The emergence of phosphatidylinositol 3-kinase (PI3Kα) in cancer development has accentuated its significance as a potential target for anticancer drug design. Twenty one derivatives of N-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using NMR (¹H and ¹³C) and HRMS. The derivatives displayed inhibitory activity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines: compounds 8 (IC₅₀ Caco-2 = 98 µM, IC₅₀ HCT-116 = 337 µM) and 16 (IC₅₀ Caco-2 = 13 µM, IC₅₀ HCT-116 = 240.2 µM). Results showed that compound 16 significantly affected the gene encoding AKT, BAD, and PI3K. The induced-fit docking (IFD) studies against PI3Kα demonstrated that the scaffold accommodates the kinase domains and forms H-bonds with significant binding residues.

(1) Background: Chronic myeloid leukemia is defined as the neoplastic development of mostly myeloid cells in the bone marrow. Several treatments, including chemotherapy, radiation, hormone treatment, and immunological therapy, can be used to control this condition. The therapeutic impact on leukemic individuals varies, and the response to therapy varies between patients due to disease heterogeneity. The primary goal of this study is to compare the effects of single and Imatinib (IM) and Hydroxyurea (HU) combined treatment on hematological parameters and gene expression in CML patients. (2) Methods: This study was conducted on 51 patients, with chronic myeloid leukemia, who were admitted to Al-Basher hospital in Amman, Jordan, for follow-up. Their hematological parameters were checked and gene expression was measured for (BCL2, PP2A, CIP2A, and WT1). (3) Results: The BCL2 gene was found to be less expressed in both IM and (HU + IM) treatments as compared to the HU group alone, while PP2A gene expression was raised. Such a thing indicates that the outcome of the combined therapy method is not ideal, since PP2A activation causes CML cells to move toward the blast crisis stage. Furthermore, CIP2A gene expression revealed that IM and (HU + IM) had the same therapeutic effect and were more successful in CML patients than HU alone. With regards to the treatment effect on hematological parameters, notably in CML patients in later stages, the combination therapy (HU + IM) raised lymphocyte count, indicating a greater response to the treatment. When compared to single medicines, the combination treatment reduced the proportion of neutrophils to normal reference ranges. Platelet counts, on the other hand, dramatically decreased in both IM and (HU + IM). (4) Conclusion: Because the studied genes (BCL2, PP2A, CIP2A, and WT1) are participating in cell proliferation and death, the findings show that the examined genes are significant to understand the efficacy of various therapies. Furthermore, it was found that there was a clear effect of the clinic-based strategic treatment on hematological indicators such as WBCs, lymphocytes, neutrophils, and platelet counts.

Centaurea virgata is broadly used as a traditional food and medicine across the globe for numerous health purposes. Although the species is reported to have antioxidant and anti‐inflammatory activities, literature data on its gastroprotective effects are scarce. Due to numerous shortcomings of conventional anti‐ulcer drugs, natural products gained renewed interest as a safer alternative. This study aimed to investigate the acute toxicity and gastroprotective effects of the aerial part extracts of Centaurea virgata (APCV) on ethanol‐induced gastric ulcers in Sprague–Dawley rats. Rats were divided into 5 groups: normal control, ulcer control (saline + EtOH), reference (lansoprazole + EtOH), APCV 100 mg/kg + EtOH, and APCV 200 mg/kg + EtOH. APCV 100 or 200 mg/kg, administered orally 1 h before the ethanol‐induced ulcer procedure delivery, increased the protective index % (26.82% and 31.40%, respectively). The histopathological results (using H&E and PAS) indicated preserved gastric defense barriers (restored mucus secretion and gastric pH) and tissue architecture as a result of APCV pretreatment. APCV intervention (100 and 200 mg/kg) increased superoxide dismutase by 24.33% and 62.14%; catalase by 59.07% and 90.37%; and upregulated IL‐10 by 24.40% and 79.52%, while significantly ( p < 0.01) lowering MDA by 25.97% and 38.77%, as well as significantly ( p < 0.001) downregulated IL‐6 by 14.67% and 33.08% and TNF‐α by 37.82% and 47.59%, respectively, compared to ulcer controls. It could also be noted that inhibited apoptosis (inhibited pro‐apoptotic Bax and increased HSP 70 appearances in gastric tissues) occurred in gastric tissues pretreated with APCV. Taken together, APCV exhibited a gastroprotective potential against gastric ulcers, which is attributed to its attenuation effects on oxidative stress, inflammatory, and apoptotic pathways.

Microcystis blooms and the related toxin known as microcystin-LR (MC-LR) put the safety of human water consumption and global irrigation practices in jeopardy. MC-LR is widely distributed in various environments, including water, sediments, plants, and other aquatic organisms. The use of...

Background: Chrysin is known for its pharmacological effects and structural resemblance to estrogen. The study explores the impact of chrysin on steroidogenesis focusing on adrenal and ovarian steroidogenic enzymes. Materials and methods: Thirty female BALB/c mice were divided into three groups: a control group and two chrysin-treated groups (50 mg and 100 mg). Gene expression of key steroidogenic enzymes was assessed in adrenal glands and ovaries using RT-qPCR. Uterine expression of estrogen receptor alpha (ERα) was also examined. Histological analysis of adrenal glands and ovaries was performed. Results: High-dose chrysin downregulated CYP17A1 expression in adrenal glands compared to control and low-dose groups. In contrast, 3β-HSD was significantly downregulated in the high-dose group. In ovaries, high dose chrysin reduced aromatase expression. Conclusion: Our findings revealed that chrysin’s impact on steroidogenesis is dose-dependent. By downregulating CYP17A1 in adrenal glands, potentially affecting androgen and estrogen synthesis, and enhancing aromatase expression in ovaries at lower doses.

Pomegranates are one of the fruits that are most frequently consumed in the Middle East andhave a medical effect. This study aimed to examine the antidiabetic and antilipidemic effect of pomegranate fruits parts including peels, seeds, and rinds extracted using ethanol on the blood glucose, cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). Control (non-treated) rats and alloxandiabetic-induced rats were used in this study. The alloxan-diabetic-induced rats were divided into four groups and each group received a subcutaneously injected either peels, seeds, or grind ethanol extract, and a group was treated with the drug glipizide for 28 days. Data showed a significant effect for the pomegranate peels and rind ethanol extract in lowering glucose levels (P = 0.0295) with no significant effect for the juice extract on blood glucose levels. Cholesterol, triglycerides, LDL, and VLDL were all significantly reduced by the pomegranate fruit component extracts employed in this study (P = 0.014). However, no significant effect was observed for any extract on the HDL levels in the blood (P > 0.5). In conclusion, the rind of the pomegranate can be used in optimizing blood lipid profile and glucose, in addition to seeds and peels.