BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and acti...BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and activation[25-hydroxylase(CYP2R1)enzyme],may influence NPC susceptibility and radiotherapy response.Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D[25(OH)D]levels,and are implicated in other cancers.However,their role in NPC-particularly in high-risk Han Chinese populations-and interaction with vitamin D status remains unclear.This case control study(360 NPC patients,550 controls)investigates these relationships to inform prevention and personalized therapy.AIM To investigate the association between vitamin D binding protein(GC)and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.METHODS A case control study design was adopted,and 360 patients with NPC and 550 healthy controls were included.TaqMan method was used to perform genotyping on GC gene loci rs4588,rs7041,and CYP2R1 gene loci rs10741657,rs12794714.Serum 25(OH)D levels were detected,and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.RESULTS The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model[odds ratio(OR)=1.68,95%CI:1.15-2.45,P=0.007]and the recessive model(OR=1.56,95%CI:1.02-2.38,P=0.039).The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup(OR=1.87,95%CI:1.11-3.15,P=0.019)and the squamous cell carcinoma subgroup(OR=1.89,95%CI:1.19-3.00,P=0.007).The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype(P<0.001).The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels(P=0.003).The rs12794714 AA genotype was associated with radiotherapy resistance(OR=1.76,95%CI:1.18-2.63,P=0.005).Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.CONCLUSION GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response,and this association may be affected by serum 25(OH)D levels.This study provides a new idea for the prevention and individualized treatment in NPC.展开更多
Constructing high-performance nanozymes for specific biomolecules is crucial but challenging for practical applications and fundamental research.Herein,through the examination of the catalytic reaction paths of natura...Constructing high-performance nanozymes for specific biomolecules is crucial but challenging for practical applications and fundamental research.Herein,through the examination of the catalytic reaction paths of natural nicotinamide adenine dinucleotide(NADH)oxidase(NOX),a novel and efficient single-atom rhodium catalyst(Rh1/NC)was developed to mimic NOX.The Rh_(1)/NC demonstrated the ability to catalyze the dehydrogenation of NADH and transfer electrons to O_(2)to generate H_(2)O_(2)through the typical two-electron pathway.Furthermore,our findings revealed that Rh_(1)/NC exhibits the ability to catalyze the conversion of produced H_(2)O_(2)into OH under mildly acidic conditions.This process amplifies the oxidation of NADH,showcasing NADH peroxidase-like activity(NPx-like).As a paradigm,this unique dual enzyme-like property of Rh_(1)/NC with a positive feedback effect holds significance in disrupting cancer cellular homeostasis.Rh_(1)/NC can effectively consume NADH via cascade biocatalytic reactions within cancer cells,further triggering the elevation of reactive oxygen species(ROS),leading to impaired oxidative phosphorylation and decreased mitochondrial membrane potential,thus damaging the adenosine triphosphate(ATP)synthesis.The resulting'domino effect'interferes with the energy metabolism homeostasis of cancer cells,ultimately promoting cell apoptosis.This study provides potential guidance for the rational design of materials with greater capabilities.展开更多
1.Objective Unlike the North China Plate where Archean and Paleoproterozoic crustal rocks are widely distributed,Early Precambrian basement rocks in the Yangtze Block of South China are locally exposed(Fig.1a),such as...1.Objective Unlike the North China Plate where Archean and Paleoproterozoic crustal rocks are widely distributed,Early Precambrian basement rocks in the Yangtze Block of South China are locally exposed(Fig.1a),such as in the Kongling Complex,the Zhongxiang Complex,and the Douling Complex(Zhao GC and Cawood PA,2012).The Dabie Orogen is the eastward extension of the Qinling Orogen.展开更多
文摘BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and activation[25-hydroxylase(CYP2R1)enzyme],may influence NPC susceptibility and radiotherapy response.Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D[25(OH)D]levels,and are implicated in other cancers.However,their role in NPC-particularly in high-risk Han Chinese populations-and interaction with vitamin D status remains unclear.This case control study(360 NPC patients,550 controls)investigates these relationships to inform prevention and personalized therapy.AIM To investigate the association between vitamin D binding protein(GC)and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.METHODS A case control study design was adopted,and 360 patients with NPC and 550 healthy controls were included.TaqMan method was used to perform genotyping on GC gene loci rs4588,rs7041,and CYP2R1 gene loci rs10741657,rs12794714.Serum 25(OH)D levels were detected,and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.RESULTS The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model[odds ratio(OR)=1.68,95%CI:1.15-2.45,P=0.007]and the recessive model(OR=1.56,95%CI:1.02-2.38,P=0.039).The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup(OR=1.87,95%CI:1.11-3.15,P=0.019)and the squamous cell carcinoma subgroup(OR=1.89,95%CI:1.19-3.00,P=0.007).The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype(P<0.001).The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels(P=0.003).The rs12794714 AA genotype was associated with radiotherapy resistance(OR=1.76,95%CI:1.18-2.63,P=0.005).Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.CONCLUSION GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response,and this association may be affected by serum 25(OH)D levels.This study provides a new idea for the prevention and individualized treatment in NPC.
基金financially supported by the National Natural Science Foundation of China(No.22207066)Taishan Scholars Program of Shandong Province(No.TS201712065)+2 种基金the Academic Promotion Program of Shandong First Medical University(No.2019QL009)the Science and Technology Funding from Jinan(No.2020GXRC018)the Traditional Chinese Medicine Science and Technology Project of Shandong Province(No.Q-2022142)。
文摘Constructing high-performance nanozymes for specific biomolecules is crucial but challenging for practical applications and fundamental research.Herein,through the examination of the catalytic reaction paths of natural nicotinamide adenine dinucleotide(NADH)oxidase(NOX),a novel and efficient single-atom rhodium catalyst(Rh1/NC)was developed to mimic NOX.The Rh_(1)/NC demonstrated the ability to catalyze the dehydrogenation of NADH and transfer electrons to O_(2)to generate H_(2)O_(2)through the typical two-electron pathway.Furthermore,our findings revealed that Rh_(1)/NC exhibits the ability to catalyze the conversion of produced H_(2)O_(2)into OH under mildly acidic conditions.This process amplifies the oxidation of NADH,showcasing NADH peroxidase-like activity(NPx-like).As a paradigm,this unique dual enzyme-like property of Rh_(1)/NC with a positive feedback effect holds significance in disrupting cancer cellular homeostasis.Rh_(1)/NC can effectively consume NADH via cascade biocatalytic reactions within cancer cells,further triggering the elevation of reactive oxygen species(ROS),leading to impaired oxidative phosphorylation and decreased mitochondrial membrane potential,thus damaging the adenosine triphosphate(ATP)synthesis.The resulting'domino effect'interferes with the energy metabolism homeostasis of cancer cells,ultimately promoting cell apoptosis.This study provides potential guidance for the rational design of materials with greater capabilities.
基金financially supported by the Open Fund of the Research Center for Petrogenesis and Mineralization of Granitoid Rocks(PMGR202014)the project of the China Geological Survey(DD20190050)。
文摘1.Objective Unlike the North China Plate where Archean and Paleoproterozoic crustal rocks are widely distributed,Early Precambrian basement rocks in the Yangtze Block of South China are locally exposed(Fig.1a),such as in the Kongling Complex,the Zhongxiang Complex,and the Douling Complex(Zhao GC and Cawood PA,2012).The Dabie Orogen is the eastward extension of the Qinling Orogen.
