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Background: Endometrial cancer is strongly associated with obesity, and tumors often harbor mutations in major cancer signaling pathways. To inform the integration of body composition into targeted therapy paradigms, this hypothesis-generating study explores the association between muscle mass, body fat, and tumor proteomics. Methods: We analyzed data from 113 patients in The Cancer Genome Atlas (TCGA) and Cancer Proteomic Tumor Analysis Consortium (CPTAC) cohorts and their corresponding abdominal CT scans. Among these patients, tumor proteomics data were available for 45 patients, and 133 proteins were analyzed. Adiposity and muscle components were assessed at the L3 vertebral level on the CT scans. Patients were stratified into tertiles of muscle and fat mass and categorized into three groups: high muscle/low adiposity, high muscle/high adiposity, and low muscle/all adiposities. Linear and Cox regression models were adjusted for study cohort, stage, histology type, age, race, and ethnicity. Results: Compared with the high-muscle/low-adiposity group, both the high-muscle/high-adiposity (HR = 4.3, 95% CI = 1.0–29.0) and low-muscle (HR = 4.4, 95% CI = 1.3–14.9) groups experienced higher mortality. Low muscle was associated with higher expression of phospho-4EBP1(T37 and S65), phospho-GYS(S641) and phospho-MAPK(T202/Y204) but lower expression of ARID1A, CHK2, SYK, LCK, EEF2, CYCLIN B1, and FOXO3A. High muscle/high adiposity was associated with higher expression of phospho-4EBP1 (T37), phospho-GYS (S641), CHK1, PEA15, SMAD3, BAX, DJ1, GYS, PKM2, COMPLEX II Subunit 30, and phospho-P70S6K (T389) but with lower expression of CHK2, CRAF, MSH6, TUBERIN, PR, ERK2, beta-CATENIN, AKT, and S6. Conclusions: These findings demonstrate an association between body composition and proteins involved in key cancer signaling pathways, notably the PI3K/AKT/MTOR, MAPK/ERK, cell cycle regulation, DNA damage response, and mismatch repair pathways. These findings warrant further validation and assessment in relation to prognosis and outcomes in these patients.

Obesity is associated with alterations in circulating IGF1, IGF1-binding proteins (IGFBPs), insulin, inflammatory markers, and hormones implicated in cardiovascular disease, diabetes, cancer, and aging. However, the effects of 4 and 6 h time-restricted eating (TRE) on circulating IGF1 and IGFBPs is uncertain. Objective: This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined. Design: An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out. Participants/Setting: This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups. Intervention: Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations. Main outcome measures: IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis. Statistical Analysis: Repeated measures ANOVA and mediation analysis were conducted. Results: Body weight significantly decreased with TRE (−3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the “higher weight loss” subgroup. Changes in insulin and HOMA-IR were related to TRE adherence. Conclusions: Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Background and Aim: Interest in plants with antimicrobial properties has been revived due to emerging problems associated with using antibiotics to eradicate Helicobacter pylori. Accordingly, this study aims to assess the antibacterial effects of Punica granatum and the possible synergistic effect of its extract along with metronidazole against H. pylori. Materials and Methods: Pomegranate peel ethanol extracts (PPEE) was tested against a control strain of H. pylori (NCTC 11916) in vitro and in vivo in female Wistar rats. Moreover, the synergistic effect of PPEE in combination with metronidazole was tested in vitro. Results: The PPEE exhibited a remarkable activity against H. pylori with a minimum inhibitory concentration (MIC) of 0.156 mg/mL. Furthermore, the extract exhibited a pronounced urease inhibitory activity (IC50 ∼6 mg/mL) against the tested strain. A synergistic effect between PPEE and metronidazole was also observed (fractional inhibitory concentrations <0.5). Oral treatment of rats with PPEE for 8 days produced a significant reduction in H. pylori gastritis and a significant decrease in both lymphocytic and positive chronicity. Conclusion: Pomegranate extract is probably safe and represents a potential alternative and complementary therapy for reducing H. pylori associated with gastric ulcers.