Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells.

The multikinase inhibitor sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but many patients become sorafenib-resistant (SR). This study investigated the efficacy of another kinase inhibitor, regorafenib (Rego), as a second-line treatment. We produced SR HCC cells, wherein the PI3K-Akt, TNF, cAMP, and TGF-beta signaling pathways were affected.

Defined Conditions Control the Morphological Dualism of Rat Primitive Extraembryonic Endoderm Stem Cells.

Rat primitive extraembryonic endoderm (pXEN) stem cell lines indefinitely preserve the characteristic features of the early extraembryonic endoderm (ExEn) in vitro, but require unknown serum factors and exhibit a hybrid (mesenchymal-epithelial) phenotype. We report two chemically defined conditions that differ by the addition of the cytokine leukemia inhibitory factor (Lif) and the β-catenin-stabilizing drug Chir99021, and enable permanent self-renewal as mesenchymal and epithelial morphotypes, respectively. The morphotypes are interconvertible and equipotent, as shown by the formation of well-differentiated organoids.

Analysis of differentially expressed long non-coding RNAs in LPS-induced human HMC3 microglial cells.

Background: Long non-coding RNAs (lncRNAs) are emerging as key modulators of inflammatory gene expression, but their roles in neuroinflammation are poorly understood. Here, we identified the inflammation-related lncRNAs and correlated mRNAs of the lipopolysaccharide (LPS)-treated human microglial cell line HMC3. We explored their potential roles and interactions using bioinformatics tools such as gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), and weighted gene co-expression network analysis (WGCNA).

The bromodomain inhibitor JQ1 up-regulates the long non-coding RNA MALAT1 in cultured human hepatic carcinoma cells.

The epigenetic reader, bromodomain-containing 4 (BRD4), is overexpressed in hepatocellular carcinoma (HCC), and BRD4 inhibition is considered as a new therapeutic approach. The BRD inhibitor JQ1 is known to inhibit the enrichment of BRD4 at enhancer sites. Gene network analyses have implicated long non-coding RNAs (lncRNAs) in the effects of JQ1, but the precise molecular events remain unexplored.

Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poor prognosis. Emerging evidence suggests that epigenetic alterations play a crucial role in HCC, suggesting epigenetic inhibition as a promising therapeutic approach. Indeed, the bromodomain and extra-terminal (BET) inhibitors inhibit the proliferation and invasion of various cancers but still lack a strong mechanistic rationale.

Targeting of noncoding RNAs encoded by a novel MYC enhancers inhibits the proliferation of human hepatic carcinoma cells in vitro.

The proto-oncogene MYC is important for development and cell growth, however, its abnormal regulation causes cancer. Recent studies identified distinct enhancers of MYC in various cancers, but any MYC enhancer(s) in hepatocellular carcinoma (HCC) remain(s) elusive. By analyzing H3K27ac enrichment and enhancer RNA (eRNA) expression in cultured HCC cells, we identified six putative MYC enhancer regions.

BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4.

Hepatocellular carcinoma (HCC) is one of the most prevalent and poorly responsive cancers worldwide. Bromodomain and extraterminal (BET) inhibitors, such as JQ1 and OTX-015, inhibit BET protein binding to acetylated residues in histones. However, the physiological mechanisms and regulatory processes of BET inhibition in HCC remain unclear.

The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line.

Microglia, resident macrophages of the brain that act as primary immune cells, play essential roles in innate immunity and neuroinflammatory pathologies. Microglial cells are rapidly activated in response to infection and inflammation/injury, associated with the expression of proinflammatory genes and secretion of cytokines. The bromodomain and extra-terminal (BET) inhibitor JQ1 has been shown to be an epigenetic agent that reduces inflammation.

Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.

Background: Toll-like receptor 4 (TLR4) ligands such as lipopolysaccharide (LPS) activate immunomodulatory functions and the migration of human mesenchymal stromal cells (hMSCs). Here, we study the migration-related gene expression of LPS-stimulated hMSCs and the role and regulation of one of the upregulated genes, encoding the interferon-induced transmembrane protein 1 (IFITM1).

Methods: Gene expression profiles were determined by whole-transcriptome analysis (RNA-seq) and quantitative real-time PCR (qRT-PCR).

Basal-type lumenogenesis in extraembryonic endoderm stem cells models the early visceral endoderm.

Cultured rat primitive extraembryonic endoderm (pXEN) cells easily form free-floating multicellular vesicles , exemplifying a poorly studied type of morphogenesis. Here, we reveal the underlying mechanism and the identity of the vesicles. We resolve the morphogenesis into vacuolization, vesiculation and maturation, and define the molecular characteristics and requirements of each step.

Effect of erosive and abrasive stress on sealing ability of different desensitizers: In-vitro study.

This in vitro study examined the sealing ability of different desensitizing agents under a chemo-mechanical stress condition. For the study, a total of 144 extracted, caries-free human third molars were used to produce 1 mm-thick dentin discs. The specimens were divided randomly into four groups: Superseal (SS), Gluma (GL), Gluma Self-etch (GS), and Tooth Coat (TC).

Intratracheal Ovalbumin Administration Induces Colitis Through the IFN-γ Pathway in Mice.

Recent studies have reported an increased incidence of inflammatory bowel disease (IBD) in patients with pulmonary diseases. Despite clinical and epidemiological studies of the interplay between colitis and asthma, the diseases' related underlying mechanisms remain unclear. In this study, we evaluated the development of colitis in a model of allergic airway inflammation.

Forkhead box O1 (FOXO1) controls the migratory response of Toll-like receptor (TLR3)-stimulated human mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) can potently regulate the functions of immune cells and are being investigated for the management of inflammatory diseases. Toll-like receptor 3 (TLR3)-stimulated human MSCs (hMSCs) exhibit increased migration and chemotaxis within and toward damaged tissues. However, the regulatory mechanisms underlying these migratory activities are unclear.

Isolation of primitive mouse extraembryonic endoderm (pXEN) stem cell lines.

Mouse blastocysts contain the committed precursors of the extraembryonic endoderm (ExEn), which express the key transcription factor Oct4, depend on LIF/LIF-like factor-driven Jak/Stat signaling, and initially exhibit lineage plasticity. Previously described rat blastocyst-derived ExEn precursor-like cell lines (XENP cells/HypoSCs) also show these features, but equivalent mouse blastocyst-derived cell lines are lacking. We now present mouse blastocyst-derived cell lines, named primitive XEN (pXEN) cells, which share these and additional characteristics with the XENP cells/HypoSCs, but not with previously known mouse blastocyst-derived XEN cell lines.

High-Resolution Mapping and Dynamics of the Transcriptome, Transcription Factors, and Transcription Co-Factor Networks in Classically and Alternatively Activated Macrophages.

Macrophages are the prime innate immune cells of the inflammatory response, and the combination of multiple signaling inputs derived from the recognition of host factors [e.g., interferon-g (IFN-γ)] and invading pathogen products (e.

Cigarette Smoking Triggers Colitis by IFN-γ CD4 T Cells.

The increased incidence of Crohn's disease in smokers has been recently reported, suggesting a strong association of cigarette smoke (CS) with colitis. However, the mechanism of the action of CS on colitis has not yet been explored. Here, we demonstrate that CS exposure is sufficient to induce colitis in mice.

Time of Application of Sodium Ascorbate on Bonding to Bleached Dentin.

This study examined the effects of different application times of sodium ascorbate (SA) on the bond strength of composite resin to bleached dentin. Specimens with an exposed dentin surface were divided into 3 groups according to the type of bleaching agent used: Group A, mixture of sodium perborate (SP) and distilled water (DW); Group B, mixture of SP and hydrogen peroxide (HP); control group, no bleaching. Each group was classified into 10 subgroups.

Alcohol Exposure and the Alteration of Histone Marks in the Developing Fetus: An Epigenetic Phenomenon of Maternal Drinking.

Ethanol is well known for its teratogenic effects during fetal development. Maternal alcohol consumption allows the developing fetus to experience the detrimental effects of alcohol exposure. Alcohol-mediated teratogenic effects can vary based on the dosage and the length of exposure.

Effect of Dentin Wetness on the Bond Strength of Universal Adhesives.

The effects of dentin wetness on the bond strength and adhesive interface morphology of universal adhesives have been investigated using micro-tensile bond strength (μTBS) testing and confocal laser scanning microscopy (CLSM). Seventy-two human third molars were wet ground to expose flat dentin surfaces. They were divided into three groups according to the air-drying time of the dentin surfaces: 0 (without air drying), 5, and 10 s.

GSK-J4-Mediated Transcriptomic Alterations in Differentiating Embryoid Bodies.

Histone-modifying enzymes are key players in the field of cellular differentiation. Here, we used GSK-J4 to profile important target genes that are responsible for neural differentiation. Embryoid bodies were treated with retinoic acid (10 μM) to induce neural differentiation in the presence or absence of GSK-J4.

Gestational Alcohol Exposure Altered DNA Methylation Status in the Developing Fetus.

Ethanol is well known as a teratogenic factor that is capable of inducing a wide range of developmental abnormalities if the developing fetus is exposed to it. Duration and dose are the critical parameters of exposure that affect teratogenic variation to the developing fetus. It is suggested that ethanol interferes with epigenetic processes especially DNA methylation.

Selective inhibition of EZH2 by a small molecule inhibitor regulates microglial gene expression essential for inflammation.

Multiple studies have documented that Enhancer of zeste homolog 2 (EZH2) could play a role in inflammation and a wide range of malignancies; however, the underlying mechanisms remain largely unaddressed. Microglial activation is a key process in the production and release of numerous pro-inflammatory mediators that play important roles in inflammation and neurodegeneration in the central nervous system (CNS). Therefore, our aim was to investigate whether inhibition of EZH2 with the selective small molecule inhibitor EPZ-6438 protects against neonatal microglial activation.