الملخص
Aim To study the regulation and mechanism of phloroglucinol in bladder smooth muscle spasm. Methods In vitro the experiment used bladder muscle strip to verify the relieving effect of phloro-glucinol on bladder spasm by different drugs. At the same time,RT-qPCR and Western blot were used to detect the expression levels of genes involved in the calcium signaling pathway caused by the antispasmodic effect of phloroglucinol. Results Phloroglucinol could relieve bladder spasm, and the antispasmodic effect was enhanced with the increase of concentration, and the expression of calponin 1 and MYLK3 in tissue cells increased. The results of RT-qPCR showed that the expression of Gprc5b G,Ppp2r5a, Chptl, Prkar2b ,Abcd2 and Rasdl genes in mouse bladder tissue significantly decreased, which was consistent with the sequencing results of RNA-seq.Conclusions Phloroglucinol can relieve bladder smooth muscle spasm, and its mechanism is related to calcium signaling pathway. Meanwhile, phloroglucinol also inhibits the expression of Rasdl gene, suggesting that it may be related to cell cycle , protein phosphorylation, choline metabolism, ATP synthesis and tumor-related pathways.
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Objective @# To observe the clinical significance of miR-135b-5p in oral squamous cell carcinoma (OSCC) tissues and to conduct a bioinformatics analysis of its predicted target genes.@*Methods @#The expression levels of miR-135b-5p in OSCC tissues and adjacent normal tissues were compared using data from TCGA and GEO databases, and the correlations of miR-135b-5p expression level with clinicopathologic characteristics were analyzed. Fresh tissues were collected in the clinic, and the expression of miR-135b-5p was verified by quantitative real-time PCR. The target genes with enriched pathways were analyzed by using bioinformatics methods. A protein-protein interaction network was constructed to screen hub genes.@*Results @#The expression levels of miR-135b-5p were significantly upregulated in OSCC tissues compared to adjacent normal tissues (P < 0.001) and had a good diagnostic capability (AUC=0.960, P < 0.001). The expression level of miR-135b-5p was positively correlated with histopathological grading (P=0.011). Enrichment analyses revealed that the target genes of miR-135b-5p were significantly associated with tumor-related signaling pathways, such as the calcium signaling pathway, the cGMP-PKG signaling pathway and the cAMP signaling pathway. Ten core target genes were obtained by screening: DLG2, ANK3, ERBB4, SCN2B, NBEA, GABRB2, ATP2B2, SNTA1, CACNA1D, and SPTBN4.@*Conclusion@#miR-135b-5p may act as an oncogene miRNA in OSCC and has the potential value of acting as a diagnostic biomarker and therapeutic target for OSCC.
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Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.
الموضوعات
Animals , Rats , Animals, Newborn , Camphanes , Chemistry , Cardiotonic Agents , Chemistry , Pharmacology , Cells, Cultured , Drugs, Chinese Herbal , Chemistry , Pharmacology , Eugenol , Chemistry , Gene Expression , Hydroxybenzoates , Chemistry , Mass Spectrometry , Models, Biological , Myocytes, Cardiac , Nitric Oxide Synthase Type III , Genetics , Phenanthrenes , Chemistry , Rats, Sprague-Dawley , Receptor, PAR-1 , Genetics , Systems Biologyالملخص
Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.
الموضوعات
Animals , Rats , Animals, Newborn , Camphanes , Chemistry , Cardiotonic Agents , Chemistry , Pharmacology , Cells, Cultured , Drugs, Chinese Herbal , Chemistry , Pharmacology , Eugenol , Chemistry , Gene Expression , Hydroxybenzoates , Chemistry , Mass Spectrometry , Models, Biological , Myocytes, Cardiac , Nitric Oxide Synthase Type III , Genetics , Phenanthrenes , Chemistry , Rats, Sprague-Dawley , Receptor, PAR-1 , Genetics , Systems Biologyالملخص
Objective To study the effects of 6-week aerobic treadmill exercise on the genes expression in skeletal muscle of C57BL/6 mice.Gene array was performed and the data was analyzed to evaluate the adaptive changes at gene level caused by exercise.Methods Twenty male C57BL/6 mice were randomly divided into two groups:control group(C) and aerobic exercise group (E).The mice from group E were forced to run on treadmill for 6 weeks.After 6 weeks,all mice were fasted for 16 hours,and then sacrificed.Their flexor muscle was removed.4 samples from each group were analyzed with gene chips to dissect the differentially expressed genes between the two groups.Results Our results showed that 723 genes were differentially expressed in E group as compared with C group after the 6 weeks aerobic exercise,among which 510 genes were up-and 213 down-regulated.There were 6 differentially expressed calcium signaling genes and 2 ofwhich(Gnall and Pdgfra) were up-regulated,while the others(Phka1,Picd4,RYR1 and Ppid)were down regulated.
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Bipolaris maydis, the causal agent of northern leaf blight of maize, forms a dome-shaped infection structure, an appressorium, to infect its host. To elucidate if calcium signaling pathway is correlated with conidium germination and appressorium formation of Bipolaris maydis induced by hydrophobic surface. Conidia were treated by three kinds of inhibitors. Microscopic examination and statistical data showed: (ⅰ)EGTA, a chelating agent selective for Ca~(2+), Verapamil which could block Ca~(2+) channels, KN93, a selective inhibitor of CaMK could inhibit germination and appressorium formation. (ⅱ)Under the same concentrations of inhibitors, appressorium formation was inhibited more strongly than conidium germination. These inhibitors caused the formation of small and abnormal appressorium. These results strongly suggested that Ca~(2+ )signaling pathway was involved in conidium germination and appressorium formation induced by hydrophobic surface.