BACKGROUND Colorectal cancer(CRC)remains one of the leading causes of cancer-related morbidity and mortality worldwide.Growing evidence suggests that gut microbial dysbiosis plays a crucial role in tumorigenesis and c...BACKGROUND Colorectal cancer(CRC)remains one of the leading causes of cancer-related morbidity and mortality worldwide.Growing evidence suggests that gut microbial dysbiosis plays a crucial role in tumorigenesis and can influence therapeutic responses.AIM To explore the associations between serum S100A12 and soluble CD14(sCD14)levels and gut microbiota alterations in patients with CRC,and to assess the predictive utility of these biomarkers in forecasting chemotherapy response.METHODS A retrospective analysis was conducted on 104 patients diagnosed with advanced CRC(CRC group)and 104 age-matched and sex-matched healthy controls.Serum concentrations of S100A12 and sCD14 were measured using enzyme-linked immunosorbent assay.Fecal samples collected before chemotherapy were subjected to 16S rRNA sequencing to profile gut microbial composition.Pearson correlation analysis was used to evaluate the relationship between biomarker levels and microbial abundance.Receiver operating characteristic(ROC)curves were used to assess the predictive performance of S100A12 and sCD14 for chemotherapy response.RESULTS CRC patients exhibited significantly higher serum levels of S100A12 and sCD14 compared to healthy individuals(P<0.05).Patients with moderate to severe gut dysbiosis showed the highest elevations of these biomarkers(P<0.05).Elevated levels of S100A12 and sCD14 were positively correlated with Fusobacterium nucleatum and Prevotella abundance,and negatively correlated with Faecalibacterium prausnitzii and Akkermansia muciniphila(P<0.05).Both biomarkers significantly decreased following chemotherapy(P<0.05).Non-responders to chemotherapy had higher pre-treatment levels of S100A12 and sCD14 compared to responders(P<0.05).Combined ROC analysis showed improved diagnostic accuracy compared to either marker alone.CONCLUSION Serum S100A12 and sCD14 levels are closely associated with gut microbiota imbalance and chemotherapy response in CRC patients.These markers may serve as promising predictive indicators for treatment efficacy and offer potential value in individualized treatment strategies.展开更多
This study aimed to identify the worst“bad actors”in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S.population,using weighted quantile sum(WQS)modeling with stratification by ra...This study aimed to identify the worst“bad actors”in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S.population,using weighted quantile sum(WQS)modeling with stratification by race/ethnicity.We conducted a comprehensive cross-sectional analysis of mixtures of pollutants in National Health and Nutrition Examination Survey datasets:(1)33,979 adults with blood levels of cadmium(Cd),lead(Pb),and mercury,including subsets with measurements of per-/polyfluoroalkyl substances(PFAS),and polychlorinated biphenyls(PCBs)/polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs);and(2)7360 adults with measurements of telomeres,Cd,and Pb.Multivariable-adjusted WQS regression examined associations between WQS mixture indices and liver injury(alanine aminotransferase(ALT)-elevation),advanced liverfibrosis(LF),and telomere length.WQSmetal indices were associated with advanced-LF in all racial/ethnic groups.The top contributor was Cd in the total population and in non-Hispanic Whites(NHW),while Pb was the top contributor in non-Hispanic Blacks(NHB).The WQSmetal-PCB-PCDD/F index was associated with ALT-elevation,with PCB126,Cd and Pb as main contributors;the odds ratio(OR)per decile was 1.50(95%CI,1.26–1.78),while the OR per decile of the WQSmetal-PFAS index was 1.03(95%CI,0.98–1.05),not significant.WQS_(metal indices)were associated with shorter telomeres.Cd was main contributor associated with advanced-LF in NHW,while Pb was the major bad actor in NHB,suggesting that NHB may be especially susceptible to Pb toxicity.Metals were associated with shorter telomeres.Metal and PCB/PCDD/F mixtures were associated with ALT-elevation.Heavy metals and organic chemicals may contribute to liver-related morbidity and healthcare disparities.展开更多
AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided ...AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided into two groups:ethanol-fed group (group E) and control group (group C). Group E was fed with ethanol(5-12 g x kg(-1) x d(-1)) and group C received dextrose instead of ethanol. Rats of the two groups were sacrificed at 4 weeks and 8 weeks. Levels of endotoxin and alanine transaminase (ALT) in blood were measured, and liver pathology was observed under light and electronic microscopy. Expressions of LBP and CD14 mRNA in liver tissues were determined by RT-PCR analysis. RESULTS: Plasma endotoxin levels were increased more significantly in group E(129+/-21) ng x L(-1) and (187+/-35) ng x L(-1) at 4 and 8 wk than in control rats(48+/-9) ng x L(-1) and (53+/-11) ng x L(-1), respectively (P【0.05). Mean values of plasma ALT levels were (1867+/-250) nkat x L(-1) and (2450+/-367) nkat x L(-1) in Group E. The values were increased more dramatically in ethanol-fed rats than in Group C after 4 and 8 weeks. In liver section from ethanol-fed rats, there were marked pathological changes (steatosis, cell infiltration and necrosis). In ethanol-fed rats, ethanol administration led to a significant increase in LBP and CD14 mRNA levels compared with the control group (P【0.05). CONCLUSION: Ethanol administration led to a significant increase in endotoxin levels in serum and LBP and CD14 mRNA expressions in liver tissues. The increase of LBP and CD14 mRNA expression might wake the liver more sensitive to endotoxin and liver injury.展开更多
In this paper we aim to analyse temporal variation of CD4 cell counts for HIV-infected individuals under antiretroviral therapy by using statistical methods. This is achieved by resorting to recursive binary regressio...In this paper we aim to analyse temporal variation of CD4 cell counts for HIV-infected individuals under antiretroviral therapy by using statistical methods. This is achieved by resorting to recursive binary regression tree approach [1]?[2]. This approach has made it possible to highlight the existence of several segments of the population of interest described by the interactions between the predictive covariates of the response to the treatment regimen.展开更多
文摘BACKGROUND Colorectal cancer(CRC)remains one of the leading causes of cancer-related morbidity and mortality worldwide.Growing evidence suggests that gut microbial dysbiosis plays a crucial role in tumorigenesis and can influence therapeutic responses.AIM To explore the associations between serum S100A12 and soluble CD14(sCD14)levels and gut microbiota alterations in patients with CRC,and to assess the predictive utility of these biomarkers in forecasting chemotherapy response.METHODS A retrospective analysis was conducted on 104 patients diagnosed with advanced CRC(CRC group)and 104 age-matched and sex-matched healthy controls.Serum concentrations of S100A12 and sCD14 were measured using enzyme-linked immunosorbent assay.Fecal samples collected before chemotherapy were subjected to 16S rRNA sequencing to profile gut microbial composition.Pearson correlation analysis was used to evaluate the relationship between biomarker levels and microbial abundance.Receiver operating characteristic(ROC)curves were used to assess the predictive performance of S100A12 and sCD14 for chemotherapy response.RESULTS CRC patients exhibited significantly higher serum levels of S100A12 and sCD14 compared to healthy individuals(P<0.05).Patients with moderate to severe gut dysbiosis showed the highest elevations of these biomarkers(P<0.05).Elevated levels of S100A12 and sCD14 were positively correlated with Fusobacterium nucleatum and Prevotella abundance,and negatively correlated with Faecalibacterium prausnitzii and Akkermansia muciniphila(P<0.05).Both biomarkers significantly decreased following chemotherapy(P<0.05).Non-responders to chemotherapy had higher pre-treatment levels of S100A12 and sCD14 compared to responders(P<0.05).Combined ROC analysis showed improved diagnostic accuracy compared to either marker alone.CONCLUSION Serum S100A12 and sCD14 levels are closely associated with gut microbiota imbalance and chemotherapy response in CRC patients.These markers may serve as promising predictive indicators for treatment efficacy and offer potential value in individualized treatment strategies.
基金supported by U01OH012263,and U01 OH012622 from the National Institute for Occupational Safety and HealthPCF 604934 from Prevent Cancer Foundation+1 种基金National Institutes of Health(NIH)/National Cancer Institute(NCI)1U01CA288425–0P30 ES023515 from the National Institute of Environmental Health Sciences.
文摘This study aimed to identify the worst“bad actors”in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S.population,using weighted quantile sum(WQS)modeling with stratification by race/ethnicity.We conducted a comprehensive cross-sectional analysis of mixtures of pollutants in National Health and Nutrition Examination Survey datasets:(1)33,979 adults with blood levels of cadmium(Cd),lead(Pb),and mercury,including subsets with measurements of per-/polyfluoroalkyl substances(PFAS),and polychlorinated biphenyls(PCBs)/polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs);and(2)7360 adults with measurements of telomeres,Cd,and Pb.Multivariable-adjusted WQS regression examined associations between WQS mixture indices and liver injury(alanine aminotransferase(ALT)-elevation),advanced liverfibrosis(LF),and telomere length.WQSmetal indices were associated with advanced-LF in all racial/ethnic groups.The top contributor was Cd in the total population and in non-Hispanic Whites(NHW),while Pb was the top contributor in non-Hispanic Blacks(NHB).The WQSmetal-PCB-PCDD/F index was associated with ALT-elevation,with PCB126,Cd and Pb as main contributors;the odds ratio(OR)per decile was 1.50(95%CI,1.26–1.78),while the OR per decile of the WQSmetal-PFAS index was 1.03(95%CI,0.98–1.05),not significant.WQS_(metal indices)were associated with shorter telomeres.Cd was main contributor associated with advanced-LF in NHW,while Pb was the major bad actor in NHB,suggesting that NHB may be especially susceptible to Pb toxicity.Metals were associated with shorter telomeres.Metal and PCB/PCDD/F mixtures were associated with ALT-elevation.Heavy metals and organic chemicals may contribute to liver-related morbidity and healthcare disparities.
基金Supported by the National Natural Science Foundation of China(No.39970719).
文摘AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided into two groups:ethanol-fed group (group E) and control group (group C). Group E was fed with ethanol(5-12 g x kg(-1) x d(-1)) and group C received dextrose instead of ethanol. Rats of the two groups were sacrificed at 4 weeks and 8 weeks. Levels of endotoxin and alanine transaminase (ALT) in blood were measured, and liver pathology was observed under light and electronic microscopy. Expressions of LBP and CD14 mRNA in liver tissues were determined by RT-PCR analysis. RESULTS: Plasma endotoxin levels were increased more significantly in group E(129+/-21) ng x L(-1) and (187+/-35) ng x L(-1) at 4 and 8 wk than in control rats(48+/-9) ng x L(-1) and (53+/-11) ng x L(-1), respectively (P【0.05). Mean values of plasma ALT levels were (1867+/-250) nkat x L(-1) and (2450+/-367) nkat x L(-1) in Group E. The values were increased more dramatically in ethanol-fed rats than in Group C after 4 and 8 weeks. In liver section from ethanol-fed rats, there were marked pathological changes (steatosis, cell infiltration and necrosis). In ethanol-fed rats, ethanol administration led to a significant increase in LBP and CD14 mRNA levels compared with the control group (P【0.05). CONCLUSION: Ethanol administration led to a significant increase in endotoxin levels in serum and LBP and CD14 mRNA expressions in liver tissues. The increase of LBP and CD14 mRNA expression might wake the liver more sensitive to endotoxin and liver injury.
文摘In this paper we aim to analyse temporal variation of CD4 cell counts for HIV-infected individuals under antiretroviral therapy by using statistical methods. This is achieved by resorting to recursive binary regression tree approach [1]?[2]. This approach has made it possible to highlight the existence of several segments of the population of interest described by the interactions between the predictive covariates of the response to the treatment regimen.
