Slow skeletal muscle troponin T acts as a potential prognostic biomarker and therapeutic target for hepatocellular carcinoma.

Slow skeletal muscle troponin T (TNNT1) as a poor prognostic indicator is upregulated in colon and breast cancers. However, the role of TNNT1 in the disease prognosis and biological functions of hepatocellular carcinoma (HCC) is still unclear. The Cancer Genome Atlas (TCGA), real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to evaluate the TNNT1 expression of human HCC. The impact of TNNT1 levels on disease progression and survival outcome was studied using TCGA analysis. Moreover, the bioinformatics analysis and HCC cell culture were used to investigate the biological functions of TNNT1. Besides, the immunoblot analysis and enzyme-linked immunosorbent assay (ELISA) were used to detect the extracellular TNNT1 of HCC cells and circulating TNNT1 of HCC patients, respectively. The effect of TNNT1 neutralization on oncogenic behaviors and signaling was further validated in the cultured hepatoma cells. In this study, tumoral and blood TNNT1 was upregulated in HCC patients based on the analyses using bioinformatics, fresh tissues, paraffin sections, and serum. From the multiple bioinformatics tools, the TNNT1 overexpression was associated with advanced stage, high grade, metastasis, vascular invasion, recurrence, and poor survival outcome in HCC patients. By the cell culture and TCGA analyses, TNNT1 expression and release were positively correlated with epithelial-mesenchymal transition (EMT) processes in HCC tissues and cells. Moreover, TNNT1 neutralization suppressed oncogenic behaviors and EMT in hepatoma cells. In conclusion, TNNT1 may serve as a non-invasive biomarker and drug target for HCC management. This research finding may provide a new insight for HCC diagnosis and treatment.

Involvement of Endothelial Nitric Oxide Synthase Activation in Midkine-Mediated Central Hypotensive Effects.

The growth factor midkine (MK) has been implicated in various biologic and pathologic events. It has been shown that the peripheral influence of MK on cardiovascular regulation is due to an influence on the renin-angiotensin system (RAS). The nucleus tractus solitarii (NTS) is the primary integrative center for cardiovascular control and other autonomic functions in the central nervous system. However, the signaling mechanisms involved in MK-mediated cardiovascular effects in the NTS remain unclear. In this study, we investigated whether the RAS and/or N-methyl-D-aspartate (NMDA) receptor-calmodulin-endothelial nitric oxide synthase (eNOS) signaling pathways were both involved in MK-mediated blood pressure (BP) regulation in the NTS of Wistar-Kyoto (WKY) rats. Intra-NTS microinjection and immunoblot analysis were used to evaluate the signal pathway. WKY rats were anesthetized with urethane. Unilateral microinjection of MK (600 fmol) into the NTS produced a dose-dependent decrease in BP and heart rate (HR). The depressor effects were observed before and after microinjection of the angiotensin-converting enzyme (ACE) inhibitor lisinopril (2.4 fmol), or the angiotensin receptor blockers (ARB) inhibitor valsartan (7.5 pmol). However, lisinopril and valsartan did not diminish the MK-mediated cardiovascular effects in the NTS. Microinjection of the NMDA receptor antagonist MK801 (1 nmol) or the NOS inhibitor N-nitro l-arginine methyl ester (L-NAME), (33 nmol), into the NTS attenuated the MK-induced hypotensive effects. Pretreatment with an eNOS inhibitor N5-iminoethyl-l-ornithine (L-NIO) (6 nmol) attenuated the MK-induced hypotensive effects. In this study, the data showed that MK might play a role in central cardiovascular regulation in the NTS. These results suggest that MK decreased BP and HR in the NTS probably acting via the NMDA receptor-calmodulin-eNOS signaling pathway.

Comparison of the recurrence risk of parameniscal cysts between patients treated with arthroscopic excision and arthroscopic decompression techniques.

PURPOSE: To compare the recurrence risk of parameniscal cysts between arthroscopic meniscectomy with open cystectomy (arthroscopic excision) and entirely arthroscopic techniques with intra-articular cyst decompression (arthroscopic decompression). METHODS: A retrospective longitudinal study was conducted at a medical centre in Taiwan between 2002 and 2012. Patients with symptomatic parameniscal cysts undergoing either arthroscopic excision or arthroscopic decompression were included. Parameniscal cyst recurrence was evaluated every 3 months after surgery. The recurrence risk associated with treatment group, cyst volume, and meniscal tear circumference was investigated. RESULTS: This study included 241 young to middle-aged men and women. Of these, 112 underwent arthroscopic excision and 129 underwent arthroscopic decompression. During an average 26-month follow-up period, the arthroscopic decompression group had a sixfold higher recurrence risk [prevalence: 4 and 21 %, respectively; hazard ratio, HR 6.0 (95 % confidence interval, CI 2.3-15.6); p < 0.001] than the arthroscopic excision group. Furthermore, meniscal tears >12 mm in circumference and a cyst volume >2.4 cm(3) conferred a fivefold higher recurrence risk than both lesions of smaller dimensions, both in the overall population and in the arthroscopic decompression group [HRs 5.3 (95 % CI 2.3-12.2) and 5.35 (95 % CI 2.2-13.3), respectively; p values <0.001 for both]. CONCLUSIONS: The suggestion of our study is that the recurrence of parameniscal cysts may be strongly related to large cystic lesions and large meniscal tears. Arthroscopic excision is preferable for treating parameniscal cysts, which are large cystic lesions with large meniscal tears, to reduce the recurrence risk. LEVEL OF EVIDENCE: III.