Reduced arterial elasticity is a hallmark of ageing in healthy humans and appears to occur independently of coexisting disease processes. Endothelial-cell injury and dysfunction may be responsible for this fall in arterial elasticity. We hypothesized that circulating endothelial progenitor cells (EPCs) are involved in endothelial repair and that lack of EPCs contributes to impaired arterial elasticity. A total of 56 healthy male volunteers were divided into young (n ¼ 26) and elderly (n ¼ 30) groups. Large and small artery elasticity indices were noninvasively assessed using pulse wave analysis. The number of circulating EPCs was measured by using flow cytometry. Cells demonstrating DiI-acLDL and FITC-ulex lectin double-positive fluorescence were identified as EPCs. C1 large artery elasticity and C2 small artery elasticity indices were significantly reduced in the elderly group compared with the young group (11.7371.45 vs 16.8871.69 ml/mm Hg  10, Po0.001; 8.4071.45 vs 10.5871.18 ml/mm Hg  100, Po0.001, respectively). In parallel, the number of circulating EPCs was significantly reduced in the elderly group compared with the young group (0.1370.02 vs 0.1770.04%, Po0.05). The number of circulating EPCs correlated with C1 large and C2 small artery elasticity indices (r ¼ 0.47, Po0.01; r ¼ 0.4, Po0.01). The present findings suggest that the fall in circulating EPCs with subsequently impaired endothelial-cell repair and function contributes to reduced arterial elasticity in humans with ageing. The decrease in circulating EPCs may serve as a surrogate biologic measure of vascular function and human age.
Vascular dysfunction in hypertensive condition is characterized by impaired endothelial function and reduced artery elasticity. Circulating endothelial microparticles (EMPs) and brachial-ankle pulse wave velocity (baPWV) are novel evaluation parameters for vascular function. However, their changes in patients with well-controlled blood pressure (BP) have not been fully acquired. To address this issue, circulating EMPs, defined as CD31 þ /CD42À MPs and baPWV were detected in 30 healthy subjects, 30 uncontrolled hypertensive (UCHT) patients and 23 well-controlled hypertensive (WCHT) patients. UCHT patients displayed elevated baPWV (Po0.01) and circulating EMPs (Po0.01) compared with healthy subjects. In WCHT patients, vascular damage represented by these two parameters constantly existed (Po0.01). Values of circulating EMPs were positively related to baPWV (Po0.01). Multivariate regression defined circulating EMPs as an independent contributor to the increase of baPWV value (Po0.05). Our study indicated that though BP was controlled, impaired endothelial function and arterial elasticity continued. The optimal therapy for patients with hypertension should include not only lowering BP but also improvement of vascular injury in parallel.
Skin plays an important role in innate immune responses to bacterial infection, but its molecular mechanism remains unclear in fish. The transcriptional profiling of the skin immune response to Aeromonas hydrophila infection of the zebrafish, Danio rerio (Hamilton), was performed by Affymetrix microarray analysis. The results showed that 538 genes were differentially expressed, of which 388 genes were up-regulated and 150 genes were down-regulated. The expression patterns for 106 representative genes were observed to be up-regulated in zebrafish skin at 24 and 36 h post-infection, and gene expression changes were clearly greater at 36 h. Gene Ontology classification indicated that 222 genes were significantly associated with the skin immunity, including complement activation, acute-phase response, stress response, chemotaxis and apoptosis. Further Kyoto Encyclopedia of Genes and Genomes analysis showed that the significant pathways included MAPK, p53, Wnt, TGF-β, Notch, ErbB, JAK-STAT, VEGF, mTOR and Calcium signalling in skin immune responses, and several genes (e.g. akt2l, frap1, nras, rac1, xiap) were found to be involved in signalling networks. Moreover, expression changes in nine selected genes were verified by real-time qPCR analysis. This is the first known report on transcriptome analysis in the skin of zebrafish against the pathogen A. hydrophila.
Large-scale sequencing studies on glioblastoma have identified numerous genetic alterations.Leucine-zipper-like transcription regulator 1 (LZTR1) is inactivated by non-synonymous mutations and copy number losses, suggesting that it is a tumor suppressor in glioblastoma.However, how LZTR1 mutations contribute to glioblastoma pathogenesis remains poorly understood. Here, we revealed that LZTR1, as an adaptor of the CUL3 E3 ubiquitin ligase complex, recognizes and triggers ubiquitin-dependent degradation of oncoprotein RIT1, a RAS-like GTPase. Wild-type LZTR1 suppresses glioblastoma cell proliferation and migration by inactivating the MAPK/ERK signaling pathway in a RIT1-dependent manner. However, the effects were abrogated by the glioblastoma-associated LZTR1 mutations. Our findings revealed the underlying molecular mechanism of LZTR1 mutations-driven glioblastoma, and provide novel therapeutic target for LZTR1 mutations-driven glioblastoma.
Berberine (BR) has been proved to promote endothelial function. However, the exact mechanisms underlying the effect of BR on endothelial function are not completely clear. It has been demonstrated that endothelial progenitor cells (EPCs) contribute to improvement of endothelial function and C2 small artery elasticity index is a surrogate parameter for the clinical evaluation of endothelial function. We hypothesized that BR-induced mobilization of circulating EPCs is associated with BR-related improvement of endothelial function. To address this assumption, 15 healthy volunteers were recruited and received BR 0.4 g three times per day for 30 days. The number of circulating CD34/KDR double-positive cells as well as C1 large and C2 small artery elasticity indices were evaluated before and after BR therapy. The number of CD34/KDR doublepositive EPCs increased significantly after BR treatment (0.030 ± 0.020% vs 0.017 ± 0.010%, Po0.01). After 30-day BR therapy C2 increased significantly (6.21±2.80 ml per mm Hg  100 vs 4.06±2.67 ml per mm Hg  100, Po0.01) and C1 remained unchanged (10.79 ± 3.27 ml per mm Hg  10 vs 10.06 ± 2.08 ml per mm Hg  10, P40.05). The increment of CD34/KDR double-positive EPCs was positively correlated with the increment of C2 (r ¼ 0.68, Po0.01). We concluded that BR-induced mobilization of circulating EPCs contributes to improvement of small artery elasticity in healthy persons.
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