Abstract:There is no licensed vaccine or therapeutics specific to Ebola virus(EBOV) currently. The outbreak strike of Ebola virus disease (EVD) in west Africa in 2014 has brought an urgent need for the study on precautions of EVD. Small molecule inhibitors of EBOV have recently become attractive, with some of them being applied in pre-clinical trial stage. Small molecule compounds are usually designed for some mechanism of the viral pathogenesis that may be shared among different viruses, and thus display an interesting broad-spectrum of anti-viral effect. The present review would summarize the research progress on EBOV small molecule inhibitors, which block some process of the viral life cycle such as viral entry, replication and budding.

Abstract:Neurotransmitter release is critical for maintaining normal organism function, it is mediated by the vesicle transportation. A bundle of proteins regulate the complicated neuronal vesicle transmission by interacting with each other. The small soluble protein Complexin (Cpx) plays an important role that can both inhibit spontaneous vesicle fusion and promote evoked Ca²⁺-dependent neurotransmitter release. In this review, we highlight the recent advances in the function of each domain of Cpx and the mechanisms of interacting with other vesicle exocytosis associated proteins such as SNARE complex and synaptotagmin.

Abstract:Neutrophils account for the largest proportion of white cells in peripheral blood, and play important roles in human nonspecific immunity. Previous studies have shown that neutrophils kill tumor cells through secreting cytokines and reactive oxygen species. However, further studies provide compelling evidence that neutrophils in tumor microenvironment could promote tumor progression. Tumor infiltrating neutrophils produce cytokines and chemokines that provide an immunosuppressive microenvironment for tumor progression and regulate the growth and metastasis of tumor cells and angiogenesis by influencing the recruitment and activation of inflammatory cells in tumor microenvironment. Tumor infiltrating neutrophils is also essential for prognosis of patients with malignant tumor.

Abstract:Polarization imaging techniques are capable of probing the structural and optical properties of anisotropic turbid media. These techniques are compatible in optical layout with the corresponding none polarized optical techniques, but can provide far richer micro structural information of the complex samples, especially the structures in the sub-wavelength scale. As a label-free, non-destructive method, polarization imaging has shown many potential applications in biomedical studies and clinical practices. In this paper, we present a brief introduction on different existing polarization imaging techniques including the difference polarization (DP), degree of polarization (DOP), rotating linear polarization imaging (RLPI), polarization microscopy and Mueller matrix imaging. Moreover, we summarize the recent progresses of these polarization imaging techniques being applied in biomedical studies and clinical practices, such as detection and diagnosis of different cancers. The Mueller matrix provides the comprehensive representation of the polarization properties which are closely linked to the micro structure of the tissues. We present the recent studies in Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) to extract from the Mueller matrix elements groups of new polarization parameters with clearer physics meanings or more explicit connections to the structural features. The MMPD parameters, which reflect the depolarization, retardance and diattenuation properties of samples, and the MMT parameters, which are closely related to the anisotropy and density of sub wavelength small scatterers, are applied to characterize the distinctive features of human skin basal carcinoma, papillary thyroid carcinoma and cervix cancer in clinical samples. With the rapid technological advances in the light sources, polarization modulation optics, detectors and processors, polarization imaging devices are likely to be made smaller, faster, cheaper and easier to operate, which will open up new frontiers in biomedical studies and clinical applications.

Abstract:Pin1 is the only known cis-trans isomerase that recognizes pThr/pSer-Pro in proteins, relevant to the pathogenesis of Alzheimer′s disease (AD). Pin1 regulates the structures and functions of some molecules that are related to AD, inhibits the main AD pathological characteristics such as neurofibrillary tangles (NFTs), senile plaques (SPs), and cerebral amyloid angiopathy (CAA), promotes the differentiation of neural progenitor cells (NPCs) to neurons, and to some extent prevents the occurrence and development of AD. Meanwhile, Pin1 dysfunction in vivo may be involved in the pathogenesis of AD. Nevertheless, whether Pin1 could be a therapeutic target for the prevention and treatment of AD still needs to be verified clinically. Considering of the poor efficacy of AD medicines that target each single molecule in brain, the "combined multiple-target medicine" focusing on Pin1 and other related molecules may be a therapeutic strategy for AD in the future.

Abstract:According to the latest IDF Diabetes Atlas, diabetes mellitus (DM) caused an estimated 5.1 million deaths worldwide in 2013. In other words, a person died from this epidemic disease every six seconds. DM has become one of three major causes of human death after cardiovascular disease and cancers. Glycated human hemoglobin HbA_1c is generated by the irreversible, non-enzymatic glycation reactions on the α-amino groups of N-terminal residue Val1 in one or both beta subunits of tetrameric Hb. Due to the direct correlation of HbA_1c with ambient glycemic concentration over a prolonged period of time, HbA_1c could be useful in assessing diabetic control for the long-term, and is also an important predictor of potential risks to diabetes complications. Therefore, ADA and WHO recommended HbA_1c with a diagnostic cut point of ≥ 6.5% as a new diagnostic criterion for diabetes in 2010 and 2011, respectively. In this review, we summarize: (1) the standardization of HbA_1c from the global IFCC reference method and designated comparison methods in the United States, Japan and Sweden; (2) the basic principles of HbA_1c detection methods commonly used in clinic including affinity chromatography, immunoassay and enzymatic analysis, and their application limitations; (3) the development of POC technology for HbA_1c measurement.

Abstract:Obesity is considered to be a trouble and risk factor to interfere health and it's a potential risk for type Ⅱ diabetes, cardiovascular diseases, and hypertension.Although the pathologic mechanisms of those diseases related to obesity are resulted from multifactor, increasing evidence demonstrated that altered adipokines (adiponectin, leptin, TNF-α) secreted by adipose tissue, and local inflammatory responses play important role in pathogenesis of the disease. The Chemerin (RARRES2 or TIG2), an adipokine has been discovered recently, serves as a ligand for the G protein-coupled receptor1 (GPR1) and has a significant role in metabolism and innate immunity. To investigate the effect of Chemerin and its receptor GPR1 in lipid accumulation of mice, we established obesity mice model successfully by given high-fat diet. Knockdown of Chemerin or GPR1 expression in C57BL/6 mice and pre-differentiation 3T3-L1 cells by siRNA interfering technology,we discovered that Chemerin and its receptor GPR1 were expressed in inguinal fat tissue and subscapular fat tissue. Meanwhile, the lipid accumulation in liver and inguinal fat tissue was inhibited by knockdown of Chemerin or GPR1 expression in C57BL/6 mice. Cultured 3T3-L1 adipocytes secrete Chemerin, which recruits GPR1 signaling in adipocytes and stimulates chemotaxis of GPR1-expressing cells. Small interfering RNA(siRNA) targeted knockdown of Chemerin or GPR1 expression in 3T3-L1 cells impaired differentiation of 3T3-L1 cells into adipocytes, reduced the lipid accumulation in adipocytes and the expression of adipocyte genes and altered metabolic functions in mature adipocytes. So, Chemerin and its receptor may play an important role in regulating lipid accumulation. In summary, Chemerin/GPR1 may be a potential signal pathway that regulates lipid accumulation in adipocytes, and provides a potential therapeutic target for metabolism disorder disease linking obesity.

Abstract:The integrins, a family of transmembrane proteins, function in cell-to-cell and cell-to-extracellular matrix (ECM) adhesive interactions, and influence cell signaling of cell growth and differentiation. Expression of integrin α6 in three bladder cancer cell lines, HCV29, KK47 and YST1 were quantitatively analyzed by LC-MS using stable isotope labeling by amino acids in cell culture (SILAC), a simple and powerful proteomic strategy. The results showed that the non-invasive bladder cancer cell line KK47 expressed the highest level of integrin α6. The expression of integrin α6 in invasive bladder cancer cell line YTS1 was also higher than in normal bladder epithelial cell line HCV29. Furthermore, these results were confirmed by Western blotting, qPCR, immunohistochemistry and flow cytometry. Clinical data of mRNA ITGA6 expression pattern from open-access database (www.oncomine.org) showed the same result during bladder cancer progression. All these indicated that integrin α6 is associated with the invasion progress of the bladder cancer. The preliminary data in this study may sparkle the fundamental role of integrin α6 in the research of bladder cancer.

Abstract:Smad ubiquitination regulatory factor 1 (Smurf1) is an HECT type E3 ligase and regulating a lot of life activity, such as nervous development, cell polarization, bone remodeling and tumor formation, etc. At present, it is in-deep that our knowledge about Smurf1, but people did not particularly distinguish its isoform Smurf1 L and Smurf1 S (the former have 26 amino acid more than the latter) in previous study, and most of related work tend to Smurf1 S. So this article provided some information about the function of Smurf1 L and Smurf1 S. By means of RT-PCR, immunofluorescence assay and Western blot, we studied the difference of Smurf1 L and Smurf1 S in some aspects, including tissue expression, subcellular localization and substrate degradation. The result suggested that: on the one hand, not only the tissue distribution of Smurf1 S is more widespread than Smurf1 L, but also its expression level is higher than Smurf1 L; on the other hand, their subcellular localization have also obvious distinction. Smurf1 L exist at spindles in mitotic phase, but Smurf1 S perhaps exist in cytoplasm. In addition, the degradation ability to substrate of Smurf1 S is stronger than Smurf1 L, and have dose-dependent. In short, these achievement have important significance for more precise research to Smurf1.

Abstract:This paper explores the quantitative correlation between diabetes and breath acetone and analyzes the factors influencing breath acetone concentration. It aims to provide reference values for the application of breath acetone analysis in diabetic testing. We utilized a pilot-scale breath acetone analyzer based on the cavity ringdown spectroscopy (CRDS) technique to conduct breath tests with 512 breath samples from 147 type 2 diabetic patients (81 male, 66 female, age 14～83 years) and 119 breath samples from 52 healthy individuals (30 male, 22 female, age 20～48 years). Relations between breath acetone and blood glucose (BG) and glycohemoglobin A1C (A1C) and several other clinical indices, such as gender, age, Body Mass Index (BMI), years of diabetes and breath samples' collection conditions were investigated. The multi-variation linear regression model was also constructed to explore the influencing factors of breath acetone. No correlations were observed between breath acetone and gender, age or BMI in 52 healthy people tested. Breath acetone concentration in the T2D subjects studied in this work was correlated with both BG (R=0.093) and A1C levels (R=0.1246). Breath Acetone concentration was significantly higher in male subjects (1.75×10^-6) than female subjects (1.15×10^-6), and male subjects' breath acetone was clearly increased with decreasing age (R=-0.154). Besides, breath acetone concentration was significantly correlated inversely with BMI (R=-0.2) in male subjects, and significantly higher in subjects with BMI under 25 (1.75×10^-6) than obese subjects with BMI over 25 (1.25×10^-6). Breath acetone was correlated positively with years of diabetes in female subjects (R=0.17,). Whereas, negatively correlated in male subjects (R=-0.14). Furtherrnore, there were variations in relation to breath samples' collection conditions in both male and female subjects. Multi-variation analysis showed that gender (β=0.374)、A1C (β=0.083)、BG (β=0.002)、breath samples' collection conditions (β=-0.289)、BMI (β=-0.046) and age (β=-0.009) affect breath acetone concentrations. In conclusion, breath acetone concentration was correlated with gender, breath samples' collection conditions, BMI, age, A1C and BG.