Decrease of 5hmC in gastric cancers is associated with TET1 silencing due to with DNA methylation and bivalent histone marks at TET1 CpG island 3'-shore.

Recent evidence has shown that the level of 5-hydroxymethylcytosine (5 hmC) in chromosomal DNA is aberrantly decreased in a variety of cancers, but whether this decrease is a cause or a consequence of tumorigenesis is unclear. Here we show that, in gastric cancers, the 5 hmC decrease correlates with a decrease in ten-eleven translocation 1 (TET1) expression, which is strongly associated with metastasis and poor survival in patients with gastric cancer. In gastric cancer cells, TET1-targeted siRNA induced a decrease in 5 hmC, whereas TET1 overexpression induced an increase in 5 hmC and reduced cell proliferation, thus correlating decreased 5 hmC with gastric carcinogenesis.

Differential Associations Between Delirium and Mortality According to Delirium Subtype and Age: A Prospective Cohort Study.

Objective: This study investigated the differential associations between delirium and mortality in terminally ill patients according to delirium subtype and age.

Methods: This was a prospective cohort study of terminally ill patients. Delirium was diagnosed using the confusion assessment method.

Arginine Thiazolidine Carboxylate Stimulates Insulin Secretion through Production of Ca2+-Mobilizing Second Messengers NAADP and cADPR in Pancreatic Islets.

Oxothiazolidine carboxylic acid is a prodrug of cysteine that acts as an anti-diabetic agent via insulin secretion and the formation of the Ca2+-mobilizing second messenger, cyclic ADP-ribose (cADPR). Here we show that a hybrid compound, arginine thiazolidine carboxylate (ATC), increases cytoplasmic Ca2+ in pancreatic β-cells, and that the ATC-induced Ca2+ signals result from the sequential formation of two Ca2+-mobilizing second messengers: nicotinic acid adenine dinucleotide phosphate (NAADP) and cADPR. Our data demonstrate that ATC has potent insulin-releasing properties, due to the additive action of its two components; thiazolidine carboxylate (TC) and L-arginine.

The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease.

miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4.

The myogenic capacity of myoblasts decreases in skeletal muscle with age. In addition to environmental factors, intrinsic factors are important for maintaining the regenerative potential of muscle progenitor cells, but their identities are largely unknown. Here, comparative analysis of microRNA (miRNA) expression profiles in young and old myoblasts uncovered miR-431 as a novel miRNA showing markedly reduced abundance in aged myoblasts.

Roles of DPY30 in the Proliferation and Motility of Gastric Cancer Cells.

Various types of histone methylation have been associated with cancer progression. Depending on the methylation site in histone proteins, its effects on transcription are different. DPY30 is a common member of SET1/MLL histone H3K4 methyltransferase complexes.

Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers.

Purpose: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH.

Methods: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study.

Factors associated with self-rated sexual function in Korean patients with schizophrenia receiving risperidone monotherapy.

Objective: This study aims to investigate the factors associated with sexual function in Korean patients with schizophrenia.

Methods: This study evaluated 169 patients with schizophrenia who were receiving risperidone monotherapy. The Visual Analog Scale was used to assess sexual function in terms of sexual desire, sexual arousal, and sexual satisfaction.

MED30 Regulates the Proliferation and Motility of Gastric Cancer Cells.

MED30 is an essential member of the mediator complex that forms a hub between transcriptional activators and RNA polymerase II. However, the expressions and roles of MED30 have been poorly characterized in cancer. In this study, we examined the functional roles of MED30 during gastric cancer progression.

Genome-wide mutation profiles of colorectal tumors and associated liver metastases at the exome and transcriptome levels.

To characterize the mutation profiles of colorectal cancer (CRC) primary tumors (PTs) and liver metastases (CLMs), we performed both whole-exome and RNA sequencing. Ten significantly mutated genes, including BMI1, CARD11, and NRG1, were found in 34 CRCs with CLMs. We defined three mutation classes (Class 1 to 3) based on the absence or presence of mutations during liver metastasis.

SERBP1 affects homologous recombination-mediated DNA repair by regulation of CtIP translation during S phase.

DNA double-strand breaks (DSBs) are the most severe type of DNA damage and are primarily repaired by non-homologous end joining (NHEJ) and homologous recombination (HR) in the G1 and S/G2 phase, respectively. Although CtBP-interacting protein (CtIP) is crucial in DNA end resection during HR following DSBs, little is known about how CtIP levels increase in an S phase-specific manner. Here, we show that Serpine mRNA binding protein 1 (SERBP1) regulates CtIP expression at the translational level in S phase.

ATOH1 Can Regulate the Tumorigenicity of Gastric Cancer Cells by Inducing the Differentiation of Cancer Stem Cells.

Cancer stem cells (CSCs) have been shown to mediate tumorigenicity, chemo-resistance, radio-resistance and metastasis, which suggest they be considered therapeutic targets. Because their differentiated daughter cells are no longer tumorigenic, to induce the differentiation of CSCs can be one of strategies which can eradicate CSCs. Here we show that ATOH1 can induce the differentiation of gastric cancer stem cells (GCSCs).

Ctbp2 Modulates NuRD-Mediated Deacetylation of H3K27 and Facilitates PRC2-Mediated H3K27me3 in Active Embryonic Stem Cell Genes During Exit from Pluripotency.

For cells to exit from pluripotency and commit to a lineage, the circuitry of a core transcription factor (CTF) network must be extinguished in an orderly manner through epigenetic modifications. However, how this choreographed epigenetic remodeling at active embryonic stem cell (ESC) genes occurs during differentiation is poorly understood. In this study, we demonstrate that C-terminal binding protein 2 (Ctbp2) regulates nucleosome remodeling and deacetylation (NuRD)-mediated deacetylation of H3K27 and facilitates recruitment of polycomb repressive complex 2 (PRC2)-mediated H3K27me3 in active ESC genes for exit from pluripotency during differentiation.

Comorbidity of depression with physical disorders: research and clinical implications.

Depression is prevalent in patients with physical disorders, particularly in those with severe disorders such as cancer, stroke, and acute coronary syndrome. Depression has an adverse impact on the courses of these diseases that includes poor quality of life, more functional impairments, and a higher mortality rate. Patients with physical disorders are at higher risk of depression.

Influence of caregiver personality on the burden of family caregivers of terminally ill cancer patients.

Objective: To determine the influence of caregiver personality and other factors on the burden of family caregivers of terminally ill cancer patients.

Method: We investigated a wide range of factors related to the patient-family caregiver dyad in a palliative care setting using a cross-sectional design. Caregiver burden was assessed using the seven-item short version of the Zarit Burden Interview (ZBI-7).

Effects of excessive dietary methionine on oxidative stress and dyslipidemia in chronic ethanol-treated rats.

Background/objective: The aim of this study was to examine the effect of high dietary methionine (Met) consumption on plasma and hepatic oxidative stress and dyslipidemia in chronic ethanol fed rats.

Materials/methods: Male Wistar rats were fed control or ethanol-containing liquid diets supplemented without (E group) or with DL-Met at 0.6% (EM1 group) or 0.

Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway.

Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling through Gαq. Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2 (MR-Rgs2) are hypertensive relative to people expressing wild-type Met-Gln-Rgs2 (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were destroyed by the Ac/N-end rule pathway, which recognizes N(α)-terminally acetylated (Nt-acetylated) proteins.

Effect of firefighters' personal protective equipment on gait.

The biomechanical experiment with eight male and four female firefighters demonstrates that the effect of adding essential equipment: turnout ensemble, self-contained breathing apparatus, and boots (leather and rubber boots), significantly restricts foot pronation. This finding is supported by a decrease in anterior-posterior and medial-lateral excursion of center of plantar pressure (COP) trajectory during walking. The accumulation of this equipment decreases COP velocity and increases foot-ground contact time and stride time, indicating increased gait instability.

Impact of elevated CO₂ and N addition on bacteria, fungi, and archaea in a marsh ecosystem with various types of plants.

The individual effects of either elevated CO2 or N deposition on soil microbial communities have been widely studied, but limited information is available regarding the responses of the bacteria, fungi, and archaea communities to both elevated CO2 and N in wetland ecosystems with different types of plants. Using a terminal restriction fragment length polymorphism (T-RFLP) analysis and real-time quantitative PCR (RT-Q-PCR), we compared communities of bacteria, fungi, and archaea in a marsh microcosm with one of seven macrophytes, Typha latifolia, Phragmites japonica, Miscanthus sacchariflorus, Scirpus lacustris, Juncus effusus, Phragmites australis, or Zizania latifolia, after exposing them to eCO2 and/or amended N for 110 days. Overall, our results showed that the elevated CO2 and N may affect the bacterial and archaeal communities, while they may not affect the fungal community in terms of both diversity and abundance.

Vitamin C facilitates dopamine neuron differentiation in fetal midbrain through TET1- and JMJD3-dependent epigenetic control manner.

Intracellular Vitamin C (VC) is maintained at high levels in the developing brain by the activity of sodium-dependent VC transporter 2 (Svct2), suggesting specific VC functions in brain development. A role of VC as a cofactor for Fe(II)-2-oxoglutarate-dependent dioxygenases has recently been suggested. We show that VC supplementation in neural stem cell cultures derived from embryonic midbrains greatly enhanced differentiation toward midbrain-type dopamine (mDA) neurons, the neuronal subtype associated with Parkinson's disease.

Identification of body fluid-specific DNA methylation markers for use in forensic science.

DNA methylation, which occurs at the 5'-position of the cytosine in CpG dinucleotides, has great potential for forensic identification of body fluids, because tissue-specific patterns of DNA methylation have been demonstrated, and DNA is less prone to degradation than proteins or RNA. Previous studies have reported several body fluid-specific DNA methylation markers, but DNA methylation differences are sometimes low in saliva and vaginal secretions. Moreover, specific DNA methylation markers in four types of body fluids (blood, saliva, semen, and vaginal secretions) have not been investigated with genome-wide profiling.

APPEX: analysis platform for the identification of prognostic gene expression signatures in cancer.

Summary: Because cancer has heterogeneous clinical behaviors due to the progressive accumulation of multiple genetic and epigenetic alterations, the identification of robust molecular signatures for predicting cancer outcome is profoundly important. Here, we introduce the APPEX Web-based analysis platform as a versatile tool for identifying prognostic molecular signatures that predict cancer diversity. We incorporated most of statistical methods for survival analysis and implemented seven survival analysis workflows, including CoxSingle, CoxMulti, IntransSingle, IntransMulti, SuperPC, TimeRoc and multivariate.

A nineteen gene-based risk score classifier predicts prognosis of colorectal cancer patients.

Colorectal cancer (CRC) patients frequently experience disease recurrence and distant metastasis. This study aimed to identify prognostic indicators, including individual responses to chemotherapy, in CRC patients. RNA-seq data was generated using 54 samples (normal colon, primary CRC, and liver metastases) from 18 CRC patients and genes associated with CRC aggressiveness were identified.