1.Amelioration of mitochondrial dysfunction in heart failure through S-sulfhydration of Ca2+/calmodulin-dependent protein kinaseⅡ
WU DAN ; HU QING-XUN ; ZHU DE-QIU ; ZHU YI-ZHUN
Chinese Journal of Pharmacology and Toxicology 2017;31(10):1025-1026
OBJECTIVE To determine the functional role of hydrogen sulfide (H2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca2 +/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) using wild type and CSE knockout mouse models. METHODS Continuous subcutaneous injection isoprenaline (7.5 mg·kg-1·d-1), once a day for 4 weeks to induce heart failure in Male C57BL/6 (6-8 weeks old) mice and CSE-/- mice. 150 μmol·L-1 H2O2 was used to induce oxidative stress in H9c2 cells. Echocardiograph was used to detect cardiac parameters. H&E stain and Masson stain was to observation histopathological changes. Western blot was used to detect protein expression and activity. The siRNA was used to silence protein expression. HPLC was used to detect H2S level. Biotin assay was used to detect the level of S- sulfhydration protein. RESULTS Treatment with S-propyl-L-cysteine (SPRC) or sodium hydrosulfide (NaHS), modulators of blood H2S levels, attenuated the development of heart failure in animals, reduced lipid peroxidation, and preserved mitochondrial function. The inhibition CaMKⅡ phosphorylation by SPRC and NaHS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds. Interestingly, CaMKⅡ activity was found to be elevated in CSE-/- mice as compared to wild type animals and the phosphorylation status of CaMKⅡ appeared to relate to the severity of heart failure. Importantly, in wild type mice SPRC was found to promote S-sulfhydration of CaMKII leading to reduced activity of this protein however, in CSE-/- mice S-sulfhydration was abolished following SPRC treatment. CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of CaMKⅡ is presented. SPRC mediated S-sulfhydration of CaMKII was found to inhibit CaMKⅡ activity and to preserve cardiovascular homeostasis.
2.Amelioration of mitochondrial dysfunction in heart failure through S-sulfhydration of Ca2+/calmodulin-dependent protein kinaseⅡ
WU DAN ; HU QING-XUN ; ZHU DE-QIU ; ZHU YI-ZHUN
Chinese Journal of Pharmacology and Toxicology 2017;31(10):976-976
OBJECTIVE To determine the functional role of hydrogen sulfide (H2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca2 +/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) using wild type and CSE knockout mouse models. METHODS Continuous subcutaneous injection isoprenaline (7.5 mg·kg-1 per day), once a day for 4 weeks to induce heart failure in male C57BL/6 (6-8 weeks old) mice and CSE-/- mice. 150 μmol·L-1 H2O2 was used to induce oxidative stress in H9c2 cells. Echocardiograph was used to detect cardiac parameters. H&E stain and Masson stain was to observation histopathological changes. Western blot was used to detect protein expression and activity. The siRNA was used to silence protein expression. HPLC was used to detect H2S level. Biotin assay was used to detect the level of S-sulfhydration protein. RESULTS Treatment with S-propyl-L-cysteine (SPRC) or sodium hydrosulfide (NaHS), modulators of blood H2S levels, attenuated the development of heart failure in animals, reduced lipid peroxidation, and preserved mitochondrial function. The inhibition CaMKⅡ phosphorylation by SPRC and NaHS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds. Interestingly, CaMKⅡ activity was found to be elevated in CSE-/- mice as compared to wild type animals and the phosphorylation status of CaMK Ⅱ appeared to relate to the severity of heart failure. Importantly, in wild type mice SPRC was found to promote S-sulfhydration of CaMKⅡ leading to reduced activity of this protein however, in CSE-/- mice S-sulfhydration was abolished following SPRC treatment. CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of CaMKⅡ is presented. SPRC mediated S-sulfhydration of CaMKⅡ was found to inhibit CaMKⅡ activity and to preserve cardiovascular homeostasis.
3.Clinical study on termination of second-trimester gestation using different doses of combined mifepristone-miso- prostol regimen
Tang-Ni QIN ; Rong-Xiang ZHOU ; Cheng-Ling SUN ; Qing-Hui ZHU ; Jin-Hu ZHU ;
Chinese Journal of Primary Medicine and Pharmacy 2006;0(10):-
Objective To evaluate the using of either 225 or 150 microgrammes of mifepristone combined with misoprostol for termination of second-trimester gestation(16~24 weeks).Methods 180 women requesting voluntary induced abortion during gestation 16~24 weeks were randomised to three groups,group 1:oral mifepris- tone 225rag,group 2:oral mifepristone 150mg,and group 3:injected 100rag rivanot by amniocentestis.The total suc- cess rate,once success rate,the interval of having-medicine to uterine-constraction,the volume of bleeding within 2 hours after labour and cervical laceration rate were observed.Results The once success rate of induced labour in group 1 was higher than that in group 2 and group 3(P
4.X-ray performance of melorheostosis in right foot:report of one case.
Qing-zhi XU ; Yan-qing HU ; Yu-xuan LIN ; Jiao-jiao HUANG ; Shu-mao YANG ; Zhu-yun CHEN
China Journal of Orthopaedics and Traumatology 2015;28(2):186-187
Adult
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Foot Diseases
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diagnostic imaging
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Humans
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Male
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Melorheostosis
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diagnostic imaging
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Radiography
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X-Rays
5.Effects of Tuina and Chinese patent drug Shuxuetong injection on deep venous thrombosis and functional rehabilitation after total knee arthroplasty.
Junlin HU ; Guilin OUYANG ; Dapeng HAN ; Qing XIA ; Yong HE ; Zheng HUANG ; Fei ZHU ; Songtao SUN
Journal of Integrative Medicine 2011;9(10):1088-93
To evaluate the efficacy of Tuina and Chinese patent drug Shuxuetong injection in preventing patients undergoing total knee arthroplasty from deep venous thrombosis and in functional rehabilitation.
6.Application of parametric image processing of contrast-enhanced ultrasound imaging in diagnosis of ovarian masses
Lu CHEN ; Li HONG ; Wenwei CHEN ; Min HU ; Debin WU ; Xuejiao ZHU ; Qing SUN ; Wenying WU
Chinese Journal of General Practitioners 2011;10(10):718-721
ObjectiveTo investigate application value of parametric image processing in contrastenhanced ultrasound imaging in diagnosis of ovarian masses. MethodsFifty cases with ovarian masses underwent routine ultrasound and contrast-enhanced ultrasound imaging using a new dedicated parametric image processing software SonoLiver to analyze patterns of vascular formation and blood stream perfusion in the ovarian mass tissues on a digital video recorder in real time, compare their morphological characteristics of time-intensity curve (TIC) and dynamic vascular patterns (DVP) curve, and analyze quantitatively all indicators generated by SonoLiver.ResultsIn ultrasound imaging of the 50 cases, there were 24 cases (86%) displaying mainly blue lowly-enhanced imaging in those with benign masses and 15 cases (68%)displaying mainly red highly-enhanced imaging in those with malignant masses, with statistical significance (P <0. 01 ). There was significantly different characteristics of TIC and DVP between patients with benign and malignant masses. In 23 cases with benign masses, their DVP were significantly higher above the baseline than in those with malignant ones ( P = 0. 000), and in 15 cases with malignant lesions, their DVP were much shorter below the baseline than in those with benign ones, with statistical significance (P <0.05). The intensity of contrast medium, the time to reach its peak intensity and average transit time were all significantly higher in those with malignant masses than in those with benign ones (all P < 0. 05 ). But, no statistical difference in the time of initial increasing between the two groups was found (P > 0. 05). ConclusionsThere is significant difference in TIC and DVP of ultrasound imaging between benign and malignant masses, which if combined with contrast enhanced ultrasound parametric image processing can provide a more visualized quantitative information of benign and malignant ovarian masses with SonoLiver software.
7.Hydrogen sulfide and mild hypothermia can selectively activate synaptic NMDARs and trigger the CREB signaling pathway
Haibin DAI ; Yimin HU ; Qing JI ; Lidong ZHANG ; Xiaolei MIAO ; Sihai ZHU ; Weiyan LI ; Manlin DUAN
Journal of Medical Postgraduates 2014;(7):686-689
Objective Research has indicated that hydrogen sulfide(H2S) can regulate the function of N-methyl-D-aspartate re-ceptors(NMDARs) in the brain, but its effect on brain resuscitation requires further investigation.The study was to speculate the effect of H2 S on brain resuscitation as well as the underlying mechanism of neuroresuscitation by investigating the effects of hydrogen sulfide and hypo-thermia on the expression of NR2A, NR2B and phospho-cAMP response element binding protein (p-CREB) of NMDARs in the hippocampus after global cerebral ischemia following by reperfusion. Methods 100 male SD rats were randomly divided into five groups(n=20):sham operation group, model group, mild hypothermia group, NaHS group, NaHS combined mild hypothermia group.Pulsinelli-Brierley four-ves-sel occlusion method was induced to build the injury rat model by reperfusion after global cerebral ischemia .After 15 minutes'ischemia, im-mediate injection of 14μmol/kg NaHS was performed intraperitoneally on NaHS group and NaHS combined mild hypothermia group , while skin cooling(rectal temperature=32-33℃) was done on mild hypothermia group and NaHS combined mild hypothermia group .6 hours late,r hip-pocampus were extracted from rat heads.Respectively, spectrophotometer was applied to measure the content of H2S, Western blot for the expres-sions of NR2 A,NR2 B and pC-REB, and RTP-CR for mRNA level of brain derived neurotrophic (BDNF). HE staining was also performed on brain tissues 72hours after reperfusion on 4 rats from each group to evaluate the pathological changes of pyramidal neurons in CA1 region. R esul ts The content of H 2 S increased in each of the four groups after ischemia-reperfusion compared with sham operation group ( 15.2 ±2.0 nmol/g) (P<0.05).In comparison to model group (25.2 ±3.5 nmol/g), NaHS group (37.5 ±4.0 nmol/g) and NaHS combined mild hypothermia group (38.7 ±4.4nmol/g ) resulted in significant high content of H2S(P<0.05), while mild hypothermia group(26.5 ±3.5nmol/g ) got a mild increase(P>0.05).The gray values of NR2A and NR2B in each group increased compared with sham operation group(P<0.05), re-sulting in NR2A/NR2B<1 in model group and mild hypothermia group while NR2A/NR2B>1 in NaHS group and NaHS combined mild hy-pothermia group.Compared with the expression of p-CREB(0.55 ±0.06) in model group, there were significant increases in mild hypother-mia group(0.99 ±0.15), NaHS group(1.05 ±0.12), NaHS combined mild hypothermia group(1.02 ±0.15)(P<0.05).Compared with the expression of BNDF mRNA(0.83 ±0.12) in model group, there were significant increases in mild hypothermia group (1.11 ±0.13), NaHS group(1.27 ±0.16), NaHS combined mild hypothermia group(1.35 ±0.16)(P<0.05).In comparison to model group, there were signifi-cant alleviation in the injury of pyramidal neurons in hippocampal CA1 region in mild hypothermia group, NaHS group, NaHS combined mild hypothermia group, with the best effect in NaHS combined mild hypothermia group . Conclusion Hydrogen sulfide combined mild hypo-thermia can selectively activate synaptic NMDA receptors and trigger the prosurvival CREB signaling pathway to exert brain resuscitation .
8.Clinical study of GeneXpert combined with T-SPOT and TB-Ab on bacterial-negative pulmonary tuberculosis
DING Xing ; DING Hai-yun ; HU Qing-gang ; LIU Gang ; ZHU Xiao-wu
China Tropical Medicine 2022;22(09):850-
Abstract: Objective To investigate the diagnostic efficacy of rifampin-resistant real-time fluorescent quantitative nucleic acid amplification detection technology (GeneXpert MTB/RIF) in bronchoalveolar lavage fluid (BALF) combined with peripheral blood tuberculosis infection T cell spot test (T-SPOT) and tuberculosis antibody (TB-Ab) in smear-negative pulmonary tuberculosis. Methods The clinical data of 114 cases of clinically diagnosed smear-negative pulmonary tuberculosis, 80 cases of non-tuberculous pulmonary diseases and 22 cases of smear-positive pulmonary tuberculosis in our hospital from January 2019 to January 2021 were retrospectively analyzed. The detection results of peripheral blood T-SPOT, TB-Ab and BALF GeneXpert in the three groups were analyzed. The sensitivity, specificity, negative predictive value, positive predictive value, false negative rate, false positive rate and Youden index of the three detection methods were compared. The differences in the positive detection rate of smear-negative pulmonary tuberculosis between the separate detection and the combined detection of the three methods were compared. The receiver operating characteristic curve (ROC) was performed to calculate the area under the curve (AUC). Results The sensitivity of BALF GeneXpert and peripheral blood T-SPOT and TB-Ab was 66.91%, 80.88% and 90.44%, respectively. The specificity was 98.75%, 73.75% and 41.25%, respectively; the diagnostic coincidence rates were 78.70%, 78.24% and 72.22%, respectively, which were higher than 70.00%. In the smear-negative pulmonary tuberculosis group, the positive detection rates of these three methods in the smear-negative pulmonary tuberculosis group were 63.15%, 79.82% and 90.35%, respectively, and the differences were statistically significant compared with those in the non-tuberculosis pulmonary disease group (all P<0.01). The positive detection rate of the three combined methods in the smear-negative pulmonary tuberculosis group was 96.49 %, which was significantly higher than that of TB-GeneXpert method and T-SPOT, and the differences were statistically significant (χ2=37.283, P<0.01; χ2=13.612, P<0.01); the Youden index of combined detection was significantly higher than that of single detection, and the AUC of combined detection was 0.977, which was significantly higher than that of single detection. Conclusion BALF GeneXpert combined with peripheral blood T-SPOT and TB-Ab can significantly improve the diagnostic rate of bacterial-negative pulmonary tuberculosis, providing a strong basis for guiding clinical treatment.
9.Expression of PED/PEA-15 and XIAP in prostate cancer cells and their effects on prostate cancer cell (PC-3) apoptosis
Xiao-Yong HU ; Xiao-Chun CHEN ; Zhao-Hui ZHU ; Fu-Qing ZENG ; Gong-Cheng LU ;
Chinese Journal of Geriatrics 2001;0(03):-
Objective To study the effect of antiapoptosis factors PED/PEA-15 and XIAP on prostate cancer cells(PC-3)apoptosis.Methods The expressions of XIAP and PED/PEA-15 in prostate cancer cells(PC-3)were respectively assayed using the RT-PCR technique.XIAP and PED/ PEA-15 specific siRNA vectors were designed and constructed and then were transiently cotransfected into PC-3 cells under induction of liposome.The effects of siRNA vectors on PED/PEA-15 and XIAP transcription were assayed by RT-PCR technique,and the effect of XIAP and PED/PEA-15 on cancer cell apoptosis were determined by flow cytometry and microscope observation.Results PED/PEA- 15 and XIAP were both highly expressed in PC-3 cells.Enzyme digestion analysis and DNA sequencing confirmed that the PED/PEA-15 and XIAP-specific siRNA expression vectors were constructed successfully.The designed siRNA sequences of PED/PEA-15 and XIAP could specifically inhibit their transcription.The PC-3 cells which were cotransfected with PED/PEA-15 and XIAP- specific siRNA vectors were more sensitive to doxorubicin.The apoptosis rate of cotransfected cells was significantly increased.Conclusions PED/PEA-15 and XIAP might be involved in the development of prostate cancer.
10.Antiproliferation and induction differentiation of rosiglitazone in human gastric carcinoma transplanted into nude mice
Fang-Zhi CHEN ; Li-Hui ZHU ; Jian-Feng HU ; Li ZHANG ; Guo-Qing LI ; Lan WEN
Cancer Research and Clinic 2000;0(06):-
Objective To investigate the antiproliferation and induction differentiation of human gas- tric carcinoma which human gastric lower-differentiation mucinous carcinoma MGC-803 cells transplanted in- to nude mice by using rosiglitazone(ROS),and to preliminarily explore the mechanism of differentiation. Methods The mice were randomly divided into five groups:model,ATRA,ROS 25 mg?kg~(-1),ROS 50 mg/kg, ROS 100 mg/kg.After that the volumes were measured and inhibition rates were calculated.The cell cycle was detected by FCM.The protein expression level of Mucin SAC was detected by immunohistochemistry. Results The volume of tumor decreased significantly in ROS treatment groups,the differences had statistical significance compared with model group(P0.05).The xenograft tumors of ROS groups demonstrated the characteristics of differentiation.Xenograft tumor cells were arrested in G_0/G_1 phase,and the cells in S phase decreased significantly,and up-regulated Mucin SAC gene expression.Conclusion ROS could inhibit the growth of tumor,and the effect were dose-dependent with ROS.ROS could induce the differentiation of Xenograft tumor cells of gastric cancer.Its mechanism might be related to the inhibit of transition from G_1 to S phase,degrade the activity of proliferation,regulate the expres- sion of Mucin 5AC.