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.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.
4.More than a "mother-benefiting" herb: cardioprotective effect of Herba leonuri.
Xin-Hua LIU ; Hong XIN ; Yi-Zhun ZHU
Acta Physiologica Sinica 2007;59(5):578-584
Herba leonuri (HL) is a famous Chinese traditional medicine with long history. Recent studies have shown that the effects of HL are versatile. In addition to its activating effect on blood flow which has been widely used in gynecological and obstetrical disorders, HL has been demonstrated to have beneficial effects on ischemic diseases including myocardial infarction (MI). Experimental studies have shown that HL ameliorated myocardial ischemia, increased coronary blood flow, and improved heart functions. The underlying mechanism is proved to be its antioxidant effects including scavenging free radicals and inhibiting the formation of reactive oxygen species in ischemic myocardium. The antioxidant effects of HL are exerted only under the condition of oxidative stress. A significant angiogenesis promoting effect is also counted for its cardioprotective effects. Clinic trials also indicated that HL could inhibit blood platelet congregating, resist coagulation, restrain thrombosis, and improve hemorheology in patients with coronary heart diseases. This paper gives a brief review on HLos cardioprotective effects based on recent research progress.
Animals
;
Antioxidants
;
Drugs, Chinese Herbal
;
pharmacology
;
therapeutic use
;
Heart
;
Humans
;
Myocardial Infarction
;
drug therapy
;
Myocardial Ischemia
;
Oxidative Stress
;
Reactive Oxygen Species
5.Expression of B7-H1 on peripheral blood mononuclear cells from chronic hepatitis B patients.
Zhun-yi XIE ; Yong-wen CHEN ; Xiao-lan FU ; Cheng-ying YANG ; Yu-zhang WU
Journal of Southern Medical University 2007;27(11):1635-1637
OBJECTIVETo investigate the expression of B7-H1 on peripheral blood mononuclear cells from patients with chronic HBV infection.
METHODSImmunofluorescent staining and flow cytometry assay were used to measure the expression of B7-H1 on peripheral blood CD3high T cells, CD19high B cells and CD14high monocytes from chronic HBV infected patients.
RESULTSNo significant difference was observed in B7-H1 expression on T cells and B cells between chronic HBV infected patients (CHB) and health controls (HC). B7-H1-expressing CD14high cells were significantly increased in chronic HBV-infected patients (19.17-/+11.64)% as compared with healthy controls [(7.30-/+5.49)%, P<0.01]. A significant positive correlation was found between B7-H1 expression on CD14high monocytes and serum ALT levels.
CONCLUSIONThere is no significant difference in B7-H1 expression on T cells and B cells between CHB patients and healthy subjects. B7-H1, which is up-regulated on monocytes from chronic HBV-infected patients, in positively correlated to serum ALT levels, and may play a role in the persistence of HBV infection.
Adult ; Aged ; Antigens, CD ; metabolism ; B-Lymphocytes ; immunology ; B7-H1 Antigen ; Case-Control Studies ; Female ; Hepatitis B, Chronic ; immunology ; metabolism ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Monocytes ; immunology ; T-Lymphocytes ; immunology ; Young Adult
6.Early magnesium sulfate combined with Nimodipine injection in treating patients with diffuse axonal injury
Zhun ZHANG ; Yi-Quan KE ; Qing-Hua WANG ; Zhi-Ping CHEN
Chinese Journal of Neuromedicine 2012;11(5):489-492
Objective To explore the serum level of magnesium in patients with diffuse axonal injury (DAI) and the effect of early magnesium sulfate combined with Nimodipine injection on the prognoses of these patients with DAI. Methods Ninety-nine patients with DAI, admitted to our hospital from September 2006 to June 2010,were randomly divided into 2 groups.The serum level of magnesium was detected on admission. And both groups were treated with Nimodipine injection intravenously 0.5-1.0 mg/h for 7 consecutive d after admission.The experimental group was treated with 250 g/L MgSO4 injection for 3 consecutive d and the control group was treated without MgSO4.Follow-up was performed to observe the relationship between prognoses and both serum level of magnesium on admission and early MgSO4 treatment. Results No significant difference on fatality rate was noted between the experimental group and the control group; however,the experimental group enjoyed a significantly higher good recovery rate and moderate disability rate than the control group (P<0.05); No significant correlation between the serum level of magnesium and Glasgow outcome scale was noted in both groups. Conclusion The serum level ofmagnesium on admission can't affect the prognoses.As compared with use of nimodipine alone,combined early treatment of 250 g/L magnesium sulfate with continuous intravenous infusion couldn't decrease the mortality rate,but can decrease the severe disability rate and improve the prognoses of patients and enhance their life qualities.
7.An investigation on the antibody levels to pertussis and diphtheria among healthy people in Wenzhou City
Zhi-Gang WANG ; Xian-Dan LIN ; Xiao-Xia YANG ; Cheng-Jian NI ; Yi-Zhun XU ; Xiao-Yao LIN
Journal of Preventive Medicine 2016;28(6):565-569,573
Objective To learn the immunity levels of pertussis and diphtheria among healthy people in Wenzhou City,and to provide scientific evidence for the effective control of the two diseases.Methods Stratified sampling method was applied in this investigation and 1 350 healthy people were investigated and provided serum samples.Vaccine immunization of pertussis and diphtheria and demographic characteristics were also collected.Enzyme linked immunosorbent assay (ELISA)was conducted to detect pertussis and diphtheria antibodies.Those with more than 1 00 IU/ml aged more than 3 years were also investigated the disease history.The estimated infection rate of pertussis for population aged more than 3 years was based on the test results.The attenuation trend of pertussis and diphtheria immunity levels after vaccination was analyzed contrastively.Results The antibody positive rate to pertussis was 36. 52%,and the median of antibody concentration was 1 9. 45 IU/m1 .The antibody positive rate and concentration was highest among 36 -60 years old people (64. 29%,36. 39 IU/ml ).The vaccination rate of population with more than 3 doses of DPT (Diphtheria Toxoid -Pertussis Vaccine-Tetanus Toxoid)was 95. 80%,and the corresponding positive rate was 24. 36%.The positive rate was 28. 57% in 0-3 month and 1 0. 71% in 1 0 -1 2 month after vaccination.The antibody concentration to pertussis had a negative correlation with days after vaccination(r=-0. 22,P<0. 05).The proportion of subjects with more than 1 00 IU/ml in population aged more than 3 years was 7. 91%.The estimated infection rate of pertussis for population aged more than 3 years was 49. 27%.The antibody positive rate to diphtheria was 96. 00%,and the median of antibody concentration was 0. 1 3 IU/m1 . The positive rate was highest (1 00%) among 1 -2 years old people and lowest (82. 5%) among newborns.Antibody positive rate (protective rate)and antibody concentration to diphtheria of population which had more doses of DPT or had vaccinated with DT were higher than those had not (P<0. 05 ).The sustainability of vaccine to diphtheria was higher than pertussis after vaccination of DPT.Conclusion Residents in Wenzhou are generally vulnerable to pertussis.Natural infection is considered to be an important influencing factor for the level of pertussis.The level of diphtheria antibodies in Wenzhou is high.The vaccine containing diphtheria is considered useful for children.However,it is suggested to conduct diphtheria booster immunization in older age group.
8.The protective effects of leonurine against acute endotoxin induced uveitis in rats
Jia-Wei XIONG ; Ji-Feng GU ; Wan-Ru SHI ; Su-Qian WU ; Shewket MARHABA ; Yi-Zhun ZHU ; Fen Xiao MO
Fudan University Journal of Medical Sciences 2018;45(3):291-296,329
Objective To investigate whether the protective effects of leonurine (SCM-198) against endotoxin induced uveitis (EIU) of SD rats caused by lipopolysaccharide (LPS) was existing,and discuss the underlying mechanisms.Methods Thirty-six normal healthy male SD rats were divided into 3 groups randomly with the same baseline bodyweight and feeding conditions.All rats received intragastric administration every day.The experimental group was devided into 4 subgroups,rats in these subgroups received SCM-198 intragastric administration by as the dose of 10,20,40 and 80 mg/kg bodyweight per day,rats in the negative control group received intragastric administration of normal saline 10 mL/kg per day,rats in the positive control group received intragastric administration ofdexamethasone (DEX) 0.5 mg/kg bodyweight per day.All rats received a 21-day-intragastric administration.The body weight of all rats was monitored every 7 days.The electroretinogram (ERG) examination was taken in the 18th day.All rats received a 100 mg S.typhi LPS intraperitoneal injection after the 21st intragastric administration.Twenty-four hours later,following anaesthesia,all rats received another ERG examination,and inflammation was scoring under microscope by 2 experienced ophthalmologists,after that the aqueous humor of all rats was collected from the left eye.The aqueous humor was kept in-80 ℃ immediately.Then the rats were sacrificed and the right eyes were immediately enucleated to finish the HE staining and immunohistochemistry (IHC) staining examination of tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1).The total amount of protein in aqueous humor was detected by BCA test.Western blot was used to examine the expression of TNF-α,interleukin-1β (IL-1β),IL-6 and ICAM-1.All data was analyzed by SPSS 19.0,and differences were considered significant at P<0.05.Results The body weight of the rats in positive control group was significantly lower (P<0.05) than the experimental group and the negative control group after the 21-day-intragastric administration.The inflammatory score of experimental group was lower than that of the negative control group,but higher than the score of positive control group.The HE staining sections showed the similar results.The a wave of ERG in 0.01 cd of rats received 20 mg/kg SCM-198 daily intragastric administration after LPS injection was significantly lower than that before the LPS injection (P<0.05),also lower than other groups after LPS injection.The expression of TNF-α,IL-6 and IL-1β in the aqueous humor of the rats in the subgroup of SCM-198 10 mg/kg daily intragastric administration was lower than other groups.Conclusions Intragastric administration of SCM-198 has protective effect against endotoxin induced uveitis in SD rats without obvious adverse reaction,which could alleviate the imflammatory reaction and the damage to the uvea construction.NF-κB plays an important role in the reaction.Thus,SCM-198 is a candidate potent compound with potential therapeutic applications in inflammation associated eye diseases.While the best mode and dose of administration should be further investigated.
9.Analysis of CSF1PO and D18S51 Loci Based on Ion Torrent PGM™ Platform.
Journal of Forensic Medicine 2018;34(5):520-525
OBJECTIVES:
To analyse and detect CSF1PO and D18S51 loci by next generation sequencing (NGS) technology for the study on their sequence polymorphism.
METHODS:
The peripheral blood samples were collected from 165 unrelated individuals of Chinese Han population. DNA samples were obtained by QIAamp DNA Mini kit. The library was constructed by Ion Plus Fragment Library. DNA sequencing analysis was performed on Ion Torrent PGM™ Platform. The newfound alleles were verified by Sanger sequencing. Data were analysed by Torrent Suite™ v5.0.2 and Integrative Genomics Viewer for the genotype identification and frequency count. The data were analysed statistically by PowerState v12.
RESULTS:
The length and sequence polymorphisms of CSF1PO and D18S51 loci were simultaneously obtained by NGS technology. A new genotype was found on CSF1PO locus, and two new genotypes on D18S51 locus. Sanger sequencing was used to verify the newfound alleles found by NGS technology, and the results of verification showed consistency.
CONCLUSIONS
The structure of core repeats on CSF1PO and D18S51 loci was detected by NGS in this study for the improvement of the identifying performance of locus.
Asian People/genetics*
;
DNA Fingerprinting
;
Genotype
;
High-Throughput Nucleotide Sequencing
;
Humans
;
Sequence Analysis, DNA
10.Investigation on the satisfaction of postgraduates majoring in public health with the teaching material of chronic disease prevention and control
Zhun YI ; Hongman YIN ; Jing YANG ; Yanfang ZHAO ; Xuetong LIU ; Zheng DAI ; Wenlan DONG ; Zhuoqun WANG
Chinese Journal of Medical Education Research 2022;21(1):125-128
Objective:To investigate the status of satisfaction of postgraduates majoring in public health with the teaching material of The prevention and control of chronic non- communicable disease, so as to provide the basis for promoting the teaching and optimizing the reprint of the teaching material. Methods:An online survey was conducted among 180 public health postgraduates of Batch 2018 to Batch 2020 from China CDC who took the selective course of "prevention and control of chronic non-communicable diseases". The survey content included the overall satisfaction of the respondents with the teaching material and such four levels of satisfaction as primary indicators at the content level, thinking level, motivation level and arrangement level and 20 secondary indicators. The statistical analysis was made by SPSS 25.0.Results:The effective response rate was 90.56% (163/180), and the overall satisfaction of postgraduates with the teaching material was 88.96%. The satisfaction of "scientificity", "comprehensiveness", "internal coordination" and "hierarchy" at the content level, "systematic thinking" and "quality education" at the thinking level, "deepening the understanding and application of relevant knowledge in the field of chronic disease prevention and control" and "the content is convenient for self-study and helps guide the construction of new knowledge" at the motivation level, and "accurate words, fluent language and easy to read and understand" and "firm binding, good paper quality and clear printing" at the arrangement level of the teaching material was more than 90.00%. Only the satisfaction of "the critical thinking" at the thinking level and "stimulating learning enthusiasm" at the motivation level was less than 85.00%.Conclusion:The teaching material of The prevention and control of chronic non- communicable disease meets the learning needs of postgraduates majoring in public health, and students have high overall satisfaction evaluation on the teaching material. It is necessary to further optimize the two aspects of "the critical thinking" and "stimulating learning enthusiasm" in the revision of the teaching material.