Dietary Flavonoids Consumption and Health: An Umbrella Review.

SCOPE: The current evidence between dietary flavonoids consumption and multiple health outcomes is inadequate and inconclusive. To summarize and evaluate the evidence for dietary flavonoids consumption and multiple health outcomes, an umbrella review of meta-analyses and systematic reviews is conducted. METHODS AND RESULTS: PubMed, Ovid-EMBASE, and the Cochrane Database of Systematic Reviews are searched up to January 2024. The study includes a total of 32 articles containing 24 unique health outcomes in this umbrella review. Meta-analyses are recalculated by using a random effects model. Separate analyses are performed based on the kind of different flavonoid subclasses. The study finds some unique associations such as flavonol and gastric cancer, isoflavone and uterine fibroids and endometrial cancer, total flavonoids consumption and lung cancer, ovarian cancer, and prostate cancer. Overall, the study confirms the negative associations between dietary flavonoids consumption and type 2 diabetes mellitus, cardiovascular diseases, breast cancer, colorectal cancer, lung cancer, and mortality, while positive associations are observed for prostate cancer and uterine fibroids. CONCLUSION: Although dietary flavonoids are significantly associated with many outcomes, firm generalizable conclusions about their beneficial or harmful effects cannot be drawn because of the low certainty of evidence for most of outcomes. More well-designed primary studies are needed.

Sex- and time-specific associations of obesity with glycaemic traits: A two-step multivariate Mendelian randomization study.

AIM: To assess the sex- and time-specific causal effects of obesity-related anthropometric traits on glycaemic traits. MATERIALS AND METHODS: We used univariate and multivariate Mendelian randomization to assess the causal associations of anthropometric traits (gestational variables, birth weight, childhood body mass index [BMI], BMI, waist-to-hip ratio [WHR], BMI-adjusted WHR [WHRadj BMI]) with fasting glucose and insulin in Europeans from the Early Growth Genetics Consortium (n ≤ 298 142), the UK Biobank, the Genetic Investigation of Anthropometric Traits Consortium (n ≤ 697 734; females: n ≤ 434 794; males: n ≤ 374 754) and the Meta-Analyses of Glucose and Insulin-related traits Consortium (n ≤ 151 188; females: n ≤ 73 089; males: n ≤ 67 506), adjusting for maternal genetic effects, smoking, alcohol consumption, and age at menarche. RESULTS: We observed a null association for gestational variables, a negative association for birth weight, and positive associations for childhood BMI and adult traits (BMI, WHR, and WHRadj BMI). In female participants, increased birth weight causally decreased fasting insulin (betaIVW , -0.07, 95% confidence interval [CI] -0.11 to -0.03; p = 1.92 × 10-3 ), but not glucose levels, which was annulled by adjusting for age at menarche. In male participants, increased birth weight causally decreased fasting glucose (betainverse-variance-weighted (IVW) , -0.07, 95% CI -0.11 to -0.03; p = 3.22 × 10-4 ), but not insulin levels. In time-specific analyses, independent effects of birth weight were absent in female participants, and were more pronounced in male participants. Independent effects of childhood BMI were attenuated in both sexes; independent effects of adult traits differed by sex. CONCLUSIONS: Our findings provide evidence for causal and independent effects of sex- and time-specific anthropometric traits on glycaemic variables, and highlight the importance of considering multiple obesity exposures at different time points in the life course.

Association between the prudent dietary pattern and blood pressure in Chinese adults is partially mediated by body composition.

High blood pressure or hypertension is one of the major risks of cardiovascular disease, which is the leading cause of death in China. This study aimed to assess the relationship between dietary patterns and blood pressure among Chinese adults. Using factor analysis of 66-item food frequency questionnaire to identify dietary patterns. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured according to standardized guidelines. Multivariate linear regressions were performed in 6849 Chinese adults (46.5% female) aged 21-70 years considering sociodemographic characteristics, lifestyle behaviors, and anthropometry data. The vegetable-rich pattern, animal-food pattern, and prudent dietary pattern were identified. After adjustment for potential confounders including age, gender, alcohol consumption, smoking status, energy intake, and physical activity, only prudent dietary pattern was negatively related to SBP (ß = -2.30, p for trend =0.0003) and DBP (ß = -1.44, p for trend =0.0006). Body mass index, waist circumstance and body fat percentage explained, respectively, 42.5%/47.8, 14.8%/17.6 and 26.0%/29.1% of the association between prudent pattern and SBP/DBP in mediation analysis. There were no association were observed between other dietary patterns and blood pressure. In conclusion, Prudent dietary pattern was associated with lower SBP and DBP among Southwest Chinese and this association was partially explained by body composition.

Optimisation of the production of a selenium-enriched polysaccharide from Cordyceps cicadae S1 and its structure and antioxidant activity.

The fermentation medium of a newly identified Cordyceps cicadae S1 was optimized by response surface methodology, with the optimal medium containing sucrose (80 g/L), yeast powder (60 g/L), KH2PO4 (5 g/L), MgSO4·7H2O (1 g/L) and Na2SeO3 (0. 1 g/L). Under these conditions, the extracellular polysaccharide yield was 8.09 g/L. A novel selenium-enriched polysaccharide (PACI-1) was isolated from Cordyceps cicadae, purified and identified as a homofructose polysaccharide with a low average molecular weight of 9.95 × 103 Da. The fine structure of PACI-1 was analyzed using NMR, CD, and AFM. Additionally, the in vitro antioxidant results showed that the PACI-1 had stronger antioxidant capacity than natural polysaccharides. These results provided a candidate strain for producing selenium polysaccharide and a new polysaccharide from C. cicadae, which showed good antioxidant activity.

Human antigen R affects the migration and invasion of human lung cancer A549 cells via regulating E-cadherin suppressor Snail.

Recent studies demonstrated that the progression and metastasis of lung cancer were associated with human antigen R (HuR), a post-transcriptional RNA-binding protein that stabilize and regulate the expression of many tumor-related genes. Although HuR was shown to affect the expressions of epithelial cadherin (E-cadherin), a tumor migration suppressor, in airway epithelial cells, esophageal squamous and colon cancer cells, direct evaluation for the effect and mechanism of HuR on the migration and invasion of lung cancer cells is not documented. In this study, HuR was knocked down via RNA interference and overexpressed using recombinant plasmid in adenocarcinomic human alveolar basal epithelial A549 cells. No apparent inhibition of cell viability was observed. HuR knocked down significantly suppressed A549 migration and invasion in scratch wound healing and transwell assays, with an increase in E-cadherin expression, while the overexpression of HuR notably facilitated A549 migration and invasion, with a decrease in E-cadherin level. In addition, immunoprecipitation study showed that HuR directly interacted with Snail, a repressor of E-cadherin, and upregulated the expression of Snail in A549 cells. These combined results suggested that the effect of HuR on A549 migration and invasion was realized by stabilizing and increasing the expression of Snail, which in-turn interfered with the expression of E-cadherin. The finding of this study revealed direct evidence that HuR affected the migration and invasion of lung cancer cells via regulating E-cadherin and Snail, providing an additional reference and mechanistic clue for further researches and therapeutic strategies in treating lung cancer.

Impact of Physiologically Relevant Genistein Exposure at Different Time Windows on Puberty Onset and Neuroendocrine Function in Female Rats.

SCOPE: Puberty timing, critical for adulthood wellbeing, is influenced by the environment, life-style, and diets. However, differential puberty-interfering effects of soy and soy isoflavone are observed in both epidemiological and toxicological studies. Additionally, their impact on neuroendocrine function at various pre-pubertal developmental windows is unclear. METHODS AND RESULTS: This study investigates the effect of genistein, a typical soy isoflavone, at neonatal, lactational, and post-weaning stages on the time of vaginal opening and determines the levels of neuroendocrine factors in female rats using immunofluorescence, immunochemistry, and enzyme-linked immunosorbent assays. A physiologically relevant dosage (10 mg kg-1 ) is used to resemble human exposure. The results show that genistein exposure at lactational stage significantly accelerates vaginal opening time, marginally increases hypothalamic gonadotropin-releasing hormone (GnRH) secretion, significantly enhances kisspeptin receptor expression, and markedly elevates blood levels of GnRH, luteinizing hormone, and follicle-stimulating hormone, while neonatal and post-weaning exposures do not induce significant alternations. CONCLUSION: Lactational stage may be an important window for genistein to impact reproductive development and neuroendocrine regulations.

Application of the Tumor Site Recognizable and Dual-Responsive Nanoparticles for Combinational Treatment of the Drug-Resistant Colorectal Cancer.

PURPOSE: Combination of PCI and chemotherapy represents a promising strategy for combating drug resistance of cancer. However, poor solubility of photosensitizers and unselectively released drugs at unwanted sites significantly impaired the treatment efficacy. Therefore, in the present study, we aimed to develop a nano-platform which could efficiently co-entrapping photosensitizers and chemotherapeutics for active targeting therapy of drug resistant cancers. METHODS: Two pro-drugs were respectively developed by covalently linking the Ce6 with each other via the GSH-sensitive linkage and the PTX with mPEG-PLA-COOH through the ROS sensitive-linker. The dual-responsive nanoparticles (PNP-Ce6) was developed by emulsion/solvent evaporation method and further modified with tLyp-1 peptides. Physicochemical properties of nanoparticles were determined by the TEM and DLC. Cellular uptake assay was investigated with the Ce6 acting as the fluorescent probe and cell growth was studied by the MTT experiment. In vivo tumor targeting and anti-tumor assay was investigated on the colorectal cancer-bearing mice. RESULTS: The developed tPNP-Ce6 were stable enough under the normal physiological conditions. However, free Ce6 and PTX were completely released when exposed the tPNP-Ce6 to the redox environment. Excellent tumor-targeting drug delivery was achieved by the tPNP-Ce6, which in turn resulted in satisfactory anit-tumor effect. Of great importance, super inhibition effect on tumor progress was achieved by the combination therapy when compared with the group only received with chemotherapy.. CONCLUSION: The results obtained in the present study indicated that the developed tPNP-Ce6 may have great potential in enhancing the therapeutic efficacy of drug-resistant colorectal cancer. Graphical Abstract Left: Targeting delivery of drug to tumor site by the tumor recognizable and dual-responsive nanoparticles and penetrating into tumor inner via the mediation of irradiation. Right: Nanoparticle distribution within tumor tissues with green represents the blood vessels stained with CD31, blue signal represents the cell nuclei stained with DAPI and red shows fluorescence of Ce6 as the indicator of the nanoparticles.