Puggaardmark8490

Cardiac hypertrophy (CH) is an enormous risk factor in the process of heart failure development, however, there is still lack of effective treatment for CH. Mitochondrial protection is an effective way against CH. Rheum palmatum L. (rhubarb) has been used to treat chronic heart diseases such as heart failure, especially to inhibit cardiac compensatory enlargement. The aim of this study was to explore the pharmacodynamic component of rhubarb and reveal its pharmacological effects and targets in the treatment of CH. BMS387032 Based on network pharmacology and machine learning approach, ingredients of rhubarb and targets for CH were extracted and surflex docking was conducted for obtaining the optimal ingredient-target combination(s) and emodin-SIRT3 was identified for further functional analysis. Transverse aortic constriction or isoproterenol induced CH mice and phenylephrine injured cardiomyocytes were used to verify the mitochondria protection effect and CH improvement of emodin in vivo and in vitro by modulation of mitochondrial SIRT3 signaling. The results showed that emodin could block agonist-induced and pressure overload-mediated CH. Emodin prevented mitochondrial dysfunction and its underlying mechanism was attributed to the activation of SIRT3, but the effect was not obvious with the presence of SIRT3 inhibitors (3-TYP)/SIRT3 siRNA. Furthermore, PGC-1ɑ was involved in the process of emodin regulating SIRT3 signaling pathway as an upstream target. Our findings clarified the main material basis and mechanism of rhubarb in the treatment of CH. Emodin, as the major ingredient of rhubarb, has therapeutic potential for CH through mitochondrial protection due to the modulation of SIRT3 signaling. Pancreatic cancer is a fatal disease. The five-year survival for patients with all stages of this tumor type is less than 10%, with a majority of patients dying from drug resistant, metastatic disease. Gemcitabine has been a standard of care for the treatment of pancreatic cancer for over 20 years, but as a single agent gemcitabine is not curative. Since the only therapeutic option for the over 80 percent of pancreatic cancer patients ineligible for surgical resection is chemotherapy with or without radiation, the last few decades have seen a significant effort to develop effective therapy for this disease. This review addresses preclinical and clinical efforts to identify agents that target molecular characteristics common to pancreatic tumors and to develop mechanism-based combination approaches to therapy. Some of the most promising combinations include agents that inhibit transcription dependent on BET proteins (BET bromodomain inhibitors) or that inhibit DNA repair mediated by PARP (PARP inhibitors). BACKGROUND & AIMS Studies to evaluate risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection treated with the nucelos(t)ide analogues entecavir or tenofovir have produced contradictory results. These differences are likely to be due to censored data, insufficient observation periods, and different observation periods for patients treated with different drugs. We aimed to compare the incidence of HCC development between patients treated with oral entecavir or tenofovir and followed for the same time periods. METHODS We performed a retrospective study, collecting data from 1560 treatment-naïve patients with chronic HBV infection who were first treated with entecavir (n=753) or tenofovir (n=807) from 2011 through 2015 at 9 academic hospitals in Korea. Clinical outcomes were recorded over a mean time period of 4.7±1.0 y, from 92.4% of patients treated with tenofovir and 92.7% of patients treated with entecavir. RESULTS Thirty-four patients in the entecavir group (4.5%) and 45 patients in the tenofovir group (5.6%) developed HCC during the follow-up period. The incidence of HCC did not differ significantly between groups, even in a 516-pair propensity score-matched population. CONCLUSIONS In a retrospective study of1560 treatment-naïve patients with chronic HBV infection, the incidence of HCC did not differ significantly between patients treated with entecavir vs tenofovir over the same observation period. Clinical trial No. KCT0003487. STUDY OBJECTIVE To describe a new modification of laparoscopic sacrohysteropexy without using mesh and report the three-year outcomes. DESIGN A prospective cohort study. SETTING Minimally Invasive Gynecology Unit, Bursa Uludag University Hospital, Turkey PATIENTS Women who were diagnosed as stage 2 or more uterine prolapse. INTERVENTION A laparoscopic sacrohysteropexy modification using polyester fiber suture instead of standard polypropylene mesh. MEASUREMENTS AND MAIN RESULTS The primary outcome was the anatomic success of the repair, with success defined as objective parameters using the POP quantification (POP-Q) system. Secondary outcomes were subjective outcomes, which were assessed by the quality of life scales. Forty-seven women who underwent the procedure followed up to a minimum of three years. 44 of 47 patients had stage 0 or 1 prolapse at the end of the second year, according to the primary outcomes. The anatomical success rate was 93.6%. In secondary outcomes, two patients were not satisfied with their pelvic floor after the second year. The subjective cure rate was 95.7%. There was a statistically significant improvement in both POP-Q scores and quality of life scores in the third postoperative year. The mean operating time was 84.6 minutes, and the mean estimated blood loss was 21.3 milliliters. There were no bladder or bowel complications in the perioperative or postoperative period. CONCLUSIONS Laparoscopic sacrohysteropexy can be performed safely with this meshless modification in uterine prolapse as an alternative. ETHNOPHARMACOLOGICAL RELEVANCE Thalictrum foliolosum DC (Ranunculaceae) is a perennial flowering herb traditionally used as a tonic, antiperiodic, diuretic, febrifuge, purgative and stomachic and for the treatment of snakebite, jaundice, and rheumatism. AIM OF THE STUDY To provide a critical assessment of the state-of-the-art related to the traditional uses, phytochemistry, and pharmacology of T. foliolosum with the ultimate objective of providing further research strategies to facilitate the exploitation of the therapeutic potential of T. foliolosum for the treatment of human disorders. MATERIALS AND METHODS Exhaustive bibliographic research related to T. foliolosum plant was carried out using scientific research engines and databases such as Google Scholar, PubMed, Web of Science covering all retrieved relevant manuscripts written in English. RESULTS Several alkaloids such as berberine, jatrorrhizine, palmatine, thalrugosidine, thalrugosaminine, thalisopine (thaligosine), thalirugidine, thalirugine, 8-oxyberberine (berlambine), noroxyhydrastinine, N,O,O-trimethylsparsiflorine, thalicarpine, thalidasine, thalfoliolosumines A and thalfoliolosumines B were reported from T.