Myostain is involved in ginsenoside Rb1-mediated anti-obesity.

CONTEXT: Obesity, one of the major public health problems worldwide, has attracted increasing attention. Ginsenoside Rb1 is the most abundant active component of Panax ginseng C.A.Mey (Araliaceae) and is reported to have beneficial effects on obesity and diabetes. However, the mechanisms by which Rb1 regulates obesity remain to be explored. OBJECTIVE: This paper intends to further explore the mechanism of Rb1 in regulating obesity. MATERIALS AND METHODS: The C57BL/6 obese mice were divided into two groups: the control (CTR) and Rb1. The CTR group [intraperitoneally (ip) administered with saline] and the Rb1 group (ip administered with Rb1, 40 mg/kg/d) were treated daily for four weeks. In vitro, Rb1 (0, 10, 20, 40 µM) was added to differentiated C2C12 cells and Rb1 (0, 20, 40 µM) was added to 3T3-L1 cells. After 24 h, total RNA and protein from C2C12 cells and 3T3-L1 cells were used to detect myostatin (MSTN) and fibronectin type III domain-containing 5 (FNDC5) expression. RESULTS: Rb1 reduced the body weight and adipocyte size. Improved glucose tolerance and increased basic metabolic activity were also found in Rb1 treated mice. MSTN was downregulated in differentiated C2C12 cells, 3T3-L1 cells and adipose tissues upon Rb1 treatment. FNDC5 was increased after Rb1 treatment. However, MSTN overexpression attenuated Rb1-mediated decrease accumulation of lipid droplets in differentiated 3T3-L1 adipocytes. DISCUSSION & CONCLUSIONS: Rb1 may ameliorate obesity in part through the MSTN/FNDC5 signalling pathway. Our results showed that Rb1 can be used as an effective drug in the treatment of human obesity.

Salvianolic acid B improves myocardial function in diabetic cardiomyopathy by suppressing IGFBP3.

BACKGROUND: Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear. METHODS: Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B. RESULTS: Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia. CONCLUSIONS: Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.

Active immunisation targeting soluble murine tumour necrosis factor alpha is safe and effective in collagen-induced arthritis model treatment.

OBJECTIVES: TNF-α has been proved to be an effective target in rheumatoid arthritis treatment. So far, all the commercialised TNF-α antagonists function as passive immunotherapy. The aim of this study was to design a complex which can trigger active immunisation and overcome self-tolerance to elicit antibodies against murine TNF-α. METHODS: The complex (KLH-TNF) was chemically synthesised by linking a selected peptide TNFα(4-23) from murine soluble TNF-α to a carrier protein, keyhole limpet haemocyanin (KLH). We evaluated its safety and antibody eliciting performance. We also evaluated its disease-regulating ability on collagen-induced arthritis models. Furthermore, the immune cells responses were analysed by T cell proliferation assay and B cell memory experiments. RESULTS: The complex was safe without cytotoxity. The anti-mTNF-α antibody titers of the KLH-TNF group were 400 times greater than the control groups (p<0.0001). The elicited antibodies could combine with soluble TNF-α. The antibody response was independent of autologous TNF-α and could be reinforced by booster immunisation. Moreover, the complex did not trigger T cell activation and B cell memory response against native TNF-α. In animal experiments, KLH-TNF immunized mice showed a lower arthritis score (p<0.001) and better weight gain (p<0.01). Histological evaluations showed milder inflammation and cartilage depletion. CONCLUSIONS: Active immunotherapy against cytokine TNF-α is feasible by conjugating cytokine peptide with carrier protein. The elicited antibodies could combine with the native TNF-α and inhibit its activity. Importantly, the antibody response is reversible and independent of autologous TNF-α.

Banana ethylene response factors are involved in fruit ripening through their interactions with ethylene biosynthesis genes.

The involvement of ethylene response factor (ERF) transcription factor (TF) in the transcriptional regulation of ethylene biosynthesis genes during fruit ripening remains largely unclear. In this study, 15 ERF genes, designated as MaERF1-MaERF15, were isolated and characterized from banana fruit. These MaERFs were classified into seven of the 12 known ERF families. Subcellular localization showed that MaERF proteins of five different subfamilies preferentially localized to the nucleus. The 15 MaERF genes displayed differential expression patterns and levels in peel and pulp of banana fruit, in association with four different ripening treatments caused by natural, ethylene-induced, 1-methylcyclopropene (1-MCP)-delayed, and combined 1-MCP and ethylene treatments. MaERF9 was upregulated while MaERF11 was downregulated in peel and pulp of banana fruit during ripening or after treatment with ethylene. Furthermore, yeast-one hybrid (Y1H) and transient expression assays showed that the potential repressor MaERF11 bound to MaACS1 and MaACO1 promoters to suppress their activities and that MaERF9 activated MaACO1 promoter activity. Interestingly, protein-protein interaction analysis revealed that MaERF9 and -11 physically interacted with MaACO1. Taken together, these results suggest that MaERFs are involved in banana fruit ripening via transcriptional regulation of or interaction with ethylene biosynthesis genes.

Bone marrow stromal cell transplantation combined with angiotensin-converting enzyme inhibitor treatment in rat with acute myocardial infarction and the role of insulin-like growth factor-1.

BACKGROUND AIMS: We investigated bone marrow stromal cell (BMSC) transplantation combined with angiotensin-converting enzyme inhibitor (ACEI) treatment in acute myocardial infarction (AMI) and the role of insulin-like growth factor-1 (IGF-1). METHODS: AMI models were established in Sprague-Dawley rats by ligation of the left anterior descending coronary artery and grouped into blank control (BC), ACEI treatment (ACEI), BMSC transplantation (BMSC) and BMSC transplantation plus ACEI (combined). Perindopril (2.5 mg/kg) was administered by gavage to ACEI and combined groups from the day after AMI. BMSC (2 × 10(8)) were injected into the border of the MI area a week later in the BMSC and combined groups. RESULTS: After 4 weeks, hemodynamics in the BMSC and combined groups were significantly improved (P < 0.05 versus BC), with the greatest improvement in the combined group (P < 0.05). In addition, an increased number of BMSC survived in the combined group (P < 0.05 versus BMSC). A proportion of BMSC was positive for troponin T, as detected by immunofluorescence. The number of apoptotic cardiomyocytes was decreased in the BMSC and ACEI groups, and even further in the combined group (P < 0.05). IGF-1 expression was up-regulated in the BMSC and combined groups (P < 0.05 versus BC), but not in the ACEI group. B cell lymphoma-2 (Bcl-2) expression was up-regulated in the ACEI, BMSC and combined groups, with the highest expression in the combined group (P < 0.05). CONCLUSIONS: Our results show that BMSC engrafted in AMI can survive well and secrete IGF-1 and preserve cardiac function significantly. These data suggest that BMSC transplantation inhibits apoptosis of cardiomyocytes by up-regulation of Bcl-2 expression in the myocardium, and this effect might be sensitized by ACEI.

Association between fibroblast growth factor 7 and the risk of chronic obstructive pulmonary disease.

AIM: Fibroblast growth factor 7 (FGF7) is involved in a number of physiological and pathological processes, including lung disease. However, relatively little is known about the effect of FGF7 gene polymorphisms on chronic obstructive pulmonary disease (COPD) susceptibility. This study aimed to investigate the association between FGF7 polymorphisms with COPD susceptibility in a Chinese Han population. METHODS: We conducted a case-control study of 279 COPD patients and 367 age- and gender-distribution-matched control subjects. The tagging SNPs rs10519225 and rs7170426 in FGF7 were genotyped by SNaPshot. The associations of each SNP genotype and haplotype constructed by these loci with COPD were analyzed. RESULTS: A multivariate analysis showed that rs10519225 was significantly associated with an increased risk of COPD (P=0.011, OR=1.535, FDR q=0.022), whereas no association was found for rs7170426. Linkage disequilibrium (LD) analysis showed that these loci were in weak LD, with an r(2) of 0.033 and a D' of 0.232 (95% CI: 0.150-0.520). The haplotype constructed by allele G at rs10519225 and allele A at rs7170426 was associated with a decreased susceptibility to COPD (P=0.012, OR=0.751, FDR q=0.048). CONCLUSION: These findings suggest that FGF7 may be one susceptibility factor for COPD.

Weak UVB Irradiation Promotes Macrophage M2 Polarization and Stabilizes Atherosclerosis.

Atherosclerosis (AS) is a chronic cardiovascular disease endangering human health and is one of the most common causes of myocardial infarction and stroke. Macrophage polarization plays a vital role in regulating plaque stability. As an important component of sunlight, ultraviolet B (UVB) has been proven to promote vitamin D and nitric oxide synthesis. This research used an AS model in ApoE-/- mice to study the effects of UVB on macrophage polarization and atherosclerotic plaque stability. In vitro, UVB irradiation increased arginase-I (Arg-I, M2 macrophage) and macrophage mannose receptor (CD206) expression, while the expression of inducible nitric oxide synthase (iNOS) (M1 macrophage) and CD86 was decreased. UVB promoted Akt phosphorylation in vitro. In vivo, UVB irradiation promoted the stabilization of atherosclerotic lesion plaques, while the phenotype of M2 macrophages increased. Our research provides new evidence for UVB in preventing and treating atherosclerosis.

Proteomic investigation of resistance to chemotherapy drugs in osteosarcoma.

BACKGROUND: Osteosarcoma, which is also termed osteogenic sarcoma or osteoma sarcomatosum, is the most common form of bone cancer. Typical osteosarcoma can occur at any age, including in infants, children, and the elderly, but more than half of cases occur in individuals who are 10-20 years old. OBJECTIVE: Here, the objective was to search for protein markers to indicate resistance to cisplatin in osteosarcoma and provide a theoretical basis for the early and accurate use of cisplatin to treat osteosarcoma. METHODS: Thirty patients with osteosarcoma were selected for the study. Experimental studies on the chemosensitivity of osteosarcoma using an in vitro kit method were performed, and cisplatin-resistant and cisplatin-sensitive osteosarcoma tissues were obtained. A representative sample was chosen to analyze and identify differentially expressed proteins in cisplatin-resistant tissues. RESULTS: The osteosarcoma-sensitive tissue was analyzed using 2-D electrophoresis and time-of-flight mass spectrometry. Differently expressed proteins were analyzed by western blotting to identify markers. Cisplatin-resistant and cisplatin-sensitive osteosarcoma tissues were obtained. Five significantly differentially expressed proteins were identified, including ALDOA and PGK1. CONCLUSIONS: The results indicate that ALDOA and PGK1 might be appropriate markers that can be used when treating osteosarcoma with cisplatin.

Measuring upper limb movement to analyze intra-body communication channel attenuation characteristics.

BACKGROUND: This experiment was designed to study the respective effects of the closed-state human palm and dynamic arm bending on intra-body communication channel attenuation. METHODS: We selected the right upper arm of a healthy adult male as the experimental object to measure channel attenuation variation in a closed or open palm, and when the arm was bent, so as to analyze channel characteristics. CONCLUSIONS: The experiment showed that, in a quasi-static stable system, the effects of a closed palm on channel attenuation were negligibly minimal. In contrast, the physiological signal of the living body significantly interfered with the channel in the low-frequency mode. In the dynamic arm-bending experiment, we found that the attenuation variation range corresponds to the intersection angle (90∘⩽θ⩽ 180∘) of the upper arm and forearm; these results provide the basis for the establishment of a theoretical model.

Modeling of sectionally continuous communication channel with inhomogeneously distributed tissues.

BACKGROUND: This study aimed to investigate effects on the transmission channel caused by heterogeneous distribution in tissues and joint characteristics. METHOD: Human arm section scans were taken using CT technology, and zoned, following which, a circumference measurement experiment was performed to analyze the effect of inhomogeneous distribution of tissues. In order to analyze the arm joint's effect on channel transmission, we proposed a piecewise modeling method in combination with connection conditions. CONCLUSIONS: It can be seen from the experiment that, in the quasi-static mode, the communication channel error caused by the inhomogeneous distribution of tissues is small enough to be negligible. The error between calculated and experimental results is reduced by 3.93 dB in this experiment relative to models that did not include joint characteristics, and the average error is lowered by 0.73 dB. The variation curve fit to experimental data is also improved in this method. As such, it can be quantitatively determined that a channel model with joint characteristics is superior to models excluding joint characteristics.

A numerical model for blast injury of human thorax based on digitized visible human.

Knowledge of the pressure distribution around human thorax in blast help to understand the injury mechanisms and their assessment. To investigate the transmission mechanism of the pressure on human thorax in blast, a three dimension surface model of human thorax was constructed in this work. To increase the precious of this model, tetrahedron element division method was applied to transfer the rough 3D surface model to hexahedral elements model. Using this model, the high pressure duration was computationally solved using numerical simulation of the hexahedral elements. Simulation results showed that the apex of lungs was subjected to the largest stress in a blast. In order to verify this result, an animal experiment was performed on a dog. The animal experimental results was shown to have a same variation tendency with the calculation results based on our numerical model of human thorax, which made this model reliable for the blast injury research.