<div>Abstract<p>Advanced glycation end-products (AGEs) are implicated in the pathogenesis of several chronic diseases including cancer. AGEs are produced endogenously but can also be consumed from foods. AGE formation in food is accelerated during cooking at high temperatures. Certain high fat or highly processed foods have high AGE values. The objective of the study was to assign and quantify N<sup>ε</sup>-carboxymethyl-lysine (CML)-AGE content in food and investigate the association between dietary AGE intake and breast cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The study included women enrolled in the intervention arm who were cancer-free at baseline and completed a baseline questionnaire and food frequency questionnaire (DQX). CML-AGE values were assigned and quantified to foods in the DQX using a published AGE database. Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer among all women, and stratified by race/ethnicity, invasiveness of disease, and hormone receptor status. After a median 11.5 years of follow-up, 1,592 women were diagnosed with breast cancer. Higher CML-AGE intake was associated with increased risk of breast cancer among all women (HR<sub>Q5VSQ1</sub>, 1.30; 95% CI, 1.04–1.62; <i>P</i><sub>trend</sub> = 0.04) and in non-Hispanic white women (HR<sub>T3VST1</sub>, 1.21; 95% CI, 1.02–1.44). Increased CML-AGE intake was associated with increased risk of <i>in situ</i> (HR<sub>T3VST1</sub>, 1.49; 95% CI, 1.11–2.01) and hormone receptor–positive (HR<sub>T3VST1</sub>, 1.24; 95% CI, 1.01–1.53) breast cancers. In conclusion, high intake of dietary AGE may contribute to increased breast cancer.</p></div>
This study aimed to evaluate AZD2816, a variant-updated COVID-19 vaccine expressing the full-length SARS-CoV-2 beta (B.1.351) variant spike protein that is otherwise similar to AZD1222 (ChAdOx1 nCoV-19), and AZD1222 as third-dose boosters.
Fructose-1, 6-bisphosphate aldolases (FBA) are cytoplasmic glycolytic enzymes, which despite lacking identifiable secretion signals, have also been found localized to the surface of several bacteria where they bind host molecules and exhibit non-glycolytic functions. Neisseria meningitidis is an obligate human nasopharyngeal commensal, which has the capacity to cause life-threatening meningitis and septicemia. Recombinant native N. meningitidis FBA was purified and used in a coupled enzymic assay confirming that it has fructose bisphosphate aldolase activity. Cell fractionation experiments showed that meningococcal FBA is localized both to the cytoplasm and the outer membrane. Flow cytometry demonstrated that outer membrane-localized FBA was surface-accessible to FBA-specific antibodies. Mutational analysis and functional complementation was used to identify additional functions of FBA. An FBA-deficient mutant was not affected in its ability to grow in vitro, but showed a significant reduction in adhesion to human brain microvascular endothelial and HEp-2 cells compared to its isogenic parent and its complemented derivative. In summary, FBA is a highly conserved, surface exposed protein that is required for optimal adhesion of meningococci to human cells.
Abstract Objective: Results of studies examining the association between a plant-based diet or animal food intake and prostate cancer have been mixed. Few studies have focused on aggressive prostate cancer in a racially diverse population. We examined the association between healthy and unhealthy plant-based and animal-based diet scores and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project, a case-only study of Black and White men in the United States. Methods: Eighteen food groups were created and classified as healthy plant foods, unhealthy plant foods, or animal foods using dietary data collected from an interviewer-administered modified version of the National Cancer Institute Diet History Questionnaire among 909 Black and 991 White men with a histologically confirmed diagnosis of prostate cancer. High aggressive prostate cancer (n=332) was defined as Gleason sum ≥8; or PSA> 20ng/ml; or Gleason sum ≥7 and clinical stage T3-T4, and the comparison group was all other prostate cancer cases (n=1,568). Logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (95% CI) for high aggressive prostate cancer by tertiles of dietary pattern scores. Results: A decreased odds of aggressive prostate cancer was observed among men in the upper compared to the bottom tertile for healthy plant-based diet score (OR: 0.82, 95% CI: 0.58, 1.15) and unhealthy plant-based diet score (OR: 0.89, 95%CI: 0.63, 1.25) while an increased odds was observed comparing extreme tertiles of the animal-based diet score (OR: 1.17. 95% CI: 0.84-1.65) after adjustment for multiple covariates, though confidence intervals were imprecise and not statistically significant. Associations tended to be stronger among White men than among Black men; e.g., for the animal-based diet score, ORs (95% CIs) were 1.41 (0.86, 2.37) and 1.02 (0.63, 1.66) for White and Black men, respectively. Conclusions: Consuming a plant-based dietary pattern may be associated with lower odds of aggressive prostate cancer while an animal-based dietary pattern may be associated with higher odds, though associations were weak and not statistically significant. Keywords: Healthy plant-based diet, unhealthy plant-based diet, animal-based diet, aggressive prostate cancer, racial disparities Conflict of interest: None Funding: PCaP is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. This research was made possible in part by Grant Numbers R01-CA259415 from NIH-NCI and T32-GM081740 from NIH-NIGMS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH. Citation Format: Jessica Sainyo, Susan E. Steck, Longgang Zhao, L. Joseph Su, Lenore Arab, David Turner, Ebonee N. Butler, Jeannette T. Bensen, Elizabeth T.H. Fontham, James L. Mohler. Associations between plant- and animal-based dietary patterns and aggressive prostate cancer in the North Carolina-Louisiana prostate cancer project (PCaP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2172.
Since 2009, increases in the incidence of invasive meningococcal disease have occurred in the United Kingdom due to a sublineage of the Neisseria meningitidis serogroup W ST-11 clonal complex (hereafter, the "original UK strain"). In 2013, a descendent substrain (hereafter, the "2013 strain") became the dominant disease-causing variant. Multiple outer-membrane proteins of meningococci are subject to phase-variable switches in expression due to hypermutable simple-sequence repeats. We investigated whether alterations in phase-variable genes may have influenced the relative prevalence of the original UK and 2013 substrains, using multiple disease and carriage isolates.Repeat numbers were determined by either bioinformatics analysis of whole-genome sequencing data or polymerase chain reaction amplification and sizing of fragments from genomic DNA extracts. Immunoblotting and sequence-translation analysis was performed to identify expression states.Significant increases in repeat numbers were detected between the original UK and 2013 strains in genes encoding PorA, NadA, and 2 Opa variants. Invasive and carriage isolates exhibited similar repeat numbers, but the absence of pilC gene expression was frequently associated with disease.Elevated repeat numbers in outer-membrane protein genes of the 2013 strain are indicative of higher phase-variation rates, suggesting that rapid expansion of this strain was due to a heightened ability to evade host immune responses during transmission and asymptomatic carriage.
The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered.
ABSTRACT A study of meningococcal carriage dynamics was performed with a cohort of 190 first-year students recruited from six residential halls at Nottingham University, United Kingdom. Pharyngeal swabs were obtained on four occasions between November 2008 and May 2009. Direct plating and culture on selective media were succeeded by identification and characterization of meningococci using PCR-based methodologies. Three serogroup Y clones and one serogroup 29E clone were highly prevalent in particular residential halls in November 2008, which is indicative of rapid clonal expansion since the start of the academic year. Persistent carriage of the same meningococcal strain for at least 5 to 6 months was observed in 45% of carriers, with infrequent evidence of antigenic variation in PorA. Sequential carriage of heterologous meningococcal strains occurred in 36% of carriers and involved strains with different capsules and antigenic variants of PorA and FetA in 83% of the cases. These clonal replacement strains also exhibited frequent differences in the presence and antigenic structures of two other surface proteins, NadA and HmbR. This study highlights the low level of antigenic variation associated with persistent carriage but, conversely, the importance of alterations in the repertoire of antigenic variants for sequential carriage of meningococcal strains. Rapid clonal expansion of potentially pathogenic strains in residential halls has implications for the implementation of public health interventions in university populations.
Supplementary Figure 1 Legend from MicroRNA-Mediated Inhibition of Prostate-Derived Ets Factor Messenger RNA Translation Affects Prostate-Derived Ets Factor Regulatory Networks in Human Breast Cancer
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