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BACKGROUND: Hydrocele on the contralateral side after surgical repair is an uncommon condition compared to surgical site recurrence. Although there has been much research on metachronous contralateral inguinal hernia in children, metachronous contralateral hydrocele, which share a common pathology with inguinal hernias, has not yet been investigated. We have investigated the incidence and risk factors for metachronous contralateral occurrence of communicating and noncommunicating hydroceles in children younger than 8 years. METHODS: From January 2017 to June 2020, 302 children younger than 8 who were diagnosed with unilateral hydroceles were treated in our hospital without surgical exploration of contralateral hydrocele. The disease was classified into communicating and noncommunicating hydroceles. We divided patients into two groups according to the presence of metachronous contralateral hydrocele and analyzed the differences between the two groups. RESULTS: Among 302 patients, the mean age was 36.4 ± 20.9 months. Metachronous contralateral hydrocele occurred in 15 (4.9%) patients as communicating hydroceles. Comparison between the two groups showed statistically significant differences in type of hydrocele (P = 0.047) at first diagnosis. CONCLUSION: Clinically evident risk of metachronous contralateral hydrocele after unilateral hydrocelectomy was 4.9%. Despite the relatively low incidence rate, the risk of metachronous contralateral occurrence should always be consulted with parents before surgical treatment of hydroceles.
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Hérnia Inguinal , Laparoscopia , Hidrocele Testicular , Masculino , Humanos , Criança , Lactente , Pré-Escolar , Hidrocele Testicular/diagnóstico , Hidrocele Testicular/epidemiologia , Hidrocele Testicular/etiologia , Hérnia Inguinal/diagnóstico , Hérnia Inguinal/etiologia , Hérnia Inguinal/epidemiologia , Incidência , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: The existing literature has comprehensively examined the benefits of specialized wound-care services and multidisciplinary team care. However, information on the development and integration of wound-dressing teams for patients who do not require specialized wound care is scarce. Therefore, the present study aimed to elucidate the benefits of a wound-dressing team by reporting our experiences with the establishment of a wound-dressing team. METHODS: The wound-dressing team was established at Korea University Guro Hospital. Between July 2018 and June 2022, 180,872 cases were managed for wounds at the wound-dressing team. The data were analyzed to assess the types of wounds and their outcomes. In addition, questionnaires assessing the satisfaction with the service were administered to patients, ward nurses, residents/internists, and team members. RESULTS: Regarding the wound type, 80,297 (45.3%) were catheter-related, while 48,036 (27.1%), 26,056 (14.7%), and 20,739 (11.7%) were pressure ulcers, dirty wounds, and simple wounds, respectively. In the satisfaction survey, the scores of the patient, ward nurse, dressing team nurse, and physician groups were 8.9, 8.1, 8.2, and 9.1, respectively. Additionally, 136 dressing-related complications (0.08%) were reported. CONCLUSION: The wound dressing team can enhance satisfaction among patients and healthcare providers with low complications. Our findings may provide a potential framework for establishing similar service models.
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Bandagens , Cicatrização , Humanos , Hospitais UniversitáriosRESUMO
AIM: This study aimed to identify the incidence and risk factors for pressure injury in patients hospitalized for non-small cell lung cancer (NSCLC). METHODS: This retrospective observational study was conducted in 645 adults who were hospitalized for NSCLC. Clinicopathological characteristics were compared between NSCLC patients with pressure injury and those without pressure injury. RESULTS: Among total 645 patients, 180 patients showed pressure injury with an incidence of 27.9%. Patients with pressure injury showed increased serum C-reactive protein (CRP) levels (P < 0.001), increased neutrophil-lymphocyte ratio (P = 0.002), and increased platelet-lymphocyte ratio (P = 0.001) more often. Increase in serum CRP levels at the time of admission was the major risk factor for development of pressure injury in NSCLC patients (OR = 2.20; 95% CI [1.40-3.45]; P = 0.001). Also, among major inflammatory markers, serum CRP levels at the time of admission showed weak negative correlation with the period from admission to the development of pressure injury (r = -0.216, P = 0.004). CONCLUSION: By checking serum CRP levels at the time of admission, the NSCLC patients at high risk for the development of pressure injury can be identified in advance and the occurrence of pressure injury can be reduced by applying more active preventive nursing care. CLINICAL TRIAL REGISTRATION NUMBER: KCT0006570.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Úlcera por Pressão , Adulto , Humanos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Incidência , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Proteína C-Reativa/metabolismo , Estudos Retrospectivos , Fatores de RiscoRESUMO
The nickel catalyzed reductive coupling of aldehydes with sorbate esters and related electron-deficient 1,3-dienes are known in the literature to occur at the π-bond proximal to the ester to afford aldol-type products. In stark contrast to this established path, a VAPOL-derived phosphoramidite ligand in combination with a bench-stable nickel precatalyst brokers a regiocomplementary course in that C-C bond formation proceeds exclusively at the distal alkene site to give deoxypropionate type products carrying an acrylate handle; they can be made in either anti- or syn-configured form. In addition to this enabling reverse pathway, the reaction is distinguished by excellent levels of chemo-, diastereo-, and enantioselectivity; moreover, it can be extended to the catalytic formation of F3C-substituted stereogenic centers. The use of a dienyl pinacolboronate instead of a sorbate ester is also possible, which opens access to valuable chiral borylated building blocks in optically active form.
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Elétrons , Níquel , Níquel/química , Estereoisomerismo , Ligantes , Aldeídos/química , Catálise , Alcenos/química , Ésteres , Polienos , AcrilatosRESUMO
The development of a visible light-mediated synthetic method for chiral 1,2-amino tertiary alcohols is described. In the presence of a chiral oxazaborolidinium ion catalyst and photosensitizer, the enantioselective addition of an α-aminoalkyl radical to aryl methyl ketones under visible light provides chiral 1,2-amino tertiary alcohol derivatives in high yields (up to 88%) with excellent enantioselectivities (up to 98% ee). With mechanistic studies such as radical trapping analysis, radical clock analysis, and the measurement of quantum yield, a plausible catalytic cycle is proposed.
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Biological roles for UFM1, a ubiquitin-like protein, are largely unknown, and therefore we screened for targets of ufmylation. Here we show that ufmylation of the nuclear receptor coactivator ASC1 is a key step for ERα transactivation in response to 17ß-estradiol (E2). In the absence of E2, the UFM1-specific protease UfSP2 was bound to ASC1, which maintains ASC1 in a nonufmylated state. In the presence of E2, ERα bound ASC1 and displaced UfSP2, leading to ASC1 ufmylation. Polyufmylation of ASC1 enhanced association of p300, SRC1, and ASC1 at promoters of ERα target genes. ASC1 overexpression or UfSP2 knockdown promoted ERα-mediated tumor formation in vivo, which could be abrogated by treatment with the anti-breast cancer drug tamoxifen. In contrast, expression of ufmylation-deficient ASC1 mutant or knockdown of the UFM1-activating E1 enzyme UBA5 prevented tumor growth. These findings establish a role for ASC1 ufmylation in breast cancer development by promoting ERα transactivation.
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Sistema y+ de Transporte de Aminoácidos/metabolismo , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/metabolismo , Proteínas/química , Sistema y+ de Transporte de Aminoácidos/química , Sistema y+ de Transporte de Aminoácidos/genética , Animais , Neoplasias da Mama/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Cisteína Endopeptidases/metabolismo , Proteína p300 Associada a E1A/genética , Ativação Enzimática/genética , Estradiol/genética , Estradiol/metabolismo , Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/genética , Feminino , Células HEK293 , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Coativador 1 de Receptor Nuclear/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , Proteínas/metabolismo , Tamoxifeno/farmacologia , Ativação Transcricional , Ubiquitina/metabolismo , Enzimas Ativadoras de Ubiquitina/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: It is quite difficult to distinguish retractile testis from gliding testis, which requires different treatment planning in the clinic setting. We evaluated practice patterns of urologists in Korea regarding the diagnosis and management of retractile and gliding testes. METHODS: We mailed or e-mailed self-completion questionnaires consisting of 20 items to 106 urologists practicing in Korean hospitals concerning the diagnosis and treatment of cryptorchidism. We collected and analyzed the responses statistically. RESULTS: Responses were received from 62 urologists. The response rate was 58.5%. Thirty-seven urologists (59.7%) actually felt they had difficulty in distinguishing retractile testis from gliding testis in the clinic setting. This rate was higher for non-pediatric urologists (78.1%) than for pediatric urologists (40.0%) (P = 0.006). In cases of infant retractile testis, only five urologists (8.1%) said that they would perform orchiopexy immediately, with 54 (87.1%) urologists saying they would do follow-up. In cases of preschool-age children with retractile testis, 17 urologists (27.4%) said that they would perform orchiopexy immediately with 41 (66.1%) urologists saying they would do follow-up. In cases of infant gliding testis, 37 urologists (59.7%) said that they would perform orchiopexy immediately with 24 (38.7%) urologists saying they would do a follow-up. CONCLUSION: More than half (59.7%) of Korean urologists revealed it challenging to distinguish retractile testis and gliding testis in the clinical setting. The more it was difficult to diagnose retractile testis with certainty, the more frequent surgical correction was chosen for treatment. Therefore, it is essential to prevent unnecessary surgical treatment by establishing a practical guideline.
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Criptorquidismo , Urologistas , Povo Asiático , Criança , Pré-Escolar , Compreensão , Criptorquidismo/diagnóstico , Criptorquidismo/cirurgia , Humanos , Lactente , MasculinoRESUMO
Pigment epithelium-derived factor (PEDF) plays a role in protecting retinal pigment epithelial (RPE) cells from oxidative stress (OS), a causative factor of RPE cell death. Genetically modified mesenchymal stem cells (MSCs) can be used to treat critical and incurable retinal diseases. Here, we overexpressed PEDF in placenta-derived MSCs (PD-MSCsPEDF, PEDF+) using a nonviral gene delivery system and evaluated the characteristics of PD-MSCsPEDF and their potential regenerative effects on RPE cells damaged by H2O2-induced OS. PD-MSCsPEDF maintained their stemness, cell surface marker, and differentiation potential characteristics. Compared to naive cells, PD-MSCsPEDF promoted mitochondrial respiration by enhancing biogenesis regulators (e.g., NRF1, PPARGC1A, and TFAM) as well as antioxidant enzymes (e.g., HMOXs, SODs, and GPX1). Compared to OS-damaged RPE cells cocultured with naive cells, OS-damaged RPE cells cocultured with PD-MSCsPEDF showed PEDF upregulation and VEGF downregulation. The expression levels of antioxidant genes and RPE-specific genes, such as RPE65, RGR, and RRH, were significantly increased in RPE cells cocultured with PD-MSCsPEDF. Furthermore, OS-damaged RPE cells cocultured with PD-MSCsPEDF had dramatically enhanced mitochondrial functions, and antiapoptotic effects improved due to cell survival signaling pathways. In the H2O2-induced retinal degeneration rat model, compared to administration of the naive counterpart, intravitreal administration of PD-MSCsPEDF alleviated proinflammatory cytokines and restored retinal structure and function by increasing PEDF expression and decreasing VEGF expression. Intravitreal administration of PD-MSCsPEDF also protected retinal degeneration against OS by increasing antioxidant gene expression and regulating the mitochondrial ROS levels and biogenesis. Taken together, PEDF overexpression in PD-MSCs improved the mitochondrial activities and induced OS-damaged RPE cell regeneration by regulating the oxidative status and mitochondrial biogenesis in vitro and in vivo. These data suggest that genetic modification of PEDF in PD-MSCs might be a new cell therapy for the treatment of retinal degenerative diseases.
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Proteínas do Olho/fisiologia , Células-Tronco Mesenquimais/fisiologia , Fatores de Crescimento Neural/fisiologia , Biogênese de Organelas , Regeneração , Epitélio Pigmentado da Retina/fisiologia , Serpinas/fisiologia , Animais , Antioxidantes/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Transplante de Células-Tronco Mesenquimais , Mitocôndrias/metabolismo , Estresse Oxidativo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Degeneração Retiniana/terapiaRESUMO
A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.
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Interneurônios/metabolismo , Prosencéfalo/crescimento & desenvolvimento , Ácido gama-Aminobutírico/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Idade Gestacional , Gravidez , Prosencéfalo/metabolismoRESUMO
Hexapeptide WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met), a ligand of formyl peptide receptor 2, exhibits anti-inflammatory and angiogenic properties in disease models. However, the therapeutic effects of WKYMVm on hepatic fibrosis have not been evaluated to date. Therefore, we investigated whether WKYMVm exerts antifibrotic effects and induces vascular regeneration in a rat model of bile duct ligation (BDL). The antifibrotic and angiogenic effects of WKYMVm on liver regeneration in the BDL rat model were analyzed using biochemical assays, qRT-PCR, western blotting, immunofluorescence, and immunohistochemistry. To determine the effects of WKYMVm on hepatic fibrosis and angiogenesis in vitro, we measured the expression levels of fibrotic factors in hepatic stellate cells (HSCs) and angiogenic factors in human umbilical vein endothelial cells (HUVECs). WKYMVm attenuated the expression of collagen type I (Col I) and α-smooth muscle actin (α-SMA) and significantly increased the levels of angiogenetic factors in the BDL model (p < 0.05). WKYMVm reduced fibrotic marker expression in transforming growth factor (TGF)-ß-induced HSCs and promoted angiogenic activity through tube formation in 5-Fluorouracil (FU)-treated HUVECs (p < 0.05). Also, WKYMVm administration enhanced hepatocyte proliferation in BDL rats (p < 0.05). The WKYMVm alleviates hepatic fibrosis by inhibiting HSC activation and promotes hepatic regeneration via vascular remodeling. These data suggest that the WKYMVm may be a new therapeutic agent for liver fibrosis.
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Cirrose Hepática/fisiopatologia , Receptores de Lipoxinas/metabolismo , Remodelação Vascular , Animais , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/patologia , Ductos Biliares/fisiopatologia , Modelos Animais de Doenças , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ligadura , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/patologia , Regeneração Hepática/efeitos dos fármacos , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/metabolismo , Remodelação Vascular/efeitos dos fármacosRESUMO
PURPOSE: The purpose of this study was to investigate the risk factors for major amputation in persons hospitalized with diabetic foot ulcers involving the midfoot. DESIGN: Retrospective study. SUBJECTS AND SETTING: Between January 2003 and May 2019, a total of 1931 patients with diabetes were admitted to the diabetic wound center for the management of foot ulcers. Among the admitted patients, 169 patients with midfoot ulcers were included in this study. One hundred fifty-four patients (91%) healed without major amputation, while 15 patients (9%) healed post-major amputation. METHODS: Data related to 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology, and serology were collected from patients in these 2 groups for comparison. Univariate and multivariate logistic regression analyses were performed to analyze risk factors for major amputation. RESULTS: Among the 88 potential risk factors, 15 showed statistically significant differences between the 2 groups. Using univariate analysis of 88 potential risk factors, 8 showed statistically significant differences. Using stepwise multiple logistic regression analysis, 3 of the 8 risk factors remained statistically significant. Multivariate-adjusted odds ratios for deep ulcers invading bone, cardiac disorders, and Charcot foot were 26.718, 18.739, and 16.997, respectively. CONCLUSION: The risk factors for major amputation in patients hospitalized with diabetic midfoot ulcers included deep ulcers invading the bone, cardiac disorders, and Charcot foot.
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Amputação Cirúrgica/métodos , Complicações do Diabetes/complicações , Pé Diabético/cirurgia , Úlcera do Pé/cirurgia , Adulto , Idoso , Amputação Cirúrgica/estatística & dados numéricos , Diabetes Mellitus , Pé Diabético/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: So far, there has been no tool to estimate activity at diagnosis and predict all-cause mortality in patients with ANCA-associated vasculitis (AAV). Hence, we determined the initial predictors of them in patients with AAV. METHODS: We retrospectively reviewed the medical records of 182 patients with AAV. Severe AAV was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 16. The cutoffs were extrapolated by the receiver operator characteristic (ROC) curve. The odds ratio (OR) and the relative risk (RR) were assessed using the multivariable logistic regression analysis and the chi-square test, respectively. RESULTS: In the comparison analysis, patients with severe AAV exhibited the higher neutrophil and platelet counts, creatinine, erythrocyte sedimentation rate and C-reactive protein, and the lower lymphocyte count, hemoglobin, and serum albumin than those without. In the multivariable logistic regression analysis, creatinine ≥ 0.9 mg/dL (OR 2.264), lymphocyte count ≤ 1430.0/mm3 (OR 1.856), and hemoglobin ≤ 10.8 g/dL (OR 2.085) were associated with severe AAV. We developed a new equation of a multivariable index for AAV (MVIA) = 0.6 × (Lymphocyte count ≤ 1430.0/mm3 ) + 0.7 × (Hemoglobin ≤ 10.8 g/dL) + 0.8 × (Creatinine ≥ 0.9 mg/dL). The optimal cutoff of MVIA for severe AAV was set as 1.35. Severe AAV was identified more frequently in patients with MVIA at diagnosis ≥1.35 than those without (RR 4.432). Patients with MVIA at diagnosis ≥1.35 exhibited the lower cumulative patient survival rate than those without. CONCLUSION: Multivariable index for AAV could assess the cross-sectional activity and predict all-cause mortality in patients with AAV.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Liver diseases, despite the organ's high regenerative capacity, are caused by several environmental factors and persistent injuries. Their optimal treatment is a liver transplantation. However, this option is limited by donor shortages and immune response issues. Therefore, many researchers have been interested in identifying the therapeutic potential in treating irreversible liver damage based on stem cells and developing suitable therapeutic agents. Mesenchymal stem cells (MSCs), which are representative multipotent stem cells, are known to be highly potential stem cell therapy compared to other stem cells in the clinical trial worldwide. MSCs have therapeutic potentials for several hepatic diseases such as anti-fibrosis, proliferation of hepatocytes injured, anti-inflammation, autophagic mechanism, and inactivation of hepatic stellate cells. There are much data regarding clinical treatments, however, the data for examining the efficacy of stem cell treatment and the correlation between the stem cell engraftment and the efficacy in liver diseases is limited due to the lack of monitoring system for treatment effectiveness. Therefore, this paper introduces the characteristics of microRNAs (miRNAs) and liver disease-specific miRNA profiles, and the possibility of a biomarker that miRNA can monitor stem cell treatment efficacy by comparing miRNAs changed in liver diseases following stem cell treatment. Additionally, we also discuss the miRNA profiling in liver diseases when treated with stem cell therapy and suggest the candidate miRNAs that can be used as a biomarker that can monitor treatment efficacy in liver diseases based on MSCs therapy.
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Terapia Baseada em Transplante de Células e Tecidos , Hepatopatias/genética , Hepatopatias/terapia , MicroRNAs/genética , Transplante de Células-Tronco , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Baseada em Transplante de Células e Tecidos/tendências , Gerenciamento Clínico , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , Hepatopatias/diagnóstico , Índice de Gravidade de Doença , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/tendências , Células-Tronco/metabolismo , Resultado do TratamentoRESUMO
We assessed the detection rate of antineutrophil cytoplasmic antibody (ANCA) and investigated the clinical significance of ANCA positivity at diagnosis in patients with IgA vasculitis (Henoch-Schönlein purpura). We retrospectively reviewed their medical records of 86 IgA vasculitis patients. We divided IgA vasculitis patients based on ANCA positivity and compared variables at diagnosis and poor outcomes and medication during follow-up between the two groups. All-cause mortality, relapse, chronic kidney disease (CKD) (stage 3-5) and end-stage renal disease (ESRD) were defined as poor outcomes. We assessed the renal histological features based on the International Study of Kidney Disease in Children (ISKDC) classification and Oxford classification. Comparison of cumulative survivals was analysed by the Kaplan-Meier survival analysis. Five of 86 IgA vasculitis patients (5.8%) had ANCA and all ANCA-positive patients had myeloperoxidase (MPO)-ANCA. IgA vasculitis patients with ANCA exhibited pulmonary and nervous involvement of IgA vasculitis more frequently than those without. There was no significant difference in renal involvement between the two groups. There were no significant differences in renal histological features and poor outcomes related to renal function between IgA vasculitis patients with and without ANCA. In addition, 5 IgA vasculitis patients did not meet the classification criteria for ANCA-associated vasculitis (AAV). Particularly, there were no significant differences in CKD and ESRD-free survival rates between IgA vasculitis patients with and without ANCA. 5.8% of IgA vasculitis patients had MPO-ANCA and poor outcomes of IgA vasculitis were not affected by the presence of ANCA.
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Anticorpos Anticitoplasma de Neutrófilos/imunologia , Vasculite por IgA/imunologia , Imunoglobulina A/imunologia , Falência Renal Crônica/imunologia , Insuficiência Renal Crônica/imunologia , Adulto , Feminino , Humanos , Vasculite por IgA/complicações , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Placenta-derived mesenchymal stem cells (PD-MSCs) were highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs)were found to mediate one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with migrated naïve PD-MSCs, migrated PRL-1(+) PD-MSCs showed improved integrin-dependent migration abilitythrough Ras homolog (RHO) family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplantedPRL-1(+) PD-MSCs through the integrin family. Additionally, an increase inplatelet-derived growth factor receptor A (PDGFRA) by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSC transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs byactivating the interleukin-6 (IL-6) signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understandingof therapeutic mechanisms based on miRNA-mediated stem-cell therapy in liver diseases.
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Falência Hepática/terapia , Fígado/fisiologia , Transplante de Células-Tronco Mesenquimais , MicroRNAs/metabolismo , Regeneração , Animais , Hipóxia Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Interleucina-6/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Placenta/citologia , Gravidez , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases/metabolismo , Ratos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais , Remodelação VascularRESUMO
Processing of amyloid precursor protein (APP) occurs through sequential cleavages first by ß-secretase and then by the γ-secretase complex. However, abnormal processing of APP leads to excessive production of ß-amyloid (Aß) in the central nervous system (CNS), an event which is regarded as a primary cause of Alzheimer's disease (AD). In particular, gene mutations of the γ-secretase complex-which contains presenilin 1 or 2 as the catalytic core-could trigger marked Aß accumulation. Olfactory dysfunction usually occurs before the onset of typical AD-related symptoms (eg, memory loss or muscle retardation), suggesting that the olfactory system may be one of the most vulnerable regions to AD. To date however, little is known about why the olfactory system is affected so early by AD prior to other regions. Thus, we examined the distribution of secretases and levels of APP processing in the olfactory system under either healthy or pathological conditions. Here, we show that the olfactory system has distinct APP processing machineries. In particular, we identified higher expressions levels and activity of γ-secretase in the olfactory epithelium (OE) than other regions of the brain. Moreover, APP c-terminal fragments (CTF) are markedly detected. During AD progression, we note increased expression of presenilin2 of γ-secretases in the OE, not in the OB, and show that neurotoxic Aß*56 accumulates more quickly in the OE. Taken together, these results suggest that the olfactory system has distinct APP processing machineries under healthy and pathological conditions. This finding may provide a crucial understanding of the unique APP-processing mechanisms in the olfactory system, and further highlights the correlation between olfactory deficits and AD symptoms.
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Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/biossíntese , Precursor de Proteína beta-Amiloide/biossíntese , Bulbo Olfatório/metabolismo , Mucosa Olfatória/metabolismo , Animais , Humanos , Camundongos , Camundongos TransgênicosAssuntos
População do Leste Asiático , Lentigo , Humanos , Lentigo/genética , Mutação , Fenótipo , Proteínas Supressoras de Tumor , Masculino , Pré-Escolar , CriançaRESUMO
Here we explored the impact of hydrogen sulfide (H2S) on biophysical properties of the primary human airway smooth muscle (ASM)-the end effector of acute airway narrowing in asthma. Using magnetic twisting cytometry (MTC), we measured dynamic changes in the stiffness of isolated ASM, at the single-cell level, in response to varying doses of GYY4137 (1-10mM). GYY4137 slowly released appreciable levels of H2S in the range of 10-275 µM, and H2S released was long lived. In isolated human ASM cells, GYY4137 acutely decreased stiffness (i.e. an indicator of the single-cell relaxation) in a dose-dependent fashion, and stiffness decreases were sustained in culture for 24h. Human ASM cells showed protein expressions of cystathionine-γ-lyase (CSE; a H2S synthesizing enzyme) and ATP-sensitive potassium (KATP) channels. The KATP channel opener pinacidil effectively relaxed isolated ASM cells. In addition, pinacidil-induced ASM relaxation was completely inhibited by the treatment of cells with the KATP channel blocker glibenclamide. Glibenclamide also markedly attenuated GYY4137-mediated relaxation of isolated human ASM cells. Taken together, our findings demonstrate that H2S causes the relaxation of human ASM and implicate as well the role for sarcolemmal KATP channels. Finally, given that ASM cells express intrinsic enzymatic machinery of generating H2S, we suggest thereby this class of gasotransmitter can be further exploited for potential therapy against obstructive lung disease.
Assuntos
Brônquios/efeitos dos fármacos , Brônquios/fisiologia , Sulfeto de Hidrogênio/farmacologia , Canais KATP/efeitos dos fármacos , Canais KATP/metabolismo , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Miócitos de Músculo Liso/efeitos dos fármacos , Brônquios/citologia , Broncodilatadores/metabolismo , Broncodilatadores/farmacologia , Células Cultivadas , Cistationina gama-Liase/metabolismo , Glibureto/farmacologia , Humanos , Sulfeto de Hidrogênio/metabolismo , Morfolinas/farmacologia , Miócitos de Músculo Liso/fisiologia , Compostos Organotiofosforados/farmacologia , Pinacidil/farmacologia , Sarcolema/efeitos dos fármacos , Sarcolema/metabolismo , Sulfetos/farmacologiaRESUMO
OBJECTIVE: The eradication rate of 10-day sequential therapy for Helicobacter pylori (H. pylori) infection was not satisfactory in Korea, probably due to antibiotic resistance. To compare the treatment efficacy of 15-day and 10-day sequential therapy of conventional 7-day proton pump inhibitor (PPI) triple therapy for the treatment of H. pylori infection. METHODS: A total of 332 patients with H. pylori infection were randomly assigned to receive either 7-day PPI triple therapy, 10-day sequential therapy or 15-day sequential therapy. Eradication rate, drug compliance, and adverse events were compared among the three regimens. RESULTS: The eradication rates by intention-to-treat analysis were 64.3% (95% CI: 55.5-73.2; 74 of 115 patients), 72.1% (95% CI: 63.6-80.5; 80 of 111 patients), and 80.2% (95% CI: 72.5-87.9; 85 of 106 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.032). The eradication rates by per-protocol analysis were 68.5% (95% CI: 59.6-77.4; 74 of 108 patients), 78.4% (95% CI: 70.3-86.5; 80 of 102 patients), and 89.5% (95% CI: 83.2-95.8; 85 of 95 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.001). There were no statistically significant differences between the three eradication therapy groups in regard to drug compliance and adverse events. CONCLUSION: The 15-day sequential therapy demonstrated improved eradication efficacy compared with 7-day PPI triple and 10-day sequential therapy in Korea.