Obesity is associated with high risk and poor prognosis of breast cancer (BC). Obesity promotes BC cells proliferation via modulating the production of adipokines, including adiponectin (anti-neoplastic adipokine), leptin (carcinogenic adipokine) and inflammatory mediators. In the present study we investigated the anti-proliferative effects of liraglutide (LG; anti-diabetic and weight reducing drug) on MCF-7 human BC cells cultured in obese adipose tissue-derived stem cells-conditioned medium (ADSCs-CM) and whether this effect is mediated via modulating the adipokines in ADSCs and cancer cells. Proliferation was investigated using AlamarBlue viability test, colony forming assay and cell cycle analysis. Levels and expression of adipokines and their receptors were assayed using ELISA and RT-PCR. LG caused 48% inhibition of MCF-7 proliferation in obese ADSCs-CM, reduced the colony formation and induced G0/G1 phase arrest. LG also decreased the levels of inflammatory mediators, suppressed the expression of leptin, while increased mRNA levels of adiponectin and their receptors in obese ADSCs and cancer cells cultured in obese ADCSs-CM. In conclusion, LG could mitigate BC cell growth in obese subjects; therefore it could be used for clinical prevention and/or treatment of BC in obese subjects. It may assist to improve treatment outcomes and, reduce the mortality rate in obese patients with BC.

5-Fluorouracil (5-FU) is an anticancer drug with intestinal mucositis (IM) as a deleterious side effect. Thymol is a monoterpene phenol which has been reported to possess an antioxidant and anti-inflammatory activity versus 5-FU-induced IM. The Notch pathway affects multiple cellular activities, such as cellular proliferation, in addition to inflammatory responses modulation. Accordingly, this work was carried out in order to elucidate the role of the Notch pathway in 5-FU-induced IM and to further elucidate the immunomodulatory protective mechanisms of thymol. Experimental rats were divided randomly into four groups: Control, 5-FU, 5-FU+thymol (60 mg/kg/day), and 5-FU+thymol (120 mg/kg/day). 5-FU was injected intraperitoneally at a dose of 150 mg/kg on days 6 and 7, while thymol was orally administered daily for 11 days. By the end of the study, intestinal tissues were collected for the determination of IL-17, CD4, CD8, Notch1, Hes-1, pSTAT3, and STAT-3 protein expressions. The effect of thymol on 5-FU cytotoxicity was also examined using WST1 assay. 5-FU induced a marked increase in IL-17 levels, along with a marked downregulation of CD4 and the upregulation of CD8, Notch1, Hes-1 protein expressions, and activation of STAT3 in the intestinal tissue when compared with the control group. Thymol ameliorated the changes that occurred in these parameters. Additionally, cytotoxicity testing revealed that thymol augmented the antiproliferative action of 5-FU against breast and colorectal human cancer cell lines. This study was the first to show that the IL-17/Notch1/STAT3 pathway is involved in the molecular mechanism of 5-FU-induced IM, as well as the immunomodulatory activity of thymol.

Major international sporting events frequently impose exogenous demands that challenge adult circadian rhythms, often leading to the misalignment of sleep-wake cycles and social schedules. This cross-sectional study investigated the impact of the FIFA 2022 World Cup on adult sleep patterns to assess the prevalence and determinants of tournament-associated circadian disruption. Through an online survey, we captured data on sleep duration, timing, and subjective quality from a diverse adult population using Pittsburgh Sleep Quality Index (PSQI) score. The results indicate that 81.3% had high problematic sleep according to PSQI scores, while only 9% perceived that their sleep pattern was impacted by watching matches during the tournament. While 83.7% of the participants had low or mild anxiety according to GAD-7 scores, we found that GAD-7 scores correlated significantly with PSQI scores. Married participants had significantly lower PSQI scores (RR 0.856, p = .005), while those who reported that their sleep hours had changed during the tournament had significantly higher PSQI scores (1.180, P-value <0.001). Males reported a significantly high impact of the tournament on their sleep (OR 2.622, P-value <0.001). In conclusion, our data demonstrate a discrepancy between self-perception of sleep quality and self-rated assessment by PSQI scores, as well as the substantial impact of major international sporting events on adult sleep hygiene. The results provide data-driven insights helpful in evaluating potential circadian risks and informing public health strategies for major sporting events such as the FIFA world cup. Graphical

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune dysregulation that leads to widespread inflammation and damage across multiple organs. B lymphocytes play a vital role in SLE, with abnormal development and activation leading to autoreactive antibody production and immune complex formation, which damages tissues. Methods: The PPARα agonist WY14643 has anti-inflammatory effects in various inflammatory conditions, including CNS diseases. We investigated whether WY14643 decreases inflammatory mediator production in CD45R⁺ cells in the MRL/lpr mouse model of SLE. Flow cytometry was used to evaluate WY14643’s impact on the expression of IFN-γ, IL-6, iNOS, MCP-1, IL-1α, IL-2, Notch-1, Notch-3, GITR, and NF-κB p65 in splenic CD45R⁺ B cells. Additionally, we assessed the effect of WY14643 on the mRNA levels of these markers in the kidney using RT-PCR. Results: WY14643 decreased inflammatory markers such as CD45R⁺IFN-γ⁺, CD45R⁺IL-6⁺, CD45R⁺iNOS⁺, CD45R⁺MCP-1⁺, CD45R⁺IL-1α⁺, CD45R⁺IL-2⁺, CD45R⁺Notch1⁺, CD45R⁺Notch3⁺, CD45R⁺GITR⁺, and CD45R⁺NF-κB p65⁺ in splenic cells from MRL/lpr mice. Furthermore, WY14643 also lowered mRNA expression of IFN-γ, IL-6, iNOS, MCP-1, IL-2, IL-1α, Notch-1, Notch-3, GITR, and NF-κB p65 in the kidney. Conclusions: This study shows that WY14643 inhibits the production of inflammatory mediators and significantly reduces autoimmune features, including kidney inflammation, in MRL/lpr mice. Our results indicate that WY14643, a PPAR-α agonist, could be a potential therapy for lupus nephritis.