Depleted nitric oxide levels in the human body play a major role in cardiovascular disease pathogenesis. Inorganic nitrate/nitrite (rich dietary sources include beetroot and spinach) can act as a ...nitric oxide donor because nitrate/nitrite can be metabolized to produce nitric oxide.
This review and meta-analysis sought to investigate the role of inorganic nitrate/nitrite in preventing or treating cardiovascular disease risk factors in humans.
Electronic databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Scopus, were searched.
Experimental trials examining the effect of oral inorganic nitrate/nitrite intake on cardiovascular disease risk factors were included for systematic analysis.
Thirty-four studies were included for qualitative synthesis, 23 of which were eligible for meta-analysis. Included studies measured the following outcomes: blood pressure, endothelial function, arterial stiffness, platelet aggregation, and/or blood lipids. Inorganic nitrate intake was found to significantly reduce resting blood pressure (systolic blood pressure: -4.80 mmHg, P < 0.0001; diastolic blood pressure: -1.74 mmHg, P = 0.001), improve endothelial function (flow-mediated dilatation: 0.59%, P < 0.0001), reduce arterial stiffness (pulse wave velocity: -0.23 m/s, P < 0.0001; augmentation index: -2.1%, P = 0.05), and reduce platelet aggregation by 18.9% (P < 0.0001).
Inorganic nitrate consumption represents a simple strategy for targeting cardiovascular disease risk factors. Future studies investigating the long-term effects of inorganic nitrate on cardiovascular disease outcomes are warranted.
ARID1A and PI3-Kinase (PI3K) pathway alterations are common in neoplasms originating from the uterine endometrium. Here we show that monoallelic loss of ARID1A in the mouse endometrial epithelium is ...sufficient for vaginal bleeding when combined with PI3K activation. Sorted mutant epithelial cells display gene expression and promoter chromatin signatures associated with epithelial-to-mesenchymal transition (EMT). We further show that ARID1A is bound to promoters with open chromatin, but ARID1A loss leads to increased promoter chromatin accessibility and the expression of EMT genes. PI3K activation partially rescues the mesenchymal phenotypes driven by ARID1A loss through antagonism of ARID1A target gene expression, resulting in partial EMT and invasion. We propose that ARID1A normally maintains endometrial epithelial cell identity by repressing mesenchymal cell fates, and that coexistent ARID1A and PI3K mutations promote epithelial transdifferentiation and collective invasion. Broadly, our findings support a role for collective epithelial invasion in the spread of abnormal endometrial tissue.
The uterus is an extremely plastic organ that undergoes cyclical remodeling including endometrial regeneration during the menstrual cycle. Endometrial remodeling and regeneration also occur during ...pregnancy and following parturition, particularly in hemochorial implanting species. The mechanisms of endometrial regeneration are not well understood. Endometrial stem/progenitor cells are proposed to contribute to endometrial regeneration in both humans and mice. BrdU label retention has been used to identify potential stem/progenitor cells in mouse endometrium. However, methods are not available to isolate BrdU label-retaining cells (LRC) for functional analyses. Therefore, we employed a transgenic mouse model to identify H2B-GFP LRCs throughout the female reproductive tract with particular interest on the endometrium. We hypothesized that the female reproductive tract contains a population of long-term LRCs that persist even following pregnancy and endometrial regeneration. Endometrial cells were labeled (pulsed) either transplacentally/translactationally or peripubertally. When mice were pulsed transplacentally/translactationally, the label was not retained in the uterus. However, LRCs were concentrated to the distal oviduct and endocervical transition zone (TZ) following natural (i.e., pregnancy/parturition induced) and mechanically induced endometrial regeneration. LRCs in the distal oviduct and endocervical TZ expressed stem cell markers and did not express ERα or PGR, implying the undifferentiated phenotype of these cells. Oviduct and endocervical TZ LRCs did not proliferate during endometrial re-epithelialization, suggesting that they do not contribute to the endometrium in a stem/progenitor cell capacity. In contrast, when mice were pulsed peripubertally long-term LRCs were identified in the endometrial glandular compartment in mice as far out as 9 months post-pulse. These findings suggest that epithelial tissue of the female reproductive tract contains 3 distinct populations of epithelial cells that exhibit stem/progenitor cell qualities. Distinct stem/progenitor-like cells localize to the oviduct, endometrium, and cervix.
Objective: To describe lifestyle behaviors (fruit and vegetable intake, alcohol intake, physical activity, sitting time, smoking, drug use, sleep, sexual health) and health risk factors (body mass ...index, food insecurity, mental health) in a sample of Australian university students. Participants: 3,077 students from the University of Newcastle (UON), Australia (mean age 27.1 ± 9.8 years, 69.4% female) were surveyed in September-October 2017. Methods: Cross-sectional self-report survey, the UON Student Healthy Lifestyle Survey 2017. Results: Participants with unhealthy lifestyle behaviors included; 89.5% not meeting vegetable recommendations, 50.3% exceeding lifetime risk guidelines for alcohol intake, and 38.1% insufficiently physically active. Rates of health risk factors included; 39.6% overweight/obese, 37.6% high or very high risk of psychological distress, and 22.0% food insecure. Conclusions: Rates of unhealthy lifestyle behaviors and related health risk factors were high within the study population, highlighting the importance of ongoing monitoring and prioritization of effective strategies to improve university student health.
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed countries. Coffee is one of the most consumed beverages in the world and has been shown to be ...beneficial in limiting progression in chronic liver disease in general. However, research surrounding the impact of coffee consumption on NAFLD progression is limited. This systematic review aimed to investigate the relationship between coffee consumption and the progression of liver disease, specifically for cases of NAFLD. MEDLINE, EMBASE, CINAHL, the Cochrane Library, and Scopus were searched for published studies that evaluated the effects of coffee consumption on the progression of NAFLD. The results are presented in a narrative synthesis with principal summary measures, including odds ratios,
-values, and differences in mean coffee intake in relation to severity of NAFLD. Five studies met the inclusion criteria and were included in this review. There was no trial evidence among NAFLD patients, rather all studies were of a cross-sectional design. Using the Academy of Nutrition and Dietetics Quality Criteria Checklist, four studies received a positive rating, with the remaining study receiving a neutral rating. Overall, four out of the five studies reported a statistically significant relationship between coffee consumption and the severity of fibrosis. Methods around capturing and defining coffee consumption were heterogeneous and therefore an effective dose could not be elucidated. Results suggest that higher coffee consumption is inversely associated with the severity of hepatic fibrosis in individuals with NAFLD. However, further research is required to elucidate the optimum quantity and form/preparation of coffee required to exert this hepatoprotective role.
Mesenchymal-epithelial transition (MET) is a mechanism of endometrial epithelial regeneration. It is also implicated in adenocarcinoma and endometriosis. Little is known about this process in normal ...uterine physiology. Previously, using pregnancy and menses-like mouse models, MET occurred only as an epithelial damage/repair mechanism. Here, we hypothesized that MET also occurs in other physiological endometrial remodeling events, outside of damage/repair, such as during the estrous cycle and adenogenesis (gland development). To investigate this,
Amhr2-Cre-YFP/GFP
mesenchyme-specific reporter mice were used to track the fate of mesenchymal-derived (MD) cells. Using EpCAM (epithelial marker), EpCAM
+
YFP
+
MD-epithelial cells were identified in all stages of the estrous cycle except diestrus, in both postpartum and virgin mice. EpCAM
+
YFP
+
MD-epithelial cells comprised up to 80% of the epithelia during estrogen-dominant proestrus and significantly declined to indistinguishable from control uteri in diestrus, suggesting MET is hormonally regulated. MD-epithelial cells were also identified during postnatal epithelial remodeling. MET occurred immediately after birth at postnatal day (P) 0.5 with EpCAM
+
GFP
+
cells ranging from negligible (0.21%) to 82% of the epithelia. EpCAM
+
GFP
+
MD-epithelial cells declined during initiation of adenogenesis (P8, avg. 1.75%) and then increased during gland morphogenesis (P14, avg. 10%). MD-epithelial cells expressed markers in common with non-MD-epithelial cells (e.g., EpCAM, FOXA2, ESR1, PGR). However, MD-epithelial cells were differentially regulated postnatally and in adults, suggesting a functional distinction in the two populations. We conclude that MET occurs not only as an epithelial damage/repair mechanism but also during other epithelial remodeling events, which to our knowledge has not been demonstrated in other tissues.
Adults with chronic health conditions need support to manage modifiable risk factors such as physical inactivity and poor diet. Disease-specific websites with health information on physical activity ...and diet quality may be effective in supporting adults in managing their chronic illnesses.
The primary aim of this review was to determine whether using websites with health information can lead to improvements in physical activity levels or diet quality in adults with chronic health conditions.
Randomized controlled trials evaluating the effectiveness of website use on levels of physical activity or diet quality in adults with chronic health conditions were included. MEDLINE, Embase, CINAHL, and the Physiotherapy Evidence Database were searched from the earliest available record until February 2023. Data for outcomes measuring physical activity levels; diet quality; and, where reported, self-efficacy and quality of life were independently extracted by 2 reviewers. The risk of bias was assessed using the Physiotherapy Evidence Database scale, and the overall certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where values were presented as the same unit of measure, postintervention scores were pooled for meta-analysis to yield an overall mean difference (MD). A standardized MD (SMD) was calculated for the pooled data in which different units for the same outcome were used. Individual trial data were described in cases where the data of trials could not be pooled.
A total of 29 trials (N=6418 participants) across 8 different disease groups with intervention periods ranging from 4 weeks to 12 months were included in the analysis. There was moderate-certainty evidence that using websites with health information increased levels of moderate to vigorous physical activity (MD=39 min/wk, 95% CI 18.60-58.47), quality of life (SMD=0.36, 95% CI 0.12-0.59), and self-efficacy (SMD=0.26, 95% CI 0.05-0.48) and high-certainty evidence for reduction in processed meat consumption (MD=1.1 portions/wk, 95% CI 0.70-1.58) when compared with usual care. No differences were detected in other measures of diet quality. There was no increased benefit for website users who were offered additional support.
The use of websites for risk factor management has the potential to improve physical activity levels, quality of life, and self-efficacy as well as reduce processed meat consumption for adults living with chronic health conditions when compared with usual care. However, it remains unclear whether using websites leads to meaningful and long-lasting behavior change.
PROSPERO CRD42021283168; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283168.
Brief interventions are effective in improving health behaviours including alcohol intake, however the effectiveness of brief interventions targeting nutrition outcomes has not been determined. The ...aim of this systematic review was to determine the effectiveness of brief nutrition interventions in adults. Seven databases were searched for RCT/pseudo RCT studies published in English to April 2016, and evaluating brief interventions (i.e. single point of contact) designed to promote change in eating behaviours in healthy adults (≥18 years). Of 4849 articles identified, 45 studies met inclusion criteria. Most studies targeted fruit and/or vegetable intake (n = 21) or fat intake (n = 10), and few targeted diet quality (n = 2). Median follow-up was 3.5 months, with few studies (n = 4) measuring longer-term outcomes (≥12 months). Studies aimed to determine whether a brief intervention was more effective than another brief intervention (n = 30), and/or more effective than no intervention (n = 20), with 17 and 11 studies, respectively, reporting findings to that effect. Interventions providing education plus tailored or instructional components (e.g. feedback) were more effective than education alone or non-tailored advice. This review suggests that brief interventions, which are tailored and instructional, can improve short-term dietary behaviours, however evidence for longer-term behaviour change maintenance is limited.
Graphical Abstract Legend: The epithelium of the adult uterus consists of a luminal epithelium (LE) that is negative for the Forkhead box A2 (FOXA2) transcription factor and a glandular epithelium ...(GE) that is positive for FOXA2 and required for fertility. We discovered that gland formation (adenogenesis) within the neonatal bovine uterus was associated with the differentiation of islands of LE cells into FOXA2+ cells (LE to GE specification). This process precedes bud formation and tubulogenesis. The LE to GE specification does not involve cellular proliferation (based on MKI67 marker). The LE to GE specification may be the initial step in gland formation that is followed by rupture of the basement membrane and penetration of the underlying stroma by FOXA2+ cells.
University food environments typically offer an abundance of unhealthy foods, including through vending machines. This review evaluated the effectiveness of nutrition interventions in vending ...machines in the university setting. Ten databases were searched for experimental studies published up to July 2019, evaluating nutrition interventions that aimed to encourage the purchase or consumption of healthier foods and drinks in vending machines in the university setting. In total, 401 articles were identified, and 13 studies were included. Studies were pre-post test (
= 7, 54%), randomized controlled trials (RCTs) (
= 5, 38%), and non-randomized controlled trial (
= 1, 8%). Most studies were from the USA (
= 10, 77%) and were published between 2014 and 2018 (
= 9, 69%). Eight interventions (62%) reported positive change in outcomes, including increased number/proportion of sales or revenue from healthier items (
= 6), improved adherence to guidelines for the ratio of healthy/unhealthy products available (
= 1), and improved consumer perception of items available (
= 1). Effective interventions involved the promotion, reduced pricing, increased availability, and/or optimized product placement of healthier items within vending machines. Strategies to improve the nutritional quality of food and drinks in vending machines are warranted. This may be achieved by making healthier options more available and promoting them; however, more robust intervention studies are needed to determine effectiveness.
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