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Association between 5-hydroxytryptamine transporter gene-linked polymorphic region and smoking behavior in Chinese males 被引量:3
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作者 CHU Shui-lian XIAO Dan WANG Chen JING Hang 《Chinese Medical Journal》 SCIE CAS CSCD 2009年第12期1365-1368,共4页
Background Tobacco use is the major risk factor for numerous health problems. However, only 5% of smokers can successfully quit without therapy owing to the highly addictive properties of nicotine. The serotoninergic ... Background Tobacco use is the major risk factor for numerous health problems. However, only 5% of smokers can successfully quit without therapy owing to the highly addictive properties of nicotine. The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine withdrawal. Serotonin transporter (5-HTT) is the most important protein, as it adjusts the serotonin concentration in the synaptic cleft. There is a polymorphism in the upstream regulatory region of the 5-HTT gene, named 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR). Compared with the L allele, the S allele of the polymorphism is associated with decreased transcription efficiency of the 5-HTT gene. In this study, we investigated the relationship between this gene polymorphism and smoking behavior in Chinese males. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find 5-HTTLPR gene polymorphisms in 144 smokers and 135 age-matched healthy non-smokers. A questionnaire was completed in all recruited subjects. Results The proportion of L/L (15.3% vs 5.2%) and S/L (50.0% vs 33.3%) genotypes was significantly higher in the smokers than that in the non-smokers (X^2=21.9; P 〈0.01). The odds ratio (OR) adjusted by age, education, effects of family members and friends who smoke, and alcohol intake was 2.9 (95%CI 1.78-4.80). In smokers, the number of cigarettes/day (L/L vs S/L vs S/S: 28±12 vs 20±8 vs 16±6, X^2=18.5, P 〈0.01), smoking index (L/L vs S/L vs S/S: 561±446 vs 393±341 vs 237±201, X^2=12.5, P 〈0.01) and score on the Fagerstrom test for nicotine dependence (FTND) (L/L vs S/L vs S/S: 7.8±1.6 vs 6.2±2.5 vs 3.5±2.1, X2=48.3, P 〈0.01) were significantly higher in smokers with an L/L or S/L genotype than that in the smokers with the S/S genotype. There were no significant differences in the proportion of starting smoking before 20 years old (P=0.219) and those who succeeded in quitting smoking for more than 1 month (P=-0.456) between individuals with different 5-HTTLPR genotypes in smokers. Conclusions 5-HTTLPR polymorphism may be associated with susceptibility to cigarette smoking in Chinese males. The proportion of the L/L and S/L genotype in smokers was higher than that in non-smokers. In smokers, the level of nicotine dependence and resultant cigarettes consumption may be much higher in individuals with an L/L or S/L genotype than those with the S/S genotype. 展开更多
关键词 Serotonin transporter nicotine dependence 5-hydroxytryptamine transporter gene-linkedpolymorphic region
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5-Hydroxytryptamine:a potential therapeutic target in amyotrophic lateral sclerosis 被引量:2
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作者 Shi-Shi Jiang Meng-Ni Gong +5 位作者 Wei Rao Wen Chai Wen-Zhi Chen Xiong Zhang Hong-Bing Nie Ren-Shi Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期2047-2055,共9页
Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*... Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*G93A transgenic(ALS mouse model) and wide-type mice.This involved intraperitoneal injections of either granisetron,piboserod,or ritanserin,which inhibit the 5-HT3,5-HT4,and 5-HT2 receptors,respectively.The transgenic mice were found to have fewer5-HT-positive cells in the spinal cord compared with wide-type mice.We found that the administration of granisetron reduced the body weight of the transgenic mice,while piboserod and ritanserin worsened the motor functioning,as assessed using a hanging wire test.However,none of the 5-HT receptor antagonists affected the disease progression.We analyzed the distribution and/or expression of TAR DNA binding protein 43(TDP-43) and superoxide dismutase 1 G93A(SOD1-G93A),which fo rm abnormal aggregates in ALS.We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists.In addition,the disease-related mislocalization of TD P-43 to the cytoplasm increased markedly for all three drugs.In ce rtain anatomical regions,the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons.These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells.5-HT co uld therefore be a potential therapeutic target for amyotrophic lateral sclerosis. 展开更多
关键词 5-hydroxytryptamine amyotrophic lateral sclerosis ASTROCYTES GRANISETRON MICROGLIA neuron piboserod RITANSERIN SOD1-G93A TAR DNA-binding protein 43
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Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease 被引量:1
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作者 Li-Fen Liu Yu-Tong Liu +5 位作者 Dan-Dan Wu Jie Cheng Na-Na Li Ya-Ni Zheng Liang Huang Qiong-Lan Yuan 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期2019-2028,共10页
Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In... Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease. 展开更多
关键词 5-hydroxytryptamin receptor 3 Alzheimer’s disease amyloid beta plaques CALCINEURIN cognitive deficits HTR3 interneurons iCa2+ nuclear factor of activated T-cells transgenic amyloid precursor protein and presenilin-1 mice TROPISETRON
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Design and Application of Intelligent Control System for Molten Iron Transportation Based on 5G Technology
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作者 Borui Wang 《Frontiers of Metallurgical Industry》 2024年第2期21-24,共4页
Molten transport is an important link in the iron and steel enterprise production,involves many complex factors,artificial management is difficult.Therefore,puts forward a kind of molten iron transport wisdom control ... Molten transport is an important link in the iron and steel enterprise production,involves many complex factors,artificial management is difficult.Therefore,puts forward a kind of molten iron transport wisdom control system based on 5G technology,which mainly contains the intelligent identification tracking system,equipment status collection information acquisition system,locomotive vehicle terminal system,etc.Combined with the analysis of the actual application situation,the system could integrate all the processes and elements of molten iron produc-tion and transportation,realize the integration of operation and management,and also promote the improvement of the turnover efficiency of molten iron tank,reduce the demand for personnel,and reduce the labor cost. 展开更多
关键词 5G technology molten iron transportation intelligent control system
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Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population 被引量:19
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作者 Emin Ozbek Ali I. Tasci +5 位作者 Volkan Tugcu Yusuf O. Ilbey Abdulmuttalip Simsek Levent Ozcan Emre C. Polat Vedat Koksal 《Asian Journal of Andrology》 SCIE CAS CSCD 2009年第3期351-355,共5页
We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the ... We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P 〈 0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences. 展开更多
关键词 5-HTTLPR POLYMORPHISM premature ejaculation selective serotonin reuptake inhibitors serotonin transporter gene
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Tong xie yao fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P 被引量:28
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作者 Yue Yin Lei Zhong +3 位作者 Jian-Wei Wang Xue-Ying Zhao Wen-Jing Zhao Hai-Xue Kuang 《World Journal of Gastroenterology》 SCIE CAS 2015年第15期4536-4546,共11页
AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1... AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS. 展开更多
关键词 Tong Xie YAO Fang IRRITABLE BOWEL SYNDROME 5-hydroxytryptamine Substance P TRADITIONAL Chinesemedicine
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Changes of 5-hydroxytryptamine and tryptophan hydroxylase expression in the ventral horn of spinal cord 被引量:5
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作者 Chuan-Xiang XU Hong-Tao LIU Jing WANG 《Neuroscience Bulletin》 SCIE CAS CSCD 2008年第1期29-33,共5页
Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further... Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further discuss the mecha- nism of exercise-induced central fatigue at spinal level. Methods Sixteen healthy adult Wistar rats were randomly divided into 2 groups: exercise-induced fatigue group and control group. Immunohistochemical staining for 5-HT and TPH in the ventral horn were performed and analysized quantitatively. The mean optic densities of 5-HT and TPH positive fibers or terminals were measured by computerized image analyzer. Results Both 5-HT and TPH positive fibers/terminals decreased in the exercise-induced fatigue group. The immunohistochemical staining was weaker and the mean optic densities decreased obviously in the fatigue group compared with those in the control group (P 〈 0.05). Conclusion 5-HT and TPH in the ventral horn of spinal cord might be involved in exercise-induced fatigue. 展开更多
关键词 ventral horn spinal cord 5-hydroxytryptamine tryptophan hydroxylase exercise-induced fatigue IMMUNOHISTO-CHEMISTRY
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Effect of the pineal gland on 5-hydroxytryptamine and γ-aminobutyric acid secretion in the hippocampus of male rats during the summer and winter 被引量:4
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作者 Ting Li Hailu Wang +3 位作者 Hewei Zhang Leilei Liu Peipei Li Shuran Ma 《Journal of Traditional Chinese Medical Sciences》 2020年第3期283-290,共8页
Objective:The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.Methods:Two time points,the summer and wint... Objective:The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.Methods:Two time points,the summer and winter solstice,which are the longest and shortest days of the year,respectively,were selected.Male Spraguee Dawley rats that underwent a sham operation without pineal excision were included as a control group.The concentrations of 5-hydroxytryptamine(5-HT)andγ-aminobutyric acid(GABA)were determined by radioimmunoassays and enzyme-linked immunosorbent assays,respectively.Results:In the winter,the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group(P<.01).A difference was also noted in GABA levels between the normal group and the sham operation group(P<.05).The concentrations of 5-HT and GABA in the hippocampal tissues of the normal group exhibited a seasonal rhythm consisting of elevation during the summer and reduction during the winter(P<.01),while the GABA levels in the sham operation group exhibited a significant difference,with elevation during the summer and reduction during the winter(P<.01).In the operation group,GABA showed the same trend(P<.01).Conclusion:The seasonal rhythm of neurotransmitter secretion by the hippocampus(5-HT and GABA)consisted of elevation during the summer and reduction during the winter.During the winter,the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus,and it exhibited seasonal selectivity with regard to the regulation of 5-HT. 展开更多
关键词 MELATONIN 5-hydroxytryptamine γ-aminobutyric acid PHOTOPERIOD Rats Seasonal rhythm Pineal excision
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Orbitofrontal cortex action of 5-hydroxytryptamine and its receptor in an acute forced swimming stress-induced depression model 被引量:2
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作者 Huipeng Li Fengli An Shucheng An 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第7期530-535,共6页
BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion. 5-hydroxytryptamine (5-HT) has been shown to be involved in human depression. OBJECTIVE: To investigate OFC actions a... BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion. 5-hydroxytryptamine (5-HT) has been shown to be involved in human depression. OBJECTIVE: To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor (5-HT1AR) in stress-induced depression.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008. MATERIALS: 5-HT, p-chlorophenylalanine (PCPA, an inhibitor to tryptophan hydroxylase) and spiperone (5-HT1AR antagonist) were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tianjin Haoyang Biological Manufacture. METHODS: A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups: control, model, 5-HT, spiperone + 5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5 pL of 5-HT (12.5 pg/pL), PCPA (20 pg/pL), spiperone (1.3 pg/pL) + 5-HT (12.5 pg/pL, 10 minutes later), and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone + 5-HT, and model groups, respectively. The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES: Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC, cingulate cortex, and piriform cortex. RESULTS: (1) Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test (P 〈 0.05); locomotion and grooming in open field test were increased, although there was no significance (P 〉 0.05). Furthermore, following PCPA microinjection into the OFC (PCPA + forced swimming stress), immobility time in forced swimming test increased dramatically (P〈 0.01), locomotion and rearing in open field test declined (P〈 0.05 and P 〈 0.01, respectively). Compared with the 5-HT group, 5-HT1AR antagonist (spiperone + 5-HT + forced swimming stress) increased immobility time in forced swimming test (P 〈 0.01), but decreased locomotion, rearing, and grooming in open field test. (2) Forced swimming stress markedly elevated 5-HT1AR expression in OFC, cingulate cortex, and piriform cortex (P〈 0.05 or P〈 0.01). CONCLUSION: 5-HT improved stress-induced depression, and 5-HT anti-depression effects are primarily achieved via 5-HT1AR. Stress-induced up regulation of 5-HT1AR expression might be a compensatory mechanism for decreased 5-HT expression. 展开更多
关键词 DEPRESSION orbitofrontal cortex 5-hydroxytryptamine forced swimming test open field test
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The PcHY5 methylation is associated with anthocyanin biosynthesis and transport in ‘Max Red Bartlett' and ‘Bartlett' pears
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作者 WEI Wei-lin JIANG Fu-dong +6 位作者 LIU Hai-nan SUN Man-yi LI Qing-yu CHANG Wen-jing LI Yuan-jun LI Jia-ming WU Jun 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2023年第11期3256-3268,共13页
The red coloring of pear fruits is mainly caused by anthocyanin accumulation. Red sport, represented by the green pear cultivar ‘Bartlett’(BL) and the red-skinned derivative ‘Max Red Bartlett’(MRB), is an ideal ma... The red coloring of pear fruits is mainly caused by anthocyanin accumulation. Red sport, represented by the green pear cultivar ‘Bartlett’(BL) and the red-skinned derivative ‘Max Red Bartlett’(MRB), is an ideal material for studying the molecular mechanism of anthocyanin accumulation in pear. Genetic analysis has previously revealed a quantitative trait locus(QTL) associated with red skin color in MRB. However, the key gene in the QTL and the associated regulatory mechanism remain unknown. In the present study, transcriptomic and methylomic analyses were performed using pear skin for comparisons between BL and MRB. These analyses revealed differential PcHY5 DNA methylation levels between the two cultivars;MRB had lower PcHY5 methylation than BL during fruit development, and PcHY5 was more highly expressed in MRB than in BL. These results indicated that PcHY5 is involved in the variations in skin color between BL and MRB. We further used dual luciferase assays to verify that PcHY5 activates the promoters of the anthocyanin biosynthesis and transport genes PcUFGT, PcGST, PcMYB10 and PcMYB114, confirming that PcHY5 not only regulates anthocyanin biosynthesis but also anthocyanin transport. Furthermore, we analyzed a key differentially methylated site between MRB and BL, and found that it was located in an intronic region of PcHY5. The lower methylation levels in this PcHY5 intron in MRB were associated with red fruit color during development, whereas the higher methylation levels at the same site in BL were associated with green fruit color. Based on the differential expression and methylation patterns in PcHY5 and gene functional verification, we hypothesize that PcHY5, which is regulated by methylation levels, affects anthocyanin biosynthesis and transport to cause the variations in skin color between BL and MRB. 展开更多
关键词 PEAR PcHY5 DNA methylation ANTHOCYANIN biosynthesis and transport
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5-Fluorocytosine–Sugar Conjugates for Glucose Transporter-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism 被引量:1
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作者 Yu Wang Xiaofei Cheng +1 位作者 Hongxia Zhao Qingzhi Gao 《Transactions of Tianjin University》 EI CAS 2019年第6期611-617,共7页
Two novel sugar-conjugated 5-fluorocytosine(5-FC)antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter(GLUT).The antitumor acti... Two novel sugar-conjugated 5-fluorocytosine(5-FC)antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter(GLUT).The antitumor activity of these compounds was evaluated in four different human cancer cell lines:A549(human lung cancer cell line),HT29(human colorectal cancer cell line),H460(human lung cancer cell line),and PC3(human prostate cancer cell line).The sugar conjugates exhibited cytotoxicity similar to or higher than 5-FC and 1-hexylcarbamoyl-5-FC in A549,HT29,H460,and PC3.Furthermore,GLUT-mediated transport of the glycoconjugate was investigated with GLUT inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing HT29 cell line.The cell-killing potency of 5-FC glycoconjugate was found to depend significantly on the GLUT inhibitor,and the cellular uptake of molecules was regulated by GLUT-mediated transport.All the results demonstrate the potential advantages of glycoconjugation for Warburg effect-targeted drug design. 展开更多
关键词 WARBURG effect Glucose transporter overexpressed 5-FLUOROCYTOSINE GLYCOCONJUGATE Tumor targeting
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A novel oral prodrug-targeting transporter MCT 1: 5-fluorouracil-dicarboxylate monoester conjugates 被引量:1
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作者 Yixin Sun Dongyang Zhao +5 位作者 Gang Wang Qikun Jiang Mengran Guo Qiming Kan Zhonggui He Jin Sun 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2019年第6期631-639,共9页
Monocarboxylate transporter 1(MCT1)is responsible for oral absorption of short-chain monocarboxylic acids from small intestine,hence,it’s likely to serve as an ideal design target for the development of oral prodrugs... Monocarboxylate transporter 1(MCT1)is responsible for oral absorption of short-chain monocarboxylic acids from small intestine,hence,it’s likely to serve as an ideal design target for the development of oral prodrugs.However,potential application of MCT1 to facilitate the oral delivery is still unclear.Irregular oral absorption,poor permeability and bioavailability greatly limit the oral delivery efficiency of 5-fluorouracil(5-FU).Herein,we design three 5-FU-fatty acid conjugates targeting intestinal MCT1 with different lipophilic linkages.Interestingly,due to high MCT1 affinity and good gastrointestinal stability,5-FUoctanedioic acid monoester prodrug exhibited significant improvement in membrane permeability(13.1-fold)and oral bioavailability(4.1-fold)compared to 5-FU.More surprisingly,stability experiment in intestinal homogenates showed that 5-FU prodrugs could be properly activated to release 5-FU within intestinal cells,which provides an ideal foundation for the improvement of oral bioavailability.In summary,good gastrointestinal stability,high membrane permeability and appropriate intestinal cell bioactivation are the important factors for high-efficiency 5-FU oral prodrugs,and such work provides a good platform for the development of novel oral prodrugs targeting intestinal transporters. 展开更多
关键词 5-FLUOROURACIL PRODRUGS Monocarboxylate transporter 1 Permeability ORAL bioavailability
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Role of 5-hydroxytryptamine expression in cerebellar Purkinje cells in obstructive sleep apnea syndrome 被引量:1
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作者 Liping Peng Jinghua Wang +8 位作者 Lihong Zhang Pan Liu Min Wang Min Huang Shengnan Liu Pingping He Li Cui Mingxian Li Shao Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第8期606-610,共5页
In the present study, electrical stimulation to the rat insular cortex induced apnea or respiratory disturbance, reduced amplitude of genioglossal electromyogram, and decreased electromyogram integrals. In addition, a... In the present study, electrical stimulation to the rat insular cortex induced apnea or respiratory disturbance, reduced amplitude of genioglossal electromyogram, and decreased electromyogram integrals. In addition, arterial blood gas analysis showed arterial blood acidosis, reduced pH values, increased alkali reserve negative values, decreased peripheral blood 5-hydroxytryptamine content, and increased 5-hydroxytryptamine expression in cerebellar Purkinje cells. Following lidocaine injection to block the habenular nucleus, abnormalities in breath, genioglossal electromyogram, and blood gas values disappeared, and peripheral blood 5-hydroxytryptamine content returned to levels prior to electric stimulation. However, 5-hydroxytryptamine expression in cerebellar Purkinje cells remained high. The results suggested that 5-hydroxytryptamine expression in Purkinje cells did not correlate with ventilation function involving insular cortex and habenular nucleus. 展开更多
关键词 sleep apnea OBSTRUCTIVE CEREBELLUM 5-hydroxytryptamine insular cortex habenular nucleus Purkinje cells
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5-hydroxytryptamine-mediated apnea caused by the habenular nucleus 被引量:1
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作者 Min Wang Weihong Lin +4 位作者 Jinghua Wang Min Huang Chunyong Wang Mingxian Li Shao Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第20期1554-1558,共5页
5-hydroxytryptamine contributes to the control of activities of the dilator muscle in the upper respiratory tract, and is derived from the raphe nuclei, in which the habenular nucleus exerts a sustaJned inhibitory eff... 5-hydroxytryptamine contributes to the control of activities of the dilator muscle in the upper respiratory tract, and is derived from the raphe nuclei, in which the habenular nucleus exerts a sustaJned inhibitory effect. In the present study, respiratory motion curve of the genJoglossus muscle and peripheral 5-hydroxytryptamine changes were observed following L-glutamate stimulation of the habenular nucleus of adult Wistar rats. Results showed that the rats had apnea and decreased plasma 5-hydroxytryptamine content after the neurons in habenular nucleus were excited. Genioglossus muscle electromyogram amplitude and integral were significantly reduced. The genioglossus myoelectric activity and respiratory motion curve were similar to obstructive sleep apnea syndrome, thus confirming that the habenular nucleus is the key nucleus involved in the pathogenesis of obstructive sleep apnea syndrome, and is the primary regulated center in the raphe nuclei. Stimulation of the habenular nucleus may suppress 5-hydroxytryptamine release and result in apnea, which is similar to obstructive sleep apnea syndrome. 展开更多
关键词 SLEEP APNEA habenular nucleus 5-hydroxytryptamine GENIOGLOSSUS neural electrophysiology neural regeneration
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Transforming liquid flow fuel cells to controllable reactors for highlyefficient oxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid at low temperature
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作者 Ye Qiang Xi Liu +2 位作者 Denghao Ouyang Zhao Jiang Xuebing Zhao 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2024年第3期621-631,I0014,共12页
Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport cha... Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism. 展开更多
关键词 5-HYDROXYMETHYLFURFURAL 2 5-Furandicarboxylic acid ELECTRODEPOSITION Electron transport chain Liquid flow fuel cell
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基于天牛须搜索算法和内点法的运输类飞机5×5谱编制方法
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作者 卫昆钰 李博文 +1 位作者 李晨迪 贺小帆 《航空科学技术》 2024年第6期104-113,共10页
载荷谱作为运输类飞机疲劳分析和试验的输入,其编制具有重要意义。针对运输类飞机载荷谱编制需求,本文基于天牛须搜索算法和内点法,提出了一种编制5×5谱的方法。首先确定飞机的任务剖面,通过对飞机实测数据进行处理与统计获得过载... 载荷谱作为运输类飞机疲劳分析和试验的输入,其编制具有重要意义。针对运输类飞机载荷谱编制需求,本文基于天牛须搜索算法和内点法,提出了一种编制5×5谱的方法。首先确定飞机的任务剖面,通过对飞机实测数据进行处理与统计获得过载累积超越数曲线,依据极值载荷对数正态分布准则,采用基于天牛须搜索算法和内点法耦合的5×5谱求解方法对各类飞行类型次数和载荷水平比进行迭代和选取;依据载荷谱形状相似准则,提出了载荷谱形状相似性指标,采用天牛须算法对5×5谱中各类飞行类型中各级载荷出现次数进行迭代,形成各任务段的5×5谱。最后给出了一个示例以阐明该5×5谱编制方法。实现了运输类飞机5×5谱的快速和高质量编制。 展开更多
关键词 运输类飞机 5×5 TWIST谱 极值对数正态分布准则 载荷谱形状相似准则
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Synthesis and Metabolism of 5-hydroxytryptamine in Peripheral Circulatory System of Suckling Piglets
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作者 ZHANG Han ZHANG Tao +3 位作者 WANG Lei ZHANG Shuang WANG An-ru TENG Ke-dao 《Animal Husbandry and Feed Science》 CAS 2009年第11期10-12,15,共4页
[ Objective] To find the rule of 5-hydroxytryptamine (5-HT) synthesis and metabolism in peripheral blood of suckling piglets with aging. [ Method ] All of 15 British Large White pigs at 0, 5 and 15 d of age were sel... [ Objective] To find the rule of 5-hydroxytryptamine (5-HT) synthesis and metabolism in peripheral blood of suckling piglets with aging. [ Method ] All of 15 British Large White pigs at 0, 5 and 15 d of age were selected as experimental animals, and their serumal concentrations of L- tryptophan (L-Trp), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in peripheral circulatory system were determined synchronously by reversed- phase high-performance liquid chromatography method with UV. [ Result] The concentration of L-Trp was (16. 92 ± 1.74) iJmol/L at birth, (59.94 ±10.88) iJmol/L at 5 d of age and (70.42± 6.48) μmol/L at 15 d of age. The concentration of 5-HT was ( 12.85 ± 1.79) iJmol/L at birth, (4.81 ±2.05) ijmol/L at 5 d of age and (5.49±1.09) μmol/L at 15 d of age. While 5-HIAA, the metabolic product of 5-HT, was not detected at all the samples selected. [ Conclusion] The L-Trp concentration of suckling piglets increase significantly with aging ( P 〈0. 05). While the concentra- tion of 5-HT and the conversion ratio of L-Trp to 5-HT are both highest at birth (P〈0.05) and keep stable at 5 and 15 d of age. 展开更多
关键词 5-hydroxytryptamine L-TRYPTOPHAN 5-hydroxyindoleacetic acid Peripheral circulatory system Suckling piglets
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Changes of 5-hydroxytryptamine and dopamine contents in brain microvessels and the influence on cerebral edema at early stage of brain injury
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作者 柯以铨 徐如祥 陈长才 《Journal of Medical Colleges of PLA(China)》 CAS 1995年第2期102-105,共4页
The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detec... The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detector(HPLC-ECD) and the influence of the 展开更多
关键词 BRAIN injury BRAIN EDEMA 5-hydroxytryptamine DOPAMINE BRAIN MICROVESSELS
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Diversity of Sodium Transporter HKT1;5 in Genus Oryza
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作者 Shalini PULIPATI Suji SOMASUNDARAM +12 位作者 Nitika RANA Kavitha KUMARESAN Mohamed SHAFI Peter CIVÁŇ Gothandapani SELLAMUTHU Deepa JAGANATHAN Prasanna Venkatesan RAMARAVI S.PUNITHA Kalaimani RAJU Shrikant S.MANTRI R.SOWDHAMINI Ajay PARIDA Gayatri VENKATARAMAN 《Rice science》 SCIE CSCD 2022年第1期31-46,I0002-I0017,共32页
Asian cultivated rice shows allelic variation in sodium transporter,OsHKT1;5,correlating with shoot sodium exclusion(salinity tolerance).These changes map to intra/extracellularly-oriented loops that occur between fou... Asian cultivated rice shows allelic variation in sodium transporter,OsHKT1;5,correlating with shoot sodium exclusion(salinity tolerance).These changes map to intra/extracellularly-oriented loops that occur between four transmembrane-P loop-transmembrane(MPM)motifs in OsHKT1;5.HKT1;5 sequences from more recently evolved Oryza species(O.sativa/O.officinalis complex species)contain two expansions that involve two intracellularly oriented loops/helical regions between MPM domains,potentially governing transport characteristics,while more ancestral HKT1;5 sequences have shorter intracellular loops.We compared homology models for homoeologous OcHKT 1;5-K and OcHKT1;5-L from halophytic O.coarctata to identify complementary amino acid residues in OcHKT1;5-L that potentially enhance affinity for Na+.Using haplotyping,we showed that Asian cultivated rice accessions only have a fraction of HKT1;5 diversity available in progenitor wild rice species(O.nivara and O.rufipogon).Progenitor HKT1;5 haplotypes can thus be used as novel potential donors for enhancing cultivated rice salinity tolerance.Within Asian rice accessions,10 non-synonymous HKT1;5 haplotypic groups occur.More HKT1;5 haplotypic diversities occur in cultivated indica gene pool compared to japonica.Predominant Haplotypes 2 and 10 occur in mutually exclusive japonica and indica groups,corresponding to haplotypes in O.sativa salt-sensitive and salt-tolerant landraces,respectively.This distinct haplotype partitioning may have originated in separate ancestral gene pools of indica and japonica,or from different haplotypes selected during domestication.Predominance of specific HKT1;5 haplotypes within the 3000 rice dataset may relate to eco-physiological fitness in specific geo-climatic and/or edaphic contexts. 展开更多
关键词 HKT1 5 diversity single nucleotide polymorphism HAPLOTYPE bacterial artificial chromosome salinity tolerance sodium transporter Oryza species
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Effects of Dezocine and Propofol Combination on Plasma 5-HT and ET Levels in Stroke Patients Undergoing Thrombolysis
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作者 Fangfang Lv Xiuhong Wang Weibo Wang 《Journal of Clinical and Nursing Research》 2024年第9期234-239,共6页
Objective: To investigate the effect of dezocine combined with propofol on brain metabolism in patients undergoing cerebral thrombosis thrombolysis. Methods: A total of 86 stroke patients admitted between July 2022 an... Objective: To investigate the effect of dezocine combined with propofol on brain metabolism in patients undergoing cerebral thrombosis thrombolysis. Methods: A total of 86 stroke patients admitted between July 2022 and December 2023 were randomly divided into two groups: Group A (study group) and Group B (control group), with 43 patients in each group. Both groups underwent intra-arterial thrombolysis therapy. Group B received dezocine for anesthesia, while Group A received a combination of dezocine and propofol. Plasma concentrations of 5-hydroxytryptamine and endothelin, as well as brain metabolic indicators, were compared between the two groups immediately after anesthesia, at 1 hour post-reperfusion, and 3 hours post-reperfusion. Results: There were no significant differences in the levels of 5-hydroxytryptamine and endothelin between the two groups immediately after anesthesia and at 1 hour post-reperfusion (P > 0.05). However, at 3 hours post-reperfusion, the levels of 5-hydroxytryptamine and endothelin in Group A were significantly lower than those in Group B. Furthermore, in Group A, the levels of 5-hydroxytryptamine and endothelin at 3 hours post-reperfusion were lower compared to the levels at 1 hour post-reperfusion (P < 0.05). Conclusion: Dezocine combined with propofol can effectively improve the quality of anesthesia and has a minimal effect on brain metabolic indices, suggesting reduced damage to brain metabolism. 展开更多
关键词 DEZOCINE PROPOFOL 5-hydroxytryptamine ENDOTHELIN Cerebral apoplexy
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