Mitofusin2 Promotes ß Cell Maturation from Mouse Embryonic Stem Cells via Sirt3/Idh2 Activation.

ß cell dysfunction is the leading cause of diabetes. Adult ß cells have matured glucose-stimulated insulin secretion (GSIS), whereas fetal and neonatal ß cells are insensitive to glucose and are functionally immature. However, how ß cells mature and acquire robust GSIS is not fully understood. Here, we explored the potential regulatory proteins of ß cell maturation process and the capacity for GSIS. Combined with the data from public databases, we found that the gene expression of Mitofusin2 (Mfn2) showed an increasing trend from mouse neonatal ß cells to mature ß cells. Moreover, its protein expression increased during mouse embryonic pancreas development and ß cell differentiation from mouse embryonic stem cells. Knocking down Mfn2 reduced Urocortin3 (Ucn3) expression, GSIS, and ATP production in induced ß cells, while overexpressing it had the opposite effect. However, neither Mfn2 knockdown nor overexpression affected the differentiation rate of insulin-positive cells. In immature and mature ß cells, Mfn2 and its correlated genes were enriched in tricarboxylic acid (TCA) cycle-related pathways. The expressions of Sirtuin 3 (Sirt3) and isocitrate dehydrogenase 2 (NADP+) and mitochondrial (Idh2) were Mfn2-regulated during ß cell differentiation. Inhibiting Idh2 or Sirt3 reduced cellular ATP content and insulin secretion levels that increased by Mfn2 overexpression. Thus, Mfn2 modulated the induced ß cell GSIS by influencing the TCA cycle through Sirt3/Idh2 activation. We demonstrated that Mfn2 promoted embryonic stem cell-derived ß cell maturation via the Sirt3/Idh2 pathway, providing new insights into ß cell development. Our data contribute to understanding diabetes pathogenesis and offer potential new targets for ß cell regeneration therapies.

3D printing hydrogel with graphene oxide is functional in cartilage protection by influencing the signal pathway of Rank/Rankl/OPG.

3Dprinting is defined as the use of printing technology to deposit living cells, and biomaterials on a given /a substrate. Graphene oxide nanoparticles (GO-np) have been used as a delivery vehicle for small molecule drugs in order to investigate the state of GO-np within 3D tissue constructs in terms of a composite 3D printing scaffold, which in turn is relevant to the protection of cartilage. We transplanted rats with hydrogel/GO-np and hydrogel, which in turn showed that hydrogel/GO-np protected the tissue of cartilage by the signal pathway of Rank/Rankl/OPG. Those findings indicated that GO-np may be potentially used to control the release of carrier materials and influence the signal pathway of Rank/Rankl/OPG.

Systematic Review of the Efficacy of Fluconazole in the Treatment of Candida Infections in Different Parts / 中国药房

OBJECTIVE:To systematically review the efficacy of fluconazole in the treatment of candida infections in different parts,and provide evidence-based reference. METHODS:Cochrane library,Medline,EMBase,PubMed,CBM,CJFD,VIP data-base and Wanfang database were retrieved to collect the randomized controlled trial(RCT)of fluconazole(test group)vs. other an-tifungal agents(control group)in the treatment of candida infections in different parts. After information collection and quality eval-uation,the Meta-analysis was performed by Rev Man 5.1 software. RESULTS:There were totally 6 literatures included,involving 1 966 patients. Meta-analysis results showed that the effectiveness in test group was lower than control group in the treatment of can-didemia [OR=0.48,95%CI(0.29,0.77),P=0.003];compared with control group,there were no significant differences in the effec-tiveness in the treatment of esophagus candidemia [OR=1.15,95%CI(0.74,1.78),P=0.52]. CONCLUSIONS:The efficacy of flu-conazole in the treatment of candidemia is no better than anidulafungin and equivalent with amphotericin B;the efficacy of flucon-azole in the treatment of esophageal candidiasis is equivalent with itraconazole,voriconazole,anidulafungin and micafungin. Due to the limit of included studies,it remains to be further verified by high-quality,large-sample and long follow-up RCTs.

Comparison of post-operative short-term and long-term outcomes between occult and frank biliary rupture of hydatid disease.

BACKGROUND/AIMS: Intrabiliary rupture (IBR) is the most common and serious complication of hepatic hydatid cyst (HHC). The aim of this retrospective study was to evaluate postoperative short-term and long-term outcome of patients treated surgically for complicated liver hydatid cysts. METHODOLOGY: A total of 168 cases with biliary communication of hydatid cyst were analyzed retrospectively, 92 of which had biliary communication with an occult rupture while 76 (45.23%) had Frank biliary rupture. Preoperative demography, ultrasonic cyst features, postoperative short-term complications, postoperative follow-up (long-term) complications and hospital stay were recorded and analyzed. RESULTS: There were no differences in the demographic characteristics and preoperative cyst features in Frank and occult group. Compared with the Frank group 9.34 +/- 1.25 (days), the postoperative stay in occult 6.97 +/- 1.62 (days) were relatively shorter. The incidence of overall postoperative short-term complications and long-term complications were insignificantly lower in occult group (22.82%) than Frank group (30.26%) with P = 0.275. Incidence of postoperative biliary leakage 8 (8.69%) and abscess 5 (5.43%) in occult group was insignificantly more common than Frank rupture with biliary leakage 5 (6.5%) and abscess 2 (2.63%) with P value was 0.609 and 0.365 respectively while long-term biliary stricture is significantly greater in Frank group (10.52%) then occult group (0%) with P = 0.01. CONCLUSIONS: Frequency of occurrence of postoperative short-term complications biliary fistula and abscess is relatively more common in occult rupture with transcystic drain due to its indolent course, inability to find and suture the rupture orifice, and incomplete decompression while biliary stricture is significantly more common in Frank group due to its involvement of major bile ducts.

Acute Toxicity Test and Diuresis Effect of Esculentoside A / 医药导报

Objective To understand the intensity and characteristics of acute toxicity of esculentoside A on mice and measure relevant parameters and observe its diuresis effect on rat. Methods After intraperitoneal injection of different concentrations of esculentoside A to mice, toxic reactions were observed. Rats with water load were intraperitoneally injected with different doses of esculentoside A. Total urine volume in six consecutive hours after the injection was determined. Results The LD50 of esculentoside A calculated by Bliss method was 26. 19 mg · kg-1 , and the 95% confidence interval was 23. 11-29. 85 mg·kg-1 . The mortality and acute toxicity of esculentoside A appeared to be dose-dependent while the blank control group had no abnormal reaction. The urine volume was significantly different between high dose group and the negative control group. No significant difference in urine volume was found between middle and the negative control group, and between low dose group and the negative control group. Conclusion Esculentoside A is poisonous to mice when single dose was intraperitoneally injected, and high dose of esculentoside A has diuresis effect on rat.

Analysis and Comparison on Essential Oil of Rhizome Atractylodes Before and After Processing / 世界科学技术-中医药现代化

This study was aimed to analyze changes of content and quantity of essential oil of processing drugs of Rhizome Atractylodes and to achieve the impact of pyrolysis characteristics for using excipients, in order to offer evi-dences for further research and its processing technology. Steam distillation was used to extract essential oil in the Rhizome Atractylodes. Infrared spectroscopy and gas chromatography were used in the qualitative and quantitative analysis on constituents of essential oil of processing products of Rhizome Atractylodes. Thermogravimetric analysis was used in the comparison of pyrolysis characteristics between Rhizome Atractylodes and its excipients. The results showed that the content of essential oil was declined after processing. However, after being processed, the content of atractylodin was increased at different degrees compared to crude product. The change of atractylodin showed differ-ent tendency in different processing drugs. The atractylodin content from high to low was in the order of products stir-baked to yellowish, products roasted by bran, products prepared with rice water, crude drug. At the temperature of more than 220oC, excipients had major impact for the pyrolysis characteristics of Rhizome Atractylodes. It was concluded that the essential oil declined, but atractylodin increased after Rhizome Atractylodes being processed. It also provided experimental basis for further research on processing technology, ormulation of quality standard and improvement of processing mechanism.