Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids.

Increased circulating branched-chain amino acids (BCAAs) have been involved in the pathogenesis of obesity and insulin resistance (IR). However, evidence relating berberine (BBR), gut microbiota, BCAAs, and IR is limited. Here, we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet (HFD)-fed mice. BBR reorganized gut microbiota populations under both the normal chow diet (NCD) and HFD. Particularly, BBR noticeably decreased the relative abundance of BCAA-producing bacteria, including order Clostridiales; families Streptococcaceae, Clostridiaceae, and Prevotellaceae; and genera Streptococcus and Prevotella. Compared with the HFD group, predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment. Accordingly, the elevated serum BCAAs of HFD group were significantly decreased by BBR. Furthermore, the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by activation of the multienzyme branched-chain α-ketoacid dehydrogenase complex (BCKDC), whereas by inhibition of the phosphorylation state of BCKDHA (E1α subunit) and branched-chain α-ketoacid dehydrogenase kinase (BCKDK). The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes. Finally, data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs. Together, our findings clarified BBR improving IR associated not only with gut microbiota alteration in BCAA biosynthesis but also with BCAA catabolism in liver and adipose tissues.

[Exploring research ideas of mechanism of dominant diseases in traditional Chinese medicine based on evidence-based medicine].

The prescription of clinical curative effect has promoted the formation and development of the dominant diseases in traditional Chinese medicine, but it has been controversial for a long time because its mechanism has not been effectively explained. Breaking the gap between animal/cell research and clinical research, and understanding the mechanism of dominant diseases in traditional Chinese medicine based on evidence-based medicine has become an important breakthrough in this scientific issue. Therefore, based on evidence-based medicine, we established the research concept that "originating from clinic, testing in experiment, returning to clinic". Taking the classic formula (Jinqi Jiangtang formula) treating diabetes as an example to find characteristic markers of diabetes supported by evidence-based medicine from clinic. We used the reverse analysis strategy of the response of characteristic markers to explore the intervention mechanism of Jinqi Jiangtang formula on characteristic markers. Then, we verified the key signaling molecules of the metabolic regulation of the Jinqi Jiangtang formula in clinic. The research ideas and key technologies for the mechanism of treatment of diabetes by Jinqi Jiangtang formula based on evidence-based medicine are formed, and it is expected to provide research reference for explaining the mechanism of dominant diseases in traditional Chinese medicine based on evidence-based medicine.

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis.

Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

Suppression of rice miR168 improves yield, flowering time and immunity.

MicroRNA168 (miR168) is a key miRNA that targets Argonaute1 (AGO1), a major component of the RNA-induced silencing complex1,2. Previously, we reported that miR168 expression was responsive to infection by Magnaporthe oryzae, the causal agent of rice blast disease3. However, how miR168 regulates immunity to rice blast and whether it affects rice development remains unclear. Here, we report our discovery that the suppression of miR168 by a target mimic (MIM168) not only improves grain yield and shortens flowering time in rice but also enhances immunity to M. oryzae. These results were validated through repeated tests in rice fields in the absence and presence of rice blast pressure. We found that the miR168-AGO1 module regulates miR535 to improve yield by increasing panicle number, miR164 to reduce flowering time, and miR1320 and miR164 to enhance immunity. Our discovery demonstrates that changes in a single miRNA enhance the expression of multiple agronomically important traits.

[Safety and Effectiveness of Ruxolitinib for Treatment of Myeloproliferative Neoplasm: A Meta-Analysis].

OBJECTIVE: To evaluate the efficacy and safety of ruxolitinib in treatment of myeloproliferative neoplasm. METHODS: Random clinical trials (~September 30, 2017) were identified from PubMed, Embase, Cochrane Library, Clinical Trials, CBM and Chinese Journal Full-text Database. The quality of RCT was assessed by Cochrane risk bias. Meta analysis was performed with Revman 5.3. RESULTS: Ruxolitinib was efficacious in relieving splenomegaly (RR 49.12, 95% CI [15.81-152.59], P<0.001). The incidence of anemia significantly increased after ruxolitinib treatment (RR 1.71, 95% CI [1.05-2.77], P=0.16), while the thrombocytopenia (RR 1.04, 95% CI [0.50-2.16], P=0.92) and neutropenia (RR 2.46, 95% CI [0.91-6.61], P=0.07) had no statistical difference as compared with that in control group. Ischemia events had no significant difference as compared with control (RR 0.57, 95% CI [0.33-1.00], P=0.05). Infection events had no significant difference as compared with the control group (RR 1.18, 95% CI [0.79-1.78], P=0.24). CONCLUSION: Ruxolitinib is an efficacious therapeutic strategy on MPD with controlling splenomegaly. However,anemia events and bleeding events may threat its clinical safety, so more high quality RCT are needed.

UPLC-QTOF/MSE and Bioassay Are Available Approaches for Identifying Quality Fluctuation of Xueshuantong Lyophilized Powder in Clinic.

Xueshuantong Lyophilized Powder (XST), consisting of a series of saponins extracted from Panax notoginseng, is widely applied to treat acute cerebral infarction, stroke, and coronary heart disease in China. However, most adverse drug reactions (ADR) in clinic are caused by quality problems of XST. In this study, six batches of certainly abnormal, four batches of possibly abnormal XST, and eight batches of normal XST were obtained from the clinical practice. Their quality fluctuations were identified by ultra-performance liquid chromatography coupled with an electrospray ionization quadrupole time-of-flight mass spectrometry operating in MSE mode (UPLC-QTOF/MSE) and bioassays including antithrombin and proplasmin assay. Fourteen potential components responsible for clinical ADR were identified by UPLC-QTOF/MSE, especially ginsenoside Rg1, Rg3, Rb1 and notoginsenoside R1. In addition, 83.3% (5/6) and 50.0% (3/6) certainly abnormal samples could be identified by UPLC-QTOF/MSE and bioassay, respectively. Interestingly, further integration of the two methods could entirely identify all the certainly abnormal samples and inferred that all the possibly abnormal samples were closely related to their quality fluctuation. It indicates that it is advisable to combine UPLC-QTOF/MSE and bioassay for identifying quality fluctuation of XST, and thus reduce its ADR in clinic.

San-Cao Granule () Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway.

OBJECTIVE: To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis. METHODS: A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor ß1 (TGF-ß1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase. RESULTS: Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-ß1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01). CONCLUSION: SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-ß1/Smad signaling pathway.

[Reseach Advances on Cancer-Testis Antigens in Multiple Myeloma -Review].

Cancer-testis antigens (CTA) are a class of tumor-associated antigens, which are mainly located in X chromosome. CTA restrictively expressed in normal testis, ovary, placenta and so on. Their expression in other normal tissues is much lower, even can not be detected. However, their expressions are aberrantly high in human cancers. Based on CTA encoding immunogenic proteins, they can be regulated by epigentics, CTA provides very attractive targets for cancer immunotherapy. Multiple myeloma (MM) is incurable and has a low cureative rate and a high relapse rate. CTA have been detected in many MM cell lines and primary MM cells, they may be relaled to clinical prognosis. This reviews briefly summarized the research advances of CTA in the immune therapy of multiple myeloma, so as to provide a valuable therapeutic idea for myeloma.

Inhibition of Sophocarpine on Poly I: C/D-GalN-Induced Immunological Liver Injury in Mice.

Increasing evidence has suggested that natural killer (NK) cells contribute to the pathogenesis of human immunological liver injury (ILI). Previous studies have demonstrated that Sophocarpine exerts activity in immune modulation. It also has a therapeutic effect on liver protection in that it can alleviate liver fibrosis by suppressing both the activation of hepatic stellate cells and the proliferation of the activated hepatic stellate cells. However, whether Sophocarpine protects the liver by regulating NK cell activity remains unclear. In this study, the modulating effect of Sophocarpine on NK cells in the liver was investigated. The results showed that Sophocarpine dramatically decreased the production of pro-inflammatory cytokines and attenuated the liver injury induced by Poly I: C/D-GalN in C57BL/6- mice. More importantly, Sophocarpine pre-treatment significantly suppressed NK cell activation and downregulated the expression of NKG2D, a receptor responsible for NK cell activation. Moreover, the protein levels of DAP12, ZAP76 and Syk decreased, as did their corresponding mRNA levels. Overall, our study demonstrates that Sophocarpine inhibits NK cell activity, thus making it a promising therapy for ILI.

[Change and clinical significance of peripheral blood T-lymphocyte functional subsets in acute graft-versus-host disease].

OBJECTIVE: This study was aimed to detect the change of T-lymphocyte functional subsets marked by CCR7 and CD45RA in the aGVHD within 100 days after allo-HSCT and to explore its clinical significance. METHODS: The peripheral blood of 42 patients after allo-HSCT was collected every two weeks since hematopoietic reconstitution. The expression of CD3, CD4, CD8, CCR7 and CD45RA-marked T-lymphocytes was detected by flow cytometry, the relationship between their expression and the prognosis of aGVHD was analyzed. RESULTS: The percentage and the absolute count of CCR7(+) T lymphocyte were significantly reduced in aGVHD. The percentage of T(naïve), T(CM), T(EM) and the absolute count of T(naïve), T(EM), TTD were sharply reduced in aGVHD, moreover has changed correspondingly with outcome of aGVHD. The percentage of CD3, CD4, CD8-marked T-lymphocyte subsets did not significantly changed. CONCLUSION: T-lymphocyte functional subsets marked by CCR7 and CD45RA are a valuable indicator to monitor early immune reconstruction for patients with the aGVHD after allo-HSCT.