Peroxisome proliferator-activated receptors (PPARs) are considered good drug targets for breast cancer because of their involvement in fatty acid metabolism that induces cell proliferation. In this study, we used the KAIMRC1 breast cancer cell line. We showed that the PPARE-Luciferase reporter gets highly activated without adding any exogenous ligand when PPAR alpha is co-transfected, and the antagonist GW6471 can inhibit the activity. Using this reporter system, we screened 240 compounds representing kinase inhibitors, epigenetic modulators, and stem cell differentiators and identified compounds that inhibit the PPARα-activated PPARE-Luciferase reporter in the KAIMRC1 cell. We selected 11 compounds (five epigenetic modulators, two stem cell differentiators, and four kinase inhibitors) that inhibited the reporter by at least 40% compared to the controls (DMSO-treated cells). We tested them in a dose-dependent manner and measured the KAIMRC1 cell viability after 48 h. All 11 compounds induced the cell killing at different IC50 values. We selected two compounds, PHA665752 and NSC3852, to dissect how they kill KAIMRC1 cells compared to the antagonist GW6741. First, molecular docking and a TR-FRET PPARα binding assay showed that compared to GW6471, these two compounds could not bind to PPARα. This means they inhibit the PPARα pathway independently rather than binding to the receptor. We further confirmed that PHA665752 and NSC3852 induce cell killing depending on the level of PPARα expression, and as such, their potency for killing the SW620 colon cancer cell line that expresses the lowest level of PPARα was less potent than for the KAIMRC1 and MDA-MB-231 cell lines. Further, using an apoptosis array and fatty acid gene expression panel, we found that both compounds regulate the PPARα pathway by controlling the genes involved in the fatty acid oxidation process. Our findings suggest that these two compounds have opposite effects involving fatty acid oxidation in the KAIMRC1 breast cancer cell line. Although we do not fully understand their mechanism of action, our data provide new insights into the potential role of these compounds in targeting breast cancer cells.

Contamination by fungi and the toxins they secrete is a worldwide health concern. One such toxin is zearalenone (Zea), which is structurally similar to the hormone estrogen, interferes with its action on the reproductive system, and is therefore classified as an endocrine disruptor. This study aims to determine the effectiveness of hispidin and magnesium nanoparticles (MgONPs) against zearalenone-induced myotoxicity, which causes polycystic ovary syndrome (PCOS) in rats. A three-month exposure study was performed using female Wistar rats (n = 42) with an average weight of 100–150 g. The animals were divided into six groups (I to VI) of seven rats each. Group I was administered distilled water as a negative control. Group II was exposed to Zea 0.1 mg/kg b.w. through gavage daily. Group III was treated with 0.1 mg/kg of hispidin through gavage daily. Group IV was given 150 µg/mL MgONPs orally each day. Group V was treated with Zea 0.1 mg/kg b.w. + 0.1 mg/kg hispidin orally each day. Group VI was treated with Zea 0.1 mg/kg b.w. and the combination treatment of 0.1 mg/kg hispidin + 150 µg/mL MgONPs through gavage every day. The effectiveness of hispidin and MgONPs against Zea toxicity was evaluated in terms of ovarian histological changes, gene expression, oxidative stress biomarkers, biochemical variables, and hormone levels. The findings showed that exposure to Zea promotes PCOS in rats, with Zea-treated rats displaying hyper-ovulation with large cysts; elevated testosterone, luteinizing hormone, insulin, and glucose; and reduced sex hormone-binding globulin. In addition, qRT-PCR for aromatase (Cyp19α1) showed it to be downregulated. Treatment with hispidin improved the histopathological and hormonal situation and rescued expression of Cyp19α. Our data indicate the potential therapeutic effects of hispidin against Zea-induced Fungal Toxicity.

Background and Aims: Many women reported experiencing abnormalities in their cycle after being vaccinated with Covid‐19 vaccination. To understand this issue further, our study aimed to evaluate the menstrual cycle patterns among women of childbearing age after receiving COVID‐19 vaccinations.Methods: A cross‐sectional study was conducted to investigate the impact of COVID‐19 vaccine on women aged 18 years and above in Saudi Arabia. A self‐administered online questionnaire was distributed among participants who had received at least one dose of COVID‐19 vaccine. The questionnaire included questions about the participants' demographic characteristics, medical history, and vaccine‐related adverse events.Results: The study included 383 female participants with an average age of 30.8 ± 8.1 years. The majority of participants, 92.7%, were Saudi, and more than half, 51.4%, were single. Of the participants, 78.9% were disease‐free, and a majority of 67.9% had no history of Coronavirus Disease 2019 infection. A significant proportion of participants reported postvaccination changes in the menstrual cycle. Specifically, 43.1% reported changes after the first dose, and 38.4% reported changes after the second dose (p = 0.044). The severity of premenstrual symptoms increased from 44 (11.5%) to 113 (29.5%) after the first dose. Reported pain on the (WONG‐BAKER) scale was also significantly elevated from 34 (8.9%) to 87 (22.7%) (p < 0.001) after the first dose.Conclusion: A relatively high prevalence of menstrual cycle irregularities was reported by Saudi vaccinated women, particularly young adults. These findings suggest the need to further research and explore the underlying causes of these irregularities and develop interventions that may help mitigate their impact on women's health. It is also recommended that women who observe long‐term changes in their menstrual cycles seek follow‐up and consultation with healthcare providers to ensure that any potential health concerns are addressed promptly.

Introduction: Boswellia carteri (B. carteri) resin is widely recognized for its anti-inflammatory, wound-healing, and immunomodulatory properties. This study examines the ability of its aqueous extracts to modulate the expression of key cytochrome P450 (CYP) enzymes—CYP1A2, CYP2B6, and CYP3A4—in Hep G2 cells, emphasizing pharmacokinetic and toxicological implications. Methods: Aqueous extracts were evaluated for endotoxin contamination and cytotoxicity to ensure suitability for in vitro experimentation. PCR analysis was employed to quantify CYP enzyme gene expression. Computational tools, including Protox-II, Swiss ADME, and molecular docking, were used to assess pharmacokinetics, CYP interactions, and biological targets. Competitive binding assays were performed to investigate the involvement of the constitutive androstane receptor (CAR) in CYP induction. Results: The results suggest that several metabolites, particularly ursodeoxycholic acid and beta-sitosterol, show potential interactions with CYP enzymes, with ursodeoxycholic acid demonstrating the highest probability of biological effects on CYP and a strong binding affinity to the Constitutive Androstane Receptor (CAR). Moreover, a receptor competitive binding assay suggested that the primary mechanism of CYP 2B6 and 3A4 induction is through activation of the CAR receptor although additional confirmatory studies are necessary. Discussion: The observed CYP enzyme induction through CAR receptor activation aligns with USFDA guidelines for CYP studies. However, the hepatotoxic potential of ursodeoxycholic acid and the associated toxicity risks of other metabolites underscore the need for caution. The findings highlight the potential for herb–drug interactions, particularly with pharmaceuticals metabolized by CYP enzymes. Conclusion: In conclusion, there is a potential for interactions between B. carteri resins and pharmaceuticals metabolized by CYP enzymes; thus, we advise caution to consumers, patients, and healthcare providers regarding their concomitant use. Although our findings provide valuable insights, further in vivo studies are essential to validate the modulatory effects of B. carteri on CYP gene expression.

Drug repurposing offers an efficient strategy to identify novel anticancer agents from marketed compounds. We screened a library of ~1400 approved drugs using a PPARE–PPAR-α luciferase reporter assay to uncover modulators of lipid metabolism that induce cancer cell death without direct binding to PPARα. This primary screen identified 224 compounds inhibiting reporter activity by >50%, of which 26 demonstrated ≥50% cytotoxicity in KAIMRC1 breast cancer and HCT116 colorectal cancer cells at 10 µM after 48 h incubation. AI-based DrTarget analysis classified these hits, with Group 1 comprising four previously unrecognized anticancer agents: antibiotics cefditoren pivoxil, tebipenem pivoxil, broxyquinoline, and cosmetic ingredient 1-hexadecanol. Dose–response studies across KAIMRC1, HCT116, and SW480 cells revealed IC₅₀ values as low as ~10 µM, comparable to daunorubicin, a well-known anti-cancer drug. Apoptosis profiling confirmed activation of intrinsic/extrinsic pathways via cytochrome c, SMAC/Diablo, TRAIL-R1/DR4, and phospho-p53 modulation. Based on these findings, we propose the repurposing of Broxyquinoline, 1-Hexadecanol, Cefditoren Pivoxil, and Tebipenem Pivoxil as potential anti-cancer drugs.