Taurine Regulates the Expression of Interleukin -17/10 and Intestinal Flora and Protects the Liver and Intestinal Mucosa in a Nonalcoholic Fatty Liver Disease Rat Model.

Purpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.

Design, synthesis, and biological evaluation of diosgenin-indole derivatives as dual-functional agents for the treatment of Alzheimer's disease.

The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against H2O2 (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aß (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by H2O2 (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aß1-42 (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aß1-42 was -40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aß1-42. The predicted values of brain/blood partition coefficient (-0.733) and polar surface area (85.118 Å2) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by H2O2. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aß-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.

Circulating Hematopoietic Stem/Progenitor Cells are Associated with Coronary Stenoses in Patients with Coronary Heart Disease.

Inflammatory cells in atherosclerotic plaque exclusively originate from hematopoietic stem/progenitor cells (HSPCs). In this study, we investigated whether circulating HSPCs frequency related to coronary stenosis in patients with coronary heart disease (CHD). Coronary angiography was performed in 468 participants who were recruited at Cardiology Centre in LuHe Hospital from March 2016 to May 2017. Among these subjects, 344 underwent echocardiography. Mononuclear cells isolated from peripheral blood were stained with an antibody cocktail containing anti-human CD34, anti-human lineage, anti-human CD38, and anti-human CD45RA. Lineage-CD38-CD45RAdimCD34+HSPCs were quantified by flow cytometry. CHD was defined as coronary stenosis ≥50% and the extent of CHD was further categorised by coronary stenosis ≥70%. A p < 0.0031 was regarded statistically significant by the Bonferroni correction. Circulating HSPCs frequency was 1.8-fold higher in CHD patients than non-CHD participants (p = 0.047). Multivariate-adjusted logistic analysis demonstrated that HSPCs was the only marker that was associated with the odds ratio of having mild vs. severe coronary stenosis (2.08 (95% CI, 1.35-3.21), p = 0.0009). Left ventricular ejection fraction was inversely correlated with HSPCs frequency and CRP in CHD patients (p < 0.05 for both). In conclusion, HSPCs frequency in circulation is intimately related to coronary stenoses in CHD patients.

[Clinical study on silicone pessary in the treatment of pelvic organ prolapse].

OBJECTIVE: To evaluate the therapeutic effect and influence factors of silicone pessary in treatment of pelvic organ prolapse (POP). METHODS: From October 2005 to October 2010, 132 with symptomatic POP managed by pessary were enrolled in this retrospective study. Validated prolapse quality of life questionnaire (pelvic floor distress inventory short form 20, PFDI-20), pelvic floor impact questionnaire short form 7 (PFIQ-7) and the patients' satisfaction degree were used to evaluate the therapeutic effect. Clinical characteristic of the patients with successful using for more than 6 months (successful fitting group), giving up within 6 months (giving up group), unsuccessful fitting (unsuccessful fitting group) were compared. Factors influencing satisfaction degree and causing discontinuation were investigated. RESULTS: One hundred and six among 132 (106/132, 80.3%) patients were in successful fitting group, 26 (26/132, 19.7%) patients were in the unsuccessful fitting group. In the successful fitting group, 86.8% (92/106) patients were followed up, the median follow-up time was 12.5 months. And 78.3% (72/92) patients continued to use pessary with the wearing time ranged 3 - 69 months; 21.7% (20/92) patients discontinued with the wearing time ranged 1 - 38 month, 14 patients (14/20) gave up in the initial 6 months. The median scores of PFDI-20 and PFIQ-7 questionnaires before pessary use were 50.0 and 47.6, which decreased to 8.9 and 0.0 after pessary use (P < 0.05). And 87.1% (61/70) patients were satisfied. There was no significantly difference among 3 groups on clinical characteristics, such as age, body mass index (BMI), pelvic surgery and so on (P > 0.05). The main factor influencing satisfaction degree and causing discontinuation was difficulties in placing and removing. CONCLUSIONS: Silicone pessary is effective for patients with POP. It could relieve discomfort symptoms and improve quality of life. The main factor influencing pessary use is difficulties in placing and removing. Thus, More suggestions are needed for patients in the initial 6 months.

[Analysis of mesh related complications after trans-vaginal mesh-augmented pelvic floor reconstruction surgery].

OBJECTIVE: To evaluate the complications after trans-vaginal mesh-augmented pelvic floor reconstruction in treatment of pelvic organ prolapse (POP). METHODS: From February 2007 to October 2009, vaginal mesh procedures were performed on 91 women with POP stage III-IV in Peking University Third Hospital. The operative complications were studied. RESULTS: Ninety patients underwent successful surgery among 91 patients. Follow-up rate was 94% (85/90) at a median follow-up of 28.4 (15 - 44) months. One patient underwent intraoperative organ injuries, and 10 patients had postoperation mesh-related complications. The rate of mesh-related complications was 2% (2/85), 2% (2/85), 4% (3/85), 4% (3/85) on 6, 6 - 12, 12 - 24 and more than 24 months following up, respectively. Seven patients underwent conservative treatment and the symptoms were improved. Three patients underwent the second surgery, and the symptoms were cured or relieved. CONCLUSION: The incidence of mesh-related complications was low, and interventions were effective in vaginal mesh procedure.

[Study on mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapse].

OBJECTIVE: To evaluate clinical outcome and complications of mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapse. METHODS: From Feb 2007 to Jan 2009, mesh-augmented vaginal reconstructive surgery were performed on 66 women with pelvic organ prolapse stage III-IV. Pre and postoperative symptoms, pelvic organ prolapse quantitation (POP-Q) stage and pelvic floor distress inventory-short form 20 (PFDI-20) measurements were studied to assess anatomic and quality-of-life outcome. Operative complications were also analyzed. RESULTS: Totally 65 patients underwent successful surgeries. The rate of follow-up was 97% (63/65) with a median follow-up of 17.2 months. Subjective cure rate and objective cure rate were both 97% (61/63) at 6 and 12 months after surgeries, 51 women completed PFDI-20 measurements and scores were 102 ± 50 before surgery, 16 ± 21 at 6 months and 15 ± 20 at 12 months. It reached statistical difference when scores were compared before and after surgeries (P < 0.05). Among 66 patients, 2 patients underwent organ injuries, 2 had recurrent prolapse, 4 had mesh-related complications and 1 had severe de novo stress urinary incontinence. Six patients underwent second surgery. CONCLUSIONS: Mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapsed brought satisfied clinical outcome. The incidence of mesh-related complications was low and secondary operative interventions were effective.

[Internal Ribosomal Entry Site-Mediated Expression of Human Multidrug Resistance 1 Gene in Human CD34(+) Cells]

In order to reach the purpose of co-transferring double drug resistance genes into human CD34(+) progenitor cells to broaden the spectrum of drug resistance, the expression efficiency of human multidrug resistance 1 (MDR1) gene mediated by the internal ribosomal entry site (IRES) was investigated. Two retroviral vectors were transferred into packaging cells. One is pSF-DIM containing double drug resistance genes, in which the translation of MDR1 gene was controlled under an IRES from encephalomyocarditis virus. The other is pSF-MDR1 which only contains MDR1 gene controlled under the same promoter of pSF-DIM. The amphotropic retroviral packaging cells PA317/pSF-DIM and PA317/pSF-MDR1 were obtained with titer of 8 x 10(4) and 1.3 x 10(5) cfu/ml respectively. Human cord blood CD34(+) cells were transduced by supernatant infection. Expression of P-gp was detected by flow cytometry. Compared with the untransduced group, the expression of P-gp in pSF-DIM transduced group and pSF-MDR1 transduced group was elevated 10.92% and 28.82% respectively. However, the expression of P-gp in pSF-MDR1 transduced group was higher than that in pSF-DIM transduced group. The result suggests that MDR1 gene can express in the human progenitor cells under control of IRES. It laid the foundation of subsequence research. The reason on the difference in MDR1 gene expression efficiency between pSF-MDR1 transduced group and pSF-DIM transduced group need further research.