MicroRNA-520b Inhibits Growth of Hepatoma Cells by Targeting MEKK2 and Cyclin D1

Growing evidence indicates that the deregulation of microRNAs (miRNAs) contributes to the tumorigenesis. We previously revealed that microRNA-520b (miR-520b) was involved in the complement attack and migration of breast cancer cells. In this report, we show that miR-520b is an important miRNA in the development of hepatocellular carcinoma (HCC). Our data showed that the expression levels of miR-520b were significantly reduced in clinical HCC tissues and hepatoma cell lines. We observed that the introduction of miR-520b dramatically suppressed the growth of hepatoma cells by colony formation assays, 5-ethynyl-2-deoxyuridine (EdU) incorporation assays and 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Moreover, ectopic expression of miR-520b was able to inhibit the growth of hepatoma cells in nude mice. Further studies revealed that the mitogen-activated protein kinase kinase kinase 2 (MEKK2) and cyclin D1 were two of direct target genes of miR-520b. Silencing of MEKK2 or cyclin D1 was able to inhibit the growth of hepatoma cells in vitro and in vivo, which is consistent with the effect of miR-520b overexpression on the growth of hepatoma cells. In addition, miR-520b significantly decreased the phosphorylation levels of c-Jun N-terminal kinase (p-JNK, a downstream effector of MEKK2) or retinoblastoma (p-Rb, a downstream effector of cyclin D1). In conclusion, miR-520b is able to inhibit the growth of hepatoma cells by targeting MEKK2 or cyclin D1 in vitro and in vivo. Our findings provide new insights into the role of miR-520b in the development of HCC, and implicate the potential application of miR-520b in cancer therapy

Bayesian inversion of synthetic AVO data to assess fluid and shale content in sand-shale media

Reservoir characterization of sand-shale sequences has always challenged geoscientists due to the presence of anisotropy in the form of shale lenses or shale layers. Water saturation and volume of shale are among the fundamental reservoir properties of interest for sand-shale intervals, and relate to the amount of fluid content and accumulating potentials of such media. This paper suggests an integrated workflow using synthetic data for the characterization of shaley-sand media based on anisotropic rock physics (T-matrix approximation) and seismic reflectivity modelling. A Bayesian inversion scheme for estimating reservoir parameters from amplitude vs. offset (AVO) data was used to obtain the information about uncertainties as well as their most likely values. The results from our workflow give reliable estimates of water saturation from AVO data at small uncertainties, provided background sand porosity values and isotropic overburden properties are known. For volume of shale, the proposed workflow provides reasonable estimates even when larger uncertainties are present in AVO data

A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

Several theories of the underlying mechanisms of Sudden Infant Death Syndrome (SIDS) have been proposed. These theories have born relatively narrow beach-head research programs attracting generous research funding sustained for many years at expense to the public purse. This perspective endeavors to critically examine the evidence and bases of these theories and determine their plausibility; and questions whether or not a safe and reasoned hypothesis lies at their foundation. The Opinion sets specific criteria by asking the following questions: 1. Does the hypothesis take into account the key pathological findings in SIDS? 2. Is the hypothesis congruent with the key epidemiological risk factors? 3. Does it link 1 and 2? Falling short of any one of these answers, by inference, would imply insufficient grounds for a sustainable hypothesis. Some of the hypotheses overlap, for instance, notional respiratory failure may encompass apnea, prone sleep position, and asphyxia which may be seen to be linked to co-sleeping. For the purposes of this paper, each element will be assessed on the above criteria

Outcomes of patients with ST-segment myocardial infarction admitted during the COVID-19 pandemic

Background!#!Since the beginning of the SARS-CoV‑2 outbreak, healthcare professionals reported that patients admitted with ST-segment myocardial infarction (STEMI) were in worse condition compared to STEMI patients admitted before the outbreak. However, data on their outcomes are sparse.!##!Methods!#!We conducted a prospective, observational, cohort study of STEMI patients admitted during the COVID-19 pandemic from March 21, 2020 to July 31, 2020 (COVID-19 group). Clinical outcomes, 30-day mortality, and reasons potentially related to a delay in patient presentation were assessed and compared with STEMI patients admitted between November 1, 2019 and March 20, 2020 (pre-COVID-19 group).!##!Results!#!A total of 124 patients were enrolled, comprising 57 patients in the pre-COVID-19 group and 67 patients in the COVID-19 group. Significantly more patients in the COVID-19 group had a time to first medical contact of greater than 24 h. Additionally, those admitted during the pandemic had a significantly lower left ventricular ejection fraction (LVEF), worse thrombolysis in myocardial infarction (TIMI) flow, received circulatory support significantly more often, and had a significantly higher 30-day mortality. Furthermore, significantly more patients stated that 'information by the media' made them hesitate to contact the emergency medical services as soon as possible.!##!Conclusion!#!Here, we show that STEMI patients admitted during the COVID-19 pandemic had significantly prolonged times to first medical contact, were in worse condition at admission, and had an increased 30-day mortality. Additionally, we found that 'information by the media' made patients during COVID-19 hesitate to contact the emergency medical services. Consequently, public health strategies have to be developed to avoid potential excess mortality of STEMI patients during the pandemic