To derive a precise estimation of the associations between the cytochrome P450 1B 1 （CYPIB1） 4326C/G variants and prostate cancer （PCa） risk or aggressiveness, a meta-analysis was performed using all eligible publ...To derive a precise estimation of the associations between the cytochrome P450 1B 1 （CYPIB1） 4326C/G variants and prostate cancer （PCa） risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYPIB1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians （OR= 1.52, 95% Ch 1.20-1.92）, and significant associations were also observed in a heterozygote comparison （OR= 1.40, 95% Ch 1.03-1.89）, a homozygote comparison （0R=2.38, 95% Ch 1.31-4.33） and in a dominant genetic model （OR = 1.52, 95% Ch 1.14-2.01）. Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa （OR= 1.13, 95% Ch 1.04-1.24）, and significant associations were observed in a heterozygote comparison （OR= 1.16, 95% Ch 1.02-1.33）, a homozygote comparison （OR= 1.24, 95% Ch 1.03-1.49） and a dominant genetic model （OR= 1.19, 95% Ch 1.05- 1.34）. The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYPIB1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.展开更多
Pain is often debilitating,and current treatments are neither universally efficacious nor without risks.Transient receptor potential(TRP)ion channels offer alternative targets for pain relief,but little is known about...Pain is often debilitating,and current treatments are neither universally efficacious nor without risks.Transient receptor potential(TRP)ion channels offer alternative targets for pain relief,but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain.Here,transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation(SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid(EET)and 19,20-EpDPA post injury.Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro,and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia(DRG)neurons.TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079,and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1.This latter effect mapped to residues Y933,G939,and S921 of TRPA1.Intra-plantar injection of 19,20-EpDPA induced acute mechanical,but not thermal hypersensitivity in mice,which was also blocked by A967079.Similarly,Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury.These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.展开更多
文摘To derive a precise estimation of the associations between the cytochrome P450 1B 1 （CYPIB1） 4326C/G variants and prostate cancer （PCa） risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYPIB1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians （OR= 1.52, 95% Ch 1.20-1.92）, and significant associations were also observed in a heterozygote comparison （OR= 1.40, 95% Ch 1.03-1.89）, a homozygote comparison （0R=2.38, 95% Ch 1.31-4.33） and in a dominant genetic model （OR = 1.52, 95% Ch 1.14-2.01）. Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa （OR= 1.13, 95% Ch 1.04-1.24）, and significant associations were observed in a heterozygote comparison （OR= 1.16, 95% Ch 1.02-1.33）, a homozygote comparison （OR= 1.24, 95% Ch 1.03-1.49） and a dominant genetic model （OR= 1.19, 95% Ch 1.05- 1.34）. The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYPIB1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.
基金funded by the Department of Defense [W81XWH-17-1-0413, USA]。
文摘Pain is often debilitating,and current treatments are neither universally efficacious nor without risks.Transient receptor potential(TRP)ion channels offer alternative targets for pain relief,but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain.Here,transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation(SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid(EET)and 19,20-EpDPA post injury.Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro,and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia(DRG)neurons.TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079,and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1.This latter effect mapped to residues Y933,G939,and S921 of TRPA1.Intra-plantar injection of 19,20-EpDPA induced acute mechanical,but not thermal hypersensitivity in mice,which was also blocked by A967079.Similarly,Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury.These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.
