HDAC3 improves intestinal function of mice by regulating cGAS-Sting pathway of intestinal glial cells.

It is found that HDAC3 may be a potential therapeutic target for intestinal related diseases. At present, the role and mechanism of HDAC3 in the pathogenesis of severe acute pancreatitis (SAP) have not been reported, which needs to be further explored. The SAP mouse model was established and the expression of HDAC3 was detected by immunohistochemistry. H&E staining showed the intestinal pathological state of SAP mice. The expression of HDAC3 was measured by real-time quantitative PCR (RT qPCR) and Western blot. Apoptosis kit was used to determine cell apoptosis rate. The level of inflammatory factors was detected by ELISA kits. The expressions of HDAC3, cGAS and Sting were significantly increased in SAP patients and SAP mice. Silencing HDAC3 promoted the proliferation and adhesion of intestinal glial cells and inhibited the inflammation and apoptosis of intestinal epithelial cells. In addition, silencing HDAC3 inhibited oxidative stress in intestinal epithelial cells. Furthermore, silencing HDAC3 inhibited the activation of cGAS-Sting pathway in intestinal glial cells. More importantly, silencing HDAC3 alleviates intestinal barrier function in SAP mice. HDAC3 inhibition improves acute pancreatitis in mice by regulating cGAS-Sting pathway of intestinal glial cells.

Hyaluronic acid-modified curcumin-copper complex nano delivery system for rapid healing of bacterial prostatitis.

Bacterial prostatitis is a bacterial infection of the prostate gland presenting with lower quadrant abdominal pain, urination disorders and poor fertility. In recent years, reports have emerged on the significantly reduced efficacy of fluoroquinolone drugs attributed to multiple drug-resistant bacteria, emphasizing the need for new drugs. In this study, we designed a targeting drug delivery system via curcumin copper complex grafted with hyaluronic acid. Subsequently, the prepared system was characterized using FT-IR, XRD, SEM, XPS and 1H NMR methods. In addition to the substantial improvement in the solubility of the carrier, its antibacterial performance and targeting ability were improved. Interestingly, the grafting of hyaluronic acid endowed the carrier with excellent CD44 receptor targeting function and good water solubility, and the complexation of copper ions greatly enhanced its antibacterial capability, especially the inhibitory effect on E. coli. The anti-prostatitis effect of the drug was evaluated comprehensively by establishing a bacterial prostatitis model infected by E. coli. Assessment of the anti-prostatitis effects in vivo indicated that the Cur-Cu@HA delivery system could effectively promote recovery from bacterial prostatitis by downregulating inflammation. In conclusion, our Cur-Cu@HA delivery system has great potential for treating bacterial prostatitis.

Hyaluronic acid/serotonin-decorated cerium dioxide nanomedicine for targeted treatment of ulcerative colitis.

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease often characterized by rapid progression and frequent comorbidities that make its treatment challenging. In colonic ulcers of UC patients, myeloperoxidase (MPO) is highly expressed, which results in an abundance of macrophages and reactive oxygen species. This study developed an active MPO-targeting hyaluronic acid/serotonin ceria nanoenzyme (HA-5-HT@CeO2) using the electrostatic interaction between CeO2 nanoparticles, 5-hydroxyserotonin-cerium oxide and hyaluronic acid. Based on the dual targeting effects of MPO and the macrophage CD44+ receptor in locating the inflammatory site in conjunction with the inflammatory area of the colon through electrostatic action, CeO2 nanoparticles along with multiple similar enzymes were used to eliminate O2, H2O2 and ˙OH and other reactive oxygen species, achieving targeted repair of the intestinal epithelial barrier through the elimination of inflammatory factors. In studies involving pharmacodynamics in vitro and DSS-induced animal models of acute colitis in vivo, HA-5-HT@CeO2 has been shown to reduce inflammation further and treat ulcerative colitis compared to traditional drugs. Additionally, active targeting of MPO inflammation can lead to accurate drug delivery to the site and can minimize the side effects associated with the drug. HA-5-HT@CeO2 is a promising novel drug for the treatment of ulcerative colitis. In addition to illustrating the benefits of this novel nanodrug delivery in treating ulcerative colitis compared to traditional medications, this study provides theoretical and experimental support for its application to any targeted therapy for ulcerative colitis.

LINC01535 Attenuates ccRCC Progression through Regulation of the miR-146b-5p/TRIM2 Axis and Inactivation of the PI3K/Akt Pathway.

lncRNAs, a group of eukaryotic cell genome-encoded transcripts, have been demonstrated to exert a notable impact on tumorigenesis. LINC01535, belonging to the lncRNA family, was reported to have an aberrant expression in certain types of cancers and thus affect cancer progression. Nevertheless, the expression pattern and potential roles of LINC01535 in clear cell renal cell carcinoma (ccRCC) remain to be elucidated. Here, LINC01535 expression was detected in ccRCC by RT-qPCR, cell proliferation by CCK-8 assays, and invasion by transwell assays. Besides, effects of LINC01535 on in vivo tumor growth were investigated by xenograft tumor models. The miR-146b-5p/LINC01535/TRIM2 interaction was evaluated via luciferase reporter assays. This study showed downregulation of LINC01535 in ccRCC. Moreover, LINC01535 upregulation attenuated in vitro ccRCC development and hindered in vivo tumor growth. Furthermore, LINC01535 sponged miR-146b-5p which had a negative correlation with LINC01535, and TRIM2 was a direct target of miR-146b-5p and mediated by LINC01535. Mechanically, LINC01535/miR-146b-5p/TRIM2 axis affected ccRCC progression by mediating the PI3K/Akt signaling. All in all, our observations suggest the LINC01535/miR-146b-5p/TRIM2 axis as a crucial role in ccRCC.

Association of finasteride with prostate cancer: A systematic review and meta-analysis.

BACKGROUND: The Prostate Cancer Prevention Trial has shown a protective effect of finasteride on prostate cancer, but it also showed that finasteride can increase the risk of high-grade prostate cancer. Several studies have investigated the relationship between finasteride and prostate cancer, but these studies have shown inconsistent results. ETHICS: The protocol was approved by the institutional review board of each study center. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki. METHODS: We performed a systematic literature review and meta-analysis to assess the association between finasteride and prostate cancer. Systematic literature searches were conducted using PubMed, EMBASE, Science Direct/Elsevier, MEDLINE, CNKI, and the Cochrane Library up to October 2018 to identify studies that involved the relationship between finasteride and prostate cancer. Meta-analysis was performed using Review Manager and Stata software. Combined ORs were identified with 95% confidence intervals (95% CI) in a random or fixed effects model. RESULTS: Eight studies were identified, including 54,335 cases of patients that used finasteride and 9197 patients who served as placebo controls. Our results illustrate that there is a significant correlation between finasteride use and prostate cancer with combined ORs of 0.70 [0.51, 0.96]. A significant correlation between finasteride use and high-grade prostate cancer was also observed with combined ORs of 2.10 [1.85, 2.38]. CONCLUSIONS: This study confirms that finasteride significantly reduced the risk of prostate cancer; however, the malignant degree of prostate cancer was increased. Studies with larger sample sizes are needed to better clarify the correlation between finasteride use and prostate cancer.

SOX30, a target gene of miR-653-5p, represses the proliferation and invasion of prostate cancer cells through inhibition of Wnt/ß-catenin signaling.

BACKGROUND: Sex-determining region Y-box containing gene 30 (SOX30) is a newly identified tumor-associated gene in several types of cancer. However, whether SOX30 is involved in the development and progression of prostate cancer remains unknown. This study investigated the potential role of SOX30 in prostate cancer. METHODS: Prostate cancer cell lines and a normal prostate epithelial cell line were used for the experiments. The expression of SOX30 was determined using quantitative real-time PCR and western blot analysis. The malignant cellular behaviors of prostate cancer were assessed using the Cell Counting Kit-8, colony formation and Matrigel invasion assays. The miRNA-mRNA interaction was validated using the dual-luciferase reporter assay. RESULTS: SOX30 expression was lower in cells of prostate cancer lines than in cells of the normal prostate epithelial line. Its overexpression repressed the proliferation and invasion of prostate cancer cells. SOX30 was identified as a target gene of microRNA-653-5p (miR-653-5p), which is upregulated in prostate cancer tissues. MiR-653-5p overexpression decreased SOX30 expression, while its inhibition increased SOX30 expression in prostate cancer cells. MiR-653-5p inhibition also markedly restricted prostate cancer cell proliferation and invasion. SOX30 overexpression or miR-653-5p inhibition significantly reduced ß-catenin expression and downregulated the activation of Wnt/ß-catenin signaling. SOX30 knockdown significantly reversed the miR-653-5p inhibition-mediated inhibitory effect on the proliferation, invasion and Wnt/ß-catenin signaling in prostate cancer cells. CONCLUSIONS: These results reveal a tumor suppressive function for SOX30 in prostate cancer and confirmed the gene as a target of miR-653-5p. SOX30 upregulation due to miR-653-5p inhibition restricted the proliferation and invasion of prostate cancer cells, and this was associated with Wnt/ß-catenin signaling suppression. These findings highlight the importance of the miR-653-5p-SOX30-Wnt/ß-catenin signaling axis in prostate cancer progression.

Suppression of microRNA-454 impedes the proliferation and invasion of prostate cancer cells by promoting N-myc downstream-regulated gene 2 and inhibiting WNT/ß-catenin signaling.

MicroRNA-454 (miR-454) is emerging as critical regulator in tumorigenesis; it may function as an oncogene or a tumor suppressor. However, the role of miR-454 in prostate cancer remains unknown. In this study, we aimed to investigate the function and molecular mechanisms of miR-454 in prostate cancer. We found that miR-454 was highly expressed in prostate cancer tissues and cell lines (*p<0.05), as detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 assay, colony formation assay and cell invasion assay showed that the inhibition of miR-454 significantly suppressed prostate cancer cell proliferation and invasion (*p<0.05), whereas the overexpression of miR-454 markedly promoted prostate cancer cell proliferation and invasion (*p<0.05). Bioinformatics analysis showed that N-myc downstream-regulated gene 2 (NDRG2), a well-known tumor suppressor, was identified as a potential target gene of miR-454. Dual-luciferase reporter assay showed that miR-454 directly targeted the 3'-untranslated region of NDRG2. RT-qPCR and western blot showed that miR-454 overexpression significantly decreased NDRG2 expression (*p<0.05), whereas miR-454 inhibition markedly promoted NDRG2 expression (*p<0.05). Spearman's correlation analysis showed that miR-454 expression was inversely correlated with NDRG2 expression in prostate cancer tissues (r=-0.8932; p<0.0001). Moreover, miR-454 inhibition significantly suppressed the protein expression of ß-catenin (*p<0.05) and blocked the activation of WNT signaling (*p<0.05). In addition, small interfering RNA mediated NDRG2 knockdown significantly reversed the antitumor effect of miR-454 inhibition on prostate cancer cell proliferation and invasion (*p<0.05). Taken together, these results reveal an oncogenic role of miR-454, which promotes prostate cancer cell proliferation and invasion by downregulation of NDRG2. These results also suggest miR-454 as a potential therapeutic target for the treatment of prostate cancer.