Fasudil alleviates the vascular endothelial dysfunction and several phenotypes of Fabry disease.

Fabry disease (FD), a lysosomal storage disorder, is caused by defective α-galactosidase (GLA) activity, which results in the accumulation of globotriaosylceramide (Gb3) in endothelial cells and leads to life-threatening complications such as left ventricular hypertrophy (LVH), renal failure, and stroke. Enzyme replacement therapy (ERT) results in Gb3 clearance; however, because of a short half-life in the body and the high immunogenicity of FD patients, ERT has a limited therapeutic effect, particularly in patients with late-onset disease or progressive complications. Because vascular endothelial cells (VECs) derived from FD-induced pluripotent stem cells display increased thrombospondin-1 (TSP1) expression and enhanced SMAD2 signaling, we screened for chemical compounds that could downregulate TSP1 and SMAD2 signaling.

Peroxiredoxin 5 regulates osteogenic differentiation through interaction with hnRNPK during bone regeneration.

Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, its function in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes in knockout () male mice.

Trovafloxacin drives inflammation-associated drug-induced adverse hepatic reaction by changing macrophage polarization.

Drug-induced liver injury (DILI) is an adverse hepatic reaction and a serious concern for public healthcare systems and pharmaceutical companies. DILI is frequently caused by a combination of direct toxic stresses and subsequent immune damage to hepatocytes. However, little is known about the mechanism by which drugs facilitate the activation of the innate immune system.

USP11 degrades KLF4 via its deubiquitinase activity in liver diseases.

Krüppel-like factor 4 (KLF4) is a zinc-finger containing DNA-binding transcription factor involved in tumorigenesis and acts as a tumour suppressor or an oncogene depending on the tissue. In hepatocellular carcinoma (HCC), KLF4 has been considered as a tumour suppressor, although the mechanism underlying its action remains largely unknown. In this study, we identified the ubiquitin-specific peptidase USP11 as a KLF4-interacting deubiquitinating enzyme using a proteomic approach.

Sappanone A Prevents Left Ventricular Dysfunction in a Rat Myocardial Ischemia Reperfusion Injury Model.

The incidence of myocardial infarction, among the causes of cardiovascular morbidity and mortality, is increasing globally. In this study, left ventricular (LV) dysfunction, including LV systolic and diastolic function, was investigated in a rat myocardial ischemia/reperfusion injury model with echocardiography. The homoisoflavanone sappanone A is known for its anti-inflammatory effects.

A cell function study on calcium regulation of a novel calcium-sensing receptor mutation (p.Tyr825Phe).

Purpose: Autosomal dominant hypocalcemia with hypercalciuria is a genetic disease characterized by hypoparathyroidism with hypercalciuria. We discovered a novel variant (p.Tyr825Phe[Y825F]) of the CASR gene in a neonate with congenital hypoparathyroidism and hypercalciuria and conducted a cell function study to determine whether the CASR-Y825F variant was pathogenic.

Efficacy of a chitosan tampon in the loop electrosurgical excision procedure: A prospective randomized controlled study.

It has been reported that chitosan has a hemostatic effect and an antibiotic activity. This study aimed to evaluate the efficacy and feasibility of using a chitosan tampon (Hemoblock-Tampon) in preventing hemorrhage and enhancing wound healing after the loop electrosurgical excision procedure (LEEP).This single-blind, prospective, randomized study included 62 consecutive patients who underwent LEEP for cervical intraepithelial neoplasia.

Exogenous Ganglioside GT1b Enhances Porcine Oocyte Maturation, Including the Cumulus Cell Expansion and Activation of EGFR and ERK1/2 Signaling.

Ganglioside GT1b is well-known for its role in cytokine production and in activating epidermal growth factor receptor (EGFR)-mediated signaling pathways in cancer cells. However, there are no reports that clearly elucidate the role of GT1b in EGFR-mediated signaling pathways in porcine oocytes during the process of in vitro maturation (IVM). In this study, we investigated the role of GT1b in EGFR-mediated activation of the ERK1/2 pathway in porcine cumulus-oocyte complexes (COCs) at 44 h of IVM.

Mito-TEMPO improves development competence by reducing superoxide in preimplantation porcine embryos.

Mito-TEMPO is a well-known mitochondria-specific superoxide scavenger. However, the effect of Mito-TEMPO on porcine embryo development, to our knowledge, has not been studied yet. In the present study, porcine embryos were classified into two groups (G1 and G2) based on the cytoplasm lipid contents at the zygote stage.

JAK1-mediated Sirt1 phosphorylation functions as a negative feedback of the JAK1-STAT3 pathway.

The type III NAD-dependent histone deacetylase Sirt1 plays important roles in a variety of pathobiological functions through targeting either the acetylated histones or transcription factors. However, the molecular mechanisms underlying how the Sirt1 functions are regulated remain vague. Herein we identified that the Janus kinase 1 (JAK1) interacts with Sirt1 and catalyzes its phosphorylation at the tyrosine residues of 280 and 301, both of which are highly conserved and located in the histone deacetylase catalytic domain of Sirt1.

Melatonin improves the meiotic maturation of porcine oocytes by reducing endoplasmic reticulum stress during in vitro maturation.

Under endoplasmic reticulum (ER)-stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an antioxidant to improve pig oocyte maturation.

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT).

Modification of cysteine 457 in plakoglobin modulates the proliferation and migration of colorectal cancer cells by altering binding to E-cadherin/catenins.

Objectives: In tissue samples from patients with colorectal cancer (CRC), oxidation of C420 and C457 of plakoglobin (Pg) within tumor tissue was identified by proteomic analysis. The aim of this study was to identify the roles of Pg C420 and C457.

Methods: Human CRC tissues, CRC and breast cancer cells, and normal mouse colon were prepared to validate Pg oxidation.

Differential expression of immunologic proteins in gingiva after socket preservation in mini pigs.

Unlabelled: During healing following tooth extraction, inflammation and the immune response within the extraction socket are related to bone resorption.

Objective: We sought to identify how the alloplastic material used for socket preservation affects the immune responses and osteoclastic activity within extraction sockets.

Material And Methods: Using a porcine model, we extracted teeth and grafted biphasic calcium phosphate into the extraction sockets.

Interaction of peroxiredoxin V with dihydrolipoamide branched chain transacylase E2 (DBT) in mouse kidney under hypoxia.

Background: Peroxiredoxin V (Prdx V) plays a major role in preventing oxidative damage as an effective antioxidant protein within a variety of cells through peroxidase activity. However, the function of Prdx V is not limited to peroxidase enzymatic activity per se. It appears to have unique function in regulating cellular response to external stimuli by directing interaction with signaling protein.

Antioxidant enzymes as redox-based biomarkers: a brief review.

The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins.

Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1.

The elevated level of CCNB1 indicates more aggressive cancer and poor prognosis. However, the factors that cause CCNB1 upregulation remain enigmatic. Herein, we identify USP22 as a CCNB1 interactor and discover that both USP22 and CCNB1 are dramatically elevated with a strong positive correlation in colon cancer tissues.

Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation.

The ubiquitin pathway plays critical roles in antigen presentation. However, the ubiquitin ligases that regulate MHC gene transcription remain unidentified. We showed that the ubiquitin ligase Hrd1, expression of which is induced by Toll-like receptor (TLR) stimulation, is required for MHC-II but not MHC-I transcription in dendritic cells (DCs).

USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation.

The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins.

Histone deacetylase sirtuin 1 deacetylates IRF1 protein and programs dendritic cells to control Th17 protein differentiation during autoimmune inflammation.

The type III histone deacetylase Sirt1 has recently emerged as a critical immune regulator by suppressing T cell immunity and macrophage activation during inflammation, but its role in dendritic cells (DCs) remains unknown. Here, we show that mice with genetic Sirt1 deletion specifically in DCs are resistant to MOG-induced experimental autoimmune encephalomyelitis. Loss of Sirt1 functions in DCs enhances their ability to produce IL-27 and interferon β (IFN-β).

Peroxiredoxin V selectively regulates IL-6 production by modulating the Jak2-Stat5 pathway.

Mammalian peroxiredoxin V (PrdxV) is a multifunctional protein that protects cells from DNA damage and inhibits stress-induced apoptosis. However, PrdxV is also known to be involved in modulating lipopolysaccharide (LPS)-induced host cell signaling, but its precise role is not fully understood. In this study, we used stably transfected RAW264.

Proteomic analysis of gingival tissue and alveolar bone during alveolar bone healing.

Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction.

Comparative proteomic analysis of cysteine oxidation in colorectal cancer patients.

Oxidative stress promotes damage to cellular proteins, lipids, membranes and DNA, and plays a key role in the development of cancer. Reactive oxygen species disrupt redox homeostasis and promote tumor formation by initiating aberrant activation of signaling pathways that lead to tumorigenesis. We used shotgun proteomics to identify proteins containing oxidation-sensitive cysteines in tissue specimens from colorectal cancer patients.

The functional role of UBA1 cysteine-278 in ubiquitination.

Although total UBA1 levels were unchanged, after oxidation for 60 min, we observed dramatic changes in the levels of BIAM-labeled UBA1 in both the membrane and cytosol fractions that suggested oxidative stress induces translocation of UBA1 from the cytosol to the membrane. Notably, in PrdxII(-/-) oxRBCs, ubiquitination levels were reduced about 75% in the membrane fraction after 90 min, even though UBA1 levels were increased. These results suggest ubiquitination levels are determined by UBA1 activity, not the level of UBA1 protein.