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Association of C(-106)T Polymorphism in Aldose Reductase Gene with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes Mellitus

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Chinese Medical Sciences Journal 2014年第1期29卷 1-6页

作者： Yu Deng Xiu-fen Yang Hong Gu Apiradee Lim Munkhtulga Ulziibat Torkel Snellingen Jun Xu Kai Ma Ning-pu Liu Department of Ophthalmology Fu Xing HospitalCapital Medical University Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology and Visual Sciences Key Laboratory Department of Mathematics and Computer Science Faculty of Science and TechnologyPrince of Songkla UniversityPattani Campus Sekwa Eye Hospital

Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM）. Methods From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy （DWR） group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C（-106）T polymorphism （rs759853） in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. Results A total of 268 T2DM patients （129 in the DR group and 139 in the DWR group） were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset （P=0.10） and gender （P=0.78）. The success rate of genotyping for the study subjects was 99.6% （267/268）, with one case of failure in the DR group. The frequencies of the T allele in the C（-106）T polymorphism were 16.0% （41/256） in the DR group and 19.4% （54/278） in the DWR group （P=0.36）. There was no signit^cant difference in the C（-106）T genotypes between the 2 groups （P=0.40）. Compared with the wild-type genotype, odds ratio （OR） for the risk of DR was 0.7 （95% CI, 0.38-1.3） for the heterozygous CT genotype and 0.76 （95% CI, 0.18-3.25） for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria （OR=4.61; 95% CI, 2.34-9.05） and insulin therapy （OR=3.43; 95% CI, 1.94-6.09）. Conclusions Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C（-106）T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.

关键词： diabetic retinopathy aldose reductase gene single nucleotide polymorphism

[Solid-phase extraction coupled with high performance liquid chromatography-triple quadrupole mass spectrometry for simultaneous determination of seven coumarins in water samples from drinking water treatment plants]

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Se pu = Chinese journal of chromatography 2025年第1期43卷 78-86页

作者： Wen-Mei Jiao Jing-Ming Yang Ce Xu Fu-Kang Gao Lu-Yao Shen Yu-Bo Yuan Zhi-fen Guo Guang Huang School of Life Sciences and Chemical Engineering Jiangsu Second Normal University Nanjing 211200 China. School of Stomatology Nanjing Medical University Nanjing 210029 China. School of public Health Nanjing Medical University Nanjing 211166 China. Key Laboratory of Modern Toxicology Ministry of Education School of Public Health Nanjing Medical University Nanjing 211166 China.

Chlorinated coumarins, which are as cytotoxic as highly toxic halobenzoquinones toward CHO-K1 cells, have recently been identified as disinfection byproducts in drinking water disinfection processes. Therefore, detecting coumarins in water samples collected at various stages from drinking water treatment plants helps assess the formation of chlorinated coumarins in drinking water. Hence, a simple, rapid, accurate, and sensitive method for quantifying coumarins in water samples is required. In this study, a method was developed based on solid-phase extraction coupled with high performance liquid chromatography-triple-quadrupole mass spectrometry for analyzing seven coumarins in water samples from drinking water treatment plants, including 6,7-dihydroxycoumarin, 7-hydroxycoumarin, 6-hydroxy-4-methylcoumarin, 8-chloro-7-hydroxycoumarin, coumarin, 7-chloro-6-hydroxy-4-methylcoumarin, and 3,8-dichloro-7-hydroxycoumarin. Sample pretreatment involved solid-phase extraction using HLB columns, followed by elution with water and methanol, each containing 0.25% formic acid. The extracted solution was separated via gradient elution using a Phenomenex Luna C18 column (100 mm×2.0 mm, 3 mm) with 0.1% formic acid aqueous solution and methanol as the mobile phases, with analytes detected by triple-quadrupole mass spectrometry equipped with electrospray ionization source in multiple reaction monitoring mode. The matrix effect, precision, and accuracy of the developed method were investigated using raw and treated water as matrices. Matrix effects of 0.84-1.12 were recorded for the detection of 6,7-dihydroxycoumarin, 7-hydroxycoumarin, 6-hydroxy-4-methylcoumarin, and coumarin in raw water, while values of 0.67-0.70 were recorded for 8-chloro-7-hydroxycoumarin, 7-chloro-6-hydroxy-4-methylcoumarin, and 3,8-dichloro-7-hydroxycoumarin in finished water. The three chlorinated coumarins exhibited matrix effects above 0.80 after the finished water matrix had been diluted four times. These re

关键词： coumarins disinfection byproducts drinking water high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) solid-phase extraction (SPE)

Combinatorial mutation on the β-glycosidase specific to 7-β-xylosyltaxanes and increasing the mutated enzyme production by engineering the recombinant yeast

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Acta Pharmaceutica Sinica B 2019年第3期9卷 626-638页

作者： Jing-Jing Chen Xiao Liang fen wang Yan-Hua Wen Tian-Jiao Chen wan-Cang Liu Ting Gong Jin-Ling Yang Ping Zhu State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College

Taxol is a 'blockbuster' antitumor drug produced by Taxus species with extremely low amount, while its analogue 7-β-xylosyl-10-deacetyltaxol is generally much higher in the plants. Both the fungal enzymes LXYL-P1à1 and LXYL-P1à2 can convert 7-β-xylosyl-10-deacetyltaxol into10-deacetyltaxol for Taxol semi-synthesis. Of them, LXYL-P1à2 is twice more active than LXYLP1à1, but there are only 11 significantly different amino acids in terms of the polarity and acidic-basic properties between them. In this study, single and multiple site-directed mutations at the 11 sites from LXYL-P1à1 to LXYL-P1à2 were performed to define the amino acids with upward bias in activities and to acquire variants with improved catalytic properties. Among all the 17 mutants, E12(A72 T/V91 S) was the most active and even displayed 2.8-and 3-fold higher than LXYL-P1à2 on β-xylosidase andβ-glucosidase activities. The possible mechanism for such improvement was proposed by homology modeling and molecular docking between E12 and 7-β-xylosyl-10-deacetyltaxol. The recombinant yeast GS115-P1 E12-7 was constructed by introducing variant E12, the molecular chaperone gene pdi and the bacterial hemoglobin gene vhb. This engineered yeast rendered 4 times higher biomass enzyme activity than GS115-3.5 K-P1à2 that had been used for demo-scale fermentation. Thus, GS115-P1 E12-7 becomes a promising candidate to replace GS115-3.5 K-P1à2 for industrial purpose.

关键词： β-Glycosidases Combinatorial mutation Improved catalytic property Molecular docking Engineered yeast Taxol

CONTROLLED/"LIVING" RADICAL POLYMERIZATION OF STYRENE IN AN AQUEOUS DISPERSION SYSTEM

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Chinese Journal of Polymer Science 2002年第5期20卷 445-451页

作者： Bin Zhang Zhao-bin Zhang Xiao-long wan Chun-pu Hu Sheng-kang Ying Lab of Living Polymerization, East China University of Science and Technology.Shanghai 200237,China E China Univ Sci & Technol Lab Living Polymerizat Shanghai 200237 Peoples R China

Atom transfer radical polymerization (ATRP) of styrene catalyzed by cuprous (CuX)/1,10-phenanthroline (Phen) and CuX/CuX2/Phen was conducted in an aqueous dispersed system. A stable latex was obtained by using ionic surfactant sodium lauryl sulfonate (SLS) or composite surfactants, such as SLS/polyoxyethylene nonyl phenyl ether (OP-10), SLS/hexadecanol and SLS/OP-10/hexadecanol, Among which SLS and SLS/OP-10/hexadecanol systems established better dispersed effect during the polymerization, It was found that Phen was a more suitable ligand than N,N,N',N',N'-pentamethyldiethylenetriamine (PMDETA) to maintain an appropriate equilibrium of the activator Cu(I) and the deactivator Cu(II) between the organic phase and the water phase, The effect of several initiators (such as EBiB, CCl4 and 1-PEBr) and the temperature on such a kind of ATRP system was also observed. The number-average molar mass (M-n) of polystyrene (PS) increased with the conversion and the molar mass distribution (M-w/M-n) remained narrow. These experimental data show that the polymerization could be controlled except for the quick increase of monomer conversion and the number-average molar mass of PS in the initial stage of polymerization. Furthermore, the initiator efficiency was found to be low (similar to57%) in CuX/Phen catalyzed system. To overcome this problem, Cu(II)X-2 (20 mol%-50 mol% based on CuX) was introduced into the polymerization system. In this case, higher initiator efficiency (60%-90%), low M-w/M-n of PS (as low as 1.08) were achieved and the molar masses of the PS fit with the theoretical ones.

关键词： controlled/'living' radical polymerization polystyrene water dispersed polymerization 1,10-Phenanthroline

ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

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Protein & Cell 2023年第9期14卷 653-667页

作者： Maomao pu Wenhui Zheng Hongtao Zhang Wei wan Chao Peng Xuebo Chen Xinchang Liu Zizhen Xu Tianhua Zhou Qiming Sun Dante Neculai Wei Liu Metabolic Medicine Center International Institutes of Medicinethe Fourth Affiliated HospitalZhejiang University School of MedicineYiwu 322000China Joint Institute of Genetics and Genomics Medicine between Zhejiang University and University of Toronto Hangzhou 310058China National Center for Protein Science Shanghai Institute of Biochemistry and Cell BiologyShanghai Institutes of Biological SciencesChinese Academy of SciencesShanghai200031China

Lipophagy,the selective engulfment of lipid droplets(LDs)by autophagosomes for lysosomal degradation,is critical to lipid and energy *** we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal *** function of oRP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/*** lipophagy induction,ORP8 has increased localization on LDs and is phosphorylated by AMPK,thereby enhancing its affinity for LC3/*** of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular *** of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice,and Osbpl8 mice exhibit liver lipid clearance *** results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.

关键词： ORP8 lipophagy lipid autophagy

Core fucosylation and its roles in gastrointestinal glycoimmunology

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World Journal of Gastrointestinal Oncology 2023年第7期15卷 1119-1134页

作者： Nian-Zhu Zhang Li-fen Zhao Qian Zhang Hui Fang wan-Li Song Wen-Zhe Li Yu-Song Ge Peng Gao Clinical Laboratory The Second Hospital of Dalian Medical UniversityDalian 116023Liaoning ProvinceChina Department of Cell Therapy Shanghai Tianze Yuntai Biomedical Co.Ltd.Shanghai 200100China Graduate School of Comprehensive Human Sciences University of TsukubaTsukuba 305-0005IbarakiJapan Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of Neurology The Second Hospital of Dalian Medical UniversityDalian 116023Liaoning ProvinceChina

Glycosylation is a common post-translational modification in eukaryotic *** is involved in the production of many biologically active glycoproteins and the regulation of protein structure and *** fucosylation plays a vital role in the immune *** immune system molecules are core fucosylated glycoproteins such as complements,cluster differentiation antigens,immunoglobulins,cytokines,major histocompatibility complex molecules,adhesion molecules,and immune molecule synthesis-related transcription *** core fucosylated glycoproteins play important roles in antigen recognition and clearance,cell adhesion,lymphocyte activation,apoptosis,signal transduction,and *** fucosylation is dominated by fucosyltransferase 8(Fut8),which catalyzes the addition ofα-1,6-fucose to the innermost GlcNAc residue of ***8 is involved in humoral,cellular,and mucosal *** immunology is associated with aberrant core ***,we summarize the roles and potential modulatory mechanisms of Fut8 in various immune processes of the gastrointestinal system.

关键词： Fucosyltransferase 8 Core fucosylation Glycoimmunology Gastrointestinal tumor immunology T cell signal pathway

Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways

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Chinese Journal of Integrative Medicine 2023年第5期29卷 448-458页

作者： wanG Yuan wanG Qiang LUO Di ZHAO pu ZHONG Sha-sha DAI Biao wanG Jia-ju wan Yi-tong LIU Zhi-bin YANG Huan College of Acu-moxibustion and Massage Shaanxi University of Chinese MedicineXianyangShaanxi Province(712046)China Department of Traditional Chinese Medicine Baotou Medical CollegeBaotouInner Mongolia Autonomous Region(014040)China

Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence *** of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(Ppus of SAMP8 mice(Ppus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicoti

关键词： electroacupuncture fibrin/amyloid-βdeposition high mobility group box protein 1/toll-like receptor 4 receptor for advanced glycation end products/nicotinamide adenine dinucleotide phosphate Chinese medicine

Intracytoplasmic sperm injection in cases with a history of in vitro fertilization failure

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Asian Journal of Andrology 2003年第1期5卷 69-72页

作者： Zhi-Ling LI, Hong LIN, Xin-Neng ZHANG, wan-fen XIAO Reproduction Center, First Affiliated Hospital, Medical College, Shantou University, Shantou 515041, China Reproduction Center First Affiliated Hospital Medical College Shantou University Shantou 515041 China. lizhilin@***

Aim: To evaluate the effect of intracytoplasmic sperm injection (ICSI) in the management of cases with a history of conventional in vitro fertilization (IVF) failure. Methods: Two groups of patients, 19 with normal semen parameters and a history of IVF failure (metaphase Ⅱ oocytes: 0~30 %) and 28 with severe male factor infertility received ICSI technology during the same period. Ovarian stimulation was achieved by conventional procedure. Transvaginal ultrasound-guided oocyte collection was done 35~37 h after human chorionic gonadotrophin (hCG) injection. Only metaphase Ⅱ oocytes were selected for microinjection. Results: Fertilization was achieved with ICSI in all the patients. The fertilization rate (75.6 %±21.1 % vs. 73.9 %±19.2 %), cleavage rate (85.1 %±19.3 % vs. 82.7 %±22.1 %), clinical pregnancy rate per embryo transfer cycle (31.6 % vs. 28.6 %) and implantation rate per embryo (15.3 % vs. 14.4 %) did not differ significantly between the two groups. Conclusion: ICSI is a valuable method for couples with a history of IVF failure. These patients may have a similar ICSI result as in severe male infertility.

关键词： intracytoplasmic sperm injection in vitro fertilization male factor infertility fertilization failure

Simultaneous enhancement of cellular and humoral immunity by the lymph node-targeted cholesterolized TLR7 agonist liposomes

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Acta Pharmaceutica Sinica B 2024年第10期14卷 4577-4590页

作者： Dandan wan Ziyi Bai Yu Zhang Li Chen Haiying Que Tianxia Lan Weiqi Hong Jiayu Huang Cai He Yuquan Wei Qiang pu Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China Department of Thoracic Surgery National Frontier Center of Disease Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling ***,their clinical application is hindered by uncontrolled systemic inflammatory ***,it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and *** this study,we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes(1V209-Cho-Lip^(+))to mitigate undesired side ***-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8^(+)T *** main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip^(+)in tumor *** immunization with 1V209-Cho-Lip^(+)+OVA,we observed a pronounced"depot effect"and enhanced trafficking to secondary lymphoid *** vaccination with 1V209-Cho-Lip^(+)^(+)OVA significantly delays tumor development,prolongs mouse survival,and establishes durable immunity against tumor ***,1V209-Cho-Lip^(+)+OVA,while used therapeutic tumor vaccine,has demonstrated its efficacy in inhibiting tumor progression,and when combined with anti-PD-1,it further enhances antitumor ***,the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine.

关键词： TLR7 agonist Cationic liposomes Lymph node Cancer nanovaccines Immunotherapy Cross-presentation Cellular immunity Humoral immunity