Ureteral procedures and complications (15)Bladder and Urothelial Cancer Treatments (13)Pediatric Urology and Nephrology Studies (10)Ferroptosis and cancer prognosis (9)Genetic Associations and Epidemiology (7)
Unhealthy diets (e.g., higher red meat consumption) and tobacco exposure are major risk factors for colorectal cancer (CRC), contributing the toxic substances exposure of polycyclic aromatic hydrocarbons (PAHs). However, the genetic regulation of PAHs metabolism-related genes involved in CRC susceptibility remains unexplored. To address this gap, we performed a meta-analysis using cross-ancestry genome-wide data, including East Asian populations (Chinese: N = 1150, N = 1342; Japanese: N = 6692, N = 27,178) and European (N = 78,473, N = 107,143) to evaluate the genetic association of 47 PAHs-metabolism-related genes with CRC risk. Expression patterns were derived from Nanjing ColoRectal Cancer cohort (NJCRC) and public datasets, including a total of 828 bulk RNA-Seq samples, 62 samples for cell-type-specific expression samples, and 50 paired protein validation samples. Finally, we observed that rs7927381 C > T in GSTP1 was associated with reduced CRC risk (odds ratio (OR) = 0.94, 95% confidence interval (CI) = 0.92-0.96, P = 1.90 × 10). Intriguingly, it downregulated the GSTP1 expression specifically in plasmablast cells. This effect may be attributed to its location in the DNA-hypersensitive regulatory region with enhancer and promoter activity, which could alter transcription factor binding. Notably, both GSTP1 mRNA and protein level were upregulated in CRC tissues, suggesting its elevation may influence PAHs metabolism through the oxidative phosphorylation and ribosome biological processes, promoting carcinogenesis. In conclusion, we identified GSTP1 rs7927381 as a cross-ancestry genetic variant affecting CRC risk through influencing PAHs metabolizing, offering new insights into the genetic mechanisms underlying CRC.
Sensitization to common foods is typically considered clinically irrelevant in individuals without symptomatic food allergies. However, recent studies found an association between IgE specific to the mammalian oligosaccharide galactose-α-1,3-galactose and cardiovascular disease (CVD). The aims of this study are to determine whether common food sensitization is associated with early vascular aging (EVA) and to examine whether healthier lifestyle behaviors modifies the association in individuals without CVD. This was a cross-sectional, population-based study of 2788 American participants aged 30 years or older without cardiovascular disease. Total and specific IgE levels for common foods were measured. EVA was defined based on the 10th percentile of the difference between chronological age (CA) and vascular age (VA). Logistic regression models were employed to assess the associations between food sensitization and EVA, and whether healthy lifestyle modified the association. Poisson regression models, ordinal logistic regression models, and linear regressions were performed as sensitivity analysis. Sensitization to at least one food allergen associated with an increased risk of EVA (odds ratio [OR] 1.91 [95% confidence interval (CI), 1.1 to 3.3]). Milk sensitization demonstrated the most robust association (OR 7.18, [95% CI, 2.5 to 20.62]). Additionally, moderate to vigorous activities (MVA) (OR 0.33 [95% CI, 0.11 to 0.97]) and sufficient sleep duration (OR, 0.21 [95% CI, 0.07 to 0.65]) mitigate the association between food sensitization and EVA. Similar results were presented in Poisson regression models, ordinal logistic regression models, and linear regressions. The findings that common foods sensitization is independently associated with EVA, and that MVA and adequate sleep duration mitigate the association, have significant public health implications. Further research is needed to elucidate the mechanisms.
Allergy to galactose-α-1,3-galactose (alpha-gal) is associated with immediate allergic manifestations and premature degeneration of the prosthesis in patients who receive bovine- or porcine-derived bioprosthetic valves. Here, we report a 72-year-old man with atrial fibrillation, aortic regurgitation, and severe alpha-gal allergy who presented for consideration of aortic valve replacement. He was premedicated with antihistamines and steroids and underwent aortic valve replacement with 25-mm INSPIRIS aortic valve (Edwards Lifesciences) and left atrial appendage occlusion with 40-mm AtriClip device (AtriCure), without immediate or short-term complications.
Early diagnosis is paramount for enhancing survival rates and prognosis in the context of malignant diseases. Hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths worldwide, poses significant challenges for its early detection. In this study, we present an innovative approach which contributed to the early diagnosis of HCC. By lanthanide encoding signal amplification to map glycan-linkages at the single-cell level, the minute quantities of "soft" glycan-linkages on single cell surface were converted into "hard" elemental tags through the use of an MS2 signal amplifier. Harnessing the power of lanthanides encoded within MS2, we achieve nearly three orders of magnitude signal amplification. These encoded tags are subsequently quantified using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS). Linear discriminant analysis (LDA) identifies seven specific glycan-linkages (α-2,3-Sia, α-Gal, α-1,2-Fuc, α-1,6-Fuc, α-2,6-Sia, α-GalNAc, and Gal-β-1,3-GalNAc) as biomarkers. Our methodology is initially validated at the cellular level with 100% accuracy in discriminating between hepatic carcinoma HepG2 cells and their normal HL7702 cells. We apply this approach to quantify and classify glycan-linkages on the surfaces of 55 clinical surgical HCC specimens. Leveraging these seven glycan-linkages as biomarkers, we achieve precise differentiation between 8 normal hepatic specimens, 40 early HCC specimens, and 7 colorectal metastasis HCC specimens. This pioneering work represents the first instance of employing single-cell glycan-linkages as biomarkers promising for the early diagnosis of HCC with a remarkable 100% predictive accuracy rate, which holds immense potential for enhancing the feasibility and precision of HCC diagnosis in clinical practice.