A phenome-wide association study of polygenic scores for selected childhood cancer: Results from the UK Biobank.

The aim of this study was to scan phenotypes in adulthood associated with polygenic risk scores (PRS) for childhood cancers with well-articulated genetic architectures-acute lymphoblastic leukemia (ALL), Ewing sarcoma, and neuroblastoma-to examine genetic pleiotropy. Furthermore, we aimed to determine which SNPs could drive associations. Per-SNP summary statistics were extracted for PRS calculation.

The Effect of Socioeconomic Status and Race/Ethnicity on the Risk of Presenting With Advanced Stage at Diagnosis in Embryonal Tumors.

We evaluated whether socioeconomic status (SES), race/ethnicity, and their interaction were associated with the presentation of advanced stage at diagnosis in embryonal tumors. Children 0 to 19 years of age diagnosed with embryonal tumors between 2006 and 2018 were identified from the US Surveillance, Epidemiology, and End Results program database specialized with Census Tract SES/Rurality. SES quintile was derived from a composite index for census tracts.

The association between maternal nutrient intake during pregnancy and the risk of sporadic unilateral retinoblastoma among offspring.

Previous studies have associated maternal diet during pregnancy with the development of sporadic unilateral retinoblastoma (RB), but few studies have focused on the role of individual nutrients. The aim of this study is to investigate the association between maternal nutrient intake during pregnancy and the development of sporadic unilateral RB in the offspring. A modified food frequency questionnaire, with additional questions on supplement use, was completed via a phone interview.

Exploration of genetic ancestry and socioeconomic status in the incidence of neuroblastoma: An ecological study.

Although global differences in the incidence of neuroblastoma have been examined, the underlying mechanism has yet to be elucidated. Previous studies have suggested genetic ancestry and human development index (HDI) as contributing factors, but few studies have been conducted at the international level. Here, we aimed to examine whether the frequency of common genomic variation associated with neuroblastoma can affect its risk at the ecological level with consideration of the HDI.

Daytime sleepiness among Midwestern firefighters.

Excessive daytime sleepiness (EDS) is the most common symptom of sleep-disorders. Although high levels of EDS have been reported among firefighters, there is a limited understanding on EDS in firefighters. A cross-sectional survey was conducted in full-time firefighters ( = 275).

Association between prenatal exposure to PM and the increased risk of specified infant mortality in South Korea.

Background: Findings from previous studies on the association between exposure to fine particulate matter (PM) and the risk of infant mortality were inconsistent. Thus, two main objectives of our study were to examine the association between exposure to PM and specified infant mortality and to identify critical trimesters.

Methods: We retrospectively created a birth cohort of singleton full-term infants born in South Korea between 2010 and 2015 using national birth and infant mortality data.

Children's Environmental Health Indicators in Context of the Sustainable Development Goals for Small Island Developing States.

The unique environmental vulnerability of small island developing states (SIDS) is likely to impact negatively on children's health. Children's environmental health indicators (CEHI) are standardized measures that can be used to assess the environmental exposures and their resulting health outcomes in children. This study sought to utilize the United Nations (UN) global Sustainable Development Goals (SDGs), with their associated targets and indicators, as a framework for a CEHI proposal for SIDS.

Does exposure to PM decrease age at menarche?

Background: There has been a consistent decrease in age at menarche in South Korea. A potential risk factor for early menarche is exposure to particulate matter (PM), because endocrine-disrupting compounds emitted into air from anthropogenic sources may be incorporated into PM. The objective of this study was to examine the association between pre-menarcheal exposure to PM ≤ 10 μm in diameter (PM) and age at menarche in adolescents of South Korea using Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012 data.

Children's Environmental Health Indicators for Low- and Middle-Income Countries in Asia.

Background: Given that low- and middle-income countries (LMICs) in Asia still have high child mortality rates, improved monitoring using children's environmental health indicators (CEHI) may help reduce preventable deaths by creating healthy environments.

Objectives: Thus, the aim of this study is to build a set of targeted CEHI that can be applied in LMICs in Asia through the CEHI initiative using a common conceptual framework.

Methods: A systematic review was conducted to identify the most frequently used framework for developing CEHI.

NFIB is a potential target for estrogen receptor-negative breast cancers.

Background: The association between nuclear factor I/B (NFIB) gene and triple negative breast cancer has been previously suggested.

Methods: We investigated the relationship between NFIB mRNA and protein expression and molecular subtypes of breast cancer as well as the effect of NFIB silencing on the proliferation and apoptosis of breast cancer cells. Also, the clinical importance of NFIB expression was investigated in 163 breast cancer patients.

Evidences for correlation between the reduced VCAM-1 expression and hyaluronan synthesis during cellular senescence of human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) undergo cellular senescence during in vitro expansion culture, which accompanies the loss of migration and homing abilities. In this study, we analyzed expression levels of several surface markers of human MSCs at different passages of expansion culture. It has been shown that expression of vascular cell adhesion molecule-1 (VCAM-1) was most markedly decreased among the tested markers in the senescent MSCs.

DNA copy number alterations and expression of relevant genes in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is defined by a lack of expression of estrogen, progesterone, and HER2 receptors, and genetically most of them fall into the basal subgroup of breast cancer. The important issue of TNBC is poorer clinical outcome and absence of effective targeted therapy. In this study, we sought to identify DNA copy number alterations and expression of relevant genes characteristic of TNBC to discover potential therapeutic targets.

Rosiglitazone promotes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP.

Death receptor 5 (DR5/TRAIL-R2) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we show that rosiglitazone sensitizes human renal cancer cells to TRAIL-mediated apoptosis, but not normal human mesangial cells. Furthermore, because rosiglitazone-enhanced TRAIL-mediated apoptosis is induced in various types of cancer cells but is not interrupted by Bcl-2 overexpression, this combinatory treatment may provide an attractive strategy for cancer treatment.

The novel phospholipase C activator, m-3M3FBS, induces apoptosis in tumor cells through caspase activation, down-regulation of XIAP and intracellular calcium signaling.

We investigated the effect of the novel phospholipase C activator, m-3M3FBS, on the apoptosis of human renal Caki cancer cells. Treatment with m-3M3FBS induced apoptosis of Caki cells, which was accompanied by accumulation of sub-G1 phase and DNA fragmentation. We found that induction of apoptosis is a common response of several cancer cell types to m-3M3FBS treatment.

Pro-oxidative DEP chemicals induce heat shock proteins and an unfolding protein response in a bronchial epithelial cell line as determined by DIGE analysis.

Ambient particulate matter (PM) induces adverse health effects through the ability of pro-oxidative chemicals to induce the production of oxygen radicals and oxidant injury. Utilizing a proteomics strategy involving 2-D DIGE, immunoblotting, and real-time PCR, we demonstrate that organic diesel exhaust particle (DEP) chemicals induce an unfolding protein response (UPR) and proinflammatory effects in the human bronchial epithelial cell line, BEAS-2B. DIGE and MS showed the induction of at least 14 proteins, among which heat shock protein 70 (HSP70), HSP40, TPR2, and T-complex protein 1 (zeta-subunit) are known to play a role in the UPR.

Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites.

Mithramycin A is a DNA-binding antitumor agent, which has been clinically used in the therapies of several types of cancer and Paget's disease. In this study, we investigated the combined effect of mithramycin A and tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) on apoptosis of cancer cells. In Caki renal cancer cells, which are resistant to TRAIL, cotreatment with subtoxic doses of mithramycin A and TRAIL resulted in a marked increase in apoptosis.

Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells.

Evodiamine is one of the major bioactive compounds that have been isolated and purified from the fruit of Evodiae fructus. Evodiamine exhibits antitumor activities against the human tumor cells, including multidrug-resistant tumor cells. However, the molecular mechanism involved in cell death induced by evodiamine treatment remains poorly understood.

A protective role for heme oxygenase-1 in INS-1 cells and rat islets that are exposed to high glucose conditions.

Heme oxygenase-1 (HO-1) has been described as an inducible protein that is capable of cytoprotection via radical scavenging and the prevention of apoptosis. Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, and this process has been termed glucose toxicity. Yet little is known about the relation between glucose toxicity and HO-1 in the islets.

Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation.

Death receptor DR5 (DR5/TRAIL-R2) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we showed that curcumin, a plant product containing the phenolic phytochemical, is a potent enhancer of TRAIL-induced apoptosis through upregulation of DR5 expression. Both treatment with DR5/Fc chimeric protein and silencing of DR5 expression using small interfering RNA (siRNA) attenuated curcumin plus TRAIL-induced apoptosis, showing that the critical role of DR5 in this cell death.

Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5).

Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis.

8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down-regulating LPS-induced activity of NF-kappaB and C/EBPbeta in Raw 264.7 cells.

In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, 8-hydroxyquinoline (8HQ) inhibited the LPS-induced expression of both iNOS protein and mRNA in a parallel dose-dependent manner.

Mechanism of angiotensin II-induced phospholipase D activation in bovine adrenal glomerulosa cells.

Based on previous data demonstrating activation of phospholipase D (PLD) in response to angiotensin II (AngII), we have hypothesized a role for PLD in mediating aldosterone secretion from bovine adrenal glomerulosa cells. In this study we demonstrate that a PLD-generated signal(s) is required for the AngII-elicited secretory response, since interfering with lipid second messenger formation using a primary alcohol inhibited AngII-induced aldosterone secretion, but not that elicited by incubation with a hydrophilic cholesterol analog, 22(R)-hydroxycholesterol, which bypasses signaling pathways. Three mechanisms for hormonal activation of PLD have been described in other systems: direct receptor coupling, activation through protein kinase C (PKC) and a combination of these two mechanisms.

Putative conventional protein kinase C inhibitor Gödecke 6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole] stimulates transglutaminase activity in primary mouse epidermal keratinocytes.

Much data in the literature suggest a role for protein kinase C (PKC) in regulating keratinocyte proliferation and differentiation. Nevertheless, the exact role of this family of isoenzymes is unclear, since PKC agonists (e.g.