Zobrazení zdroje stránky Hansenvelazquez2773

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. [https://www.selleckchem.com/products/Dapagliflozin.html see more] Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p  less then  10-8) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p  less then  0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p  less then  0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.<br /><br /> Mesenchymal stem cells (MSCs) isolated from bone marrow have different developmental origins, including neural crest. MSCs can differentiate into neural progenitor-like cells (NPCs) under the influence of bFGF and EGF. NPCs can terminally differentiate into neurons that express beta-III-tubulin and elicit action potential. The main aim of the study was to identify key genetic markers involved in differentiation of MSCs into NPCs through transcriptomic analysis.<br /><br /> Total RNA was isolated from MSCs and MSCs-derived NPCs followed by cDNA library construction for transcriptomic analysis. Sample libraries that passed the quality and quantity assessments were subjected to high throughput mRNA sequencing using NextSeq®500. Differential gene expression analysis was performed using the DESeq2 R package with MSC samples being a reference group. The expression of eight differentially regulated genes was counter validated using real-time PCR.<br /><br /> In total, of the 3,252 differentially regulated genes between MSCs and NPCs profiles between NPCs and MSCs revealed a set of markers that can identify the differentiation stage of NPCs as well as provide new targets to enhance MSCs differentiation into NPCs.<br /><br />The vast differences in the transcriptomic profiles between NPCs and MSCs revealed a set of markers that can identify the differentiation stage of NPCs as well as provide new targets to enhance MSCs differentiation into NPCs.<br /><br /> Asthma is one of the main intractable diseases recognized by the international medical community. The current widely used bronchodilators for asthma-β2-adrenal receptor agonists-have limited therapeutic effects, necessitating the development of novel antiasthma drugs with increased efficacy and fewer adverse effects. In this study, we investigated the relaxant effects and underlying mechanism of an ethyl acetate extract from dandelion (EAED) on mouse airway smooth muscle.<br /><br /> The effects of EAED on agonist-induced precontraction in mouse airway smooth muscle were evaluated with force measurement. Mouse lung slices were used to study the effects of EAED on bronchial smooth muscle. The intracellular Ca<br /><br /> concentration was measured using a calcium imaging system. L-type voltage-dependent calcium channel (VDLCC) and non-selective cationic channel (NSCC) currents were measured by patch-clamp. The lung functions of healthy and asthmatic mouse groups were assessed via the forced oscillation technique.<br /><br /> EAED inhibits acetylcholine-induced sustained contractions of whole airway smooth muscle by inhibiting VDLCCs, NSCCs, and some unknown channels, reduces the agonist-induced increase in the cytosolic free Ca<br /><br /> concentration in airway smooth muscle cells, blocks VDLCC and NSCC currents, and relieves the respiratory resistance of healthy and asthmatic mice.<br /><br /> EAED may have potential beneficial effects on mitigating asthma attacks.<br /><br />EAED may have potential beneficial effects on mitigating asthma attacks.<br /><br /> Glioblastoma (GBM) is an immunosuppressive, highly vascular and devastating malignant brain tumor. Even with progressive combination treatment that includes surgery, radiotherapy, and chemotherapy, the prognosis for GBM patients is still extremely poor. Oncolytic adenovirus (OAd) can specifically replicate in GBM cells, permitting the rapid copy of the therapeutic genes it carries. Moreover, E1A is an essential gene in adenoviral replication and is the first gene expressed upon viral infection. E1A expression can be regulated by the Ki67 promoter, while the CMV promoter drives therapeutic gene expression. However, the efficacy of a double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 against GBM cells has not been investigated.<br /><br /> Fluorescence microscopy was performed to evaluate infection ability in the viruses. Cell viability was detected by CCK-8 assay. Levels of cytokines in different supernatants were determined by ELISA, and IL-15 gene expression was measured by RT-PCR. Angiogenic capacity was analyzed by tube formation assay.<br /><br /> We successfully constructed a double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 that selectively infected and killed GBM cells while sparing normal cells. The adenoviruses prime IL-15 gene expression to significantly enhance anti-GBM efficacy through effective activation of microglial cells. Moreover, OAd not only directly inhibits angiogenesis but exhibits potent antiangiogenic capacity mediated by the reduction of VEGF secretion.<br /><br /> These results provide new insight into the effects of a novel double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 in glioblastoma treatment, which may help in the development of novel therapies in solid tumors.<br /><br />These results provide new insight into the effects of a novel double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 in glioblastoma treatment, which may help in the development of novel therapies in solid tumors.