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.

EphB1 and Ephrin-B, New Potential Biomarkers for Squamous Cell/adenosquamous Carcinomas and Adenocarcinomas of the Gallbladder

Yuan, Yuan,Yang, Zhu-Lin,Miao, Xiong-Ying,Liu, Zi-Ru,Li, Dai-Qiang,Zou, Qiong,Li, Jing-He,Liang, Lu-Feng,Zeng, Gui-Xiang,Chen, Sen-Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC ($P_{SC/ASC}$ =0.000) or AC ($P_{AC}$ =0.000 or $P_{AC}$ =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.

The miR-145-5p/CD36 pathway mediates PCB2-induced apoptosis in MCF-7 cells

Yuan Yuan,Caihua Xue,Qiang Wu,Mengjie Wang,Jiahua Liu,Longfei Zhang,Qianwen Xing,Jingyan Liang,Hua Wu,Zhi Chen 한국유전학회 2021 Genes & Genomics Vol.43 No.2

Background Procyanidin B2 (PCB2) can increase the levels of anti-infammatory and immune mediators. Objectives However, its molecular mechanism in human breast cancer remains unclear. This study aimed to investigate the antitumor efect of PCB2 on MCF-7 cells and to examine the underlying mechanism. Methods The fow cytometry and EdU incorporation assays were measured the PCB2-induced BMECs. The expression levels of infammatory factors and immune response genes were upregulated in MCF-7 cells, high-throughput sequencing was used to detect diferentially expressed genes in blank and PCB2-treated MCF-7 cells. Results The results showed that PCB2 induced the apoptosis of MCF-7 cells. CD36 profles were afected in MCF-7 cells. Additionally, prediction software identifed a miR-145-5p binding site in the CD36 sequence. Luciferase reporter assays and Western blot analysis were used to verify the regulatory relationships between the diferentially expressed miRNA miR145-5p and CD36. MiR-145-5p and its key target (CD36) constitute a potential miRNA-mRNA regulatory pair. Functional studies in MCF-7 cells revealed that CD36 promotes but miR-145-5p inhibits apoptosis. Conclusion Overall, these data suggest that miR-145-5p inhibits the enhancing efect of PCB2 on CD36 expression by binding CD36 and subsequently regulating apoptosis, the immune response and anti-infammatory pathways. These results provide theoretical and experimental support for the treatment of breast cancer.

The study of switched reluctance motor for 4-DOF bearingless motor

Ye Yuan,Yukun Sun,Qianwen Xiang,Yuan Ren,Qiang Liu 대한전기학회 2019 Journal of Electrical Engineering & Technology Vol.14 No.1

High integration, low loss and high-reliability are the main development trends of flywheel battery. Thus this study presents the first prototype of a novel high-integration four degrees of freedom (4-DOF) bearingless motor with the advantages of weak coupling and low power consumption. The proposed bearingless motor can realize energy conversion and produce 4-DOF radial forces compared with the conventional bearingless motor for improving the integration of system. A biased flux for producing radial levitation forces is provided by the permanent magnets, which reduce the power consumption of the system. Moreover, a decoupling between the torque and the suspension systems is realized through a structural design, thereby improving the controllability. Structure and winding configurations are introduced and the operation principle of the 4-DOF bearingless motor is discussed. Magnetic circuits analysis and parameter design method are present and a three-dimensional finite element model is established. Electromagnetic characteristics that focus on the high integration, low loss and high reliability are discussed and validated comprehensively. Finally, a favorable controllability of radial suspension forces are verified using finite-element analysis and some experimental results.

Demethylation of CpG islands in the 5` upstream regions mediates the expression of the human testis-specific gene MAGEB16 and its mouse homolog Mageb16

( Yun Qiang Liu ),( Mei Ling Wang ),( Si Yuan Jiang ),( Yong Jie Lu ),( Da Chang Tao ),( Yuan Yang ),( Yong Xin Ma ),( Si Zhong Zhang ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.2

Tissue-specific gene expression is regulated by epigenetic modification involving trans-acting factors. Here, we identified that the human MAGEB16 gene and its mouse homolog, Mageb16, are only expressed in the testis. To investigate the mechanism governing their expression, the promoter methy-lation status of these genes was examined in different samples. Two CpG islands (CGIs) in the 5` upstream region of MAGEB16 were highly demethylated in human testes, whereas they were methylated in cells without MAGEB16 expression. Similarly, the CGI in Mageb16 was hypomethylated in mouse testes but hypermethylated in other tissues and cells without Mageb16 expression. Additionally, the expression of these genes could be activated by treatment with the demethylation agent 5`-aza-2`- deoxycytidine (5`-aza-CdR). Luciferase assays revealed that both gene promoter activities were inhibited by methylation of the CGI regions. Therefore, we propose that the testis-specific expression of MAGEB16 and Mageb16 is regulated by the methylation status of their promoter regions. [BMB Reports 2014; 47(2): 86-91]

The MTHFR C677T Polymorphism and Risk of Acute Lymphoblastic Leukemia: an Updated Meta-analysis Based on 37 Case-control Studies

Jiang, Yuan,Hou, Jing,Zhang, Qiang,Jia, Shu-Ting,Wang, Bo-Yuan,Zhang, Ji-Hong,Tang, Wen-Ru,Luo, Ying Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for the MTHFRC677T polymorphism and ALL risk. Methods: Electronic searches of PubMed and the Chinese Biomedicine database were conducted to select case-control studies containing available genotype frequencies of C677T and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of any association. Results: Case-control studies including 6,371 cases and 10,850 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had decreased risk of ALL (OR= 0.776, 95% CI: 0.687~0.877, p< 0.001) in Caucasians (OR= 0.715, 95% CI: 0.655~0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591~1.005, p= 0.055) and others (OR=0.913, 95% CI: 0.656~1.271, p= 0. 590) did not suggest an association. A symmetric funnel plot, the Egger's test (P=0.093), and the Begg- test (P=0.072) were all suggestive of the lack of publication bias. Conclusion: This meta-analysis supports the idea that the MTHFR C677T genotype is associated with risk of ALL in Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between the MTHFRC677T polymorphism and ALL.

MicroRNA-214-mediated UBC9 expression in glioma

( Zhi Qiang Zhao ),( Xiao Chao Tan ),( Ani Zhao ),( Li Yuan Zhu ),( Bin Yin ),( Jiang Ang Yuan ),( Bo Qin Qiang ),( Xiao Zhong Peng ) 생화학분자생물학회(구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.11

It has been reported that ubiquitin-conjugating enzyme 9 (Ubc9), the unique enzyme2 in the sumoylation pathway, is up-regulated in many cancers. However, the expression and regulation of UBC9 in glioma remains unknown. In this study, we found that Ubc9 was up-regulated in glioma tissues and cell lines compared to a normal control. UBC9 knockdown by small interfering RNA (siRNA) affected cell proliferation and apoptosis in T98G cells. Further experiments revealed that microRNA (miR)-214 directly targeted the 3` untranslated region (UTR) of UBC9 and that there was an inverse relationship between the expression levels of miR-214 and UBC9 protein in glioma tissues and cells. MiR-214 overexpression suppressed the endogenous UBC9 protein and affected T98G cell proliferation. These findings suggest that miR-214 reduction facilitates UBC9 expression and is involved in the regulation of glioma cell proliferation.

In Vitro Activity of Taurine-5-Bromosalicylaldehyde Schiff Base Against Planktonic and Biofilm Cultures of Methicillin-Resistant Staphylococcus aureus

( Ru Qiang Yuan ),( Yun Peng Diao ),( Wen Li Zhang ),( Yuan Lin ),( Shan Shan Huang ),( Houli Zhang ),( Li Ma ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.8

Staphylococcus aureus is a major human pathogen, implicated in both community and hospital acquired infections. The therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections is becoming more difficult because of multidrug resistance and strong biofilmforming properties. Schiff bases have attracted attention as promising antibacterial agents. In this study, we investigated the in vitro activity of taurine-5-bromosalicylaldehyde Schiff base (TBSSB) against MRSA. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) were determined using a microtiter broth dilution method. TBSSB effectively inhibited planktonic MRSA, with an MIC of 32 μg/ml. The time-kill curve confirmed that TBSSB exhibited bactericidal activity against MRSA. TBSSB was also found to significantly inhibit MRSA biofilm formation at 24 h, especially at 1×MIC and sub-MIC levels. Furthermore, scanning electron microscopy and transmission electron microscopy showed remarkable morphological and ultrastructural changes on the MRSA cell surface, due to exposure to TBSSB. This study indicated that TBSSB may be an effective bactericidal agent against MRSA.

Phosphorylation of Silk Fibroin via Maillard Reaction and Its Behavior of Biomimetic Mineralization

Jingjing Yuan,Qian Zhou,Ping Wang,Chao Deng,Jiugang Yuan,Qiang Wang 한국섬유공학회 2019 Fibers and polymers Vol.20 No.8

Silk fibroin (SF) has the characteristics of non-toxicity, good biocompatibility and low immunogenicity, andexhibits many potential applications in biomaterial fields. In the present work, chemical phosphorylation of SF was carriedout via the Maillard reaction using D-glucose-6-phosphate (GP), aiming at increasing the number of binding-sites forcalcium ion and promoting the biomimetic mineralization of SF films. Changes in the molecular weight of SF before andafter GP grafting were analyzed by SDS-PAGE and SEC chromatogram. Structures, morphologies, and elementalcompositions for the fibroin-based films before and after mineralization were evaluated by the means of EDS, SEM, FTIR,and XRD. The results indicated that GP was successfully grafted onto SF surfaces, companying with a slight decrease in themolecular weight. Biomimetic mineralization led to a noticeable deposition of hydroxyapatite (HAp) on the film of SF-g-GP, and higher contents of calcium and phosphorous were detected on the mineralized material, revealing thatphosphorylation promoted the mineralization processing. Meanwhile, biocompatibility of the obtained SF-g-GP/HAp wasabove the acceptable level according to ISO 10993-5-2009. The present work provides an alternative to prepare the fibroinbasedbone repair materials.

A Coding Method for Mathematical Problems in the TIMSS 1999 Video Study and its Applications

( Zhi Qiang Yuan ) 한국수학교육학회 2010 수학교육연구 Vol.14 No.2