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1.
Life Sci ; 248: 117475, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32119963

RESUMO

AIMS: Liver fibrosis is a crucial pathological feature which could result in cirrhosis and hepatocarcinoma. But until now, there is no favourable treatment for it. Apigenin (APG) is a flavonoid, which exhibits efficient anti-liver fibrosis activity, but its underlying mechanisms were rarely studied. So this work aims to estimate the potential therapeutic action of APG on liver fibrosis rats and to gain insight into its system-level mechanisms. MAIN METHODS: Hepatic fibrosis was induced by CCl4 in Wistar rats, and APG was given in the light of the regimen. Biochemical indexes, histopathological change and immunohistochemistry of liver were evaluated. The optimal effect group of APG was selected for further transcriptomic and proteomic analysis. KEY FINDINGS: APG ameliorated liver fibrosis via reducing the levels of AST, ALT, ALP, LDH, Hyp, TP, TB, DB, HA, LN, PCIII and IV-C, mitigating fibrosis and inflammation of liver in H&E and Masson staining. Mechanistically, APG elevated the activity of ALB, SOD and GSH-PX with reducing the level of MDA. The results of microarray and TMT revealed that 4919 genes and 4876 proteins were differentially expressed in the APG and model groups. Besides, transcriptomics and proteomics analyses unfolded 120 overlapped proteins, enriched in 111 GO terms containing apoptotic process, angiogenesis, cell migration and proliferation, etc. Meanwhile, KEGG pathway analysis showed that 26 pathways containing HIF-1/MAPK/eNOS/VEGF/PI3K/Akt signaling pathway, regulation of actin cytoskeleton and focal adhesion mostly. SIGNIFICANCE: APG can ameliorate CCl4-induced liver fibrosis via VEGF-mediated FAK phosphorylation through the MAPKs, PI3K/Akt, HIF-1, ROS, and eNOS pathways, which may hopefully become the anti-liver fibrosis activity of natural product.


Assuntos
Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Albuminas/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Bilirrubina/sangue , Tetracloreto de Carbono/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Proteômica/métodos , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
2.
Medicine (Baltimore) ; 99(11): e18963, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176028

RESUMO

High levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are associated with increased diabetes risk. In the present study, we investigated the combined effects of ALT and GGT on the development of diabetes in a Korean population. A total of 9405 individuals (4020 women and 5385 men) without diabetes were enrolled in this study. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in ALT and GGT quartile levels, was analyzed. In addition, we analyzed the quartiles of ALT and GGT together to determine any synergistic effect from the fourth quartile of ALT and GGT on the development of diabetes. The development of diabetes gradually increased with an increase in the circulating levels of ALT and GGT. For the fourth quartile ALT and GGT, the hazard ratios of diabetes compared with the first quartile were 1.892 (95% confidence interval [CI]: 1.26-2.83, P = .002) and 3.526 (95% CI: 2.12-5.85, P < .001) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both fourth quartiles of ALT and GGT were 3.663 (95% CI: 2.42-5.52, P < .001), as compared with the first and second quartiles. Serum ALT and GGT levels are well associated with diabetes in Koreans after adjusting for confounders, and a combination of ALT and GGT levels can have a synergy in predicting the development of diabetes.


Assuntos
Alanina Transaminase/sangue , Diabetes Mellitus/enzimologia , gama-Glutamiltransferase/sangue , Biomarcadores/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco
3.
Medicine (Baltimore) ; 99(11): e19492, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176089

RESUMO

Despite many studies, the molecular mechanisms of hepatocellular carcinoma (HCC) development remain unclear. Thyroid hormone (TH) levels may vary in many chronic diseases including cirrhosis. The aim of this study was to evaluate TH status in patients with cirrhosis and HCC and to investigate the relationship between THs and HCC development.Five hundred seventy-seven patients with cirrhosis who applied to Demiroglu Bilim University, Faculty of Medicine, Gastroenterology Department between 2004 and 2019 were included the study. Three hundred sixty-seven patients who applied to Internal Medicine Unit for general health check-up were included in the study as healthy control group. Demographic, laboratory, and imaging findings of study groups were retrospectively reviewed and recorded from hospital information system.In the cirrhosis group, 252 patients had HCC (43.67%), and 325 patients had non-HCC cirrhosis (56.33%). Free thyroxine (FT4) levels were higher in the control group than in the cirrhotic group but there was no significant difference (P = .501). Thyroid-stimulating hormone (TSH) and FT4 levels were similar between groups, while free triiodothyronine (FT3) levels were significantly different between HCC group, non-HCC cirrhosis group, and control group (P = .299 for TSH, P = .263 for FT4, P < .001 for FT3). FT3 levels were significantly higher in HCC group than non-HCC cirrhosis group, but significantly lower than control group (P < .05).Our study confirmed the presence of hypothyroidism in cirrhosis patients and clearly demonstrated a strong relationship between FT3 levels and HCC development.


Assuntos
Carcinoma Hepatocelular/complicações , Hipotireoidismo/complicações , Cirrose Hepática , Neoplasias Hepáticas/complicações , Hormônios Tireóideos/sangue , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Hipotireoidismo/sangue , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Testes de Função Tireóidea
4.
Medicine (Baltimore) ; 99(8): e19201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080106

RESUMO

Hepatitis B virus (HBV) is one of the commonest chronic infections, especially in Asia and Africa, which put a heavy burden worldwide. With the advanced knowledge of HBV, early detection, primary care, and hepatology have made huge progression than before. However, the relationship between gender, age, and different key parameters in HBV patients remains to be determined.In this study, we measured various physiological and biochemical indexes in a large cohort of HBV patients as well as healthy control. We investigated the strength of correlations among those indexes and reported instantaneous imaging results. Moreover, we examined the effects of various grouping modes such as by gender or age on liver stiffness measurement (LSM) and controlled attenuation parameters (CAPs). We compared their diagnostic values for hepatic fibrosis in HBV patients.The results showed that specimens from a healthy control were obviously clustering tightly together, while the specimens from the HBV patients were clustering into several subgroups. Direct bilirubin (DB), total bilirubin (TB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) occurred together with the diagnosis of HBV. Furthermore, groups categorized by Gender had significant effects on fibrotouch measurement not only in HBV patients but also in healthy control.Our research was to evaluate the actual effects of various parameters on Fibrotouch and make improvement of the critical value of those medical indexes.


Assuntos
Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
5.
Medicine (Baltimore) ; 99(7): e18882, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049787

RESUMO

RATIONALE: Procalcitonin (PCT) is used as a biomarker for identifying the occurrence of sepsis. Previous studies have reported high levels of PCT with acetaminophen intoxication without evidence of infection. Here, we report two patients with acetaminophen intoxication with high levels of PCT without showing any symptoms of bacterial infection. PATIENT CONCERNS: This case study examined two unrelated patients with acetaminophen intoxication admitted to emergency at different times. The first patient was admitted to the emergency department after ingesting approximately 8000 mg (153.8 mg/kg) of acetaminophen. On admission, C-reactive protein (CRP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were normal. PCT and acetaminophen levels were 31.89 ng/mL and below 0.5 µg/mL, respectively. The second patient was admitted to the emergency department 8 h after ingesting ∼23,600 mg (280.6 mg/kg) of acetaminophen. By the second day of admission, GOT and GPT increased to 2508 and 1473 IU/L, respectively. PCT was 45.66 ng/mL with acetaminophen level at 116.9 µg/mL. Both patients were clear of symptoms associated with bacterial infection. DIAGNOSIS: Acetaminophen intoxication. INTERVENTIONS: N-acetylcysteine was given intravenously to both patients for 20 h per protocol. OUTCOMES: Both patients were discharged without complications. LESSONS: Observations suggests that elevated levels of PCT in patients intoxicated with acetaminophen may be associated with involvement of other organs impacted by cytokine stimuli from sterile inflammation resulting from hepatic damage rather than PCT secretion directly caused by hepatic cell damage.


Assuntos
Acetaminofen/toxicidade , Acetilcisteína/administração & dosagem , Overdose de Drogas/tratamento farmacológico , Pró-Calcitonina/metabolismo , Acetilcisteína/uso terapêutico , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Proteína C-Reativa/análise , Overdose de Drogas/diagnóstico , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
6.
Medicine (Baltimore) ; 99(3): e18754, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011459

RESUMO

The purpose of this study was to evaluate related risk factors for gallstone disease in Shanghai.We analyzed successive physical examinations of 2288 adults who were recruited at the Jinshan Branch of the Sixth People's Hospital of Shanghai and Jinshan Hospital Affiliated to Fudan University Hospital from July 2010 to December 2012. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the influence factors on the risks of gallstone development.The incidence of gallstone disease was 4.11% (94/2,288). Older age (OR: 1.02; 95% CI: 1.00-1.03; P = .039), higher body weight (OR: 1.02; 95% CI: 1.00-1.04; P = .021), alanine transaminase activity (ALT) (OR: 1.02; 95% CI: 1.01-1.03; P = .001), total standard bicarbonate (SB) (OR: 1.04; 95% CI: 1.02-1.06; P < .001), free SB (OR: 1.17; 95% CI: 1.12-1.21; P < .001), and low density lipoprotein (LDL) levels (OR: 1.59; 95% CI: 1.32-1.91; P < .001) were associated with an increased risk of gallstone disease. Based on univariate logistic analysis, increased triglyceride (TG) levels were associated with a reduced risk of gallstone disease (OR: 0.76; 95% CI: 0.60-0.97; P = .024). The results of multivariable logistic regression analysis showed higher LDL levels correlated with an increased risk of gallstone disease (OR: 1.92; 95% CI: 1.31-2.81; P < .001), while age, weight, ALT, total SB, free SB, and TG levels did not affect the risk of gallstone disease.The although unadjusted results showed age, weight, ALT, total SB, free SB, TG, and LDL levels to be associated with the risk of gallstone disease, adjusting for potential factors revealed only increased LDL levels to be associated with an increased risk of gallstone disease.


Assuntos
Cálculos Biliares/epidemiologia , Fatores Etários , Alanina Transaminase/sangue , Biomarcadores/sangue , Peso Corporal , China/epidemiologia , Feminino , Humanos , Incidência , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
7.
Life Sci ; 248: 117464, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097667

RESUMO

AIMS: The present study was carried out to investigate the influences of Selenium/Zinc-Enriched probiotics (SeZnP) on growth performance, serum enzyme activity, antioxidant capability, inflammatory factors and gene expression associated with Wistar rats inflated under high ambient thermal-stress. MAIN METHODS: Sixty male rates with six-weeks of age were randomly allocated into five groups (12 per group) and fed basal diet (Control), basal diet supplemented with probiotics (P), Zinc-Enriched probiotics (ZnP, 100 mg/L), Selenium-Enriched Probiotics (SeP, 0.3 mg/L) and Selenium/Zinc-Enriched probiotics (SeZnP, 0.3 mg + 100 mg/L). The experiment lasted 30 days. Blood and Tissues samples were taken to investigate serum enzyme activity, antioxidants capability and inflammatory factors by using of commercial kits and antioxidant, heat shock and inflammatory related molecules expressions were determined by qRT-PCR. KEY FINDINGS: Data analysis revealed that thermal stress significantly increased the level of Aspartate-aminotransferase, Alanine-aminotransferase, Lactate-dehydrogenase, Creatine-kinase, blood urea nitrogen, Creatinine and Alkaline phosphatase compared to P, ZnP, SeP or SeZnP groups (P < 0.01). However, supplementation of ZnP, SeP, and SeZnP significantly enhanced glutathione content, glutathione-peroxidase & superoxide-dismutase activity, and decreased malondialdehyde content (P < 0.05). Moreover, the concentration of IL-2, IL-6 and IL-8 were significantly increased while IL-10 was significantly decreased (P < 0.05). Furthermore, the expression of GPx1 and SOD1 genes were significantly increased, but COX-2, iNOS, HSP70 and 90 mRNA levels were significantly decreased (P < 0.05). Finally, the highest influence of the mentioned parameters was observed in SeZnP supplemented group. SIGNIFICANCE: Our study suggests that SeZnP supplementation serves as possible and best nutritive than ZnP or SeP for Wistar rats raising under high ambient temperature.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Probióticos/administração & dosagem , Selênio/administração & dosagem , Zinco/administração & dosagem , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Nitrogênio da Ureia Sanguínea , Creatina Quinase/genética , Creatina Quinase/metabolismo , Creatinina/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Resposta ao Choque Térmico/genética , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
8.
Life Sci ; 246: 117416, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32035927

RESUMO

AIMS: Diabetes is a common metabolic disease which damages many organs including the liver and causes endoplasmic reticulum (ER) stress, which originates from non-folded proteins. Sonic hedgehog (Shh) pathway plays a role in liver regeneration and repair. To our knowledge, there is no study showing the relation between ER stress and Shh pathway in the liver in diabetes. Thus, the aim of this study was to investigate the interaction between ER stress and Shh pathway in the liver of diabetic mice. MAIN METHODS: Six groups of male mice were formed as control, diabetes (streptozotocine-treated), Shh activator (SAG-treated), Shh inhibitor (SANT1-treated), diabetes + SAG and diabetes + SANT1. At the end of the experiment, mice were weighed, anaesthetized and euthanized. Blood samples were collected, livers were excised and weighed. Thereafter, blood glucose, serum ALT and AST levels, TOS and TAC levels in liver tissue were measured. ER stress marker (GRP78) and Shh pathway molecules (Gli1 and Smo) were evaluated by immunohistochemistry, H-score and western blot analyses. Besides, histopathological examination was performed. KEY FINDINGS: Results showed that GRP78, Gli1 and Smo were increased in liver due to Type 1 diabetes. The SAG agent decreased GRP78 and increased Gli1 and Smo, leading to liver repair, while the inhibitor SANT1 increased GRP78 and decreased Gli1and Smo, causing progression of the liver stress induced by diabetes. SIGNIFICANCE: In conclusion, the Shh pathway is related to ER stress and may provide a new strategy for its treatment, especially liver stress induced by diabetes.


Assuntos
Diabetes Mellitus Experimental/complicações , Estresse do Retículo Endoplasmático , Proteínas Hedgehog/metabolismo , Hepatopatias/etiologia , Transdução de Sinais , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/análise , Western Blotting , Diabetes Mellitus Experimental/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Camundongos
9.
J Sports Sci ; 38(6): 682-691, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32050850

RESUMO

This study aimed to verify the effect of a multicomponent intervention on cardiometabolic risk factors (CMRF), and to determine the prevalence of responders on CMRF among children and adolescents with overweight/obesity. This is a quasi-experimental study, developed with 35 children and adolescents with overweight/obesity (control group (CG) = 18; intervention group (IG) = 17), aged between 7 and 13 years. Participants in IG underwent a multicomponent intervention for 12 weeks. The following variables were evaluated: anthropometric measures, maturational stages and CMRF (body fatness, HOMA-IR, triglycerides, high-density and low-density lipoprotein) (HDL-C, LDL-C), total cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST/ALT ratio. Mixed analysis of variance and the prevalence of responders were used for statistical analysis. There was a significant time x group interaction on body fatness (p < 0.001), HOMA-IR (p = 0.01), HDL-C (p < 0.001), LDL-C (p = 0.009) and TC (p < 0.001). The prevalence of responders for CMRF in IG and CG was respectively: body fatness (47%; 0%; p = 0.04), HOMA-IR (58.8%; 16.6%; p = 0.04); triglycerides (17.6%; 5.5%; p = 0.31); HDL-C (76.4%; 5.5%; p = 0.01), LDL-C (35.3%; 5%; p = 0.08), TC (64.7%; 5%; p = 0.01), AST (5.8%; 0%; p = 0.87), ALT (29.4%; 11.1%; p = 0.24) and AST/ALT ratio (24.4%; 22.2%; p = 0.67). Multicomponent intervention induced positive changes on CMRF along with a higher prevalence of positive adaptations in IG than the CG in some of the cardiometabolic outcomes assessed.


Assuntos
Exercício , Sobrepeso/prevenção & controle , Pais/psicologia , Obesidade Pediátrica/prevenção & controle , Apoio Social , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Distribuição da Gordura Corporal , Criança , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Homeostase , Humanos , Resistência à Insulina/fisiologia , Masculino , Fatores de Risco , Triglicerídeos/sangue
10.
Braz Oral Res ; 34: e008, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049109

RESUMO

This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.


Assuntos
Prótese Ancorada no Osso , Dieta Hiperlipídica/psicologia , Osseointegração/fisiologia , Estresse Psicológico/fisiopatologia , Tíbia/fisiopatologia , Titânio , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/análise , Colesterol/sangue , Implantação Dentária Endo-Óssea/métodos , Feminino , Distribuição Aleatória , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Tíbia/patologia , Tíbia/cirurgia , Fatores de Tempo , Triglicerídeos/sangue
11.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 65-70, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958933

RESUMO

Objective: To study the relationship of liver function index alanine aminotransferase and aspartate aminotransferase ratio (LSR) with clinicopathological factors in patients with gastric cancer and its clinical significance in predicting the survival of patients. Methods: A retrospective case-control study was used. Retrospective analysis was conducted on 891 patients with advanced gastric cancer who underwent gastric cancer surgery at the Gastrointestinal Surgery Department of Harbin Medical University Cancer Hospital from January 2007 to December 2010, having complete postoperative clinicopathological and follow-up data. Case inclusion criteria: (1) preoperative definite diagnosis of gastric cancer, residual gastric cancer and other gastric tumors were excluded; (2) no neoadjuvant therapy before surgery; (3) no other serious diseases such as acute coronary heart disease, cirrhosis, chronic renal failure, etc.; (4) radical gastrectomy was performed, palliative treatment or open laparotomy cases were excluded; (5) complete postoperative pathological data, complete follow-up information; (6) cause of death was associated with gastric cancer. Blood examination was performed during hospitalization. The best cut-off points of LSR, hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were obtained by using receiver operating characteristic curve(ROC). Patients were divided into two groups according to best LSR cut-off points. The relationship between LSR and clinicopathological factors was analyzed, and the overall survival rate of different LSR groups was compared. Relevant clinical factors and LSR were included in the univariate and multivariate survival analysis using the Cox method. Results: The best cut-off point of LSR in ROC curve was 1.43, and 682 cases in LSR<1.43 group, 209 cases in LSR≥1.43 group. The best cut-off points of hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were 130.2 g/L, 18.0%, 4.75 cm, 68.1 U/L, 16.55 U/L, 5.58 µmol/L and 135.8 U/L, respectively. Between patients with LSR<1.43 and LSR≥1.43, age (χ(2)=4.412, P=0.036), depth of tumor invasion (χ(2)=64.306, P<0.001), histological type (χ(2)=8.026, P=0.005), alkaline phosphatase (χ(2)=8.217, P=0.004), glutamyl transpeptidase (χ(2)=33.207, P<0.001), total bilirubin (χ(2)=14.012, P<0.001) and lactate dehydrogenase (χ(2)=63.630, P<0.001) were significantly different. The 1-, 3- and 5-year survival rates of LSR<1.43 group and LSR≥1.43 group were 70.8%, 31.3%, 25.0% and 64.9%, 24.4%, 11.3% respectively, whose difference was significant (χ(2)=10.140, P=0.001). Univariate analysis showed that age, hemoglobin, TNM stage, depth of invasion, lymph node metastasis rate, lymph node metastasis, histological type, maximum diameter of tumors, glutamyl transferase, total bilirubin and LSR were associated with overall survival of gastric cancer (all P<0.05). Multivariate analysis showed that tumor TNM stage (HR=1.605, 95%CI: 1.332 to 1.936, P<0.001), tumor invasion depth (HR=1.299, 95%CI: 1.168 to 1.445, P<0.001), lymph node metastasis rate (HR=2.400, 95%CI:1.873 to 3.076, P<0.001), lymph node metastasis (HR=1.263, 95%CI: 1.106 to 1.478, P=0.007), maximum tumor diameter (HR=1.375, 95%CI: 1.134 to 1.669, P=0.001), and LSR (HR=1.427, 95%CI: 1.190 to 1.711, P<0.001) were independent risk factors for the prognosis of patients with gastric cancer. Conclusions: LSR is an independent risk factor for the prognosis of gastric cancer patients, and the detection is simple and easy. It is a potential marker for the prognosis of gastric cancer. Therefore, in the preoperative comprehensive management stage, it should be possible to restore and improve the liver function in order to obtain a better prognosis of gastric cancer and prolong the survival time of patients.


Assuntos
Alanina Transaminase/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Transaminases/sangue , Gastrectomia/mortalidade , Humanos , Hepatopatias/sangue , Hepatopatias/mortalidade , Testes de Função Hepática , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
12.
J Zoo Wildl Med ; 50(4): 1021-1025, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926541

RESUMO

Hematology and serum biochemistry profiles are used to evaluate the health status of animals ongoing rehabilitation. The aim of this project was to develop blood and biochemistry ranges for harbor seal pups (Phoca vitulina) after rehabilitation; thus, 22 different blood parameters in 60 animals were tested before release. The second goal was to test for differences due to sex, stranding location, body condition at admission, and presence or absence of umbilical cord. The alanine aminotransferase, ALT (or glutamate pyruvate transaminase, GPT), (ALT-GPT) differed significantly (P bq = 0.00851) between sexes. Lower leukocyte counts and higher liver enzyme values were the most remarkable findings when comparing the results of this study to other published data. This is the first study to report blood reference ranges for harbor seal pups in the Dutch Wadden Sea after rehabilitation.


Assuntos
Contagem de Eritrócitos/veterinária , Hematócrito/veterinária , Contagem de Leucócitos/veterinária , Phoca/sangue , Contagem de Plaquetas/veterinária , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Glicemia , Nitrogênio da Ureia Sanguínea , Creatinina , Feminino , Hemoglobinas , Masculino
13.
J Biochem Mol Toxicol ; 34(2): e22427, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31777137

RESUMO

The study aimed to examine the effects of nobiletin on the toxicity model induced with acetaminophen (APAP). For this purpose, 24 adult male rats were equally divided into four groups. The groups were the control group (group 1); dimethyl sulfoxide only, the APAP group (group 2) received a single dose of APAP 1000 mg/kg on the 10th day of experiment; the Nobiletin group (group 3), nobiletin (10 mg/kg) for 10 days; and the APAP + Nobiletin group (group 4), nobiletin (10 mg/kg) for 10 days with a single dose of APAP (1000 mg/kg) administered on the 10th day and the experiment ended after 48 hours. At the end of the study, a significant increase in malondialdehyde, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels and a significant decrease in glutathione levels, glutathione peroxidase activities and nuclear factor erythroid-derived 2-like 2 (Nrf-2) and heme oxygenase-1 (HO-1) expressions were observed with APAP application in liver and kidney tissues. Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, and creatinine levels were also significantly increased in the APAP group. However, nobiletin treatment in group 4 reversed oxidative stress and inflammatory and histopathological signs caused by APAP. It is concluded that nobiletin may be a beneficial substance that confers hepatorenal protection to APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms.


Assuntos
Acetaminofen/efeitos adversos , Acetaminofen/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonas/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Creatinina/sangue , Citocinas/metabolismo , Flavonas/uso terapêutico , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Ureia/sangue
14.
Gene ; 729: 144233, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759980

RESUMO

Collagen ß (1-O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via ß (1-O) linkages in collagen. However, the role of Glt25d1 in liver fibrogenesis is still unknow. Recently, we generated a Glt25d1 knockout mouse to elucidate the role of Glt25d1 in vivo. However, we found that complete deletion of the Glt25d1 gene resulted in embryonic lethality at E11.5. Histopathological analysis revealed that dysplasia in Glt25d1-/- labyrinth with defects of the vascular network. Immunohistochemical showed that the decrease in proliferation of Glt25d1-/- liver and the developing central nervous system (CNS). The role of Glt25d1 in liver fibrogenesis was explored by Glt25d1+/- mice. Glt25d1+/- mice and wild-type (WT) mice were injected intraperitoneally with the same dose of CCl4. The higher level of serum alanine aminotransferase was observed in Glt25d1+/- mice. Reverse transcription-quantitative polymerase chainreaction demonstrated that the mRNA expression levels of the inflammatory cytokines such as, Tnf-α, Cxcl-1 and Mcp-1, showed a significantly increase in CCl4-treated Glt25d1+/- mice. Collagen-I, collagen-III and α-SMA transcripts accumulation was markedly increased in the Glt25d1+/- mice. However, Masson's trichrome staining revealed a trend to decrease in the ECM proteins deposition of Glt25d1+/- liver. Immunohistochemistry and Western blots revealed that the protein expression of Collagen-III was reduced and a trend to a decrease in collagen-I was observed in the Glt25d1+/- liver compared with those of WT mice. Our results demonstrate that Glt25d1 knockout results in embryonic lethality and down-regulation of Glt25d1 may inhibit collagen secretion during liver fibrogenesis.


Assuntos
Colágeno/metabolismo , Galactosiltransferases/metabolismo , Cirrose Hepática/metabolismo , Alanina Transaminase/metabolismo , Animais , Colágeno/antagonistas & inibidores , Regulação para Baixo , Matriz Extracelular/metabolismo , Feminino , Galactosiltransferases/genética , Glicosilação , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Gravidez
15.
Chem Biol Interact ; 316: 108912, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31830458

RESUMO

The transmission of T-2 toxin and its metabolites into the edible tissues of poultry has potential effects on human health. The bile acid and xenobiotic system composes an intricate physiological network of chemoprotective and transporter-related functions, which ensures the detoxification and removal of harmful xenobiotic and endobiotic compounds from the body. This study revealed that cholic acid (CA), as one of the bile acids, promoted the metabolism of T-2 toxin in vivo by inducing the xenobiotic metabolism enzymes expression, thereby increasing the stress resistance and attenuating the oxidative stress. This study also indicated that dietary supplementation of 1% CA alleviated the mortality caused by T-2 toxin. Liver histology results demonstrated that CA supplementation significantly reduced inflammatory cell infiltration, sinusoidal expansion and congestion. Biochemistry results showed that the elevations of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and the increase in concentration of hydrogen peroxide (H2O2) in liver induced by the T-2 toxin were decreased by dietary supplementation of 1% CA. Additionally, CA supplementation led to the increase in superoxide dismutase (SOD) activity, but the decrease in catalase (CAT) activity in broiler chicken livers. Based on these findings, we propose that activation of FXR promotes T-2 toxin xenobiotic metabolism, and FXR plays a hepatoprotection role in liver injury induced by T-2 toxin.


Assuntos
Ácido Cólico/farmacologia , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Toxina T-2/toxicidade , Xenobióticos/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Catalase/metabolismo , Galinhas , Cromatografia Líquida de Alta Pressão , Peróxido de Hidrogênio/metabolismo , Inativação Metabólica , Fígado/efeitos dos fármacos , Fígado/patologia , Receptores Citoplasmáticos e Nucleares/agonistas , Superóxido Dismutase/metabolismo , Toxina T-2/sangue , Toxina T-2/metabolismo , Espectrometria de Massas em Tandem
16.
J Sci Food Agric ; 100(4): 1787-1796, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31849065

RESUMO

BACKGROUND: This study evaluated the effects of hydroalcoholic extract of spinach (HES) on nonalcoholic fatty liver disease (NAFLD). In the prevention phase, 18 Sprague-Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg kg-1 HES, or a chow diet for 7 weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg kg-1 HES, a chow diet, or chow diet plus 400 mg kg-1 HES for 4 weeks (n = 6). RESULTS: Weight gain (P = 0.01), food intake (P < 0.01), serum glucose (P = 0.01), triglyceride (TG) (P = 0.02), low-density lipoprotein cholesterol (LDL-c) (P = 0.01), aspartate aminotransferase (AST) (P = 0.02), liver steatosis, and the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) (P < 0.01) in the high-fat group were statistically higher than in the other groups at the end of the prevention phase. Feeding spinach extract to rats on a high-fat diet decreased serum glucose (P = 0.01), total cholesterol (TCh) (P < 0.01), AST (P = 0.01), alkaline phosphatase (ALP) (P < 0.01), and liver steatosis (P < 0.01) in the treatment phase. CONCLUSION: Overall, spinach extract showed beneficial effects in the prevention and treatment of NAFLD. © 2019 Society of Chemical Industry.


Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Spinacia oleracea/química , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
17.
Biosci Biotechnol Biochem ; 84(1): 171-177, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31476130

RESUMO

We tested the hypothesis that α-lactalbumin inhibits the disruption of intestinal barrier function and liver cirrhosis by restoring gut-liver axis function in thioacetamide (TAA) -treated rats. Rat diets were supplemented with α-lactalbumin replacing 50% of dietary protein. After consuming α-lactalbumin for one week, rats were intraperitoneally injected with TAA twice a week for 14 weeks. The α-lactalbumin-enriched diet significantly inhibited the elevation of plasma alanine aminotransferase, aspartate aminotransferase, and hyaluronic acids. The supplement significantly reduced plasma lipopolysaccharide levels and increased occludin mRNA level. Hepatic fibrosis and regenerative nodules was developed and intestinal villi were shortened by TAA; α-Lactalbumin attenuated these histopathological changes. These results indicated that α-lactalbumin improved intestinal barrier function, suppressing endotoxin levels. These data also suggested that α-lactalbumin ameliorated the impairment of the gut-liver axis by TAA, inhibiting the development of liver cirrhosis.


Assuntos
Suplementos Nutricionais , Trato Gastrointestinal/efeitos dos fármacos , Lactalbumina/uso terapêutico , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/dietoterapia , Fígado/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Tioacetamida/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Fibrose/tratamento farmacológico , Trato Gastrointestinal/metabolismo , Expressão Gênica/efeitos dos fármacos , Ácido Hialurônico/sangue , Injeções Intraperitoneais , Lipopolissacarídeos/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/prevenção & controle , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Tioacetamida/administração & dosagem , Proteínas de Junções Íntimas/genética
18.
PLoS Negl Trop Dis ; 13(12): e0007817, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31805088

RESUMO

BACKGROUND: Hepatic dysfunction and coagulopathy are common in acute dengue illness. We analyzed the trajectories of the above parameters in the survivors and fatal patients in the outbreak in Tainan, 2015. METHODS: A retrospective study was conducted using data from a tertiary hospital between January and December 2015. Multilevel modeling (MLM) was used to identify the changes in aminotransferase (AST), alanine aminotransferase (ALT), activated partial thromboplastin time (aPTT), and platelet counts from Day 0 to Day 7 of the onset of dengue infection. The machine-learning algorithm was used by purity measure assumption to calculate the accuracy of serum transaminases and coagulation variables to discriminate between the fatal and survival groups. RESULTS: There were 4,069 dengue patients, of which 0.9% died in one week after illness onset (i.e., early mortality). Case fatality rate was the highest for those aged ≥70 years. Both AST and ALT values of the fatal group were significantly higher than those of the survivor group from Day 3 (AST median, 624 U/L vs. 60 U/L, p < 0.001; ALT median, 116 U/L vs. 29 U/L, p = 0.01) of illness onset and peaked on Day 6 (AST median, 9805 U/L vs. 90 U/L, p < 0.001; ALT median, 1504 U/L vs. 49 U/L, p < 0.001). AST ≥ 203 U/L, ALT ≥ 55 U/L, AST2/ALT criteria ≥337.35, or AST/platelet count ratio index (APRI) ≥ 19.18 on Day 3 of dengue infection had a high true positive rate, 90%, 78%, 100%, or 100%, respectively, of early mortality. The platelet counts of the fatal group declined significantly than those of the survivor group since Day 3 of illness onset (median, 19 x103/µl vs. 91 x103/µl, p < 0.01), and aPTT values of the fatal group significantly prolonged longer since Day 5 (median, 68.7 seconds vs. 40.1 seconds, p < 0.001). CONCLUSIONS: AST, ALT, and platelet counts should be monitored closely from Day 0 to Day 3 of dengue infection, and aPTT be followed up on Day 5 of infection to identify the individuals at risk for early mortality.


Assuntos
Testes de Coagulação Sanguínea/métodos , Dengue/diagnóstico , Dengue/mortalidade , Testes de Função Hepática/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Criança , Pré-Escolar , Dengue/epidemiologia , Dengue/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taiwan/epidemiologia , Centros de Atenção Terciária , Adulto Jovem
19.
Int J Nanomedicine ; 14: 8943-8959, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819411

RESUMO

Objective: The study was designed to investigate the therapeutic potential of lactobionic acid (LA) conjugated quercetin (Q) loaded organically modified silica nanoparticles (LA-Q-ORMOSIL) with bulk quercetin to mitigate cyclophosphamide (CP) induced liver injury. Methodology: Q-ORMOSIL nanoparticles were synthesized and characterized using UV-Vis spectroscopy, TEM, Zeta sizer, FTIR and EDX. Further, encapsulation efficiency and in vitro release kinetic study was done. Q-ORMOSIL nanoparticles surface were modified with lactobionic acid, a ligand for the asialoglycoprotein receptor on the hepatocyte surface. The hepatoprotective effects of Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles were evaluated in vivo. Cyclophosphamide (20 mg/kg/day, i.p) was co-administered for seven days with bulk quercetin (50mg/kg/day) and quercetin nanoparticles (50µg/kg/day). After seven days, the number of biomarkers for liver function test and oxidative stress were determined in liver homogenate. Histopathological changes were also analyzed in control and treated liver tissues. Results: Physiochemical characterization of LA-Q-ORMOSIL nanoparticles depicts that the particles formed were of approx. 80 nm, spherical, monodispersed in nature and showed sustain drug release in in vitro study. Our results further suggested that Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles significantly decreased tissue TBARS, ROS levels and ALT, AST, and ALP activities compared to CP induced group. On the other hand, tissue antioxidant levels (GSH, GST, and catalase) showed a significant increase in LA-Q-ORMOSIL treated group compared to the CP treated group confirming its high therapeutic efficacy during liver injury. Conclusion: Targeted nanoquercetin demonstrated a significant hepatoprotective effect compared to bulk quercetin against CP-induced hepatotoxicity and it considerably reduced bulk quercetin dose level to many folds. Bulk quercetin has low bioavailability and thus, from obtained data we suggest that LA-Q-ORMOSIL nanoparticles provide high therapeutic value in protecting experimental animals against CP-induced liver injury. We also propose multifunctional dye-doped LA-modified ORMOSIL nanoparticles for future studies in facilitating nanoparticles uptake to hepatocytes for liver diagnosis and treatment.


Assuntos
Ciclofosfamida/efeitos adversos , Dissacarídeos/química , Fígado/patologia , Nanopartículas/química , Quercetina/farmacologia , Dióxido de Silício/química , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Liberação Controlada de Fármacos , Cinética , Fígado/efeitos dos fármacos , Masculino , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
20.
Acta Cir Bras ; 34(10): e201901003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851211

RESUMO

PURPOSE: To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury. METHODS: We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology. RESULTS: The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. CONCLUSIONS: This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.


Assuntos
Conexina 43/deficiência , Modelos Animais de Doenças , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/metabolismo , Alanina Transaminase/análise , Animais , Aspartato Aminotransferases/análise , Conexina 43/análise , Técnicas de Genotipagem , Fígado/patologia , Camundongos Knockout , Necrose , Reação em Cadeia da Polimerase , Valores de Referência , Traumatismo por Reperfusão/patologia , Fatores de Tempo , gama-Glutamiltransferase/análise
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