The Ameliorative Effects of Saikosaponin in Thioacetamide-Induced Liver Injury and Non-Alcoholic Fatty Liver Disease in Mice.

Liver disorders are a major health concern. Saikosaponin-d (SSd) is an effective active ingredient extracted from Bupleurum falcatum, a traditional Chinese medicinal plant, with anti-inflammatory and antioxidant properties. However, its hepatoprotective properties and underlying mechanisms are unknown. We investigated the effects and underlying mechanisms of SSd treatment for thioacetamide (TAA)-induced liver injury and high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in male C57BL/6 mice. The SSd group showed significantly higher food intake, body weight, and hepatic antioxidative enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) and lower hepatic cyclooxygenase-2 (COX-2), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and fibroblast growth factor-21 (FGF21) compared with controls, as well as reduced expression of inflammation-related genes (nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)) messenger RNA (mRNA). In NAFLD mice, SSd reduced serum ALT, AST, triglycerides, fatty acid-binding protein 4 (FABP4) and sterol regulatory element-binding protein 1 (SREBP1) mRNA, and endoplasmic reticulum (ER)-stress-related proteins (phosphorylated eukaryotic initiation factor 2α subunit (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). SSd has a hepatoprotective effect in liver injury by suppressing inflammatory responses and acting as an antioxidant.

Data Mining-based Analysis of Regularities in Acupoint Prescriptions for Stroke Disorders in Ancient Books / 上海针灸杂志

Objective To summarize regularities in acupoint prescriptions for acupuncture treatment of stroke disorders by using data mining techniques to analyze 150 ancient acupuncture books from the Han dynasty to the end of Qing dynasty. Method A standard database and a ancient book database were established by a manual entry and proofreading method. The sentences containing stroke disorders, acupoints, meridians and needling moxibustion method in the ancient books were selected according to the key words in the standard database using a variety of data mining techniques and a regular relation to establish corresponding disease, acupoint, needling moxibustion method and meridian databases. They were classified into two types: prescriptions for stroke disorders and acupoint indications containing stroke disorders. The results from selection were reviewed manually and standardized. A multilevel analysis of regularities in acupuncture prescriptions for stroke disorders in the ancient books was performed by statistical analysis and apriori algorithm on association rules with support degree and confidence level. Result There were a total of 536 records on acupuncture point prescription for stroke disorders. Single acupoint prescriptions accounted for 34.89% of the total number of prescriptions. The single acupoint that was used most frequently was Baihui(GV20). Thedouble acupoints that were combined most frequently were Quchi(LI11) and Baihui. In three acupoint combination, Quchi and Fengshi(GB31) were separately combined most frequently with Baihui, Jianyu(LI15) and Xuanzhong(GB39). The three meridians that were used most frequently were the Du Meridian, the Large Intestine Meridian of Hand-Yangming and the Gallbladder Meridian of Foot-Shaoyang. The two meridians that were combined most frequently were the Gallbladder Meridian of Foot-Shaoyang and the Stomach Meridian of Foot-Yangming. Crossing points and Five-Shu points were selected most frequently in specific points. He-Sea points were used most frequently in Five-Shu points. Conclusion The prescriptions for stroke disorders in ancient acupuncture books focus on selecting the confluence of all yang meridians and yang meridian points. Specific points are the important composition of the prescriptions. Crossing points and He-Sea points are mainly used in specific points.

A novel role of the tumor suppressor GNMT in cellular defense against DNA damage.

Glycine N-methyltransferase (GNMT) is a folate binding protein commonly diminished in human hepatoma yet its role in tumor development remains to be established. GNMT binds to methylfolate but is also inhibited by it; how such interactions affect human carcinogenesis is unclear. We postulated that GNMT plays a role in folate-dependent methyl group homeostasis and helps maintain genome integrity by promoting nucleotide biosynthesis and DNA repair. To test the hypothesis, GNMT was over-expressed in GNMT-null cell lines cultured in conditions of folate abundance or restriction. The partitioning of folate dependent 1-carbon groups was investigated using stable isotopic tracers and GC/MS. DNA damage was assessed as uracil content in cell models, as well as in Gnmt wildtype (Gnmt(+/+)), heterozygote (Gnmt(+/-)) and knockout (Gnmt(-/-)) mice under folate deplete, replete, or supplementation conditions. Our study demonstrated that GMMT 1) supports methylene-folate dependent pyrimidine synthesis; 2) supports formylfolate dependent purine syntheses; 3) minimizes uracil incorporation into DNA when cells and animals were exposed to folate depletion; 4) translocates into nuclei during prolonged folate depletion. In conclusion, loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. To our best knowledge, the role of GNMT in folate dependent 1-carbon transfer in nucleotide biosynthesis has never been investigated. The present study gives new insights into the underlying mechanism by which GNMT can participate in tumor prevention/suppression in humans.

Risk of ovarian cancer in women with pelvic inflammatory disease: a population-based study.

BACKGROUND: Ovarian cancer is commonly fatal and incidence has persistently risen in Taiwan over the past 20 years. Prevention strategies, however, are limited. Pelvic inflammatory disease (PID) has been suggested to increase the risk of developing ovarian cancer, but the results of studies have been inconsistent. Therefore, we investigated whether PID increases the risk of developing ovarian cancer in a large, nationwide cohort. METHODS: From the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan, we obtained data for women aged 13-65 years for whom a diagnosis of PID, confirmed by multiple episodes, had been recorded between Jan 1, 2004, and Dec 31, 2005. We also obtained data for two controls per patient, matched for age and the year of first entry into the LHID2005. All patients were followed up from the date of entry in the LHID2005 until they developed ovarian cancer or to the end of 2006, whichever was earlier. We used Cox's regression models to assess the risk of developing ovarian cancer, with adjustment for age, comorbid disorders, and socioeconomic characteristics. FINDINGS: We identified 67,936 women with PID and 135,872 controls. Among these 90 had developed ovarian cancer during the 3-year follow-up period (42 patients with PID and 48 controls, incidence 2·78 and 1·44 per 10,000 person-years, respectively). The adjusted hazard ratio for ovarian cancer in patients with PID was 1·92 (95% CI 1·27-2·92) compared with controls, which rose to 2·46 (1·48-4·09) in women who had had at least five episodes of PID. The adjusted hazard ratio was slightly higher for women aged 35 years or younger with PID than in older women with PID (2·23, 1·02-4·79 vs 1·82, 1·10-3·04). INTERPRETATION: We found an association between PID and ovarian cancer. PID might, therefore, be a useful marker for ovarian cancer, and early treatment could help to improve prognosis. Whether pelvic inflammation itself accelerates the growth of ovarian cancers or affects cancer-cell differentiation in ways that adversely alter prognosis needs to be investigated. FUNDING: None.

Ameliorative effects of Vaccaria segetalis extract on osteopenia in ovariectomized rats.

The purpose of this study was to determine the ameliorative effects of a crude extract of Vaccaria segetalis (Neck.) Garcke (Caryophyllaceae) (VSE) on osteopenia in ovariectomized (OVX) rats over 12 weeks. Rats were divided into the sham and OVX groups. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into four groups treated with water, 17beta-estradiol (30 microg/kg, daily subcutaneous injection), or VSE (0.5 or 1.0 g/kg, daily, orally) for 6 weeks. In OVX rats, the increases of serum total cholesterol were significantly decreased by VSE or 17beta-estradiol treatment. There were decreases in bone density and calcium content, including the left femur and the fourth lumbar vertebra, when compared with the sham control rats. Treatment with 17beta-estradiol or VSE ameliorated these changes induced by OVX. In addition, ovariectomy increased urinary deoxypyridinoline (DPD) amounts (P < 0.001). The increases were suppressed by 17beta-estradiol and 0.5 or 1.0 g/kg VSE (P < 0.01, P < 0.05, P < 0.01, respectively). Our results demonstrated that VSE ameliorates ovariectomy-induced osteopenia by inhibition of bone resorption.

Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats.

AIM OF THE STUDY: We investigated the preventive effect of Momordica charantia Linn. (Cucurbitaceae) fruit, commonly known as bitter melon, on hyperglycemia and insulin resistance in rats fed with a fructose-enriched diet. MATERIALS AND METHODS: First, rats were divided randomly into two groups: the control group was fed with control diet, whereas the experimental group was fed with a 60% high-fructose diet for 8 weeks. After the first 6 weeks, the fructose-treated rats were further subdivided into six groups and were orally fed with or without Momordica charantia L. or rosiglitazone (ROS) for 2 weeks while rats were still on fructose diet. RESULTS: We demonstrated that bitter melon was effective in ameliorating the fructose diet-induced hyperglycemia, hyperleptinemia, hyperinsulinemia, and hypertriglyceridemia as well as in decreasing the levels of free fatty acid (FFA) (P<0.001, P<0.05, P<0.05, P<0.05, P<0.05, respectively). Bitter melon reversed fructose diet-induced hypoadiponectinemia (P<0.05), which provides a therapeutic advantage to insulin resistance in improving insulin sensitivity. Additionally, bitter melon decreased the weights of epididymal (P<0.05) and retroperitoneal white adipose tissue (WAT) (P<0.05). Bitter melon increased the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) in white adipose tissue (WAT). Conversely, bitter melon decreased the expression of leptin in WAT. Furthermore, we demonstrate that bitter melon significantly increases the mRNA expression and protein of glucose transporter 4 (GLUT4) in skeletal muscle. CONCLUSIONS: This study demonstrates, for the first time, the beneficial effects of two different extracts of bitter melon on insulin resistance in rats fed a high-fructose diet thereby producing evidence of the role of changes in expression of PPAR gamma and GLUT4.