Evaluation of the effect of taurine on the matrix metalloproteinase-9 and the expression changes of miRNA-21 and miRNA-146a in SH-SY5Y cell line.

OBJECTIVES: Alzheimer's disease (AD), a brain disorder, is the leading cause of dementia among older adults. Taurine, an amino acid abundantly present in the brain, and shows potential neuroprotective properties. Therefore, we investigated the effects of taurine on Matrix Metalloproteinase-9 (MMP-9) levels and the expression changes of miRNA-21 and miRNA-146a in the SH-SY5Y cell line. METHODS: Taurine's impact on the SH-SY5Y cell line was evaluated via the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. MMP-9 levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while the expression of miRNA-21 and miRNA-146a genes was assessed through Real-Time PCR analysis. RESULTS: The MTT assay revealed no toxic effects on SH-SY5Y cells with increasing concentrations of taurine. Analysis of gene expression indicated a rise in miRNA-21 expression and a decline in miRNA-146 expression with increasing taurine concentration, with the most notable change observed at 1 mg/mL taurine (p<0.001). ELISA results demonstrated a significant increase in MMP-9 levels in the SH-SY5Y cell line treated with 1 mg/mL taurine compared to the untreated group (p<0.001). CONCLUSIONS: Our study revealed that taurine can alter the expression of miRNA-146a and miRNA-21. In conclusion, taurine therapy presents promising therapeutic avenues for treating AD or mitigating severe symptoms. Nonetheless, further research is necessary to comprehensively grasp the precise mechanisms at play.

The role of endoplasmic reticulum stress in promoting aerobic glycolysis in cancer cells: An overview.

Aerobic glycolysis, also known as the Warburg effect, is a metabolic phenomenon frequently observed in cancer cells, characterized by the preferential utilization of glucose through glycolysis, even under normal oxygen conditions. This metabolic shift provides cancer cells with a proliferative advantage and supports their survival and growth. While the Warburg effect has been extensively studied, the underlying mechanisms driving this metabolic adaptation in cancer cells remain incompletely understood. In recent years, emerging evidence has suggested a potential link between endoplasmic reticulum (ER) stress and the promotion of aerobic glycolysis in cancer cells. The ER is a vital organelle involved in protein folding, calcium homeostasis, and lipid synthesis. Various cellular stresses, such as hypoxia, nutrient deprivation, and accumulation of misfolded proteins, can lead to ER stress. In response, cells activate the unfolded protein response (UPR) to restore ER homeostasis. However, prolonged or severe ER stress can activate alternative signaling pathways that modulate cellular metabolism, including the promotion of aerobic glycolysis. This review aims to provide an overview of the current understanding regarding the influence of ER stress on aerobic glycolysis in cancer cells to shed light on the complex interplay between ER stress and metabolic alterations in cancer cells. Understanding the intricate relationship between ER stress and the promotion of aerobic glycolysis in cancer cells may provide valuable insights for developing novel therapeutic strategies targeting metabolic vulnerabilities in cancer.

STAT3 signaling in pancreatic ductal adenocarcinoma: a candidate therapeutic target.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor prognosis which is lethal in over 90% of cases despite the standard therapies. Mainly activated by Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) is a key transcription factor, capable of exerting the expression of multitude of genes involved in survival. Moreover, STAT3 activity is regulated by the interleukin 28 receptor α (IL28RA) and glutathione s-transferase mu-3 (GSTM3), up-regulation of both contributes to the invasiveness of pancreatic cancer cells. In this regard, STAT3 overactivity has an important pathogenic role in the development of PDAC as it is associated with enhanced cell proliferation, survival, angiogenesis, and metastasis. STAT3-associated expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 3 and 9 are implicated in the angiogenic and metastatic behavior of the PDAC. Multitude of evidence underline the protective role of STAT3 inhibition against PDAC both in cell cultures and in tumor grafts. However, specific inhibition of STAT3 was not feasible until recently, when a selective potent chemical STAT3 inhibitor, termed N4, were developed and it turned out to be highly effective against PDAC in vitro, as well as in vivo. This review aims to discuss the most recent advances in our understanding of STAT3 role in the pathogenesis of PDAC and its therapeutic applications.