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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disease of the heart muscle. Clinical challenges remain, however, in identifying patients with ARVC in the early or concealed stages with subtle clinical manifestations. Therefore, we wanted to identify potential targets by immunohistochemical (IHC) analysis in comparison with controls. Pathogenic mutations were identified in 11 of 37 autopsied patients with ARVC. As observed from IHC analysis of the RV, expression of αT-catenin and plakophilin-2 is significantly decreased in autopsied patients with ARVC as compared to controls, and the decreased expression is consistent in patients with and without pathogenic mutations. Furthermore, ARVC specimens demonstrated a reduced localization of αT-catenin, desmocollin-2, desmoglein-2, desmoplakin, and plakophilin-2 on intercalated discs. These findings have been validated by comparing RV specimens obtained via endomyocardial biopsy between patients with ARVC and those without. The pathogenic mutation was present in 3 of 5 clinical patients with ARVC. In HL-1 myocytes, siRNA was used to knockdown CTNNA3, and western blotting analysis demonstrated that the decline in αT-catenin expression was accompanied by a significant decline in the expression of plakophilin-2. The aforementioned effect was directed towards protein degradation rather than mRNA stability. Plakophilin-2 expression decreases concurrently with the decline in CTNNA3 expression. Therefore, the expression of αT-catenin and plakophilin-2 could be potential surrogates for the diagnosis of ARVC. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) regulate a diverse array of cellular processes at the transcriptional, post-transcriptional, translational, and post-translational levels. Accumulating evidence suggests that lncRNA MEG3 exerts a large repertoire of regulatory functions in cellular stemness. This review focuses on the molecular mechanisms by which lncRNA MEG3 functions as a signal, scaffold, guide, and decoy for multi-lineage differentiation and even cancer progression. The role of MEG3 in various types of stem cells and cancer stem cells is discussed. Here, we provide an overview of the functional versatility of lncRNA MEG3 in modulating pluripotency, differentiation, and cancer stemness. [ABSTRACT FROM AUTHOR]

From the stems of Liriodendron tulipifera, seventeen known compounds have been extracted, isolated and purified. By using spectroscopic analysis, the structures of these pure constituents were determined as three lignans, four steroids and ten benzenoids. Identified compounds were screened for antioxidant abilities using: 1,1-diphenyl-2-picrylhydrazul (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging free radical activity assays; metal chelating power test; and ferric reducing/antioxidant power (FRAP) examination. The result revealed that seventeen compounds had potential anti-oxidative capabilities. In addition, the anti-tyrosinase effect was determined by calculating the hydroxylation of L-tyrosine to L-dopa and the oxidization of L-dopa to dopaquinone, according to in vitro mushroom tyrosinase evaluation platform. Furthermore, based on assays on B16F10 cell line, our data suggest that five compounds isolated from L. tulipifera would be able to inhibit tyrosinase activity and reduce the melanin content in animal cells. Therefore, some of the examined compounds could be potentially used in the cosmetic skin whitening business, therapeutic applications or the food industry. [ABSTRACT FROM AUTHOR]

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined. [ABSTRACT FROM AUTHOR]