Conversion of soluble α-synuclein into insoluble and fibrillar inclusions is a hallmark of Parkinson's disease and other synucleinopathies. Accumulating evidence points towards a relationship between its generation at nerve terminals and structural synaptic pathology. Little is known about the pathogenic impact of α-synuclein conversion and deposition at nigrostriatal dopaminergic synapses ...

ABSTRACT: Autoantibodies and complement opsonization have been implicated in the process of demyelination in the major human CNS demyelinating disease multiple sclerosis (MS), but scavenger receptors (SRs) may also play pathogenetic roles. We characterized SR mRNA and protein expression in postmortem brain tissue from 13 MS patients in relation to ...

BACKGROUND & AIMS: A gain-of-function variation within the locus that encodes protein tyrosine phosphatase non-receptor type (PTPN)22 is associated with a reduced risk for Crohn's disease (CD), whereas a loss-of-function variant seems to promote autoimmune disorders. We investigated how loss of PTPN22 could contribute to chronic inflammation of the intestine. ...

MicroRNAs (miRs) regulate cellular processes by modulating gene expression. Although transcriptomic studies have identified numerous miRs differentially expressed in diseased versus normal cells, expression analysis alone cannot distinguish miRs driving a disease phenotype from those merely associated with the disease. To address this limitation, we developed miR-HTS, a method for ...

Human constitutive androstane receptor (hCAR, NR1I3) is a member of the orphan nuclear receptor family and regulates transcription of many drug-metabolizing enzymes and drug transporters. Previous studies have shown that the hCAR gene produces a number of different kinds of mRNA splicing variants (SVs) in non-Asian ethnicities. In the present ...

The urothelium plays a crucial role in integrating urinary bladder sensory outputs, responding to mechanical stress and chemical stimulation by producing several diffusible mediators, including ATP and, possibly, neurotrophin nerve growth factor (NGF). Such urothelial mediators activate underlying afferents and thus may contribute to normal bladder sensation and possibly to ...

In vivo and in vitro aggrecanases degrade proteoglycan aggrecan in articular cartilage. However, the expression of aggrecanases in patients in different stages of osteoarthritis (OA) has not been investigated. This study detected the expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) and ADAMTS-5 and their proteolytic products, ...

MicroRNA are small RNAs that provide specificity for the RNA induced silencing complex, which forms the basis of an exquisite combinatorial system for posttranscriptional regulation. This system, essential for complex metazoans, is exemplified in the development of the cerebral cortex. To explore the complexity of human cortical miRNA expression in ...

Neuroinflammation is an integral component of neurodegenerative disorders, CNS infection and trauma. Astroglial chemokines, such as CXCL10, are instrumental in neuroinflammatory signaling as well as neurotoxicity. We have utilized proinflammatory-induced CXCL10 expression in normal human astrocytes (NHA) as a model in which to assess the anti-inflammatory actions of the selective, ...

Cutaneous β-human papillomavirus (β-HPV) E6 proteins inhibit NOTCH signaling by associating with the transcriptional coactivator MAML1. NOTCH has tumor suppressor activities in epithelial cells and is activated during keratinocyte differentiation. Here we report that HPV type 8 (HPV8) E6 subverts NOTCH activation during keratinocyte differentiation by inhibiting RBPJ/MAML1 transcriptional activator ...

BACKGROUND: Transformer (Tra) 2β is a member of the serine/arginine-rich (SR)-like protein family that regulates alternative splicing of numerous genes in a concentration-dependent manner. Several types of cancer cells up-regulate Tra2β expression, while the regulatory mechanism of Tra2β expression remains to be elucidated. In this study, we examined the transcriptional ...

OBJECTIVES: To investigate the presence of β-adrenoceptor subtypes in the human ureter, and to examine whether β(3) -adrenoceptors modulate relaxation of the human ureter. METHODS: Expression of messenger ribonucleic acid of β-adrenoceptors in the human ureter was determined by reverse transcription polymerase chain reaction, and distribution of β-adrenoceptors was examined ...

Epithelial ovarian cancer (EOC) accounts for the most gynecological malignancy-associated deaths in the United States. Enhancer of zeste homolog 2 (EZH2), which silences gene expression through generating trimethylation on lysine 27 residue of histone H3 (H3K27Me3), is often overexpressed in EOC and has been suggested as a therapeutic target. However, ...

When bound to the vitamin D receptor (VDR), the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of osteoblast transcription. Less clear is the impact of 1,25D on post-transcriptional events in osteoblasts, such as the generation and action of microRNAs (miRNAs). Microarray analysis using replicate (n ...

Abstract Cyclooxygenase 1b (COX-1b) is a splice variant of COX-1, containing a retained intron 1 within the signal peptide sequence. COX-1b mRNA is found in many species, but the existence of a functionally active protein is controversially discussed, possibly related to different species-dependent lengths of intron 1. The human intron ...

BACKGROUND CONTEXT: Destruction of extracellular matrix (ECM) leads to intervertebral disc degeneration (IDD), which underlies many spine-related disorders. Matrix metalloproteinases (MMPs), and disintegrins and metalloproteinases with thrombospondin motifs (ADAMTSs) are believed to be the major proteolytic enzymes responsible for ECM degradation in the intervertebral disc (IVD). PURPOSE: To summarize the ...

Porphyromonas gingivalis lipopolysaccharide (LPS) induces the expression of the cyclooxygenase-2 (COX-2), which contributes to the process of periodontitis. Curcumin, a constituent of turmeric, exhibits anti-inflammatory properties. We have investigated the anti-inflammatory effect of curcumin in human gingival fibroblasts (HGFs) stimulated by P. gingivalis LPS and its mechanism of action. HGFs ...

OBJECTIVE: To investigate whether hypoxia or the female sex steroids exert direct effects on angiopoietin-1 (ANGPT1), ANGPT2, and vascular endothelial growth factor (VEGF) in human endometrial stromal cells (ESCs) to clarify the regulatory function of these local angiogenic factors in the endometrium. STUDY DESIGN: Human endometrial tissues were obtained from ...

BACKGROUND AIMS: Toll-like receptors (TLRs) play an important role in innate and adaptive immunity by recognizing pathogen-associated molecular patterns (PAMPs). METHODS: In the present study, we investigated the expression and role of TLRs on human umbilical cord mesenchymal stem cells (UC-MSCs). The proliferation, differentiation and immunoregulatory activity of UC-MSCs primed ...

ABSTRACT: INTRODUCTION: Osteoarthritis (OA) is the most common degenerative joint disease that involving in degradation of articular cartilage. The exact etiology of OA is not completely understood. CCN4 is related to up-regulation in the cartilage of patient with osteoarthritis. Previous studies have shown that CCN4 might be associated with the ...

ABSTRACT: BACKGROUND: Sebaceous glands are components of the skin essential for its normal lubrication by the production of sebum. This contributes to skin health and more importantly is crucial for the skin barrier function. A mechanistic understanding of sebaceous gland cells growth and differentiation has lagged behind that for keratinocytes, ...

Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as circulating mediator between the gut microbiota and fat storage. Here we show that transcription and secretion of ANGPTL4 in human T84 and HT-29 colon adenocarcinoma cells is highly induced by physiological concentrations of short chain fatty acids (SCFA). SCFA induce ANGPTL4 by ...

Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a ...

The adipokine leptin elicits changes in the expression of the activation markers CD40 and CD69 in PBMCs and DCs, yet its effect on PRRs remains to be elucidated. Serum leptin concentrations are elevated in obesity and T2DM, which are both diseases associated with a proinflammatory state. We therefore investigated a ...

FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory ...

Impaired brain glucose uptake and metabolism precede the appearance of clinical symptoms in Alzheimer disease (AD). Neuronal glucose transporter 3 (GLUT3) is decreased in AD brain and correlates with tau pathology. However, what leads to the decreased GLUT3 is yet unknown. In this study, we found that the promoter of ...

Livin is a new member of the inhibitor of apoptosis proteins family of proteins that interacts with downstream caspases, such as caspase-3, caspase-7, and caspase-9, however, its role in human ampullary carcinoma has not been clearly defined. Immunohistochemistry was used to evaluate tissue samples from patients with ampullary carcinomas (n=71) ...

Recent studies suggested a role for the human endogenous retrovirus group HERV-K(HML-2) in melanoma because of upregulated transcription and expression of HERV-K(HML-2) encoded proteins. Very little is known about which HML-2 loci are transcribed in melanoma. We assigned >1,400 HML-2 cDNA sequences generated from various melanoma and related samples to ...

Natural antisense transcripts (asRNAs) are frequently transcribed from mammalian genes. Recently, we found that non-coding asRNAs are transcribed from the 3' untranslated region (3'UTR) of the rat and mouse genes encoding inducible nitric oxide synthase (iNOS), which catalyzes the production of the inflammatory mediator nitric oxide. The iNOS asRNA stabilizes ...

P-cadherin serves as a major topobiological cue in mammalian epithelium. In human hair follicles (HFs), it is prominently expressed in the inner hair matrix that harbors the HF pigmentary unit. However, the role of P-cadherin in normal human pigmentation remains unknown. Since patients with mutations in the gene that encodes ...

Human leukocyte cell-derived chemotaxin 2 (LECT2) is a chemotactic factor for neutrophils and a 16-kDa secreted protein consisting of 133 amino acids with three intramolecular disulfide bonds. Here, we propose an efficient method for the preparation of human LECT2 using a high hydrostatic pressure (HHP, 200 MPa) refolding technique. When ...

Recombinant human erythropoietin (rhEPO), a glycohormone, is one of the leading biopharmaceutical products. The production of rhEPO is currently restricted to mammalian cell expression systems because of its highly complex glycosylation pattern, which is a major determinant for drug-efficacy. Here we evaluated the ability of plants to produce different glycoforms ...

OBJECTIVE.: To determine the effect of hypoxia on both anabolic and catabolic pathways in human articular cartilage and to elucidate the roles played by HIFs in these responses. METHODS.: Normal human articular cartilage from a range of donors was obtained from above-knee amputations due to sarcomas not involving the joint ...

The use of anticoagulants has been associated with systemic osteoporosis and increased risk for poor fracture healing but is inevitable following major orthopedic surgery of lower limbs. Rivaroxaban A (R) is an anticoagulant recently introduced in the clinical setting, which is a specific factor Xa inhibitor. We reported previously that ...

Voltage-dependent K (+) (Kv) channels are tightly regulated during the immune system response. Leukocytes have a limited repertoire of Kv channels, whose physiological role is under intense investigation. A functional Kv channel is an oligomeric complex composed of pore-forming and ancillary subunits. The KCNE gene family is a novel group ...

OBJECTIVE: Dyslipidemia contributes to endothelial dysfunction in type 2 diabetes mellitus. Fenofibrate (FF), a ligand of the peroxisome proliferator-activated receptor-α (PPARα), has beneficial effects on microvascular complications. FF may act on the endothelium by regulating vasoactive factors, including endothelin-1 (ET-1). In vitro, FF decreases ET-1 expression in human microvascular endothelial ...

OBJECTIVES: To investigate the mechanism of matrix metalloproteinase (MMP)-13 expression in chondrocytes via pattern recognition receptors (PRRs) for double-stranded (ds) RNA. METHODS: Differential expression of PRRs was determined by real-time RT-PCR of RNA from osteoarthritis (OA) and neck of femur (NOF) fracture patients. Isolated human articular chondrocytes and the chondrosarcoma ...

The capacity of EPCs to repair injured tissues is limited. The role of miRNAs in EPCs is largely unknown. We tested whether miRNAs may be useful to enhance the regenerative capacity of EPCs. Early EPCs were isolated from human PBMCs, and late EPCs were amplified from enriched human peripheral CD34(+) ...

Hepatocyte growth factor activator inhibitor-2 (HAI-2) is an inhibitor of many proteases in vitro, including the membrane-bound serine protease, matriptase. Studies of knock-out mice have shown that HAI-2 is essential for placental development only in mice expressing matriptase, suggesting that HAI-2 is important for regulation of matriptase. Previous studies have ...

Mutant K-Ras and survivin both contribute to oncogenesis, but little is known about K-Ras requirement for the maintenance of the high levels of survivin in human tumors. Here we demonstrate that K-Ras depletion significantly decreases survivin levels in human cancer cells that harbor mutant but not wild type K-Ras. K-Ras ...

Cells from a human chondrocyte cell line were studied in 1% oxygen and/or a lower glucose concentration (5.5 mM), compared to the routine culture conditions of normoxia and high glucose. HIF-1α, IL-1β, IL-6, IL-8, COX-2, TNFα, LIF, MMP-3, MMP-13, and reactive oxygen species (ROS) were evaluated, respectively. Effects of hypoxia ...

The ammonia transporter family member, Rh B Glycoprotein (Rhbg), is essential for ammonia transport by the rodent kidney, but in the human kidney mRNA but not protein expression has been reported. Because ammonia transport is fundamental for acid-base homeostasis, the current study addressed RhBG expression in the human kidney. Two ...

Many brain disorders, including epilepsy, migraine and depression, manifest with episodic symptoms that may last for various time intervals. Transient alterations of neuronal function such as related to serotonin homeostasis generally underlie this phenomenon. Several nucleotide polymorphisms (SNPs) in gene promoters associated with these diseases have been described. For obvious ...

Linkage, association and expression studies previously pointed to the human QKI, KH domain containing, RNA-binding (QKI) as a candidate gene for schizophrenia. Functional studies of the mouse ortholog Qk focused mainly on its role in oligodendrocyte development and myelination, while its function in astroglia remained unexplored. Here we show that ...

Background:The Wnt signaling pathway is a conserved pathway and plays a crucial role in regulating trophoblast functions. Abnormal expression of the Wnt pathway may result in the dysfunction of the trophoblast that can contribute to the pathogenesis of preeclampsia (PE). However, published data regarding the association between Wnt pathway and ...

Cone-rod dystrophy 6 (CORD6) is an inherited blindness that presents with defective cone photoreceptor function in childhood, followed by loss of rod function. CORD6 results from mutations in GUCY2D, the human gene encoding retinal guanylate cyclase 1 (RETGC-1). RETGC-1 functions in phototransduction, synthesising cGMP to open ion channels in photoreceptor ...

Expression of the antioxidant enzyme EcSOD in normal human mammary epithelial cells was not recognized until recently. Although expression of EcSOD was not detectable in non-malignant human mammary epithelial cells (HMEC) cultured in conventional two-dimensional (2D) culture conditions, EcSOD protein expression was observed in normal human breast tissues, suggesting that ...

Human endogenous retroviruses (HERVs) are remnants of ancestral exogenous retroviral infections fixed in the germ-line DNA. Although no longer infectious, they may be transcriptionally active and have recently been implicated in melanomagenesis because of the observation of HERV-K mRNA and proteins in melanoma tissue and antibodies to HERV proteins in ...

MicroRNAs (miRNAs) are single-stranded noncoding regions of approximately 21 nucleotides that regulate protein synthesis by targeting mRNAs for translational repression or degradation at the post-transcriptional level. These classes of RNAs are highly conserved across species and are known to regulate several protein-coding genes in humans. Therefore, their dysregulation is synonymous ...

A critical role of proinflammatory mediators including cytokines, prostaglandins, and extracellular matrix remodeling enzymes in the processes of human labor and delivery, at term and preterm, has been demonstrated. In nongestational tissues, apelin plays an important role in a number of physiologic processes, including the regulation of inflammation. However, the ...