Overexpression of Cancer-Associated Genes via Epigenetic Derepression Mechanisms in Gynecologic Cancer

Like other cancers, most gynecologic cancers are caused by aberrant expression of cancer-related genes. Epigenetics is one of the most important gene expression mechanisms, which contribute to cancer development and progression by regulating cancer-related genes. Since the discovery of differential gene expression patterns in cancer cells when compared with normal cells, extensive efforts have been made to explore the origins of abnormal gene expression in cancer. Epigenetics, the study of inheritable changes in gene expression that do not alter DNA sequence is a key area of this research. DNA methylation and histone modification are well-known epigenetic mechanisms, while microRNAs and alternative splicing have recently been identified as important regulators of epigenetic mechanisms. These mechanisms not only affect specific target gene expression but also regulate the functioning of other epigenetic mechanisms. Moreover, these diverse epigenetic regulations occur simultaneously. Epigenetic regulation of gene expression is extraordinarily complicated and all epigenetic mechanisms to be studied at once to determine the exact gene regulation mechanisms. Traditionally, the contribution of epigenetics to cancer is thought to be mediated through the inactivation of tumor suppressor genes expression. But recently, it is arising that some oncogenes or cancer-promoting genes (CPGs) are overexpressed in diverse type of cancers through epigenetic derepression mechanism, such as DNA and histone demethylation. Epigenetic derepression arises from diverse epigenetic changes, and all of these mechanisms actively interact with each other to increase oncogenes or CPGs expression in cancer cell. Oncogenes or CPGs overexpressed through epigenetic derepression can initiate cancer development, and accumulation of these abnormal epigenetic changes makes cancer more aggressive and treatment resistance. This review discusses epigenetic mechanisms involved in the overexpression of oncogenes or CPGs via epigenetic derepression in gynecologic cancers. Therefore, improved understanding of these epigenetic mechanisms will provide new targets for gynecologic cancer treatment

The Decline of Physical Activity with Age in School-Aged Children with Cerebral Palsy: A Single-Center Cross-Sectional Observational Study

Maintaining physical activity is important for children with cerebral palsy (CP). This study examined whether age predicted habitual physical activity (HPA) or cardiorespiratory fitness (CRF) in school-aged children with CP and clarified the relationship between HPA and CRF. We utilized cross-sectional data from 39 children with CP (18 girls and 21 boys; mean age 7.44 years; mean body weight 24.76 kg; mean body mass index 15.97 kg/m2; hemiplegic or diplegic CP). The participants wore an accelerometer (ActiGraph) for five days to measure HPA, physical activity energy expenditure (kcal/kg/d), sedentary physical activity (%SPA), light physical activity, moderate-to-vigorous physical activity (%MVPA), and activity counts (counts/min). Participants underwent cardiopulmonary exercise tests on a treadmill using a modified Naughton protocol. Linear regression and correlation analyses were performed. p-value (two-tailed) \u3c 0.05 was considered statistically significant. Age was positively associated with SPA. MVPA negatively correlated with resting heart rate (HR), and activity counts were negatively correlated with resting HR. In conclusion, our study found strong evidence of a negative association between HPA and age in school-aged children with CP. It highlights the importance of creating and improving recreational opportunities that promote physical activity in all children with CP, regardless of whether they are considered therapeutic

The association between motor capacity and motor performance in school-aged children with cerebral palsy: An observational study

Background This study aimed to investigate the association between motor capacity and motor performance in children with cerebral palsy (CP) aged 6–12 years with Gross Motor Function Classification System (GMFCS) levels I to III. Methods Forty-six children with CP (24 boys and 22 girls) classified as GMFCS levels Ⅰ, Ⅱ, or Ⅲ were included. Motor capacity was measured by the Gross motor function measure (GMFM), Pediatric balance scale (PBS), Timed up and go (TUG), and 6-min walk test (6MWT). Motor performance was measured by triaxial accelerometers. Estimations of physical activity energy expenditure (PAEE) (kcal/kg/day), percentage of time spent on physical activity (% sedentary physical activity; %SPA; % light physical activity, %LPA; % moderate physical activity, %MPA; % vigorous physical activity %VPA; and moderate-to-vigorous physical activity, %MVPA), and activity counts (counts/minute) were obtained. Results Children with GMFCS level I showed a significantly higher motor capacity (GMFM-66, GMFM-88, D-dimension and E-dimension, PBS and 6MWT) than those with level II or III. Children with GMFCS level II and/or III had significantly lower physical activity (PAEE, % MPA, % VPA, %MVPA, and activity counts) than children with GMFCS level I. Multiple linear regression analysis (dependent variable, GMFM-66) showed that %MVPA was positively associated with GMFM-66 in the GMFCS level II & III children but not in GMFCS level I children

High triglyceride/HDL cholesterol ratio is associated with silent brain infarcts in a healthy population

Background Triglycerides (TG)/high-density lipoprotein (HDL) cholesterol ratio is a marker of small/dense low-density lipoprotein particles, which are closely associated with various metabolic and vascular diseases. However, the role of TG/HDL cholesterol ratio in cerebrovascular diseases has not been well studied. In this study, we evaluated the relationship between TG/HDL cholesterol ratio and the presence of silent brain infarct (SBI) in a neurologically healthy population. Methods We retrospectively evaluated consecutive participants in health check-ups between January 2006 and December 2013. SBI was defined as an asymptomatic, well-defined lesion with a diameter of ≥3 mm on T1- or T2-weighted images. TG/HDL cholesterol ratio was calculated after dividing absolute TG levels by absolute HDL cholesterol levels. Results Of 3172 healthy participants, 263 (8.3%) had SBI lesions. In multivariate analysis, TG/HDL cholesterol ratio was independently associated with SBI (adjusted odds ratio [aOR] = 1.16, 95% confidence interval [CI] = 1.00 to 1.34, P = 0.047). This association was prominent in males (aOR = 1.23, 95% CI = 1.03 to 1.48, P = 0.021), but not in females. In the analyses of the relationships between lipid parameters and SBI lesion burden, TG/HDL cholesterol ratio was positively correlated, and total cholesterol/TG ratio was negatively correlated with SBI lesion burden, in dose-response manners (P for trend = 0.015 and 0.002, respectively). Conclusions The TG/HDL cholesterol ratio was positively associated with the prevalence of SBI in a neurologically healthy population

High triglyceride-glucose index is associated with subclinical cerebral small vessel disease in a healthy population: a cross-sectional study

The triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases. However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD). In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH). We assessed health check-up participants aged 40–79years from 2006 to 2013. The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD. SBI was measured for both prevalence and burden. The WMH volume was quantitatively rated using a computer-assisted semi-automated technique. Results A total of 2615 participants were evaluated (median age: 56years, male sex: 53%). In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06–1.81). Further quantitative analyses showed a positive dose–response relationship between the TyG index and SBI burden (P for trend = 0.006). In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (β = 0.084; 95% CI = 0.013 to 0.154). Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR. A high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population. This marker of IR could be a convenient and useful predictor of cSVD

Microspinning: Local Surface Mixing via Rotation of Magnetic Microparticles for Efficient Small-Volume Bioassays

The need for high-throughput screening has led to the miniaturization of the reaction volume of the chamber in bioassays. As the reactor gets smaller, surface tension dominates the gravitational or inertial force, and mixing efficiency decreases in small-scale reactions. Because passive mixing by simple diffusion in tens of microliter-scale volumes takes a long time, active mixing is needed. Here, we report an efficient micromixing method using magnetically rotating microparticles with patterned magnetization induced by magnetic nanoparticle chains. Because the microparticles have magnetization patterning due to fabrication with magnetic nanoparticle chains, the microparticles can rotate along the external rotating magnetic field, causing micromixing. We validated the reaction efficiency by comparing this micromixing method with other mixing methods such as simple diffusion and the use of a rocking shaker at various working volumes. This method has the potential to be widely utilized in suspension assay technology as an efficient mixing strategy

Capric Acid Inhibits NO Production and STAT3 Activation during LPS-Induced Osteoclastogenesis

Capric acid is a second medium-chain fatty acid, and recent studies have shown that fatty acids are associated with bone density and reduce bone turnover. In this study, we investigated the effects of capric acid on lipopolysaccharide (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, an osteoclast differentiation marker, without inhibiting cell viability. LPS strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA expression. Subsequently, we investigated various intracellular signaling proteins, including nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 1 (STAT1) and STAT3 associated with osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the NF-κB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited LPS-induced phosphorylation of Ser727 in STAT3. Additionally, stattic (a STAT3 inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by suppressing NO production via the STAT3 pathway. These results suggest that capric acid has important therapeutic implications for treating bone diseases associated with excessive osteoclastogenesis

Ultrasound features of secondary appendicitis in pediatric patients

Purpose The purpose of this study was to evaluate the ultrasonographic findings of secondary appendicitis (SA) and to discuss the differential findings compared with primary appendicitis. Methods In this study, we analyzed the ultrasonographic findings of 94 patients under 15 years old of age treated at our institution from May 2005 to May 2014 who had bowel inflammation and an inflamed appendix with a maximal outer diameter >6 mm that improved with nonsurgical treatment (the SA group). Ninety-nine patients with pathologically proven acute appendicitis (the primary appendicitis [PA] group) from June 2013 to May 2014 and 44 patients with pathologically negative appendectomy results from May 2005 to May 2014 were also included to compare the ultrasonographic features of these conditions. A retrospective review of the ultrasonographic findings was performed by two radiologists. The clinical and laboratory findings were also reviewed. The results were statically analyzed using analysis of variance, the Pearson chi-square test, and the two-tailed Fisher exact test. Results Compared with PA, cases of SA had a smaller diameter (9.8 mm vs. 6.6 mm, P<0.001), and were less likely to show periappendiceal fat inflammation (98% vs. 6%, P<0.001) or an appendicolith (34% vs. 11%, P<0.001). SA showed mural hyperemia on color Doppler ultrasonography as frequently as PA (P=0.887). Conclusion The ultrasonographic features of SA included an increased diameter compared to a healthy appendix and the same level of hyperemia as in PA. However, the diameter was commonly in the equivocal range (mean diameter, 6.6 mm), and periappendiceal fat inflammation was rarely present in SA