Threshold effects and inflection points of flavonoid intake in dietary anti-inflammatory effects: Evidence from the NHANES.

Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007-2010, 2017-2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database. Weighted multiple linear regression was used to assess linear relationships between flavonoid intake and Dietary inflammation index (DII). Smoothed curve fit and a generalized additive model were used to investigate the nonlinear relationships and threshold effects, the 2-tailed linear regression model was used to find potential inflection points. A total of 12,724 adults were included in the study. After adjusting for potential confounders, flavonoid intake was significantly associated with DII, with the strongest negative association effect for flavonols (-0.40 [-0.45, -0.35]). In subgroup analyses stratified by sex, race, age, body mass index, education levels, and diabetes, flavonol intake maintained a significant negative linear correlation with DII. In addition, we found significant nonlinear relationships (L-shaped relationships) and threshold effects between total flavonoids, flavan-3-ols, and flavanols and DII, with inflection points of 437.65 mg/days, 157.79 mg/days, and 46.36 mg/days, respectively. Our results suggest a threshold for the dietary anti-inflammatory capacity of flavonoid intake in U.S. adults.

E2F2 Promotes Wound Healing of Diabetic Foot Ulcer by Regulating CDCA7L Transcription.

OBJECTIVE: The E2F2 transcription factor can accelerate cell proliferation and wound healing. However, its mechanism of action in a diabetic foot ulcer (DFU) remains unclear. Therefore, this study explores the influence of E2F2 on wound healing in DFU by examining cell division cycle-associated 7-like (CDCA7L) expression. METHODS: CDCA7L and E2F2 expression in DFU tissues were analyzed with databases. CDCA7L and E2F2 expression were altered in human umbilical vein endothelial cells (HUVECs) and spontaneously transformed human keratinocyte cell culture (HaCaT) cells. Cell viability, migration, colony formation, and angiogenesis were evaluated. Binding of E2F2 to the CDCA7L promoter was examined. Subsequently, a diabetes mellitus (DM) mouse model was established and treated with full-thickness excision followed by CDCA7L overexpression. Wound healing in these mice was observed and recorded, and vascular endothelial growth factor receptor 2 (VEGFR2) and hematopoietic progenitor cell antigen CD34 (CD34) expression were determined. E2F2 and CDCA7L expression levels in cells and mice were evaluated. The expression of growth factors was tested. RESULTS: CDCA7L expression was downregulated in DFU tissues and wound tissues from DM mice. Mechanistically, E2F2 bound to the CDCA7L promoter to upregulate CDCA7L expression. E2F2 overexpression enhanced viability, migration, and growth factor expression in HaCaT cells and HUVECs, and augmented HUVEC angiogenesis and HaCaT cell proliferation, which was nullified by silencing CDCA7L. In DM mice, CDCA7L overexpression facilitated wound healing and elevated the expression level of growth factors. CONCLUSIONS: E2F2 facilitated cell proliferation and migration and fostered wound healing in DFU cells through binding to the CDCA7L promoter.

Race and Gender Differences in the Associations Between Cadmium Exposure and Bone Mineral Density in US Adults.

Several previous studies have found the deleterious effects of cadmium exposure on bone. However, studies on the effects of cadmium exposure on bone mineral density (BMD) in gender- and race-specific groups are still lacking. The aim of this study was to investigate the relationship between cadmium exposure and BMD in adults and the gender and racial differences therein. Weighted multivariate regression, generalized weighted model, and smoothed curve fitting were used to explore the relationship between lumbar BMD with blood cadmium (B-Cd) and urine cadmium (U-Cd) based on data from the National Health and Nutrition Examination Survey (NHANES). In addition, subgroup analyses were further used to investigate the differential associations across gender and race. Of the 4335 adult participants. After adjusting for primary demographic variables, B-Cd [- 0.018 (- 0.028, - 0.008)] and U-Cd [- 0.010 (- 0.020, - 0.001)] were shown to be negatively related to lumbar BMD. In the fully adjusted model, the negative association between B-Cd and lumbar BMD was maintained [- 0.010 (- 0.018, - 0.002)]. In the subgroup analysis stratified by gender and race, this relationship was retained in females and non-Hispanic blacks. Furthermore, these negative associations were most pronounced among non-Hispanic black women [B-Cd and lumbar BMD, - 0.046 (- 0.076, - 0.017); U-Cd and lumbar BMD, -0.034 (- 0.063, - 0.006)]. Our findings suggest that there are significant sex and race differences in the negative association between cadmium exposure and BMD. This negative association was most prominent in non-Hispanic black females.