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ObjectiveTo provide a new idea for exploring the molecular genetic approach to the pathogenesis of schizophrenia via construction of microRNA-messenger RNA （miRNA-mRNA） regulatory network in schizophrenia. MethodsThe microarray datasets of GSE54578 miRNA expression profiles in peripheral blood and GSE145554 mRNA expression in the anterior cingulate in postmortem brain of schizophrenic subjects were downloaded from Gene Expression Omnibus （GEO） database since July 2021. The GEO2R was used to identify the differentially expressed miRNAs and mRNAs， screen the miRNA with target differentially expressed mRNA， and predict their potential upstream transcription factors. The overlapping genes from the mRNA targeted by the differentially expressed miRNA and the mRNA differentially expressed in GSE145554 dataset were collected. Then the biological features of hub genes were analyzed via Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis， and the protein-protein interaction （PPI） network and miRNA-mRNA regulatory network of hub genes were constructed. ResultsA total of 8 up-regulated differentially expressed miRNAs with targeted mRNA were screened out in GSE54578 datasets regarding schizophrenia， which involved in the regulation of 10 transcription factors， 247 down-regulated differentially expressed mRNAs were screened out in GSE145554 datasets， and 17 overlapping mRNAs were obtained. GO analysis showed that the target mRNAs were mainly involved in astrocyte differentiation and development. KEGG pathway enrichment analysis showed that the target mRNAs were mainly involved in Rap1 and Ras signaling pathways. PPI network analysis showed that the mRNAs （KRAS and CD28） might be key genes in schizophrenia. ConclusionThe integrated bioinformatics analysis based on GEO database can identify potential susceptibility genes in schizophrenia， and it also contributes to the construction of miRNA-mRNA regulatory network in schizophrenia.
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There exists a complex relationship between liver and thyroid hormones. Liver plays an important role in the activation, inactivation, transportation, and metabolism of thyroid hormones. At the same time, thyroid hormones also affect hepatocytes activity and liver metabolism, such as lipid and bilirubin metabolism. Importantly, thyroid hormone levels often change abnormally in patients with liver cirrhosis. Therefore, studying the change of thyroid hormone levels in patients with liver cirrhosis has a certain clinical value for assessing the severity, prognosis, diagnosis and treatment. This paper reviews the research progress on the relationship between liver cirrhosis and thyroid hormone.
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Humans , Bilirubin , Liver/metabolism , Liver Cirrhosis/metabolism , Thyroid Hormones/metabolismABSTRACT
Aim To investigate the changes of autoph- A gy in rat testis and its effect on blood-testis barrier during aging. Methods HE staining was used to observe the morphological changes of testis in SD male rats at 6, 12, 18 and 24 months old. Western blot was used to detect the relative expression of autophagy-re-lated proteins Beclinl, ATG5, ATG7 and 1X13II, and the blood-testis barrier related connexins Occludin and (3-catenin. Immunofluorescence was used to detect the expression and localization of the autophagy-associated proteins Beclinl and LC3, as well as the protein of the cell connexin p-catenin. Results HE staining showed that the morphology and structure of rat testis changed significantly during the aging process, the seminiferous tubules atrophied, the number of spermatogenic cells decreased, the gap between cells increased, and partial shedding occurred. Western blot results showed that the relative expression of autophagy-related proteins Beclinl, ATG5, ATG7 and LC3II, and the blood-testis barrier-related proteins Occludin and p-catenin gradually decreased during aging. The results of immunofluorescence showed that the autophagy marker proteins Beclinl and LC3 were down-regulated in rat seminiferous epithelial cells during the aging process, and the expression of the blood-testis barrier marker protein p-catenin also gradually decreased. Conclusions During the aging process, the spermato-genic function of the testis is reduced in rats, and the mechanism is related to the decrease of the autophagy level of testicular spermatogenic epithelial cells, which in turn destroys the integrity of the blood testis barrier.
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Objective: To study the protective effects of icariin on DNA damage of testicular germ cells in natural aging rats and explore the possible mechanism. Methods: In the study, the SD rats were separated into four groups at random, with eight rats in each group: adult control group (2 months old), aging model group (16 months old), low and high doses of icariin-treated groups (2 mg/kg and 6 mg/kg, 16 months old). The adult control group and the aging model group were fed with normal diet for four months. Icariin-treated groups were given medicated feed for four months. After fasting for 12 h, all the rats were put to death. The testicular morphology was observed using HE staining. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in testicular tissue were detected by xanthine oxidase method and thiobarbituric acid method, respectively. The protein expression of Nrf2 and γ-H2AX were detected by immunofluorescence. The relative protein expression levels of Nrf2, HO-1, NQO1, γ-H2AX, p-p53, and p21 were detected by Western blotting. Results: HE staining results showed that icariin significantly improved the structure of testicular tissue of natural aging rats. Compared with the aging model group, icariin significantly increased the SOD activity and decreased the MDA content in testis. In addition, immunofluorescence results showed that icariin significantly decreased the expression of DNA damage response protein γ-H2AX and increased the protein expression of Nrf2 in testicular germ cells of aging rats.Moreover, Western blotting results showed that icariin significantly increased the relative protein expression levels of Nrf2, HO-1 and NQO1 in testis, when compared with aging model group. In parallel, the relative protein expression levels of γ-H2AX, p-p53, and p21 were significantly decreased. Conclusion: Icariin attenuates DNA damage in testicular germ cells of natural aging rats, which may be associated with the activation of Nrf2/HO-1 signaling pathway.
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To study the protective effects of Wuzi Yanzong recipe on testis germ cell apoptosis in natural ageing rats through endoplasmic reticulum stress (ERS), 16-month-old male SPF grade SD rats were randomly divided into three groups: ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1 and 4 g·kg⁻¹), with 10 rats in each group. In addition, 2-month-old SD male rats were used as adult control group. The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given the medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately collected. The change of testicular tissue morphology was observed by HE staining. The expression levels of ER stress-related proteins GRP78, p-PERK, p-eif2, ATF4, p-IRE1, XBP1, ATF6 and apoptosis-related proteins CHOP, caspase12 and p-JNK in testes were detected by Western blot. Compared with the ageing model group, Wuzi Yanzong recipe alleviated the morphological changes of testicular tissue. Western blot results showed that Wuzi Yanzong recipe significantly increased the expression levels of endoplasmic reticulum stress-related proteins GRP78, p-PERK, p-eif2, ATF4, p-IRE1, XBP1, ATF6 and significantly decreased the expression levels of endoplasmic reticulum-induced apoptosis-related proteins CHOP, caspase 12 and p-JNK. In conclusion, Wuzi Yanzong recipe can alleviate the ageing-related apoptosis of testicular germ cells in natural ageing rats by regulating endoplasmic reticulum stress.
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Animals , Male , Rats , Aging , Apoptosis , Drugs, Chinese Herbal , Pharmacology , Endoplasmic Reticulum Stress , Germ Cells , Rats, Sprague-Dawley , TestisABSTRACT
To study the protective effects of Wuzi Yanzong recipe on DNA oxidative damage of testis germ cells in natural ageing rats based on Nrf2/HO-1 signaling pathway and base excision repair (BER). In the study, 16-month-old SPF grade male SD rats were randomly divided into three groups, namely ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1, 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately removed. The vitality of superoxide dismutase (SOD) and malondialdehyde (MDA) content in testis were detected by xanthine oxidase method and thiobarbituric acid (TBA) method. The levels of Nrf2 and 8-OHdG were detected by immunofluorescence. The protein expression levels of Nrf2, HO-1, NQO1, APE1, OGG1 and XRCC1 were detected by Western blot. Compared with the ageing model group, WZ significantly increased the SOD vitality and decreased MDA content of testis. In addition, immunofluorescence results showed that WZ significantly attenuated testicular DNA oxidative damage and improved antioxidant capacity. Such changes were accompanied by the down-regulation of DNA oxidative damage response protein 8-OHdG levels and the up-regulation of Nrf2 levels. Moreover, Western blot results showed that WZ significantly increased the protein expression levels of Nrf2, HO-1 and NQO1 of the testis germ cells, when compared with ageing model group. In parallel, the protein expression levels of APE1, OGG1 and XRCC1 were significantly decreased. In conclusion, WZ improves ageing-related DNA oxidative damage via Nrf2/HO-1 and BER pathways.
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OBJECTIVE: To analyze the cost-effectiveness of irbesartan and bisoprolol using Markov model for the purpose of choosing a secure and effective therapy for hypertension with heart failure. METHODS: Markov state transition model was built to simulate the dynamic changes of the four states (event free, non-fatal myocardial infarction, non-fatal stoke and death) in the hypertension with heart failure patients who received the irbesartan or bisoprolol treatment. Markov model was applied using roll back analysis, Markov cohort simulation to project the costs and effectiveness for the hypertension with heart failure who had been long-term treated with irbesartan or bisoprolol. One way sensitivity analysis was carried out to determine the robustness of this baseline results. RESULTS: The results of cost-effectiveness analysis showed that patients receiving irbesartan cumulative costs and effects were 60 635.48 yuan and 6.22 quality-adjusted life years gained. Patients receiving bisoprolol cumulative costs and effects were 58 185.12 yuan and 6.17 quality-adjusted life years gained and the ICER was 49 007.20 yuan/QALYs. According to the sensitivity analysis, the change of key parameters in the set range did not affect the model results. CONCLUSION: Bisoprolol treatment is more economical than irbesartan treatment for hypertension with heart failure patients. This study could be used as methodology reference of pharmacoeconomics on the hypertension with heart failure diseases for Chinese pharmacoeconomist.
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<p><b>OBJECTIVE</b>To explore the effect of Wnt signaling suppression on proliferation of non small cell lung cancer to gefitinib, and its related mechanisms.</p><p><b>METHODS</b>PC9 and PC9/AB2 cells of both gefitinib sensitive and resistant were treated with different concentrations of gefitinib, and the proliferation index was measured using CCK8 kit. The members of Wnt signaling pathway were detected by Western blot. Dual luciferase reportor gene assay (TOP Flash) was used to document the transcriptional level of β-catenin. β-catenin siRNA was transfected into PC9/AB2 cells to suppress the Wnt signaling transcription, followed by treatment with different concentrations of gefitinib. Western blot was then used to detect the expression of EGFR and its downstream signaling after inhibit the expression of β-catenin.</p><p><b>RESULTS</b>Treating with different concentrations of gefitinib, the resistance of PC9/AB2 cells to gefitinib was significantly increased (P < 0.05). The members of Wnt signaling expressed at higher level in PC9/AB2 cells than in PC9 cells (t = 24.590, P = 0.000). TOP Flash examination showed that the endogenous transcriptional activity of Wnt signaling was higher in PC9/AB2 cell than that in PC9 cell (t = 4.983, P = 0.008). Compared with the negative control group, apoptotic rate and sensitivity to gefitinib significantly increased in interfered group (P < 0.05). The expression of p-ERK1/2 significantly decreased after Wnt signaling suppression, although other proteins showed no significant alterations.</p><p><b>CONCLUSION</b>Suppressing the activity of Wnt signaling can partly reverse the celluar resistance to gefitinib in non small cell lung cancer.</p>
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Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Lung Neoplasms , Metabolism , Pathology , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Phosphorylation , Quinazolines , Pharmacology , Wnt Signaling Pathway , beta Catenin , MetabolismABSTRACT
Berberine, a constituent of some traditional Chinese medicinal plants, has been reported to have cytotoxicity effects on different human cancer cell lines. There is no available information about the effects and mechanism of action of berberine on human colon cancer cell line HCT-8. In this paper, the cytotoxicity of berberine on HCT-8 cancer cells was investigated by MTT assay, fluorescence microscopy and flow cytometry analysis. Our data revealed that berberine could significantly inhibit the growth of HCT-8 cells in a dose- and time-dependent manner. Morphology of apoptotic cells was studied with acridine orange/ethidium bromide staining. The concentrations of lactate dehydrogenase and both acid and alkaline phosphatases were significantly increased in cell supernatants after berberine treatment, suggesting cell death. Furthermore, flow cytometry analysis showed that berberine could arrest HCT-8 cells at S phase in a time-dependent manner. To further investigate the apoptotic molecular mechanism, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting methods were used. The up-regulated mRNA and/or protein expressions of Fas, FasL, TNF-a, caspase-3 and down-regulation of pro-caspase-3 suggest that the death receptor pathway may be involved in the apoptotic pathway induced by berberine. Decrease of Bcl-2 and increase of Bax in mRNA and/or protein expressions showed that the Bcl-2 family proteins were involved in berberine-induced apoptosis. We also found that berberine-induced apoptosis was associated with an up-regulated expressions of p53 and prohibitin (PHB), and decreased vimentin expression. These results suggest that berberine can suppress cell growth and reduce cell survival by arresting the cell-cycle and by inducing apoptosis of HCT-8 cells.