The metabolite 3-hydroxiglutaric acid effectively reduces glioblastoma growth in vivo by affecting the structural integrity of tumor vasculature. | LitMetric
3-Hydroxiglutaric acid (3-OH-GA) is a disease-specific metabolite that accumulates in tissues and body fluids of patients with Glutaric aciduria type I (GAI) and has been associated with vascular abnormalities in these kindreds. Here, we demonstrate that 3-OH-GA also affects the integrity of tumor vessels leading to tumor growth inhibition in a subcutaneous model of human glioblastoma multiforme (GBM). This effect correlated with a marked decrease of VE-Cadherin expression in endothelium of 3-OH-GA-treated tumors. Furthermore, in vitro observations indicated also a direct effect of 3-OH-GA in glioma cells that showed defective mitosis and significant proliferation inhibition. In summary, the GAI-specific metabolite 3-OH-GA significantly inhibited growth of GBM xenografts by affecting the structural integrity of tumor blood vessels and in addition by causing defective mitosis and proliferation inhibition of tumor cells.
During mitosis, chromosomes condense, align to form a metaphase plate and segregate to the two daughter cells. Mitosis is one of the most complex recurring transformations in the life of a cell and requires a high degree of reliability to ensure the error-free transmission of genetic information to the next cell generation. An abnormally prolonged mitosis indicates potential defects that compromise genomic integrity.
This study evaluates the protective effects of sinapic acid (SA), a polyphenolic compound with diverse biological activities, against ethanol-induced gastric ulcers in rats. A gastric ulcer model was established using ethanol (ETH), and the experimental groups received either omeprazole (OMEP, 20 mg/kg) or SA at doses of 20 mg/kg and 40 mg/kg via oral gavage for 14 days. Biochemical markers, including total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA), and myeloperoxidase (MPO) activity, were assessed alongside proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6) using ELISA.
PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that bind to the PIWI subclass of the Argonaute protein family and are essential for maintaining germline integrity. Initially discovered in , PIWI proteins safeguard piRNAs, forming ribonucleoprotein (RNP) complexes, crucial for regulating gene expression and genome stability, by suppressing transposable elements (TEs). Recent insights revealed that piRNAs and PIWI proteins, known for their roles in germline maintenance, significantly influence mRNA stability, translation and retrotransposon silencing in both stem cells and bodily tissues.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency accounts for approximately 95% of all CAH cases and is one of the most common inborn errors of metabolism. While glucocorticoid therapy has significantly improved patient outcomes, the focus has shifted towards managing the long-term effects. Numerous adverse outcomes have been associated with CAH, including those resulting from supraphysiological doses of glucocorticoid and mineralocorticoid replacement, excessive adrenal androgen secretion, and elevated levels of steroid precursors and adrenocorticotropic hormone (ACTH).
