Associations between colorectal cancer risk and dietary intake of tomato, tomato products, and lycopene: evidence from a prospective study of 101,680 US adults

BackgroundPrevious epidemiological studies have yielded inconsistent results regarding the effects of dietary tomato, tomato products, and lycopene on the incidence of colorectal cancer (CRC), possibly due to variations in sample sizes and study designs.MethodsThe current study used multivariable Cox regression, subgroup analyses, and restricted cubic spline functions to investigate correlations between CRC incidence and mortality and raw tomato, tomato salsa, tomato juice, tomato catsup, and lycopene intake, as well as effect modifiers and nonlinear dose-response relationships in 101,680 US adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.ResultsDuring follow-up 1100 CRC cases and 443 CRC-specific deaths occurred. After adjustment for confounding variables, high consumption of tomato salsa was significantly associated with a reduced risk of CRC incidence (hazard ratio comparing the highest category with the lowest category 0.8, 95% confidence interval 0.65–0.99, p for trend = 0.039), but not with a reduced risk of CRC mortality. Raw tomatoes, tomato juice, tomato catsup, and lycopene consumption were not significantly associated with CRC incidence or CRC mortality. No potential effect modifiers or nonlinear associations were detected, indicating the robustness of the results.ConclusionIn the general US population a higher intake of tomato salsa is associated with a lower CRC incidence, suggesting that tomato salsa consumption has beneficial effects in terms of cancer prevention, but caution is warranted when interpreting these findings. Further prospective studies are needed to evaluate its potential effects in other populations

The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID‐19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran’s Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results.ResultsWe found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92–0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy.ConclusionsOur study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels

Development and Application of Loop-Mediated Isothermal Amplification Assays for Rapid Visual Detection of cry2Ab and cry3A Genes in Genetically-Modified Crops

The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs) containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP) method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM) crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field

Associations between colorectal cancer risk and dietary intake of tomato, tomato products, and lycopene: evidence from a prospective study of 101,680 US adults

Background Previous epidemiological studies have yielded inconsistent results regarding the effects of dietary tomato, tomato products, and lycopene on the incidence of colorectal cancer (CRC), possibly due to variations in sample sizes and study designs.Methods The current study used multivariable Cox regression, subgroup analyses, and restricted cubic spline functions to investigate correlations between CRC incidence and mortality and raw tomato, tomato salsa, tomato juice, tomato catsup, and lycopene intake, as well as effect modifiers and nonlinear dose-response relationships in 101,680 US adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.Results During follow-up 1100 CRC cases and 443 CRC-specific deaths occurred. After adjustment for confounding variables, high consumption of tomato salsa was significantly associated with a reduced risk of CRC incidence (hazard ratio comparing the highest category with the lowest category 0.8, 95% confidence interval 0.65-0.99, p for trend = 0.039), but not with a reduced risk of CRC mortality. Raw tomatoes, tomato juice, tomato catsup, and lycopene consumption were not significantly associated with CRC incidence or CRC mortality. No potential effect modifiers or nonlinear associations were detected, indicating the robustness of the results.Conclusion In the general US population a higher intake of tomato salsa is associated with a lower CRC incidence, suggesting that tomato salsa consumption has beneficial effects in terms of cancer prevention, but caution is warranted when interpreting these findings. Further prospective studies are needed to evaluate its potential effects in other populations.Funding Agencies|This research was funded by Natural Science Foundation of Sichuan Province, China (Grant No. 2022NSFSC0764) and the Fundamental Research Funds for the Central Universities (Grant No.2022SCU12025 and 2022SCU12020). [2022SCU12025]; Natural Science Foundation of Sichuan Province, China [2022SCU12020]; Fundamental Research Funds for the Central Universities; [2022NSFSC0764]</p

Establishment and Validation of Reference Genes of Brassica napus L. for Digital PCR Detection of Genetically Modified Canola

As an effective tool for genetically modified organism (GMO) quantification in complex matrices, digital PCR (dPCR) has been widely used for the quantification of genetically modified (GM) canola events; however, little is known about the quantification of GM canola events using endogenous reference gene (ERG) characteristics by dPCR. To calculate and quantify the content of GM canola using endogenous reference gene (ERG) characteristics, the suitability of several ERGs of canola, such as cruciferin A (CruA), acetyl-CoA carboxylase (BnAcc), phosphoenolpyruvate carboxylase (PEP), cruciferin storage (BnC1), oleoyl hydrolase (Fat(A)), and high-mobility-group protein I/Y (HMG-I/Y), was investigated by droplet dPCR. BnAcc and BnC1 were more specific and stable in copy number in the genome of Brassica napus L. than the other genes. By performing intra-laboratory validation of the suitability of ERG characteristics for the quantification of GM canola events, the ddPCR methods for BnAcc and BnC1 were comprehensively demonstrated in dPCR assays. The methods could provide technical support for GM labeling regulations

Prognostic value and biological function of LRRN4 in colorectal cancer

Background Several nervous and nerve-related biomarkers have been detected in colorectal cancer (CRC) and can contribute to the progression of CRC. However, the role of leucine-rich repeat neuronal 4 (LRRN4), a recently identified neurogenic marker, in CRC remains unclear. Methods We examined the expression and clinical outcomes of LRRN4 in CRC from TCGA-COREAD mRNA-sequencing datasets and immunohistochemistry in a Chinese cohort. Furthermore, colony formation, flow cytometry, wound healing assays and mouse xenograft models were used to investigate the biological significance of LRRN4 in CRC cell lines with LRRN4 knockdown or overexpression in vitro and in vivo. In addition, weighted coexpression network analysis, DAVID and western blot analysis were used to explore the potential molecular mechanism. Results We provide the first evidence that LRRN4 expression, at both the mRNA and protein levels, was remarkably high in CRC compared to controls and positively correlated with the clinical outcome of CRC patients. Specifically, LRRN4 was an independent prognostic factor for progression-free survival and overall survival in CRC patients. Further functional experiments showed that LRRN4 promoted cell proliferation, cell DNA synthesis and cell migration and inhibited apoptosis. Knockdown of LRRN4 can correspondingly decrease these effects in vitro and can significantly suppress the growth of xenografts. Several biological functions and signaling pathways were regulated by LRRN4, including proteoglycans in cancer, glutamatergic synapse, Ras, MAPK and PI3K. LRRN4 knockdown resulted in downregulation of Akt, p-Akt, ERK1/2 and p-ERK1/2, the downstream of the Ras/MAPK signaling pathway, overexpression of LRRN4 leaded to the upregulation of these proteins. Conclusions Our results suggest that LRRN4 could be a biological and molecular determinant to stratify CRC patients into distinct risk categories, and mechanistically, this is likely attributable to LRRN4 regulating several malignant phenotypes of neoplastic cells via RAS/MAPK signal pathways.Funding Agencies|Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972592]; 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYGD20007, ZYJC18011]; Space Medical Experiment Project of China Manned Space Program [HYZHXM01004]</p

The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID-19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochrans Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results.ResultsWe found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92-0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy.ConclusionsOur study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.Funding Agencies|This study was supported by Natural Science Foundation of Sichuan Province, China (Grant No. 2022NSFSC0764) and Post-Doctor Research Project of Sichuan University (Grant Nos.2022SCU12025 and 2022SCU12020). [2022SCU12025]; Natural Science Foundation of Sichuan Province, China [2022SCU12020]; Post-Doctor Research Project of Sichuan University; [2022NSFSC0764]</p

DataSheet_2_The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study.xlsx

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID‐19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran’s Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results.ResultsWe found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92–0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy.ConclusionsOur study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.</p