Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that ...

MicroRNAs (miRNAs) are endogenous, non-coding RNA transcripts that regulate gene expression. Here, we report 175 putative novel miRNAs identified in uterine cancers profiled by Next Generation Sequencing. Our data indicate that one of these putative miRNAs (BCM-173) is conserved across multiple species and is expressed at levels similar to known ...

ABSTRACT: BACKGROUND: Prostaglandin (PG) E2 plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE2 catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE2 content, as well as ...

MEF2C is a selectively expressed transcription factor involved in different transcriptional complexes. Originally identified as an essential regulator of muscle development, ectopic expression of MEF2C as a result of chromosomal rearrangements is now linked to leukemia. Specifically, high MEF2C expression has been linked to mixed lineage leukemia-rearranged acute myeloid leukemia ...

The human solute linked carrier (SLC) 13A4 gene is primarily expressed in the placenta where it is proposed to mediate the transport of nutrient sulfate from mother to fetus. The molecular mechanisms involved in the regulation of SLC13A4 expression remain unknown. To investigate the regulation of SLC13A4 gene expression, we ...

The nuclear lamina consists of A- and B-type lamins. Mutations in LMNA cause many human diseases, including progeria, a premature aging syndrome, whereas LMNB1 duplication causes adult-onset autosomal dominant leukodystrophy (ADLD). LMNB1 is reduced in cells from progeria patients, but the significance of this reduction is unclear. In this paper, ...

AIM: Test whether human periodontal ligament fibroblasts (PDLFs) retain homeostatic responses to a physiological compressive force during chronic periodontitis. MATERIAL AND METHODS: Six cell lines were established from periodontally healthy individuals (H-PDLFs) and another six were cultured from patients diagnosed with chronic periodontitis (D-PDLFs). Compressive force at 150 psi was applied ...

BACKGROUND & AIMS: Studies of the transcriptional networks that regulate nuclear receptor-mediated proliferation of quiescent hepatocytes could lead to new information about liver growth and hepatoprotective strategies. METHODS: We used quantitative real-time PCR to analyze expression of neuron-derived orphan receptor 1 (Nor-1) and its target genes during liver regeneration after ...

All members of the EGF family are produced as transmembrane precursors that are proteolytically processed into soluble forms by a disintegrin and metalloproteinases (ADAMs) for autocrine/paracrine pathways. In turn, ligand-activated EGF receptor (EGFR) induces the expression of EGF family members, so-called ″autoinduction″. However, it is not well understood how this ...

The C1q/TNF-related protein (CTRP) family represents a growing family of adiponectin paralogous proteins. CTRP-5 was detected in adipose tissue of mice and plays a role in the context of the metabolic syndrome. It was the aim to investigate the detailed expression profile of CTRP-5 in a variety of adipocytic cells ...

The ZIC transcription factors are key mediators of embryonic development and ZIC3 is the gene most commonly associated with situs defects (Heterotaxy) in humans. Half of patient ZIC3 mutations introduce a premature termination codon (PTC). In vivo, PTC-containing transcripts may be targeted for nonsense mediated decay (NMD). NMD efficiency is ...

Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpG-binding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 3' untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the ...

The retrovirus restriction factor SAMHD1 is the first identified mammalian deoxynucleoside triphosphate (dNTP) triphosphohydrolase that is highly expressed in human myeloid-lineage cells and CD4+ T-lymphocytes. While SAMHD1 expression is variable in human cell lines and tissue types, mechanisms underlying SAMHD1 gene regulation have not been defined. Recent studies showed that ...

Cardiac fibroblasts (CF) play a central role in the repair and remodeling of the heart following injury and are important regulators of inflammation and extracellular matrix (ECM) turnover. ECM-regulatory matricellular proteins are synthesized by several myocardial cell types including CF. We investigated the effects of pro-inflammatory cytokines on matricellular protein ...

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a pro-carboxypeptidase B-like pro-enzyme that upon activation attenuates fibrinolysis and inflammatory processes. There is a large inter-individual variability in plasma TAFI levels within the population which is primarily due to epigenetic factors. Novel associations between plasma TAFI levels and sex steroids have triggered interest in ...

Angiogenin (ANG) is a potent angiogenic factor that is up-regulated by hypoxia. ANG expression is well documented in normal tissues and in common tumours, but its expression has not been reported in the normal human kidney or in Wilms' tumours (WT). We examined ANG expression in WTs, human fetal kidney ...

Goldberg-Shprintzen syndrome (GOSHS, MIM #609460) is an autosomal recessive disorder of intellectual disability, specific facial gestalt, and Hirschsprung disease. In 2005, homozygosity mapping in a large consanguineous family identified KIAA1279 as the disease-causing gene. KIAA1279 encodes KIF-binding protein (KBP), whose function is incompletely understood. Studies have identified either the mitochondria ...

Ultraviolet (UV) radiation damages human skin and causes skin diseases such as epidermal hyperplasia, sunburn, inflammatory responses, and photoaging. Photoaging is associated with upregulated matrix metalloproteinase (MMP) expression and downregulated collagen synthesis. Fucosterol, which is isolated from marine brown algae, has been reported to possess antioxidant and anticancer activities; however, ...

The mitotic kinesin superfamily protein KIF14 is essential for cytokinesis and chromosome segregation and increased KIF14 expression is related to a variety of human cancers. In this study, we investigate KIF14 expression in association with clinical variables and the role of KIF14 during tumorigenesis. We found that KIF14 is overexpressed ...

Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of lncRNAs may have ...

The melanocortin 4 receptor (MC4R) is an essential regulator of energy homeostasis and metabolism, and MC4R mutations represent the most prevalent monogenetic cause of obesity in humans known to date. Hypothalamic MC4Rs in rodents are well characterized in neuroanatomical and functional terms, but their expression pattern in the human hypothalamus ...

A 76-kDa Ral-interacting protein (RLIP76) has been implicated in the pathogenesis of cancer and diabetes. It is often overexpressed in human malignant cell lines and human tumor samples and has been associated with metastasis and chemoresistance. RLIP76 homozygous knockout mice exhibit increased insulin sensitivity, hypoglycemia, and hypolipidemia, and resist cancer ...

We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells. AhR-dependent reporter gene expression in transfected HepG2 cells was increased by pelargonidin in a concentration-dependent manner at 24h. Similarly, pelargonidin ...

Recent molecular and biochemical analyses have revealed the presence of corticotropin-releasing factor (CRF) and urocortin (Ucn), together with their corresponding receptors in mammalian skin. The melanosomal enzyme tyrosinase-related protein 1 (TRP1) is involved in modulation of pigment production in response to stressors. Although CRF and Ucn are thought to have ...

ABSTRACT: BACKGROUND: Ultraconserved regions (UCR) are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed from these regions. These UCR-encoded transcripts ...

Sclerostin, encoded by the SOST gene, is specifically expressed by osteocytes, Osteoblasts bear a heavily methylated SOST promoter and therefore do not express SOST. Thus, studying the regulation of human SOST is challenged by the absence of human osteocytic cell lines. Herein, we explore the feasibility of using the induction ...

ABSTRACT: INTRODUCTION: Increased expression of aggrecanase-1 (ADAMTS-4) has emerged as an important factor in osteoarthritis (OA) and other joint diseases. This study aimed to determine whether the expression of ADAMTS-4 in human chondrocytes is regulated by miRNA. METHODS: MiRNA targets were identified using bioinformatics. Chondrocytes were isolated from knee cartilage ...

ABSTRACT: BACKGROUND: Interleukin-32 (IL-32) is an important factor in innate and adaptive immune responses, which activates the p38MAPK, NF-kappa B and AP-1 signaling pathways. Recent reports have highlighted that IL-32 is regulated during viral infection in humans. METHODS: Enzyme-linked immunosorbent assays (ELISA) were carried out to detect IL-32 levels in ...

Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele ∼28 kb upstream of BIN1, which increased (i) ...

Vampire bats are notorious for being the sole mammals that strictly feed on fresh blood for their survival. While their saliva has been historically associated with anticoagulants, only one antihemostatic (plasminogen activator) has been molecularly and functionally characterized. Here, RNAs from both principal submandibular and accessory glands of Desmodus rotundus ...

Human UDP-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds such as bilirubin and SN-38. UGT1A1 is predominantly expressed in the liver and intestine, but not in the kidney. The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing ...

C-terminal binding protein 2 (CtBP2) is a transcriptional co-repressor involved in cell migration, apoptosis, and tumorization. Up-regulation of CtBP2 is implicated in various human cancers including breast cancers. In our present study, we found that the C-terminus of Hsc70-interacting protein (CHIP) regulated the steady-state level of CtBP2. CHIP interacted with ...

PURPOSE: A comparative immunolocalisation study of perlecan, HS, FGF-18 and FGFR-3 in the 12-20-week gestational age human foetal spine was undertaken to identify spatiotemporal associations between these components to provide insights into prospective roles in spinal development. METHODS: Comparative immunolocalisations of matrix and cell associated components in Histochoice-fixed paraffin-embedded human ...

Engagement of Toll-like receptor 4 (TLR4) by Lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species ...

ABSTRACT: Humans are symbiotic organisms; our genome is populated with a substantial number of endogenous retroviruses (ERVs), some remarkably intact, while others are remnants of their former selves. Current research indicates that not all ERVs remain silent passengers within our genomes; re-activation of ERVs is often associated with inflammatory diseases. ...

BACKGROUND: MicroRNAs (miRNAs) regulate several aspects of the morphogenesis and homeostasis of the skin and its appendages, and miRNA deregulation has been shown to be associated or even causally related to several skin diseases. OBJECTIVE: To evaluate the differential expression of miRNAs during sebaceous lipogenesis. METHODS: Inhibition of global miRNA ...

The aim of the present study was to determine the role of hcrcn81 in the regulation of the mammalian target of rapamycin (mTOR) pathway in human colorectal adenocarcinoma cells. The effect of rapamycin treatment on hcrcn81 expression was evaluated by examining the mRNA and protein expression of hcrcn81 in rapamycin‑treated ...

Low dietary intake of β-carotene is associated with chronic disease and vitamin A deficiency. β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-15,15-monoxygenase (BCMO1) to support vision, reproduction, immune function, and cell differentiation. Considerable variability for this key step in vitamin A metabolism, as reported in ...

Overexpression of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have long been suggested to play crucial roles in the progression of osteoarthritis. Studies have showed that selective MMPs, iNOS and COX-2 inhibitors possess great potential as chondroprotective agents for osteoarthritis. Therefore, there have been intensive efforts ...

Context:Wnt signaling regulates adipogenesis and adipocyte function. Secreted frizzled-related proteins (SFRPs) are a family of secreted proteins (SFRP1-5) that bind and inhibit Wnts. Several members, including SFRP5, have recently been implicated in adipocyte dysfunction in obesity.Objective:Our objective was to characterize the expression, secretion, and function of the SFRP family in ...

Myeloid ELF1-like factor (MEF/ELF4), a member of the ETS transcription factors, can function as an oncogene in murine cancer models and is overexpressed in various human cancers. Here, we report a mechanism by which MEF/ELF4 may be activated by a common leukemia-associated mutation in the nucleophosmin gene. By using a ...

The extracellular matrix proteoglycan biglycan (BGN) is involved in cardiovascular disease pathophysiology, as it mediates the subendothelial retention of atherogenic apolipoprotein B-containing lipoproteins, affects adaptive remodeling after myocardial infarction, and exerts proinflammatory effects in macrophages. In a cardiovascular disease-related setting of vascular endothelial cells and human monocytes, we examined the ...

The submandibular and parotid glands are the main sources of immunoglobulins A (IgAs) in human and rat saliva. These glands express the polymeric immunoglobulin receptor (pIgR), which transports IgAs into saliva. The main source of IgAs in saliva and pIgR expression in salivary glands has not been well documented in ...

ABSTRACT: INTRODUCTION: The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11), at least partially through a ...

Context:Growth of endometriotic lesions in rodent model of endometriosis is inhibited by resveratrol, a natural polyphenol with antiproliferative and antiinflammatory properties, and simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) activity.Objective:The objective of the investigation was to study the mechanism of action of resveratrol and its interactions with simvastatin, focusing ...

Background:Defensins are antimicrobial peptides expressed on mucosal surfaces that contribute to maintaining intestinal homeostasis by providing innate defense mechanisms for the epithelia. Defensin expression is altered in a number of diseases that affect mucosal surfaces, such as atopic dermatitis, allergic rhinitis, and inflammatory bowel disease. Similar to atopic dermatitis, eosinophilic ...

A range of biological and molecular effects caused by nicotine are considered to effect bone metabolism. Vitamin C functions as a biological antioxidant. This study was to evaluate the in vitro effects of nicotine on human bone marrow stromal cells and whether Vitamin C supplementation show the antagonism action to ...

Barrett's esophagus (BE) is considered a complication of the inflammation provoked by acid and bile reflux. Endothelin-1 (ET-1) expresses in various cells during inflammatory process. However, the role of ET-1 in human inflamed and uninflamed esophageal tissue is unknown. The present study aimed to examine the expression of ET-1 and ...

BACKGROUND: Dermokine-β is abundant in stratified epithelia and in differentiating keratinocytes in culture. We have recently shown that treatment of keratinocytes with dermokine-β attenuates phosphorylation of extracellular signal-regulated kinase, however, the roles of dermokine-β in vivo remain unknown. OBJECTIVE: Dermokine-β is overexpressed in marginal keratinocytes during wound healing. This study ...

Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA ...