Is NRP2 linked to Breast cancer?3 answersNeuropilin-2 (NRP2) is linked to breast cancer, specifically triple negative breast cancer (TNBC). Overexpression of NRP2 has been found in TNBC cells, and it is associated with the oncogenic effects of LRP11-AS1, a long noncoding RNA (lncRNA). NRP2 acts as a co-receptor for vascular endothelial growth factor (VEGF)-C, and its upregulation has been shown to promote tumor growth and chemoresistance. Inhibition of NRP2 has been found to enhance tumor growth inhibition and sensitivity to chemotherapy and targeted therapy. Additionally, NRP2 has been identified as a prognostic indicator for reduced survival in bladder cancer patients. The correlation between NRP2 and the glioma-associated oncogene family zinc finger 2 (GLI2) transcripts has been observed in bladder cancer patients and cell lines. Furthermore, NRP2 has been shown to regulate downstream signaling pathways, including the transforming growth factor-beta 1 (TGFβ1) pathway, and positively regulate secreted phosphoprotein 1 (SPP1/OPN/Osteopontin).
What is the function of hif2a?5 answersHIF2A, or hypoxia-inducible factor 2 alpha, plays a crucial role in oxygen sensing and adaptation to hypoxia. It is involved in regulating the expression of genes related to angiogenesis, erythropoiesis, and cancer signaling pathways. HIF2A mutations have been associated with various conditions, including erythrocytosis, thrombosis, vascular complications, and hepatocellular carcinoma (HCC). Studies have shown that HIF2A is essential for the growth and survival of oxygen-sensitive glomus cells in the carotid body, which are responsible for ventilatory responses to hypoxia. HIF2A mutations can result in a gain-of-function phenotype, leading to the stabilization and activation of HIF2A protein, as well as the upregulation of its target genes. Overall, HIF2A plays a critical role in oxygen homeostasis, angiogenesis, and the development and progression of certain diseases, making it an important therapeutic target for various conditions associated with hypoxia signaling.
What is the role of FGF23 in the pathogenesis of type 2 diabetes?4 answersFGF23 plays a role in the pathogenesis of type 2 diabetes by influencing glucose metabolism and insulin resistance. It has been found that serum FGF23 levels are significantly higher in patients with type 2 diabetes and hypertension compared to healthy individuals. These elevated FGF23 levels are positively correlated with body shape parameters such as weight, waistline, and BMI. Furthermore, FGF23 resistance has been observed in patients with hypertension in type 2 diabetes, suggesting that high levels of FGF23 may be a compensatory reaction to offset hypertension. Additionally, FGF23 has been shown to modulate the production of alpha-2-HS-glycoprotein (AHSG) in the liver, which is involved in inflammation and cardiovascular disease, suggesting a potential therapeutic target for chronic kidney disease. Overall, FGF23 appears to be involved in the complex interactions between type 2 diabetes, inflammation, and cardiovascular disease.
Is Nrf2 present in all eukaryotes and prokaryotes?2 answersNrf2 is not present in all eukaryotes and prokaryotes. It is a transcription factor that regulates the response to oxidative stress in cells. Studies have shown that Nrf2 is widely expressed in various tissues and plays a role in controlling megakaryocytic and/or erythroid cell function. However, the presence of Nrf2 in prokaryotes is not mentioned in the abstracts provided. The abstracts mainly focus on the distribution and function of NAD(P)-dependent enzymes, the differences between eukaryotic and prokaryotic polypeptide release factors, and the transcription factors involved in the response to oxidative stress in bacteria, yeast, and mammalian cells. Therefore, based on the information provided, it cannot be concluded that Nrf2 is present in all eukaryotes and prokaryotes.
In which organisms is Nrf2 present?3 answersNrf2 is present in a variety of organisms including fish (European eel Anguilla anguilla), mammals (macrophages), humans (alcoholic liver disease), adipocytes (white adipose tissue), and animal cells (central to redox homeostasis).
What are the three druggable sites of nrf2 pathway?5 answersThe three druggable sites of the NRF2 pathway are the cysteine sensors in KEAP1, the Kelch domain of KEAP1, and the proteasomal degradation of KEAP1. Compounds that target these sites have been developed, including electrophiles that bind covalently to cysteine sensors in KEAP1, non-electrophilic protein-protein interaction inhibitors that bind to the Kelch domain of KEAP1, and heterobifunctional proteolysis-targeting chimeras (PROTACs) that promote the proteasomal degradation of KEAP1. These compounds have shown promise in preclinical and clinical studies, with two compounds, dimethyl fumarate and RTA-408, already in clinical practice for the treatment of multiple sclerosis and Friedreich's ataxia, respectively.