RESUMO
Cholesterol is an essential lipid in vertebrates, but excess blood cholesterol promotes atherosclerosis. In the liver, cholesterol is metabolized to bile acids by cytochrome P450, family 7, subfamily a, polypeptide 1 (CYP7A1), the transcription of which is negatively regulated by the ERK pathway. Fibroblast growth factor 21 (FGF21), a hepatokine, induces ERK phosphorylation and suppresses Cyp7a1 transcription. Taurine, a sulfur-containing amino acid, reportedly promotes cholesterol metabolism and lowers blood and hepatic cholesterol levels. However, the influence of long-term feeding of taurine on cholesterol levels and metabolism remains unclear. Here, to evaluate the more chronic effects of taurine on cholesterol levels, we analyzed mice fed a taurine-rich diet for 14-16 weeks. Long-term feeding of taurine lowered plasma cholesterol and bile acids without significantly changing other metabolic parameters, but hardly affected these levels in the liver. Moreover, taurine upregulated Cyp7a1 levels, while downregulated phosphorylated ERK and Fgf21 levels in the liver. Likewise, taurine-treated Hepa1-6 cells, a mouse hepatocyte line, exhibited downregulated Fgf21 levels and upregulated promoter activity of Cyp7a1. These results indicate that taurine promotes cholesterol metabolism by suppressing the FGF21/ERK pathway followed by upregulating Cyp7a1 expression. Collectively, this study shows that long-term feeding of taurine lowers both plasma cholesterol and bile acids, reinforcing that taurine effectively prevents hypercholesterolemia.
Assuntos
Ácidos e Sais Biliares , Taurina , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Colesterol na Dieta/metabolismo , Dieta , Fígado/metabolismo , Camundongos , Taurina/metabolismo , Taurina/farmacologiaRESUMO
Alterations in adipocyte characteristics are highly implicated in the pathology of obesity. In a recent article, we demonstrated that high-fat diet-induced obesity impairs lysosomal function, thereby suppressing autophagy in mice white adipose tissue. Taurine, an amino acid naturally contained in the normal diet and existing ubiquitously in tissues, has been reported to improve insulin resistance and chronic inflammation in animal models, but underlying mechanisms remain unclear. From these findings, we hypothesized that improvement of obese pathology by taurine may be mediated through recovery of autophagy. In matured 3T3-L1 mouse adipocytes, treatment with taurine-promoted autophagy. Moreover, taurine-induced nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy- and lysosome-related factors. As this translocation is regulated by several kinase pathways, including extracellular signal-related kinase 1 and 2 (ERK1/2) and mechanistic target of rapamycin protein kinase complex 1 (MTORC1), we examined related signaling elements. Consequently, taurine-reduced phosphorylation levels of ERK1/2 but did not alter the phosphorylation of MTORC1 pathway-associated adenosine monophosphate-activated protein kinase or ribosomal protein S6 kinase. Taken together, these results suggest that taurine may enhance TFEB nuclear translocation through ERK1/2 to accelerate autophagy. The effect discovered in this study may represent a novel mechanism for the improvement of obesity-related pathology by taurine.
Assuntos
Adipócitos/metabolismo , Autofagia/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Taurina/farmacologia , Adipócitos/citologia , Animais , Linhagem Celular , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismoRESUMO
The purpose of this study was to classify patients with severe COVID-19 into more detailed risk groups using coagulation/fibrinolysis, inflammation/immune response, and alveolar/myocardial damage biomarkers, as well as to identify prognostic markers for these patients. These biomarkers were measured every day for eight intensive care unit days in 54 adult patients with severe COVID-19. The patients were classified into survivor (n = 40) and non-survivor (n = 14) groups. Univariate and multivariate analyses showed that the combined measurement of platelet count and presepsin concentrations may be the most valuable for predicting in-hospital death, and receiver operating characteristic curve analysis further confirmed this result (area under the curve = 0.832). Patients were consequently classified into three groups (high-, medium-, and low-risk) on the basis of their cutoff values (platelet count 53 × 103/µL, presepsin 714 pg/mL). The Kaplan-Meier curve for 90-day survival by each group showed that the 90-day mortality rate significantly increased as risk level increased (P < 0.01 by the log-rank test). Daily combined measurement of platelet count and presepsin concentration may be useful for predicting in-hospital death and classifying patients with severe COVID-19 into more detailed risk groups.
Assuntos
COVID-19 , Adulto , Humanos , Prognóstico , Mortalidade Hospitalar , Contagem de Plaquetas , Biomarcadores , Curva ROC , Fragmentos de Peptídeos , Receptores de LipopolissacarídeosRESUMO
C-X-C motif chemokine ligand 9 (CXCL9), a candidate biomarker, reflects type 1 (T1) inflammation pathology. Here, we report the analytical performance and clinical characteristics of a new CXCL9 reagent for a fully automated immunoassay device. We evaluated the limits of blank, detection, and quantitation (LoQ) along with other efficacy parameters, and the ability of the assay to report patient health, COVID-19 status, and the presence of asthma and/or interstitial lung diseases (ILDs). The coefficient of variation for 5-day total precision using two instruments was 7% across two controls, serum, and plasma panels. LoQ of 2.2 pg/mL suggested the efficacy of the assay in detecting T1 inflammation in plasma or serum; no cross-reactivity or interference was observed. We identified high serum CXCL9 levels in samples from patients with acute COVID-19 infections (n = 57), chronic bird-related hypersensitivity pneumonitis (n = 61), asthma (n = 194), and ILDs (n = 84) compared to healthy individuals (< 39.0 pg/mL). Furthermore, CXCL9 levels increased with age in asthma patients, and an opposite trend was observed for T2 inflammatory factors. These results suggest the utility of the automated CXCL9 immunoassay for measuring CXCL9 in clinical samples and reflect its role in T1 inflammation.
Assuntos
Asma , COVID-19 , Doenças Pulmonares Intersticiais , Humanos , COVID-19/diagnóstico , Imunoensaio/métodos , Biomarcadores , Asma/diagnóstico , Inflamação , Quimiocina CXCL9 , Quimiocina CXCL10RESUMO
PURPOSE: The aim of the present prospective study was to compare material-related complications using biodegradable and titanium miniplates after bilateral sagittal split mandibular setback surgery. PATIENTS AND METHODS: The subjects included 200 Japanese adults (67 men and 133 women, age range 18 to 45 years) with jaw deformities diagnosed as mandibular prognathism. All patients were prospectively and consecutively randomized to 2 study groups, receiving biodegradable or titanium fixation plates. Of the 200 patients, 110 underwent bilateral sagittal split ramus osteotomy with a biodegradable fixation plate and 90 underwent bilateral sagittal split ramus osteotomy with a titanium metal plate. The clinical records and radiologic findings of the patients were reviewed, and the incidence of material-related complications was compared. RESULTS: The incidence of postoperative complications and breakage in the biodegradable group was 8.2% (9 cases) and in the titanium group was 3.3% (3 cases). No statistically significant difference in the incidence of complications was found between the 2 groups. Fractures of the biodegradable plate occurred at a significantly greater frequency in patients with asymmetry than in patients without asymmetry. CONCLUSION: Biodegradable plates were reliable with minimal material-related complications. However, the use of biodegradable plates should be recommended for minimally loaded situations.
Assuntos
Implantes Absorvíveis/efeitos adversos , Materiais Biocompatíveis/efeitos adversos , Placas Ósseas/efeitos adversos , Osteotomia Sagital do Ramo Mandibular/instrumentação , Titânio/efeitos adversos , Adolescente , Adulto , Fenômenos Biomecânicos , Cefalometria/métodos , Falha de Equipamento , Assimetria Facial/cirurgia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteotomia Sagital do Ramo Mandibular/efeitos adversos , Dor Pós-Operatória/etiologia , Satisfação do Paciente , Complicações Pós-Operatórias , Prognatismo/cirurgia , Estudos Prospectivos , Infecção da Ferida Cirúrgica/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
Treatment of severe and critical cases of coronavirus disease 2019 (COVID-19) is still a top priority in public health. Previously, we reported distinct Th1 cytokines related to the pathophysiology of severe COVID-19 condition. In the present study, we investigated the association of Th1 and Th2 cytokine/chemokine endotypes with cell-mediated immunity via multiplex immunophenotyping, single-cell RNA-Seq analysis of peripheral blood mononuclear cells, and analysis of the clinical features of COVID-19 patients. Based on serum cytokine and systemic inflammatory markers, COVID-19 cases were classified into four clusters of increasing (I-IV) severity. Two prominent clusters were of interest and could be used as prognostic reference for a targeted treatment of severe COVID-19 cases. Cluster III reflected severe/critical pathology and was characterized by decreased in CCL17 levels and increase in IL-6, C-reactive protein CXCL9, IL-18, and IL-10 levels. The second cluster (Cluster II) showed mild to moderate pathology and was characterized by predominated CXCL9 and IL-18 levels, levels of IL-6 and CRP were relatively low. Cluster II patients received anti-inflammatory treatment in early-stage, which may have led prevent disease prognosis which is accompanied to IL-6 and CRP induction. In Cluster III, a decrease in the proportion of effector T cells with signs of T cell exhaustion was observed. This study highlights the mechanisms of endotype clustering based on specific inflammatory markers in related the clinical outcome of COVID-19.
Assuntos
COVID-19 , Citocinas , Humanos , Interleucina-10 , Interleucina-18 , Proteína C-Reativa , Interleucina-6 , Leucócitos Mononucleares , Quimiocinas , BiomarcadoresRESUMO
OBJECTIVE: Left ventricular (LV) remodeling alters the contractile and relaxation properties and induces myocardial stiffness. As LV remodeling progresses, the amount of collagen type III (Col3) is gradually decreased, being replaced by collagen type I (Col1). We evaluated whether Col3 overexpression improved cardiac function and remodeling in a rat with ischemic cardiomyopathy (ICM). We also investigated the functional motif and mechanism of thrombin-cleaved N-terminal osteopontin (N-OPN) on cardiac remodeling. METHODS: The rats with ICM were divided into 3 groups: ligation only (Control) group and groups transplanted with nontransfected fibroblast sheets (normal Fb group) or with Col3-secretory fibroblast sheets (Col3 Fb group). A gelatin hydrogel containing the N-terminal fragment (N-OPN), N-OPN lacking the SVVYGLR sequence (â¿SV), the Arg-Gly-Asp (RGD) sequence (â¿RGD), RGD and SVVYGLR sequences (â¿RGD-SV), SVVYGLR alone (SV), or a random SV peptide was implanted into an ICM model rat. RESULTS: The Col3 Fb group exhibited significantly attenuated LV systolic dysfunction. LV dilatation, myocyte hypertrophy, and LV fibrosis at the infarcted area were also attenuated by Col3 Fb implantation. Furthermore, N-OPN, â¿RGD, and SV peptide suppressed the depression of cardiac function, LV dilatation, and myocyte hypertrophy, and also induced increased Col3 expression and reduction in the ratio of Col1 to Col3 in the infarcted and border areas. CONCLUSIONS: Overexpression of Col3 improved cardiac function by changing the balance of collagen distribution in LV remodeling. The SVVYGLR motif of the thrombin-cleaved N-OPN and SV peptide attenuated cardiac dysfunction by increasing Col3 and changing the pattern of collagen balance in the impaired area.
Assuntos
Cardiomiopatias/cirurgia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Colágeno Tipo III/metabolismo , Fibroblastos/transplante , Terapia Genética/métodos , Miocárdio/metabolismo , Osteopontina/farmacologia , Fragmentos de Peptídeos/farmacologia , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Células Cultivadas , Colágeno Tipo I/metabolismo , Colágeno Tipo III/genética , Modelos Animais de Doenças , Fibroblastos/metabolismo , Masculino , Miocárdio/patologia , Ratos Endogâmicos Lew , SístoleAssuntos
Adenoma Pleomorfo/patologia , Neoplasias Palatinas/patologia , Palato Mole/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Adenoma Pleomorfo/irrigação sanguínea , Adulto , Humanos , Masculino , Necrose , Neoplasias Palatinas/irrigação sanguínea , Palato Mole/irrigação sanguínea , Neoplasias das Glândulas Salivares/irrigação sanguínea , Glândulas Salivares Menores/irrigação sanguíneaRESUMO
The aim of this retrospective study was to evaluate the risk factors associated with breakage of biodegradable plate systems after bilateral sagittal split mandibular setback. We studied 169 Japanese adults (62 men, 107 women; age range 16-53 years) with deformities of the jaw diagnosed as mandibular prognathism. All patients were treated by bilateral sagittal split osteotomy (BSSO) with 2 biodegradable fixation plates and screws at the anterior mandibular ramus. We collected the following data from the medical records and radiological findings: sex; age; degree of setback; presence of asymmetry; presence of open bite; operation; design of the plate; operating time; and blood loss. Multiple logistic regression analysis was used to find the factors that were independently associated with the dependent variable: breakage of the biodegradable plate system. In 10 of the 169 patients (6%) the biodegradable plate system for the BSSO broke. Factors that influenced whether or not the biodegradable plate system fractured were if they were asymmetrical (odds ratio (OR) 5.35; P=0.02) and had an open bite (OR 5.20; P=0.02). Asymmetry or open bite was significantly associated with breaks in the biodegradable plate system. Biodegradable plates should be used only when loading is minimal.
Assuntos
Implantes Absorvíveis , Placas Ósseas , Osteotomia Sagital do Ramo Mandibular/instrumentação , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Parafusos Ósseos , Cefalometria/métodos , Desenho de Equipamento , Falha de Equipamento , Assimetria Facial/cirurgia , Feminino , Seguimentos , Mentoplastia/métodos , Humanos , Ácido Láctico/química , Masculino , Mandíbula/cirurgia , Osteotomia Mandibular/instrumentação , Pessoa de Meia-Idade , Mordida Aberta/cirurgia , Duração da Cirurgia , Osteotomia de Le Fort/métodos , Poliésteres , Polímeros/química , Prognatismo/cirurgia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
We report an extremely rare case of epidermal choristoma in the midline of the maxillary gingiva. A 2-month-old Japanese boy presented with a polypoid mass in the midline of the maxillary gingiva. The initial clinical diagnosis was congenital epulis. Microscopic examination revealed a granular cell layer and melanin pigmentation within the basal cell layer. Furthermore, sebaceous glands and hair follicles were observed within the connective tissue. The histological diagnosis was therefore epidermal choristoma, based on clinical microscopic observations.
Assuntos
Coristoma/diagnóstico , Doenças da Gengiva/diagnóstico , Neoplasias Gengivais/congênito , Pele/patologia , Diagnóstico Diferencial , Epitélio/patologia , Folículo Piloso/patologia , Humanos , Lactente , Masculino , Maxila/patologia , Melaninas/análise , Glândulas Sebáceas/patologiaRESUMO
BACKGROUND: Although many histopathological characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, no factor is completely accurate and unequivocal. This study evaluated the association between the loss of syndecan-1 expression and the histological grade of malignancy at the deep invasive front in O-SCC. METHODS: The expression of syndecan-1 at the invasive tumor front of O-SCC was examined immunohistochemically using archived tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23-90 years) and the male-female ratio was 1.3:1 (41 men, 31 women). There were 26, 24, 11, and 11 cases classified as stages I-IV respectively. The correlation between the intensity of syndecan-1 immunostaining and the clinicopathological factors, especially the histological grade of malignancy at the deep invasive front (invasive front grade) was analyzed. RESULTS: Of the 72 cases, seven (9.7%), 29 (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1 staining respectively. There were significant differences between syndecan-1 expression and prognosis, differentiation, and pattern of invasion at the deep invasive front. Moreover, the invasive front grade scores, based on the intensity of syndecan-1 staining, were 5.6 +/- 1.0, 8.0 +/- 2.1, and 10.2 +/- 2.3 points with strong, intermediate, and weak or negative intensity respectively; and the difference was significant (P < 0.0001). Patients with intermediate or strong intensity for syndecan-1 had significantly better prognoses than did those with negative or weak intensity (P = 0.0138). CONCLUSION: This study demonstrated that the reduced expression of syndecan-1 seems to be a useful marker of histological malignancy at the deep tumor invasive front and may be a useful prognostic factor in O-SCC.