Chemotherapy remains to be the method of choice used by clinicians to treat acute myeloid leukemia (AML) patients. However, the most common problem usually faced in the course of treatment is multidrug resistance (MDR). Nowadays, combination therapy involving natural products as adjuvant therapy to chemotherapy and radiotherapy has been used for many of health problems. Coumarin is a natural compound with known chemotherapeutic activity, as well as other pharmacological properties. We focused on the combination of coumarin and doxorubicin in overcoming of drug-resistance in acute myeloid leukemia. Cell viability, Apoptotic and necrotic cell death with FACS, oxidative stress detection, and protein expression analysis were used in this study. Coumarin as a single drug exerts a significant cell death on Human acute myeloid leukemia (HL60); however, it does not show the same effect on drug-resistant acute myeloid leukemia (HL60/ADR). Comparing the effects of doxorubicin and coumarin as single drugs versus a combination of coumarin and doxorubicin showed a significant apoptotic cell death. In AML patients, the development of multiple drug resistance (MDR) is the biggest challenge in treating AML patients. Combination therapy with coumarin may be a good choice to overcome the drug resistance in AML patients.

Several microRNAs (miRNAs) are known to participate in adipogenesis. However, their role in this process, especially in the differentiation of bovine preadipocytes, remains to be elucidated. This study was intended to clarify the effect of microRNA-33a (miR-33a) on the differentiation of bovine preadipocytes by cell culture, real-time fluorescent quantitative PCR (qPCR), Oil Red staining, BODIPY staining, and Western blotting. The results indicate that overexpression of miR-33a significantly inhibited lipid droplet accumulation and decreased the mRNA and protein expression of adipocyte differentiation marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), and fatty acid-binding protein 4 (FABP4). In contrast, the interference expression of miR-33a promoted lipid droplet accumulation and increased the expression of marker genes. Additionally, miR-33a directly targeted insulin receptor substrate 2 (IRS2) and regulated the phosphorylation level of serine/threonine kinase (Akt). Furthermore, miR-33a inhibition could rescue defects in the differentiation of bovine preadipocytes and the Akt phosphorylation level caused by small interfering IRS2 (si-IRS2). Collectively, these results indicate that miR-33a could inhibit the differentiation of bovine preadipocytes, possibly through the IRS2–Akt pathway. These findings might help develop practical means to improve the quality of beef.

Pumpkin has received significant attention due to its nutritional compounds that have antioxidant, antifatigue, and anti‐inflammatory effects. This study is aimed at assessing the antidepressant‐like effect of L. Cucurbita pepo, sweet pumpkin, in an animal model of chronic unpredictable mild stress (CUMS) and investigating its effect on the histological structure of hippocampus compared to fluoxetine. Forty male albino rats assigned into the negative control, positive control (CUMS), and Flu‐treated and pumpkin‐treated groups (n = 10) were utilized in this study. Exposing rats to CUMS continued for 28 days, and treatments used were applied during the last 14 days of exposure. Behavioral, biochemical, and histopathological changes were assessed after 28 days. In this study, pumpkin significantly reduced the immobility time (p = 0.02), corticosterone (p < 0.001), TNF‐α, IL‐6 (p < 0.001), and malondialdehyde (p = 0.003), whereas it significantly increased the level of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in the serum of rats exposed to CUMS. Pumpkin markedly relieved the degenerative and atrophic changes observed in the CA3 region and the dentate gyrus of the hippocampus. It significantly reduced caspase‐3 and increased glial fibrillary acidic protein (GFAP) immunoexpression in the CA3 and DG. In conclusion, administration of pumpkin extract improved the behavioral, biochemical, and hippocampal pathological alternations induced in rats after exposure to CUMS in a comparable pattern to fluoxetine. This study highlighted the potential efficacy of pumpkin in alleviating depression disorder either alone or in conjugation with conventional antidepressant therapy.

Gastric cancer (GC) remains a major global health concern due to its frequent late-stage diagnosis, persistent chemoresistance, and high metastatic potential, all of which contribute to poor clinical outcomes. TRIM26, an E3 ubiquitin ligase with emerging tumor-suppressive functions, has been implicated in various malignancies; however, its precise role in GC has not been fully elucidated. This study elucidates in ferroptosis and chemoresistance while uncovering stromal-tumor crosstalk mechanisms underlying its suppression. Using public databases and clinical GC specimens and established cell lines (MGC-803, HGC27, MKN45), we observed significant downregulation of TRIM26 expression in tumor tissues compared to adjacent normal counterparts (p < 0.001), which correlated with advanced clinical stage and unfavorable prognosis. Functional assays including CCK-8, wound healing, colony formation, and Transwell migration, demonstrated that TRIM26 knockdown significantly enhanced GC cell proliferation, migration, and invasion, whereas TRIM26 overexpression reversed these malignant phenotypes. Mechanistically, TRIM26 induced ferroptosis via HSF1 ubiquitination and degradation, leading to reduced glutathione (GSH) levels and elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Additionally, we identified cancer-associated fibroblast (CAF)-derived exosomal miR-24-3p as a key upstream regulator that directly targets the 3' untranslated region (3' UTR) of TRIM26, thereby suppressing its expression, as confirmed by luciferase reporter assays. In cisplatin-resistant GC models (MGC803/DDP and AGS/DDP), prolonged cisplatin exposure resulted in a pronounced reduction in TRIM26 expression, corresponding with a 5.6-fold increase in IC₅₀ and a heightened metastatic profile. TRIM26 silencing further potentiated chemoresistance and invasive behavior, which coincided with epithelial-mesenchymal transition (EMT), as evidenced by decreased E-cadherin and increased N-cadherin and Vimentin expression. In contrast, TRIM26 restoration re-sensitized resistant GC cells to cisplatin and mitigated their metastatic capacity. Collectively, these findings reveal TRIM26 as a pivotal suppressor of GC progression, acting through the regulation of ferroptosis and EMT while being modulated by stromal exosomal miR-24-3p Therapeutic strategies aimed at restoring TRIM26 expression or disrupting the miR-24-3p/TRIM26/HSF1 axis may offer promising avenues for overcoming chemoresistance and limiting metastasis in GC.

Metagenomic approach was used to detect microbial gene abundance and relative abundance in the rhizosphere of Moringa oleifera and surrounding bulk soil and to detect the response of soil microbes to watering. Expectedly, the number and abundance of non-redundant genes were extremely higher in bacteria followed by archaea, eukaryota and viruses. Results demonstrated unexpected high abundance of some microbes (ex., endophyte genus Nocardioides) in the rhizosphere that are supposed to exist mainly in other rhizocompartments. We suggest this differential distribution of microbes is due to the specific pattern of host-microbe interaction. Other endosymbiont microbes, ex., fungi Mucoromycota and Ascomycota, were highly abundant in the bulk soil possibly because they are phytopathogens where plant exudates might inhibit their growth or force these fungi to approach reverse chemotaxis. Our data indicated high abundance of other symbiont microbes in the rhizosphere of M. oleifera at phylum (ex., Actinobacteria) and genus (ex., Streptomyces) levels. Watering experiment indicated that phylum Actinobacteria and the descending genus Streptomyces are among the highest. Rhizobiome of M. oleifera seems to harbor a wealth of new species of the genus Streptomyces that are required to be deciphered for function in order to be eventually utilized in pharmaceutical and agricultural applications.