1.Retinol-binding protein 4 rises significantly in women with gestational diabetes mellitus
Yuxia SU ; Qun YAN ; Jie HONG ; Chunfang SHEN ; Weiqiong GU ; Yifei ZHANG ; Meng DAI ; Min XU ; Zhenni CHI ; Yuwen ZHANG ; Xiaoying LI ; Guang NING ; Minmin WANG ; Duanduan LA
Chinese Journal of Endocrinology and Metabolism 2010;26(6):468-470
To investigate the relationship between serum retinol-binding protein 4(RBP4) and gestational diabetes mellitus (GDM) in Chinese Han pregnant women.195 (23-42 years) pregnant women were recruited (July 2005 to December 2007) from the Department of Gynecology and Obstetric in Ruijin Hospital during their visiting for routine prenatal examination.99 subjects belonged to GDM group,and 96 belonged to the group with normal glucose tolerance (NGT).65 non-pregnant healthy women served as control.Serum RBP4 was measured using sandwich enzyme linked immunosorbent assay (ELISA).Pregnant women had higher level of serum RBP4 than that of non-pregnant control.The concentration of serum RBP4 was significantly increased in GDM group as compared with NGT group[(43.04±1.85 vs 33.84±2.17) rag/L,P<0.01].Multiple stepwise regression analysis showed that triglycerides and homeostasis assessment for insulin resistance (HOMA-IR) were independent variables of RBP4 (r2 =0.165) in pregnant women.The results suggest that serum RBP4 level is significantly increased in pregnant women.Women with GDM had even higher RBP4 level than that of normal pregnant women,and RBP4 levele was positively correlated with triglycerides and HOMA-IR.
2.α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo.
Yan SHI ; Candy LEE ; Peng SANG ; Zaid AMSO ; David HUANG ; Weixia ZHONG ; Meng GU ; Lulu WEI ; Vân T B NGUYEN-TRAN ; Jingyao ZHANG ; Weijun SHEN ; Jianfeng CAI
Acta Pharmaceutica Sinica B 2023;13(4):1648-1659
Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t 1/2 > 14 days) compared to t 1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.
3.Conditioned Place Preference and Self-Administration Induced by Nicotine in Adolescent and Adult Rats.
Hafiz Muhammad AHSAN ; June Bryan I DE LA PENA ; Chrislean Jun BOTANAS ; Hee Jin KIM ; Gu Yong YU ; Jae Hoon CHEONG
Biomolecules & Therapeutics 2014;22(5):460-466
Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine.
Adolescent*
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Adult*
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Animals
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Humans
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Models, Animal
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Nicotine*
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Rats*
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Reward
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Substance-Related Disorders
4.The relationship between polymorphisms at 17 gene sites and hypertension among the Aboriginal Tibetan people.
Kui LI ; Yu LIANG ; Yin SUN ; Ling Xia ZHANG ; Xin YI ; Yong CHEN ; Gu Sang LA MU ; Jian WANG
Biomedical and Environmental Sciences 2012;25(5):526-532
OBJECTIVEThe incidence of hypertension in Tibet ranks highest among all Chinese provinces. This may be due to genetic changes caused by Tibet's unique natural environment and agrarian lifestyle, prompting us to investigated the relationship between gene polymorphisms and hypertension.
METHODSBlood samples were collected from 229 hypertensive participants and 372 healthy (control) participants from five Tibetan counties. Seventeen single nucleotide polymorphisms were investigated for their connection to hypertension.
RESULTSThe C allele at rs2070744 of the NOS3 gene was shown to be significantly associated with hypertension (P=0.0443; OR=1.636). Additionally, the T allele of rs4961 of the ADD gene was correlated with hypertension in women (P=0.03124; OR=1.584).
CONCLUSIONIn this study we found that the NOS3 and ADD genes were related to a high incidence of hypertension among Tibetans. NOS3 gene plays a role in regulating vascular tone and blood vessel diameter, which may be altered by the low-oxygen environment of Tibet. ADD is involved in water and salt metabolism, which is consistent with the high-salt diet of Tibetans. The correlations elucidated by our study were different from those of other ethnic groups, indicating that these findings may be specific to the Tibetan people.
Adult ; Animals ; Asian Continental Ancestry Group ; genetics ; Female ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Tibet
5.Survey of infection of Toxoplasma gondii in infertile couples in Suzhou countryside.
Yong-Hua ZHOU ; Yong-Juan LU ; Rui-Bing WANG ; La-Mei SONG ; Fang SHI ; Qing-Feng GAO ; Ya-Fang LUO ; Xing-Feng GU ; Pei WANG
National Journal of Andrology 2002;8(5):350-352
OBJECTIVESTo determine the level of anti-Toxoplasma antibody in serum of infertile couples to explore the relationship between toxoplasma infection and infertility.
METHODSEnzyme-linked immunosorbent assay (ELISA) was applied to detect the anti-Toxoplasma antibody, antisperm antibody (AsAb) and anticardiolipin antibody (ACA) in serum of 178 couples with infertility and 190 couples who had normal pregnant history.
RESULTSThe positive result of Toxoplasma infection in the infertile couples was significantly higher than that in fertile couples which was 34.83% vs 12.11% (chi 2 = 26.72, P < 0.01) with the odds ratio 3.88. The positive result of serum AsAb in the Toxoplasma infected group was significantly higher than that in the no Toxoplasma infected group (32.50% vs 15.94%, chi 2 = 10.76, P < 0.01) with the odds ratio 2.54.
CONCLUSIONSToxoplasma infection was related to infertility. The Toxoplasma infection and was posibly related to the antisperm antibodies which can be involved in the pathogenisis of infertility.
Animals ; China ; epidemiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infertility, Male ; epidemiology ; etiology ; parasitology ; Male ; Toxoplasma ; Toxoplasmosis ; complications ; epidemiology ; parasitology
7.Oligomeric Procyanidins (OPCs) Inhibit Procollagen Type I Secretion of Fibroblasts.
Byung Jun KIM ; Jung Keun PARK ; Byeong Kyu KIM ; Soo Jin PARK ; Min Kyung KIM ; Chang won LEE ; La Mee CHOI ; Ji An HUR ; Sang Hyon KIM ; Jaewon BEOM ; Jung Yoon KIM ; Byung Mo OH ; Tae Hyun CHOI ; Sukwha KIM
Tissue Engineering and Regenerative Medicine 2017;14(3):297-306
Wound healing is composed of a complex process that requires harmonies of various cell populations where fibroblasts play the main role. Oligomeric procyanidins (OPC) are main components of grape (Vitis vinifera) seed extracts, and recent studies showed OPC's effects on inflammation, cell migration, and proliferation. We investigated the effect of OPC on fibroblasts to regulate wound healing process. Human dermal fibroblast known as Hs27 cells were treated with various concentrations of OPC (0, 2.5, 5, 10, and 20 µg/µl). Cell cytotoxicity was evaluated by the Cell Counting Kit assay, and the expression levels of secreted procollagen were analyzed. Procollagen levels in OPC treated cells exposed to transforming growth factor beta 1 (TGF-β1) or ascorbic acid were evaluated using Western blot and immunocytochemistry. Relative mRNA expressions of procollagen, molecular chaperone such as HSP47, P4H were determined by real-time PCR in OPC treated cells. OPC showed no cytotoxicity on Hs27 cells at every concentration but inhibited procollagen secretion in a dose-dependent manner. The inhibitory effect also appeared under TGF-β1 induced collagen overproduction. Immunocytochemistry showed that higher levels of intracytoplasmic procollagen were accumulated in TGF-β1 treatment group, whereas ascorbic acid induced a release of accumulated procollagen under OPC treatment. The mRNA expressions of procollagen, molecular chaperone were not affected by OPC, but procollagen level was increased when exposed to TGF-β1. OPC inhibits procollagen secretion from fibroblasts with no effects on cell proliferations even under the environment of TGF-b1-induced collagen overproduction. OPC could regulate the diseases and symptoms of abnormal overabundant collagen production.
Ascorbic Acid
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Blotting, Western
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Cell Count
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Cell Movement
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Collagen
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Collagen Type I*
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Fibroblasts*
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Humans
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Immunohistochemistry
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Inflammation
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Molecular Chaperones
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Proanthocyanidins*
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Procollagen*
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Real-Time Polymerase Chain Reaction
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RNA, Messenger
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Transforming Growth Factor beta
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Vitis
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Wound Healing
9.Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes.
Ying GU ; Guang-Hui LIU ; Nongluk PLONGTHONGKUM ; Christopher BENNER ; Fei YI ; Jing QU ; Keiichiro SUZUKI ; Jiping YANG ; Weiqi ZHANG ; Mo LI ; Nuria MONTSERRAT ; Isaac CRESPO ; Antonio DEL SOL ; Concepcion Rodriguez ESTEBAN ; Kun ZHANG ; Juan Carlos IZPISUA BELMONTE
Protein & Cell 2014;5(1):59-68
With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT(+)) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.
Cell Differentiation
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Cell Line
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DNA Methylation
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Embryonic Stem Cells
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cytology
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metabolism
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Epigenesis, Genetic
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Gene Expression Profiling
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Gene Expression Regulation
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Gene Regulatory Networks
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Humans
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Myocytes, Cardiac
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cytology
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metabolism
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Transcription, Genetic