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OBJECTIVE: The objectives of this study are to analyze the association between anti-mitochondrial antibody (AMA) and cardiac involvement in idiopathic inflammatory myopathy (IIM) and to evaluate the diagnostic value of AMA for cardiac involvement in IIM patients. METHODS: We conducted a comprehensive search in PubMed, Web of Science, EMBASE, and the Cochrane Library to identify English-language studies published before November 19, 2021. Stata 12.0 software (Stata Corp., College Station, TX, USA) was used for the statistical analyses. We used the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curve to evaluate the diagnostic value of AMA for cardiac involvement in IIM patients. Statistical heterogeneity of studies was assessed using the I2 statistic with 95% confidence intervals (95% CIs). RESULTS: Seven studies were included in the final analyses, with a total of 2308 IIM patients (including 171 AMA-positive and 2137 AMA-negative patients). The pooled sensitivity of AMA for cardiac involvement in IIM patients was 0.29 (95% CI: 0.19-0.43) and specificity was 0.92 (95% CI: 0.88-0.96). The pooled PLR was 3.9 (95% CI: 2.82-5.38), NLR was 0.76 (95% CI: 0.66-0.88), and the diagnostic odds ratio (DOR) was 5 (95% CI: 3-7). The area under the SROC curve was 0.76 (95% CI: 0.72-0.79). CONCLUSION: The overall diagnostic value of AMA may not be very high for cardiac involvement in IIM patients.
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Context: Apigenin displays antioxidant and anti-inflammatory effects. However, effects of apigenin magnesium (AM) complex on these aspects remain unknown.Objective: This study investigated the effects of AM complex on oxidative stress and inflammatory responses in hydrogen peroxide (H2O2)-induced rat hepatic stellate cells (HSCs).Materials and methods: The antioxidant and anti-inflammatory effects of AM complex at concentrations of 0.625, 1.25, and 2.5 mg/mL were evaluated, comparing to HSCs treated by H2O2 alone. Cell viability, reactive oxygen species (ROS), the activity of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), interleukin 6 (IL-6), and nuclear factor-kappa B (NF-κB) levels were measured. Moreover, cell apoptosis, mRNA expression levels of transforming growth factor-ß (TGF-ß), NF-κB, and inducible nitric oxide synthase (iNOS) were assessed.Results: AM complex significantly inhibited oxidative stress and inflammatory response at concentrations of 0.625, 1.25, and 2.5 mg/mL (IC50 = 1.679 mg/mL). AM complex elevated the survival rate of H2O2-treated HSCs and had no toxic effects on HSCs. AM complex also promoted SOD activity and GSH levels but suppressed ROS, MDA, and NO levels. Additionally, AM complex decreased IL-6 and NF-κB levels, gene expression of TGF-ß, NF-κB, and iNOS, as well as induced apoptosis of HSCs.Discussion and conclusions: Data indicated that AM complex mitigated oxidative stress and inflammatory responses on H2O2-treated HSCs, suggesting that AM complex is a possible candidate for anti-hepatic diseases. Additional efforts, both in vivo and in humans, are required to assess of AM complex as a potential therapeutic drug in liver diseases.
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Apigenina/administração & dosagem , Células Estreladas do Fígado/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Mediadores da Inflamação/antagonistas & inibidores , Magnésio/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células Estreladas do Fígado/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Oxidantes/toxicidade , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50 ] values, HepG2: 2.98 ± 1.11 µM and WSU-DLCL2: 4.34 ± 0.84 µM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 µM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing.
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Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Células Hep G2 , Humanos , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Piridinas/síntese química , Piridinas/química , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
In this study, a series of novel pyridine and pyrimidine-containing derivatives were designed, synthesized and biologically evaluated for their c-Met inhibitory activities. In the biological evaluation, half of the target compounds exhibited moderate to potent c-Met inhibitory activities. Among which, it is noteworthy that compounds 13d not only showed most potent c-Met inhibitory potency but also displayed excellent anti-proliferative activity (IC50=127nM against EBC-1 cell line) as well as an acceptable kinase selectivity profile. Moreover, the western blot assay indicated that 13d inhibited c-Met phosphorylation in EBC-1 cells in a dose-dependent manner, with complete abolishment at 0.1mM. All these experimental results suggested that 13d could be served as a promising lead compound for the development of anticancer agents.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Piridinas/química , Piridinas/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismoRESUMO
OBJECTIVE: To investigate the effect of apigenin on the protein expression levels of peroxisome proliferator-activated receptors (PPARs) in liver tissues of rats with nonalcoholic steatohepatitis (NASH). METHODS: The NASH rat model was established by feeding of a high-fat diet. Unmodeled rats served as the normal controls. The modeled rats were divided into a model control group, Essentiale treatment grouP(300 mg/kg/day),and three apigenin treatment groups for low-dose (15 mg/kg/day), moderate-dose (30 mg/kg/day) and high-dose (60 mg/kg/day). After 13 weeks of treatment,changes in insulin sensitivity from pre-treatment baseline were assessed by measuring the alanine aminotransferase (ALT), aspartate aminotransferase (AST),total cholesterol (TC),triglycerides (TG),low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C),fasting blood glucose (FBG) and fasting insulin (FINS).The liver index and HOMA-IR were also calculated.Protein and gene expression of PPARα and PPARgamma in liver tissue were assessed by immunohistochemistry and RT-PCR.Statistical analysis was performed by the LSD test and Games-Howell test. RESULTS: The apigenin-treated groups showed a significantly greater change in insulin sensitivity than the untreated model group,with the most significant change occurring in the high-dose grouP(P less than 0.05).Compared with the untreated model group,the apigenin-treated groups showed lower levels of ALT (95.4+/-7.3),AST (183.7+/-14.3),TC (1.61+/-0.25),TG (1.23+/-0.21),LDL-C (1.86+/-0.14),FBG (5.29+/-1.45) and FINS (0.76+/-0.86),but a higher level of HDL-C (1.04+/-0.17); again,the high-dose group showed the greatest change (all P less than 0.05).Compared to the untreated model group,the apigenin-treated groups showed significantly lower liver index (3.75+/-0.25 vs.2.90+/-0.17) and HOMA-IR (1.34+/-0.06 vs.0.18+/-0.04),with the high-dose group showing the greatest change (both P less than 0.05). Compared to the untreated model group,the apigenin-treated groups showed higher levels of protein and mRNA of PPARα (18.27+/-4.05 and 0.63+/-0.02,respectively) and PPARgamma(8.48+/-5.05 and 0.39+/-0.02),with the high-dose group showing the greatest change (all P < 0.05). CONCLUSION: Apigenin can improve glucose tolerance,lipid metabolism and insulin resistance while decreasing blood levels of TC,TG,LDL-C,FBG,FINS and HOMA-IR,and increasing HDL-C in NASH,as shown in a high-fat diet induced rat model, and may have therapeutic potential.
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Apigenina/farmacologia , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Insulina/metabolismo , Metabolismo dos Lipídeos , Fígado/enzimologia , PPAR alfa/metabolismo , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismoRESUMO
This study aims to investigate the preparation process and in vitro release behavior of artesunate polylactic acid microspheres, in order to prepare an artesunate polylactic acid (PLA) administration method suitable for hepatic arterial embolization. With PLA as the material and polyvinyl alcohol (PVA) as the emulsifier, O/W emulsion/solvent evaporation method was adopted to prepare artesunate polylactic acid microspheres, and optimize the preparation process. With drug loading capacity, encapsulation efficiency and particle size as indexes, a single factor analysis was made on PLA concentration, PVA concentration, drug loading ratio and stirring velocity. Through an orthogonal experiment, the optimal processing conditions were determined as follows: PLA concentration was 9. 0% , PVA concentration was 0. 9% , drug loading ratio was 1:2 and stirring velocity was 1 000 r x min(-1). According to the verification of the optimal process, microsphere size, drug loading and entrapment rate of artesunate polylactic acid microspheres were (101.7 +/- 0.37) microm, (30.8 +/- 0.84)%, (53.6 +/- 0.62)%, respectively. The results showed that the optimal process was so reasonable and stable that it could lay foundation for further studies.
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Artemisininas/química , Composição de Medicamentos/métodos , Ácido Láctico/química , Microesferas , Polímeros/química , Artesunato , Calibragem , Poliésteres , Álcool de Polivinil/químicaRESUMO
BACKGROUND: Frail patients with atrial fibrillation (AF) are thought to be at a higher risk for cerebral infarction and death than patients who are not frail, making preventive interventions important. Anticoagulants should be used in frailty patients with AF. However, there are limited data about anticoagulants in frail patients with AF. Therefore, we concucted this meta-analysis to find the best anticoagulation strategy. METHODS: Systematic electronic searches were conducted on 4 July 2022 4 July 2022, in PubMed, Embase (Ovid), and Cochrane Library. Relevant and eligible cohort studies were included. A random-effects model was used to estimate the pooled Hazard ratio (HR) and 95% confidence intervals (CI). Furthermore, we performed a publication bias analysis and subgroup analysis to explore the source of heterogeneity. RESULT: 3 publications (10 cohorts, 188573 participants) met our inclusion criteria. The pooled analysis showed that ischemic strokes (HR: 0.75; 95%CI: 0.71 to 0.79; I2 = 60.2%), systemic embolism (HR: 0.75; 95%CI: 0.64 to 0.87; I = 68.6%), major bleeding(HR: 0.76; 95%CI: 0.64 to 0.89; I2 = 97.4%), intracranial hemorrhage (HR: 0.57; 95%CI: 0.45 to 0.71; I2 = 54.6%) and cardiovascular death(HR: 0.61; 95%CI: 0.51 to 0.70; I2 = 83.2%) were lower in NOACs as compared with warfarin. Regarding gastrointestinal bleeding, meta-analysis showed no significant differences in the risk of gastrointestinal bleeding (HR: 0.97; 95%CI: 0.69 to 1.36; I2 = 95.9%). . CONCLUSION: NOAC was more effective and safety than warfarin in frail patients with AF.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Idoso , Varfarina/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Idoso Fragilizado , Administração Oral , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/tratamento farmacológicoRESUMO
The neutrophil-lymphocyte ratio(NLR) has been used for diagnosing venous thromboembolism (VTE). We aimed to assess the accuracy of NLR to diagnose VTE by meta-analysis. Systematic electronic searches were conducted June 2, 2021 in PubMed, Embase(Ovid), and Cochrane Library. The search did not have any language or time restriction applied. Our search strategy was based on keywords in combination with both medical subject headings (MeSH) terms and text words. The diagnostic odds ratio, summary receiver operating characteristics, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were estimated. 10 articles with 1513 VTE participants and 2593 control participants were included for quantitative synthesis. The pooled values were as follows: sensitivity = 0.68(95% CI 0.45-0.84), specificity = 0.73(95% CI 0.6-0.83), positive likelihood ratio = 2.5(95% CI 1.8-3.4), negative likelihood ratio = 0.44(95% CI 0.26-0.75), diagnostic odds ratio = 6(95% CI 3-11), and SROC = 0.76(95% CI: 0.73-0.8). NLR could be diagnostic factor for the detection of potential VTE, the accuracy thereof in the current meta-analysis exhibited moderate accuracy for diagnosing VTE. Furthermore, further large cohort studies are needed to determine optimal cut-off values of NLR.
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Tromboembolia Venosa , Humanos , Linfócitos , Neutrófilos , Razão de Chances , Curva ROC , Tromboembolia Venosa/diagnósticoRESUMO
A case who revealed the longest duration of viral shedding (67 days) in current reports, presented complicated characteristic on the relapse of COVID-19 due to the inconsistent performance of chest radiography and SARS-CoV-2-RNA detection after discharge. Lopinavir-interferon α2b boosted ribavirin following with lopinavir boosted budesonide might be a potent treatment for viral clearance.
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COVID-19/virologia , SARS-CoV-2/fisiologia , Assistência ao Convalescente , COVID-19/diagnóstico por imagem , COVID-19/fisiopatologia , Feminino , Hospitalização , Humanos , Lopinavir/uso terapêutico , Pessoa de Meia-Idade , Alta do Paciente , RNA Viral/genética , RNA Viral/isolamento & purificação , Recidiva , Ribavirina/uso terapêutico , SARS-CoV-2/genética , Tórax/diagnóstico por imagem , Eliminação de Partículas Virais/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
Backgroud: The outbreak of COVID-19 has brought unprecedented perils to human health and raised public health concerns in more than two hundred countries. Safe and effective treatment scheme is needed urgently. Objective: To evaluate the effects of integratedTCM and western medicine treatment scheme on COVID-19. Methods: A single-armed clinical trial was carried out in Hangzhou Xixi Hospital, an affiliated hospital with Zhejiang Chinese Medical University. 102 confirmed cases were screened out from 725 suspected cases and 93 of them were treated with integrated TCM and western medicine treatment scheme. Results: 83 cases were cured, 5 cases deteriorated, and 5 cases withdrew from the study. No deaths were reported. The mean relief time of fever, cough, diarrhea, and fatigue were (4.78 ± 4.61) days, (7.22 ± 4.99) days, (5.28 ± 3.39) days, and (5.28 ± 3.39) days, respectively. It took (14.84 ± 5.50) days for SARS-CoV-2 by nucleic acid amplification-based testing to turn negative. Multivariable cox regression analysis revealed that age, BMI, PISCT, BPC, AST, CK, BS, and UPRO were independent risk factors for COVID-19 treatment. Conclusion: Our study suggested that integrated TCM and western medicine treatment scheme was effective for COVID-19.
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With the continued transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world, identification of highly suspected COVID-19 patients remains an urgent priority. In this study, we developed and validated COVID-19 risk scores to identify patients with COVID-19. In this study, for patient-wise analysis, three signatures, including the risk score using radiomic features only, the risk score using clinical factors only, and the risk score combining radiomic features and clinical variables, show an excellent performance in differentiating COVID-19 from other viral-induced pneumonias in the validation set. For lesion-wise analysis, the risk score using three radiomic features only also achieved an excellent AUC value. In contrast, the performance of 130 radiologists based on the chest CT images alone without the clinical characteristics included was moderate as compared to the risk scores developed. The risk scores depicting the correlation of CT radiomics and clinical factors with COVID-19 could be used to accurately identify patients with COVID-19, which would have clinically translatable diagnostic and therapeutic implications from a precision medicine perspective.
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COVID-19/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , SARS-CoV-2/isolamento & purificação , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. RESULTS: Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. CONCLUSIONS: Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.
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Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pneumonia Viral/diagnóstico , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Testes SorológicosRESUMO
The evidence of long-term clinical dynamic on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA re-positive case are less. We performed a 108 days follow-up on dynamic clinical presentations in a case, who hospitalized three times due to the positive recurrence of SARS-CoV-2 RNA after discharge, to understand the prognosis of the 2019-Coronavirus disease (COVID-19). In this case, positive SARS-CoV-2 recurred even after apparent recovery (normal CT imaging, no clinical symptoms, negative SARS-CoV-2 on stool sample and negative serum IgM test) from COVID-19, viral shedding duration lasted for 65 days, the time from symptom onset to disappearance was up to 95 days. Erythrocyte-associated indicators, liver function and serum lipid metabolism presented abnormal throughout during the observation period. Awareness of atypical presentations such as this one is important to prompt the improvement of the management of COVID-19.
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Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Pneumonia Viral/sangue , Pneumonia Viral/virologia , RNA Viral/genética , Eliminação de Partículas Virais , Adulto , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Biomarcadores/sangue , COVID-19 , HDL-Colesterol/sangue , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Hospitalização , Humanos , Interferon alfa-2/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/tratamento farmacológico , RNA Viral/isolamento & purificação , Recidiva , SARS-CoV-2 , Tomografia Computadorizada por Raios X , gama-Glutamiltransferase/sangueRESUMO
The evolution of an image with a local intensity minimum (LIM image) during hot image formation caused by translucent obscuration is theoretically and numerically investigated for the first time to our knowledge. The existence of the LIM image is proved, and the functional relationship describing the intensity of the LIM image is derived by using transfer matrix theory. Furthermore, the influences of the parameters of the obscuration and the nonlinear medium on the intensity of the LIM image are also discussed. The results show that the intensity of the LIM image increases with the increase of the amplitude coefficients of the obscuration, but declines with increasing the thickness of the nonlinear medium within a certain scope. We also found that the distance from the rear surface of the nonlinear medium to the LIM image plane is approximately equal to that from the obscuration plane to the rear surface of the nonlinear medium.
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BACKGROUND AND AIMS: Hyperuricemia is a risk factor for nonalcoholic fatty liver disease (NAFLD), however, the effect of gender on the hyperuricemia-related NAFLD development remains unclear. Here, we evaluated the clinical characteristics of NAFLD patients with hyperuricemia, and experimentally recapitulated this condition in male rats in order to gain insights on the possible impact of gender on the development of NAFLD in patients with hyperuricemia. METHODS: The clinical characteristics of 238 NAFLD patients, together with the impacts of hyperuricemia on the major parameters related to the development of NALFD were analysed. In animal studies, NAFLD with hyperuricemia was induced in male SD rats using high-yeast high-fat diet containing potassium oxonate. The impact of uric acids on liver pathology, and the expression patterns of key molecules involved in the development of NAFLD, including silent information regulator 1 (SIRT1), nuclear factor kappa B subunit p65 (NF-κB p65), fork-head box class O-3a (FOXO3a), androgen receptor (AR), and xanthine oxidase (XO) were analysed. RESULTS: Male NAFLD patients with hyperuricemia displayed more frequent and extensive liver injury than those in female patients. In male rats, hyperuricemia was associated with increased levels of insulin, alanine aminotransferase (ALT) and triglyceride (TG). At the molecular level, hyperuricemia was associated with decreased expression of SIRT1 and its phosphorylation, phosphorylation of FOXO3a, increased expression of AR and XO, and deacetylation of NF-κB P65. CONCLUSIONS: Hyperuricemia is a compounding factor for NAFLD, particularly in males. The severer hepatic injury observed in male NAFLD patients may be attributed to the suppression of SIRT1 signalling induced by hyperuricemia.
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Hiperuricemia/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Caracteres Sexuais , Adulto , Animais , Feminino , Humanos , Hiperuricemia/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Ratos Sprague-Dawley , Ácido Úrico/sangueRESUMO
With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane. Markers of lipid peroxidation include malondialdehyde, superoxide dismutase and lactic dehydrogenase. Recent studies have demonstrated that N-acetylcysteine (NAC) is able to dilate blood vessels, prevent oxidative damage, improve immunity, inhibit apoptosis and the inflammatory response and promote glutathione synthesis in cells. NAC also improves the systolic function of myocardial cells and cardiac function, prevents myocardial apoptosis, protects ventricular remodeling and vascular remodeling, reduces opiomelanocortin levels in the serum and increases the content of nitric oxide in the serum, thus improving vascular endothelial function. Therefore, NAC has potent pharmacological activity; however, the relatively fast metabolism of NAC, along with its large clinical dose and low bioavailability, limit its applications. The present study combined NAC with medicinal activated carbons, and prepared N-acetylcysteine activated carbon sustained-release microcapsules (ACNACs) to overcome the limitations of NAC. It was demonstrated that ACNACs exerted greater effective protective effects than NAC alone on myocardial IR injury in rats.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies and a major cause of cancer-related deaths. HCC often has an insidious onset, fast progression, and high tendency of metastasis and recurrence, hence it is a highly fatal malignant tumor. The origin of HCC is still a topic of debate but studies over the past decade have clearly identified liver cancer stem cells (LCSCs) being a cardinal source of liver cancer. LCSCs are a small subset of cells with the unlimited ability of self-renewal, differentiation, and uncontrollable growth. LCSCs are also resistant to conventional therapies and are thus believed to be responsible for treatment failure. Recent studies have indicated that long noncoding RNA (lncRNAs) may play important roles in the regulation of the biological functions of cancer stem cells (CSCs). The roles of lncRNAs on the biological properties of LCSCs are unknown. In this review, we briefly summarize the published studies on the functions and underlying mechanisms of commonly reported lncRNAs in the regulation of LCSCs.
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Carcinoma Hepatocelular/metabolismo , Diferenciação Celular , Proliferação de Células , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Metástase Neoplásica , Células-Tronco Neoplásicas , RNA Longo não Codificante/genética , RNA Neoplásico/genéticaRESUMO
The transforming growth factor (TGF)-ß-inducible early gene-1 (TIEG1) plays a crucial role in modulating cell apoptosis and proliferation in a number of diseases, including pancreatic cancer, leukaemia and osteoporosis. However, the functional role of TIEG1 in the heart has not been fully defined. In this study, we first investigated the role of TIEG1 in ischaemic heart disease. For in vitro experiments, cardiomyocytes were isolated from both TIEG1 knockout (KO) and wile-type (WT) mice, and the apoptotic ratios were evaluated after a 48h ischaemic insult. A cell proliferation assay was performed after 7 days of incubation under normoxic conditions. In addition, the angiogenic capacity of endothelial cells was determined by tube formation assay. For in vivo experiments, a model of myocardial infarction (MI) was established using both TIEG1 KO and WT mice. Echocardiography was performed at 3 and 28 days post-MI, whereas the haemodynamics test was performed 28 days post-MI. Histological analyses of apoptosis, proliferation, angiogenesis and infarct zone assessments were performed using terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) staining, BrdU immunostaining, α-smooth muscle actin (α-SMA)/CD31 immunostaining and Masson's trichrome staining, respectively. Changes in the expression of related proteins caused by TIEG1 deficiency were confirmed using both reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Our results demonstrated that the absence of TIEG1 prevented cardiomyocytes from undergoing apoptosis and promoted higher proliferation; it stimulated the proliferation of endothelial cells in vitro and in vivo. Improved cardiac function and less scar formation were observed in TIEG1 KO mice, and we also observed the altered expression of phosphatase and tensin homolog (Pten), Akt and Bcl-2/Bax, as well as vascular endothelial growth factor (VEGF). On the whole, our findings indicate that the absence of TIEG1 plays a cardioprotective role in ischaemic heart disease by promoting changes in Pten/Akt signalling.
Assuntos
Fatores de Transcrição de Resposta de Crescimento Precoce/deficiência , Fatores de Transcrição Kruppel-Like/deficiência , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Apoptose , Biomarcadores , Proliferação de Células , Modelos Animais de Doenças , Ecocardiografia , Células Endoteliais , Testes de Função Cardíaca , Camundongos , Camundongos Knockout , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Neovascularização Fisiológica/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl4)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl4-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl4-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl4-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.
Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Heme Oxigenase (Desciclizante)/metabolismo , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoproteção , Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)/genética , Fígado/enzimologia , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Hepatocyte injury is a common pathological effect of cisplatin (CDDP) in various solid tumor therapies. Thus, strategies for minimizing CDDP toxicity are of great clinical interest. N-acetylcysteine (NAC), a known antioxidant, is often used as an antidote for acetaminophen overdose in the clinic due to its ability to increase the levels of glutathione (GSH). In the present study, the aim was to investigate the protective effects of NAC against CDDP-induced apoptosis in human-derived HepG2 cells. The results showed that upon exposure of the cells to CDDP, oxidative stress was significantly induced. DNA damage caused by CDDP was associated with cell apoptosis. NAC pre-treatment significantly reduced the malondialdehyde (MDA) levels and ameliorated the GSH modulation induced by CDDP. NAC also protected against DNA damage and cell apoptosis. These data suggest the protective role of NAC against hepatocyte apoptosis induced by CDDP was achieved through the inhibition of DNA damage and alterations of the redox status in human derived HepG2 cells. These results indicate that NAC administration may protect against CDDP-induced damage.