Increasing evidence suggests that large intervening non-coding RNAs (lincRNAs) regulate key pathways in cancer invasion and metastasis. In this observational retrospective study, the expression of the oncogenic lincRNA HOX transcript antisense RNA (HOTAIR) gene was measured in 63 patients with hepatocellular carcinoma (HCC) following hepatic resection. The HOTAIR gene was significantly overexpressed in HCC tissues compared with adjacent non-tumour tissues. Patients with high HOTAIR gene expression in their tumours had an increased risk of recurrence after hepatectomy. There was also a significant correlation between HOTAIR expression and lymph node metastasis. In vitro assays in the HCC cell line Bel7402 demonstrated that knockdown of HOTAIR lincRNA reduced cell proliferation and was associated with reductions in levels of matrix metalloproteinase-9 and vascular endothelial growth factor protein, which are important for cell motility and metastasis. In conclusion, HOTAIR lincRNA might be a potential biomarker for the existence of lymph node metastasis in HCC.

Sepsis triggered by endotoxinemia may impair cardiac function. A decline in tolerance to septic shock occurs with aging. This study addressed the hypothesis that aging negatively impairs expression of gelsolin, and axerts the regulatory effects on the water channel protein aquaporin-l (AQP-l) and endotoxin-inducible nitric oxide synthase (iNOS). We explored whether the age-related gene changes are associated with the cardiac dysfunction induced by endotoxic stress exposure. Male mice at young (-3-month) and old (-12-month) ages received intraperitoneal injections of saline or lipopolysaccharide (LPS, 30mg/Kg). Cardiac performance and morphology were analyzed by echocardiography at baseline and 2 and 24 hafter injection. At the end of treatment, the animals were sacrificed, and cardiac tissues were collected for assessing expression of gelsolin, AQP-l, iNOS, and transcription-3 (STAT3). LPS administration led to a decreased contractility while increasing cardiac dimensions in both young and old mice. LPS also markedly induced expression of gelsolin in both animal groups. However, compared to young mice, old mice showed compromised induction of gelsolin and cardiac performance in response to endotoxin. Meanwhile, the LPS-exposed old animals exhibited higher levels of AQP-l, iNOS, and phosphorylated STAT3. Gelsolin-null mice had increased expression of glycosylated AQP-l and STAT3 phosphorylation as well as cardiac dysfunction. Thus, endotoxin administration induces expression of gelsolin, AQP-l and pro-inflammatory genes, such as iNOS. Our data suggest that changed expression of gelsolin, AQP-l and iNOS may contribute to dysfunction of hearts in aged subjects with septic endotoxinemia.Sepsis ischaracterizedby multi-organ dysfunction, including cardiovascular dysfunction. Although the precise mechanism of the myocardial dysfunction that occurs during endotoxic stress exposure is not well defined, increasing experimental evidence suggests that the main molecular mechanisms include activation of various cytokines and inflammatory factors, increased vascular permeability, cytoskeleton remodeling, and induction of nitric oxide synthase (iNOS) with the subsequent generation of nitric oxide (NO). Sepsis predominantly affects older persons, and yet experimental data exploring septic

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Funding Acknowledgements Type of funding sources: None. Background Cardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced coexpression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti-apoptotic, pro-survival and pro-angiogenic activities of MSCs isolated from the adipose tissue (AT-MSCs), may increase CSC survival, favoring their paracrine activities. Aim To investigate the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment toward the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT-MSCs overexpressing TERT and MYOCD (T/M AT-MSCs). Methods and Results Murine CSCs were isolated with the cardiosphere (CSps) isolation technique. T/M AT-MSCs and their secretome improved spontaneous intracellular calcium changes (Figure 1) and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT-MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28±4 vs 10±3%, p=0.02). Pretreatment with CM (15±2, p=0.02) or with the EV-enriched fraction (10±1%, p=0.02) obtained from mock-transduced AT-MSCs in normoxia reduced cell death after SI/R. The effect was more prononunced with CM (7±1%, p=0.01) or the EV-enriched fraction (2±1%, p=0.01) obtained from T/M AT-MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase-3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α-actinin and cardiac actin. Conclusions The T/M AT-MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.