Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; ) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA).
View Article and Find Full Text PDFAcetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific knockout ( LKO) mice.
View Article and Find Full Text PDFAutism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children.
View Article and Find Full Text PDFThe dopamine precursor 3,4‑dihydroxyphenyl‑ l‑alanine (L‑DOPA) is the most widely used symptomatic treatment for Parkinson's disease (PD); however, its prolonged use is associated with L‑DOPA‑induced dyskinesia in more than half of patients after 10 years of treatment. The present study investigated whether co‑treatment with β‑Lapachone, a natural compound, and L‑DOPA has protective effects in a 6‑hydroxydopamine (6‑OHDA)‑induced mouse model of PD. Unilateral 6‑OHDA‑lesioned mice were treated with vehicle or β‑Lapachone (10 mg/kg/day) and L‑DOPA for 11 days.
View Article and Find Full Text PDFThe growth arrest and DNA damage-inducible beta (Gadd45β) protein have been associated with various cellular functions, but its role in progressive renal disease is currently unknown. Here, we examined the effect of Gadd45β deletion on cell proliferation and apoptosis, inflammation, and renal fibrosis in an early chronic kidney disease (CKD) mouse model following unilateral ureteral obstruction (UUO). Wild-type (WT) and Gadd45β-knockout (KO) mice underwent either a sham operation or UUO and the kidneys were sampled eight days later.
View Article and Find Full Text PDFParkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary medication for the management of type 2 diabetes.
View Article and Find Full Text PDFThe NAD(P)H:quinone oxidoreductase 1 (NQO1) gene encodes a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones to hydroquinones. A polymorphic form of NQO1 is associated with mood disorders such as schizophrenia. However, the role of NQO1 in dopaminergic system has not yet been elucidated.
View Article and Find Full Text PDFHumulus japonicus (HJ) is a widely used herbal medicine in Asia with anti‑oxidative, anti‑microbial, and anti‑inflammatory effects. We investigated the potential therapeutic effects of HJ in rheumatoid arthritis (RA) using a mouse model of collagen‑induced arthritis (CIA) and a lipopolysaccharide‑stimulated murine macrophage cell line (RAW 264.7).
View Article and Find Full Text PDFThe hallmark of renal tubulointerstitial fibrosis is the accumulation of myofibroblasts and extracellular matrix proteins. Fyn, a member of the Src family of kinases, has diverse biological functions including regulation of mitogenic signaling and proliferation and integrin-mediated interaction. Src family proteins promote pulmonary fibrosis by augmenting transforming growth factor-β signaling, but their role in renal fibrosis is less understood.
View Article and Find Full Text PDFVascular calcification, a pathologic response to defective calcium and phosphate homeostasis, is strongly associated with cardiovascular mortality and morbidity. In this study, we have observed that pyruvate dehydrogenase kinase 4 (PDK4) is upregulated and pyruvate dehydrogenase complex phosphorylation is increased in calcifying vascular smooth muscle cells (VSMCs) and in calcified vessels of patients with atherosclerosis, suggesting that PDK4 plays an important role in vascular calcification. Both genetic and pharmacological inhibition of PDK4 ameliorated the calcification in phosphate-treated VSMCs and aortic rings and in vitamin D3-treated mice.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
November 2015
Objective: Vascular calcification which refers to ectopic mineralization in vascular cells is associated with several conditions, such as chronic kidney disease, atherosclerosis, and diabetes mellitus. Estrogen-related receptor (ERR)γ is a member of the orphan nuclear receptor superfamily, which plays diverse roles in regulating homeostatic and metabolic processes. However, the role of ERRγ in vascular calcification has not been investigated to date.
View Article and Find Full Text PDFIschemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene.
View Article and Find Full Text PDFVascul Pharmacol
October 2014
Background: Retinoic acid-related orphan receptor α (RORα) has been implicated in the progression of atherosclerosis, but its role in the proliferation of vascular smooth muscle cells (vSMCs) has not been fully examined. We previously reported that RORα activates AMP-activated protein kinase (AMPK), which is associated with the suppression of vSMC proliferation. Therefore, we investigated the suppressive function of RORα on the proliferation of vSMCs and the molecular mechanisms involved.
View Article and Find Full Text PDFObjectives: The purpose of this study was to design an integrated data management system based on the POCT1-A2, LIS2-A, LIS2-A2, and HL7 standard to ensure data interoperability between mobile equipment, such as point-of-care testing equipment and the existing hospital data system, its efficiency was also evaluated.
Methods: The method of this study was intended to design and realize a data management system which would provide a solution for the problems that occur when point-of-care testing equipment is introduced to existing hospital data, after classifying such problems into connectivity, integration, and interoperability. This study also checked if the data management system plays a sufficient role as a bridge between the point-of-care testing equipment and the hospital information system through connection persistence and reliability testing, as well as data integration and interoperability testing.
The present study was undertaken to overcome the problems associated with solubility, dissolution and oral bioavailability of a poorly water-soluble ionizable drug, telmisartan (TMS). For these purposes, a solubility test was carried to select the appropriate formulation composition from various carriers and alkalizers. Solid dispersions (SDs) of TMS were prepared at different drug-to-carrier ratios by the spray-drying technique, and were characterized by dissolution and aqueous solubility studies.
View Article and Find Full Text PDFTGF-β plays a key role in the development of renal fibrosis. Suppressing the TGF-β signaling pathway is a possible therapeutic approach for preventing this disease, and reports have suggested that Nrf2 protects against renal fibrosis by inhibiting TGF-β signaling. This study examines whether dimethylfumarate (DMF), which stimulates Nrf2, prevents renal fibrosis via the Nrf2-mediated suppression of TGF-β signaling.
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