Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials

Yuan-Yuan Gao,Wen Tian,Hui-Nan Zhang,Yang Sun,Jing-Ru Meng,Wei Cao,Xiao-Qiang Li 대한약학회 2021 Archives of Pharmacal Research Vol.44 No.4

Canonical transient receptor potential channels(TRPCs) are nonselective, high calcium permeability cationicchannels. The TRPCs family includes TRPC1, TRPC2,TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7. These channelsare widely expressed in the cardiovascular and nervoussystems and exist in many other human tissues and celltypes, playing several crucial roles in the human physiologicaland pathological processes. Hence, the emergenceof TRPCs modulators can help investigate these channels’applications in health and disease. It is worth noting that theTRPCs subfamilies have structural and functional similarities,which presents a signifi cant diffi culty in screening anddiscovering of TRPCs modulators. In the past few years,only a limited number of selective modulators of TRPCswere detected; thus, additional research on more potent andmore selective TRPCs modulators is needed. The presentreview focuses on the striking desired therapeutic eff ectsof TRPCs modulators, which provides intel on the structuralmodifi cation of TRPCs modulators and further pharmacologicalresearch. Importantly, TRPCs modulators cansignifi cantly facilitate future studies of TRPCs and TRPCsrelated diseases.

ADPRT Val762Ala and XRCC1 Arg194Trp Polymorphisms and Risk of Gastric Cancer in Sichuan of China

Wen, Yuan-Yuan,Pan, Xiong-Fei,Loh, Marie,Tian, Zhi,Yang, Shu-Juan,Lv, Si-Han,Huang, Wen-Zhi,Huang, He,Xie, Yao,Soong, Richie,Yang, Chun-Xia Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: Gastric cancer remains a major health problem in China. We hypothesized that XRCC1 Arg194Trp and ADPRT Val762Ala may be associated with risk. Methods: We designed a multicenter 1:1 matched case-control study of 307 pairs of gastric cancers and controls between October 2010 and August 2011. XRCC1 Arg194Trp and ADPRT Val762Ala were sequenced, and demographic data as well as lifestyle factors were collected using a self-designed questionnaire. Results: Individuals carrying XRCC1 Trp/Trp or Arg/Trp variant genotype had a significantly increased risk of gastric cancer (OR, 1.718; 95% CI, 1.190-2.479), while the OR for ADPRT Val762Ala variant genotype (Ala/Ala or Val/Ala) was 1.175 (95% CI, 0.796-1.737). No gene-gene or gene-environment interactions were found. In addition, family history of cancer and drinkers proportion were higher among cases than among controls (P<0.05). Conclusions: XRCC1 194 Arg/Trp or Trp/Trp genotype, family history of cancer, and drinking are suspected risk factors of gastric cancer from our study. Our findings may offer insight into further similar large gene-environment and gene-gene studies in this region.

Methylenetetrahydrofolate Reductase Genetic Polymorphisms and Esophageal Squamous Cell Carcinoma Susceptibility: A Meta-analysis of Case-control Studies

Wen, Yuan-Yuan,Yang, Shu-Juan,Zhang, Jian-Xing,Chen, Xin-Yue Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methods: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: 19 studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.

Interleukin-4 and -8 Gene Polymorphisms and Risk of Gastric Cancer in a Population in Southwestern China

Pan, Xiong-Fei,Wen, Ying,Loh, Marie,Wen, Yuan-Yuan,Yang, Shu-Juan,Zhao, Zhi-Mei,Tian, Zhi,Huang, He,Lan, Hui,Chen, Feng,Soong, Richie,Yang, Chun-Xia Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Gastric carcinogenesis is a complicated process that involves environmental and genetic factors like interleukin-4 (IL-4) and IL-8. Single nucleotide polymorphisms in their genes are associated with changed levels of gene expression. Here, we investigated the association between IL4-590 C>T and IL8-251T>A and gastric cancer (GC) risk in Sichuan of Southwestern China. Materials and Methods: We surveyed the research subjects using a self-designed questionnaire with questions on demographic factors and putative risk factors. Approximately 2-5ml of whole blood was collected after field survey to analyze IL4-590 C>T and IL8-251T>A genotypes using MALDI-TOF MS. Results: Our study recruited 308 pairs of GC patients and controls, including 224 (72.7%) men and 84 (27.3%) women in each group. There were 99 cardia and 176 noncardia GC patients in the case group. The case and control groups had an average age of $57.7{\pm}10.6$ ($mean{\pm}SD$) and $57.6{\pm}11.1$ years. GC patients reported a significantly greater proportion of family history of cancer (29.9% vs 10.7%, p<0.01) and drinking (54.6% vs 43.2%, p<0.01) than did controls. Variant genotypes of IL-4-590 C>T and IL-8-251 T>A were not associated with overall GC risk (adjusted OR, 0.89; 95%CI, 0.61-1.28 for CT or CC vs TT; adjusted OR, 1.14; 95%CI, 0.86-1.79 for TA or AA vs TT). Stratification analysis of two SNPs for risk by subsites only found that variant IL-8-251 TA or AA genotype was associated with increased noncardia GC risk (adjusted OR, 2.58; 95%CI, 1.19-5.57). We did not observe interactions between the IL-8-251 T>A genotype and smoking (adjusted OR, 0.38; 95%CI, 0.08-1.79) or drinking (adjusted OR, 0.36; 95%CI, 0.08-1.65) for risk of noncardia GC. Conclusions: Our data indicate no association between the two SNPs of IL-4-590 and IL-8-251 with overall GC risk, while the IL-8-251 TA or AA genotype conferred risk of cardia GC. Our findings contribute to the evidence body for risk of SNPs associated with the development of gastric cancer in this region.

GPS-based monitoring and modeling of the ionosphere and its applications for high accuracy correction in China

Yuan Yunbin,Ou Jikun,Huo Xingliang,Wen Debao,Liu Genyou,Chai Yanji,Yang Renggui,Luo Xiaowen 한국항해항만학회 2006 한국항해항만학회 학술대회논문집 Vol.2 No.-

The main research conducted previously on GPS ionosphere in China is first introduced. Besides, the current investigations include as follows: (1) GPS-based spatial environmental, especially the ionosphere, monitoring, modeling and analysis, including ground/space-based GPS ionosphere electron density (IED) through occultation/ tomography technologies with GPS data from global/regional network, development of a GNSS-based platform for imaging ionosphere and atmosphere (GPFIIA), and preliminary test results through performing the first 3D imaging for the IED over China, (2) The atmospheric and ionospheric modeling for GPS-based surveying, navigation and orbit determination, involving high precisely ionospheric TEC modeling for phase-based long/ median range network RTK system for achieving CM-level real time positioning, next generation GNSS broadcast ionospheric time-delay algorithm required for higher correction accuracy, and orbit determination for Low-Earth-orbiter satellites using single frequency GPS receivers, and (3) Research products in applications for national significant projects: GPS-based ionospheric effects modeling for precise positioning and orbit determination applied to China’s manned space-engineering, including spatial robot navigation and control and international space station intersection and docking required for related national significant projects.

Comparison of Gadobenate Dimeglumine and Gadopentetate Dimeglumine for Breast MRI Screening: a Meta-analysis

Yang, Xiao-Ping,Han, Yue-Dong,Ye, Jian-Jun,Chen, Gang,Luo, Ying,Ma, Hong-Xia,Yu, Xue-Wen,Niu, Juan-Qin,Ren, Fang-Yuan,Guo, You-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: As a common and essential contrast medium at present, gadobenate dimeglumine has shown better performance than some other agents when applied to Breast Magnetic Resonance Imaging Screening (Breast MRI Screening). Nevertheless, reports on the diagnostic performance of these two mediums (gadobenate dimeglumine and gadopentetate dimeglumine) are not completely consistent. Objective: To assess the diagnostic value of gadobenate dimeglumine and gadopentetate dimeglumine for Breast MRI Screening in patients suffering from breast cancer and to provide more convinced evidence to guide clinical practice in terms of appropriate contrast agents. Data Sources and Review Methods: Original articles in English and Chinese published before January 2013 were selected from available databases (The Cochrane Library, PUBMED, EMBASE, Chinese Biomedical Literature Database, Chinese Scientific Journals Full-text Database, Chinese Journal Full-text). The criteria for inclusion and exclusion were based on the standard for diagnosis tests. Meta-Disc software (Version 1.4) was used for data analysis. Then, the area under curve (AUC) of SROC and the spearman rank correlation of sensitivity against (1-specificity) were calculated. Results: Total of 17 researches involving 1934 patients were included. The pooled sensitivity of gadobenate dimeglumine and gadopentetate dimeglumine were 0.99 (0.97, 1.00) and 0.93 (0.88, 1.00) respectively. The pooled specificity for these two contrast agents were 0.924 (0.902, 0.943) and 0.838 (0.817, 0.858) respectively, and the AUC of SROC curve were 0.9781 and 0.9215 respectively. Conclusions: Gadobenate dimeglumine can be regarded as a more effective and feasible contrast medium for Breast MRI Screening. At least 5% differences in diagnostic performance are usually considered as clinically relevant.

Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

Yuan, Zhi-Jun,Zhou, Wen-Wu,Liu, Wei,Wu, Bai-Ping,Zhao, Jin,Wu, Wei,He, Yi,Yang, Shuo,Su, Jing,Luo, Yi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results: There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

Acoustic Beamforming and Beam Steering Using Speaker Array

Yuan Wen,Jun Yang,Woon Seng Gan 한국소음진동공학회 2003 한국소음진동공학회 국제학술대회논문집 Vol.2003 No.8

Thermo-mechanical stress analysis of feed-water valves in nuclear power plants

Wen-qing Li,Lei Zhao,Yang Yue,Jia-yi Wu,Zhi-jiang Jin,Jin-yuan Qian 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.3

Feed-water valves (FWVs) are used to regulate the flow rate of water entering steam generators, whichare very important devices in nuclear power plants. Due to the working environment of relatively highpressure and temperature, there is strength failure problem of valve body in some cases. Based on thethermo-fluid-solid coupling model, the valve body stress of the feed-water valve in the opening processis investigated. The flow field characteristics inside the valve and temperature change of the valve bodywith time are studied. The stress analysis of the valve body is carried out considering mechanical stressand thermal stress comprehensively. The results show that the area with relatively high-velocity areamoves gradually from the bottom of the cross section to the top of the cross section with the increase ofthe opening degree. The whole valve body reaches the same temperature of 250C at the time of 1894 s. The maximum stress of the valve body meets the design requirements by stress assessment. This workcan be referred for the design of FWVs and other similar valves.

Simultaneous Measurement of Dopamine Transporters and D2/D3 Receptors in Drug Naïve Schizophrenic Patients

Yuan-Hwa Chou,Wen-Sheng Huang,Ju-Wei Hsu,Shin-Min Lee,An-Shoei Yang,Kai-Chun Yang 대한정신약물학회 2010 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.8 No.2

Objective: Previous single photon emission computed tomography (SPECT) studies have demonstrated that co-injection of radiotracers 99mTc-TRODAT and 123IBZM can assess both presynaptic, dopamine transporters (DATs), and postsynaptic, dopamine D2/D3 receptors, markers of dopaminergic system simultaneously. The aim of this study was to determine both DATs and dopamine D2/D3 receptors in drug naïve schizophrenic patients. Methods: Severn drug naïve schizophrenic patients and eleven age-matched healthy controls were recruited. Each subject received one SPECT measurement after intravenous co-administration of 99mTc-TRODAT and 123IBZM and one brain MRI scan. A ratio equilibrium model was applied to calculate the specific uptake ratio (SUR) which corresponds to the ratio of Bmax (receptor density) and KD (affinity). Results: The results showed that the SUR of DATs binding was not significantly different between healthy controls and drug naïve schizophrenic patients (2.92±0.62 vs. 2.65±0.27, p=0.052) and, however, the SUR of dopamine D2/D3 receptors binding was significantly lower in drug naïve schizophrenic patients than those in healthy controls (2.79±0.54 vs. 3.90±0.58, p=0.001). Additionally, there was a significant correlation between left and right binding for both DATs (r=0.80, p=0.003) and dopamine D2/D3 receptors (r=0.96, p=0.000) in healthy controls but not seen in drug naïve schizophrenic patients (r=0.54, p=0.20 for DATs, r=0.70, p=0.08 for dopamine D2/D3 receptors). Conclusion: This study provides evidences to support the idea that abnormalities of dopaminergic system in schizophrenia and further elucidates the disruption of inter-hemispheric interaction of postsynaptic and presynaptic markers.