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Background and Aim Host interleukin-28 B ( IL-28 B) genetic variants determine a sustained virological response ( SVR) in hepatitis C virus genotype 1 ( HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated. Methods IL-28 B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin. Results The SVR rate was 60.0% and was significantly higher in previous relapsers than in nonresponders (72.7% and 13.3%, P < 0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [ OR]/95% confidence interval [ CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of rs8099917 TT genotype ( OR/95% C. I.: 7.67/1.27-46.49, P = 0.03). Comparing to patients with TG/ GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002), and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly low between previous nonresponders with different rs8099917 genotypes (12.5% vs 14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/ GG genotype (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype ( OR/95% CI:18.50/1.82-188.39, P = 0.014). Conclusions Host IL-28 B genetic variants played a role in Asian relapsers but not nonresponders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28 B genotype. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to investigate the regulation and involvement of miR-221 in the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs). The relationships between miR-221 and pro-inflammatory markers and adipokines were also explored. Methods: Eight adipose tissues were obtained from four obese (mean body mass index (BMI) =31.7 kg/m2) and four lean (mean BMI= 21.5 kg/m2) women. hASCs were induced to differentiate, and the related gene expression were measured in the hASC-differentiated adipocytes using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). Results: During adipogenesis, miR-221 was significantly down-regulated; furthermore, miR-221 levels were lower in hASC-differentiated adipocytes from obese subjects than in the corresponding adipocytes from lean subjects. Higher TNF-α mRNA levels were associated with lower levels of miR-221. In addition, the miR-221 levels in the adipocytes were inversely correlated with BMI. Conclusion: Our results support the link between miR-221 and obesity development as well as obesity related inflammatory status. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. A study from Japan reported that G to A substitution of a single-nucleotide polymorphism (SNP) located in the 5′-untranslated region of caspase 3 (CASP3) (rs72689236), which was associated with nuclear factor of activated T cell-mediated T-cell activation, is responsible for susceptibility to KD. This study was conducted to investigate whether the polymorphism of CASP3 is responsible for susceptibility and coronary artery lesion (CAL) formation in KD in the Taiwanese population. A total of 1092 subjects (341 KD patients and 751 controls) were investigated to identify an SNP of rs72689236 using Invader assays (Third Wave Technologies). Our data provided a borderline significant association between the genotypes and allele frequency of rs72689236 in control subjects and KD patients (P=0.0535 under the dominant model; P=0.0575 under the allelic model). The A allele of rs72689236 in KD patients and in patients with CAL and intravenous immunoglobulin resistance was seen in a higher frequency. Importantly, a significant association was obtained between rs72689236 and KD patients with aneurysm formation (P=0.009, under the recessive model). The A allele of rs72689236 is very likely to be a risk allele in the development of aneurysm in patients with KD. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Connexin 37, encoded by the GJA4 gene, protects against atherosclerosis. A recent study reported an association between polymorphism rs1764391 at GJA4 and ischemic stroke in a Chinese population. We aimed to replicate this result. Materials and Methods: A total of 958 ischemic stroke patients and 2196 controls were enrolled for the study. All participants were Chinese residing in Taiwan. Logistic regression analysis with adjustment for traditional risk factors was used to estimate the genetic effect. We also performed stratification analyses by sex and stroke subtypes. Literature reviews were conducted for available genetic association studies investigating rs1764391 and cardiovascular phenotypes. Results: We did not find any significant association for overall stroke (p=0.87) or from any subset analyses. Eight studies addressing the associations between rs1764391 and cardiovascular phenotypes had a sample size greater than 1000. Including the present study, five out of the eight large-scale studies found no association. Conclusions: GJA4 polymorphism is not associated with stroke risk in the Taiwanese population. [Copyright &y& Elsevier]

CORRECTION TO:: European Journal of Human Genetics (2003); doi:10.1038/sj.ejhg.5201091; Published online 15 October 2003. [ABSTRACT FROM AUTHOR]

Aims Amyloid beta-peptide (A β), the main component of senile plaques in the Alzheimer's disease ( AD) brains, is generated from sequential cleavage of amyloid precursor protein ( APP) by β- and γ-secretase. Hyperglycemia in diabetes may compromise barrier integrity in endothelial cells ( ECs). However, the roles of endothelial APP in response to high glucose ( HG) remain to be delineated. The aims of this study were to test whether HG may increase A β secretion, thereby leading to heightened paracellular permeability in ECs. Methods We determined the effects of HG on production of A β, expression of full-length APP, intercellular permeability, and expression levels of specific junctional proteins in human umbilical vein endothelial cells ( HUVECs). Results HG at 30 mM significantly stimulated expression of full-length APP accompanied by heightened secretion of A β1-42, increased paracellular permeability, and attenuated expression of zona occluden-1 ( ZO-1), claudin-5, occludin, and junctional adhesion molecule ( JAM)-C in HUVECs; all of which were abolished by the γ-secretase inhibitor BMS299897. Exogenous application of A β1-42, but not the reverse peptide A β42-1, was sufficient to downregulate the expression of the same junction proteins. Conclusion Hyperglycemia enhances APP expression with increased A β production, which downregulates junctional proteins causing increased intercellular permeability in ECs. [ABSTRACT FROM AUTHOR]

Highlights: [•] PBMC–miR125b is inversely associated with treatment outcome in HCV-1 patients. [•] PBMC–miR125b is independent to the most important baseline factor IL28B genotype. [•] PBMC–miR125b is the only factor associated with treatment success in nonRVR patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] UVB activates the PI3K/AKT/ERK pathways by reducing the SIRT1 expression. [•] SIRT1 activator prevents the UVB damage by inhibiting AKT and ERK phosphorylation. [•] SIRT1 may be regulator on protecting the UVB-induced RPE cells damage. [Copyright &y& Elsevier]

Abstract: Background: Both interleukin-28B genetic variants and on-treatment virological responses are factors predictive of treatment outcome in hepatitis C virus genotype 1 (HCV-1) patients. We aimed to compare the clinical significance of the two factors. Methods: Rs8099917 genotype and on-treatment responses were determined in 182 HCV-1 patients with 48-week peginterferon/ribavirin. Results: Comparing to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, 46.2% vs. 19.2%, P =0.01) and sustained virological response (SVR, 85.3% vs. 42.3%, P <0.001) rates. Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/95% confidence intervals [OR/CI]: 4.25/1.39-13.01). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 57.22/6.23-525.37), followed by the carriage of rs8099917 TT genotype (OR/CI: 10.06/3.12-32.44). However, while on-treatment factors were taken into account, the cEVR was the most important determinant to an SVR (OR/CI:54.98/9.07-333.38), whereas the influence of rs8099917 genotype became non-significant in non-RVR patients. Conclusions: Rs8099917 TT genotype is significantly independently predictive of on-treatment virological responses, which were the major determinants of an SVR, in Asian HCV-1 patients. [Copyright &y& Elsevier]

Ultraviolet B (UVB) radiation may cause the inflammation of retinal pigment epithelium (RPE) cells and play a role in development of age-related macular degeneration (AMD). The activation of the complement factor B (CFB) gene has been shown to be involved in formation of AMD. Here our results revealed that UVB induces IL-6/STAT3 signaling activation and the UVB-induced STAT3 is able to regulate the CFB expression in ARPE-19 cells. Tannic acid (TA) is a kind of water-soluble polyphenol and may have anti-inflammation effects. We also found that TA attenuates the UVB-induced IL-6 protein production, the STAT3 phosphorylation and the CFB expression. Taken together, these findings suggest UVB-induced inflammation of RPE can be mediated through the IL-6/STAT3/CFB pathway, and TA has a protected effect via the inhibition to the inflammatory response. [ABSTRACT FROM AUTHOR]

Abstract: Background: Gallstone disease (GSD) is a common disease that can be caused by environmental influences, common genetic factors and their interactions. Mucin glycoproteins may be one important factor for GSD. We conducted a case–control study to investigate the relationship between the mucin-like protocadherin (MUPCDH) gene polymorphisms and GSD. Methods: The study included 452 GSD cases and 491 healthy controls who had no evidence of gallstones by ultrasound examination. Two common tagging single nucleotide polymorphism (SNP) rs3758650 and rs7932167, and four non-synonymous SNPs rs34362213, rs2740375, rs7108757 and rs2740379 were genotyped. The genetic effects were evaluated using the multivariate regression model. Results: The genotypes of these SNPs were all in Hardy–Weinberg equilibrium. Three non-synonymous SNPs (rs34362213, rs7108757 and rs2740379) were monomorphic. The single SNP analysis showed two SNPs (rs7932167 and rs2740375) were not associated with GSD and only SNP rs3758650 had the association of the presence of GSD with an odds ratio (OR) of 1.59 (adjusted P=0.013) for the AG genotype and 5.82 (adjusted P=0.007) for the AA genotype when compared with the reference GG genotype. The haplotype analysis of the three polymorphic SNPs showed GCA was significant for GSD (adjusted p=0.001) with an odds ratio (OR) of 1.41 when compared to other haplotypes. Conclusions: The MUPCDH genetic polymorphism rs3758650 was considered a genetic marker to predict symptomatic GSD subjects. It may be of importance for GSD patients with the risk SNPs to be frequently checked because they may develop symptomatic GSD. [Copyright &y& Elsevier]

Abstract: Aim of the study: San-Huang-Xie-Xin-Tang (SHXXT) is a traditional Chinese medicine and it has been shown to have an anti-inflammatory effect. Since inflammation is one of the major mechanisms of atherosclerosis, we aimed to investigate anti-atherosclerotic effect of SHXXT in human aortic smooth muscle cells (HASMCs). Materials and methods: Human aortic smooth muscle cells (HASMCs) were used in the present study, and rendered atherosclerosis by adding lipopolysaccharides. We first tested the effects of SHXXT on HASMC migration and proliferation as they present the major morphological change of atherosclerosis. We also examined whether SHXXT can influence the production of several biomarkers of inflammation and atherosclerosis including reactive oxygen species (ROS), COX-2, ERK1/2, IL-1β, IL-6, IL-8 and MCP-1. Results: Using the dimethyl-thiazol-diphenyltetrazoliumbromide (MTT) and wound repair assay, SHXXT was shown to significantly reduce HASMC proliferation and migration, respectively. From the fluorometric assay, SHXXT significantly reduced ROS production. SHXXT down regulated mRNA and protein levels for the COX-2 gene. In addition, phosphorylated ERK1/2 levels were suppressed by SHXXT suggesting HASMC division can be inhibited under pro-inflammatory condition. SHXXT significantly inhibited the production of IL-1β, IL-6, IL-8 and MCP-1 after LPS stimulation. Conclusions: Our results indicated that SHXXT can influence several mechanisms involved in atherosclerosis, which suggests that SHXXT may have a therapeutic potential for cardiovascular disease associated with atherosclerosis. [Copyright &y& Elsevier]

Abstract: Lead (Pb2+) is one of the most common heavy metal pollutants, which can cause chronic cardiovascular diseases. To clarify the mechanism by which Pb2+ induces inflammatory reactions, we examined the expression of inflammatory genes including encoding cyclooxygenase-2 (COX-2), cytosolic phospholipase A2 (cPLA2), and their down stream product prostaglandin E2 (PGE2) in CRL1999 cells that is a vascular smooth muscle cell line from human aorta. The expression of COX-2/cPLA2 genes and PGE2 secretion was increased markedly after cells were exposed to 1μM Pb2+. PD098059, a MEK inhibitor, suppressed Pb2+-mediated inflammatory reactions; this indicates the involvement of the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Furthermore, Pb2+-induced activation of the COX-2/cPLA2 genes was inhibited by both epidermal growth factor receptor (EGFR) inhibitors (AG1478 and PD153035) and EGFR siRNA. Short-term stimulation with Pb2+ induced EGFR phosphorylation at the Tyr residue (position, 1173). Importantly, overexpression of EGFR resulted in a significant potentiation effect on Pb2+-induced gene expression. Taken together, our results indicate that 1μM Pb2+ can induce PGE2 secretion by upregulating the transcription of COX-2/cPLA2 genes. EGFR is the key target in the plasma membrane responsible for transmitting Pb2+ signals in order to trigger downstream inflammatory cascades. [ABSTRACT FROM AUTHOR]

Abstract: Background: Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. This study tested the association between functional VEGF +405 C>G (rs2010963), −2578C>A (rs699947) polymorphisms, and coronary collaterals in patients with coronary artery disease (CAD). Method: The collateral scoring system developed by Rentrop was used to classify 393 patients according to their collaterals as either “poor” (grades 0 and 1) or “good” (grades 2 and 3). Gene polymorphisms were analyzed by TaqMan assay. Results: The frequency of +405C and −2578A alleles was higher in the good collaterals group (p=0.007 and 0.005, respectively). For the +405C>G allele, the odds ratio (OR) of good collaterals for CC to GG genotype was 2.54 (p=0.003). For the −2578A allele, the OR of good collaterals for AA to CC genotype was 2.31 (p=0.038). Univariate and logistic regression analysis found 2 polymorphisms in the additive model for associations with collateral development: +405C>G (p=0.005 and 0.010) and −2578C>A (p=0.006 and 0.006). The VEGF +405C>G polymorphism and DM revealed an interactive effect on collateral development (p=0.027). Conclusions: The VEGF +405C>G and −2578C>A polymorphisms might be novel genetic factors affecting collateral development in Chinese patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Glutathione peroxidase 3 (GPX3) can enhance an antioxidant''s capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer. Methods: We first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs. Results: Among five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls, 3 SNPs were significant: intronic SNP rs3805435 (OR=0.70, P =0.037), intronic SNP 3828599 (OR=0.68, P =0.025), and 3′ UTR SNP rs2070593 (OR=0.48, P =0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D′=0.91). Conclusions: The reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P =0.004), whereas the 3′UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk. [Copyright &y& Elsevier]

Abstract: Background: Osteopontin (OPN) is an important modulator of urolithiasis formation. Three functional polymorphisms (-66T/G, -156delG/G, and -443T/G) on the promoter region of the OPN gene have been found to affect the gene expression and transcriptional activity. This study investigated the association of those three functional polymorphisms with the risk of calcium urolithiasis. Methods: A total of 249 cases diagnosed with calcium urolithiasis and 247 age- and sex-matched healthy controls were recruited from Kaohsiung Medical University Hospital between June, 2003 and February, 2007. All subjects completed a detailed questionnaire survey, and provided blood and urine samples for biochemical evaluations. Three single nucleotide polymorphisms were determined by using TaqMan 5′ allelic discrimination assay. Results: In-156delG/G polymorphism, subjects who carried delG allele had a significantly higher risk of developing calcium urolithiasis than those with G allele (odds ratio=1.39; 95% confidence interval=1.02–1.90; P =0.037). In stone cases, subjects with delG/G and delG/delG genotypes also had significantly higher urinary ratio of calcium to OPN than those with G/G genotype (11.8±15.9 vs 7.08±5.26, P =0.021). Conclusions: The -156 delG/G polymorphism of OPN gene could serve as a candidate genetic marker used to evaluate the risk of calcium urolithiasis. [Copyright &y& Elsevier]

Abstract: Objectives: To identify candidate genes in relation to plasma lipid levels in Caribbean Hispanics. Design and methods: A total of 114 single nucleotide polymorphisms (SNPs) at 17 lipid-related genes were genotyped in 477 Caribbean Hispanics from the Northern Manhattan Study (NOMAS). Analyses for each SNP and haplotype were performed to evaluate the associations with four lipid traits: high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), triglyceride (TG) and total cholesterol (TC). Results: We identified 19 SNPs at 10 genes that were significantly related to lipids (p <0.01), including nine involved in the reverse cholesterol transport pathway, and one involved in bile acid synthesis. Three genes, namely the apolipoprotein A5, apolipoprotein B and cytochrome p450 polypeptide 7A1 genes, accounted for the largest proportion of variation in HDL-C/TG, TC and LDL-C respectively. Conclusions: The cumulative effects of multiple genetic variants led to a substantially better prediction of inter-individual variations in lipid levels. [Copyright &y& Elsevier]

Abstract: Background: Matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) trigger the signal cascade instigating cardiac remodeling and fibrosis, which lead to changes of repolarization variables. We investigate the influence of MMP9-1562 C/T and TIMP2-418 G/C gene polymorphisms on repolarization parameters including QT dispersion (QTd) and the peak and the end of the T wave interval (Tpe) in a prospective cohort. Methods: Of 1500 people screened, 106 elderly Chinese without organic heart disease were recruited and received electrocardiography at the baseline, second and 4th year follow-ups. The QTc (corrected QT), QTd, QTc dispersion (QTcd) and Tpe were manually calculated. Results: Age was 72.7±4.1 y (range 62–81 y). QTd, QTcd and Tpe were significantly prolonged (all p <0.001 at the 2nd and 4th year). At the 4th year the magnitude of QTd prolongation but not Tpe was significantly higher in subjects carrying the TIMP2 C-allele than non C-allele carriers (p =0.033) as well as QTcd (p =0.010). This association was still significant in multivariate analyses (p =0.012 and p =0.003 for QTd and QTcd, respectively) but not in MMP9 genotype. Conclusions: The elderly Chinese with TIMP2 C-allele have higher magnitude of QTd and QTcd prolongation. [Copyright &y& Elsevier]

: PurposeTo compare the measurement of refractive errors (sphere, cylinder, and axis) between the hand-held Retinomax and on-table Topcon autorefractors in cyclopleged and noncyclopleged young children. The average bias and measurement agreement were assessed.: DesignObservational cross-sectional study.: MethodsThe study included 114 cyclopleged and 156 noncyclopleged young children. The mean difference between the two methods and the 95% limits of agreement were calculated to evaluate the average bias. Two types of analyses were conducted to assess the degree of agreement. First, the proportion of the absolute mean differences was presented in different ranges (≤0.25, 0.25–0.5, 0.5–0.75, 0.75–1.0, and >1.0 diopters for sphere and cylinder; 0–10, 11–20 and >20 degrees for axis). Second, the paired t test was conducted to evaluate the consistency of two types of measurements.: ResultsThe data by the Retinomax had mild bias (0.59 diopters) toward a lower sphere data under noncycloplegia but no bias under cycloplegia. For cylinder and axis, there was either no bias or clinically acceptable bias (0.02–0.13 diopters for cylinder and 2–7 degrees for axis) regardless of cycloplegia. Besides the sphere data under noncycloplegia, in general 90% of the mean differences of sphere and cylinder were within 0.5 diopters. More than 97% of the difference in axis under cycloplegia and 68% under noncycloplegia were within 20 degrees. After adjusting for mild bias, the paired t test showed very consistent results.: ConclusionsThe data by the Retinomax were consistent with those by the Topcon. The Retinomax is a useful instrument to screen refractive errors in young children. [Copyright &y& Elsevier]

In vivo and in vitro studies have demonstrated that thrombospondin-1 (TSP-1) is involved in atherosclerotic pathogenesis. However, the role of TSP-1 in clinical atherosclerosis remains unknown. This cross-sectional study investigated the relationship between TSP-1 and carotid intima-media thickness (IMT) and examined whether it interacts with conventional cardiovascular risk factors. A total of 587 participants were enrolled from February 2018 to December 2021. TSP-1 was dichotomized based on median value. Carotid IMT was measured bilaterally in each segment, and the average value was taken as the overall IMT variable. Analysis of covariance models were used to ascertain the main and interaction effects of cardiovascular risk factors and circulating TSP-1 levels on carotid IMT. Those with high TSP-1 (n = 294) had significantly higher carotid IMT than did those with low TSP-1 (n = 293; 0.74 ± 0.12 vs 0.72 ± 0.11 mm; p = 0.011). After the combined effects of TSP-1 and vascular risk factors on carotid IMT were evaluated, an interaction effect on IMT was observed between TSP-1 and hypertension (adjusted F = 8.760; p = 0.003). Stratification analysis revealed that individuals with hypertension and high TSP-1 had significantly higher IMT than did those with low TSP-1 (adjusted p = 0.007). However, this difference was not observed in normotensive individuals (adjusted p = 0.636). In conclusion, this is the first study to provide clinical data supporting the correlation between TSP-1 and atherosclerosis. TSP-1 may be a crucial marker of increased susceptibility to atherosclerosis in individuals with hypertension., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We previously reported anti-miR-328 therapy for dry eye disease (DED). Since decreased mucin secretion is a risk factor for DED, we aimed to explore whether anti-miR-328 affects mucin expression and goblet cells. MiR-328 was increased in goblet cells when they were under desiccating stress or treated with benzalkonium chloride (BAC), both of which are risk factors for DED. Based on bioinformatics tool results, miR-328 was predicted to directly target the transcription factor CREB1 that has been known to promote the expression of mucin5AC. The inhibitory effect of miR-328 on CREB1 was confirmed by the transfection assay. A miR-328 binding site on the CREB1 gene was confirmed by the luciferase assay. Furthermore, anti-miR-328 increased CREB1 and mucin5AC in cultured goblet cells according to qPCR, Western blot, and IF staining experiments. Anti-miR-328 increased mucin5AC secretion from the cultured goblet cells based on an ELISA assay for the cultured medium. Finally, impression cytology data revealed anti-miR-328 increased conjunctival goblet cells in the DED rabbits induced by BAC. In conclusion, anti-miR-328 increases CREB1 expression leading to an increase in mucin5AC production and secretion. Furthermore, anti-miR-328 also increases conjunctival goblet cells. These results warrant the further development of anti-miR-328 therapy for DED.

Aim: To test for the association between genome-wide methylation and myopia in human and mice., Methods: Long interspersed nucleotide element 1 (LINE-1) methylation levels were used to surrogate genome-wide methylation level. We first tested for the association between high myopia (<-6 D) and LINE-1 methylation in leukocytes in 220 cases and 220 control subjects. Secondly, we validated the results of LINE-1 methylation in eyes from the form deprivation myopia (FDM) mice. Furthermore, we calculated the correlation of LINE-1 methylation levels between leukocyte DNA and ocular DNA in the mice. We also tested whether dopamine can alter LINE-1 methylation levels., Results: The LINE-1 methylation level was significantly higher in the myopic human subjects than controls. The upper and middle tertiles of the methylation levels increased an approximately 2-fold ( P ≤0.002) risk for myopia than the lower tertile. Similarly, FDM mice had high LINE-1 methylation levels in the leukocyte, retina and sclera, and furthermore the methylation levels detected from these three tissues were significantly correlated. Immunohistochemical staining revealed higher levels of homocysteine and methionine in the rodent myopic eyes than normal eyes. Dopamine treatment to the cells reduced both LINE-1 methylation and DNA methyltransferase levels., Conclusion: LINE-1 hypermethylation may be associated with high myopia in human and mice. Homocysteine and methionine are accumulated in myopic eyes, which may provide excess methyl group for genome-wide methylation.

MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.

Background and Purpose: Large artery stiffness is considered to be a marker for cardiovascular disease. Serum matrix metalloproteinase-9 (MMP-9) level has been found to correlate with arterial stiffness and predict cardiovascular risk. This study was aimed to investigate the relationship between the MMP-9 genotypes and artery stiffness, and to examine whether the genetic effect is sex specific., Methods: Three carotid stiffness modalities were assessed in 1218 (704 females) stroke- and myocardial infarction-free volunteers aged 21-86 years old. The genotypes of MMP-9 promoter polymorphism (-1562C/T) were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Analysis was conducted to test for the overall and sex specific effect using multivariate regression model., Results: T allele carriers (CT and TT) had stiffer arteries than CC homozygotes after adjusting for age and sex (p = 0.013, 0.028, and 0.017 for Ep, β, and PWV, respectively). Further sex-stratified analysis showed that the significant association only existed in women. Women with the T allele had significantly stiffer arteries than CC homozygotes after adjusting for age (p = 0.003, 0.018, and 0.006 for Ep, β, and PWV, respectively), and this association remained significant after adjusting for known covariates. When menopausal status was further considered, all three carotid stiffness modalities were significantly different between T allele carriers and CC homozygotes in menopausal but not in pre-menopausal women., Conclusions: This study indicates that individuals carrying the -1562T allele are predisposed to stiffer arteries, especially among menopausal women. Women with the T allele should be considered at high risk for cardiovascular disease., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)