Background/Aims: Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating lung cancer growth and progression are not fully identified yet. Methods: In this study, the expression of miR-142-5p was measured in non-small cell lung cancer tissue and cell lines by qRT-PCR. The functional assays including the cell viability, colony formation, cell migration and invasion were performed in miR-142-5p mimic or inhibitor transfected cell lines (in vitro) and the cell tumorigenesis in nude mice (in vivo). The fluorescence ratios of cell viability were recorded using a multi-plate reader (Synergy 2, BioTek, Winooski, VT, USA) and the colonies were counted using an ELIspot Bioreader 5000 (BIO-SYS, Karben, GE). Results: MiR-142-5p was significantly downregulated in non-small cell lung cancer tissue and cell lines compared to normal human lung tissues. Overexpression of miR-142-5p resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-142-5p overexpression markedly suppressed cell proliferation in vitro and in vivo. Conversely, inhibition of miR-142-5p promoted lung cancer growth. Mechanistic studies showed that PIK3CA was a potential target of miR-142-5p and it mediated reduction of PIK3CA resulting in suppression of PI3K/Akt pathway. Conclusions: Our results demonstrate that miR-142-5p functions as a growth suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in non-small cell lung cancer.

Necrosis was considered to be the solo mechanism for ischemia/reperfusion (I/R)-induced cell death. Recent evidence from I/R models of the heart, liver, kidney, and brain indicates that apoptosis is a major contributor to I/R-induced cell death. However, evidence of I/R-induced apoptosis in skeletal muscle is sparse and divided. The purpose for the present study was to investigate I/R-induced necrosis and apoptosis in the cells isolated from rat skeletal muscle. A rat gracilis muscle model was used. After surgical preparation, clamps were applied on the vascular pedicle to create 4 h of ischemia and released for 24 h of reperfusion (I/R, n ¼ 10). Clamping was omitted in sham I/R rats (sham I/R, n ¼ 10). The muscle samples were harvested after 24 h of reperfusion for the process of cell isolation. Cells were stained by Propidium Iodide (PI) or Annexin V-FITC or both. Twenty thousand cells from each muscle sample were scanned and analyzed by flow cytometry. The average percentage of live cells was 45 AE 2% in the I/R group versus 65 AE 3% in the sham I/R group (p < 0.01). The average percentage of necrotic cells was 18 AE 1% in I/R versus 12 AE 1% in sham I/R (p < 0.01). The average percentage of apoptotic cells was 40 AE 3% in I/R versus 27 AE 3% in sham I/R (p < 0.01). Our results clearly demonstrated that I/R not only causes necrosis, but also accelerates apoptosis in the cells isolated from rat skeletal muscle.ß

The purpose of this study was to determine microcirculatory effects and response of nitric oxide synthase (NOS) to melatonin in skeletal muscle after prolonged ischemia. A vascular pedicle isolated rat cremaster muscle model was used. Each muscle underwent 4 hr of zero-flow warm ischemia followed by 2 hr of reperfusion. Melatonin (10 mg/kg) or saline as a vehicle was given by intraperitoneal injection at 30 min prior to reperfusion and the same dose was given immediately after reperfusion. After reperfusion, microcirculation measurements including arteriole diameter, capillary perfusion and endothelial-dependent and -independent vasodilatation were performed. The cremaster muscle was then harvested to measure endothelial NOS (eNOS) and inducible NOS (iNOS) gene expression and enzyme activity. Three groups of rats were used: sham-ischemia/reperfusion (I/R), vehicle + I/R and melatonin + I/R. As compared with vehicle + I/R group, administration of melatonin significantly enhanced arteriole diameter, improved capillary perfusion, and attenuated endothelial dysfunction in the microcirculation of skeletal muscle after 4 hr warm ischemia. Prolonged warm ischemia followed by reperfusion significantly depressed eNOS gene expression and constitutive NOS activity and enhanced iNOS gene expression. Administration of melatonin did not significantly alter NOS gene expression or activity in skeletal muscle after prolonged ischemia and reperfusion. Melatonin provided a significant microvascular protection from reperfusion injury in skeletal muscle. This protection is probably attributable to the free radical scavenging effect of melatonin, but not to its anti-inflammatory effect.

The aim of the present meta-analysis was to evaluate the effect of vitamin D supplementation on patients with polycystic ovary syndrome (PCOS). A literature search was performed to identify all of the relevant studies comparing the effect of vitamin D supplementation with placebo in PCOS patients, in the PubMed, Embase and Web of Science databases. All statistical analyses were performed on case-control studies using Review Manager 5.3 software, provided by the Cochrane Collaboration. A total of 11 studies involving 483 participants were included in the current meta-analysis. Vitamin D supplementation appeared to lead to an improvement in the levels of total testosterone [weighted mean differences (WMD) = -0.10, 95% CI (-0.18, -0.02)], homeostasis model assessment of insulin resistance [WMD = -0.44, 95% CI (-0.86, -0.03)], homeostasis model assessment of β-cell function [WMD = -16.65, 95% CI (-19.49, -13.80)], total cholesterol [WMD = -11.90, 95% CI (-15.67, -8.13)] and low-density lipoprotein-cholesterol [WMD = -4.54; 95% CI (-7.29, -1.80)]. The results failed to show a positive effect of vitamin D supplementation on the body mass index, dehydroepiandrosterone sulfate, triglyceride levels or high-density lipoprotein-cholesterol. In conclusion, the data from the available randomized controlled trials (RCTs) suggested vitamin D supplementation reduced insulin resistance and hyperandrogenism, as well improving the lipid metabolism of patients with PCOS to an extent. Further high-quality RCTs from a variety of regions in the world are required to determine the effectiveness of vitamin D supplementation in PCOS patients, and to determine a suitable dose and unit of vitamin D.

The purpose of this study was to determine the effect of melatonin on superoxide generation in arterial wall at an early phase of reperfusion and on endothelial dysfunction of microvasculature and cell viability of cremaster muscle at late phase of reperfusion (24 hr) after prolonged ischemia. Bilateral vascular pedicles which supply blood flow to the cremaster muscle were exposed. After surgical preparation, microvascular clamps were applied on the right iliac, femoral and spermatic arteries to create 4 hr of ischemia in both feeding vessels and the unexposed cremaster muscle. The vascular clamping was omitted on the left iliac, femoral and spermatic arteries and served as an internal control. Melatonin or Vehicle was via by intravenous injection at 10 min prior to reperfusion and 10 min after reperfusion. In the first experiment, the vascular pedicle was harvested after reperfusion to measure superoxide generation in real time by lucigenin-derived chemiluminescence. In the second experiment, endothelial-dependent and -independent vasodilatation was examined in the terminal arteriole of cremaster muscle which was then harvested to examine cell viability by WST-1 assay on day 2. Superoxide generation in arterial wall peaked at first 5-min of reperfusion and declined to near baseline after 60 min of reperfusion. Melatonin treatment significantly reduced superoxide generation in arterial walls and improved cell viability in cremaster muscles. Melatonin treatment also significantly reduced microvascular endothelial dysfunction which was still observable in the microcirculation of cremaster muscle after 24 hr of reperfusion. Melatonin reduces superoxide generation in the early phase of reperfusion resulting in attenuating endothelial dysfunction and muscle cell death in the late phase of reperfusion.

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Background:Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with poor prognosis, requiring risk stratification. However, the prognosis of ENKTL is not fully defined and needs supplementation. We hypothesised that fasting blood glucose (FBG) may be a new prognostic factor for ENKTL.Methods:We retrospectively analysed 130 patients newly diagnosed with ENKTL.Results:Both univariate analysis and multivariate analysis revealed that FBG >100 mg dl−1 was associated with a poor outcome. Patients with FBG >100 mg dl−1 at diagnosis had more adverse clinical features, achieved lower complete remission rates (P=0.003) and had worse overall survival (P<0.001) and progression-free survival (P<0.001) compared with low-FBG patients. Measurement of FBG was helpful in differentiating between low-risk patients using the International Prognostic Index (IPI) and Prognosis Index for peripheral T-cell lymphoma (PIT) scoring and patients in a different category using the Korean Prognostic Index (KPI) scores with different survival outcomes (P<0.05).Conclusion:Our data suggest that measuring FBG levels at diagnosis is a novel, independent predictor of prognosis in ENKTL and helps to distinguish low-risk patients with poor survival, and this holds true in patients considered low-risk by IPI, PIT and KPI.

Background: The metronidazole resistance of Helicobacter pylori strains has increased rapidly. Aim: To evaluate the efficacy and safety of new 1‐week regimens containing ranitidine bismuth citrate, furazolidone and either amoxicillin or tetracycline. Methods: One hundred and twenty patients with H. pylori‐positive inactive duodenal ulcer or non‐ulcer dyspepsia diagnosed by endoscopy were recruited randomly to receive one of two regimens for 7 days: ranitidine bismuth citrate, 350 mg b.d., furazolidone, 100 mg b.d., and either amoxicillin, 1000 mg b.d. (n=60), or tetracycline, 500 mg b.d. (n=60). H. pylori infection was identified by rapid urease testing and histology. 13C‐Urea breath test was performed to evaluate the cure of H. pylori infection at least 4 weeks after completion of triple therapy. Results: The eradication rates of H. pylori by ranitidine bismuth citrate–furazolidone–amoxicillin and ranitidine bismuth citrate–furazolidone–tetracycline regimens were 82% and 85% (P > 0.05), respectively, by intention‐to‐treat analysis, and 85% and 91% (P > 0.05), respectively, by per protocol analysis. Adverse effects were mild in both ranitidine bismuth citrate–furazolidone–amoxicillin and ranitidine bismuth citrate–furazolidone–tetracycline groups. Conclusions: One‐week regimens containing ranitidine bismuth citrate, furazolidone and amoxicillin or tetracycline are well tolerated and effective for the eradication of H. pylori.