1.Improvement effect of captopril on insulin resistance mediated by PPARγin vascular endothelial cells
Guoqiang YAN ; Chunxiang CHUN ; Fanghui CHEN ; Yan GAO ; Jiajia CHU ; Teng LI ; Qiren HUANG
Chinese Pharmacological Bulletin 2015;(4):532-536,537
Aim To investigate the role of captopril in insulin resistance of endothelial cells induced by high glucose.Methods 1 .Improvement effect of captopril on insulin resistance in HUVECs was observed.The HUVECs were seeded in a 6-well plate and were ran-domly divided into 5 groups,namely,control group, IR group,IR together with different Cap concentrations (low,medium and high concentration),respectively. 2.Improvement effect of Cap on insulin resistance was mediated by PPARγin HUVECs.HUVECs were ran-domly divided into 6 groups,namely,control group, control +PPARγinhibitor (PI)(1 .0 μmol · L -1 ) group,IR group,IR +PI(1 .0 μmol·L -1 )group,IR +Cap(1 ×1 0 -5 mol·L -1 ) group,and IR +Cap +PI (1 .0 μmol·L -1 )group.All indicators were detected. Results After HUVECs were incubated with media containing 33 mmol·L -1 of glucose for 48 h,the NO levels were significantly decreased while ET-1 levels were significantly elevated,showing a significant differ-ence between IR group and control group (P <0.01 ). The expression levels of PPARγmRNA and its protein were somewhat up-regulated,but there was no signifi-cant difference between IR group and control group (P>0.05).When the HUVECs in IR group were treated with DMEM containing glucose (33 mmol·L -1 )for 48 h and insulin for 30 min,the expression levels of PPARγmRNA and its protein in Cap groups were simi-lar to those in the IR group,and there was no signifi-cant difference between the two groups (P >0.05 );however, the expression levels of phosphorylated PPARγprotein in Cap groups were increased compared with IR group (P <0.05).The levels of NO were sig-nificantly increased whereas the levels of ET-1 were decreased in Cap groups,which had significant differ-ences compared with IR group (P <0.05).Nonethe-less,pre-treating with GW9662,a PPARγinhibitor, the improvement effects of Cap were markedly abol-ished.Conclusions Captopril could improve high glucose-induced insulin resistance of endothelial cells mediated by PPARγ,and the underlying mechanisms are related to the activation of PPARγ,rather than its expression.
2.The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells.
Chun Yu LIU ; Tzu Ting HUANG ; Pei Yi CHU ; Chun Teng HUANG ; Chia Han LEE ; Wan Lun WANG ; Ka Yi LAU ; Wen Chun TSAI ; Tzu I CHAO ; Jung Chen SU ; Ming Huang CHEN ; Chung Wai SHIAU ; Ling Ming TSENG ; Kuen Feng CHEN
Experimental & Molecular Medicine 2017;49(8):e366-
Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis*
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Breast Neoplasms
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Disease-Free Survival
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Humans
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Protein-Tyrosine Kinases*
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RNA, Small Interfering
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Triple Negative Breast Neoplasms*
;
Tyrosine*
3.Migraine Susceptibility Genes in Han Chinese of Fujian Province.
Qi Fang LIN ; Zi Chun CHEN ; Xian Guo FU ; Jing YANG ; Luo Yuan CAO ; Long Teng YAO ; Yong Tong XIN ; Gen Bin HUANG
Journal of Clinical Neurology 2017;13(1):71-76
BACKGROUND AND PURPOSE: Five single-nucleotide polymorphisms (SNPs) (rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321) were recently identified in a Western population with migraine. These migraine-associated SNPs have not been evaluated in a Han Chinese population. This study investigated the associations of specific SNPs with migraine in a Han population. METHODS: This was a case-control study of Han Chinese residing in Fujian Province. Polymerase chain reaction—restriction-fragment-length polymorphism analysis and direct sequencing were used to characterize the relationships of SNPs in a control group of 200 subjects and in a migraine group of 201 patients. RESULTS: The frequencies of the five SNPs did not differ between patients with migraine and healthy non migraine controls. However, subgroup analysis indicated certain SNPs were more strongly associated with migraine with aura or migraine without aura than with controls. The CT genotype of rs4379368 was more common in migraine patients with aura (75%) than in migraine patients without aura (47.9%) and controls (48.5%) (p<0.05), and the TT genotype of rs10504861 was more common in migraine patients with aura than in controls (8.3% vs. 0.5%) (p<0.05). Meanwhile, the CC genotype of rs12134493 was less common in migraine patients without aura than in controls (80.6% vs. 88%) (p<0.05). CONCLUSIONS: Our findings suggest that the rs4379368 and rs10504861 SNPs are markers for susceptibility to migraine with aura and that rs12134493 is a marker for the risk of migraine without aura in this Han population. Future studies should further explore if these associations vary by ethnicity.
Asian Continental Ancestry Group*
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Case-Control Studies
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Epilepsy
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Genotype
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Humans
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Migraine Disorders*
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Migraine with Aura
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Migraine without Aura
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Polymorphism, Single Nucleotide
4.Growth and accumulation of shikonin compounds of two kinds of cells in suspension culture of Arnebia euchroma.
Sheng WANG ; Teng XIE ; He-Chun YE ; Shu-Fang LIN ; Yan ZHANG ; Mei-Lan CHEN ; Lu-Qi HUANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2013;38(8):1138-1144
Via studying the phenotype, growth curve and secondary metabolites of two kinds of suspension culture cell of Arnebia euchroma, the kinetics parameters of growth and accumulation of shikonin compounds in cell suspension culture of A. euchroma was obtained through simulating and modeling. This Study found that the red high-yielding one was a fine cell line for producing shikonin compounds, and the white low-yielding one may be a mutant. The first-order and second-order derivative of the fitting function were obtained by fitting the Logistic model of growth curve to get the growth rate and growth acceleration curve of the suspended cells. It is found that the best period to subculture was the 15th day cultured in fresh medium, and the best period of the induction process was the 13th-14th day. When compared the growth rate of the red line and the shikonin compounds accumulation curve, it is found that the rapid growth of the biomass of cells was not conducive to the synthesis and accumulation of shikonin compounds.
Boraginaceae
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chemistry
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cytology
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metabolism
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Cell Culture Techniques
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Cell Proliferation
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Naphthoquinones
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metabolism
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Plant Cells
5.Immunosuppression induced by Measles virus in adult patients is not related to CD4+ CD25+ regulatory T cell induction
Mei-Zhong LI ; Fu-De XU ; Xue-Huan HUANG ; Xin-Chun CHEN ; Qi-Wen DENG ; Shui-Teng LIU ; Yan LIU ; Liu-Mei XU ; Huo-Sheng WANG ; Jian-Jun CUI
Chinese Journal of Experimental and Clinical Virology 2008;22(3):211-213
Objective To investigate of the relationship of the immunosuppression induced by Measles virus in adult patients and CD4+ CD25+ regulatory T cell. Methods Thirty-four patients with measles and 27healthy control subjects were included in this study. The whole blood was collected and CD4+ CD25+ cell andFoxP33 cell were analyzed by flow cytometry, and CD4+ CD25- and CD4+CD25+ T lymphocytes were isolated from PBMCs of patients with measles or healthy donors, CD4+ CD25- T cells were cultured in absence or presence of anti-CD3, or BCG, or live attenuated MV. The cell culture supernatant was collected after 72 hours and the concentration of IFN-γ and IL-10 was determined. Results Compared to healthy donors, we observed a reduction of the number of white blood cells and lymphocytes in patients with measles, but there was not significantly different in the frequency of CD4+ CD25+ T cells and CD4+ CD25high T cells with in the total CD4+ population in the blood. Treg from both measles patients and healthy controls significantly inhibited IFN-γ production by CD4+ CD25- T cells in response to anti-CD3 stimulation. Conclusion Induction and expansion of Treg may not represent a mechanism involved in the establishment of immune suppression by MV.
6.Mental health status and its influencing factors among residents in Zhuhai
Ning WEI ; Jingju QUAN ; Yixuan WU ; Yongyong TENG ; Chun MAO ; Jiaju HUANG ; Yunfei KE ; Yajun SUN
Sichuan Mental Health 2024;37(5):457-463
Background Currently,there has been a gradual increase in the incidence of mental diseases,becoming a problem that has attracted great concern of the general public.Zhuhai is a core city of the Guangdong-Hong Kong-Macao Greater Bay Area,and the local government have attached great importance to the mental health of residents.The systematic study on the mental health has focused largely on pregnant women and medical workers,yet few are on the adult residents.Objective To investigate the prevalence and its influencing factors of anxiety and depression among adult residents in Zhuhai,so as to provide references for formulating targeted psychological intervention strategies.Methods From September 1 to December 1,2021,a cohort of 5 600 permanent residents aged 18 years and above in Zhuhai were selected through multistage sampling.All participants were subjected to complete Patients' Health Questionnaire Depression Scale-9 item(PHQ-9),Generalized Anxiety Disorder Scale-7 item(GAD-7)and National Mental Health Literacy Questionnaire based on Wenjuanxing software.Then Logistic regression was employed to identify the factors associated with anxiety and depression among the residents.Results Among the 5 600 residents,depressive symptoms were detected in 842(15.04%)residents and anxiety symptoms in 579(10.34%)residents.Logistic regression analysis yielded that female gender(OR=1.488),living in Doumen district(OR=1.942),junior college/undergraduate level(OR=3.602),postgraduate and above(OR=5.904),irregular meal pattern(OR=3.320),comorbid chronic diseases(OR=3.244),disqualification of self-assessment(OR=3.414)and disqualification of mental health skill(OR=2.131)were risk factors for depression symptoms,whereas age≥25 years old(of all age groups OR<1),monthly per capita income>20 000 yuan(OR=0.438)and exercising≥3 times a week(OR=0.431)were protective factors for depression symptoms.Age of 25~34 years old(OR=2.051),living in Jinwan district(OR=1.729)or Doumen district(OR=1.901),junior college/undergraduate level(OR=2.955),postgraduate and above(OR=6.662),irregular meal pattern(OR=2.741),comorbid chronic diseases(OR=3.535),disqualification of self-assessment(OR=3.325)and disqualification of mental health skill(OR=1.838)were risk factors for anxiety symptoms,while monthly per capita income of 6 001~9 000 yuan(OR=0.665)and exercising≥3 times a week(OR=0.572)were protective factors for anxiety symptoms.Conclusion The mental health status of adult residents in Zhuhai is affected by various factors,including gender,age,region of residence,education level,meal pattern,exercise frequency and chronic diseases.
7.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
8.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
9.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
10.Patients suffered from enlarged vestibular aqueduct syndrome in Chifeng deaf and dumb school detected by Pendred's syndrome gene hot spot mutation screening.
Pu DAI ; Xiu-Hui ZHU ; Yong-Yi YUAN ; Qing-Wen ZHU ; Guo-Chun TENG ; Xin ZHANG ; Li-Xian LIU ; Jia-Ling WANG ; Bo FENG ; Suo-Qiang ZHAI ; Dong-Yang KANG ; Xin LIU ; De-Liang HUANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2006;41(7):497-500
OBJECTIVETo investigate the incidence of hot spot mutation of PDS gene by genetic screening testing method in Chifeng City, Inner Mongolia. The feasibility and effectiveness of genetic screening method in finding enlarged vestibular aqueduct syndrome were confirmed by temporal bone CT scan.
METHODSDNA were extracted from peripheral blood of 141 students of Chifeng Deaf and Dumb school. PDS IVS7-2 A-G mutation, the most common PDS mutation in Chinese population, was analyzed by direct sequencing for PDS exon 7, exon 8 with intron 7. The individuals found with homozygous or heterozygous PDS IVS7-2 A-G mutation were given further temporal CT scan, ultrasound scan of thyroid and thyroid hormone assays. The results of PDS genetic screening and temporal bone CT scan were compared with each other.
RESULTSThe sequencing results revealed twenty cases carrying PDS IVS7-2 A-G mutation, of whom nine cases were homozygous mutation and eleven cases were heterozygous mutation. Eighteen cases underwent temporal bone CT scan except two cases that left the school due to other health problem. Sixteen cases were confirmed to be enlarged vestibular aqueduct syndrome (EVAS) by CT scan and the shape and function of thyroid were clinically normal by ultrasound scan of thyroid and thyroid hormone assays, respectively.
CONCLUSIONSThe patients suffered from EVAS can be diagnosed by the screening for the PDS hot spot mutation which has unique advantage in epidemiologic study in large scale deaf population. The preliminary data of this study suggested relatively high incidence of EVAS in Chifeng area.
Adolescent ; Child ; Child, Preschool ; China ; Female ; Genetic Testing ; Hearing Loss ; genetics ; Humans ; Membrane Transport Proteins ; genetics ; Point Mutation ; Syndrome ; Vestibular Aqueduct ; pathology ; Vestibular Diseases ; genetics ; Young Adult