Gender differences in gliomas: from epidemiological trends to changes at the hormonal and molecular levels.

Gender plays a crucial role in the occurrence and development of cancer, as well as in the metabolism of nutrients and energy. Men and women display significant differences in the incidence, prognosis, and treatment response across various types of cancer, including certain sex-specific tumors. It has been observed that male glioma patients have a higher incidence and worse prognosis than female patients, but there is currently a limited systematic evaluation of sex differences in gliomas. The purpose of this study is to provide an overview of the association between fluctuations in sex hormone levels and changes in their receptor expression with the incidence, progression, treatment, and prognosis of gliomas. Estrogen may have a protective effect on glioma patients, while exposure to androgens increases the risk of glioma. We also discussed the specific genetic and molecular differences between genders in terms of the malignant nature and prognosis of gliomas. Factors such as TP53, MGMT methylation status may play a crucial role. Therefore, it is essential to consider the gender of patients while treating glioma, particularly the differences at the hormonal and molecular levels. This approach can help in the adoption of an individualized treatment strategy.

Sitagliptin inhibits the survival, stemness and autophagy of glioma cells, and enhances temozolomide cytotoxicity.

The standard regimen treatment has improved GBM outcomes, but the survival rate of patients is still unsatisfactory. Temozolomide (TMZ) resistance is one of main reasons limiting the therapeutic efficacy of GBM. However, there are currently no TMZ-sensitizing drugs available in the clinic. Here we aimed to study whether the antidiabetic drug Sitagliptin can inhibit the survival, stemness and autophagy of GBM cells, and thus enhance TMZ cytotoxicity. We used CCK-8, EdU, colony formation, TUNEL and flow cytometry assays to assess cell proliferation and apoptosis; sphere formation and limiting dilution assays to measure self-renewal and stemness of glioma stem cells (GSCs); Western blot, qRT-PCR or immunohistochemical analysis to measure the expression of proliferation or stem cell markers; Western blot/fluorescent analysis of LC3 and other molecules to evaluate autophagy formation and degradation in glioma cells. We found that Sitagliptin inhibited proliferation and induced apoptosis in GBM cells and suppressed self-renewal and stemness of GSCs. The in vitro findings were further confirmed in glioma intracranial xenograft models. Sitagliptin administration prolonged the survival time of tumor-bearing mice. Sitagliptin could inhibit TMZ-induced protective autophagy and enhance the cytotoxicity of TMZ in glioma cells. In addition, Sitagliptin acted as a dipeptidyl peptidase 4 inhibitor in glioma as well as in diabetes, but it did not affect the blood glucose level and body weight of mice. These findings suggest that Sitagliptin with established pharmacologic and safety profiles could be repurposed as an antiglioma drug to overcome TMZ resistance, providing a new option for GBM therapy.

Prolonged dietary selenium deficiency or excess does not globally affect selenoprotein gene expression and/or protein production in various tissues of pigs.

We previously determined the effects of dietary selenium (Se) deficiency or excess on mRNA abundance of 12 selenoprotein genes in pig tissues. In this study, we determined the effect of dietary Se on mRNA levels of the remaining porcine selenoprotein genes along with protein production of 4 selenoproteins (Gpx1, Sepp1, Selh, and Sels) and body glucose homeostasis. Weanling male pigs (n = 24) were fed a Se-deficient (<0.02 mg Se/kg), basal diet supplemented with 0, 0.3, or 3.0 mg Se/kg as Se-enriched yeast (Angel Yeast) for 16 wk. Although mRNA abundance of the 13 selenoproteins in 10 tissues responded to dietary Se in 3 patterns, there was no common regulation for any given gene across all tissues or for any given tissue across all genes. Dietary Se affected (P < 0.05) 2, 3, 3, 5, 6, 7, 7, and 8 selenoprotein genes in muscle, hypothalamus, liver, kidney, heart, spleen, thyroid, and pituitary, respectively. Protein abundance of Gpx1, Sepp1, Selh, and Sels in 6 tissues was regulated (P < 0.05) by dietary Se concentrations in 3 ways. Compared with those fed 0.3 mg Se/kg, pigs fed 3.0 mg Se/kg became hyperinsulinemic (P < 0.05) and had lower (P < 0.05) tissue levels of serine/threonine protein kinase. In conclusion, dietary Se exerted no global regulation of gene transcripts or protein levels of individual selenoproteins across porcine tissues. Pigs may be a good model for studying mechanisms related to the potential prodiabetic risk of high-Se intake in humans.