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Purpose@#The incidence and prognostic implications of atrial fibrillation (AF) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are controversial, especially for Korean patients. Furthermore, the pattern of antithrombotic therapy for these patients is unknown. The present study sought to identify the impact of AF on Korean patients undergoing TAVI and demonstrate the status of antithrombotic therapy for these patients. @*Materials and Methods@#A total of 660 patients who underwent TAVI for severe AS were recruited from the nationwide K-TAVI registry in Korea. The enrolled patients were stratified into sinus rhythm (SR) and AF groups. The primary endpoint was all-cause death at 1-year. @*Results@#AF was recorded in 135 patients [pre-existing AF 108 (16.4%) and new-onset AF 27 (4.1%)]. The rate of all-cause death at 1 year was significantly higher in patients with AF than in those with SR [16.2% vs. 6.4%, adjusted hazard ratio (HR): 2.207, 95% confidence interval (CI): 1.182–4.120, p=0.013], regardless of the onset timing of AF. The rate of new pacemaker insertion at 1 year was also significantly higher in patients with AF than in those with SR (14.0% vs. 5.5%, adjusted HR: 3.137, 95%CI: 1.621–6.071, p=0.001).Among AF patients, substantial number of patients received the combination of multiple antithrombotic agents (77.8%), and the most common combination was that of aspirin and clopidogrel (38.1%). @*Conclusion@#AF was an independent predictor of 1-year mortality and new pacemaker insertion in Korean patients undergoing TAVI.
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Syringobulbia is a rare neurological disorder characterized by a fluid-filled cavity in the brainstem. In this study, clinical signs, features on magnetic resonance imaging (MRI), and the diseases present concurrently with syringobulbia were investigated in 33 small breed dogs. Most dogs (97%) had concurrent syringomyelia, and some dogs (24%) presented with vestibular or cranial nerve symptoms associated with the medulla oblongata. MRIs revealed slit-like, bulbous, and vertical linear shapes of the cavities on T2-weighted hyperintense and T1-weighted hypointense signals similar to the cerebrospinal fluid. Chiari-like malformations were identified in all dogs. This study highlights the association of syringobulbia with syringomyelia and Chiari-like malformations in small breed dogs with or without brainstem-associated clinical signs.
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Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor.Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion.KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.
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Background/Aims@#Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction. However, since its benefits are uncertain, we aimed to establish whether it has better clinical outcomes. @*Methods@#The patients with acute malignant left-sided colon obstruction enrolled from January 2009 to December 2018 in National Health Insurance Service Ilsan Hospital. The patients were enrolled to undergo colonic stenting as a bridge to elective surgery or emergency surgery. The following oncological outcomes were assessed: incidence of complete remission, disease progression, local recurrence, and systemic recurrence. @*Results@#Out of 40 patients, 33 received self-expanding metallic stent (SEMS) as a bridge-tosurgery, and 7 underwent emergency surgery. More stoma was made in case of emergency surgery with statistical significance (p < 0.001). There were no significant differences in complete remission rate in curable left-sided malignant colonic obstruction between SEMS as a bridgeto-surgery and emergency surgery. Complete remission was achieved for 3 patients (42.9%) in the non-stent group and 27 patients (81.8%) in the stent group. There was no statistically significant difference in oncologic outcomes between the two groups (p = 0.069). According to multi-variate analysis, advanced TNM stage, Adjuvant chemotherapy, and SEMS bridge-tosurgery were significantly associated with disease-free survival. Disease-free survival rate differed significantly between the two groups (p = 0.024). @*Conclusions@#SEMS as a bridge-to-surgery might be an effective strategy and reduce stoma formation in acute malignant left-sided colon obstruction.
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OBJECTIVE@#SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA).@*METHODS@#In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund's adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23 days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3.@*RESULTS@#Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1β, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3.@*CONCLUSION@#These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.
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Far-infrared rays (FIR) are known to have various effects on atoms and molecular structures within cells owing to their radiation and vibration frequencies. The present study examined the effects of FIR on gene expression related to glucose transport through microarray analysis in rat skeletal muscle cells, as well as on mitochondrial biogenesis, at high and low glucose conditions. FIR were emitted from a bio-active material coated fabric (BMCF). L6 cells were treated with 30% BMCF for 24 h in medium containing 25 or 5.5 mM glucose, and changes in the expression of glucose transporter genes were determined. The expression of GLUT3 (Slc2a3) increased 2.0-fold (p < 0.05) under 5.5 mM glucose and 30% BMCF. In addition, mitochondrial oxygen consumption and membrane potential (ΔΨm) increased 1.5- and 3.4-fold (p < 0.05 and p < 0.001), respectively, but no significant change in expression of Pgc-1a, a regulator of mitochondrial biogenesis, was observed in 24 h. To analyze the relationship between GLUT3 expression and mitochondrial biogenesis under FIR, GLUT3 was down-modulated by siRNA for 72 h. As a result, the ΔΨm of the GLUT3 siRNA-treated cells increased 3.0-fold (p < 0.001), whereas that of the control group increased 4.6-fold (p < 0.001). Moreover, Pgc-1a expression increased upon 30% BMCF treatment for 72 h; an effect that was more pronounced in the presence of GLUT3. These results suggest that FIR may hold therapeutic potential for improving glucose metabolism and mitochondrial function in metabolic diseases associated with insufficient glucose supply, such as type 2 diabetes.
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Bioactivity-guided fractionation by preliminary screening using interleukin-1β production in lipopolysaccharides (LPS)-induced J774A.1 cell line led to the isolation of fourteen structures including chromone, isocoumarins, flavanoids, and triterpenes from the aerial part of Agrimonia pilosa Ledeb. All structures were determined by measuring their spectroscopic data and comparing their spectroscopic data with the literatures. All the isolates were tested for their inhibitory activities against interleukin-1β production in LPSinduced J774A.1 cell. Of the tested compounds, (S)-(+)-5,7-dihydroxy-2-(1-methylpropyl)chromone (1), agrimonolide-6-O-β-D-glucopyranoside (5), agrimonolide-6-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (6), and catechin (10) were found to be active. Furthermore, compound 1 suppressed the protein expressions of NLRP3 and NLRC4 in murine macrophage.
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Far-infrared rays (FIR) are known to have various effects on atoms and molecular structures within cells owing to their radiation and vibration frequencies. The present study examined the effects of FIR on gene expression related to glucose transport through microarray analysis in rat skeletal muscle cells, as well as on mitochondrial biogenesis, at high and low glucose conditions. FIR were emitted from a bio-active material coated fabric (BMCF). L6 cells were treated with 30% BMCF for 24 h in medium containing 25 or 5.5 mM glucose, and changes in the expression of glucose transporter genes were determined. The expression of GLUT3 (Slc2a3) increased 2.0-fold (p < 0.05) under 5.5 mM glucose and 30% BMCF. In addition, mitochondrial oxygen consumption and membrane potential (ΔΨm) increased 1.5- and 3.4-fold (p < 0.05 and p < 0.001), respectively, but no significant change in expression of Pgc-1a, a regulator of mitochondrial biogenesis, was observed in 24 h. To analyze the relationship between GLUT3 expression and mitochondrial biogenesis under FIR, GLUT3 was down-modulated by siRNA for 72 h. As a result, the ΔΨm of the GLUT3 siRNA-treated cells increased 3.0-fold (p < 0.001), whereas that of the control group increased 4.6-fold (p < 0.001). Moreover, Pgc-1a expression increased upon 30% BMCF treatment for 72 h; an effect that was more pronounced in the presence of GLUT3. These results suggest that FIR may hold therapeutic potential for improving glucose metabolism and mitochondrial function in metabolic diseases associated with insufficient glucose supply, such as type 2 diabetes.
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In cryptogenic stroke patients, early detection of new-onset atrial fibrillation (AF) and recurrent stroke is required to prevent poor clinical outcomes. Therefore, we investigated the predictors of new-onset AF and recurrent stroke in cryptogenic stroke patients without previously diagnosed AF. In total, 390 patients who were diagnosed with stroke and non-sustained atrial tachycardia (NSAT) on 24-hour Holter monitoring were followed up to assess new-onset AF and recurrent stroke. The 5-year event-free survival as well as the predictors of recurrent stroke or new-onset AF were investigated. Based on receiver operating characteristic analysis, frequent premature atrial contractions (PACs) were defined as PACs >44 beats/day. The median follow-up period was 35 months. The composite event rate was 11.5%. In Kaplan-Meier analysis, the 5-year cumulative incidence of composite events was higher in cryptogenic stroke patients with frequent PACs than in those without frequent PACs. Multivariate analysis revealed that current smoking, increased left atrial volume index, and frequent PACs were poor prognostic predictors of composite event, and frequent PACs were an independent poor prognostic factor of new-onset AF in cryptogenic stroke patients. Therefore, frequent PACs might be associated with poor clinical outcomes (new-onset AF and recurrent stroke) in cryptogenic stroke patients with concomitant NSAT.
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ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.
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Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G 2/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.
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Purpose@#To identify the clinical role of Advanced Practice Nurses (APN), and evaluate how other medical personnel perceive their work(difficulty, importance). @*Methods@#A questionnaire survey was performed with 277 health care providers (APN 52, nurses 88, and medical doctors 137 [professors 51, fellows 44, & residents 42]) in a single, tertiary hospital. The questionnaire was categorized into 6 domains (total 40 tasks): 6 tasks on identifying health issues (A); 3 tasks on prescribing and conducting diagnostic tests (D); 18 tasks on disease treatment (T); 4 tasks regarding prescribing medicine (M); 3 tasks regarding medical collaboration (C); 6 tasks regarding patient education (E). The survey measured the frequency, difficulty, and importance of APN’s clinical tasks, and evaluated the willingness of authorizing clinical tasks to APN. Results: The most frequent tasks for APN were A domain, lowest were T domain. The scores for perceived job difficulty were lower than those for job importance in all groups. The proportion of willingness to legally delegate clinical practices to APN was higher in A and E domains, but lower in D and T domains. However, professors, who spent the most time with APN, showed a higher willingness to legally delegate clinical practice. The participants favored medical doctors as substitutes for tasks which were not legislated for delegated job performance. @*Conclusion@#In this study identified clinical roles that medical doctors considered possible for legal delegation to APN were identified.The results can be used as evidence for the legalization of the practice of APN.
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BACKGROUND/AIMS: Dysbiosis is an important factor in the pathogenesis of irritable bowel syndrome (IBS). Several studies have reported promising results using probiotics for the treatment of IBS. This study evaluated the efficacy of novel probiotics isolated from Kimchi, a Korean fermented food, and the feces of healthy Vietnamese people in a murine model of IBS.METHODS: Lactobacillus paracasei DK121 was isolated from Kimchi, and L. salivarius V4 and L. plantarum V7 were isolated from the feces of healthy Vietnamese people residing in Korea. Forty rats were allocated to receive one of the study strains, a mixture of the strains, or the vehicle. After 5 days of administration, the rats were restrained in a cage to induce IBS. The effects of the probiotics on IBS were analyzed by evaluating the stool weights and stool consistency scores.RESULTS: The primary outcome was analyzed upon the completion of a three-week experiment. The rats in the V7 group showed lower stool weights than those in the control group at week 2 (median: 1.10 [V7] vs. 2.35 [control], p=0.04, Mann-Whitney U-test) and week 3 (median: 1.10 [V7] vs. 2.80 [control], p=0.017). The rats in the DK121 (median: 2.00, p=0.007), V7 (median: 2.00, p=0.004), and mixture (median: 1.50, p=0.001) groups showed better stool consistency scores at week 2 than the control group (median: 3.00).CONCLUSIONS: The novel probiotics have beneficial effects on defecation in a murine model of IBS. Human studies confirming the efficacy are warranted.
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A crude drug “Dang-Gui”, belonging to the genus Angelica, has been used as a traditional herbal medicine in Asia. Various studies have investigated the chemical components and pharmacological activities of Dang-Gui worldwide. However, domestic research results published in Korean are undervalued in international academia due to language barriers. Therefore, it is necessary to summarize the domestic research findings systematically for greater accessibility. This review focuses on the results published in four Korean pharmaceutical journals between 1970 and 2018, which detail the botanical, phytochemical, and pharmacological properties of three Angelica species (A. gigas, A. sinensis, and A. acutiloba) used as “Dang-Gui” in Korea, China, and Japan.
Subject(s)
Angelica , Angelica sinensis , Asia , China , Communication Barriers , Herbal Medicine , Japan , KoreaABSTRACT
PURPOSE: Although an increased incidence of gallbladder (GB) stone formation after gastrectomy has been reported, its etiology remains uncertain. The goal of this study was to explore the incidence of gallstone formation after gastrectomy in gastric cancer patients and investigate the risk factors therein.MATERIALS AND METHODS: Medical records of patients who underwent curative gastrectomy, performed by a single surgeon between August 2012 and December 2015 at the Asan Medical Center, were retrospectively reviewed. Baseline characteristics and surgical outcomes, including GB stone gallstone formation after gastrectomy, were analyzed.RESULTS: Of 561 patients included in the study, 36 presented with GB stone formation after gastrectomy for gastric cancer. The incidence of gallstone formation was 6.4%. The mean interval between gallstone formation and gastrectomy was 21.9 months. In multivariate analyses, the incidence of gallstone formation increased in patients 63 years or older, with greater than 6.2 kg weight loss in the first 6 months after the procedure, a preoperative serum total bilirubin level greater than 0.5 mg/dL, and in patients who did not receive adjuvant chemotherapy.CONCLUSIONS: This study presented risk factors for GB stone formation after gastric cancer surgery, and special attention should be afforded to patients with such risk factors.
Subject(s)
Humans , Bilirubin , Chemotherapy, Adjuvant , Cholecystolithiasis , Gallbladder , Gallstones , Gastrectomy , Incidence , Medical Records , Multivariate Analysis , Retrospective Studies , Risk Factors , Stomach Neoplasms , Weight LossABSTRACT
Lung cancer is the most common cause of cancer deaths worldwide and several molecular signatures have been developed to predict survival in lung cancer. Increasing evidence suggests that proliferation and migration to promote tumor growth are associated with dysregulated ion channel expression. In this study, by analyzing high-throughput gene expression data, we identify the differentially expressed K⁺ channel genes in lung cancer. In total, we prioritize ten dysregulated K⁺ channel genes (5 up-regulated and 5 down-regulated genes, which were designated as K-10) in lung tumor tissue compared with normal tissue. A risk scoring system combined with the K-10 signature accurately predicts clinical outcome in lung cancer, which is independent of standard clinical and pathological prognostic factors including patient age, lymph node involvement, tumor size, and tumor grade. We further indicate that the K-10 potentially predicts clinical outcome in breast and colon cancers. Molecular signature discovered through K⁺ gene expression profiling may serve as a novel biomarker to assess the risk in lung cancer.
Subject(s)
Humans , Breast , Colonic Neoplasms , Gene Expression , Gene Expression Profiling , Ion Channels , Lung Neoplasms , Lung , Lymph Nodes , Potassium Channels , PotassiumABSTRACT
Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.
Subject(s)
Animals , Mice , Biomarkers , Calcium , Calcium Signaling , Citric Acid , Citric Acid Cycle , Cytokines , Dermatitis, Atopic , Gene Ontology , Genome , Metabolism , Microarray Analysis , Mitochondria , Muscle Cells , Muscle Contraction , Muscle, Skeletal , Myoblasts , Myocardium , Oxidation-Reduction , Protein Interaction Maps , Pyroglyphidae , Receptors, Antigen, T-Cell , SkinABSTRACT
Despite increased evidence of bio-activity following far-infrared (FIR) radiation, susceptibility of cell signaling to FIR radiation-induced homeostasis is poorly understood. To observe the effects of FIR radiation, FIR-radiated materials-coated fabric was put on experimental rats or applied to L6 cells, and microarray analysis, quantitative real-time polymerase chain reaction, and wound healing assays were performed. Microarray analysis revealed that messenger RNA expressions of rat muscle were stimulated by FIR radiation in a dose-dependent manner in amount of 10% and 30% materials-coated. In 30% group, 1,473 differentially expressed genes were identified (fold change [FC] > 1.5), and 218 genes were significantly regulated (FC > 1.5 and p < 0.05). Microarray analysis showed that extracellular matrix (ECM)-receptor interaction, focal adhesion, and cell migration-related pathways were significantly stimulated in rat muscle. ECM and platelet-derived growth factor (PDGF)-mediated cell migration-related genes were increased. And, results showed that the relative gene expression of actin beta was increased. FIR radiation also stimulated actin subunit and actin-related genes. We observed that wound healing was certainly promoted by FIR radiation over 48 h in L6 cells. Therefore, we suggest that FIR radiation can penetrate the body and stimulate PDGF-mediated cell migration through ECM-integrin signaling in rats.
Subject(s)
Animals , Rats , Actins , Cell Movement , Extracellular Matrix , Focal Adhesions , Gene Expression , Homeostasis , Infrared Rays , Integrins , Microarray Analysis , Muscle, Skeletal , Platelet-Derived Growth Factor , Real-Time Polymerase Chain Reaction , RNA, Messenger , Wound HealingABSTRACT
Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a , Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.
Subject(s)
Animals , Mice , Biological Phenomena , Chemotaxis , Classification , Cytokines , Dermatitis, Contact , Gene Expression , Gene Ontology , Genome , Hypersensitivity , Immune System , Interleukin-6 , Models, Animal , Neutrophils , Pruritus , RNA , Sensation , Sequence Analysis, RNA , Signal Transduction , Skin , Transcriptome , Transient Receptor Potential Channels , Up-Regulation , Wound HealingABSTRACT
An isoform of NADPH oxidase (NOX), NOX2 is a superoxide-generating enzyme involved in diverse pathophysiological events. Although its potential as a therapeutic target has been validated, there is no clinically available inhibitor. Herein, NOX2-inhibitory activity was screened with the constituents isolated from Schisandra chinensis, which has been reported to have antioxidant and reactive oxygen species (ROS)-scavenging effects. Among the partitions prepared from crude methanolic extract, a chloroform-soluble partition showed the highest NOX2-inhibitory activity in PLB-985 cell-based NOX2 assay. A total of twenty nine compounds (1 – 29) were identified from the chloroform fraction, including two first isolated compounds; dimethyl-malate (25) and 2-(2-hydroxyacetyl) furan (27) from this plants. Of these constituents, two compounds (gomisin T, and pregomisin) exhibited an NOX2-inhibitory effect with the IC₅₀ of 9.4 ± 3.6, and 62.9 ± 11.3 µM, respectively. They are confirmed not to be nonspecific superoxide scavengers in a counter assay using a xanthine-xanthine oxidase system. These findings suggest the potential application of gomisin T (6) and other constituents of S. chinensis to inhibit NOX2.