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In this research, we investigated the impact of drought stress on secondary metabolite production in cumin plants and the associated transcriptional changes in biosynthetic genes. Drought stress induced a significant increase in the levels of beta-carotene, lycopene, terpenes, anthocyanin, phenolic compounds, flavonoids, and alkaloids, indicating an adaptive metabolic shift in response to adverse conditions. Concurrently, there was an upregulation in the expression of key biosynthetic genes, including Phenylalanine ammonia-lyase (PAL), 3-deoxy-7-phosphoheptulonate synthase (DAHP synthase), Deoxy xylose phosphate reductase (DXS), 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGR), and Geranyl diphosphate synthase (GPPS), which corroborated the metabolite findings. Notably, while most secondary metabolites exhibited an increasing trend under drought stress, flavonoids displayed a disproportionate elevation, even as there was an overall decrease in phenolic compounds and other metabolites. This observation suggests the potential activation of alternative flavonoid synthesis pathways or the conversion of phenolic compounds to flavonoids during stress. Strong correlations were identified between the expression of biosynthetic genes and their respective metabolite concentrations, underscoring the central role of transcriptional regulation in secondary metabolite synthesis during drought stress. Collectively, our results provide a comprehensive understanding of the transcriptional and metabolic adaptations of cumin plants when exposed to drought stress. Such insights can be pivotal in designing drought-resilient crops, with significant implications for food security amidst escalating climatic challenges.

Abstract Despite advances in glioblastoma (GBM) treatments, current approaches have failed to improve the overall survival of patients. The oncogene BMI-1, a core member of the polycomb group proteins, is a potential novel therapeutic target for GBM. To enhance the efficacy and reduce the toxicity, PTC209, a BMI-1 inhibitor, was loaded into a PLGA–PEG nanoparticle conjugated with CD133 antibody (Nano-PTC209) and its effect on the behavior of human GBM stem-like cells (GSCs) and the human glioblastoma cell line (U87MG) was assessed. Nano-PTC209 has a diameter of ~ 75 nm with efficient drug loading and controlled release. The IC50 values of Nano-PTC209 for GSCs and U87MG cells were considerably lower than PTC209. Nano-PTC209 significantly decreased the viability of both GSCs and U87MG cells in a dose-dependent manner and caused a significant enhancement of apoptosis and p53 levels as well as inhibition of AKT and JNK signaling pathways. Furthermore, Nano-PTC209 significantly inhibited the migration ability, decreased the activity of metalloproteinase-2 and -9, and increased the generation of reactive oxygen species in both GSCs and U87MG cells. Our data indicate that PLGA–PEG nanoparticle conjugated with CD133 antibody could be an ideal nanocarrier to deliver PTC209 and effectively target BMI-1 for potential approaches in the treatment of GBM.

Background & objectives: In the pathogenesis of endometriosis, a variety of genes are involved. The aim of this study was to investigate the GATA2 gene expression changes in endometriosis rat model following a period of aerobic exercise and vitamin B6 intake. Methods: For this purpose, 25 adult Wistar rats were randomly divided into 5 groups, including: healthy control, patient control, patient+training, patient+vitamin, patient+vitamin+ training. In order to create an endometriosis model, rats were first anesthetized and after opening abdominal muscle, ovarian tissue and part of uterine tissue were removed and were inserted into a sterile container with one cc of PBS and sliced. Tissue fragments were transplanted into the abdominal and ovarian areas. The amount of vitamin intake was 60mg/kg and swimming program lasted 8 weeks, 30 minutes a day, five days a week. One-way ANOVA test and Tukey post hoc test were used for data analysis. Result: The results showed that a period of swimming exercise program in the patient + training group significantly increased the GATA2 level compared to the patient control group (p≤0.001). Also, the GATA2 gene expression level was significantly increased in the patient + training + vitamin group compared to the patient control group (p=0.002). However, its level in the patient group was significantly lower than that of the healthy control group (p≤0.001). Conclusion: Regular aerobic exercise combined with intake of vitamin B6 may decrease GATA2 gene expression level in endometrial rat model.