RESUMO
Objective: To investigate the influence of varied oxygen (O2) concentration environments on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMC) and the mechanism of pulmonary hypertension. Methods: Primary rat PASMC were isolated and cultured through the process of enzymatic digestion. Following identification, the stable passaged PASMC were subjected to a 6-hour incubation in sealed containers with normal O2 content (group C) and relative O2 content comprising 55% (group H55), 75% (group H75), and 95% (group H95). mRNA and protein expression of α-Actin (α-SMA), smooth muscle 22α (SM22α), osteopontin (OPN), and matrix metalloproteinase-2 (MMP-2) were measured using real-time quantitative PCR and western blot analysis. Results: The H55 group displayed no significant difference from the C group in terms of mRNA and relative protein expression levels for α-SMA, SM22α, OPN, and MMP-2 (all P>0.05). On the other hand, groups H75 and H95 exhibited a reduction in mRNA and relative protein expression of α-SMA and SM22α, along with an increase in mRNA and relative protein expression of OPN and MMP-2 when compared with both the C and H55 groups (all P<0.05). The H95 group showed a higher relative mRNA expression of MMP-2 as compared to the H75 group (P<0.05). Conclusions: Oxygen concentration environments of 75% or higher can serve as the foundation for the pathogenesis of pulmonary hypertension, essentially by inducing a phenotypic transformation in PASMC towards adopting a robust secretory function. This induction is contingent upon the concentration of oxygen present.
Assuntos
Hiperóxia , Hipertensão Pulmonar , Ratos , Animais , Artéria Pulmonar/patologia , Metaloproteinase 2 da Matriz/genética , Hiperóxia/metabolismo , Hiperóxia/patologia , Actinas/genética , Actinas/metabolismo , Miócitos de Músculo Liso/metabolismo , Oxigênio/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células CultivadasRESUMO
Portal vein thrombosis (PVT) refers to the thrombosis of the main portal vein and/or branches, with or without mesenteric vein and splenic vein thrombosis, and is the most common cause of extrahepatic portal vein obstruction. It is latent under chronic conditions and is often detected accidentally during physical examinations or liver cancer screenings. Notably, the understanding of PVT management is still limited, both at home and abroad. Therefore, the purpose of this article is to provide a reference for clinical diagnosis and treatment of PVT formation by summarizing the basis and standards for clinical diagnosis and treatment based on representative research with a large sample size and new perspectives with recent guidelines and consensus.
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Hepatopatias , Trombose , Trombose Venosa , Humanos , Veia Porta/patologia , Cirrose Hepática/patologia , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Trombose Venosa/terapia , Hepatopatias/patologia , Trombose/patologiaRESUMO
Objective: To investigate the feasibility of application of non-fasting dyslipidemia cutoff values in community population. Methods: Self-control study was used. 839 physical examinees (292 males and 547 females) were recruited in clinical laboratory of Guang'an men Hospital from January to October 2018. The median (interquartile range) of age was 60 (54, 66) years. Blood samples were collected before and at 4 h after a standard breakfast. Comparison of fasting and postprandial lipoprotein levels was performed using Paired-Samples T Test or Two-Related-Samples Wilcoxon. The changes of 4-hour postprandial blood lipid levels and the percentages of postprandial dyslipidemia according to different stratification of fasting dyslipidemia were performed using one-way ANOVA and χ2 test, respectively. Results: Compared with fasting, 4-hour postprandial total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) decreased slightly, postprandial triglyceride (TG) increased by 0.72 mmol/L, and postprandial remnant-like lipoprotein cholesterol (RLP-C) increased by 0.27 mmol/L (t or Z values = 10.26,22.94,24.22,4.71,16.61,26.92,-23.58,-19.35, P<0.05, respectively). According to the non-fasting dyslipidemia cut-off values recommended by the European consensus, there were 10%, 16.6%, 10.1%, 12.3%, 30% and 34.9% of the population in the appropriate levels of fasting TC, LDL-C, HDL-C, non-HDL-C, TG and RLP-C distributed in elevated levels of postprandial, respectively. The changes of 4-hour postprandial TC, LDL-C, non-HDL-C and HDL-C increased with the elevation of fasting level (F=9.50,6.18,8.07,3.86,P<0.01), and the maximum changes of TC≤3.5%, LDL-C≤6.8%, non-HDL-C≤2.9%, HDL-C≤6.3%; the change of 4-hour postprandial TG increased slightly first and then decreased significantly (51.3% vs. 57.9% vs. 39.2%, F=19.05, P<0.01); the change of 4-hour postprandial RLP-C decreased (50.8% vs. 33.2%, F=10.40, P<0.01). The cut-off values of 4-hour postprandial dyslipidemia were TC ≥5.1 mmol/L, LDL-C ≥3.2 mmol/L, HDL-C ≤0.9 mmol/L, non-HDL-C ≥4.0 mmol/L and RLP-C ≥1.0 mmol/L. The cut-off values of borderline elevated and elevated TG levels were ≥2.2 mmol/L and ≥3.4 mmol/L, respectively. Conclusions: The cut-off values of postprandial dyslipidemia including TC, LDL-C, HDL-C, non-HDL-C and RLP-C were preliminarily established in community population, which could be applied to the routine lipid profile evaluation in the physical examination population. And it might be needed that postprandial TG was managed hierarchically according to different cut-off values.
Assuntos
Jejum , Lipídeos , Pequim , HDL-Colesterol , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , TriglicerídeosRESUMO
Chronic liver diseases caused by a variety of causes can lead to the formation of liver fibrosis, and further develop into liver cirrhosis, which is a serious threat to human life and health. As a new research field, lipidomics has been developing vigorously in recent years and has shown great potential in the field of liver fibrosis research. This article introduces lipidomics technology, and discusses its pathogenesis, lipotoxicity biomarkers and emerging therapeutic targets, so as to provide a prospects for the future development of lipidomics in the field of liver fibrosis.
Assuntos
Lipidômica , Hepatopatias , Biomarcadores , Humanos , Metabolismo dos Lipídeos , Cirrose HepáticaRESUMO
Osteoporosis is a bone loss disease caused by the imbalance of osteoblast and osteoclast. It is a common complication of patients with liver cirrhosis, cholestatic liver disease, and liver transplantation. Over the past few decades, many researchs have raised the awareness of immune cell activation, chronic inflammation, intestinal microflora, etc. in liver cirrhosis and secondary osteoporosis. This article reviews the progress of the epidemiology, pathogenesis, diagnosis and treatment of liver cirrhosis and secondary osteoporosis.
Assuntos
Doenças Ósseas Metabólicas , Colestase , Transplante de Fígado , Osteoporose , Humanos , Cirrose Hepática/complicações , Osteoporose/epidemiologia , Osteoporose/etiologiaRESUMO
Objective: This study aims to investigate the expression of E3 ubiquitin-ligase (WWP1) in chronic lymphocytic leukemia (CLL) patients and analyze its correlation with clinical prognostic indicators (TP53, CD38, IGHV mutation) and its prognostic value. Methods: A total of 48 CLL patients and 9 age-matched normal subjects were enrolled in the study. The WWP1 expression was detected by SYBR Green-based real-time PCR, and the clinical relationship was analyzed by GraphPad Prism software. Results: The WWP1 median expression was 0.007 (95% CI 0.005-0.010) in the normal control group and 0.031 (95% CI 0.019-0.044) in the CLL group (P<0.001) . A sub-groups analysis implicated a statistically significant result (P=0.022) , showing that the median time from a relatively high and low transcription level of WWP1 to the first treatment was 24 months and 35 months, respectively. Positive CD38 and ZAP-70 expressions were associated with a higher WWP1 expression (P=0.012 and 0.029, respectively) . Conclusion: An abnormal WWP1 mRNA expression was found in CLL patients with significant correlation with ZAP-70 and CD38 expressions, and WWP1 may become a new supplement of CLL prognostic markers.
Assuntos
Leucemia Linfocítica Crônica de Células B , Ubiquitina-Proteína Ligases/genética , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Ubiquitina-Proteína Ligases/metabolismoRESUMO
This study aimed to compare the efficacy and safety of the EC-T (4 cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 75 mg/m2) and TCb (6 cycles of docetaxel 75 mg/m2, intravenous drip (ID), day 1 + carboplatin AUC 6, ID, day 1) neoadjuvant regimens in patients with TOP2A-normal stage II-III breast cancer. This study analyzed 280 patients enrolled from three studies registered with ClinicalTrials.gov (NCT03140553, NCT03154749, NCT03507465) with early TOP2A-normal stage II-III breast cancer who received neoadjuvant chemotherapy, including 100 patients who received the EC-T regimen and 180 patients who received the TCb regimen. The primary endpoint was the ratio of RCB 0/1 (residual cancer burden 0/1) after neoadjuvant chemotherapy. The secondary endpoint was the safety of the two groups. There was no significant difference in the ratio of RCB 0/1 between the two groups (23% vs. 23.9%, p=0.614). Among the triple-negative breast cancer patients, the efficacy did not differ between the two groups (40% vs. 32%, p=0.52). Among the lymph node metastasis patients, the efficacy of the EC-T group was significantly better than that of the TCb group (14% vs. 2.6%, p=0.03). Regarding the side effects, the incidence of grade 3/4 anemia was higher in the EC-T group than in the TCb group (21.0% vs. 8.33%, p=0.002), while the incidence of grade 3/4 neutropenia was higher in the EC-T group than in the TCb group (17% vs. 14.44%, p=0.570), and the incidence of grade 3/4 thrombocytopenia was low in each group (EC-T group: 6 % and TCb group: 7.22%, p=0.697). In the EC-T group, grade 3/4 nausea and vomiting occurred in 5 patients. The EC-T group showed a higher rate of grade 3/4 myalgia than the TCb group (7% and 4.44%, respectively, p=0.363). To conclude, the TCb regimen can be used as an alternative regimen for TOP2A-normal stage II-III breast cancer patients in neoadjuvant chemotherapy. However, in patients with node-positive tumors, EC-T is still recommended. Though no difference of grade 3/4 thrombocytopenia in two groups, grade 4 thrombocytopenia caused by the carboplatin-containing regimen should be taken seriously.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carboplatina/uso terapêutico , Quimioterapia Adjuvante , Ciclofosfamida/uso terapêutico , Docetaxel/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Humanos , Estadiamento de Neoplasias , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the mechanism microRNA-378 in smoking-induced airway inflammation and mucus hypersecretion. MATERIALS AND METHODS: Human bronchial epithelial (HBE) cells were treated with cigarette smoke extract (CSE) to construct the in vitro COPD model. Expression levels of microRNA-378, inflammatory factors and MUC5AC in CSE-treated HBE cells were determined by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and enzyme-linked immunosorbent assay (ELISA). The regulatory effects of microRNA-378 on expressions of inflammatory factors and mucin 5AC (MUC5AC) were observed in CSE-treated HBE cells overexpressing microRNA-378. We verified whether tumor necrosis factor-α (TNF-α) was the target gene of microRNA-378 through dual-luciferase reporter gene assay. Expression levels of TNF-α and p-p65 in CSE-treated HBE cells were examined. Finally, CSE-treated HBE cells were co-overexpressed with microRNA-378 and TNF-α to elucidate whether microRNA-378 exerted its function in regulating the development of COPD through targeting TNF-α. RESULTS: CSE treatment downregulated microRNA-378 expression, but upregulated expressions of inflammatory factors and MUC5AC in HBE cells. MicroRNA-378 overexpression markedly inhibited the elevated levels of inflammatory factors and MUC5AC in CSE-treated HBE cells. Dual-luciferase reporter gene assay verified that TNF-α was the target gene of microRNA-378. Moreover, TNF-α expression in CSE-treated HBE cells was time-dependently elevated. TNF-α overexpression partially reversed the decreased levels of inflammatory factors and MUC5AC in HBE cells overexpressing microRNA-378. CONCLUSIONS: MicroRNA-378 inhibits the inflammatory response by targeting TNF-α, which may be a potential therapeutic target for COPD.
Assuntos
Brônquios/citologia , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/genética , Fumar Tabaco/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Brônquios/efeitos dos fármacos , Brônquios/imunologia , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Regulação da Expressão Gênica , Humanos , Modelos Biológicos , Doença Pulmonar Obstrutiva Crônica/imunologia , Transdução de Sinais , Fumar Tabaco/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: MiR-155-5p has various biological cellular functions in diverse pathology, including cardiovascular disease. Nevertheless, the role of miR-155-5p in atherosclerosis is still not well known. PATIENTS AND METHODS: The levels of miR-155-5p and AKT Serine/Threonine Kinase 1 (AKT1) in plasma samples from patients with atherosclerotic CAD were detected using quantitative Real-time PCR (qRT-PCR). Cell counting kit-8 (CCK-8) assay was used to analyze the proliferation of vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) in vitro. The migration of VSMCs and HUVECs was detected using wound healing assay. The invasion of VSMCs and HUVECs using was determined using the transwell invasion assay. The expression of AKT1 was measured using immunofluorescence staining analysis. RESULTS: MiR-155-5p was down-regulated in patients with atherosclerotic CAD. Up-regulation of miR-155-5p inhibited the proliferation, migration and invasion of VSMCs and HUVECs. Bioinformatics analysis and luciferase reporter assay indicated that AKT1 was the direct target of miR-155-5p and miR-155-5p bound to the 3'-untranslated region (3'-UTR) of AKT1. The expression of AKT1 was reduced in cell that was transfected with miR-155-5p. Up-regulation of AKT1 rescued the suppressive effect of miR-155-5p on the growth, migration and invasion of VSMCs and HUVECs. Down-expression of AKT1 partially neutralized the impacts of miR-155-5p on the growth, invasion and migration of VSMCs and HUVECs. Finally, we found that AKT1 was over-regulated in plasma samples of patients with atherosclerotic CAD and its level was negative with the level of miR-155-5p. CONCLUSIONS: Our study demonstrates that miR-155-5p suppresses the proliferation, migration and invasion of VSMCs and HUVECs through regulating AKT1, which provides the new insights into the precise role of miR-155-5p in atherosclerosis.
Assuntos
Aterosclerose/complicações , Doença da Artéria Coronariana/genética , Células Endoteliais da Veia Umbilical Humana/citologia , MicroRNAs/genética , Músculo Liso Vascular/citologia , Proteínas Proto-Oncogênicas c-akt/genética , Regiões 3' não Traduzidas , Aterosclerose/genética , Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Células Cultivadas , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated disease that share common pathologic, serologic and clinical features. IgG4- RD may include inflammatory pseudotumor, IgG4-related autoimmune hepatitis, and type 1 autoimmune pancreatitis mainly involving liver and clinically classified into three types. IgG4-related sclerosing cholangitis is a rare disease. It is frequently present in association with type 1 autoimmune pancreatitis, so it needs to be distinguishing from primary sclerosing cholangitis.
Assuntos
Colangite Esclerosante/diagnóstico , Imunoglobulina G/sangue , Pancreatite/diagnóstico , Doenças Autoimunes , Colangite Esclerosante/sangue , Diagnóstico Diferencial , Hepatite Autoimune , Humanos , Pancreatite/sangueRESUMO
Objective: To determine the frequency and extent of left ventricular amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction (HFpEF). Methods: A total of 43 patients aged 85 to 100 years old were enrolled in this study based on the autopsy database of Beijing Hospital from February 1, 2003 to October 31, 2016. The frequency and extent of left ventricular amyloid deposition and myocardial fibrosis were determined in left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n=28) and from control subjects (n=15) post Congo red staining and Masson's trichrome staining. Kappa test was used to evaluate the consistency of the myocardial amyloidosis and fibrosis. Results: The heart weight of the patients in HFpEF group and in control group were similar((452.7±107.7)g vs. (415.0±70.8)g, t=-1.218, P=0.23)). Positive Congo-red staining was found in 24 examples (24/28) in HFpEF group and 5 examples (5/15) in the control group; severe amyloid deposition was found in 7 examples (7/28) in HFpEF group, but not in the control group. Amyloid deposition was more severe in HFpEF group than in control group (χ(2)=12.205, P<0.01). Masson's trichrome staining evidenced moderate to severe fibrosis in 19 cases (19/28) in HFpEF group and 8 cases (8/15) in control group (χ(2)=1.019, P=0.35). A consistent evaluation of the degree of myocardial fibrosis and the degree of myocardial amyloid deposition in all selected participants was performed and results showed that these two parameters were not consistent (Kappa value=0.2, P=0.820). Conclusion: Amyloid deposition is common in the elderly patients with heart failure and preserved ejection fraction, suggesting that myocardial amyloidosis may be related to the development of HFpEF. There is no significant correlation between myocardial amyloidosis and myocardial fibrosis in this cohort.
Assuntos
Amiloide/metabolismo , Insuficiência Cardíaca , Ventrículos do Coração , Miocárdio , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias , Ventrículos do Coração/metabolismo , Humanos , Miocárdio/metabolismo , Volume SistólicoRESUMO
Hepatic fibrosis is a common pathological process in the development of various chronic liver diseases into liver cirrhosis. Based on current research findings, it is widely believed that the process of hepatic fibrosis is reversible, and effective treatment cannot only delay the development of hepatic fibrosis into liver cirrhosis, but also alleviate the degree of hepatic fibrosis. Therefore, the research on the treatment of hepatic fibrosis is of great clinical significance. The article reviews the recent research advances in the treatment of hepatic fibrosis.
Assuntos
Cirrose Hepática/terapia , Hepatopatias , Progressão da Doença , Humanos , Cirrose Hepática/patologiaRESUMO
Esophageal and gastric varices are common complications of liver cirrhosis and are seen in 50% of patients with liver cirrhosis. The annual incidence rate of esophagogastric variceal bleeding is 5%-15%, and even if the recommended treatment is used, the 6-week mortality rate is still as high as 15%-20%. Spontaneous bacterial peritonitis (SBP) is a common complication of end-stage liver disease and has an incidence rate of 10%-30% in patients with severe liver damage. SBP refers to the bacterial infection of the peritoneum and/or ascites that occurs in the absence of any inflammation in adjacent tissues (e.g., intestinal perforation and intestinal abscess). Hepatic encephalopathy (HE) is the clinical syndrome manifesting as cognitive impairment in patients with chronic liver disease, and its pathogenesis has not yet been fully elucidated and may be associated with ammonia poisoning theory, γ-aminobutyric acid and endogenous benzodiazepine complex receptor theory, and inflammatory pathway theory. This article introduces the advances in the treatment of upper gastrointestinal bleeding in patients with liver cirrhosis, SBP, and HE in 2016.
Assuntos
Varizes Esofágicas e Gástricas/complicações , Encefalopatia Hepática/complicações , Cirrose Hepática/complicações , Ascite/complicações , Infecções Bacterianas/complicações , Hemorragia Gastrointestinal/etiologia , Humanos , Peritonite/complicaçõesRESUMO
Objective:To evaluate the accuracy of Xpert MTB/RIF assay in the diagnosis of cervical tuberculous lymphadenitis.Method:A total of 160 patients with cervical lymph node tuberculosis confirmed by pathology in Wuhan Pulmonary Hospital between January 2015 and June 2016 were enrolled. Cervical lymph node biopsy tissue specimens from these patients were collected and tested with acid-fast bacilli smear, TB-DNA assays, culture, and Xpert Mtb/RIF, respectively. The results were analyzed using SPSS 17.0 statistical software.Result:Using pathological diagnosis as the standard, the sensitivity of acid-fast bacilli smear was 8.12%(13/160), the sensitivity of TB-DNA assay was 69.38%(111/160), the sensitivity of culture was 31.88%(51/160), and the sensitivity of Xpert Mtb/RIF was 74.38%(119/160). The detection rate of multidrug-resistant lymphoid tuberculosis using a combination of Xpert Mtb/RIF, line probe assay (LPA), and culture methods was 9.38%(15/160).Conclusion:Xpert Mtb/RIF can rapidly detect cervical lymph node tuberculosis and assess rifampicin resistance. TB-DNA assay exhibited similar sensitivity as compared to Xpert Mtb/RIF and can detect both isoniazid and rifampicin resistant genes through LPA.These two methods are more effective than the traditional culture and smear methods.
Assuntos
Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Escarro/microbiologia , Tuberculose dos Linfonodos/microbiologia , Tuberculose dos Linfonodos/patologia , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Biópsia por Agulha Fina , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNA/métodosRESUMO
OBJECTIVE: To explore the effect of inherent depression on chronic visceral hypersensitivity. The differences of visceral sensitivity, colitis, and brain activation between Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were identified after neonatal colon acetate stimulation. METHODS: The specific pathogen free Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were used to establish irritable bowel syndrome (IBS) model. The visceral sensitivity was measured by colorectal distension (CRD). The expression of 5-hydroxytryptamine (5-HT), mast cell (MC), indoleamine 2,3-dioxygenase (IDO) in colon and IDO in specific cerebral regions were detected through immunohistochemistry. RESULTS: Abdominal withdrawal reflex (AWR) scores showed that visceral sensitivity of acetate-enema groups was significantly higher than that of saline-enema groups (FH/Wjd:2.44 ± 0.04 vs.1.96 ± 0.07, P < 0.05; SD: 1.75 ± 0.13 vs.1.32 ± 0.05, P < 0.05). Furthermore, FH/Wjd rats of IBS group scored significantly higher than SD rats of IBS group (2.44 ± 0.04 vs.1.75 ± 0.13, P < 0.05). The MC amounts of both SD and FH/Wjd IBS group rats were significantly more than those of their control groups (FH/Wjd:43.24 ± 1.72 vs. 24.92 ± 1.38, P < 0.01. SD: 23.80 ± 1.28 vs. 14.24 ± 0.92, P < 0.01). Besides, the MC amounts of control and IBS group of FH/Wjd rats were significantly more than that of SD IBS group rats (P < 0.01). The IDO and 5-HT positive cells in colonic mucosa of IBS group of both SD and FH/Wjd rats were significantly more than those of their control groups, respectively(P < 0.01). The IDO, 5-HT positive cells in colonic mucosa of both control and IBS group of FH/Wjd rats were significantly more than those of both control and IBS group of SD rats (control:IDO,24.64 ± 2.22 vs. 15.52 ± 1.39;5-HT,21.32 ± 1.26 vs. 12.72 ± 1.12. IBS: IDO,44.92 ± 2.31 vs. 20.85 ± 1.72; 5-HT, 31.84 ± 1.57 vs. 19.65 ± 1.09.P <0.01). The expression of IDO in prelimbic cortex (PrL) areas of FH/Wjd IBS rats was significantly higher than that of IBS group of SD rats (49.60 ± 4.31 vs. 35.60 ± 2.42, P <0.01), and the expression of IDO in rostral anterior cingulate cortex (rACC) areas of FH/Wjd IBS rats was significantly more than that of FH/Wjd control rats (45.44 ± 1.16 vs. 34.08 ± 2.76, P <0.01). CONCLUSION: Inherent depressive FH/Wjd rats were more sensitive to neonatal colon acetate stimulation, presenting as visceral hypersensitivity which maybe associated with increased MC amounts and over-expression of 5-HT and IDO in colon, suggesting that depression disorder may aggravate functional disturbance of gastrointestinal tract by regulating the response to inflammatory stimulation.
Assuntos
Depressão/fisiopatologia , Hipersensibilidade/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Acetatos , Animais , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Síndrome do Intestino Irritável/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismoRESUMO
Serum liver enzyme levels are often used effectively for the evaluation of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the associations between serum liver enzyme levels and risks for NAFLD in over 8000 cases in a large-scale analysis. A cross-sectional survey with multiple stages and random samplings was performed from May 2007 to May 2009 on 8102 workers at Tongji University. A questionnaire was given, assessments of physical measurements, plasma glucose, lipid profiles, and liver enzymes were made, and real-time liver ultrasounds conducted. The prevalence of NAFLD in Tongji University was 22.2%. It was higher in males than in females (P = 0.0023). The body mass index, waist-to-hip ratio, serum total triglycerides, serum total cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) values were all higher in the NAFLD group than in the control group. For moderate and severe NAFLD patients, the ALT, AST and GGT values were significantly increased, high density lipoprotein cholesterol was decreased, and drinking much, heavy entertainment and less exercise were more prevalent (P < 0.001). There were strong correlations between serum liver enzyme levels and NAFLD (P < 0.001), with GGT being a more sensitive marker for NAFLD than ALT or AST. ALT and GGT were independent predictors for NAFLD, and GGT was a better predictor than ALT for NAFLD.
Assuntos
Fígado/enzimologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Testes de Função Hepática , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
This study was designed to show whether rat liver epithelial cells could undergo epithelial-mesenchymal transition (EMT), thereby directly contributing to liver fibrosis. The role of the ratio of transforming growth factor-ß1 (TGF-ß1)/bone morphogenetic protein-7 (BMP-7) was evaluated in the progression of EMT or mesenchymal-epithelial transition. Primary rat liver epithelial cells were stimulated with different ratios of TGF-ß1/BMP-7 and examined for evidence of transition to a mesenchymal or epithelial phenotype. Liver sections were labeled to detect antigens associated with liver epithelial cells [E-cadherin (E-cad)], EMT [fibroblast-specific protein-1 (FSP-1), vimentin], myofibroblasts [α-smooth muscle actin (α-SMA)], and intracellular signal-transduction mediated by forming liver fibrosis undergo EMT, resulting in the formation of invasive fibroblasts; this process may be driven or impeded by a response to local TGF-ß1 or BMP-7. BMP-7 downregulated α-SMA and phosphorylated Smad2/3. Stimulation of cultured cells with TGF-ß1 induced the expression of pSmad2/3, FSP-1, and α-SMA. Stimulation of cultured cells with BMP-7 induced the expression of E-cad. We demonstrated that the cells upregulated E-cad release compared with untreated cells, but TGF-ß1 was different. We found that the equilibrium of the ratio of TGF-ß1/BMP-7 was 1/10. In summary, the mechanism for this process was not determined. Demonstration of the contribution of what the ratio of TGF-ß1/BMP-7 induced to EMT to the chronic liver diseases would provide a new basis for understanding pathogenesis and potential treatment.
Assuntos
Proteína Morfogenética Óssea 7/metabolismo , Transição Epitelial-Mesenquimal , Fígado/patologia , Fator de Crescimento Transformador beta1/metabolismo , Actinas/metabolismo , Animais , Caderinas/genética , Caderinas/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Fibrose , Regulação da Expressão Gênica , Fígado/metabolismo , RatosRESUMO
To investigate the variance of exogenous gene expression driven by different promoters by in vivo electroporation, 3 plasmid vectors carrying different promoters were selected, and their driving strength was compared in developing chicken embryos. The 3 promoters included: 1) the CAG promoter (containing the cytomegalovirus (CMV) immediate early enhancer and the chicken ß-actin promoter), 2) the CMV promoter (the human CMV immediate early region enhancer), and 3) the SV40 promoter (Simian virus 40). The intensity of GFP expression driven by the 3 promoters was detected by fluorescence microscopy. The results clearly showed that the expression intensity of the reporter gene differed significantly among the 3 promoters. Chicken ß-actin promoter induced the highest intensity of GFP expression, while SV40 promoter induced the lowest intensity. Our results indicate that plasmids with appropriate promoters should be carefully selected to obtain strong exogenous gene expression by in vivo electroporation.