1.The therapeutic effects of newly formulated Tadalafil tablets on rats with pathological cardiac hypertrophy through regulation of NF-κB signaling pathway
Xue-di ZHANG ; Ye-ding SONG ; Li-mei LI ; Hao-yan CHEN ; Hua-sui CUI ; Zheng-gang ZHAO ; Zi-jian ZHAO ; Yun-ping MU ; Fang-hong LI
Chinese Pharmacological Bulletin 2025;41(8):1485-1492
Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P<0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P<0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.
2.The therapeutic effects of newly formulated Tadalafil tablets on rats with pathological cardiac hypertrophy through regulation of NF-κB signaling pathway
Xue-di ZHANG ; Ye-ding SONG ; Li-mei LI ; Hao-yan CHEN ; Hua-sui CUI ; Zheng-gang ZHAO ; Zi-jian ZHAO ; Yun-ping MU ; Fang-hong LI
Chinese Pharmacological Bulletin 2025;41(8):1485-1492
Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P<0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P<0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.
3.Comparison of antibiotic resistance spectrum between methicillin-resistant and methicillin-susceptible coagulase-negative staphylococci nasal isolates among 1 001 HIV infectors
Sui-ping HE ; Jia-ping YE ; Chan BAI ; Ling-hua LI ; Li-ya LI ; Wei-ping CAI ; Ying-ying WANG ; Ying LI ; Wen-cui ZHANG ; Ning LIU ; Zi-jun GONG ; Zhen-jiang YAO
Chinese Journal of Disease Control & Prevention 2019;23(12):1527-1530
Objective We aimed to elucidate the prevalence and the antibiotic resistance spectrum of nasal coagulase-negative staphylococci (CoNS) colonization among HIV infectors in Guangzhou. Method After isolation and identification, all CoNS isolates were tested for the antibiotic susceptibility, and the antibiotic resistance genes. Result Among the 1 001 HIV infectors, the prevalence of CoNS and MRCoNS were 57.44% and 48.15%, respectively. The three predominant resistant antibiotics of MRCoNS isolates were penicillin, erythromycin and trimethoprim-sulfame thoxazole, while predominant detection rates of genes were Aac(6’)-aph(2’)、ermC and linA genes. The multidrug resistance rate of MRCoNS isolates were significantly higher than methicillin-susceptible coagulase-negative staphylococci (MSCoNS) isolates (80.69% versus 39.66%, P<0.001, OR=6.36). Conclusions The prevalence and multidrug resistant rates of nasal colonization CoNS and MRCoNS are high among HIV infectors in Guangzhou. MRCoNS isolates were 6.36 times more likely to be of multidrug resistance than MSCoNS isolates.
4.Change of Ankyrin G Promoter Activity Following Treatment with Sodium Valproate at Different Concentrations.
Cui LIU ; Jie WU ; Xiao-long SUI ; Yan-hong LI ; Yun-lin HAN ; Yu-huan XU ; Lan HUANG ; Hua ZHU ; Shu-li SHENG ; Chuan QIN
Acta Academiae Medicinae Sinicae 2015;37(5):508-513
OBJECTIVETo investigate whether sodium valproate (VPA) directly regulates the activity of Ankyrin G(AnkG) promoter in vitro.
METHODSThe mouse AnkG promoter sequence was identified by comparing both human and mouse AnkG promoter sequences. The promoter was amplified from C57BL/6 mouse genome DNA and cloned into pGL3 Luciferase reporter vector. The Luciferase activity was detected in N2a and 293T cells and then treated with 0,0.5, and 1 mmol/L VPA for 12 h. The transcription activity of AnkG promoter in cells and the activity of VPA-treated Luciferase reporter vector in cells were detected using dual Luciferase reporter assay.
RESULTSThe AnkG promoter clone and its expression vector were successfully established, as confirmed by enzyme digestion and sequencing. The AnkG promoter showed high transcription activity in both N2a and 293T cells. The Luciferase activity was significantly induced following 0.5 mmol/L VPA treatment in both N2a and 293T cells. CONCLUSIONS VPA can up-regulate the AnkG expression via directly increasing its transcription activity. Thus, the in vivo AnkG expression may be directly regulated by the VPA at transcriptional level.
Animals ; Ankyrins ; Cell Line ; Genetic Vectors ; Humans ; Luciferases ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; Up-Regulation ; Valproic Acid
5.Effects of Tanyu Tongzhi recipe on hemorheology, blood lipid and inflammatory factors in rats with mycardial ischemia-reperfusion injury and hyperlipidemia.
Dan-Li TANG ; Lin TONG ; Hua-Min ZHANG ; Yu SUI ; Hai-Feng CUI
China Journal of Chinese Materia Medica 2013;38(2):249-252
OBJECTIVETo investigate the influence of Tanyu Tongzhi (TYTZ) recipe on chemorheology, blood lipid and inflammatory factors of hyperlipidemia and myocardial ischemia-reperfusion injury in rats.
METHODSixty SD male rats were divided into 5 groups randomly, sham-operated group, model group, high dose group of reproduced by ligation of left descending artery for 30 min followed by releasing the TYTZ and low group of TYTZ. The model of MI/RI injury of the myocardium was ligation for 2 hours in rats. Serum contents of CHO, TG, HDL-L, LDL-L and whole blood viscosity, plasma viscosity and ICAM-1, TNF-alpha, IL-10 were measured after myocardial reperfusion injury.
RESULTCompared with sham-operated group, the levels of CHO, TG, LDL-L, whole blood viscosity (1.0,3.0) plasma viscosity and the contents of ICAM-1 were significantly higher, however, HDL-L, IL-10 levels were lower in model group (P < 0.01 and P < 0.05). CHO, TG, whole blood viscosity (1.0, 3.0, 30) and expression of ICAM-1, TNF-alpha were obviously lower in low group than the model group (P < 0.01 and P < 0.05).
CONCLUSIONThe TYTZ recipe can relieve reperfusion injury through regulating blood lipid, improving hemorheological characteristic and inhibiting inflammatory reaction.
Animals ; Blood Proteins ; analysis ; metabolism ; Blood Viscosity ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart ; drug effects ; Hemorheology ; drug effects ; Hyperlipidemias ; drug therapy ; Inflammation ; blood ; prevention & control ; Lipids ; blood ; Male ; Myocardial Reperfusion Injury ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley
6.A cross-sectional study on the prevalence of HIV drug resistance in patients receiving antiretroviral treatment in Shenqiu county, Henan province
Wei-Guo CUI ; Xiu-Juan XUE ; Jia LIU ; Guo-Qing SUN ; Chun-Hua LIU ; Sui-An TIAN ; Zhe WANG ; Han-Ping LI ; Jing-Yun LI
Chinese Journal of Epidemiology 2013;34(3):218-220
Objective To understand the prevalence of drug resistance in AIDS patients who had been receiving HAART in a long run,in Shenqiu county,Henan province.Methods This crosssectional study included 120 HIV infected patients who began receiving ART (antiretroviral therapy) in 2003.Viral loads and CD4 +T cells counts were measured,and In-house drug resistance test was performed in VL > 1000 copies/ml patients.Results 114 cases out of 120 patients had complete viral load data.Among them,33 cases having viral loads less than 50 copies/ml,and the remaining viral loads showed an average of lg (4.09 ± 1.10) copies/ml.The average of CD4+ T cell counts was (377 ±2 1 8) cells/ml,with 64 (53.3%) cases showing their CD4+ T cell counts higher than 350 cells/ml.In 67 patients,58 of them showed genotypic resistance,and 40 cases showed reverse transcriptase inhibitors (RTIs) resistance.The ratios of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) resistance were 53.4% (31/58) and 67.2% (39/58),respectively.There were no differences of drug resistance ratio in the three treatment programs.The highest drug resistance rates in NRTIs and NNRTIs were zidovudine,lamivudin,nevirapine.However,protease inhibitors (PIs) resistance variants were not found.Conclusion The prevalence of drug-resistant strains seemed to be high in Shenqiu country,Henan province.Long-term follow-up monitoring strategy should be developed to optimize the timely treatment programs.
7.Expression and significance of vitamin D and its receptor mRNA in the peripheral blood of initial immune thrombocytopenic patients.
Wei MU ; Wei WANG ; Zhong-Guang CUI ; Ai-Hua SUI
Journal of Experimental Hematology 2013;21(3):684-687
To investigate the effect of vitamin D in pathogenesis and clinical treatment of patients with immune thrombocytopenic (ITP), ELISA was used to detect the level of 25-hydroxylate vitamin D3[25(OH)D3] and 1,25-dihydroxyvitamin D3[1,25(OH)2D3] in peripheral blood from 45 ITP patients and 30 normal controls. Vitamin D receptor (VDR) mRNA expression was detected by RT-PCR. The results showed that the levels of 25(OH)D3 (10.6 ± 7.7 ng/ml) and 1,25(OH)2D3 (69.9 ± 29.0 pg/ml) in peripheral blood of the initial ITP patients were lower than those in peripheral blood of normal controls (13.7 ± 9.1 ng/ml, 87.3 ± 19.9 pg/ml) (P < 0.05). The expression of VDR gene obviously increased in peripheral blood of initial ITP patients (1.588 ± 0.127), as compared with that in peripheral blood of normal controls (1.055 ± 0.734) (P < 0.05). It is concluded that vitamin D level and its receptor expression may play an important role in ITP, and vitamin D and its similarities may be a new agent to treat patients with ITP.
Adolescent
;
Adult
;
Aged
;
Case-Control Studies
;
Cells, Cultured
;
Female
;
Humans
;
Male
;
Middle Aged
;
RNA, Messenger
;
genetics
;
Receptors, Calcitriol
;
blood
;
Thrombocytopenia
;
blood
;
Vitamin D
;
blood
;
Young Adult
8.Epidemiological survey on the hepatitis C virus and its genotyping analysis in Henan province in 2012.
Wei-guo CUI ; Xiu-juan XUE ; Chun-hua LIU ; Guo-qing SUN ; Jia LIU ; Pan-ying FAN ; Sui-an TIAN ; Ding-yong SUN ; Wen-ge XING ; Zhe WANG
Chinese Journal of Preventive Medicine 2013;47(6):518-522
OBJECTIVETo investigate the prevalence and distribution of hepatitis C virus (HCV) genotypes in Henan province in 2012.
METHODSA total of 32 203 permanent residents (1 to 74 years old) in Henan were recruited using multi-stage random samping method from March to June 2012. All participants were asked to complete a questionnaire to collect demographic information, past medical history and the exposure history of risk factors. A blood sample of 5 ml was collected at the same time. The condition of anti-HCV and HCV RNA was determined through the ELISA test and nested RT-PCR. HCV RNA positive samples were further subject to the nonstructural protein 5 region (NS5B) gene amplification and sequencing. The sequence was amplified for the phylogenetic tree and genetic analysis. The differences of the positive rate of anti-HCV and HCV RNA and the HCV genetic subtype distribution in different respondents'characteristics were analyzed.
RESULTSAmong 32 203 subjects, the overall positive rate of anti-HCV and HCV RNA were 0.48% (153/32 203) and 0.24% (78/32 203), in which men were 0.42% (65/15 634), and 0.23% (36/15 634), and women were 0.53% (88/16 569) and 0.25% (42/16 596). The differences between men and women were not statistically significant (χ(2) values were 2.26, 0.18, respectively, both P values > 0.05). The results of NS5B genotyping and molecular evolution analysis showed that there were six subtypes in the 71 HCV RNA positive samples.In those six subtypes, the proportion of genotypes 1b, 6a, 3a, 2a, 3b and 1a were 56.3% (40/71), 19.7% (14/71), 11.3% (8/71), 8.5% (6/71), 2.8% (2/71) and 1.4% (1/71), respectively. The HCV genetic subtypes of infestor were mainly present with two branches of 1b and 6a, and the two subtypes Bootstrap values were 0.95.
CONCLUSIONThe prevalence of HCV infection was high in Henan. The major HCV genotypes in patients with HCV infection were 1b and 6a.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Genotype ; Hepacivirus ; classification ; genetics ; Hepatitis C ; epidemiology ; virology ; Humans ; Infant ; Male ; Middle Aged ; Phylogeny ; RNA, Viral ; genetics ; Sequence Analysis, DNA ; Young Adult
9.The primary HIV drug resistance in partial region of Henan province.
Xiu-juan XUE ; Kun-xue HONG ; Wei-guo CUI ; Chun-hua LIU ; Jia LIU ; Sui-an TIAN ; Guo-qing SUN ; Zhe WANG
Chinese Journal of Preventive Medicine 2012;46(11):992-994
OBJECTIVETo study the prevalence of primary HIV drug resistance in antiretroviral therapy (ART) areas of Henan province.
METHODSA total of 121 drug-naive long-term infected individuals and 154 patients with newly diagnosed from January 2011 to March 2012 were recruited, the questionnaires were surveyed and whole blood were collected to analyze the CD4(+)T cell counts and viral load. In-house method for genotypic resistance test was determined in those with viral load > 1000 copies/ml samples, the differences of demographic characteristics, immunological parameters and primary drug resistance were compared between the two groups.
RESULTSA total of 121 cases of long-term individuals who had infected (12.50 ± 3.21) years were mainly previous paid blood donors, and the age was (46.61 ± 9.32) years old. The infection route of the newly diagnosed were diversity, including blood, sexual transmission and others, the cases were 73, 73, 8, respectively, the confirmatory year was (0.91 ± 0.28) years, and average age was (22.21 ± 3.11) years old. The difference were statistically significant in the route of transmission, age and infection time from demographic analysis of the two groups (P < 0.05). The absolute M(P(25)-P(75)) counts of CD4(+)T lymphocytes of long-term group was 322 (217 - 422) cell/µl, which was lower than the newly diagnosed was 434(308 - 578) cell/µl (P < 0.05), and viral load was 4.0 (2.96 - 4.64) copies/ml, 3.77 (2.94 - 4.53) copies/ml, the difference was not significant (P > 0.05). The prevalence of primary drug resistance in long-term group and newly diagnosed was 5.79% (7/121), 9.09% (14/154), respectively, and the difference was statistically different (P < 0.05), and one PI-resistant strain was found in the newly diagnosed group.
CONCLUSIONThe primary drug resistant strains in untreated patients were found in Henan province of ART areas, and there was difference in degree of resistance between long-term infected individuals and newly diagnosed.
Adult ; Anti-HIV Agents ; pharmacology ; therapeutic use ; China ; epidemiology ; Drug Resistance, Viral ; Female ; HIV Infections ; drug therapy ; epidemiology ; virology ; Humans ; Male ; Middle Aged ; Viral Load
10.Men who have sex with men and its relationship with HIV-1 strains prevailing in the paid blood donors from Zhengzhou city, Henan
Zhe WANG ; Wei-Guo CUI ; Guo-Qing SUN ; Jia LIU ; Sui-An TIAN ; Chun-Hua LIU ; Xiu-Juan XUE ; Lin LI ; Jing-Yun LI
Chinese Journal of Epidemiology 2012;33(9):888-892
Objective To clarify the genetic characteristics of human immunodeficiency virus (HIV) circulated in the population of men who have sex with men (MSM) in Zhengzhou,Henan and to analyze its relationship with HIV-1 prevailing in the paid blood donors (PBDs).Methods Thirty-one MSM who were confirmed as HIV positive individuals in 2010 together with 41 HIV-positive former PBDs were enrolled in the study.Information on related epidemiological characteristics and their plasma were collected.RT-PCR was used to amplify HIV-1 full length gag (1584 bp),pol (3147 bp) genes and partial env gene (C2V3 segment,558 bp) followed by sequencing on those subjects.Online software available at LosAlamos HIV Database was used to identify the HIV subtypes based on the findings of the sequences.Phylogenetic tree was used to identify thc possible relationship of transmission.Results Fifty-three full length gag,38 full length pol and 48 partial env (C2V3) genes were collected from 72 participants.Among the 31 HIV ( + )MSM individuals,14 CRF01_AE strains,5 CRF07BC_ strains and 12 subiype B ( 1 subtype B and 11B' ) strains were identified respectively.All of the 41 strains identified from former PBDs were infected by B' strains.The CRF01_AE strains identified in MSM showed a close relationship to those identified from both Hebei and Liaoning provinces.The CRF07 BC strains showed a close relationship with those from Shijiazhuang and Beijing cities.Among the 12 subtype B strains,8 sequences grouped into 1 cluster with 1 sequence from the former PBDs.Two sequences grouped with 02HNseq4 suggested that B' had been prevailed in the MSM population might come from the former PBDs and were closely related to the strains identified in the MSM population.Conclusion Complicated genetic background and multiple introductions of HIV in the MS population in Zhengzhou,were found.This was also the first report which noticed that the subtype B epidemic among Zhengzhou MSM was mainly originated from the B' among the former PBDs.

Result Analysis
Print
Save
E-mail