markers. This review aimed to systematically assess case-control studies investigating the 28 association of circulating microRNAs with acute ischemic stroke. Medline, CINAHL, Cochrane 29Library, Web of Science Scopus, and PubMed were searched for studies that examined the 30 association of circulating microRNAs in acute ischemic stroke patients. Studies meeting specific 31 inclusion and exclusion criteria (such as blood sample were obtained within 24 hours of an acute 32 ischemic stroke) were selected for data extraction. Two authors extracted data from the included 33 studies relevant to study design, patient characteristics, and relative microRNA expression. Eight 34 studies were included involving 572 cases and 431 healthy controls. Twenty-two microRNAs 35 (12 up-regulated and 10 downregulated) were reported as differentially expressed. Only one 36 microRNA, miR-106b, was reported as differentially expressed in at least 2 studies. Significant 37 heterogeneity in the design and methods of the included studies was noted. Differential 38 expression of a large number of microRNAs has been reported early following acute ischemic 39 stroke. More research is required in larger patient populations to further evaluate the diagnostic 40 potential of the reported microRNAs.

Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood–brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: –3.02; 95% confidence intervals: –4.41, –1.63; p < 0.001; n = 171 animals) and improved blood–brain barrier integrity (standardized mean difference: –2.02; 95% confidence intervals: –3.27, –0.77; p = 0.002; n = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function; however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood–brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.

Liver cancer is a poor prognosis cancer with limited treatment options. To develop a new therapeutic approach, we derived HCC cells from a known model of murine hepatocellular carcinoma (HCC). We treated adiponectin (APN) knock-out mice with the carcinogen diethylnitrosamine, and the resulting tumors were 7-fold larger than wild-type controls. Tumors were disassociated from both genotypes and their growth characteristics evaluated. A52 cells from APN KO mice had the most robust growth in vitro and in vivo , and presented with pathology similar to the parental tumor. All primary tumors and cell lines exhibited activity of the mammalian target of Rapamycin (mTOR) and Src pathways. Subsequent combinatorial treatment, with the mTOR inhibitor Rapamycin and the Src inhibitor Dasatinib reduced A52 HCC growth 29-fold in vivo . Through protein and histological analyzes we observed activation of these pathways in human HCC, suggesting that targeting both mTOR and Src may be a novel approach for the treatment of HCC.