 via miRNA microarray analysis and 3'UTR reporter assays. Taken together, our results suggest that the miR-107/MCM7/PAK2 pathway may participate in cancer progression and that MCM7 may serve as a prognostic biomarker in CRC [ABSTRACT FROM AUTHOR]

Clematichinenoside AR (AR) is a saponin extracted for traditional Chinese medicine with the effects of improving the expression of tight junction (TJ) proteins and mediating anti-inflammatory activities. However, its effect on Crohn's disease (CD) is still unknown. We aimed to investigate the impact of AR on CD-like colitis and determine the mechanism underlying its effects. Interleukin-10 gene knockout (Il-10 −/−) mice (male, fifteen weeks old) with spontaneous colitis were allocated to the positive control and AR-treated (32 mg/kg AR administered every other day by gavage for 4 weeks) groups. Wild-type (WT) mice (male, fifteen weeks old) composed the negative control group. The effects of AR on intestinal barrier function and structure and T cell responses as well as the potential mechanisms underlying these effects were investigated. AR treatment significantly improved spontaneous colitis in Il-10 −/− mice as demonstrated by reductions in the inflammatory score, disease activity index (DAI) and levels of inflammatory factors. The effects of AR on colitis in Il-10 −/− mice were related to protecting intestinal barrier function and maintaining immune system homeostasis (regulatory T cell (Treg)/T helper 17 (Th17) cell balance). The anticolitis effect of AR may partly act by downregulating PI3K/Akt signaling. AR may have therapeutic potential for treating CD in humans. [ABSTRACT FROM AUTHOR]