The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
Circular RNAs(circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circRNAs play an important role in ...Circular RNAs(circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circRNAs play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges,interacting with proteins, modulating the expression of related genes and translating into peptides or proteins.CircRNAs have also been used as biomarkers for a number of diseases, which could improve clinical practice.This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circRNAs as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circRNAs to facilitate their clinical transformation into disease treatment.展开更多
Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide ...Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.展开更多
Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women (approximately 4:1). Here, we summarize the bladder cancer-related risk factors, ...Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women (approximately 4:1). Here, we summarize the bladder cancer-related risk factors, including environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk factors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study (GWAS) has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction studies need to be conducted to provide more information for the etiology of bladder cancer.展开更多
The increasing occurrence of cyanobacterial blooms in water bodies is a serious threat to the environment. Efficient in-lake treatment methods for the control of cyanobacteria proliferation are needed, their in-vivo d...The increasing occurrence of cyanobacterial blooms in water bodies is a serious threat to the environment. Efficient in-lake treatment methods for the control of cyanobacteria proliferation are needed, their in-vivo detection to obtain a real-time response to their presence, as well as the information about their physiological state after the applied treatment. In-vivo fluorescence measurements of photosynthetic pigments have proved to be effective for quantitative and qualitative detection of phytoplankton in a water environment. In the experiment, chlorophyll and phycocyanin fluorescence sensors were used concurrently to detect stress caused by electrochemical oxidation applying an electrolytic cell equipped with borondoped diamond electrodes on a laboratory culture of cyanobacteria Microcystis aeruginosa PCC 7806. The inflicted injuries were reflected in a clear transient increase in the phycocyanin fluorescence signal(for 104 %? 43%) 24 h after the treatment, which was not the case for the chlorophyll fluorescence signal. In the next 72 h of observation, the fluorescence signals decreased(on 40% of the starting signal) indicating a reduction of cell number, which was confirmed by cell count(24% reduction of the starting concentration) and analysis of extracted chlorophyll and phycocyanin pigment. These results demonstrate the viability of the combined application of two sensors as a useful tool for in-vivo detection of induced stress, providing real-time information needed for the evaluation of the efficiency of the in-lake treatment and decision upon the necessity of its repetition. The electrochemical treatment also resulted in a lower free microcystins concentration compared to control.展开更多
The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes wo...The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to investigate the aggregated genetic effects of single nucleotide polymorphisms(SNPs)assigned to candidate genes.The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses.Gene expression was calculated using databases obtained from The Cancer Genome Atlas(TCGA)and The Gene Expression Omnibus(GEO).Kaplan‐Meier plotter was used to evaluate the association between gene expression with gastric cancer survival.Tumor Immune Estimation Resource 2.0(TIMER 2.0)was applied to determine the correlation between selected gene expression and the immune cell infiltration degree.We identified that the G allele of rs2990912 in KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 expression was related to immune cell infiltration and positively correlated with PD-L1 expression.Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility,which may provide important insights into the diagnosis,prognosis,and treatment of gastric cancer.展开更多
Although tobacco and alcohol consumption are two common risk factors of head and neck cancer (HNC), other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood....Although tobacco and alcohol consumption are two common risk factors of head and neck cancer (HNC), other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Human DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic variants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms (SNPs) in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly increased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus interactions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway-based analyses of DNA repair genes derived from genome-wide association studies (GWASs) in HNC are needed.展开更多
Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk....Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.展开更多
Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. ...Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. Here, LC-associated hypomethylation in alpha-1,3-fucosyltransferase VII (FUT7) is identified via the Illumina 850K array in a discovery study and validated by mass spectrometry in two independent casecontrol studies with blood samples from 1720 LC patients (86.8% LC at stage I, blood is collected before surgery and treatment) and 3143 healthy controls. Compared to the controls, blood-based FUT7 hypomethylation is identified in LC patients at stage I, and even in LC patients with malignant nodules ≤1 cm and in patients with adenocarcinoma in situ. Gender plays a role in the LC-associated FUT7 hypomethylation in blood, which is more significant in males than in females. We also reveal that FUT7 hypomethylation in LC could be enhanced by the advanced stage of cancer, involvement of lymph nodes, and larger tumor size. Based on a large sample size and semi-quantitative methods, our study reveals a strong association between blood-based FUT7 hypomethylation and LC, suggesting that methylation signatures in blood may be a group of potential biomarkers for detection of early-stage LC.展开更多
Cyanobacterial blooms are global phenomena that can occur in calm and nutrient-rich(eutrophic) fresh and marine waters. Human exposure to cyanobacteria and their biologically active products is possible during water s...Cyanobacterial blooms are global phenomena that can occur in calm and nutrient-rich(eutrophic) fresh and marine waters. Human exposure to cyanobacteria and their biologically active products is possible during water sports and various water activities, or by ingestion of contaminated water. Although the vast majority of harmful cyanobacterial products are confined to the interior of the cells, these are eventually released into the surrounding water following natural or artificially induced cell death. Electrochemical oxidation has been used here to damage cyanobacteria to halt their proliferation, and for microcystin degradation under in-vitro conditions. Partially spent Jaworski growth medium with no addition of supporting electrolytes was used. Electrochemical treatment resulted in the cyanobacterial loss of cell-buoyancy regulation, cell proliferation arrest, and eventual cell death. Microcystin degradation was studied separately in two basic modes of treatment: batch-wise flow, and constant flow, for electrolytic-cell exposure. Batch-wise exposure simulates treatment under environmental conditions, while constant flow is more appropriate for the study of boron-doped diamond electrode efficacy under laboratory conditions. The effectiveness of microcystin degradation was established using high-performance liquid chromatography–photodiode array detector analysis, while the biological activities of the products were estimated using a colorimetric protein phosphatase-1 inhibition assay. The results indicate potential for the application of electro-oxidation methods for the control of bloom events by taking advantage of specific intrinsic ecological characteristics of bloom-forming cyanobacteria. The applicability of the use of boron-doped diamond electrodes in remediation of water exposed to cyanobacteria bloom events is discussed.展开更多
Three immunizing haptens of bisphenol A(BPA), including two new haptens, were used to produce highly sensitive and specific polyclonal antibodies. The spacer arms of haptens for coupling to the protein carrier were lo...Three immunizing haptens of bisphenol A(BPA), including two new haptens, were used to produce highly sensitive and specific polyclonal antibodies. The spacer arms of haptens for coupling to the protein carrier were located at different positions in BPA, and different length spacer arms were tested. Highly sensitive polyclonal antibodies were obtained and characterized using indirect competitive enzyme-linked immunosorbent assay(ic ELISA). Under optimized conditions, the half maximal inhibitory concentration(IC50) value of the best polyclonal antibody was 2.1 mg·L^(-1), based on coating heterogeneous antigens, and this optimal polyclonal antibody was highly sensitive toward BPA and displayed negligible crossreactivity with bisphenol B and bisphenol E. A sensitive ic ELISA method utilizing the polyclonal antibody was developed for the determination of BPA in milk. In spiked samples(5, 10 and 20 mg·L^(-1)), the recovery ranged from 80% to 102% with a coefficient of variation(CV) value below 15.8%. The limit of detection of ic ELISA was1.95 mg·L^(-1). These results indicate that the ic ELISA method is suitable for the detection of BPA in milk.展开更多
What is already known on this topic?The global efforts to address the hepatitis C virus(HCV)are progressing,but there are still significant gaps in the diagnosis and treatment of HCV,leading to an increasing number of...What is already known on this topic?The global efforts to address the hepatitis C virus(HCV)are progressing,but there are still significant gaps in the diagnosis and treatment of HCV,leading to an increasing number of deaths related to HCV.What is added by this report?An extensive investigation was conducted to assess HCV RNA diagnosis,treatment uptake,and associated factors among individuals infected with HCV within Jiangsu Province.The study encompassed a large geographical area and utilized a substantial sample size.What are the implications for public health practice?Implementing focused interventions to improve the timely diagnosis of HCV RNA and increase the uptake of HCV treatment could effectively reduce the future burden of HCV-related health problems,deaths,and healthcare expenses.This is essential for achieving the global target of eliminating hepatitis C.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
基金supported in part by the National Natural Science Foundation of China(Grant No.82130096)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)。
文摘Circular RNAs(circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circRNAs play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges,interacting with proteins, modulating the expression of related genes and translating into peptides or proteins.CircRNAs have also been used as biomarkers for a number of diseases, which could improve clinical practice.This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circRNAs as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circRNAs to facilitate their clinical transformation into disease treatment.
基金The current study was supported by the National Natural Science Foundation of China(Grant Nos.82130096 and 82373537)Collaborative Innovation Center for Cancer Personalized Medicine and Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.
基金supported by National Natural Science Foundation of China (No.81230068, and No.81102089)the Natural Science Foundation of Jiangsu Province (No.BK2011773)+3 种基金the Key Program for Basic Research of Jiangsu Provincial Department of Education (No.12KJA330002,and No.11KJB330002)Jiangsu Provincial Graduates Innovative Project (CXZZ12_0594)the Qing Lan Project of Jiangsu Provincial Department of Educationthe Priority Academic Program Development of Jiangsu Higher Education Institution (Public Health and Preventive Medicine)
文摘Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women (approximately 4:1). Here, we summarize the bladder cancer-related risk factors, including environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk factors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study (GWAS) has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction studies need to be conducted to provide more information for the etiology of bladder cancer.
基金Supported by the ARRS Project L1-5456(Control of Harmful Cyanobacteria Bloom in Fresh-Water Bodies)LIFE+Project:LIFE12 ENV/SI/00083 LIFE Stop CyanoBloom
文摘The increasing occurrence of cyanobacterial blooms in water bodies is a serious threat to the environment. Efficient in-lake treatment methods for the control of cyanobacteria proliferation are needed, their in-vivo detection to obtain a real-time response to their presence, as well as the information about their physiological state after the applied treatment. In-vivo fluorescence measurements of photosynthetic pigments have proved to be effective for quantitative and qualitative detection of phytoplankton in a water environment. In the experiment, chlorophyll and phycocyanin fluorescence sensors were used concurrently to detect stress caused by electrochemical oxidation applying an electrolytic cell equipped with borondoped diamond electrodes on a laboratory culture of cyanobacteria Microcystis aeruginosa PCC 7806. The inflicted injuries were reflected in a clear transient increase in the phycocyanin fluorescence signal(for 104 %? 43%) 24 h after the treatment, which was not the case for the chlorophyll fluorescence signal. In the next 72 h of observation, the fluorescence signals decreased(on 40% of the starting signal) indicating a reduction of cell number, which was confirmed by cell count(24% reduction of the starting concentration) and analysis of extracted chlorophyll and phycocyanin pigment. These results demonstrate the viability of the combined application of two sensors as a useful tool for in-vivo detection of induced stress, providing real-time information needed for the evaluation of the efficiency of the in-lake treatment and decision upon the necessity of its repetition. The electrochemical treatment also resulted in a lower free microcystins concentration compared to control.
基金the National Key R&D Program of China(Grants No.2018YFC1313100 and No.2018YFC1313102)the National Natural Science Foundation of China(Grants No.81773538 and No.81773539)Collaborative Innovation Center for Cancer Personalized Medicine,and the Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to investigate the aggregated genetic effects of single nucleotide polymorphisms(SNPs)assigned to candidate genes.The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses.Gene expression was calculated using databases obtained from The Cancer Genome Atlas(TCGA)and The Gene Expression Omnibus(GEO).Kaplan‐Meier plotter was used to evaluate the association between gene expression with gastric cancer survival.Tumor Immune Estimation Resource 2.0(TIMER 2.0)was applied to determine the correlation between selected gene expression and the immune cell infiltration degree.We identified that the G allele of rs2990912 in KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 expression was related to immune cell infiltration and positively correlated with PD-L1 expression.Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility,which may provide important insights into the diagnosis,prognosis,and treatment of gastric cancer.
文摘Although tobacco and alcohol consumption are two common risk factors of head and neck cancer (HNC), other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Human DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic variants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms (SNPs) in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly increased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus interactions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway-based analyses of DNA repair genes derived from genome-wide association studies (GWASs) in HNC are needed.
文摘Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.
基金supported by the Nanjing Social Supporting Department and Social Supporting Ministry of Jiangsu Province granted from 2018 to 2020,and the Nanjing TANTICA Co.Ltd(grant no.2018LC01.1).
文摘Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. Here, LC-associated hypomethylation in alpha-1,3-fucosyltransferase VII (FUT7) is identified via the Illumina 850K array in a discovery study and validated by mass spectrometry in two independent casecontrol studies with blood samples from 1720 LC patients (86.8% LC at stage I, blood is collected before surgery and treatment) and 3143 healthy controls. Compared to the controls, blood-based FUT7 hypomethylation is identified in LC patients at stage I, and even in LC patients with malignant nodules ≤1 cm and in patients with adenocarcinoma in situ. Gender plays a role in the LC-associated FUT7 hypomethylation in blood, which is more significant in males than in females. We also reveal that FUT7 hypomethylation in LC could be enhanced by the advanced stage of cancer, involvement of lymph nodes, and larger tumor size. Based on a large sample size and semi-quantitative methods, our study reveals a strong association between blood-based FUT7 hypomethylation and LC, suggesting that methylation signatures in blood may be a group of potential biomarkers for detection of early-stage LC.
基金supported by the Slovenian Research Agency(Research Programme P1-0245ARRS:Ecotoxicology,Toxicogenomics and Carcinogenesis)Research Project L1-5456(Control of harmful cyanobacterial bloom in freshwater bodies),with co-funding from the Ministry of Defence,Administration for Civil Protection and Disaster Relief(Contract No URSZR 4300-1117/2009-1)the framework of the Life+Project(LIFE12ENV/SI/783 LIFE Stop Cyanobloom)
文摘Cyanobacterial blooms are global phenomena that can occur in calm and nutrient-rich(eutrophic) fresh and marine waters. Human exposure to cyanobacteria and their biologically active products is possible during water sports and various water activities, or by ingestion of contaminated water. Although the vast majority of harmful cyanobacterial products are confined to the interior of the cells, these are eventually released into the surrounding water following natural or artificially induced cell death. Electrochemical oxidation has been used here to damage cyanobacteria to halt their proliferation, and for microcystin degradation under in-vitro conditions. Partially spent Jaworski growth medium with no addition of supporting electrolytes was used. Electrochemical treatment resulted in the cyanobacterial loss of cell-buoyancy regulation, cell proliferation arrest, and eventual cell death. Microcystin degradation was studied separately in two basic modes of treatment: batch-wise flow, and constant flow, for electrolytic-cell exposure. Batch-wise exposure simulates treatment under environmental conditions, while constant flow is more appropriate for the study of boron-doped diamond electrode efficacy under laboratory conditions. The effectiveness of microcystin degradation was established using high-performance liquid chromatography–photodiode array detector analysis, while the biological activities of the products were estimated using a colorimetric protein phosphatase-1 inhibition assay. The results indicate potential for the application of electro-oxidation methods for the control of bloom events by taking advantage of specific intrinsic ecological characteristics of bloom-forming cyanobacteria. The applicability of the use of boron-doped diamond electrodes in remediation of water exposed to cyanobacteria bloom events is discussed.
基金supported by the National Natural Science Foundation of China (31622057)
文摘Three immunizing haptens of bisphenol A(BPA), including two new haptens, were used to produce highly sensitive and specific polyclonal antibodies. The spacer arms of haptens for coupling to the protein carrier were located at different positions in BPA, and different length spacer arms were tested. Highly sensitive polyclonal antibodies were obtained and characterized using indirect competitive enzyme-linked immunosorbent assay(ic ELISA). Under optimized conditions, the half maximal inhibitory concentration(IC50) value of the best polyclonal antibody was 2.1 mg·L^(-1), based on coating heterogeneous antigens, and this optimal polyclonal antibody was highly sensitive toward BPA and displayed negligible crossreactivity with bisphenol B and bisphenol E. A sensitive ic ELISA method utilizing the polyclonal antibody was developed for the determination of BPA in milk. In spiked samples(5, 10 and 20 mg·L^(-1)), the recovery ranged from 80% to 102% with a coefficient of variation(CV) value below 15.8%. The limit of detection of ic ELISA was1.95 mg·L^(-1). These results indicate that the ic ELISA method is suitable for the detection of BPA in milk.
文摘What is already known on this topic?The global efforts to address the hepatitis C virus(HCV)are progressing,but there are still significant gaps in the diagnosis and treatment of HCV,leading to an increasing number of deaths related to HCV.What is added by this report?An extensive investigation was conducted to assess HCV RNA diagnosis,treatment uptake,and associated factors among individuals infected with HCV within Jiangsu Province.The study encompassed a large geographical area and utilized a substantial sample size.What are the implications for public health practice?Implementing focused interventions to improve the timely diagnosis of HCV RNA and increase the uptake of HCV treatment could effectively reduce the future burden of HCV-related health problems,deaths,and healthcare expenses.This is essential for achieving the global target of eliminating hepatitis C.
