Harmful alcohol use among mothers of under-five child: findings from the Panel Study on Korean Children

Background Harmful alcohol use in young mothers as a primary caregiver has a profound impact on their own health and interaction with the child. We studied the epidemiology of harmful alcohol use among Korean mothers and their partners of under-five children. Methods We used a longitudinal data of 2,150 Korean mothers of the Panel Study on Korean Children (PSKC). We assessed temporal trend and risk factors for harmful alcohol use in mothers using generalized estimating equation (GEE) model. To estimate the impact of maternal harmful alcohol use on the child, the association between neurodevelopment of the child measured by the Korean-Ages & Stages Questionnaire (K-ASQ) and maternal harmful alcohol use was analyzed using GEE and generalized linear mixed model. We included mothers age, education, preterm, year of the survey and time-varying covariates (including maternal working status, monthly household income, plan for additional childbirth, psychological stress related with childcare, current smoking, and partners harmful alcohol use) in the model. Results Mean age of mothers at the baseline was 31.3 years. Annual prevalence of harmful alcohol use increased from 0.7% in the 1st year to 2.6% in the 4th year (P for linear trend < 0.001). Prevalence of harmful alcohol use increased by 48% per year among the mothers (adjusted odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.22, 1.78). Lower education than college or university graduation was associated with higher odds of harmful alcohol use (2.52, 95% CI: 1.43, 4.45). Current smoking (7.44, 95% CI: 3.00, 18.45), harmful use of alcohol of partner (2.66, 95% CI: 1.57, 4.49) were associated with higher risk of harmful alcohol use in mothers. The association between low K-ASQ score and maternal harmful alcohol use was toward positive which did not reach statistical significance. Conclusions In a cohort of Korean mothers participating in the PKSC, risk of harmful alcohol use increases over time and is associated with harmful alcohol use of their partners. We suggest an approach targeting both parents can be more effective in controlling the harmful alcohol use of mothers.This research was supported by a Korea University Grant (K2022961) and a Korea University Medical Center Grant (K2025301). This funding source had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publica‑tion. The contents of this report are solely the responsibility of the authors and do not necessarily represent the ofcial views of the sponsoring organizatio

MicroRNA-143 and-145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis

Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype. Global miRNA profiling revealed that miR-143 and miR-145 were differentially upregulated in RA-FLSs compared to OA-FLSs. miR-143 and miR-145 were highly expressed in independent RA-FLSs. The miRNA-target prediction and network model of the predicted targets identified insulin-like growth factor binding protein 5 (IGFBP5) and semaphorin 3A (SEMA3A) as potential target genes downregulated by miR-143 and miR-145, respectively. IGFBP5 level was inversely correlated with miR-143 expression, and its deficiency rendered RA-FLSs more sensitive to TNFα stimulation, promoting IL-6 production and NF-κB activity. Moreover, SEMA3A was a direct target of miR-145, as determined by a luciferase reporter assay, antagonizing VEGF165-induced increases in the survival, migration and invasion of RA-FLSs. Taken together, our data suggest that enhanced expression of miR-143 and miR-145 renders RA-FLSs susceptible to TNFα and VEGF165 stimuli by downregulating IGFBP5 and SEMA3A, respectively, and that these miRNAs could be therapeutic targets. © 2017 KSBMB4

TCF/β-catenin plays an important role in HCCR-1 oncogene expression

<p>Abstract</p> <p>Background</p> <p>Oncogene <it>HCCR-1 </it>functions as a negative regulator of the p53 and contributes to tumorigenesis of various human tissues. However, it is unknown how <it>HCCR-1 </it>contributes to the cellular and biochemical mechanisms of human tumorigenesis.</p> <p>Results</p> <p>In this study, we showed how the expression of <it>HCCR-1 </it>is modulated. The luciferase activity assay indicated that the <it>HCCR-1 </it>5'-flanking region at positions -166 to +30 plays an important role in <it>HCCR-1 </it>promoter activity. Computational analysis of this region identified two consensus sequences for the T-cell factor (TCF) located at -26 to -4 (Tcf1) and -136 to -114 (Tcf2). Mutation at the Tcf1 site led to a dramatic decrease in promoter activity. Mobility shift assays (EMSA) revealed that nuclear proteins bind to the Tcf1 site, but not to the Tcf2 site. LiCl, Wnt signal activator by GSK-3β inhibition, significantly increased reporter activities in wild-type Tcf1-containing constructs, but were without effect in mutant Tcf1-containing constructs in HEK/293 cells. In addition, endogenous <it>HCCR-1 </it>expression was also increased by treatment with GSK-3β inhibitor, LiCl or AR-A014418 in HEK/293 and K562 cells. Finally, we also observed that the transcription factor, TCF, and its cofactor, β-catenin, bound to the Tcf1 site.</p> <p>Conclusion</p> <p>These findings suggest that the Tcf1 site on the <it>HCCR-1 </it>promoter is a major element regulating <it>HCCR-1 </it>expression and abnormal stimulation of this site may induce various human cancers.</p

Identification of novel urinary biomarkers for assessing disease activity and prognosis of rheumatoid arthritis

To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates-gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)-in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals.1

Multimodality Imaging Can Help to Doubt, Diagnose and Follow-Up Cardiac Mass

Primary cardiac lymphoma is a very rare form of lymphoma primarily or mainly involving the heart, as in the two cases presented in this report. Various imaging modalities, including coronary computed tomography angiography, cardiac magnetic resonance imaging and positron emission tomography were useful for the characterization and diagnosis of cardiac mass. Pathologic confirmation was successful with endomyocardial biopsy under echocardiographic guidance, intra- and extracardiacally. In primary cardiac lymphoma, diagnosis using multiple modalities may be useful for mass characterization, and for response monitoring after chemotherapy

Serial Measurement of WT1 Expression and Decrement Ratio Until Hematopoietic Cell Transplantation as a Marker of Residual Disease in Patients with Cytogenetically Normal Acute Myelogenous Leukemia

AbstractUsing real-time quantitative PCR, we monitored Wilms tumor gene 1 (WT1) expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in adult patients with cytogenetically normal acute myelogenous leukemia (CN-AML) and FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104 patients. Data collected after induction chemotherapy were available for all patients, but only 68 patients were treated with HSCT. Significant WT1 expression cut-offs were determined by receiver operation characteristic curve analysis, and rates of overall survival (OS) and disease-free survival (DFS) were estimated. WT1 decrement ratios (DR) at postinduction chemotherapy and at pre- and post-HSCT compared with the diagnostic level were calculated. Higher WT1 expression at diagnosis, postinduction chemotherapy, and pre-HSCT showed inferior OS (P = .015, <.001, and .002) and DFS (P = .006, <.001, and .003). The cut-offs were determined at the median for diagnostic WT1 expression and at the 25% level from the top for other time points excluding post-HSCT. The WT1 DR ≥ 1-log after induction chemotherapy showed superior OS and DFS (P = .009 and .002) and WT1 DR ≥ 1-log preceding HSCT also showed superior OS and DFS (P = .009 and .003). Results of WT1 DR were consistently applicable in each subgroup with higher (≥1.0) and lower (<1.0) WT1 expression at diagnosis and also in NPM1-wild-type/FLT3-ITD–negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT more accurately than did the diagnostic WT1 expression. WT1 expression may serve as a reliable marker for residual disease and WT1 DR as a prognostic indicator, particularly in NPM1-wild-type/FLT3-ITD–negative CN-AML. These measures may be applied throughout the course of treatment and even after HSCT

Attenuation of Rheumatoid Inflammation by Sodium Butyrate Through Reciprocal Targeting of HDAC2 in Osteoclasts and HDAC8 in T Cells

Rheumatoid arthritis (RA) is a systemic autoimmune disease caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental factor that affects the development of RA. Metabolites secreted by the gut microbiota maintain homeostasis in the gut through various mechanisms [e.g., butyrate, which is one of the major metabolites of gut microbiota, exerts an anti-inflammatory effect by activating G-protein-coupled receptors and inhibiting histone deacetylases (HDACs)]. Here, we focused on the inhibition of the HDACs by butyrate in RA. To this end, we evaluated the therapeutic effects of butyrate in an animal model of autoimmune arthritis. The arthritis score and incidence were lower in the butyrate-treated group compared to the control group. Also, butyrate inhibited HDAC2 in osteoclasts and HDAC8 in T cells, leading to the acetylation of glucocorticoid receptors and estrogen-related receptors α, respectively. Additionally, control of the TH17/Treg cell balance and inhibition of osteoclastogenesis were confirmed by the changes in target gene expression. Interleukin-10 (IL-10) produced by butyrate-induced expanded Treg cells was critical, as treatment with butyrate did not affect inflammatory arthritis in IL-10-knockout mice. This immune-cell regulation of butyrate was also detected in humans. These findings suggest that butyrate is a candidate agent for the treatment of RA

Second Primary Glioblastoma Multiforme Following Autologous Hematopoietic Stem Cell Transplantation in a Patient with Acute Myelogenous Leukemia

Glioblastoma multiforme (GM) is one of the most aggressive primary brain tumors, and has a poor prognosis despite intensive treatment. GM is also the most malignant astrocytoma, with histopathological features that include cellular polymorphism, rapid mitotic activity, microvascular proliferation, and necrosis. The causes of GM remain obscure, but several reports have shown associations between GM and genetic alterations and radiation exposure. Furthermore, high-dose chemotherapy/radiotherapy with autologous stem cell transplantation is increasingly being used to treat patients with leukemia, and patients who undergo stem cell transplantation have a higher risk of solid tumor cancer development later in life. Based on these associations, we discuss GM development in a patient who underwent chemoradiotherapy conditioning prior to stem cell transplantation

Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice

Bile acids (BAs) control metabolism and inflammation by interacting with several receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA) decreases serum pro-inflammatory cytokines, normalizes hypotension, protects against renal injury, and prolongs mouse survival during sepsis. TDCA increases the number of granulocytic myeloid-derived suppressor cells (MDSCLT) distinctive from MDSCs obtained without TDCA treatment (MDSCL) in the spleen of septic mice. FACS-sorted MDSCLT cells suppress T-cell proliferation and confer protection against sepsis when adoptively transferred better than MDSCL. Proteogenomic analysis indicated that TDCA controls chromatin silencing, alternative splicing, and translation of the immune proteome of MDSCLT, which increases the expression of anti-inflammatory molecules such as oncostatin, lactoferrin and CD244. TDCA also decreases the expression of pro-inflammatory molecules such as neutrophil elastase. These findings suggest that TDCA globally edits the proteome to increase the number of MDSCLT cells and affect their immune-regulatory functions to resolve systemic inflammation during sepsis