Abstract:Change is the soul of biomarker. Early changes in vivo are subject to be removed from blood because of homeostasis mechanisms of the body. Without homeostasis mechanisms, urine can accommodate more changes and therefore is an excellent source of biomarkers. Especially in the early stage of disease occurrence, the new biomarkers are more likely to be found in the urine. In biomarker studies, the effects of the therapeutic drugs must be taken into account. Various confounding factors can be effectively circumvented interference on urinary biomarker studies based on urine biomarker roadmap research. A novel membrane storage technique enables large-scale urine sample collection and storage economically and efficiently. Biomarkers discovery of kidney diseases are introduced and discussed also here. It can be expected that urine biomarker studies will greatly promote the development of medical technology such as human disease diagnosis, prevention, treatment or prognosis.

Abstract:Shigella, an enteric pathogen, causes widespread bacillary dysentery around the world. Over the past few years, the emergence of resistance to multiple antimicrobials and new serotypes has brought new challenges to the surveillance and prevention of Shigella. The rapid development of genomics contributes to a better understanding of origins, mechanisms of variation and spreading principles, and has great scientific significance to control the spread of bacillary dysentery. From the perspective of genetic source, this essay focuses on the evolutionary relationship between Shigella and E. coli, as well as the possible molecular mechanisms. For the purpose of providing reference for researching and prevention of Shigella, the article also outlines the advances on genome evolution of S. flexneri, S. sonnei and S. dysentery type 1 with a detailed description of their features on temporal and spatial distribution and of the function of variation in resistance genes during evolution.

Abstract:Epicardial adipose tissue (EAT) is a unique fat depot which has multifaceted effect on local and systemic. EAT has a special anatomical location. The metabolic and histological features are distinguished from other fat depots. Under normal physiological conditions, EAT has thermogenic and mechanical characteristics, which is beneficial for the heart. Under pathological conditions, however, EAT secrete a variety of proinflammatory cytokinesis and adipokines involved in the pathological process of cardiovascular diseases. Thickness/volume and chronic inflammation of EAT was significantly positively correlated with the severity of cardiovascular disease. Exercise, weight loss and some drugs can restore the protective functions of EAT for cardiovascular system, suggesting that EAT maybe serve as a novel indicator for diagnosis, treatment and prognostic evaluation of cardiovascular disease. In this review, we summary the anatomy, function and regulation of EAT, and then discuss the potential roles of the EAT in cardiovascular diseases including vascular remodeling after injury, atherosclerosis, hypertension, arrhythmias and heart failure, which may provide new targets for the prevention and treatment of cardiovascular diseases.

Abstract:Enzyme responsive peptide hydrogel has been an emerging hot issue in the field of material. It can be used for the release of controlled release drug, and it has antibacterial and anti-tumor effect. In this paper, enzyme responsive hydrogel systems of peptides developed at home and abroad in recent years were summarized. Several enzymes that catalyze the material’s response were introduced emphatically, including transglutaminase, kinase, phosphatase, lysyl oxidase (plasma amine oxidase), protease, esterase, β-lactamase and matrix metalloproteinase. Under their catalysis, the macroscopic structure of the hydrogel changes, such as the formation, destruction or dynamic translation of the hydrogel; furthermore, their catalyzing mechanisms were summarized. In addition, the applications of enzyme responsive peptide hydrogel were introduced. It had broad prospects for development, which was one of the developing directions of intelligent response materials in the future.

Abstract:The tyrosine kinase Src is activated in a large number of human malignancies and plays significant roles in the development of cancers. Activation of Src in human cancers employs a variety of mechanisms mainly including covalent modification, allosteric regulation, gene mutation. Covalent modifications of Src mainly include phosphorylation and oxidization. Tyr530, Tyr419, Thr34, Thr46, Ser72, Tyr138 and Tyr213 are phosphorylation sites of Src, among which Tyr530 and Tyr419 are the most important ones. Allosteric regulations of Src involve its regulatory Src homology 3 (SH3) or SH2 domains，which interacts with allosteric regulators, such as FAK, PR, ER, AR, P130Cas, PDGF, PDGFR, EGFR, HER2, IGF-1R, FGFR-1, c-Met, p13, Nef and Sin. In this review, we summarize the key mechanisms regulating Src kinase activity in cancer cells.

Abstract:Mitochondrion is semi-autonomous organelle with genetic system. Through migration, isolation and evolution of human, mitochondrial DNA (mtDNA) formed a wide range of mitochondrial genome polymorphisms. Mitochondrial haplotype is referred to as the set of the same mtDNA SNP loci from a common ancestor. Different mitochondrial haplotypes affect the mitochondrial function to a certain extent, thus affecting the growth of cell, leading to diseases of individuals, such as Leber’s hereditary optic neuropathy, maternally inherited deafness, type Ⅱ diabetes, Parkinson disease and cancer. This review summarized several mitochondrial diseases related to mitochondrial haplotypes (A, B, D, F, G, H, J, K, M, N, R, T, U, Y,etc.) and some special mitochondrial polymorphic sites (G11778A, A1555G, T3394C, G10398A, etc.).

Abstract:Reactive oxygen species (ROS) and NO free radicals generated from oxidative stress play an important role in the pathogenesis of neurodegenerative disease and cardiovascular and cerebrovascular diseases. Excessive NO production can cause free radical damage and induce neuron death. As one of the traditional Chinese medicine, Emodin have valuable and widely clinical applications. Recently, Emodin has been reported to have antioxidant, immunomodulatory, antibacterial, anti-inflamatory functions etc. FOXO1 is a vital member of the Forkhead family of transcription factors known to regulate the transcription of genes involved in cell cycle arrest, DNA repair in response to oxidative stress or apoptosis. However, it is unclear how the NO effect on FOXO1. In this study, we observed vital role of FOXO1 dependent transcriptional activation on neuronal death in response to Nitric oxide over-production. We found that NO donor GSNO or L-Arginine significantly increased the FOXO1 transcriptional activity, which induce the FOXO1 downstream proapoptotic genes (FasL, Bim) expression and finally induce neuronal death. In addition, we screen natural Chinese herb extracts targets to regulating FOXO1 activity. Emodin shows dramatically effect in suppression of FOXO1 transcription activity and protein levels. What’s more, Emodin can attenuate neuronal death induced by L-Arg. The current study first demonstrate that Nitric Oxide could regulate FOXO1 transcriptional activity to damage neuronal cell, which will benefit to deep understanding the neurotoxicity of NO free radical. Secondly, by Chinese herb extracts and antioxidants screen, we identified Emodin as one FOXO1 activity modulator which can attenuate neurotoxicity induced by NO. The current study will also provide a new insight for explaining the mechanisms of pathology of neurodegenerative disease and neuroprotective effects of Emodin.

Abstract:The active-site architecture of cellulase is a functional area composed of multiple amino acid residues which can bind and catalyze substrates. Aromatic residues, such as tryptophan, play important roles in the function of this region. In this study, the dynamic of binding process between tryptophan in active-site architecture of cellulase ChCel5A and substrate was quantitatively analyzed using fluorescence spectrum. The substrate concentration range when tryptophan can specifically bind the substrate was determined and the change of binding constant caused by a single amino acid mutation in active-site architecture of ChCel5A was measured through quantitative analysis of tryptophan fluorescence quenching. Compared with the measurement of kinetic parameters, fluorescence spectroscopy could accurately characterize the binding affinity between cellulase and substrate, as well as the change of kinetic parameter caused by a single residue mutation. Besides, when using pNPC as the ligand, the binding constant could be overestimated for 20-100 times due to the increase of strong electrophilic groups. Fluorescent spectrometry can measure the kinetic parameter of cellulase-substrate binding process in a sensitive and rapid way, providing a new perspective for the quantitatively analyzing the interaction between proteins and substrates.

Abstract:To predict circRNAs and target genes for seven known Wnt1-targeting miRNAs, then further analyze the interaction among these seven miRNAs and their corresponding circRNAs and target genes, seven reported Wnt1-targeting miRNAs including let-7e, miR-21, miR-34a, miR-122, miR-148a, miR-148b and miR-152 were predicted for their interacting circRNAs and target genes by Starbase and miRWALK softwares, respectively. Then the network analysis of miRNA and their interaction circRNAs and target genes was built by Cytoscape3.2.1 software. DAVID was performed to analyze singaling pathway according to miRNAs predicted target genes. The number of target circRNAs predicted by Starbase software for these 7 different miRNAs were 58, 15, 41, 20, 28, 28 and 28, respectively. Comparing the relationship between miRNAs and their target gene in more than 7～9 softwares predicted by miRWALK, we found that the CHD7 gene is the only one corresponding with miR-21, miR-148-a and miR-148 and miR-152 in more than 7 softwares predications. CNOT6, NBEA, ZFYVE26 and ZDHHC17 were the target genes equivalent with at least 4 miRNAs predicted by both 7 and 8 different softwares in miRWALK. For KEGG signaling pathways, Focl adhesion, MAPK, Notch and TGF-beta signaling pathways were all predicted by seven miRNAs’ target genes in more than 7 different predication softwares of miRWALK. In the MAPK signaling pathway, DUSP1 was found to have interaction with miR-21,miR-148a, miR-148b and miR-152 simultaneously, MRPS35_hsa_circ_001042 was also predicted to interact with these four miRNAs. We found that the DUSP1 and MRPS35_hsa_circ_001042 in the MAPK signaling pathway, are the target genes and circRNA, interacted with miR-21,miR-148a, miR-148b, and miR-152, respectively. In the study, we analyzed known Wnt1-targeting miRNAs and their corresponding circRNAs and predicted target genes, signaling pathway and interaction network were also involved. The study laid the foundation for the further analysis of the interaction among Wnt1-targeting miRNAs, circRNAs and target genes.

Abstract:Cell capturing and separation is frequently involved in researches in immunology, diagnostics and pathology．In recent years, different new methods for cell capturing and separation based on microfluidic platform have been developed．With microfluidic chip, rapid and low cost detection can be implemented with small sample and reagent volumes．In this review, two methods of microfluidic cell separation, immune-capture and label-free separation, are introduced．Immuno-capture, a more traditional method, can separate cells with high specificity and provide highly purified target cells．Newly developed label-free method performs separation by utilizing the physical and biological features of target cells, and can keep cell’s integrity and activity．Although there are a couple of issues to be resolved before microfluidic cell separation gets widespread commercial use, such as multi-system integration and industrial-scale manufacture, it has already attracted extraordinary research attention and has been in the path on rapid development．It is believed that cell capturing and separation methods based on microfluidic chip have broad application prospect in life science and biomedical field．