ABSTRACT
Objective: Investigating the interaction between Mast cells (MCs) and Mononuclear Phagocytes (MPs) in the tumor microenvironment (TME) of blader cancer (BCa) to uncover potential immunotherapeutic targets. Methods: Single-cell RNA sequencing (scRNA-Seq) was conducted on 12 BCa patients to identify distinct subgroups of MCs and MPs. Transcriptome data was analyzed to characterize the phenotype, gene enrichment, cell-cell communication, and biological processes. The expression levels of cytokines were assessed by enzyme-linked immunosorbent assay (ELISA), while the chemotactic effects of cytokines were evaluated through Transwell assay. Results: In muscle-invasive bladder cancer (MIBC), the proportion of interferon-stimulated MC subtype (Mast-ISG15) increased. Mast-IL13 subgroup and Mast-CCL2 subgroups were functionally enriched in interferon (IFN) and nuclear factor kappa-B (NF-κB) signaling pathways. The Mast-CCL2 subgroup overexpressed the CCL2 gene, which could chemoattract MPs through CCL2. In vitro experiments confirmed that under stimulation, activated MCs activated IFN and NF-κB signaling, increasing the secretion of CCL2 and IL-13, chemoattracted THP-1 monocyte. Conclusion: This study revealed the vital role of MCs in shaping the TME of BCa. And provides new insights for the precise treatment of BCa.
ABSTRACT
Aldosterone, a hormone synthesized by the adrenal cortex, plays a crucial role in regulating sodium and potassium levels in the kidneys through interaction with the mineralocorticoid receptor (MR) in the distal tubules and collecting ducts. While aldosterone aids in maintaining fluid balance by promoting sodium reabsorption and potassium secretion, elevated levels can lead to inflammation, oxidative stress, and organ damage. Experimental evidence highlights aldosterone's involvement in renal inflammation, collagen deposition, and fibrosis, often exacerbating the effects of therapies like angiotensin-converting enzyme inhibitors (ACEIs) by increasing proteinuria and vascular damage. Conversely, mineralocorticoid receptor antagonists (MRAs) show promise in mitigating these harmful effects. This review integrates current knowledge on aldosterone and MRAs, emphasizing their roles in renal health from both clinical and experimental perspectives. Additionally, the novel drug finerenone has shown favorable renal and cardiovascular outcomes in patients with diabetes and chronic kidney disease (CKD), warranting exploration of its potential use in other disease populations in future research.