血浆同型半胱胺酸和D-二聚体水平与急性期脑梗死各亚型的关系

Purpose-To study plasma homocysteine(Hcy)/D-dimer levels in patients with differernt subtype of acute cerebral infarction for early etiology diagnosis. Methods: The subjects were 246 acute cerebral infarction patients in the first 24 hours of stroke onset at our hospital. We divided them into large –artery atherosclerosis(LAA) group(n=66), small artery occlusion(SAO) group(n=76), cardio embolism(CE) group(n=40),stroke of other demonstrated etiology(SOE) group (n=11)and stroke of other undemonstrated etiology(SUE) group(n=51) according to the TOAST classification. Plasma homocysteine and D-diamer were determined within the first 24 hours of admission, the differences in subgroups and control group(n=121) were analyzed. Results:Plasma homocysteine levels in LAA group were signficantly higher than other groups(P<0.05), no differences in non-LAA groups(P>0.05);Plasma D-diamer levels in CE group were significant higher than other groups(P<0.05), no differences in non-CE groups(P>0.05). Conclusions: Plasma homocysteine and D-diamer level are associated with subtypes of acute cerebral infarction, and it contributed to early classification diagnosis and individual treatment of patients with acute cerebral infarction.目的：探讨血浆同型半胱胺酸和D-二聚体在急性期各亚型脑梗死之间的差异，为临床脑梗死亚型的病因学诊断提供理论依据。方法：收集我院246例24 h内发病的脑梗死患者，根据TOAST分型方法进行病因学分型：大动脉粥样硬化性脑卒中(1arge—artery atherosclerosis，LAA；n=66)、小动脉闭塞性脑卒中(small-artery occlusion ,SAO；n=76)、心源性脑栓塞(cardio embolism，CE；n=40)、其他确定原因引发的缺血性脑卒中(stroke of other demonstrated etiology，SOE；n=11)和不明原因的缺血性脑卒中(stroke of other undemonstrated etiology，SUE；n=51)。在入院24小时内测定血浆同型半胱胺酸（Hcy）和D-二聚体（DD）的含量，并与121例对照组进行比较，分析二者在不同亚型脑梗死及对照组之间的差异。结果：LAA组同型半胱氨酸水平明显高于其它4组及对照组(P<0．05) ，其他 4个亚型(SAA、CA、SOE、SUE)及对照组组间比较差异无统计学意义(P>0．05)。CE组血浆D-二聚体含量最高,显著高于其他各亚型组及对照组(P<0.05); 其他 4个亚型(SAA、CA、SOE、SUE)及对照组组间比较差异无统计学意义(P>0．05)。结论：急性期各亚型脑梗死之间血浆同型半胱胺酸和D-二聚体升高程度不同,这对于临床早期分型诊断及个体化治疗有着重要指导意义

MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer

Background We recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis. Methods We measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay. Results Expression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells. Conclusions MiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy

CXCR4 Antagonist AMD3100 Modulates Claudin Expression and Intestinal Barrier Function in Experimental Colitis

Ulcerative colitis is a gastrointestinal disorder characterized by local inflammation and impaired epithelial barrier. Previous studies demonstrated that CXC chemokine receptor 4 (CXCR4) antagonists could reduce colonic inflammation and mucosal damage in dextran sulfate sodium (DSS)-induced colitis. Whether CXCR4 antagonist has action on intestinal barrier and the possible mechanism, is largely undefined. In the present study, the experimental colitis was induced by administration of 5% DSS for 7 days, and CXCR4 antagonist AMD3100 was administered intraperitoneally once daily during the study period. For in vitro study, HT-29/B6 colonic cells were treated with cytokines or AMD3100 for 24 h until assay. DSS-induced colitis was characterized by morphologic changes in mice. In AMD3100-treated mice, epithelial destruction, inflammatory infiltration, and submucosal edema were markedly reduced, and the disease activity index was also significantly decreased. Increased intestinal permeability in DSS-induced colitis was also significantly reduced by AMD3100. The expressions of colonic claudin-1, claudin-3, claudin-5, claudin-7 and claudin-8 were markedly decreased after DSS administration, whereas colonic claudin-2 expression was significantly decreased. Treatment with AMD3100 prevented all these changes. However, AMD3100 had no influence on claudin-3, claudin-5, claudin-7 and claudin-8 expression in HT-29/B6 cells. Cytokines as TNF-α, IL-6, and IFN-γ increased apoptosis and monolayer permeability, inhibited the wound-healing and the claudin-3, claudin-7 and claudin-8 expression in HT-29/B6 cells. We suggest that AMD3100 acted on colonic claudin expression and intestinal barrier function, at least partly, in a cytokine-dependent pathway

Exploring the common pathogenesis of Alzheimer’s disease and type 2 diabetes mellitus via microarray data analysis

BackgroundAlzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated.PurposeThe primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM.MethodsDownload the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein–protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs).ResultsThe subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG. For the characteristic Aβ and Tau pathology of AD, RAPGEF3 was associated significantly positively with AD and NF1 significantly negatively with AD. In addition, we also found ADCY5 and NF1 significant correlations with DM phenotypes. Other datasets verified that NF1, RAB14, ADCY5, and RAPGEF3 could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases.ConclusionThe common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases

A Peptide That Binds Specifically to the β-Amyloid of Alzheimer's Disease: Selection and Assessment of Anti-β-Amyloid Neurotoxic Effects

The accumulation of the amyloid-β peptide (Aβ) into amyloid plaques, an essential event in Alzheimer's disease (AD) pathogenesis, has caused researchers to seek compounds that physiologically bind Aβ and modulate its aggregation and neurotoxicity. In order to develop new Aβ-specific peptides for AD, a randomized 12-mer peptide library with Aβ1-10 as the target was used to identify peptides in the present study. After three rounds of selection, specific phages were screened, and their binding affinities to Aβ1-10 were found to be highly specific. Finally, a special peptide was synthesized according to the sequences of the selected phages. In addition, the effects of the special peptide on Aβ aggregation and Aβ-mediated neurotoxicity in vitro and in vivo were assessed. The results show that the special peptide not only inhibited the aggregation of Aβ into plaques, but it also alleviated Aβ-induced PC12 cell viability and apoptosis at appropriate concentrations as assessed by the cell counting kit-8 assay and propidium iodide staining. Moreover, the special peptide exhibited a protective effect against Aβ-induced learning and memory deficits in rats, as determined by the Morris water maze task. In conclusion, we selected a peptide that specifically binds Aβ1-10 and can modulate Aβ aggregation and Aβ-induced neuronal damage. This opens up possibilities for the development of a novel therapeutic approach for the treatment of AD

Carrier Management via Integrating InP Quantum Dots into Electron Transport Layer for Efficient Perovskite Solar Cells

Metal oxides are the most efficient electron transport layers (ETLs) in perovskite solar cells (PSCs). However, issues related to the bulk (i.e., insufficient electron mobility, unfavorable energy level position) and interface of metal oxide/perovskite (detrimental surface hydroxyl groups) limit the transport kinetics of photoinduced electrons and prevent PSCs from unleashing their theoretical efficiency potential. Herein, the inorganic InP colloid quantum dots (CQDs) with outstanding electron mobility (4600 cm2 V-1 s-1) and carboxyl (−COOH) terminal ligands were uniformly distributed into the metal oxide ETL to form consecutive electron transport channels. The hybrid InP CQD-based ETL demonstrates a more N-type characteristic with more than 3-fold improvement in electron mobility. The formation of the Sn–O–In bond facilitates electron extraction due to suitable energy level alignment between the ETL and perovskite. The strong interaction between uncoordinated Pb2+ at the perovskite/ETL interface and the −COO- in the ligand of InP CQDs reduces the density of defects in perovskite. As a result, the hybrid InP CQD-based ETL with an optimized InP ratio (18 wt %) boosts the power conversion efficiency of PSCs from 22.38 to 24.09% (certified efficiency of 23.43%). Meanwhile, the device demonstrates significantly improved photostability and atmospheric storage stability

Phage display mediated immuno-PCR

Immuno-PCR (IPCR) is a powerful detection technology in immunological study and clinical diagnosis due to its ultrasensitivity. Here we introduce a new strategy termed phage display mediated immuno-PCR (PD-IPCR). Instead of utilization of monoclonal antibody (mAb) and chemically bond DNA that required in the conventional IPCR, a recombinant phage particle is applied as a ready reagent for IPCR experiment. The surface displayed single chain variable fragment (scFv) and phage DNA themselves can directly serve as detection antibody and PCR template, respectively. The aim of the design is to overcome shortcoming of low detection sensitivity of scFv so as to largely facilitate the real application of scFv in immunoassay. The idea has been demonstrated by applying hantaan virus nucleocapsid protein (NP) and prion protein (PrP) as detection targets in three experimental protocols (indirect, sandwich and real-time PD-IPCR assays). The detection sensitivity was increased 1000- to 10 000-folds compared with conventional enzyme-linked immunosorbent assays (ELISAs). This proof-of-concept study may serve as a new model to develop an easy to operate, low cost and ultrasensitive immunoassay method for broad applications