TNF-α Pretreated Hematopoietic Stem Cells Inhibit the Migration and Inflammatory Response of HUVECs and Attenuate GVHD.

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 Ecadherin, 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.

CTNNB1 Knockdown Inhibits Cell Proliferation and Aldosterone Secretion Through Inhibiting Wnt/ß-Catenin Signaling in H295R Cells.

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 ß-catenin expression and inhibited proliferation of H295 R cells. CTNNB1 knockdown inhibited Wnt/ß-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/ß-catenin signaling pathway, indicating that targeting Wnt/ß-catenin signaling pathway may be an important approach to decrease aldosterone secretion in the treatment of aldoster-producing adenomas.

[Long-term outcomes of 125I brachytherapy combined with maximal androgen blockade for metastatic prostate cancer].

OBJECTIVE: To investigate the long-term clinical value of prostate 125I brachytherapy (BT) combined with maximal androgen blockade (MAB) in the treatment of metastatic prostate cancer (mPCa). METHODS: We retrospectively analyzed the clinical data on 173 cases of mPCa treated by MAB (n = 126) or BT+MAB (n = 47) from December 2011 to December 2016 and followed up for 6－76 (44.17 ± 19.73) months. We compared the PSA level, prostate volume, IPSS, progression-free survival, and the rates of 3- and 5-year overall survival between the two groups. RESULTS: After treatment, the minimum PSA level was significantly lower in the BT+MAB than in the MAB group ï¼»3.77 ± 4.14ï¼½ vs ï¼»5.96 ± 7.01ï¼½ ng/ml, P = 0.046) and the time to reach the minimum level was shorter in the former than in the latter (ï¼»5.19 ± 2.83ï¼½ vs ï¼»6.52 ± 3.34ï¼½ mo, P = 0.016). The prostate volume was markedly reduced in both of the groups at 1, 3 and 5 years after treatment as compared with the baseline, even more significantly in the BT+MAB than in the MAB group (P < 0.01), though with no statistically significant difference between the two groups before treatment (P = 0.307). The IPSS was remarkably decreased in both of the groups at 1 and 3 years (P < 0.01) but showed no significant difference at 5 years after treatment as compared with the baseline (P > 0.05) or between the two groups before and after treatment (P > 0.05). The progression-free survival was obviously longer in the BT+MAB than in the MAB group (ï¼»37.29 ± 15.73ï¼½ vs ï¼»29.41 ± 14.37ï¼½ mo, P = 0.011), and the rates of 3- and 5-year overall survival were higher in the former than in the latter (74.60% and 60.70% vs 62.60% and 51.50%, P = 0.227 and P = 0.356). Kaplan-Meier survival curves showed no statistically significant difference in the overall survival between the two groups (P = 0.105). CONCLUSIONS: Both MAB and BT+MAB are effective therapies for mPCa, but the latter can achieve a longer progression-free survival.