Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerization

While changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumour DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumour. Matched tumour, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select epithelial cells from normal tissue, and neoplastic cells from tumour for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. We identified substantially more CpG loci that were differentially methylated between contralateral-normal and tumour (63,271 CpG loci q \u3c 0.01), than between ipsilateral-normal and tumour (38,346 CpG loci q \u3c 0.01). We identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p \u3c 0.01). In this comparison, hypomethylated loci were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3 and hypermethylated loci were significantly enriched for CpG island shore regions. In addition, progression of shore hypermethylation was observed in tumours compared to matched ipsilateral normal tissue, and these alterations tracked to several well-established tumour suppressor genes. Our results indicate an epigenetic field effect in surrounding histologically normal tissue. This work offers an opportunity to focus investigations of early DNA methylation alterations in breast carcinogenesis and potentially develop epigenetic biomarkers of disease risk

The B subunits of cholera and Escherichia coli heat-labile toxins enhance the immune responses in mice orally immunised with a recombinant live P-fimbrial vaccine for avian pathogenic E. coli

This study aimed to investigate the adjuvant effect of recombinant attenuated Salmonella expressing cholera toxin B subunit (CTB) and Escherichia coli heat-labile enterotoxin B subunit (LTB) for the P-fimbriae subunit-based vaccine of avian pathogenic E. coli (APEC) in a murine model. The PapA-specific sIgA and IgG responses were significantly enhanced after immunisation with the Salmonella-PapA vaccine in the presence of CTB or LTB. The group immunised with the Salmonella-LTB strain promoted Th1-type immunity, whereas that immunised with the Salmonella-CTB strain produced Th2-type immunity. We concluded that both Salmonella-CTB and -LTB strains can enhance the immune response to PapA, and that the LTB strain may be a more effective adjuvant for APEC vaccination, which requires higher Th1-type immunity for protection. Thus, our findings provide evidence that immunisation with an adjuvant, LTB, is one of the strategies of developing effective vaccines against P-fimbriated APEC

Phytochemicals as novel agents for the induction of browning in white adipose tissue

Obesity and its associated metabolic syndrome continue to be a health epidemic in westernized societies and is catching up in the developing world. Despite such increases, little headway has been made to reverse adverse weight gain in the global population. Few medical options exist for the treatment of obesity which points to the necessity for exploration of anti-obesity therapies including pharmaceutical and nutraceutical compounds. Defects in brown adipose tissue, a major energy dissipating organ, has been identified in the obese and is hypothesized to contribute to the overall metabolic deficit observed in obesity. Not surprisingly, considerable attention has been placed on the discovery of methods to activate brown adipose tissue. A variety of plant-derived, natural compounds have shown promise to regulate brown adipose tissue activity and enhance the lipolytic and catabolic potential of white adipose tissue. Through activation of the sympathetic nervous system, thyroid hormone signaling, and transcriptional regulation of metabolism, natural compounds such as capsaicin and resveratrol may provide a relatively safe and effective option to upregulate energy expenditure. Through utilizing the energy dissipating potential of such nutraceutical compounds, the possibility exists to provide a therapeutic solution to correct the energy imbalance that underlines obesity

Do Birth Outcomes of Parents With Discordant vs. Concordant Self-Reported Race/Ethnicity Differ When Accounting for Social Determinants of Health?

Purpose of Study Differences in maternal race, social determinants of health and adverse life events are all linked to disparities in birth outcomes. There is a paucity of data on birth outcomes of discordant race/ethnicity parents. Our objective was to identify associations between self-reported parental race/ethnicity, socioeconomic characteristics and adverse life events with birth outcomes to parents of discordant race/ ethnicities. Methods Used This is a cross-sectional analysis (2016-2020) of survey data of parents (≥18 years) of singleton live-born infants. Outcomes including NICU admission (NICU), small for gestational age and preterm birth (PTB, \u3c37 weeks) were obtained from birth certificate data and analyzed by selfreported parental race/ethnicity. Parents selecting White/Caucasian were categorized as White. Non-White category included any of the following: Black, Hispanic, or Other (American Indian/Alaskan native/Hawaiian/Pacific Islander/ Asian). Covariates included: adverse life events, lifestyle behaviors, high-risk pregnancy conditions, and other sociodemographic data. Summary of Results 362 mother-father dyads were analyzed and grouped as (W=White, NW=Non-White, M=Mother, F=Father): WM-NWF (9%), NWM-WF (9%), WM-WF (37%) and NWM-NWF (45%). WM-WF had higher rates of parental education, exercise, substance use and maternal adverse life events (p\u27s\u3c0.05). NWM-NWF parents were more likely to be foreign born, insured by Medicaid and have a high-risk pregnancy (p\u27s\u3c0.05). In adjusted analyses, WM-NWF had higher odds of NICU [OR 3.75 (95% CI 1.22 - 11.51)] and PTB [4.38 (95% CI 1.07 - 17.87)] compared to WM-WF. NWM-WF and NWM-NWF did not differ from WM-WF in odds of adverse birth outcomes. Conclusions Infants born to WM-NWF have higher odds of NICU & PTB compared to WM-WF. We speculate that increased stress WM-NWF dyads face may increase risk of these adverse birth outcomes. Our results suggest self-reported parental race/ethnicity should be assessed prenatally to provide additional support as needed to potentially mitigate the observed differences