Min Zhi

Effect of silybin on high-fat-induced fatty liver in rats

Silybin, a natural antioxidant, has been traditionally used against a variety of liver ailments. To investigate its effect and the underlying mechanisms of action on non-alcoholic fatty liver in rats, we used 60 4-6-week-old male Sprague-Dawley rats to establish fatty liver models by feeding a high-fat diet for 6 weeks. Hepatic enzyme, serum lipid levels, oxidative production, mitochondrial membrane fluidity, homeostasis model assessment-insulin resistance index (HOMA-IR), gene and protein expression of adiponectin, and resistin were evaluated by biochemical, reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Compared with the model group, silybin treatment (26.25 mg·kg(-1)·day(-1), started at the beginning of the protocol) significantly protected against high-fat-induced fatty liver by stabilizing mitochondrial membrane fluidity, reducing serum content of alanine aminotransferase (ALT) from 450 to 304 U/L, decreasing hepatic malondialdehyde (MDA) from 1.24 to 0.93 nmol/mg protein, but increasing superoxide dismutase (SOD) and glutathione (GSH) levels from 8.03 to 9.31 U/mg protein and from 3.65 to 4.52 nmol/mg protein, respectively. Moreover, silybin enhanced the gene and protein expression of adiponectin from 215.95 to 552.40, but inhibited that of resistin from 0.118 to 0.018. Compared to rosiglitazone (0.5 mg·kg(-1)·day(-1), started at the beginning of the protocol), silybin was effective in stabilizing mitochondrial membrane fluidity, reducing SOD as well as ALT, and regulating gene and protein expression of adiponectin (P < 0.05). These results suggest that mitochondrial membrane stabilization, oxidative stress inhibition, as well as improved insulin resistance, may be the essential mechanisms for the hepatoprotective effect of silybin on non-alcoholic fatty liver disease in rats. Silybin was more effective than rosiglitazone in terms of maintaining mitochondrial membrane fluidity and reducing oxidative stress.

Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg-1·day-1 silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.

Decreased Expression of the FOXO3a Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma Patients

Background FOXO3a, a member of the forkhead class ‘O’ (FOXO) transcription factor family, controls a wide spectrum of biological processes, such as DNA damage repair, apoptosis, and cell cycle regulation. FOXO3a has been shown to be a tumor suppressor in various cancers. This study investigated the expression of FOXO3a in primary gastric adenocarcinomas and its prognostic value for primary gastric adenocarcinoma patients. Methods Real-time quantitative RT-PCR (qRT-PCR), western blotting, and immunohistochemical staining were used to detect FOXO3a expression in primary gastric cancerous surgical specimens and adjacent non-tumorous tissues. Results Our data showed that the expression of FOXO3a mRNA (p = 0.03) and protein (p = 0.019) was lower in cancerous tissues compared with their adjacent non-tumorous tissues. In addition, the chi-square test revealed that low FOXO3a expression was significantly correlated with larger tumor size (p = 0.007), poor histopathological classification (p = 0.029), depth of invasion (p = 0.049), local lymph node metastasis (p = 0.013), distant metastasis (p = 0.013) and AJCC staging (p<0.001). Kaplan-Meier survival analysis demonstrated that low expression of FOXO3a was significantly correlated with a poor prognosis for gastric cancer patients (p<0.001). The multivariate analysis showed that FOXO3a expression was an independent prognostic factor of the overall survival rate of patients with primary gastric adenocarcinoma. Conclusion Our study suggested that decreased FOXO3a expression may play an important role in the progression of gastric cancer. FOXO3a could be a valuable prognostic marker as well as a potential molecular therapy target for gastric cancer patients.

Plateletcrit: A sensitive biomarker for evaluating disease activity in Crohn's disease with low hs‐CRP

This study aimed to investigate whether PLT indices could act as non‐invasive biomarkers for active Crohns disease (CD).

Body Mass Index Is a Marker of Nutrition Preparation Sufficiency Before Surgery for Crohn's Disease From the Perspective of Intra-Abdominal Septic Complications: A Retrospective Cohort Study.

AbstractPoor preoperative nutritional status for individuals with Crohns disease (CD) is associated with intra-abdominal septic complications (IASCs). The present study aimed to investigate the association of the common nutrition indices serum albumin and body mass index (BMI) with IASCs. Sixty-four CD patients who had received elective intestinal operations were retrospectively investigated. Among these patients, 32 had received individualized fortified nutrition support. IASCs occurred in 7 patients (10.9%). Compared with non-IASC patients, IASC patients had a lower BMI (17.6 ± 2.7 vs 15.6 ± 1.3 kg/m2, P = 0.048). The area under the receiver operating characteristic curve according to the BMI-based IASC prediction was 0.772 (95% confidence interval [CI], 0.601–0.944; P = 0.020) with an optimum diagnostic cutoff value of 16.2 kg/m2. A BMI < 16.2 kg/m2 significantly increased the risk of developing an IASC (odds ratio [OR], 10.286; 95% CI, 1.158–91.386). Even after correction with the simplified CD activity index (CDAI), a low BMI level remained associated with IASCs (OR, 7.650; 95% CI, 0.808–72.427; P = 0.076). Serum albumin was not associated with IASCs. Although the fortified nutrition support group had an albumin level comparable to the control group, this group had a higher simplified CDAI score, a lower BMI level, and a comparable incidence rate of IASCs. Thus, BMI more accurately reflects the basic preoperative nutritional status of CD patients than serum albumin. BMI can aid in guiding preoperative nutrition support and judging the appropriate operation time for CD.

Efficacy of exclusive enteral nutrition in complicated Crohn’s disease

Abstract Aim: To investigate the efficacy of exclusive enteral nutrition (EEN) in induction of remission in adult active Crohn’s disease (CD) complicated with intestinal fistula/abdominal abscess or inflammatory intestinal stricture. Method: Patients diagnosed with active CD with complications were recruited between July 2013 and July 2015. Patients were offered EEN for 12 weeks. Patients with abscess received antibiotic treatment with or without percutaneous drainage. Clinical variables were recorded (ClinicalTrials.gov Identifier: NCT02887287). Results: Forty-one patients with CD and with intestinal fistula/abdominal abscess or inflammatory intestinal stricture aged 18–60 years, were included. Ten patients were accompanied with stenosis and 33 with intestinal fistula/abscess. After 12 weeks of EEN, the Crohns disease activity index significantly decreased (223.43 ± 65.5 vs. 106.77 ± 42.73, p ≤ .001), and 80.5% of patients achieved full clinical remission totally. Fistula closure after EEN was observed in 75% of patients with entero-cutaneous fistula. In patients with stenosis, 20% had no response to EEN and were transferred for surgery. Partial remission and full remission were observed in 20% and 60% of patients after 12 weeks of EEN, respectively. Intra-abdominal abscess resolved in 76% of patients. Seventeen patients who had mucosal ulcers underwent colonoscopy before and after EEN, 47% achieved mucosal healing after the treatment. The inflammatory index of patients significantly decreased (p ≤ .01), nutritional parameters increased (p ≤ .01) and the European Nutritional Risk Screening (2002) decreased (p ≤ .01). Conclusion: EEN is effective in inducing early clinical remission, mucosal healing, promoting fistula closure and reducing the size of abscess in adult CD patients with complications.

Inhibition of the interleukin-23/interleukin-17 pathway by anti-interleukin-23p19 monoclonal antibody attenuates 2,4,6-trinitrobenzene sulfonic acid-induced Crohn's disease in rats.

The interleukin (IL)-23/IL-17 pathway is considered to be important in the pathogenesis of Crohns disease (CD). The present study aimed to evaluate the effects of targeting the IL‑23/IL‑17 pathway using the anti-IL-23p19 monoclonal antibody (mAb) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD rats. A total of 60 Sprague-Dawley rats were randomly divided into a control group, model group and an anti-IL-23p19 mAb treatment group (administered intramuscularly every week at a dose of 1 ml/mg). Disease activity index (DAI), colon macroscopic damage index (CMDI) and tissue damage index (TDI) were then evaluated. The mRNA expression of IL-23p19, p40 (IL-23/12), retinoic acid-related orphan receptor-γt (ROR‑γt) and IL‑17 in colonic tissues were detected by reverse transcription‑polymerase chain reaction and levels of serum IL-23p19, p40, ROR-γt and IL-17 were measured using an enzyme‑linked immunosorbent assay. Anti‑IL‑23p19 mAb was found to effectively attenuate colonic inflammation demonstrated by reduced DAI, CMDI and TDI scores, improvement in pathological evaluation and downregulation of expression levels of IL‑23p19, p40 (IL-23/12), ROR-γt and the downstream proinflammatory cytokine, IL-17. Anti-IL-23p19 mAb attenuated TNBS-induced CD in model rats. The possible underlying mechanisms may be associated with inhibition of the IL-23/IL-17 pathway by inhibiting the expression of IL‑23p19 and downregulating the downstream proinflammatory cytokine IL‑17. Targeting the IL-23/IL-17 pathway may be a relevant and realistic therapeutic approach for the development of additive and alternative treatments to the biologics currently available in the treatment of CD.

A Survey of Pregnancy Outcomes for Women of Childbearing Age with Inflammatory Bowel Disease in South China

Purpose: Women of childbearing age with inflammatory bowel disease (IBD) in South China were studied to understand the effects of IBD on pregnancy outcomes. Materials and Methods: One hundred thirty-nine women treated at two large IBD centers participated. Pregnancy outcome data were collected by telephone interviews. Results: Ninety patients (90/139; 64.7%) did not pursue pregnancy after IBD diagnosis because of concerns regarding adverse effects. Fifteen Crohn’s disease (CD) and 12 ulcerative colitis (UC) patients pursued pregnancy and achieved successful conception. Twenty-five patients were treated with drugs before pregnancy; however, 15 (15/25; 60%) discontinued the use of all drugs 3 months before pregnancy. The other 10 patients continued mesalazine and one continued azathioprine during pregnancy. Four CD and five UC patients had mild disease at conception; the others were in remission. Two CD patients and one UC patient experienced mild disease relapse during pregnancy. They refused all drugs except mesalazine. One UC patient with mild disease during pregnancy had pregnancy-induced hypertension. All newborns were healthy. There was no difference between pregnancy outcomes of CD and UC patients (P > 0.05). No relationship was found between disease activity and pregnancy outcomes (P > 0.05). Patients with active disease during pregnancy tended to choose cesarean delivery, especially in CD patients with active disease (P = 0.028). Conclusion: Many female IBD patients may not pursue pregnancy because of concerns regarding adverse effects on the pregnancy. Patients were more willing to conceive during disease remission. Some refused all IBD medications except mesalazine. Relapse was uncommon or mild during pregnancy. Disease activity had an obvious effect on the delivery mode of CD patients.

Thalidomide results in diminished ovarian reserve in reproductive age female Ibd patients

Abstract The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function. Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016. Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P < 0.05), and both groups were higher than control group 33.3%, P < 0.05. Anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) in group A were lower than group B, P < 0.05, while estradiol (E2) and follicle-stimulating hormone (FSH) levels were no different between 2 groups. Crohn Disease Endoscopic Index of Severity (CDEIS) and thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P < 0.05), but they may recover after stopping (P < 0.05). Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping.

Methotrexate for Refractory Crohn's Disease Compared with Thiopurines: A Retrospective Non-head-to-head Controlled Study

Background: This study assessed the efficacy and safety of methotrexate (MTX) compared with thiopurines (TPs) for refractory Crohns disease. Methods: Fifty-one consecutive patients who were refractory or intolerant to TPs and steroid-dependent were retrospectively analyzed. MTX (20 mg/wk, subcutaneous) was adopted for inducing and maintaining clinical remission (CR). Fifty-seven patients who were naive to immunosuppressant and prescribed azathioprine (2 mg·kg−1·d−1) or mercaptopurine (1 mg·kg−1·d−1) were simultaneously recruited. Results: By week 16, the CR rate was 68.6% and 78.9% in the MTX and TPs groups, respectively (P = 0.222). Patients with disease duration ⩽3 years were more likely to achieve CR with MTX (odds ratio = 7.667, P = 0.019). By week 64, the CR rate of patients achieved remission at week 16 was 45.7% and 44.4% in the MTX and TPs groups, respectively (P = 0.910). Normalization of high-sensitivity C-reactive protein level (relative risk = 11.221, P = 0.003) and platelet count (relative risk = 9.672, P = 0.004) at week 16 predicted the efficacy of maintaining remission with MTX. Among patients with remission at week 16, the mucosal healing rates at week 36 were 47.4% with MTX and 47.1% with TPs (P ≈ 1.000). Fifteen (29.4%) patients on MTX and 25 (43.9%) on TPs experienced adverse events (P = 0.121). Conclusions: MTX is effective in inducing and maintaining CR and achieving mucosal healing in patients with refractory Crohns disease, and its efficacy is comparable to that of TPs for naive patients. The side effects of MTX were mild and tolerable.