Functional responses to angiotensin Ⅱ (AT-Ⅱ) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats. Our data showed that AT-Ⅱ-stimulated extracellular acidification rate (E...Functional responses to angiotensin Ⅱ (AT-Ⅱ) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats. Our data showed that AT-Ⅱ-stimulated extracellular acidification rate (ECAR), which was measured by Cytosensor microphysiometry, was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals. The ability of AT-Ⅱ to promote formation of inositol phosphates, the second messenger produced by the activation of Gq-coupled receptors, was also considerably suppressed in the cirrhotic VSMCs. Furthermore, the maximal p42/44 MAPK phosphorylation stimulated by AT-Ⅱ was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs. Taken together, our data clearly demonstrated that the functional responses to AT-Ⅱ was severely suppressed in aortic VSMCs in cirrhosis, indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.展开更多
Objective： The aim of the study was, （1） to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer （NSCLC）; （2） to explore whethe...Objective： The aim of the study was, （1） to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer （NSCLC）; （2） to explore whether there is difference in the efficacy of icotinib hydrochloride among the subgroups of sex, age, smoking history, classification of CEA, histological type, multi-line treatment and PS score. Methods： The study was conducted to collect 138 patients taking icotinib hydrochloride with advanced non-small cell lung cancer in hospitals of Dalian （China） from September 1st 2011 to June 14th 2012. All patients had taken icotinib hydrochloride （125 mg three times a day） until the disease was progressed or the adverse reactions could not be tolerated. During the period of taking it, other anti-tumor treatments were forbidden. We observed the symptoms, such as cough, short breath, hemoptysis, pain. The objective efficacy was evaluated by RECIST criteria, and the adverse reactions related to the treatment was assessed on the basis of NCl-CTC 3.0. Results： Of all patients, CR was 1 （0.7%）, PR was 59 （42.8%）, SD was 37 （26.8%）, PD was 41 （29.7%）. And ORR was 43.5% （60/138）, DCR 70.3% （97/138）. The DCR of females was 83.5% （71/85） versus 49.1% （26/53） of males. The difference of ORR and DCR between the two subgroups had statistical significance （X2 = 8.065, P = 0.05; X2 = 18.577, P = 0.000）. The difference of ORR and DCR between the subgroups of patients after or before 70 years old had no statistical significance. The difference of ORR and DCR between the subgroups of smoking and non-smoking had statistical significance （X2 = 8.492; X2 = 13.602）. The difference of ORR and DCR between the CEA subgroups had statistical significance （X2 = 14.141; X2 = 14.160）, showed 81 patients with abnormal CEA before the treatment with ORR 56.8.0% （46/81）, DCR 81.5% （66/81）; 57 patients of normal CEA before the treatment with ORR 24.6% （14/57）, DCR 52.6% （30/57）. The 36 patients （26.1%） using icotinib hydrochloride as the first-line treatment, 78 patients （56.5%） using icotinib hydrochloride as the second-line, 20 patients （14.5%） using icotinib hydrochloride as the third-line, and 4 patients （2.9%） with tyrosine kinase inhibitor （TKI） resistance, there was statistical difference of DCR among the multi-groups above （~2 = 11.734, P = 0.008）. ORR was 31.1% （14/45） versus DCR 53.3% （24/45） in 45 patients with PS 3-4 points, and ORR was 49.4% （46/93） versus DCR 78.5% （73/93） in 93 patients with PS 0-2 points, and there was statistical difference （X2 = 4.156; X2 = 9.149）. The main adverse reactions were rash （26.8%）, diarrhea （13.8%）, mild liver function abnormal （10.9%）. Conclusion： The short-term efficacy of icotinib hydrochloride on the treatment of advanced NSCLC is positive, and the relevant adverse reactions are mild. The efficacy is better when the patient is female, non-smoker, treated as first-line, with higher CEA before treatment and lower PS scores.展开更多
Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidatio...Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidation stress of myocardial cells. Methods: Primary cultured neonate rat myocardial cells were cultured with TSN (1×10-4 mol/L) for 24 hours, and then the medium was supplemented with 200 μmol/L hydrogen peroxide for 2 h to initiate myocardial cell oxidative stress injury. PHB in myocardial cells was knocked down by small interfering RNA (siRNA), and the expression level of PHB was determined by western blot analysis. Flow cytometry was used to detect the apoptosis rate, intracellular calcium ion concentration ([Ca2+]i) and mitochondrial membrane potential (MMP). Results: The PHB expression, [Ca2+]i and the apoptotic rate significantly increased, and the MMP significantly decreased in the oxidative stress group compared with the control. The PHB expression, apoptosis rate and [Ca2+]i decreased, and MMP increased significantly in the TSN group compared with the oxidative stress group. Compared with the siRNA negative control group, the PHB expression level in myocardial cells was down-regulated, and the apoptosis rate and [Ca2+]i increased, and MMP decreased significantly in the siRNA group. Conclusion: TSN can reduce PHB expression in oxidative stress-injured myocardial cells hence protecting the myocardial cells.展开更多
Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric disorders.However,the molecular and circuit mechanisms underlying the dysregulation remain elusive.Here,by ...Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric disorders.However,the molecular and circuit mechanisms underlying the dysregulation remain elusive.Here,by using a mouse model of chronic social defeat stress(CSDS),we observed that the dysregulation varied drastically across individual projection neurons(PNs)in the basolateral amygdala(BLA),one of the kernel amygdala subregions critical for stress coping.While persistently reducing the extrasynaptic GABAAreceptor(GABA_(A)R)-mediated tonic current in the BLA PNs projecting to the ventral hippocampus(BLA→v HPC PNs),CSDS increased the current in those projecting to the anterodorsal bed nucleus of stria terminalis(BLA→adBNST PNs),suggesting projection-based dysregulation of tonic inhibition in BLA PNs by CSDS.Transcriptional and electrophysiological analysis revealed that the opposite CSDS influences were mediated by loss-and gain-of-function ofδ-containing GABA_(A)Rs(GABA_(A)(δ)Rs)in BLA→vHPC and BLA→adBNST PNs,respectively.Importantly,it was the lost inhibition in the former population but not the augmentation in the latter population that correlated with the increased anxiety-like behavior in CSDS mice.Virally mediated maintenance of GABA_(A)(δ)R currents in BLA→vHPC PNs occluded CSDS-induced anxiety-like behavior.These findings clarify the molecular substrate for the dysregulated GABAergic inhibition in amygdala circuits for stress-associated psychopathology.展开更多
Objective: To observe the effects of thermal stress on proliferation of human vascular endothelial cells (VECs) and explore its significance. Methods: Changes of VECs proliferation were investigated with 3H TdR incorp...Objective: To observe the effects of thermal stress on proliferation of human vascular endothelial cells (VECs) and explore its significance. Methods: Changes of VECs proliferation were investigated with 3H TdR incorporation method after ECV304 was treated at 43℃ for 2 hours, while expressions of intercellular adhesion molecule 1 (ICAM 1), inhibitor of differentiation 1 (ID1), and P16 and P21 proteins were determined by Western Blotting. Results: The effect of inhibition of VECs growth after thermal stress was detected by 3H TdR incorporation experiment. Western blotting showed ICAM 1, a marker of activated endothelial cells, was increased markedly after thermal stress. Expression of ID1 protein declined gradually with increasing expressions of its downstream genes, P16 and P21 following the thermal stress. Conclusions: Thermal stress could strongly activate VECs and inhibit proliferation of VECs through ID1, thus down regulating cyclin dependent kinase inhibitors, P16 and P21, which might be an essential pathway for recovery of VECs after thermal stress.展开更多
文摘Functional responses to angiotensin Ⅱ (AT-Ⅱ) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats. Our data showed that AT-Ⅱ-stimulated extracellular acidification rate (ECAR), which was measured by Cytosensor microphysiometry, was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals. The ability of AT-Ⅱ to promote formation of inositol phosphates, the second messenger produced by the activation of Gq-coupled receptors, was also considerably suppressed in the cirrhotic VSMCs. Furthermore, the maximal p42/44 MAPK phosphorylation stimulated by AT-Ⅱ was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs. Taken together, our data clearly demonstrated that the functional responses to AT-Ⅱ was severely suppressed in aortic VSMCs in cirrhosis, indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.
文摘Objective： The aim of the study was, （1） to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer （NSCLC）; （2） to explore whether there is difference in the efficacy of icotinib hydrochloride among the subgroups of sex, age, smoking history, classification of CEA, histological type, multi-line treatment and PS score. Methods： The study was conducted to collect 138 patients taking icotinib hydrochloride with advanced non-small cell lung cancer in hospitals of Dalian （China） from September 1st 2011 to June 14th 2012. All patients had taken icotinib hydrochloride （125 mg three times a day） until the disease was progressed or the adverse reactions could not be tolerated. During the period of taking it, other anti-tumor treatments were forbidden. We observed the symptoms, such as cough, short breath, hemoptysis, pain. The objective efficacy was evaluated by RECIST criteria, and the adverse reactions related to the treatment was assessed on the basis of NCl-CTC 3.0. Results： Of all patients, CR was 1 （0.7%）, PR was 59 （42.8%）, SD was 37 （26.8%）, PD was 41 （29.7%）. And ORR was 43.5% （60/138）, DCR 70.3% （97/138）. The DCR of females was 83.5% （71/85） versus 49.1% （26/53） of males. The difference of ORR and DCR between the two subgroups had statistical significance （X2 = 8.065, P = 0.05; X2 = 18.577, P = 0.000）. The difference of ORR and DCR between the subgroups of patients after or before 70 years old had no statistical significance. The difference of ORR and DCR between the subgroups of smoking and non-smoking had statistical significance （X2 = 8.492; X2 = 13.602）. The difference of ORR and DCR between the CEA subgroups had statistical significance （X2 = 14.141; X2 = 14.160）, showed 81 patients with abnormal CEA before the treatment with ORR 56.8.0% （46/81）, DCR 81.5% （66/81）; 57 patients of normal CEA before the treatment with ORR 24.6% （14/57）, DCR 52.6% （30/57）. The 36 patients （26.1%） using icotinib hydrochloride as the first-line treatment, 78 patients （56.5%） using icotinib hydrochloride as the second-line, 20 patients （14.5%） using icotinib hydrochloride as the third-line, and 4 patients （2.9%） with tyrosine kinase inhibitor （TKI） resistance, there was statistical difference of DCR among the multi-groups above （~2 = 11.734, P = 0.008）. ORR was 31.1% （14/45） versus DCR 53.3% （24/45） in 45 patients with PS 3-4 points, and ORR was 49.4% （46/93） versus DCR 78.5% （73/93） in 93 patients with PS 0-2 points, and there was statistical difference （X2 = 4.156; X2 = 9.149）. The main adverse reactions were rash （26.8%）, diarrhea （13.8%）, mild liver function abnormal （10.9%）. Conclusion： The short-term efficacy of icotinib hydrochloride on the treatment of advanced NSCLC is positive, and the relevant adverse reactions are mild. The efficacy is better when the patient is female, non-smoker, treated as first-line, with higher CEA before treatment and lower PS scores.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30572435)
文摘Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidation stress of myocardial cells. Methods: Primary cultured neonate rat myocardial cells were cultured with TSN (1×10-4 mol/L) for 24 hours, and then the medium was supplemented with 200 μmol/L hydrogen peroxide for 2 h to initiate myocardial cell oxidative stress injury. PHB in myocardial cells was knocked down by small interfering RNA (siRNA), and the expression level of PHB was determined by western blot analysis. Flow cytometry was used to detect the apoptosis rate, intracellular calcium ion concentration ([Ca2+]i) and mitochondrial membrane potential (MMP). Results: The PHB expression, [Ca2+]i and the apoptotic rate significantly increased, and the MMP significantly decreased in the oxidative stress group compared with the control. The PHB expression, apoptosis rate and [Ca2+]i decreased, and MMP increased significantly in the TSN group compared with the oxidative stress group. Compared with the siRNA negative control group, the PHB expression level in myocardial cells was down-regulated, and the apoptosis rate and [Ca2+]i increased, and MMP decreased significantly in the siRNA group. Conclusion: TSN can reduce PHB expression in oxidative stress-injured myocardial cells hence protecting the myocardial cells.
基金supported by National Natural Science Foundation of China(82125010,81930032,31970953,81741759,31700916,and 81601179)Natural Science Foundation of Jiangxi Province(20172BCB22005,20192ACB20023,and 20192ACB21024)。
文摘Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric disorders.However,the molecular and circuit mechanisms underlying the dysregulation remain elusive.Here,by using a mouse model of chronic social defeat stress(CSDS),we observed that the dysregulation varied drastically across individual projection neurons(PNs)in the basolateral amygdala(BLA),one of the kernel amygdala subregions critical for stress coping.While persistently reducing the extrasynaptic GABAAreceptor(GABA_(A)R)-mediated tonic current in the BLA PNs projecting to the ventral hippocampus(BLA→v HPC PNs),CSDS increased the current in those projecting to the anterodorsal bed nucleus of stria terminalis(BLA→adBNST PNs),suggesting projection-based dysregulation of tonic inhibition in BLA PNs by CSDS.Transcriptional and electrophysiological analysis revealed that the opposite CSDS influences were mediated by loss-and gain-of-function ofδ-containing GABA_(A)Rs(GABA_(A)(δ)Rs)in BLA→vHPC and BLA→adBNST PNs,respectively.Importantly,it was the lost inhibition in the former population but not the augmentation in the latter population that correlated with the increased anxiety-like behavior in CSDS mice.Virally mediated maintenance of GABA_(A)(δ)R currents in BLA→vHPC PNs occluded CSDS-induced anxiety-like behavior.These findings clarify the molecular substrate for the dysregulated GABAergic inhibition in amygdala circuits for stress-associated psychopathology.
基金ThisprojectwassupportedbyNational"973"MajorBudget (No .G19990 5 42 0 5 )
文摘Objective: To observe the effects of thermal stress on proliferation of human vascular endothelial cells (VECs) and explore its significance. Methods: Changes of VECs proliferation were investigated with 3H TdR incorporation method after ECV304 was treated at 43℃ for 2 hours, while expressions of intercellular adhesion molecule 1 (ICAM 1), inhibitor of differentiation 1 (ID1), and P16 and P21 proteins were determined by Western Blotting. Results: The effect of inhibition of VECs growth after thermal stress was detected by 3H TdR incorporation experiment. Western blotting showed ICAM 1, a marker of activated endothelial cells, was increased markedly after thermal stress. Expression of ID1 protein declined gradually with increasing expressions of its downstream genes, P16 and P21 following the thermal stress. Conclusions: Thermal stress could strongly activate VECs and inhibit proliferation of VECs through ID1, thus down regulating cyclin dependent kinase inhibitors, P16 and P21, which might be an essential pathway for recovery of VECs after thermal stress.
