Causal relationship between smoking status, smoking frequency and bladder cancer: a Mendelian randomization study

Pang Lei,Ding Zijun,Chai Hongqiang,Li Fei,Wu Ming,Shuang Weibing 한국유전학회 2023 Genes & Genomics Vol.45 No.2

Background Smoking is a well-established risk factor for bladder cancer. However, it remained unclear that whether smoke status and smoke frequency increase bladder cancer. Objective We aim to explore the causal relationship between smoking status, smoking frequency and the risk of bladder cancer by Mendelian randomization. Methods Large sample size of the genome-wide association(GWAS) database of smoking status, smoking frequency and bladder cancer were obtained. Smoking status included never, previous and current whereas smoking frequency included cigarettes smoked per day, number of cigarettes currently smoked daily and pack years of smoking. Six sets of instrumental variables and 78 related single nucleotide polymorphic(SNP) loci were identified (P < 5 × 10–8. Linkage disequilibrium R2 < 0.001). The causal relationship between smoking status and bladder tumor was studied by inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analysis were also performed. Results There is no causal effect from smoke status on bladder cancer risk while significantly positive relationship between smoking frequency on bladder cancer risk were found. IVW results showed that cigarettes smoked per day, number of cigarettes currently smoked daily and pack years of smoking increase bladder cancer (OR 1.001, 95% CI 1.000–1.002, P = 0.047; OR 1.003, 95% CI 1.000–1.005, P = 0.028; OR 1.004, 95% CI 1.001–1.006, P = 0.003). Sensitivity analysis showed that genetic pleiotropy did not bias the results. Conclusion The results of two sample Mendelian randomization analysis show that there is a positive causal relationship between smoking frequency and the risk of bladder cancer.

Pentagalloylglucose induces autophagy and caspase-independent programmed deaths in human PC-3 and mouse TRAMP-C2 prostate cancer cells.

Hu, Hongbo,Chai, Yubo,Wang, Lei,Zhang, Jinhui,Lee, Hyo Jeong,Kim, Sung-Hoon,Lü,, Junxuan American Association for Cancer Research, Inc 2009 Molecular Cancer Therapeutics Vol.8 No.10

<P>Penta-1,2,3,4,6-O-galloyl-beta-d-glucose (PGG) suppresses the in vivo growth of human DU145 and PC-3 prostate cancer xenografts in nude mice, suggesting potential utility as a prostate cancer chemotherapeutic or chemopreventive agent. Our earlier work implicates caspase-mediated apoptosis in DU145 and LNCaP prostate cancer cells as one mechanism for the anticancer activity. We show here that, in the more aggressive PC-3 prostate cancer cell line, PGG induced programmed cell deaths lacking the typical caspase-mediated apoptotic morphology and biochemical changes. In contrast, PGG induced patent features of autophagy, including formation of autophagosomes and lipid modification of light chain 3 after 48 hours of PGG exposure. The 'autophagic' responses were also observed in the murine TRAMP-C2 cells. Caspase inhibition exacerbated PGG-induced overall death. As for molecular changes, we observed a rapid inhibition of the phosphorylation of mammalian target of rapamycin-downstream targets S6K and 4EBP1 by PGG in PC-3 and TRAMP-C2 cells but not that of mammalian target of rapamycin itself, along with increased AKT phosphorylation. Whereas the inhibition of phosphatidylinositol 3-kinase increased PGG-induced apoptosis and autophagy, experiments with pharmacologic inducer or inhibitor of autophagy or by knocking down autophagy mediator Beclin-1 showed that autophagy provided survival signaling that suppressed caspase-mediated apoptosis. Knocking down of death receptor-interacting protein 1 kinase increased overall death without changing light chain 3-II or caspase activation, thus not supporting death receptor-interacting protein 1-necroptosis for PGG-induction of autophagy or other programmed cell death. Furthermore, PGG-treated PC-3 cells lost clonogenic ability. The induction by PGG of caspase-independent programmed cell death in aggressive prostate cancer cell lines supports testing its merit as a potential drug candidate for therapy of caspase-resistant recurrent prostate cancer.</P>

Triptolide Inhibits Histone Methyltransferase EZH2 and Modulates the Expression of Its Target Genes in Prostate Cancer Cells

Tamgue, Ousman,Chai, Cheng-Sen,Hao, Lin,Zambe, John-Clotaire Daguia,Huang, Wei-Wei,Zhang, Bin,Lei, Ming,Wei, Yan-Ming Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

The histone methyltransferase EZH2 (enhancer of zeste homolog 2) plays critical roles in prostate cancer (PCa) development and is a potential target for PCa treatment. Triptolide possesses anti-tumor activity, but it is unknown whether its therapeutic effect relates with EZH2 in PCa. Here we described EZH2 as a target for Triptolide in PCa cells. Our data showed that Triptolide suppressed PCa cell growth and reduced the expression of EZH2. Overexpression of EZH2 attenuated the Triptolide induced cell growth inhibition. Moreover, Triptolide treatment of PC-3 cells resulted in elevated mRNA levels of target genes (ADRB2, CDH1, CDKN2A and DAB2IP) negatively regulated by EZH2 as well as reduced mRNA levelsan of EZH2 positively regulated gene (cyclin D1). Our findings suggest the PCa cell growth inhibition mediated by Triptolide might be associated with downregulation of EZH2 expression and the subsequent modulation of target genes.

Synthesis and biological evaluation of novel fluconazole analogues bearing 1,3,4-oxadiazole moiety as potent antifungal agents

Jun Liao,Fan Yang,Lei Zhang,Xiaoyun Chai,Qing-Jie Zhao,Shichong Yu,Yan Zou,Qingguo Meng,Qiuye Wu 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.4

A novel series of fluconazole based mimicsincorporating 1,3,4-oxadiazole moiety were designed andsynthesized. All the title compounds were characterized by1H-NMR, 13C-NMR, and Q-TOF-MS. Preliminary resultsrevealed that most of analogues exhibited significant antifungalactivity against seven pathogenic fungi. Compounds9g and 9k (MIC80 B 0.125 lg/mL, respectively) werefound more potent than the positive controls itraconazoleand fluconazole as broad-spectrum antifungal agents. Theobserved docking results showed that the 1,3,4-oxadiazolemoiety enhanced the affinity binding to the cytochromeP450 14a-demethylase (CYP51).

Vibration test method of aero-engine 3D printing pre-swirl nozzle based on equivalent installation stiffness

Yujie Zhao,Yeda Lian,Lei Li,Xu Gong,Xianghai Chai,Wei Liu 대한기계학회 2023 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.37 No.2

Pre-swirl nozzle is an important cooling component that is located inside of aero-engine and exposed to complex vibration excitation, and exploring its vibration characteristics and durability is of significant importance, especially for 3D printing pre-swirl nozzle. The present study provides a novel vibration test method based on equivalent installation stiffness. Firstly, the vibration characteristics of pre-swirl nozzle in real engine assembly state is calculated by the finite element method, and the equivalent constraint fixture is designed and checked based on this. The check results indicate that the designed fixture can well restore the installation stiffness of engine and the strength of the test fixture elements is enough in the vibration test process. Then, the modal characteristics of pre-swirl nozzle are measured by modal test, based on which the accuracy of the finite element model is verified. Finally, a test program of vibration durability is established to evaluate the vibration durability of pre-swirl nozzle, in which the excitation frequency is determined by combining logarithmic frequency sweep and linear frequency sweep and the location of maximum stress is determined based on a novel method (density increasing method). Besides, the calibration of relation between vibration stress and excitation amplitude is completed. Based on the proposed test program, vibration durability test is performed. The results show that the natural frequency of pre-swirl nozzle only decreases by 0.62 % after 5×10 7 cycles, which indicates that the specimen is always in the stage of fatigue crack initiation over the test duration.

Shaking Table Model Test of Loess Tunnel Structure under Rainfall

Xinhai Zhou,Xuansheng Cheng,Lei Qi,Ping Wang,Shaofeng Chai,Yinjun Liu 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.6

A large number of loess tunnels are being built or have been put into operation due to the vigorous development of highways and railways. Due to the broken, porous and multiphase of loess microstructure, the loess will lose its strength rapidly under the loading conditions of rainfall and dynamic, while the shaking table test can be used to simulate this dynamic process much better. Based on the shaking table model of 1/40 loess tunnel and considering the adverse conditions of El-Centro bidirectional seismic wave and rainfall, the seismic response law of loess tunnel is studied in this paper; the damping effect of the loess tunnel structure is discussed by setting the damping layer. The results show that under the action of rainfall and earthquake, the damage of surrounding rock structure precedes that of lining structure; the acceleration of the lining structure changes little under different rainfall conditions, but the strain tends to increase; under the cumulative effect of ground motion, the failure time of surrounding rock structure appears early in the case of heavy rainfall, and the width and depth of crack finally formed are also larger; the setting of damping layer can obviously reduce the strain under different rainfall.

Chorea in Sporadic Creutzfeldt-Jakob disease

Ai Huey Tan,Tsun Haw Toh,Soon Chai Low,Si Lei Fong,Kah Kian Chong,Kee Wei Lee,Khean Jin Goh,Shen-Yang LIM 대한파킨슨병및이상운동질환학회 2018 Journal Of Movement Disorders Vol.11 No.3

Glutathione disulfide sensitizes hepatocytes to TNFα-mediated cytotoxicity via IKK-β S-glutathionylation: a potential mechanism underlying non-alcoholic fatty liver disease

Xiaobing Dou,Songtao Li,Linfeng Hu,Lei Ding,Yue Ma,Wang Ma,Hui Chai,Zhenyuan Song 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Oxidative stress and TNFα are critically involved in the initiation and progression of non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of dysregulated glutathione homeostasis, a principal feature of oxidative stress, on TNFα-induced hepatotoxicity and its mechanistic implications in NAFLD progression. We showed that mice fed a high-fat diet (HFD) for 12 weeks developed hepatic steatosis and liver injuries, which were associated with not only TNFα overproduction but also hepatic glutathione dysregulation, characterized by GSH reduction and GSSG elevation. Moreover, consuming a HFD increased protein S-glutathionylation (protein-SSG formation) in the liver. Subsequent cell culture studies revealed that GSSG accumulation, as opposed to GSH reduction, sensitized hepatocytes to TNFα killing by reducing the TNFα-triggered NF-κB activity. GSSG prevented TNFα-induced activation of IKK-β, an upstream kinase in the NF-κB signaling pathway, by inducing IKK-β glutathionylation (IKK-β-SSG formation). In animal studies, in comparison to a control diet, HFD consumption resulted in increased hepatic IKK-β- SSG formation, leading to suppressed IKK-β activation and subsequent NF-κB suppression. Furthermore, we found that HFD consumption also led to decreased hepatic expression of glutaredoxin, a key enzyme for de-glutathionylation. Similarly, CdCl2, a chemical inhibitor of glutaredoxin, sensitized hepatocytes to TNFα-mediated cytotoxicity. In conclusion, our data suggest that GSSG is a potent and clinically relevant sensitizer for TNFα-induced hepatotoxicity in NAFLD, which represents a potential therapeutic target for NAFLD.

Mechanical Performance of Prefabricated External Wall Panel under Horizontal Displacement

Ying Xu,Shuai-Ying Wang,Lei Chai,Cong-Cong Luo 대한토목학회 2018 KSCE JOURNAL OF CIVIL ENGINEERING Vol.22 No.11

In this paper, experiment and Finite Element Method (FEM) approaches are employed to study the mechanical performance of prefabricated external wall panel under lateral displacement. Tensile bond strength test and Z-shaped specimen direct shear test of the bonding interface of mortar to ceramsite concrete are performed, the normal and shear mechanical property of the interface is studied respectively. Scaled model test of prefabricated external wall panel under lateral displacement is then performed to obtain loaddisplacement curve, and mechanical behavior of prefabricated external wall panel in different stages is studied. Moreover, ABAQUS finite element analysis model for scaled model test panel is established based on previous study about bond interface and the results from experiment and FEM analysis are relatively consistent with each other. It is found that with the gradual increase in tangential contact stiffness of joint interfaces, the overall lateral stiffness of wall panels will approach complete joint consolidation conditions before the peak load. However, when the tangential contact stiffness of joint interfaces increases to a certain extent, there will be little change in initial lateral stiffness.

Molecular Cloning and Characterization of Two Brassica napus TTG1 Genes Reveal Genus-Specific Nucleotide Preference, Extreme Protein-Level Conservation and Fast Divergence of Organ-Specificity

Jun Lu,Jia Na Li,Bo Lei,San Gen Wang,You Rong Chai 한국유전학회 2009 Genes & Genomics Vol.31 No.2

Encoding a WD40 protein, Arabidopsis thaliana TRANSPARENT TESTA GLABRA1 (AtTTG1) regulates trichome and root hair differentiation as well as flavonoids and seed mucilage deposition in plants. Here, two Brassica napus TTG1 (BnTTG1) genes were isolated, and Southern hybridization also generated only two bands. The 1511-bp BnTTG1-1 and the 1555-bp BnTTG1-2 both have one intron, and show alternative sites for transcription start, polyadenylation and intron right border splicing. EST and GSS tags suggested that BnTTG1-1 was derived from B. rapa, while BnTTG1-2 from B. oleracea. Evidence implies that TTG1 was possibly triplicated in Brassiceae, but some triplicated members were lost soon, which might involve fragmental rearrangements. BnTTG1-1 shares 88.7% genomic and 95.7% mRNA identities with BnTTG1-2. Deduced BnTTG1-1 and BnTTG1-2 proteins both are 337 aa, differed only by substitution of a similar residue. They resemble AtTTG1 in WD40 domain and all conserved motifs. TTG1/AN11-type WD40 proteins are extremely conserved even across kingdoms. Homological and structural characterizations identified BnTTG1-1 and BnTTG1-2 to be orthologs of AtTTG1. Several non-coding motifs are conserved between AtTTG1 and BnTTG1. BnTTG1 coding regions tend to evolve high GC contents through T/A→C/G substitutions especially T→C transition, but AtTTG1 shows opposite base preference. BnTTG1 genes also evolve a GA-stretch in the leader sequence. RT-PCR detected complementation in organ-specificity between BnTTG1-1 and BnTTG1-2. BnTTG1-2 is more like AtTTG1 and is expressed in all major organs. BnTTG1-1 is more organ-specific with lower expression in seed and root, possibly withdrawing from regulating seed coat pigment/mucilage deposition and root hair formation.