Overexpression of Kdr in adult endocardium induces endocardial neovascularization and improves heart function after myocardial infarction

Dear Editor, Coronary artery disease is a leading cause of mortality and morbidity worldwide.Blockade of effective blood flow to heart muscles results in cardi...     

Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response

For highly conserved mammalian protein, chicken is a suitable immune host to generate antibodies. Monoclonal antibodies have been successfully targeted with immunity checkpoint proteins as a means of cancer treatment; this treatment enhances tumor-specific immunity responses through immunoregulation. Studies have identified the importance of B7-H4 in immunoregulation and its use as a potential target for cancer treatment. High levels of B7-H4 expression are found in tumor tissues and are associated with adverse clinical and pathological characteristics. Using the phage display technique, this study isolated specific single-chain antibody fragments (scFvs) against B7-H4 from chickens. Our experiment proved that B7-H4 clearly induced the inhibition of T-cell activation. Therefore, use of anti-B7-H4 scFvs can effectively block the exhaustion of immunity cells and also stimulate and activate T-cells in peripheral blood mononuclear cells. Sequence analysis revealed that two isolated scFv S2 and S4 have the same VH complementarity-determining regions (CDRs) sequence. Molecule docking was employed to simulate the complex structures of scFv with B7-H4 to analyze the interaction. Our findings revealed that both scFvs employed CDR-H1 and CDR-H3 as main driving forces and had strong binding effects with the B7-H4. The affinity of scFv S2 was better because the CDR-L2 loop of the scFv S2 had three more hydrogen bond interactions with B7-H4. The results of this experiment suggest the usefulness of B7-H4 as a target for immunity checkpoints; the isolated B7-H4-specific chicken antibodies have the potential for use in future cancer immunotherapy applications.     

河南省16个主栽小麦品种抗叶锈基因分析

为了明确河南省小麦品种的抗叶锈性及抗叶锈基因的分布,为小麦品种推广与合理布局、叶锈病防治及抗病育种提供依据,本研究利用2015年采自河南省的5个小麦叶锈菌流行小种混合菌株,对近几年河南省16个主栽小麦品种进行了苗期抗性鉴定,然后选用12个小麦叶锈菌生理小种对这些品种进行苗期基因推导,同时利用与24个小麦抗叶锈基因紧密连锁(或共分离)的30个分子标记对该16个品种进行了抗叶锈基因分子检测。结果显示,供试品种苗期对小麦叶锈菌混合流行小种均表现高度感病;基因推导与分子检测结果表明,供试品种可能含有Lr1、Lr16、Lr26和Lr30这4个抗叶锈基因,其中先麦8号含有Lr1和Lr26;郑麦366和郑麦9023含有Lr1;西农979和怀川916含有Lr16;中麦895、偃展4110、郑麦7698、平安8号、众麦1号、周麦16、衡观35和矮抗58含有Lr26;周麦22中含有Lr26,还可能含有Lr1和Lr30;豫麦49-198和洛麦23可能含有本研究中检测以外的其他抗叶锈基因。因此,河南省主栽小麦品种的抗叶锈基因丰富度较低,今后育种工作应注重引入其他抗叶锈性基因,提高抗叶锈性,有效控制小麦叶锈病。     

The broad-spectrum antibiofilm activity of amyloid-forming hexapeptides

Evidence suggests that short amyloid-forming peptides derived from bacterial proteomes have functional roles; however, the reported activities are diverse and the underlying mechanisms remain unclear. In this study, we simulated short amyloid-forming peptides from the amyloid-forming truncated protein C123 of Streptococcus mutans (S. mutans), studied their biological functions in microbial proliferation and biofilm formation, and further investigated the underlying mechanism. Fourteen hexapeptides were simulated, 13 of which were successfully synthesized. We found that the amyloid-forming hexapeptides (AFhPs) displayed efficient broad-spectrum antibiofilm activity against the Gram-positive bacteria S. mutans, Streptococcus sanguis and Staphylococcus aureus, Gram-negative bacteria Escherichia coli and fungus Candida albicans, by aggregating into rigid amyloid fibres agglutinating microbes, whereas the non-amyloid-forming hexapeptides (non-AFhPs) did not. The AFhPs did not kill microbes and showed little or no cytotoxicity. Furthermore, a set of AFhPs displayed broad-spectrum antibiofilm activity, regardless of its source. The microbial cell wall carbohydrates, peptidoglycan (PGN), lipoteichoic acid (LTA), glucan and zymosan A, mediated AFhP binding and triggered significant AFhP fibrillation. Although amyloid fibres agglutinated lipid membrane model – large unilamellar vesicles (LUVs) – and LUVs facilitated AFhP fibrillation, the roles of lipid membranes in AFhP antibiofilm activities remain to be elucidated. We highlight the potential use of AFhPs as novel antibiofilm agents.     

Tumor Suppressor Candidate 1 Suppresses Cell Growth and Predicts Better Survival in Glioblastoma

Glioblastoma (GBM) is the most common malignant brain tumor with poor prognosis and limited treatment options. Tumor suppressor candidate 1 (TUSC1) was recently identified as a potential tumor suppressor in human cancers. However, the expression and potential function of TUSC1 in GBM remain unclear. Herein, we report that TUSC1 is significantly decreased in GBM tissues and cell lines. Patients with high levels of TUSC1 displayed a significant better survival compared with those with low levels of TUSC1. Functional experiments demonstrated that exogenous expression of TUSC1 inhibited GBM cell proliferation and induced G1 phase arrest by down-regulating CDK4. Moreover, overexpression of TUSC1 retarded tumor growth in vivo. Together, our findings revealed that TUSC1 might be a crucial tumor suppressor gene and a novel therapeutic target for GBM.     

FAK contributes to proteinuria in hypercholesterolaemic rats and modulates podocyte F‐actin re‐organization via activating p38 in response to ox‐LDL

Focal adhesion kinase (FAK) is a non‐receptor protein tyrosine kinase that regulates cell adhesion, proliferation and differentiation. In the present study, a rat model of high fat diet‐induced hypercholesterolaemia was established to investigate the involvement of FAK in lipid disorder‐related kidney diseases. We showed focal fusion of podocyte foot process that occurred at as early as 4 weeks in rats consuming high fat diet, preceding the onset of proteinuria when aberrant phosphorylation of FAK was found. These abnormalities were ameliorated by dietary intervention of TAE226, a reported inhibitor of FAK. FAK is also an adaptor protein initiating cascades of intracellular signals including c‐Src, Rho GTPase and mitogen‐activated protein kinase (MAPK). P38 MAPK belongs to the latter and is centrally involved in kidney diseases. Our cell culture data revealed oxidized low‐density lipoprotein (ox‐LDL) triggered hyper‐phosphorylation of FAK and p38, ectopic expression of cellular markers (manifested as decreased WT1, podocin and NEPH1, and increased vimentin and mmp9), and re‐arrangement of F‐actin filaments with enhanced cell motility; these mutations were significantly rectified by FAK shRNA. Notably, pre‐treatment of p38 inhibitor did not alter FAK activation, albeit its deletion of p38 hyper‐activity and attenuation of cellular abnormalities, demonstrating that p38 acted as a downstream effector of FAK signalling and ox‐LDL damaged podocytes in a FAK/p38‐dependent manner. This was further identified by animal data that p38 activation was also abrogated by TAE226 treatment in hypercholesterolaemic rats, suggesting that FAK/p38 axis might also be involved in in vivo events. These findings provided a potential early mechanism of hypercholesterolaemia‐related podocyte damage and proteinuria.     

Morphology and Phylogenetic Placement of Three New Zoothamnium species (Ciliophora: Peritrichia) from Coastal Waters of Southern China

The morphology, infraciliature, and silverline system of three peritrichous ciliates, Zoothamnium bucciniiformum sp. n., Zoothamnium florens sp. n., and Zoothamnium zhanjiangense sp. n., were investigated based on both living and silver‐stained specimens. Zoothamnium bucciniiformum sp. n., collected from coastal waters (salinity 30‰) off Zhanjiang, southern China, can be distinguished by the following characters: dichotomously branched stalk, peristomial lip with medial circumferential infolding, contractile vacuole apically positioned, 32–49 silverlines between the anterior end and the aboral trochal band, 15–26 between the aboral trochal band and the scopula; two kineties in peniculus 3, not parallel to each other. Zoothamnium florens sp. n., collected from a mangrove wetland (salinity 13‰) off Zhanjiang, is characterized by its large conical zooid, tuberculate peristomial lip, asymmetrical dichotomously branched colony, 59–81 silverlines between the anterior end and the aboral trochal band and 29–36 between the aboral trochal band and the scopula. Zoothamnium zhanjiangense, collected from a mangrove wetland (salinity about 9.5‰) off Zhanjiang, differs from its congeners by the alternately branched stalk, peristomial lip with medial circumferential infolding, 40–63 silverlines from the peristomial area to the aboral trochal band and 13–24 from the aboral trochal band to the scopula. The comparison and analysis of SSU rDNA sequences also support present identifications.