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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
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ADP‐Induced Ca 2+ Signaling and Proliferation of Rat Ventricular Myofibroblasts Depend on Phospholipase C‐Linked TRP Channels Activation Within Lipid Rafts
Nucleotides released during heart injury affect myocardium electrophysiology and remodeling through P2 purinoceptors activation in cardiac myofibroblasts. ATP and UTP endorse [Ca 2+ ] i accumulation and growth of DDR‐2/α‐SMA‐expressing myofibroblasts from adult rat ventricles via P2Y 4 and P2Y 2 receptors activation, respectively. Ventricular myofibroblasts also express ADP‐sensitive P2Y 1 , P2Y 12 , and P2Y 13 receptors as demonstrated by immunofluorescence confocal microscopy and western blot analysis, but little information exists on ADP effects in these cells. ADP (0.003–3 mM) and its stable analogue, ADPßS (100 μM), caused fast [Ca 2+ ] i transients originated from thapsigargin‐sensitive internal stores, which partially declined to a plateau sustained by capacitative Ca 2+ entry through transient receptor potential (TRP) channels inhibited by 2‐APB (50 μM) and flufenamic acid (100 μM). Hydrophobic interactions between G q/11 ‐coupled P2Y purinoceptors and TRP channels were suggested by prevention of the ADP‐induced [Ca 2+ ] i plateau following PIP 2 depletion with LiCl (10 mM) and cholesterol removal from lipid rafts with methyl‐ß‐cyclodextrin (2 mM). ADP [Ca 2+ ] i transients were insensitive to P2Y 1 , P2Y 12 , and P2Y 13 receptor antagonists, MRS2179 (10μM), AR‐C66096 (0.1 μM), and MRS2211 (10μM), respectively, but were attenuated by suramin and reactive blue‐2 (100 μM) which also blocked P2Y 4 receptors activation by UTP. Cardiac myofibroblasts growth and type I collagen production were favored upon activation of MRS2179‐sensitive P2Y 1 receptors with ADP or ADPßS (30 μM). In conclusion, ADP exerts a dual role on ventricular myofibroblasts: [Ca 2+ ] i transients are mediated by fast‐desensitizing P2Y 4 receptors, whereas the pro‐fibrotic effect of ADP involves the P2Y 1 receptor activation. Data also show that ADP‐induced capacitative Ca 2+ influx depends on phospholipase C‐linked TRP channels opening in lipid raft microdomains. J. Cell. Physiol. 232: 1511–1526, 2017. © 2016 Wiley Periodicals, Inc.
Semaphorin 3A Negatively Affects Proliferation of Mouse Thymus Epithelial Cells In Vitro
We studied effects of semaphorin 3A, keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and their combinations on the proliferative activity of cortical (cTEC1-2) and medullary (mTEC3-10) thymus epithelium cell lines. Semaphorin 3A inhibited the proliferative activity of epithelial cells, while HGF and KGF, in contrast, exerted a stimulating effect. The effect of KGF and semaphorin 3A on different cell lines depended on the expression of receptors for these two factors. When the combination of two factors was used, semaphorin 3A was able to neutralize the stimulating effect of HGF and KGF. It can be assumed that semaphorin 3A synthesized in the thymus stroma, can act as a functional antagonist of HGF and KGF and have an inhibitory effect when these drugs are administered into the body for the therapeutic purpose of restoring thymus functions.
Identification of important invasion and proliferation related genes in adrenocortical carcinoma
Adrenocortical carcinoma (ACC) is an end‐stage hormonal syndrome. Although profound attempts have been made to illuminate the pathogenesis, the molecular mechanisms of ACC remain to be clarified. To identify the important genes in the progression of ACC, microarray datasets GSE19775 was downloaded from the gene expression omnibus database. The differentially-expressed genes (DEGs) were identified, and pathway and GO enrichment analyses were performed. The protein–protein interaction (PPI) network was constructed and the module analysis was performed using the protein interaction network analysis and Cytoscape. Also constructed target genes–miRNA regulatory network and target genes–TF regulatory network. Correlation of the hub genes were analyzed in The Cancer Genome Atlas. The prognostic values of hub genes were further validated by online tool UALCAN. Mutation analysis was done by online tool CBio Cancer Genomics Portal. A total of 884 DEGs were identified, with 441 in up regulation and 443 in down regulation. Pathways in catecholamine biosynthesis, aldosterone synthesis and secretion, pyrimidine deoxyribonucleosides salvage and systemic lupus erythematosus were the most significantly enriched for DEGs (up and down regulated). Blood vessel morphogenesis and cell cycle phase transition were the most significantly enriched term in biological processes, while extracellular matrix and chromosome, centromeric region were in cellular component and heparin binding and protein dimerization activity were in molecular function. Among the PPI networks and its module, target genes–miRNA regulatory network and target genes–TF regulatory network, hub genes were YWHAZ, FN1, GRK5, VCAM1, GATA6, TXNIP, HSPA1A, and F11R. Hub genes such as YWHAZ, STAT1, ICAM1, SH3BP5, CD83, FN1, TK1, HIST1H1C, CABLES1, and MCM3 were associated with poor overall survival, while hub genes such as STAT1, ICAM1, CD83, FN1, TK1, HIST1H1C, and MCM3 were highly expressed in stage 4. In conclusion, DEGs and hub genes diagnosed in this study may deepen our understanding of molecular mechanisms underlying the progression of ACC, and provide important targets for diagnosis and treatment of ACC.
CD27{sup -}CD45{sup +} γδ T cells can be divided into two populations, CD27{sup -}CD45{sup int} and CD27{sup -}CD45{sup hi} with little proliferation potential
In addition to the majority of T cells which carry the αβ T cell receptor (TCR) for antigen, a distinct subset of about 1–5% of human peripheral blood T cells expressing the γδ TCR contributes to immune responses to infection, tissue damage and cancer. T cells with the Vδ2{sup +} TCR, usually paired with Vγ9, constitute the majority of these γδ T cells. Analogous to αβ T cells, they can be sorted into naive (CD27{sup +}CD45RA{sup +}), central memory (CD27{sup +}CD45RA{sup −}), effector memory (CD27{sup −}CD45RA{sup −}), and terminally-differentiated effector memory (CD27{sup −}CD45RA{sup +}) phenotypes. Here, we found that CD27{sup −}CD45RA{sup +} γδ T cells can be further divided into two populations based on the level of expression of CD45RA: CD27{sup −}CD45RA{sup int} and CD27{sup −}CD45RA{sup hi}. Those with the CD27{sup −}CD45RA{sup hi} phenotype lack extensive proliferative capacity, while those with the CD27{sup −}CD45RA{sup int} phenotype can be easily expanded by culture with zoledronate and IL-2. These CD27{sup -}CD45RA{sup hi} potentially exhausted γδ T cells were found predominantly in cancer patients but also in healthy subjects. We conclude that γδ T cells can be divided into at least 5 subsets enabling discrimination of γδ T cells with poor proliferative capacity. It was one of our goals to predict the feasibility of γδ T cell expansion to sufficient amounts for adoptive immunotherapy without the necessity for conducting small-scale culture tests. Fulfilling the ≥1.5% criterion for γδ T cells with phenotypes other than CD27{sup −}CD45RA{sup hi}, may help avoid small-scale culture testing and shorten the preparation period for adoptive γδ T cells by 10 days, which may be beneficial for patients with advanced cancer. - Highlights: • CD27{sup -}CD45{sup +} γδ T cells can be divided into two populations, CD27{sup -}CD45{sup hi} and CD27{sup -}CD45{sup int}. • CD27{sup -}CD45{sup hi} γδ T cells are detected in the peripheral blood of both cancer patients and healthy subjects. • CD27{sup -}CD45{sup hi} γδ T cells are distinct from so-called terminally differentiated CD27{sup -}CD45{sup int} γδ T cells. • CD27{sup -}CD45{sup hi} γδ T cells lack vigorous proliferative potential.
PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway
Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention. - Highlights: • PRRT2 is decreased in glioma and is targeted by miR-30a-5p. • PRRT2 exhibits tumor-suppressive effects on glioma cells. • PRRT2 correlates genes involved in unfolded protein response. • Over-expressed PRRT2 induces unfolded protein response in glioma in vitro.
CNPY2 promoted the proliferation of renal cell carcinoma cells and increased the expression of TP53
Renal cell carcinoma (RCC) is the most common type of kidney cancer. However, the mechanisms underlying the progression of the disease are not well understood. The data in this report suggest that canopy FGF signaling regulator 2 (CNPY2) is a promoter of RCC progression. We found that CNPY2 significantly promoted growth of RCC cells and upregulated TP53 gene expression. Although TP53 is widely known as a tumor suppressor, in RCC TP53 promoted tumor cell growth. A typical p53 target gene, CDKN1A, was upregulated by both p53 and CNPY2 in RCC cells, suggesting that CNPY2 increased the expression level of TP53. Consistent with these results, CNPY2 and TP53 expression levels were positively correlated in RCC patients. These findings suggested that CNPY2 promoted cancer cell growth in RCC through regulating TP53 gene expression. - Highlights: • CNPY2 promoted growth of renal cell carcinoma (RCC) cells. • TP53 expression levels were increased by CNPY2 in RCC cells. • Growth of RCC cells was promoted by TP53. • CNPY2 expression positively correlated with TP53 expression in RCC patients.
Catalpol suppresses osteosarcoma cell proliferation through blocking epithelial-mesenchymal transition (EMT) and inducing apoptosis
Highlights: • Catalpol inhibits cell viability and EMT in osteosarcoma cell lines. • Catalpol induces apoptosis in osteosarcoma cell lines by Bcl-2/Caspase-8 signaling. • Catalpol induces ROS generation and suppresses STAT3 pathway activation. • Catalpol is able to suppresses osteosarcoma growth in vivo. Catalpol, an iridoid glucoside compound, is reported to possess diverse pharmacological actions. However, its effects on osteosarcoma are little to be known. In the present study, we showed that catalpol could strongly suppress osteosarcoma progression. Catalpol dose-dependently reduced the cancer cell viability. The migration of osteosarcoma cells was also consistently suppressed by catalpol treatment using the wound healing and transwell migration analysis. Catalpol reduced the expressions of Kras, receptor for activated C-kinase 1(RACK1) and matrix metalloproteinase (MMP)-2 in a dose-dependent manner, revealing the blockage of migration. Moreover, both intrinsic and extrinsic apoptosis were triggered by catalpol, as evidenced by improved cleaved Caspase-8/-9/-3 and Poly-(ADP-ribose) polymerase (PARP). Release of Cyto-c in cytoplasm and Bax up-regulation in total cells were observed in catalpol-treated cells, while mitochondrial Cyto-c and cellular Bcl-2 were down-regulated by catalpol. Reactive oxygen species (ROS) production was also involved in catalpol-induced cell death. Further, ROS scavenger, N-acetylcysteine (NAC), impeded catalpol-caused apoptosis. And suppression of signal transducer and activator of transcription 3/Janus kinase 2 gene/Src (STAT3/JAK2/Src) was involved in catalpol-induced cell death. In vivo, catalpol showed effective ability to reduce the tumor growth. Our results illustrated that catalpol might be considered as a promising pharmacological agent to suppress osteosarcoma.
PUM1 promotes ovarian cancer proliferation, migration and invasion
Highlights: • This is the first investigation about PUM1 gene function in ovarian cancer. • PUM1 levels were significantly higher in ovarian cancer than in normal tissues. • PUM1 induces ovarian cancer cell growth, migration, and invasion in vitro. Abnormal expression of the PUM1 gene (pumilio RNA binding family member 1) is closely related to chromosomal mutations and carcinogenesis. However, there is no report about expression or function of PUM1 in ovarian cancer. The present study explored the role of PUM1 in the development and progression of ovarian cancer.
LncRNA snaR upregulates GRB2-associated binding protein 2 and promotes proliferation of ovarian carcinoma cells
The functionality of lncRNA snaR has only been characterized in breast cancer and colon cancer. The aim of the current study is to explore the involvement of lncRNA snaR in ovarian carcinoma (OC).
Downregulation of KMT2D suppresses proliferation and induces apoptosis of gastric cancer
Histone lysine methyltransferase 2D (KMT2D/MLL2) is a known cancer-related protein; however, its function in gastric cancer (GC) remains uncharacterized. The present study sought to investigate the expression pattern and the role of KMT2D in GC.
BAF53A regulates androgen receptor-mediated gene expression and proliferation in LNCaP cells
The actin-like protein of the SWI/SNF complex, BAF53A, regulates gene expression by the gene-specific chromatin remodeling of target genes. However, the function of BAF53A in the androgen receptor pathway in prostate cancer cells remains unclear. Here, we demonstrated that BAF53A positively regulates the expression of endogenous AR target genes (e.g. PSA, TMPRSS2, FKBP5, and KLK2) in LNCaP cells. It functions as a coactivator in AR-mediated transcription by interacting with other nuclear receptor coactivators, such as p300 and FLII, and is associated with AR in the presence of dihydrotestosterone (DHT). The DHT-induced recruitment of BAF53A to the proximal and distal androgen response elements (AREs) of the PSA gene in the presence of BRG1 (but not BRM) was inhibited by an AR antagonist, suggesting the coactivator function of BAF53A in the SWI/SNF complex. Depletion of BAF53A in LNCaP cells resulted in a significant decrease in growth rate. Furthermore, the expression of BAF53A in prostate cancer tissue was significantly elevated, compared to that in normal prostate tissue, and correlated with the expression of AR, and BRG1, but not BRM. Therefore, our results suggested that BAF53A plays an important role in the expression of AR target genes in prostate cancer, and can be used clinically for the treatment of prostate cancer.
Iron chelator-induced up-regulation of Ndrg1 inhibits proliferation and EMT process by targeting Wnt/β-catenin pathway in colon cancer cells
Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), as the novel iron chelator, has been reported to inhibit the tumorigenesis and progression of various cancer cells. However, whether Dp44mT has anticancer effects in colon cancer cells is still unknown. Here, we investigated the antitumor action of Dp44mT in colon cancer and its underlying mechanisms, and the connections between Dp44mT and N-myc downstream-regulated genes 1(Ndrg1). We used cell viability, migration and invasion assay, flow cytometry, western blot and qRT-PCR to examine the anticancer effects of Dp44mT and Ndrg1. We found that Dp44mT suppressed cell viability, migration, invasion and induced apoptosis of colon cancer cells and over-expression of Ndrg1 also suppressed cell viability, migration, invasion and induced apoptosis of colon cancer cells. Dp44mT attenuated the TGF-β1-induced EMT in colon cancer cells, and Dp44mT could up-regulate Ndrg1 expression level. Overexpression of Ndrg1 attenuates the TGF-β1-induced EMT, Dp44mT and Ndrg1 suppressed EMT through activation of Wnt/β catenin signaling pathway. In conclusion, our data demonstrated that Dp44mT/Ndrg1 have effective anticancer capability in colon cancer cells and that may represent a promising treatment strategy for human colon cancer.
221S-1a inhibits endothelial proliferation in pathological angiogenesis through ERK/c-Myc signaling
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