Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the ...detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
Circadian rhythms are endogenous oscillations of physiological and behavioral phenomena with period length of ∼24 hr. A mutation in human Period 2 (hPER2), a gene crucial for resetting the central ...clock in response to light, is associated with familial advanced sleep phase syndrome (FASPS), an autosomal dominant condition with early morning awakening and early sleep times. The FASPS hPER2 S662G mutation resulted in PER2 being hypophosphorylated by casein kinase I (CKI) in vitro. We generated transgenic mice carrying the FASPS hPER2 S662G mutation and faithfully recapitulate the human phenotype. We show that phosphorylation at S662 leads to increased PER2 transcription and suggest that phosphorylation at another site leads to PER2 degradation. Altering CKIδ dosage modulates the S662 phenotype demonstrating that CKIδ can regulate period through PER2 in vivo. Modeling a naturally occurring human variant in mice has yielded novel insights into PER2 regulation.
Summary
This study aimed to evaluate the effect of acupuncture and intervention types on weight loss. We searched electronic databases, including Embase, PubMed, CENTRAL, RISS, KISS and CNKI, for ...randomized controlled trials that used acupuncture to treat obesity before June 2017. We found 27 trials involving 32 intervention arms and 2,219 patients. Acupuncture plus lifestyle modification (LM) was more effective than LM alone (Hedges' g = 1.104, 95% CI = 0.531–1.678) and sham acupuncture plus LM (Hedges' g = 0.324, 95% CI = 0.177–0.471), whereas acupuncture alone was not more effective than sham acupuncture alone and no treatment. Auricular acupuncture (Hedges' g = 0.522, 95% CI = 0.152–0.893), manual acupuncture (Hedges' g = 0445, 95% CI = 0.044–0.846) and pharmacopuncture (Hedges' g = 0.411, 95% CI = 0.026–0.796) favoured weight loss. Finally, acupuncture treatment was effective only in subjects with overweight (25 ≤ body mass index < 30, Hedges' g = 0.528, 95% CI = 0.279–0.776), not in subjects with obesity (body mass index ≥30). Our study suggests that the effect of acupuncture on weight loss may be maximized when auricular and manual acupuncture or pharmacopuncture treatment is combined with LM in patients with overweight.
MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer ...(CRC).
This study was divided into three phases: (1) marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of five patients with CRC, along with plasma from five healthy individuals as controls; (2) marker selection and validation by real-time quantitative RT-PCR on a small set of plasma; and (3) independent validation on a large set of plasma from 90 patients with CRC, 20 patients with gastric cancer, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls.
Of the panel of 95 miRNAs analysed, five were upregulated both in plasma and tissue samples. All the five miRNAs were validated on the plasma of 25 patients with CRC and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in the patients with CRC (p<0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 patients with CRC (p<0.05). Further validation with an independent set of plasma samples (n = 180) indicated that miR-92 differentiates CRC from gastric cancer, IBD and normal subjects. This marker yielded a receiver operating characteristic curve area of 88.5%. At a cut-off of 240 (relative expression in comparison to RNU6B snRNA), the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects.
MiR-92 is significantly elevated in plasma of patients with CRC and can be a potential non-invasive molecular marker for CRC screening.
Aims
Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE‐EPS), a lactic acid bacteria isolated from Kimchi (a Korean fermented vegetable product), was preliminary characterized and its ...immunostimulating effects were analysed.
Methods and Results
In this study, we used interferon‐γ (IFN‐γ)‐primed RAW 264·7 macrophages and CD3/CD28‐stimulated splenocytes to determine the immunotimulatory activities of PE‐EPS. Upon exposure to PE‐EPS, IFN‐γ‐primed RAW 264·7 macrophages showed significant increases in the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6 and IL‐1β. Molecular data using reporter gene assay and electrophoretic mobility shift assay (EMSA) revealed that PE‐EPS upregulated transcriptional activity, DNA binding and the nuclear translocation of nuclear factor‐κB (NF‐κB). Furthermore, PE‐EPS enhanced anti‐CD3/CD28‐specific proliferation and the productions of IL‐2 and IFN‐γ in primary splenocytes. In cyclophosphamide‐induced immunosuppressed mice, pretreatment with PE‐EPS (5, 15 or 45 mg kg−1 day−1, p.o.) increased thymus and spleen indices, and improved lymphocyte and neutrophil counts.
Conclusion
PE‐EPS stimulated the IFN‐γ‐primed macrophages and primary splenocytes to induce immune responses and improved the cyclophosphamide‐induced immunosuppression in mice.
Significance and Impact of the Study
The results in this study improved our understanding of immunostimulating activity of PE‐EPS and supported its potential treatment option as a natural immunostimulant.
In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events ...of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig’s epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.
Recently, a subtype of obesity characterized as a metabolically healthy but obese (MHO) individual has been identified. However, limited data are available on these MHO individuals' metabolic and ...inflammatory profiles, and the effect of weight loss on these profiles. We investigated metabolic and inflammatory markers in MHO women to determine the effects of a 12-week weight loss on those markers.
One hundred and twenty-nine overweight-obese Korean women participated for 12 weeks in a clinical intervention study involving a 300 kcal/day intake reduction. The subjects were divided into two groups: MHO and metabolically abnormal obese (MAO) individuals.
Computed tomography was performed. C-reactive protein (CRP), interkeukin-6 (IL-6) and oxidized low-density lipoprotein (LDL), as well as blood lipids, glucose and insulin concentrations were determined at baseline and after weight loss.
At baseline, plasma CRP (P<0.001), IL-6 (P<0.05) and oxidized LDL (P<0.001) levels were significantly lower in the MHO group than in the MAO group. Visceral fat at L1 (P<0.005) and visceral fat at L4 (P<0.001) were significantly lower in the MHO group than in the MAO group. The treatment induced weight loss averaging 3.11% of initial body weight, and the degree of weight loss between the two groups was similar. Visceral fat at L1 and L4 was reduced from its initial values by 3.2 and 5.4%, respectively, after weight loss. The levels of CRP (P<0.05) and oxidized LDL (P<0.01) were significantly reduced in the MAO group after the 12-week weight loss, whereas these effects were not seen in the MHO group.
Our results showed that MHO individuals exhibited lower visceral fat accumulation and more favorable metabolic and inflammatory states than MAO individuals. After a 12-week weight loss program, significant reductions in blood lipids, CRP and oxidized LDL levels were observed in MAO individuals. However, there was no measurable effect of weight loss on lipid profiles and inflammation in MHO individuals, indicating differing effects of weight loss on these markers between MAO and MHO groups.
A
bstract
The Reactor Experiment for Neutrino Oscillation (RENO) experiment has been taking data using two identical liquid scintillator detectors since August 2011. The experiment has observed the ...disappearance of reactor neutrinos in their interactions with free protons, followed by neutron capture on hydrogen (n-H). Based on 1500 live days of data taken with 16.8 GW
th
reactors at the Hanbit Nuclear Power Plant in Korea, the near (far) detector observes 567690 (90747) electron antineutrino candidate events with the n-H data. This provides an independent measurement of neutrino mixing angle
θ
13
and a consistency check on the validity of the result obtained from the data with neutron capture on Gadolinium (n-Gd). Furthermore, it provides an important cross-check on the systematic uncertainties of the n-Gd measurement. Based on a rate-only analysis, we obtain sin
2
2
θ
13
= 0
.
086 ± 0
.
008(stat
.
) ± 0
.
014(syst
.
). The combination of this result with that of n-Gd is also reported.
Fatty liver disease, especially non-alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. ...Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance.
We examined the clinical and laboratory data of 7860 subjects without diabetes who underwent general routine health evaluations at the Asan Medical Center in 2007 and had returned for follow-up examinations in 2011. Fatty liver index was calculated using an equation that considers serum triglyceride levels, γ-glutamyltransferase, waist circumference and BMI.
During a 4-year period, 457 incident diabetes cases (5.8%) were identified. The odds ratios for the development of Type 2 diabetes were significantly higher in the group with a fatty liver index ≥ 60 (fatty liver index-positive) than in the group with a fatty liver index < 20 (fatty liver index-negative) after adjusting for various confounding variables including homeostasis model assessment of insulin resistance. Odds ratios were significant regardless of the insulin resistance status at baseline.
Our results suggest that fatty liver index as a simple surrogate indicator of hepatic steatosis is valuable in identifying subjects at high risk for Type 2 diabetes. In addition, fatty liver disease itself contributes to the development of Type 2 diabetes independently of systemic insulin resistance.
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