The low expression of miR-451 predicts a worse prognosis in non-small cell lung cancer cases

Purpose miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migration inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451. Methods We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration. Results The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration. Conclusion This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC

Morphological and Functional Changes in the Retina after Chronic Oxygen-Induced Retinopathy

The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment

Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients

Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients.BackgroundThe relationship between blood pressure (BP) and mortality in hemodialysis patients has remained controversial. Some studies suggested that a lower pre- or postdialysis BP was associated with excess mortality, while others showed poorer outcome in patients with uncontrolled hypertension. We conducted a multicenter prospective cohort study to evaluate the impact of hemodialysis-associated hypotension on mortality.MethodsWe recruited 1244 patients (685 males; mean age, 60 ± 13 years) who underwent hemodialysis in 28 units during the two-year study period beginning in December 1999. Pre-, intra-, and postdialysis BP, and BP upon standing soon after hemodialysis, were measured in all patients at entry. Logistic regression analysis was used to assess the effect on mortality of pre-, intra-, and postdialysis BP, a fall in BP during hemodialysis, and a fall in BP upon standing soon after hemodialysis.ResultsDuring the study period, 149 patients died. Logistic models identified the lowest intradialysis systolic blood pressure (SBP) and degree of fall in SBP upon standing soon after hemodialysis as significant factors affecting mortality, but not pre- or postdialysis SBP and diastolic BP. The adjusted odds ratio for death was 0.79 (95% CI 0.64–0.98) when the lowest intradialysis SBP was analyzed in increments of 20 mm Hg, and was 0.82 (95% CI 0.67–0.98) when the fall in SBP upon standing soon after hemodialysis was analyzed in increments of 10 mm Hg.ConclusionThese results suggest that intradialysis hypotension and orthostatic hypotension after hemodialysis are significant and independent factors affecting mortality in hemodialysis patients

Exhaust gas analysis and formation mechanism of SiC nanowires synthesized by thermal evaporation method

Silicon carbide nanowires (SiCNWs) are a set of promising reinforcement materials due to their superior properties. However, formation mechanism of the SiCNWs synthesized by the thermal evaporation method without metal catalyst is still unclear. To understand the formation mechanism, SiCNWs were synthesized by the thermal evaporation method at 1350 °C using a pre-oxidized Si powder and CH4 gas as precursors. SiCNWs obtained by this method were β-SiC/SiO2 core–shell nanowires with average diameter about 55 nm and with a length up to 1 mm. The exhaust gases during the SiCNWs synthesis process were examined by gas chromatography and the photographs of growth activity of SiCNWs inside the furnace were captured. CO gas was detected during the active formation of SiCNWs. It was clarified that CO gas was one of the byproducts from SiCNWs synthesis process, and the formation reaction of SiCNWs should be 3SiO(g) + 3C(s) → 2SiC(s) + SiO2(s) + CO(g). The formation of SiCNWs was discussed based on the oxide-assisted-growth mechanism

Epidemiology of mechanically ventilated patients treated in ICU and non-ICU settings in Japan: a retrospective database study

Abstract Background In most countries, patients receiving mechanical ventilation (MV) are treated in intensive care units (ICUs). However, in some countries, including Japan, many patients on MV are not treated in ICUs. There are insufficient epidemiological data on these patients. Here, we sought to describe the epidemiology of patients on MV in Japan by comparing and contrasting patients on MV treated in ICUs and in non-ICU settings. A preliminary comparison of patient outcomes between ICU and non-ICU patients was a secondary objective. Methods Data on adult patients receiving MV for at least 3 days in ICUs or non-ICU settings from April 2010 through March 2012 were obtained from the Quality Indicator/Improvement Project, a voluntary data-administration project covering more than 400 acute-care hospitals in Japan. We excluded patients with cancer-related diagnoses. Patient demographic data and the critical care provided were compared between groups. Results Over the study period, 17,775 patients on MV were treated only in non-ICU settings, whereas 20,516 patients were treated at least once in ICUs (46.4% vs. 53.6%). Average age was higher in non-ICU patients than in ICU patients (72.8 vs. 70.2, P < 0.001). Mean number of ventilation days was greater in non-ICU patients (11.7 vs. 9.5, P < 0.001). Hospital mortality was higher in non-ICU patients (41.4% vs. 38.8%, P < 0.001). Standard critical care (e.g., arterial line placement, enteral nutrition, and stress-ulcer prevention) was provided significantly less often in non-ICU patients. Multivariate analysis showed that ICU admission significantly decreased hospital mortality (adjusted odds ratio 0.713, 95% CI 0.676 to 0.753). Conclusions A large proportion of Japanese patients on MV were treated in non-ICU settings. Analysis of administrative data indicated preliminarily that hospital mortality rates in these patients were higher in non-ICU settings than in ICUs. Prospective analyses comparing non-ICU and ICU patients on MV by severity scoring are needed