Aldosterone-producing adenomas (APA) is one of the causative factors of primary aldosteronism. Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Cell proliferation and aldosterone secretion of H295 R cells in response to angiotensin Ⅱ (Agn Ⅱ) were analyzed. We found that CTNNB1 knockdown reduced β-catenin expression and inhibited proliferation of H295 R cells. CTNNB1 knockdown inhibited Wnt/β-catenin signaling pathway and downregulated expression of downstream genes including axin 2, lymphoid enhancer binding factor 1 ( LEF1), and cyclin D1. In addition, CTNNB1 knockdown decreased responses of H295 R cells to Agn Ⅱ and decreased aldosterone secretion. Our findings suggest that CTNNB1 knockdown can inhibit H295 R cell proliferation and decrease aldosterone secretion in the responses of H295 R cells to Ang II through inhibiting Wnt/β-catenin signaling pathway, indicating that targeting Wnt/β-catenin signaling pathway may be an important approach to decrease aldosterone secretion in the treatment of aldoster-producing adenomas.

Background: Hematologic diseases have seriously threatened human health. Although hematopoietic stem cell transplantation (HSCT) is an effective curative option, the complications, especially graft-versus-host disease (GVHD), are a big problem. Methods: TNF-α pretreatment of hematopoietic stem cells. Apoptosis was detected by flow cytometry, Transwell, and wound healing assays were used to assess cell migration and invasion, E-selectin expression was observed by fluorescence imaging, the levels of NO were measured by a kit, the expression of E-cadherin, MMP2, and MMP9 was detected in cells by qRT-PCR, and western blot was used to analyze the expression of E-cadherin, CXCL12, MCP-1, MCP-3, MMP2, and MMP9. Results: TNF-α induces a high apoptosis rate of CD3, CD19, and CD133 and a low apoptosis rate of CD34. The level of Fas and TNF-R1 was significantly high than that of TNF-R2. HSCs treated with TNF-α declined the invasion and migration of HUVECs. E-selectin, MMP2 and MMP9 mRNA levels of HUVECs and MMP2, CXCL12, MCP-1, and MCP-3 were decreased after HSCs-TNF-α treatment, while the E-cadherin mRNA and protein level of HUVECs was enhanced with HSCs-TNF-α treatment. Conclusion: TNF-α pretreated HSCs can lead to reduced levels of migration, adhesion, and chemokines of HUVECs, thereby declining the inflammatory response and GVHD.

Infectious ureteral stones often lead to sepsis. This study investigated the effect of meloxicam on renal injury caused by sepsis. A sepsis kidney injury model was established using lipopolysaccharide (LPS). HK-2 cells were divided into three groups: control, LPS, and LPS+Mel. The expression of TNF-α, IL-6, Bcl-2, and Bax mRNA and protein were detected using PCR and Western blot. The inflammation of HK-2 cells was observed using IL-1β immunofluorescence. Apoptosis was investigated using LDH content, TUNEL staining, and flow cytometry. The viability of HK-2 cells was detected using a CCK-8 assay. The protein expression of the PI3K/AKT pathway was examined to investigate the mechanism of action of Mel. LPS treatment increased TNF-α, IL-6, and Bax expression while decreasing Bcl-2 expression. However, Mel treatment reversed these effects. Mel also decreased the number of TUNEL-positive cells and the apoptotic rate and LDH content in the LPS+Mel group. Additionally, Mel up-regulated the p-PI3K and p-AKT expression, indicating that Mel inhibits inflammation and apoptosis of HK-2 cells treated with LPS by activating the PI3K/AKT pathway. In conclusion, Mel could inhibit inflammation and apoptosis of HK-2 cells treated with LPS via activation of PI3K/AKT pathway.