Wenxin Granule (WXKL) is a traditional Chinese medicine used for treatment of myocardial infarction (MI) and arrhythmias. However, the genomic pathological mechanisms of MI and mechanisms of WXKL are largely unknown. This study aims to investigate a comprehensive miRNA expression profile, and the predicted correlation pathways to be targeted by differentially expressed miRNAs in MI, and mechanisms of WXKL from a gene level. MI rat model was established by a coronary artery ligation surgery. miRNA expression microarrays were performed and the data were deposited in Gene Expression Omnibus (GEO number GSE95855). And, pathway analysis was performed by using the DIANA-miRPath v3.0 online tool. The expressions of miR-1, miR-133, Cx43, and Cx45 were detected by quantitative real-time PCR. It was found that 35 differentially expressed miRNAs and 23 predicted pathways, including miR-1, miR-133, and gap junction pathway, are involved in the pathogenesis of MI. And, WXKL increased the expressions of miR-1 and miR-133, while also increased the mRNA levels of Cx43 and Cx45, and, especially, recovered the Cx43/Cx45 ratio near to normal level. The results suggest that regulatory effects on miR-1, miR-133, Cx43, and Cx45 might be a possible mechanism of WXKL in the treatment of MI at the gene level.

Objective. To explore the mechanism of cardioprotective effects of Chinese medicine, Yiqi Huoxue recipe, in rats with myocardial infarction- (MI-) induced heart failure. Methods. Male Sprague-Dawley rats underwent left anterior descending artery (LAD) ligation or sham operation. The surviving MI rats were divided randomly into three groups: MI (5 mL/kg/d NS by gavage), MI + Metoprolol Tartrate (MT) (12 mg/kg/d MT by gavage), and MI + Yiqi Huoxue (5 mL/kg recipe by gavage). And the sham operation rats were given 5 mL/kg/d normal saline. Treatments were given on the day following surgery for 4 weeks. Then rats were detected for heart structure and function by transthoracic echocardiography. Apoptosis in heart tissues was detected by TUNEL staining. To determine whether the endoplasmic reticulum (ER) stress response pathway is included in the cardioprotective function of the recipe, ER stress related proteins such as GRP78 and caspase-12 were examined. Results. Yiqi Huoxue recipe attenuated heart function injury, reversed histopathological damage, alleviated myocardial apoptosis and inhibited ER stress in MI rats. Conclusion. All the results suggest that Yiqi Huoxue recipe improves the injured heart function maybe through inhibition of ER stress response pathway, which is a promising target in therapy for heart failure.

BackgroundXian-Fang-Huo-Ming-Yin (XFHM), a traditional herbal formula, has been used to treat sores and carbuncles for hundreds of years in Asia. Nowadays, its clinical effects in treatment of rheumatoid arthritis (RA) have been validated. In this study, we want to study its possible molecular mechanisms of regulating the differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis (CIA) mice for RA treatment.MethodsA high performance liquid chromatography-electrospray ionization/mass spectrometer (HPLC-ESI/MSn) system was used to analyze the constituents of XFHM granules. An arthritics mouse model was induced by collagen and leflunomide (LEF) was used as a positive control medicine. Pathological changes at the metatarsophalangeal joint were studied through Safranin O and immunohistochemical staining. The differentiation of T, B and NK cells was examined by flow cytometry and pro-inflammatory cytokines were assayed using an Inflammation Antibody Array assay. The expression of key molecules of the nuclear factor κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in spleen were studied by western-blot analysis.ResultsIn our study. 21 different dominant chemical constituents were identified in XFHM. Treatment with XFHM suppressed the pathological changes in arthrosis of CIA. Additionally, XFHM down-regulated the proliferation and differentiation of CD3+ T cells and CD3−CD19+ B cells significantly. However, XFHM had no significant effect on CD3−NK1.1+ NK cells. Further study showed that the production of pro-inflammatory cytokines had been suppressed by inhibiting the activation of NF-κB and JAK/STAT signaling.ConclusionsXFHM can regulate and maintain the immunologic balance of lymphocytic immunity and inhibit the production of pro-inflammatory cytokines, thus suppressing the pathological changes of RA. Therefore, XFHM may be used as an application of traditional medicine against RA in modern complementary and alternative therapeutics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1526-x) contains supplementary material, which is available to authorized users.

Atherosclerosis (AS) is the main pathological cause of acute cardiovascular and cerebrovascular diseases, such as acute myocardial infarction and cerebral apoplexy. As an immune-mediated inflammatory disease, the pathogenesis of AS involves endothelial cell dysfunction, lipid accumulation, foam cell formation, vascular smooth muscle cell (VSMC) migration, and inflammatory factor infiltration. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in lipid metabolism, inflammation, and apoptosis by antagonizing the Wnt/β-catenin pathway and regulating cholesterol efflux and inflammatory factors. Importantly, PPARγ-dependant fatty acid uptake is critical for metabolic programming. Activated PPARγ can exert an anti-atherosclerotic effect by inhibiting the expression of various inflammatory factors, improving endothelial cell function, and restraining the proliferation and migration of VSMCs. Regulatory T cells (Tregs) are the only subset of T lymphocytes that have a completely negative regulatory effect on the autoimmune response. They play a critical role in suppressing excessive immune responses and inflammatory reactions and widely affect AS-associated foam cell formation, plaque rupture, and other processes. Recent studies have shown that PPARγ activation promotes the recruitment of Tregs to reduce inflammation, thereby exerting its anti-atherosclerotic effect. In this review, we provide an overview of the anti-AS roles of PPARγ and Tregs by discussing their pathological mechanisms from the perspective of AS and immune-mediated inflammation, with a focus on basic research and clinical trials of their efficacies alone or in combination in inhibiting atherosclerotic inflammation. Additionally, we explore new ideas for AS treatment and plaque stabilization and establish a foundation for the development of natural PPARγ agonists with Treg recruitment capability.

Chiral amplification is an interesting phenomenon in supramolecular chemistry mainly observed in complicated systems in which cooperative effect dominate. Herein, chiral, supramolecular, propeller-like architectures have been constructed through coassembly of an achiral disk-shaped molecule and chiral amino acid derivatives driven by intermolecular hydrogen bonding. Both the "sergeants-and-soldiers" principle and "majority-rules" effect are applicable in these discrete four-component supermolecules, which are the simplest supramolecular system ever reported that exhibit chiral amplification.

Xingnaojing (XNJ) is commonly extracted from Angongniuhuang, a classic Chinese emergency prescription, and widely used in the treatment of nervous system disorders including consciousness disturbance in China.To evaluate the beneficial and adverse effects of XNJ injection, on consciousness disturbance.Seven major electronic databases were searched to retrieve randomized controlled trials designed to evaluate the clinical efficacy of XNJ alone or combined with Western medicine in treating consciousness disturbance caused by conditions such as high fever, poisoning, and stroke. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook for Systematic Review of Interventions, and analyzed using the RevMan 5.3.0 software.Seventeen randomized controlled trials on XNJ were included in this study and the trials generally showed low methodological quality. The results revealed that XNJ alone or in combination with other medicines and adjuvant methods had a positive effect on patients with fever-, poisoning-, and stroke-induced coma.XNJ effectively treated consciousness disturbances that were caused by high fever, poisoning, or stroke.

Phosphorus is a crucial macronutrient for plant growth and development. The mechanisms for maintaining inorganic phosphate (Pi) homeostasis in rice are not well understood. The ubiquitin-conjugating enzyme variant protein OsUEV1B was previously found to interact with OsUbc13 and mediate lysine63-linked polyubiquitination. In the present study, we found OsUEV1B was specifically inhibited by Pi deficiency, and was localized in the nucleus and cytoplasm. Both osuev1b mutant and OsUEV1B-RNA interference (RNAi) lines displayed serious symptoms of toxicity due to Pi overaccumulation. Some Pi starvation inducible and phosphate transporter genes were upregulated in osuev1b mutant and OsUEV1B-RNAi plants in association with enhanced Pi acquisition, and representative Pi starvation responses, including stimulation of acid phosphatase activity and root hair growth, were also activated in the presence of sufficient Pi. A yeast two-hybrid screen revealed an interaction between OsUEV1B and OsVDAC1, which was confirmed by bimolecular fluorescence complementation and firefly split-luciferase complementation assays. OsVDAC1 encoded a voltage-dependent anion channel protein localized in the mitochondria, and OsUbc13 was shown to interact with OsVDAC1 via yeast two-hybrid and bimolecular fluorescence complementation assays. Under sufficient Pi conditions, similar to osuev1b, a mutation in OsVDAC1 resulted in significantly greater Pi concentrations in the roots and second leaves, improved acid phosphatase activity, and enhanced expression of the Pi starvation inducible and phosphate transporter genes compared with wild-type DongJin, whereas overexpression of OsVDAC1 had the opposite effects. OsUEV1B or OsVDAC1 knockout reduced the mitochondrial membrane potential and adenosine triphosphate levels. Moreover, overexpression of OsVDAC1 in osuev1b partially restored its high Pi concentration to a level between those of osuev1b and DongJin. Our results indicate that OsUEV1B is required for rice phosphate homeostasis.

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