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1.
Medicine (Baltimore) ; 99(21): e20234, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481298

RESUMO

BACKGROUND: The prevalence of chronic kidney disease (CKD) has been rapidly increasing and has become one of the most concerned global health problems. It is of good importance to improve therapeutic efficiency of CKD and delay disease progression to end stage renal disease (ESRD). Traditional Chinese Medicine (TCM) is a widely used complementary therapy for patients with CKD. The aim of this study is to evaluate whether basic treatment combined with Chinese herbs mixture Qi Gui Yi Shen decoction could achieve better therapeutic effect on CKD patients. METHODS: To determine whether traditional Chinese medicine Qi Gui Yi Shen decoction could achieve better therapeutic effect, we will conduct a randomized controlled trial. A total of 100 CKD patients that meet the inclusion criteria will be enrolled and divided into 2 groups: Qi Gui Yi Shen group (QGYS group) and placebo group. Each group will receive 6-monthly basic treatment in combination with TCM or placebo 3 times per day. Efficacy of Qi Gui Yi Shen decoction is evaluated by analyzing renal function and TCM symptoms, other efficacy assessments include serum level of PAI-I, expression of transforming growth factor beta1 (TGF-beta1). Routine blood count, plasma albumin (ALB), and alanine transaminase (ALT) are evaluated as side effect and safety profile. DISCUSSION: The results from the clinical trial will provide evidence for the effectiveness and safety of Qi Gui Yi Shen Decoction as a treatment for CKD patients. Furthermore, this will propose a new theory and method for CKD treatment. TRIAL REGISTRATION: Registered with Chinese Clinical Trials Registry at www.chictr.org. (Registration number: ChiCTR1900021622) on 1 March 2019.


Assuntos
Terapia Combinada/métodos , Medicina Tradicional Chinesa/métodos , Insuficiência Renal Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/prevenção & controle , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Segurança , Albumina Sérica/análise , Fator de Crescimento Transformador beta1/sangue , Adulto Jovem
2.
Gene ; 744: 144633, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32240778

RESUMO

BACKGROUND: Several studies have examined the association between transforming growth factor-ß (TGF-ß) genetic polymorphisms and chronic obstructive pulmonary disease (COPD) risk, but the results remained inconclusive and controversial. AIMS: We aimed to examine the correlation between TGF-ß genetic polymorphisms and COPD risk through a comprehensive meta-analysis. Additionally, changes in circulating TGF-ß concentrations across genotypes of TGF-ß genetic polymorphisms were analyzed. METHODS: Literature search, quality assessment, and data extraction were completed independently and in duplicate. Data are expressed in odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: A total of 12 articles, involving 14 independent studies and 7 170 participants, were meta-analyzed for the correlation of five polymorphisms (rs2241712, rs1800469, rs1982073, rs6957, and rs2241718) in TGF-ß gene with COPD risk. Under the allele model, no statistical significance was observed for all polymorphisms associated with COPD risk. Subsidiary analyses indicated that country, COPD stage, and diagnosis of COPD were potential sources of between-study heterogeneity. Filled full plots revealed no missing studies for all studied polymorphisms, except rs1982073. Genotype-phenotype analyses showed that carriers of rs1800469 CT genotype had significantly higher concentrations of circulating TGF-ß than those with CC genotype in COPD patients (WMD: 0.28 pg/ml, 95% CI: 0.01 to 0.56). CONCLUSION: Our findings failed to support the candidacy of TGF-ß gene in the development of COPD, whereas the contribution of TGF-ß gene to COPD might be ethnicity- and stage-dependent.


Assuntos
Doença Pulmonar Obstrutiva Crônica/genética , Fator de Crescimento Transformador beta1/genética , Correlação de Dados , Genótipo , Humanos , Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/sangue , Fatores de Risco , Fator de Crescimento Transformador beta1/sangue
3.
Acta Haematol ; 143(1): 19-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31212277

RESUMO

OBJECTIVE: This study aims to investigate the association of circulating T follicular helper (cTfh) cells and T follicular regulatory (cTfr) cells with acute myeloid leukemia (AML) patients. METHODS: A total of 22 newly diagnosed, untreated AML patients as well as 26 healthy controls were enrolled. Percentages of cTfh and cTfr cells were detected using flow cytometry. RESULTS: Compared to healthy controls, a significantly higher percentage of cTfr cells was observed in AML patients (4.10 ± 11.18 vs. 0.63 ± 0.38%) (p < 0.05). In addition, a significantly lower cTfh/cTfr ratio was found in the AML patients' group when compared to the control group (9.04 ± 9.19 vs. 11.66 ± 5.68) (p < 0.05). A lower level of plasma IL-2 and TGF-ß1 was found in AML patients. Based on the complete remission (CR) response after one cycle of inductive chemotherapy, patients were divided into two groups at sample collection: AML with and without CR. Significantly lower percentages of cTfr cells and a higher cTfh/cTfr ratio were found in the group of AML patients with CR than in the AML patients without CR. CONCLUSION: There was a significantly higher percentage of cTfr cells in AML patients. cTfr cells may have a potential association with the pathogenesis of AML patients.


Assuntos
Leucemia Mieloide Aguda/sangue , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Reguladores/citologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-2/sangue , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta1/sangue , Adulto Jovem
4.
Environ Toxicol ; 35(5): 582-590, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31875359

RESUMO

The roles of long noncoding RNAs (lncRNAs) have been shown to play critical roles in tumor progression. Here, it was identified that lncRNA MIR4435-2HG was highly expressed in lung cancer tissues, especially in nonsmall cell lung cancer (NSCLC). A consistent result was obtained in lung cancer cells. Functional experiments showed that knockdown of MIR4435-2HG reduced the proliferation and migration ability of NSCLC cells. Transcriptome-sequencing analysis indicated that TGF-ß signaling was mostly enriched in NSCLC cells with MIR4435-2HG knockdown. Furthermore, MIR4435-2HG was identified as an miRNA sponge for TGF-ß1 and thus activated TGF-ß signaling. Additionally, re-activation of TGF-ß1 rescued MIR4435-2HG knockdown-mediated inhibition on the progression of NSCLC cells. Therefore, this work indicates a novel MIR4435-2HG/TGF-ß1 axis responsible for NSCLC cell progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Pulmonares/patologia , MicroRNAs/sangue , RNA Longo não Codificante/sangue , Fator de Crescimento Transformador beta1/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Ativação Transcricional , Fator de Crescimento Transformador beta1/sangue , Regulação para Cima
5.
PLoS One ; 14(11): e0225482, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31770396

RESUMO

As debate rumbles on about whether anti-hepatitis B virus (HBV) nucleos(t)ide analogue treatments modulate host immune system during end-stage liver diseases, we studied effects of two potent anti-HBV agents, telbivudine or entecavir, on humoral immune activities including cytokine secretion, immunoglobulin production, and IgG-Fc agalactosylation, which is known to induce proinflammatory responses, in liver cirrhosis. Serum IgG-Fc N-glycan structures in patients with HBV-related liver cirrhosis, who had received either telbivudine treatment or entecavir treatment for at least 48 weeks were analyzed using liquid chromatography tandem-mass spectrometry. Levels of cytokines and each immunoglobulin isotype were measured using enzyme-linked immunosorbent assays. Results showed that 48 weeks of entecavir treatment caused HBV DNA loss, alanine aminotransferase normalization, and an amelioration of hypergammaglobulinemia in cirrhotic patients; however, telbivudine treatment, though possessing similar efficacies on HBV suppression and an improvement in liver inflammation to entecavir treatment, did not mitigate IgG-related hypergammaglobulinemia. Levels of IgG and transforming growth factor (TGF)-ß1 in sera of the cirrhotic patients before and during treatment were positively correlated. In vitro assays revealed that telbivudine treatment induced TGF-ß1 expression in human macrophagic cells. Moreover, recombinant TGF-ß1 treatment stimulated cell proliferation and IgG overproduction in human IgG-producing B cell lines. Finally, we found that telbivudine treatment enhanced the proportion of serum IgG-Fc agalactosylation in cirrhotic patients, which was associated with enhanced levels of TGF-ß1 and IgG. In conclusion, telbivudine therapy was associated with TGF-ß1 hyperactivity, IgG-related hypergammaglobulinemia, and IgG-Fc agalactosylation in HBV-related liver cirrhosis.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hipergamaglobulinemia/patologia , Imunoglobulina G/sangue , Cirrose Hepática/patologia , Telbivudina/uso terapêutico , Fator de Crescimento Transformador beta1/sangue , Adulto , Idoso , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Feminino , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Humanos , Hipergamaglobulinemia/complicações , Cirrose Hepática/etiologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/farmacologia , Estudos Retrospectivos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
6.
Life Sci ; 239: 117088, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759039

RESUMO

AIMS: Diabetic nephropathy (DN) is a common chronic microvascular complication of both types of diabetes mellitus, which leads to renal dysfunction and subsequent need of dialysis and organ transplantation. Advanced glycation end products (AGEs) are metabolic consequence of hyperglycemia and are main contributory factor in the DN pathogenesis through mediating establishment of oxidative status and chronic inflammatory milieu. This study aimed to explore the impact of vanillin on preventing the progression of DN. MAIN METHODS: Experimental DN model was established in rats utilizing streptozotocin. Serum concentration of AGEs and Interleukin-6 (IL-6) and transforming growth factor ß1 (TGFß1) levels in kidney homogenate were assessed using ELISA technique. Also, we evaluated the expression of nuclear factor kappa B (NF-κB) using immunohistochemistry. KEY FINDINGS: Treatment with vanillin for 8 weeks significantly ameliorated DN. Vanillin significantly decreased hyperglycemia and improved kidney function reflected by decreased serum levels of blood urea nitrogen, creatinine, and decreased proteinuria. Also, vanillin significantly decreased malondialdehyde content and elevated superoxide dismutase activity in renal tissues. Moreover, vanillin decreased renal expression of NF-κB and renal concentrations of IL-6, TGFß1 and collagen. In addition, vanillin significantly decreased serum AGEs concentration. Also, vanillin attenuated histological abnormalities in kidney architecture. SIGNIFICANCE: Vanillin, which is a cheap and abundant natural product, exhibited anti-AGEs, antioxidant, anti-inflammatory and anti-fibrotic activities. These activities might be helpful and potent mechanisms in preventing the progression of DN.


Assuntos
Benzaldeídos/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Benzaldeídos/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Interleucina-6/análise , Interleucina-6/sangue , Rim/metabolismo , Masculino , NF-kappa B/análise , NF-kappa B/sangue , Estresse Oxidativo/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Estreptozocina/farmacologia , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/sangue
7.
Acta Med Indones ; 51(3): 245-252, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31699948

RESUMO

BACKGROUND: MiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but other factors involved in postmenopausal osteoporosis still unknown. This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF-ß1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis (PMOP) compared with no osteoporosis (PMNOP), with point of interest on the expression of serum miR-21. METHODS: this study was conducted by comparative cross-sectional design. The subjects were divided into 2 groups of PMOP and PMNOP. We used an absolute quantification real-time PCR method to determine serum miR-21 expressions level. RESULTS: Median of serum miR-21 expression at the PMOP group was significantly higher compared to PMNOP group (p = 0.001). Serum miR-21 expression, RANKL, RANKL/OPG ratio, and physical activity were significantly correlated with BMD values in the PMOP group. Moderate physical activity was significantly negatively correlated with serum miR-21 expression. We also obtained a linear regression equation BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL (R2 = 52.5%). CONCLUSION: serum miR-21 expression in PMOP was higher compared with PMNOP. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8.5%. Obtained equation of BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL can explain the value of spinal BMD by 52.5%.


Assuntos
MicroRNAs/sangue , MicroRNAs/genética , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/genética , Densidade Óssea , Cálcio/sangue , Estudos Transversais , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose Pós-Menopausa/diagnóstico , Osteoprotegerina/sangue , Ligante RANK/sangue , Coluna Vertebral/diagnóstico por imagem , Fator de Crescimento Transformador beta1/sangue
8.
Proc Natl Acad Sci U S A ; 116(47): 23505-23511, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31685628

RESUMO

Comorbidity is common as age increases, and currently prescribed treatments often ignore the interconnectedness of the involved age-related diseases. The presence of any one such disease usually increases the risk of having others, and new approaches will be more effective at increasing an individual's health span by taking this systems-level view into account. In this study, we developed gene therapies based on 3 longevity associated genes (fibroblast growth factor 21 [FGF21], αKlotho, soluble form of mouse transforming growth factor-ß receptor 2 [sTGFßR2]) delivered using adeno-associated viruses and explored their ability to mitigate 4 age-related diseases: obesity, type II diabetes, heart failure, and renal failure. Individually and combinatorially, we applied these therapies to disease-specific mouse models and found that this set of diverse pathologies could be effectively treated and in some cases, even reversed with a single dose. We observed a 58% increase in heart function in ascending aortic constriction ensuing heart failure, a 38% reduction in α-smooth muscle actin (αSMA) expression, and a 75% reduction in renal medullary atrophy in mice subjected to unilateral ureteral obstruction and a complete reversal of obesity and diabetes phenotypes in mice fed a constant high-fat diet. Crucially, we discovered that a single formulation combining 2 separate therapies into 1 was able to treat all 4 diseases. These results emphasize the promise of gene therapy for treating diverse age-related ailments and demonstrate the potential of combination gene therapy that may improve health span and longevity by addressing multiple diseases at once.


Assuntos
Envelhecimento , Diabetes Mellitus Experimental/terapia , Fatores de Crescimento de Fibroblastos/fisiologia , Terapia Genética , Glucuronidase/genética , Insuficiência Cardíaca/terapia , Falência Renal Crônica/terapia , Obesidade/terapia , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Fator de Crescimento Transformador beta1/genética , Animais , Dependovirus/genética , Diabetes Mellitus Experimental/etiologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fibrose , Vetores Genéticos/uso terapêutico , Glucuronidase/sangue , Glucuronidase/fisiologia , Resistência à Insulina , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Medula Renal/patologia , Longevidade/genética , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Fenótipo , Receptor do Fator de Crescimento Transformador beta Tipo II/fisiologia , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/fisiologia , Obstrução Ureteral/complicações
9.
Mol Biol Rep ; 46(6): 6353-6360, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31541390

RESUMO

The disturbed immune homeostasis is involved in the pathogenesis of an array of autoimmune diseases like rheumatoid arthritis (RA). The adenosine monophosphate-activated protein kinase (AMPK) with a pivotal role in immunometabolism process, also plays a regulatory function in the immune system. This study aims to evaluate the alteration of AMPK gene expression in peripheral blood leukocytes of RA patients and its effects on disease severity as well as plasma levels of anti-inflammatory cytokines. 60 RA patients, including 30 newly diagnosed and 30 patients whose disease were under controlled with the combinational disease-modifying anti-rheumatic drug (DMARD), as well as 30 healthy subjects, were enrolled in our study. The gene expression of AMPK was evaluated using real-time PCR method. The plasma concentrations of IL-10 and TGF-ß1 were measured using sandwich ELISA. The gene expression of AMPK was significantly lower in the newly diagnosed RA patients in comparison with the control group (P = 0.049). Inversely, in RA patients who received DMARD therapy, the gene expression of AMPK was significantly higher than the control group (P = 0.003). There was no significant correlation between AMPK gene expression and plasma levels of IL-10 and TGF-ß1. The plasma levels of TGF-ß1 was significantly higher in both newly diagnosed and under-treatment patients compared with healthy subjects (P < 0.001). The impaired gene expression of AMPK in peripheral blood leukocytes and elevated levels of plasma TGF-ß1 can be contributed in RA pathogenesis.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Regulação para Baixo , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Estudos de Casos e Controles , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Interleucina-10/sangue , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/sangue
10.
Artigo em Chinês | MEDLINE | ID: mdl-31495108

RESUMO

Objective: To investigate the protective effect of oligomeric proanthocyanidins (OPCs) in paraquat-exposed mice. Methods: An acute lung injury model was established by a single intraperitoneal injection of paraquat (PQ) in BALB/c mice. The mice were randomized into control group, paraquat-exposed group (PQ group) , oligomeric proanthocyanidins group (OPCs group) , and paraquat and oligomeric proanthocyanidins-exposed group (PQ+OPCs group) , with 10 mice in each group. Only normal saline was intraperitoneally injected into the mice in the control group. The mice in the PQ group were divided into 8 subgroups according to the dose of poison administered, i.e., 0, 25, 50, 75, 100, 150, 200, and 300 mg/kg; the mice in each subgroup were given a single intraperitoneal injection of PQ and were observed and recorded for death at 3, 6, 12, 24, 36, 48, 60, 84, and 96 hours after PQ injection. Origin 8.0 was used to calculate the median lethal dose (LD(50)) of the mice at 24, 36, 48, and 60 hours after PQ injection, and the PQ dose (100 mg/kg, ip) was chosen based on the accumulated mortality rate. An OPCs-treated experimental model was established by an intraperitoneal injection of OPCs followed by a single PQ injection (100 mg/kg, ip) 1 hour later to observe the effects of OPCs on the apparent poisoning effect and fatality rate in PQ-induced mice. Immunohistochemistry was used to determine the effect of OPCs on PQ-induced lung tissue lesions. The peripheral blood samples of the mice were collected to determine the effects of OPCs on PQ-induced inflammatory factors such as tumor necrosis factor-α (TNF-α) , interleukine-1ß (IL-1ß) , and transforming growth factor-ß1 (TGF-ß1) using enzyme-linked immunosorbent assay. Results: The mortality rate was significantly correlated with the dose and exposure time in PQ-exposed mice; the mortality rate gradually increased with increasing dose and exposure time of the poison (P<0.05) . The LD(50) values for the mice were 216.67, 124.11, and 71.24 mg/kg at 24, 48, and 72 hours after PQ exposure, respectively. PQ could induce animal death at 12 hours after injection, and the mortality rate of the animals was 40% (4/10) at 48 hours after PQ exposure. The PQ-induced mortality rate of the mice in the PQ+OPCs group was reduced, and the mortality rate of the animals was 10% (1/10) at 48 hours after PQ exposure. Compared with treatment in the control group, OPCs exposure alone had no significant effect on the expression of TNF-α and TGF-ß1 in the peripheral blood (P>0.05) , but it significantly inhibited the expression of IL-1ß (P<0.05) . After 48 hours, the expression of TNF-α, TGF-ß1, and IL-1ß in peripheral blood significantly increased by 39%, 45%, and 38%, respectively, in the PQ group (P<0.05) , but they significantly decreased by 31%, 13%, and 22%, respectively, in the OPCs+PQ group as compared with the PQ group (P<0.05) . Conclusion: OPCs pretreatment can significantly alleviate PQ-induced poisoning effect.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Paraquat/toxicidade , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Interleucina-1beta/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Fator de Crescimento Transformador beta1/sangue , Fator de Necrose Tumoral alfa/sangue
11.
Inflamm Res ; 68(11): 933-943, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414141

RESUMO

OBJECTIVE: The aim of this study was to evaluate the association between rs3761548 FOXP3 (-3279 C > A) variant and multiple sclerosis (MS), disability, disability progression, as well as transforming growth factor (TGF)-ß1 and interleukin (IL)-10 plasma levels in MS patients. METHODS AND SUBJECTS: The study included 170 MS patients and 182 controls. Disability was evaluated using Expanded Disability Status Scale (EDSS) and categorized as mild (EDSS ≤ 3) and moderate/high (EDSS > 3). Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS). The rs3761548 variant was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of TGF-ß1 and IL-10 were determined using immunofluorimetric assay. RESULTS: CA and AA genotypes were associated with MS [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.66-3.53, p = 0.012; OR 8.19, 95% CI 3.04-22.07, p < 0.001, respectively). With the dominant model, the CA + AA genotypes were associated with MS (OR 2.57, 95% CI 1.50-4.37, p < 0.001). In the recessive model, the AA genotype was also associated with MS (OR 5.38, 95% CI 2.12-13.64, p < 0.001). After adjustment by age, ethnicity, BMI and smoking, all these results remained significant, as well as female patients carrying the CA + AA genotypes showed higher TGF-ß1 than those carrying the CC genotype (OR 1.35, 95% CI 1.001-1.054, p = 0.043). No association was observed between the genotypes and disability, disability progression and IL-10 levels. CONCLUSION: These results suggest that the A allele of FOXP3 -3279 C > A variant may exert a role in the T regulatory cell function, which could be one of the factors involved in the susceptibility for MS in females.


Assuntos
Fatores de Transcrição Forkhead/genética , Esclerose Múltipla/sangue , Esclerose Múltipla/genética , Fator de Crescimento Transformador beta1/sangue , Adulto , Brasil , Feminino , Variação Genética , Genótipo , Humanos , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais
12.
Cardiology ; 143(3-4): 77-84, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31466059

RESUMO

BACKGROUND: Connective tissue growth factor (CTGF) and transforming growth factor ß1 (TGF-ß1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-ß1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). METHODS: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-ß1, and B-type natriuretic peptide (BNP) were determined. RESULTS: The plasma CTGF and TGF-ß1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-ß1 levels were correlated with echocardiographic parameter E/e' and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. CONCLUSIONS: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/sangue , Insuficiência Cardíaca Diastólica/sangue , Peptídeo Natriurético Encefálico/sangue , Fator de Crescimento Transformador beta1/sangue , Idoso , Idoso de 80 Anos ou mais , Diástole , Ecocardiografia , Feminino , Insuficiência Cardíaca Diastólica/diagnóstico por imagem , Insuficiência Cardíaca Diastólica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
13.
Biomed J ; 42(3): 178-186, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31466711

RESUMO

BACKGROUND: Acute necrotizing encephalopathy (ANE), a fulminant encephalopathy, is often found in childhood. It is still uncertain whether adult patients with ANE display clinical features different from patients with typical pediatric onset. Furthermore, alterations in neuroinflammatory factors in patients with ANE have not been well-characterized. Here, we present an adult patient with ANE, and review all reported adult ANE cases in the literature. METHODS: Serum levels of five cytokines were checked in an adult patient with ANE and compared with gender/age-matched controls. Literature search was performed with PubMed, using the term as "acute necrotizing encephalopathy" with the filter of adult 19 + years. RESULTS: A total of 13 adult patients were reviewed. Compared with pediatric patients, adult ANE patients had similar clinical symptoms, biochemical data, and neuroimage findings, whereas adult ANE were more female-biased (female:male, 9:4) with a worse prognosis. Elevated cytokine levels in the serum and/or CSF is found in both adult-onset and pediatric-onset ANE. We found significantly elevated serum levels of IL-6 (17.17 pg/mL; healthy control: 1.43 ± 1.22 pg/mL) and VCAM-1 (3033.92 ng/mL; healthy control: 589.71 ± 133.13 ng/mL), and decreased serum TGF-ß1 level (14.78 ng/mL, healthy controls: 25.81 ± 6.97 ng/mL) in our patient. CONCLUSIONS: Our findings clearly delineate the clinical features and further indicate the potential change in cytokine levels in adult patients with ANE, advancing our understanding of this rare disease.


Assuntos
Encefalopatias/sangue , Encéfalo/metabolismo , Citocinas/sangue , Chaperonas Moleculares/sangue , Doença Aguda , Adulto , Idoso de 80 Anos ou mais , Encéfalo/patologia , Encefalopatias/tratamento farmacológico , Encefalopatias/patologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Fator de Crescimento Transformador beta1/sangue
14.
Acta Biochim Biophys Sin (Shanghai) ; 51(9): 953-959, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31435668

RESUMO

LncRNA MIR4435-2HG is characterized as an oncogene in lung cancer. However, its role in ovarian carcinoma (OC) is unclear. In this study, we aimed to investigate the role of MIR4435-2HG in OC. We found that both MIR4435-2HG and transforming growth factor beta 1 (TGF-ß1) were upregulated in OC. MIR4435-2HG is associated with tumor metastasis but not with tumor size. Upregulation of MIR4435-2HG distinguished early stage (Stage I and II) OC patients from healthy controls. Correlation analysis showed that plasma levels of MIR4435-2HG and TGF-ß1 were positively correlated only in OC patients. qPCR and western blot analysis results showed that MIR4435-2HG overexpression led to upregulation of TGF-ß1 in OC cells, while TGF-ß1 treatment did not significantly affect MIR4435-2HG expression. Transwell invasion and migration assays showed that MIR4435-2HG and TGF-ß1 promoted the invasion and migration of OC cells while TGF-ß inhibitor suppressed the invasion and migration of these cells. Further analysis of the Transwell invasion and migration assay results showed that TGF-ß inhibitor reduced the effects of MIR4435-2HG overexpression. Therefore, our results suggested that lncRNA MIR4435-2HG may promote OC by upregulating TGF-ß1. Further characterization of the functions of MIR4435-2HG in OC may provide novel targets for cancer therapies.


Assuntos
Biomarcadores Tumorais/fisiologia , Carcinoma/diagnóstico , MicroRNAs/fisiologia , Neoplasias Ovarianas/diagnóstico , RNA Longo não Codificante/fisiologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma/sangue , Linhagem Celular Tumoral , Feminino , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , RNA Longo não Codificante/sangue , Fator de Crescimento Transformador beta1/sangue
15.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443470

RESUMO

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg-1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg-1) showed positive impacts on the anti-inflammatory TGF-ß1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg-1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg-1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/prevenção & controle , Intestinos/efeitos dos fármacos , Lauratos/farmacologia , Monoglicerídeos/farmacologia , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Fezes/microbiologia , Inflamação/sangue , Inflamação/imunologia , Mediadores da Inflamação/sangue , Interleucinas/sangue , Intestinos/microbiologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta1/sangue
16.
Medicine (Baltimore) ; 98(29): e16531, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335733

RESUMO

BACKGROUND: To identify the clinical correlations between mechanical power and transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) in acute respiratory distress syndrome (ARDS) patients, their clinical significance in pulmonary structural remodeling in ARDS patients was investigated. METHODS: Ninety-five patients with moderate or severe ARDS, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from January 2017 to February 2019. Their mechanical power was monitored and recorded, the TGF-ß1 and CTGF levels were detected by enzyme-linked immunosorbent assay (ELISA), their relevance was analyzed, and the relationship between mechanical power and 28-day survival rate was investigated. According to the high-resolution computed tomography (HRCT) examination, the patients were divided into an ARDS group and an ARDS pulmonary fibrosis (ARDS-PF) group. The differences in mechanical power, TGF-ß1, and CTGF between the 2 groups were compared, and the significance of TGF-ß1 and CTGF in the diagnosis of ARDS pulmonary interstitial fibrosis were evaluated. RESULTS: A significant positive correlation between mechanical power and serum TGF-ß1 and CTGF in patients with ARDS was found and the correlation coefficients were 0.424 and 0.581, respectively. The difference between mechanical power and 28-day survival rate was statistically significant (P < .05), while the area under the receiver operating characteristic curves of TGF-ß1 and CTGF for the diagnosis of ARDS pulmonary fibrosis was 0.838 and 0.884, respectively (P < .05). CONCLUSION: A significant correlation between mechanical power and serum fibrosis biomarkers TGF-ß1 and CTGF in ARDS patients was found, and its level was related to the survival prognosis of patients. Mechanical power, TGF-ß1, and CTGF were clinically evaluated for the assessment of lung structural remodeling, such as ARDS pulmonary fibrosis. This study has particular significance to the early prevention of ventilator-induced lung injury and pulmonary fibrosis in patients with ARDS receiving mechanical ventilation.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/sangue , Fibrose Pulmonar/diagnóstico , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/terapia , Fator de Crescimento Transformador beta1/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/patologia , Tomografia Computadorizada por Raios X , Lesão Pulmonar Induzida por Ventilação Mecânica/diagnóstico
17.
BMC Pulm Med ; 19(1): 137, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349846

RESUMO

BACKGROUND: Th17 cells are believed to be important proinflammatory cells in the pathogenesis of chronic obstructive pulmonary disease (COPD). Recent evidence demonstrates that Th17 cells display substantial developmental plasticity, giving rise to Th17/Th1 cells that secret both IL-17 and IFN-γ and are more pathogenic in inflammatory diseases. The aim of this study was to examine the distribution of circulating Th17/Th1 subpopulation and its association with disease severity in patients with COPD. METHODS: Blood samples were obtained from 21 never-smokers, 31 smokers with normal lung function and 83 patients with COPD. The frequencies of Th17 cells and the Th17/Th1 subset were measured using flow cytometry. Plasma concentrations of IL-6, transforming growth factor (TGF)-ß1 and IL-12 were determined by ELISA. The associations of Th17/Th1 cells with lung function and smoking were evaluated. RESULTS: In peripheral blood, significantly increased proportions of Th17/Th1 cells among CD4 cells and Th17 cells were found in COPD patients compared with never-smokers and smokers with normal lung function. The percentages of Th17/Th1 cells showed correlations with forced expiratory volume in 1 (FEV1) % predicted value (r = - 0.244, p < 0.05), and higher proportions of Th17/Th1 cells in GOLD stage IV patients compared with stage I patients. The percentages of Th17/Th1 cells were significantly higher in current smokers compared with ex-smoker COPD patients, and positively correlated with pack-years of smoking (r = 0.352, p < 0.01). The plasma concentrations of IL-6, TGF-ß1 and IL-12 were significantly increased in patients with COPD compared with never-smokers and smokers with normal lung function. CONCLUSION: Our results revealed correlations of proportions of IFN-γ-producing Th17/Th1 cells with lung function and smoking, suggesting that increased Th17/Th1 cells may play a role in COPD progression.


Assuntos
Interferon gama/biossíntese , Doença Pulmonar Obstrutiva Crônica/imunologia , Células Th1/imunologia , Células Th17/imunologia , Idoso , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Interleucina-12/sangue , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumar , Fator de Crescimento Transformador beta1/sangue
18.
Egypt J Immunol ; 26(1): 31-42, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332994

RESUMO

About 40-50% of all patients with systemic lupus erythematosus (SLE) patients are associated with significant morbidity and a poor prognosis. The transforming growth factor ß-1(TGF-ß1) is a member of cytokines families which has emerged as an important player in the pathogenesis of autoimmune diseases, including SLE. In this study we aimed to evaluate TGF-ß1 as a noninvasive diagnostic test for early diagnosis of LN and to assess the correlations between TGFß-1 and clinic-pathologic characteristics as well as disease activity of SLE. This case-control study included 188 patients with SLE, stratified into two subgroups LN group and Non-LN group. We assessed diseases activity by SLE disease activity index and measured TGEß-1 by using ELISA. Our results showed that LN patients had significant lower values of serum TGF-ß1 compared with non-LN patients (P < 0.001). Moreover, there were significant differences between LN histopathological classes. The lowest levels values of serum TGFß1 was in Class V. There were significant negative correlations between levels of TGF-ß1 and SLEDAI, fever, arthritis, proteinuria, hematuria, serum creatinine, thrombocytopenia, lymphopenia, ESR, ANA, pus cell and cellular cast's, all (P < 0.01). In lupus nephritis patients, TGF-ß1 levels were positively correlated with eGFR, C3 and C4 (P < 0.001). Linear regression analysis revealed that, eGFR, CRP, thrombocytopenia, and serum creatinine were independently correlated with TGF-ß1 among lupus nephritis patients (P < 0.001). According to Receiver Operating Characteristic analysis, the sensitivity and specificity of TGF-ß1 were 91% and 65.5%, respectively in the diagnosis of LN among SLE patients. As LN group had significantly lower values of serum TGFß1 and the values further decreased with more damage of kidney tissues and progression of SLE activity. We conclude that serum TGF- ß1 could be a valuable non-invasive marker for assessment of LN activity and organ damage.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Fator de Crescimento Transformador beta1/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos
19.
Mol Med Rep ; 20(2): 1039-1048, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173196

RESUMO

Extending the release cycle of growth factors to match the cycle of bone remodeling is difficult. When using concentrated growth factors (CGFs), the release of growth factors is excessively rapid. In the present study, CGF samples were prepared by centrifugation. CGF samples were then lyophilized and grinded into a powder, which was termed freeze­dried CGF. The freeze­dried CGF samples were mixed with chitosan­alginate composite hydrogels, and the mixture was lyophilized. The result was a chitosan­alginate composite CGF membrane, which was called sustained­release CGF. This study investigated whether freeze­dried CGF in a chitosan­alginate composite gel can release CGF steadily to achieve effective osteogenesis. The proliferation and osteogenic expression of MC3T3­E1 cells induced by the supernatants from incubation with freeze­dried CGF and sustained­release CGF were evaluated. The concentrations of the growth factors, transforming growth factor ß1 (TGF­ß1), insulin­like growth factor­1 (IGF­1), platelet­derived growth factor­AB (PDGF­AB) and vascular endothelial growth factor (VEGF), in these two experimental groups at different times were determined by ELISA kits. The freeze­dried CGF showed better osteogenic performance than the sustained­release CGF in the early stages. At later stages, the sustained­release CGF had significant advantages over freeze­dried CGF in terms of promoting osteogenic mineralization. By characterizing the biologic properties of the CGF in the two different forms in vitro, we obtained a better understanding of their clinical effects.


Assuntos
Preparações de Ação Retardada/química , Fator de Crescimento Insulin-Like I/farmacologia , Osteogênese/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/farmacologia , Fator de Crescimento Transformador beta1/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Adulto , Alginatos/química , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quitosana/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Liofilização , Humanos , Fator de Crescimento Insulin-Like I/isolamento & purificação , Fator de Crescimento Insulin-Like I/metabolismo , Cinética , Masculino , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Fator de Crescimento Derivado de Plaquetas/isolamento & purificação , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/isolamento & purificação , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/isolamento & purificação
20.
Med Sci Monit ; 25: 4244-4249, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31173579

RESUMO

BACKGROUND Long noncoding RNAs (lncRNA) NF-kappaß-interacting long noncoding RNA (NKILA) is downregulated in various types of cancers, while its involvement in other diseases is unknown. In the present study we found that plasma lncRNA NKILA was expressed at higher levels in active ankylosing spondylitis patients than in healthy controls. MATERIAL AND METHODS According to Youden's index, active disease patients were divided into high and low lncRNA NKILA groups. RESULTS Patients in the high lncRNA NKILA level group had significantly longer length of treatment and higher re-hospitalization rate at 3 years after discharge. Plasma levels of TGF-ß1 were also higher in active ankylosing spondylitis patients than in healthy controls. Levels of plasma lncRNA NKILA and TGF-ß1 were significantly and positively correlated in ankylosing spondylitis patients but not in healthy controls. CONCLUSIONS Overexpression of lncRNA NKILA in ankylosing spondylitis is correlated with active disease and predicts length of treatment. LncRNA NKILA may participate in ankylosing spondylitis through the interaction with TGF-ß1, which is a key player in this disease.


Assuntos
RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Espondilite Anquilosante/genética , Fator de Crescimento Transformador beta1/sangue , Adulto , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Prognóstico , RNA Longo não Codificante/sangue , Transdução de Sinais , Espondilite Anquilosante/sangue , Fator de Crescimento Transformador beta1/genética , Adulto Jovem
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