1.Tissue distribution of exendin-4 in rats
Guo AI ; Zhihang CHEN ; Chengqi SHAN ; Jinjing CHE ; Yunan HOU ; Yuanguo CHENG
Chinese Journal of Pharmacology and Toxicology 2008;22(2):95-101
AIM To investigate the tissue distribution of exendin-4 after administration in healthy rats. METHODS Exendin-4 was radioiodinated by the Iodo-GenTMmethod. Tissue distribution of [125I]exendin-4 was investigated after sc administration of [125I]exendin-4 at 3 μg·kg-1 in rats. Both total radioactivity and trichloroacetic acid (TCA) precipitated radioactivity were used to calculate the levels of [125I]exendin-4 in rats plasma and tissue samples after sc administration. RESULTS The tissue distribution of [125I]exendin-4 after sc injection showed substantial disposition in kidneys, lungs, bladder and pancreas. The rank order of normalized tissue distribution was kidneys>lungs>bladder>pancreas>intestine>plasma>adrenals>jejunum>lymph>liver>spleen>heart>marrow>thymus>testicles>brain>muscle>adipose. CONCLUSION [125I]Exendin-4 underwent a rapid and wide distribution in the tissues throughout the whole body within the time course examined. TCA precipitated radioactivity in kidneys was the highest, however, only trace amounts of [125I]exendin-4 was detected in the brain.
2.Preparation of anti-cancer water-soluble paclitaxel prodrug and its anti-cancer effect
Suhua ZHAO ; Xiuqin YANG ; Wei ZHU ; Pengcheng ZHENG ; Jinjing WANG ; Lingling SHAN
Chinese Pharmacological Bulletin 2016;32(12):1711-1717
Aim Paclitaxel(PTX)has shown an effect against human cancer. However, serious drawbacks hamper PTX clinical use.Overcoming paclitaxel limi-tations is one of the best approaches to enhance water solubility.Methods In this study,water-soluble pa-clitaxel prodrug was prepared,folic acid-polyethylene glycol-glutamic-paclitaxel (FA-PEG-Glu-PTX ) com-posed of folic acid (FA,target),amino acids (Glu, linker),and polyethylene glycol(PEG)in order to im-prove the solubilization and stability. The chemical structure and physicochemical property of prodrug were measured by LC-MS,solubility,drug release rate to e-valuate the antitumor activity and cytotoxicity of FA-PEG-Glu-PTX.MTT assays were conducted on MDA-MB-231,MCF-7,A549 and HELF cell lines.FA-PEG-Glu-PTX prodrugs were labeled with 5 amino flu-orescence visible fluorescent dye (5 AF ) for fluores-cence microscopy.Results The successful conjugation of FA-PEG-Glu-PTX was confirmed by LC-MS,and had better water solubility,release rate curve.In vitro studies indicated that foliate receptor(FR-α)mediated uptake of PTX-conjugated multi-small molecules carri-ers induced highly targeting ability,and antitumor ac-tivity,as well as reduced side toxicity effects of PTX. Conclusion FA-PEG-Glu-PTX has a good antitumor activity.
3.Molecular genetic analysis of genes from MNS, Duffy and Kell blood groups in the China Xinjiang Uygur population
Guoyue LIN ; Xiaolu DU ; Jinjing SHAN ; Yanan ZHANG ; Yuqiang ZHANG ; Yuanzhou ZHANG
Chinese Journal of Tissue Engineering Research 2016;20(1):123-127
BACKGROUND:Screening of fare blood types has been successively implemented and completed in Europe, America and Japan, but there is a large gap in China. Previous studies have mainly focused on the southern Han populations, and little is reported on PCR-SSP systematic analysis of gene frequencies of rare blood groups in Xinjiang Uygur populations. OBJECTIVE:To investigate the gene frequency distribution of RBC MNS, Duffy, Kel, Dombrock, Diego, Kidd, Scianna, Colton and Lutheran blood groups from Xinjiang Uygur populations, thereby providing a strategic support for human population genetics and clinical blood deployment. METHODS:PCR-SSP method was used to make genotyping and statistical analysis in 158 Xinjiang Uygur persons from nine rare blood groups. RESULTS AND CONCLUSION: Gene frequencies of these nine rare blood groups were M=0.579 1, N=0.420 9, S=0.174 3, s=0.800 9, Fya=0.699 4, Fyb=0.300 6, K1=0.015 8, K2=0.984 2, Doa=0.234 2, Dob=0.765 8, Dia=0.047 4, Dib=0.952 6, JKa=0.541 2, JKb=0.452 6, Sc1=1.000, Sc2=0, Coa=0.994, Cob=0.005 9, Lua=0, Lub=1.000, Aua=0.810 2, Aub=0.189 9. Results from chi-square test showed that the observed value and expected value of genotypes were in line with the law of Hardy-Weinberg equilibrium (P > 0.05), and in the MNS blood group of Xinjiang Uygur population, it was rarely found that S-s- frequency was 0.025 3 in four cases and Jka-b- frequency was 0.006 3 in one case. This study demonstrates that the frequency distribution of MNS, Duffy, Dombrock and Diego blood groups in the Xinjiang Uygur population, with its own unique frequency distribution characteristics, is different from that in other ethnic populations; the gene distribution of Kel, Kidd and Colton blood groups shows either similarity or difference between the Xinjiang Uygur population and reported Tibet and Han populations; Scianna and Lutheran blood groups show a monomorphic distribution in the Xinjiang Uygur population, which is similar to that in the Tibet and Han populations. These findings provide the basic data for exploring the origin and evolution, ethnic hematology and construction of rare blood database of the Xinjiang Uygur population. Cite this article:Lin GY, Du XL, Shan JJ, Zhang YN, Zhang YQ, Zhang YZ.Molecular genetic analysis of genes from MNS, Duffy and Kel blood groups in the China Xinjiang Uygur population. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):123-127.
4.Correlation between cognitive impairment and diabetic nephropathy in patients with Type 2 diabetes mellitus.
Xiajie SHI ; Yuren ZHANG ; Hongtao NIU ; Ran WANG ; Jinjing SHEN ; Shanlei ZHOU ; Haobo YANG ; Shan WANG ; Jing WU
Journal of Central South University(Medical Sciences) 2016;41(2):143-150
OBJECTIVE:
To explore the correlation between diabetic nephropathy (DN) and cognitive impairment through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus patients at different stages of renal function.
METHODS:
Eighty six patients with Type 2 diabetes mellitus (T2DM) were enrolled for this study. According to the urinary albumin excretion rate (UAER), the patients were divided into a T2DM without DN group (DM group, n=33), an early DN group (DN-III group, n=26) and a clinical stage group (DN-IV group, n=27). Thirty healthy adults were selected as a control group (NC group). Biochemical indexes and UAER were measured, and glomerular filtration rate (GFR) was detected by single-photon emission computed tomography (SPECT). The cognitive function was measured by Montreal Cognitive Assessment (MoCA, Beijing version) and mini-mental state examination (MMSE). The peak areas of N-acetylasparte (NAA), creatine (Cr), choline-containing compounds (Cho) were detected by proton magnetic resonance spectroscopy (1H-MRS).
RESULTS:
1) There was no statistical difference in MMSE scores between the DM group and the control group. The scores of MoCA in the DN-III group or in the DN-IV group were significant less than that in the NC group (F=3.66, P<0.05); 2) There was significant difference in left N-acetylaspartate (LNAA), left choline (LCho) among the diabetes groups. Compared with the DM group, the level of LNAA was decreased significantly (t=3.826, P<0.05) while the LCho was increased significantly (t=4.373, P<0.05) in the DN groups, with statistic difference between the 2 groups (t=3.693, P<0.05); 3) The MoCA scores of T2DM patients were negatively correlated with UAER (r=-0.285, P<0.05), while positively correlated with GFR (r=0.379, P<0.05); 4) Logistic regression analysis indicated that UAER and GFR were the major risky factors for diabetic cognitive impairment.
CONCLUSION
Diabetic cognitive impairment is closely correlated with the nephropathy in patients with Type 2 diabetes. With the decline in glomerular filtration function, the cognitive disorder tends to be aggravated. The hippocampal brain metabolism may have some changes in left side of Cho/Cr in patients with diabetic nephropathy.
Adult
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Aspartic Acid
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analogs & derivatives
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metabolism
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Case-Control Studies
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Cerebrum
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metabolism
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Choline
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metabolism
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Cognition
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Cognition Disorders
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epidemiology
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Creatine
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metabolism
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Diabetes Mellitus, Type 2
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physiopathology
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Diabetic Nephropathies
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epidemiology
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Glomerular Filtration Rate
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Humans
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Neuropsychological Tests