Prognostic and immune roles of UROC1 in human cancers: from mechanism exploration of NAFLD and HCC to pan-cancer analysis.

OBJECTIVE: Both non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are prevalent diseases worldwide. This study aimed to explore the underlying mechanisms of NAFLD and HCC and identify new therapeutic targets for human cancers. MATERIALS AND METHODS: NAFLD and HCC gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify co-expressed genes associated with NAFLD and HCC. Public databases were consulted to find common targets of NAFLD and HCC. Enrichment analysis and CIBERSORT techniques were employed to analyze the pathways enriched with DEGs and the attributes of infiltrating immune cells. Furthermore, the expression data of UROC1 and clinical information of patients were acquired from The Cancer Genome Atlas (TCGA) database. Finally, the expression of the UROC1 was validated by immunohistochemistry (IHC). RESULTS: Through a comprehensive bioinformatics analysis, eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1) were identified. Enrichment analysis indicated that inflammatory and immune response may be common features between NAFLD and HCC. CIBER-SORT analysis revealed an imbalance of plasma cells and macrophages in NAFLD and HCC. Pan-cancer analysis demonstrated that UROC1 expression was related to clinical outcomes and tumor immunity in various cancers. Moreover, a strong correlation was exhibited between UROC1 expression and crucial elements, including tumor mutation burden (TMB), microsatellite instability (MSI), multiple immune checkpoints (ICP), and tumor microenvironment (TME). Importantly, an adverse clinical prognosis of HCC was linked to decreased UROC1 expression, which was consistent with IHC results. CONCLUSIONS: We identified eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1), which may become early diagnostic and therapeutic targets for NAFLD and HCC. The pan-cancer analysis of UROC1 provides new evidence for its broad application prospects in the field of HCC and other cancers.

In vitro investigation of nanohydroxyapatite/poly(L-lactic acid) spindle composites used for bone tissue engineering.

Calcium phosphate ceramics such as synthetic hydroxyapatite and tricalcium phosphate are widely used in the clinic, but they stimulate less bone regeneration. In this paper, nano-hydroxyapatite/poly(L-lactic acid) (nano-HA/PLLA) spindle composites with good mechanical performance were fabricated by a modified in situ precipitation method. The HA part of composite, distributing homogenously in PLLA matrix, is spindle shape with size of 10-30 nm in diameter and 60-100 nm in length. The molar ratio of Ca/P in the synthesized nano-HA spindles was deduced as 1.52 from the EDS spectra, which is close to the stoichiometric composition of HA (Ca/P & 1.67). The compress strength is up to 150 MPa when the HA content increase to 20 %. The in vitro tests indicate that HA/PLLA bio-composites have good biodegradability and bioactivity when immersed in simulated body fluid solutions. All the results suggested that HA/PLLA nano-biocomposites are appropriate to be applied as bone substitute in bone tissue engineering.

Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats.

Human dCTP pyrophosphatase 1 promotes breast cancer cell growth and stemness through the modulation on 5-methyl-dCTP metabolism and global hypomethylation.

Human DCTPP1 (dCTP pyrophosphatase 1), also known as XTP3-transactivated protein A, belongs to MazG-like nucleoside triphosphate pyrophosphatase (NTP-PPase) superfamily. Being a newly identified pyrophosphatase, its relevance to tumorigenesis and the mechanisms are not well investigated. In the present study, we have confirmed our previous study that DCTPP1 was significantly hyperexpressed in breast cancer and further demonstrated its strong association with tumor progression and poor prognosis in breast cancer. Knockdown of DCTPP1 in breast cancer cell line MCF-7 cells remarkably retarded proliferation and colony formation in vitro. The capacity of mammosphere formation of MCF-7 was suppressed with the silence of DCTPP1, which was consistent with the enhanced mammosphere-forming ability in DCTPP1-overexpressed MDA-MB-231 cells. To further dissect the mechanisms of DCTPP1 in promoting tumor cell growth and stemness maintenance, its biochemical properties and biological functions were investigated. DCTPP1 displayed bioactive form with tetrameric structure similar to other MazG domain-containing pyrophosphatases based on structure simulation. A substrate preference for dCTP and its methylated or halogen-modified derivatives over the other canonical (deoxy-) NTPs was demonstrated from enzymatic assay. This substrate preference was also proved in breast cancer cells that the intracellular 5-methyl-dCTP level increased in DCTPP1-deficient MCF-7 cells but decreased in DCTPP1-overexpressed MDA-MB-231 cells. Moreover, global methylation level was elevated in DCTPP1-knockdown MCF-7 cells or mammosphere-forming MCF-7 cells but decreased significantly in DCTPP1-overexpressed MDA-MB-231 cells and its mammospheres. Our results thus indicated that human DCTPP1 was capable of modulating the concentration of intracellular 5-methyl-dCTP. This in turn affected global methylation, contributing to a known phenomenon of hypomethylation related to the cancer cell growth and stemness maintenance. Our current investigations point to the pathological functions of DCTPP1 overexpression in breast cancer cells with aberrant dCTP metabolism and epigenetic modification.

Factors influencing ablation of atherosclerotic plaque with argon laser.

The ablative effect of argon laser delivered fibreoptically in vitro on 234 segments of atherosclerotic human aorta was studied. The variables such as energy density, type of atheroma and immersion media were included, and all irradiated specimens were subsequently submitted to histological examination and crater volumes in mm3 to micrometer measurements under light microscope. The results showed 1) a linear relationship between energy dose and crater volume in fibrous atheroma, 2) significantly greater damage or surrounding in the higher energy dose groups, 3) a lower dose response in calcified tissue than in fatty streaks or fibrous atheroma, and 4) immersion of tissue in blood during ablation resulted in a significantly greater dose response than immersion in plasma or saline, and the corresponding surrounding tissue damage was greatest when immersed in blood. Thus, argon laser is both effective and predictable in response during ablating of atheromatous tissue. The efficacy of the process is dependent on immersion medium, while the degree of surrounding tissue damage is dependent on energy dose.