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In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids (MitoHCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OHand ROOinduced lipid peroxidation. HOproduction was decreased significantly by increasing glutathione peroxidase and catalase activities. In addition, cell proliferation data from three cell lines (HepG2, L02 and WI38) indicated that the MitoHCAs were selective for cancer cells. Interestingly, the MitoHCAs both with or without Catriggered mitochondrial dysfunction by inducing mitochondrial swelling, collapsing the mitochondrial membrane potential and causing cytochromerelease. In particular, an inhibitor of the mitochondrial permeability transition pore (mPTP), cyclosporin A, attenuated mitochondrial damage and cell apoptosis, indicating that mPTP may be involved in the antiproliferative activity of MitoHCAs. Further studies focused on structural optimization of these compounds are onging.
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Objective To observe the clinical efficacy of abdominal acupuncture in treating perimenopausal insomnia.Method Sixty patients with perimenopausal insomnia were randomized into a treatment group and a control group, 30 in each group. The treatment group was intervened by abdominal acupuncture, while the control group was by regular body acupuncture. The FSH, LH, and E2 contents, and Pittsburgh Sleeping Quality Indext (PSQI) were observed before and after intervention, and the clinical efficacies were compared.Result The total effective rate was 90.0% in the treatment group versus 86.7% in the control group, and the difference was statistically insignificant (P>0.05). The PSQI score was changed significantly in both groups after intervention (P0.05). The FSH, LH, and E2 contents were significantly changed after intervention in both groups (P0.05).Conclusion Abdominal acupuncture in an effective method in treating perimenopausal insomnia.
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bThis study explored whether the transplantation of modified marrow stromal cells (MSCs) has angiogenic effects in a left middle cerebral artery occlusion infarction/reperfusion (MCAO I/R) rat model and preliminarily examined the mechanism of angiogenesis following cerebral infarction. MSCs were isolated by using a direct adherent method and cultured. Vascular endothelial growth factor (VEGF) was transfected into MSCs by employing the liposome transfection. The transfection efficiency was measured by the optical density method. The protein expression of VEGF gene before and after transfection was measured by Western blotting. SD rat model of transient occlusion of the left middle cerebral artery was established by using an approach of intra-luminal occlusion. Tetrazolium (TTC) and HE staining were performed to observe the cerebral infarction. ELISAs were used to measure the levels of VEGF in the rat cerebral tissues. The expression patterns of angiopoietin-2 (Ang-2) and CD34 in cells surrounding the area of infarction were immunohistochemistrically observed. Ang-2 protein expression in the tissue surrounding the area of infarction was measured by Western blotting. VEGF expression in the MSCs increased after transfection at a rate of approximately 28%±3.4%. ELISA showed that the expression of VEGF in the cerebral tissue was significantly increased after induction of infarction, peaking on the 4th day and decreasing to the levels of the sham surgery group (normal) within 7 to 10 days. The VEGF level was significantly higher at each time point in the VEGF-MSC and MSC groups compared to the model group. Moreover, the VEGF level was higher in the VEGF-MSC group than in the MSC group and stayed relatively high until the 10th day. The immunohistochemical results showed that 10 days after the infarction, the number of Ang-2 and CD34-expressing cells in the area surrounding the infarction was significantly higher in the VEGF-MSC group and the MSC group compared to the model group. Moreover, the VEGF level was higher in the VEGF-MSC group than the MSC group. A similar trend in Ang-2 protein expression was revealed by Western blotting. In the MCAO rat model transfected with modified MSCs over-expressing VEGF, compared to the MSC transplantation group, the concentration of VEGF was significantly increased in the brain tissue after cerebral infarction. In addition, the level of Ang-2 was up-regulated, with angiogenesis promoted, the blood supply to the areas surrounding the cerebral infarction increased, and neurological function improved. We are led to speculate that the synergistic effects of VEGF and Ang-2 may be responsible for the angiogenesis following cerebral infarction.
Subject(s)
Animals , Male , Rats , Angiopoietin-2 , Genetics , Metabolism , Bone Marrow , Metabolism , Pathology , Cerebral Infarction , Genetics , Metabolism , Pathology , Neovascularization, Pathologic , Genetics , Pathology , Rats, Sprague-Dawley , Stromal Cells , Metabolism , Pathology , Vascular Endothelial Growth Factor A , Genetics , MetabolismABSTRACT
BACKGROUND: Transformation growth factor β1 (TGF-β1) can promote bone marrow mesenchymal stem cells (BMSCs) migration and proliferation, but the underlying mechanisms remain unclear.OBJECTIVE: To observe the invasiveness of TGF-β1 on BMSCs cultured in vitro, and to investigate regulatory effect on Snail and matrix metalloproteinase 2 (MMP-2) expression.METHODS: Rat BMSCs were isolated and cultured with density gradient centrifugalization and adherence method. The influence of different concentrations of TGF-β1 on the BMSC migration was detected using the modified Transwell chambers. Small interfering RNA for Snail gene was synthesized and transfected into BMSCs by liposomel before TGF-β1 was treated, and the expression of Snail and MMP-2 before and after transfection were measured by western blot assay.RESULTS AND CONCLUSION: The exogenous TGF-β1 can induce a dose-dependent increase in cell migration, which peaked at 2 μg/L. The expression levels of Snail mRNA and MMP-2 mRNA were significantly increased after 2 μg/L TGF-β1 treatment. Snail gene can effectively inhibit the expression of MMP-2 promoted by TGF-β1. Experimental findings indicate that TGF-β1 could increase the MMP-2 expression and then promote the BMSCs migration through the upregulation of the Snail expression.
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bThis study explored whether the transplantation of modified marrow stromal cells (MSCs) has angiogenic effects in a left middle cerebral artery occlusion infarction/reperfusion (MCAO I/R) rat model and preliminarily examined the mechanism of angiogenesis following cerebral infarction. MSCs were isolated by using a direct adherent method and cultured. Vascular endothelial growth factor (VEGF) was transfected into MSCs by employing the liposome transfection. The transfection efficiency was measured by the optical density method. The protein expression of VEGF gene before and after transfection was measured by Western blotting. SD rat model of transient occlusion of the left middle cerebral artery was established by using an approach of intra-luminal occlusion. Tetrazolium (TTC) and HE staining were performed to observe the cerebral infarction. ELISAs were used to measure the levels of VEGF in the rat cerebral tissues. The expression patterns of angiopoietin-2 (Ang-2) and CD34 in cells surrounding the area of infarction were immunohistochemistrically observed. Ang-2 protein expression in the tissue surrounding the area of infarction was measured by Western blotting. VEGF expression in the MSCs increased after transfection at a rate of approximately 28%±3.4%. ELISA showed that the expression of VEGF in the cerebral tissue was significantly increased after induction of infarction, peaking on the 4th day and decreasing to the levels of the sham surgery group (normal) within 7 to 10 days. The VEGF level was significantly higher at each time point in the VEGF-MSC and MSC groups compared to the model group. Moreover, the VEGF level was higher in the VEGF-MSC group than in the MSC group and stayed relatively high until the 10th day. The immunohistochemical results showed that 10 days after the infarction, the number of Ang-2 and CD34-expressing cells in the area surrounding the infarction was significantly higher in the VEGF-MSC group and the MSC group compared to the model group. Moreover, the VEGF level was higher in the VEGF-MSC group than the MSC group. A similar trend in Ang-2 protein expression was revealed by Western blotting. In the MCAO rat model transfected with modified MSCs over-expressing VEGF, compared to the MSC transplantation group, the concentration of VEGF was significantly increased in the brain tissue after cerebral infarction. In addition, the level of Ang-2 was up-regulated, with angiogenesis promoted, the blood supply to the areas surrounding the cerebral infarction increased, and neurological function improved. We are led to speculate that the synergistic effects of VEGF and Ang-2 may be responsible for the angiogenesis following cerebral infarction.
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Objective To investigate the correlation of plasma lysophosphatidic acid (LPA) and matrix metalloproteinase-9 (MMP-9) with carotid atheromatous plaque stability in patients with cerebral infarction. Methods The duplex uhrasonography and transcranial Doppler-detected microemboli were performed in the carotid arteries of all the 87 patients with cerebral infarction located in arteriae carotis interna system. The patients were divided into the intima thickening group (n=16),unstable plaque group (n=41), stable plaque group (n=21) and non-plaque group (n=9). And there were 27 patients with positive microembolic signal and 60 patients with negative microembolic signal.The plasma levels of LPA and MMP-9 were determined by quantitative determination of inorganic phosphorus and enzyme-linked immunosorbent assay. Results The levels of LPA and MMP-9 were significantly higher in unstable plaque group than in the other three groups (F=49.98 and 106.49,both P<0.01), MMP-9 in intima thickening group and stable plaque group were both higher than in non-plaque group (q=7.04 and 7.51, both P=0. 00). LPA was higher in intima thickening group than in stable plaque group (q=7.37, P=0. 00), and higher in the above two groups than in non-plaque group (both P<0.05). The levels of LPA and MMP-9 were higher in microembolic signal-positive patients than in signal-negative patients (t=42.57 and 16.61, both P=0.00). LPA level was positively correlated with MMP-9 (r=0.22, P<0.05). Conclusions LPA and MMP-9 may serve as a potential risk signal to hint the formation and rupture of unstable carotid atheromatous plaque which may cause ischemic cerebrovascular disease.
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AIM: To study the acute toxicity of bioactive compounds from paecilomyces tenuipes (BCPT) and the effect of BCPT on lipid peroxidation of brain in chronic stress model (CMS) of depression in rats. METHODS: The depression animal model was induced by chronic unforeseeable stress (CUS). The maximally tolerated dose (MTD) was used to detect the acute toxicity of BCPT. UV spectrophotometer analysis technique was used to detect the activity of SOD, GSH-PX and CAT, and content of MDA and NO in rat's brain. RESULTS: The MTD of BCPT was 9 g?kg -1 . BCPT could obviously enhance the activities of SOD, GSH-PX and CAT, and also significantly inhibit the increase of MDA and NO content in brain in CMS rats. CONCLUSION: BCPT has little toxicity and produces an antidespressant-like effect in antioxidation in CMS rats.
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Aim Exploration of the effects of bioactive compound from paecilomyces tenuipes (BCPT) on the behavior, ultrastructure of hippocampus, and expressions of BDNF and Bax of cerebral cortex in CUS rats. Methods The depression model rat was induced by chronic unpredictable stress(CUS). The Open field test was used to observe the behavior of CUS rats. The expressions of BDNF and Bax of cerebral cortex were studied using immunohistochemical method, and average optical density of cortical neuron was calculated by image analysis. Morphology of hippocampus was observed by transmission electron microscope. Results Compared with model group, BCPT could obviously increase the activity of ambulation and rearing and the number of positive neuron of BDNF, decrease the number of positive neuron of Bax, and effectively prevent pathological damage induced by chronic unpredictable stress. Conclusion BCPT may exhibit the effects of antidepression, up-regulate the expression of BDNF, down-regulate the expression of Bax, and improve of the ultrastructure of hippocampus.
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Aim To study the effect of bioactive compounds from paecilomyces tenuipes(BCPT) on antioxidization and lymphocyte proliferation in chronic unpredictable mild stress(CUMS) model of depression in rats.Methods Depression animal model was reproducted in CUMS,UV spectrophotometer analysis technique was used to detect the activity of SOD、GSH-PX and CAT,and content of MDA and NO in rat serum;lymphocyte proliferation was tested with MTT method.Results BCPT could obviously enhance the activities of SOD、GSH-PX and CAT,and also significantly inhibit the increase of MDA and NO content in serum in CUMS rats;BCPT decreased the serum from depressive rat inhibited ConA-induced lymphocyte proliferation.Conclusion BCPT produces an antidespressant-like effect in antioxidation and cellular immunological function in CUMS rats.
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Aim To study the effect of bioactive compounds from paecilomyces tenuipes(BCPT) on AVP content of hypothalamus,pituitary and expression of AVP mRNA of hypothalamus and behaviour in chronic unpredictable stress model of depression in rats.Methods The depression animal model was induced by chronic unpredictable stress.The behaviour of rats was tested in the open field.The effect of BCPT on AVP content in hypothalamus and pituitary was tested by radioimmunoassay.RT-PCR was used to test the expression of AVP mRNA in hypothalamus.Results BCPT could decrease the expression of AVP mRNA of hypothalamus and decrease AVP content of hypothalamus and pituitary in chronic stressed rats obviously.BCPT could increase ambulation and rearing score of chronic stressed rats in the open-field test.Conclusion BCPT exhibited an antidepressant-like effect may in part be associated with the decreasing AVP content of hypothalamus and pituitary,and the expression of AVPmRNA of hypothalamus in chronic unpredictable stress model of depression in rats
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OBJECTIVE:To explore the antidepressant effects of bioactive compounds from paecilomyces tenuipes(BCPT)on expression of hippocampus and cortex mineralocorticoid receptor(MR),glucocorticoid receptor(GR)mRNA in CUS(chronic unpredictable stress)rats.METHODS:The depression model rat was produced by CUS,the therapy effect of BCPT was observed in CUS rats.It detected expression of hippocampus and cortex MR,GR mRNA with RT-PCR in CUS rats.RESULTS:BCPT could enhance the expression of hippocampus and cortex MR,GR mRNA or decrease the ratio of MR/GR mRNA in CUS rats.CONCLUSION:BCPT could obviously enhance the expression of hippocampus and cortex MR,GR mRNA or decrease the ratio of MR/GR mRNA in CUS rats,the result of this study suggested that BCPT possess certain antidepressant effect.