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1.
Int Immunopharmacol ; : 106004, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31780370

RESUMO

Butyrate has multiple protective effects in inflammation-related intestinal diseases. Previous studies have found that butyrate could inhibit inflammation in rheumatoid arthritis. Inflammation is a pivotal inducement in the degeneration progress of the intervertebral disc. The anti-inflammatory treatment has an apparent curative effect in the symptomatic treatment of spine-related disease. Herein we investigated whether butyrate plays a protective role in degenerated intervertebral disc model. To mimic the lumbar disc local inflammatory environment, human primary nucleus pulposus cells were cultured with interleukin-1ß (IL-1ß, 10 ng/ml) to build a nucleus pulposus cell inflammation model. Butyrate was added to the cell culture medium to test the effect of butyrate on disc inflammation. Furthermore, a cultured nucleus pulposus tissue model was treated with butyrate (1 mM) to simulate the local treatment of intervertebral disc disease. Herein, we found that butyrate could downregulate the production of the inflammatory mediator caused by IL-1ß stimulation in the cell culture model. Additionally, butyrate inhibits the secretion of pro-inflammatory cytokines or graded enzymes in disc tissues from lumbar disc herniation patients. Furthermore, the anti-inflammatory function of butyrate in lumbar disc degenerated model may be caused by inhibiting the activation of the nuclear factor kappa B (NF-κB) signal pathway. This study presents butyrate as a candidate therapeutic method to treat lumbar disc degenerative disease.

2.
Medicine (Baltimore) ; 98(40): e17369, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577738

RESUMO

This study aimed to analyze the correlation between the efficiency coefficient of right ventricular-pulmonary artery coupling (ηvv) and the prognosis of patients with pulmonary arterial hypertension (PAH).A total of 64 patients who underwent right heart catheterization (RHC) were enrolled and divided into PAH and control groups depending on the RHC results. Pressure and volumetric methods were adopted to analyze the results of RHC and cardiac magnetic resonance imaging examination. The ηvv of patients in 2 groups were calculated, and the relationship between ηvv calculated by the 2 methods and the 2-year prognosis of patients with PAH was evaluated.The hemodynamic index and right ventricular-pulmonary artery coupling parameter of patients with PAH were significantly higher than those in the control group (P < .05). The right ventricular volume parameter in the PAH group was significantly different from that in the control group (P < .05). For patients with PAH, the end-systolic elastance/effective arterial elastance (Ees/Ea) calculated by the volumetric method was significantly related to the prognosis of patients (odds ratio = 0.192, 95% confidence interval: 0.042-0.868, P = .032). When Ees/Ea <0.67 was calculated by the volumetric method, the adverse prognosis of patients with PAH increased significantly (P < .05).The Ees/Ea calculated by the volumetric method may be better an independent factor for the prognosis of patients with PAH.


Assuntos
Hemodinâmica/fisiologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Função Ventricular Direita/fisiologia , Adolescente , Adulto , Idoso , Cateterismo Cardíaco , Criança , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Prognóstico , Artéria Pulmonar/diagnóstico por imagem , Volume Sistólico , Adulto Jovem
3.
Int Immunopharmacol ; 72: 138-147, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30981079

RESUMO

Interleukin-17 (IL-17) is the production of T helper type 17 (Th17) cells and has been reported to play a pro-inflammatory role in the immunopathogenesis of intervertebral disc degeneration. Peroxisome proliferator-activated receptor γ (PPAR-γ) activators display anti-inflammatory and anti-degeneration roles in osteoarthritis and rheumatoid arthritis. However, the expression level of PPAR-γ and related regulatory mechanisms in the nucleus pulposus tissues are not clear. Herein we report that PPAR-γ was down-regulated both in the nucleus pulposus tissue of intervertebral disc degeneration patient and in the cultured nucleus pulposus cells stimulated with IL-17. This study was undertaken to investigate the potential therapeutic effect of pioglitazone, as a PPAR-γ ligand, and its underlying molecular mechanism in IL-17-induced human intervertebral disc degeneration model in vitro. Our results indicate that pioglitazone administration suppressed the production of pro-inflammatory cytokines and down-regulated the mRNA expression levels of inflammatory mediators in the cultured human nucleus pulposus cells and tissue. Consistently, pioglitazone decreased the levels of metalloproteinase and maintained the expression of critical matrix components, such as aggrecan and type II collagen. Moreover, the activation of NF-κB signaling in the nucleus pulposus tissue during the intervertebral disc degeneration development was antagonized by pioglitazone administration. In conclusion, our current findings provide scientific evidence for the assessment of pioglitazone as a potential therapeutic approach to treat the intervertebral disc degeneration.


Assuntos
Anti-Inflamatórios , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , NF-kappa B/metabolismo , PPAR gama/agonistas , Pioglitazona , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/imunologia , Feminino , Humanos , Degeneração do Disco Intervertebral/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Núcleo Pulposo/citologia , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
4.
J Med Econ ; 22(4): 336-343, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30663458

RESUMO

BACKGROUND AND OBJECTIVE: Dapagliflozin is the first SGLT2 inhibitor available in China, where the disease burden of diabetes and its complications is very heavy. Because a new diabetes treatment strategy for diabetes should consider its cost-effectiveness, compared with an existing treatment, this study aimed to examine the cost-effectiveness between dapagliflozin and metformin treatment in China. METHODS: The Cardiff Diabetes Model (CDM) was used to estimate cost effectiveness and macro- and micro-vascular outcomes of dapagliflozin vs metformin. The CDM effectiveness inputs were derived from indirect comparative efficacy data from meta-analysis of 71 studies comparing monotherapy and add-on therapy of dapagliflozin vs metformin: dapagliflozin or metformin monotherapy, add-on therapy with other oral hypoglycemic agents, and add-on therapy with insulin. Direct medication costs and medical costs on treating diabetes were calculated based on published and local sources. A discount rate of 3% was applied to both costs and health effects. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess uncertainties. RESULTS: The total healthcare costs accumulated over the lifetime on dapagliflozin treatment arm was 8,626 Chinese yuan higher than the metformin treatment arm for an individual patient, and the quality adjusted life years (QALYs) gained with dapagliflozin treatment was 0.8 more than metformin treatment. Therefore, an incremental cost-effectiveness ratio was 10,729 yuan per QALY gained for dapagliflozin treatment arm vs metformin treatment arm. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSION: Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients. However, the findings of favorable cost-effectiveness results for dapagliflozin are largely driven by the effects of favorable weight profile on clinical, utility, and costs in the Cardiff model.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Metformina/economia , Metformina/uso terapêutico , Administração Oral , Fatores Etários , Idade de Início , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/economia , Peso Corporal , China , Colesterol/sangue , Análise Custo-Benefício , Complicações do Diabetes/economia , Complicações do Diabetes/epidemiologia , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/economia , Hemoglobina A Glicada , Gastos em Saúde , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Metformina/efeitos adversos , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Inibidores do Transportador 2 de Sódio-Glicose/economia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
5.
Adv Sci (Weinh) ; 5(10): 1800510, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30356942

RESUMO

As a novel 2D material, black phosphorus (BP) nanosheets are considered as a promising candidate for drug delivery platform for synergistic chemo/photothermal therapy. However, the intrinsic instability of bare BP poses a challenge in its biomedical applications. To date, some strategies have been employed to prevent BP from rapid ambient degradation. Unfortunately, most of these strategies are not suitable for the drug delivery systems. Here, a simple polydopamine modification method is developed to enhance the stability and photothermal performance of bare BP nanosheets. Then, this nanocapsule is used as a multifunctional codelivery system for the targeted chemo, gene, and photothermal therapy against multidrug-resistant cancer. The enhanced tumor therapy effect is demonstrated by both in vitro and in vivo studies.

6.
J Orthop Sci ; 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30219602

RESUMO

BACKGROUND: Dyslipidaemia is a well-known risk factor for the development of atherosclerosis, however, little is known about the effect of dyslipidaemia on intervertebral disc degeneration (IVDD). Thus, the purpose of this study is to investigate the relationship between dyslipidaemia and IVDD, and to identify the possible mechanism by which dyslipidaemia aggravates the degeneration of intervertebral discs. METHODS: Hyperlipidaemia rats were induced, thirty male Wistar rats were randomly divided into two groups: normal chow diet control group (CON) and high-fat diet group (HFD) for 8 weeks. And then, a rat disc degeneration model was established, rats were divided into three experimental groups: the normal chow diet + sham surgery group (CON-Sham); the normal chow diet + needle puncture group (CON-NP); and the high-fat diet + needle puncture group (HFD-NP), all rats were continually fed with normal chow diet or HFD 8 weeks. At the end of the experiment, the discs were harvested and histomorphological analysis, immunohistochemistry staining, real-time PCR and western blot were performed for all groups. RESULTS: The degenerative histological score of disc in the HFD-NP group was significantly higher than the CON-NP group. Immunohistochemical analysis revealed remarkable reductions in aggrecan and collagen type II expressions, and significant increases in IL-1ß, TNF-α, MMP-13, HIF-1α and P65 expression in the HFD-NP group. RT-PCR and western blot analysis showed that the mRNA levels and protein expressions of MMP-13 and TIMP-1 were higher in the HFD-NP group. CONCLUSIONS: Hyperlipidaemia resulted in an exaggerated degenerative changes and altered expression and transcription of the degeneration-associated molecules in the rat disc tissue. These results raise the possibility that hyperlipidaemia may accelerate the progression of disc degeneration.

7.
Orthopedics ; 41(6): 344-350, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30125034

RESUMO

The purpose of this study was to evaluate the superiority of total disk replacement (TDR) using a cervical disk prosthesis vs anterior cervical diskectomy and fusion (ACDF). Ninety-six patients with a diagnosis of degenerative disk disease with radiculopathy or myeloradiculopathy at 2 contiguous levels from C-3 to C-7 were randomly allocated to the TDR group (n=48) or the ACDF group (n=48). Outcome measures were recorded preoperatively and 1 week and 3, 6, 12, 24, and 81 months postoperatively. A total of 80 patients completed the follow-up, including 38 in the TDR group and 42 in the ACDF group. Japanese Orthopaedic Association, visual analog scale, and Neck Disability Index scores showed statistically significant improvement from baseline in both groups. Moreover, compared with the TDR group, the ACDF group had statistically greater visual analog scale scores from 12 months and Neck Disability Index scores from 3 months. Compared with the ACDF group, the TDR group had statistically greater range of motion at both the superior and the inferior treated levels at 3, 6, 12, 24, and 81 months postoperatively. Compared with the TDR group, the ACDF group had statistically greater range of motion at the superior adjacent levels at 6, 12, 24, and 81 months and at the inferior adjacent levels at 24 and 81 months postoperatively. The occurrence of adjacent-segment degeneration at both the superior and the inferior adjacent levels was greater in the ACDF group than in the TDR group. Total disk replacement was safe and effective and a statistically superior alternative to ACDF for degenerative disk disease at 2 contiguous levels. It could reduce the occurrence of adjacent-segment degeneration at the superior and the inferior adjacent segments by reducing the range of motion. [Orthopedics. 2018; 41(6):344-350.].

8.
Chin Med J (Engl) ; 131(13): 1605-1612, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29941715

RESUMO

Background: Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities. Methods: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding. Results: This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population. Conclusions: The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.

9.
Pak J Pharm Sci ; 31(3(Special)): 1093-1097, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29735456

RESUMO

Deep venous thrombosis is one of the common complications after major surgery in the Department of Orthopedics. The selective knee replacement of the lower extremities is more likely to cause the occurrence of DVT. The most commonly used anticoagulants in the Department of Orthopedics now include low molecular weight heparin (LMWH), Rivaroxaban, ordinary heparin, aspirin and warfarin. At present, the clinical application of low molecular weight heparin is the most, and the effect is the most accurate. This study compared the efficacy and safety of three commonly used anticoagulants such as aspirin, LMWH and Rivaroxaban in preventing VTE after hip and knee arthroplasty, so as to provide a theoretical basis for selecting suitable anticoagulant drugs in clinic. It has been proved that LMWH has good efficacy and safety in the prevention of VTE after hip and knee arthroplasty and is a priority anticoagulant. Rivaroxaban can effectively control the occurrence of DVT and the drug is convenient, but it will increase the risk of bleeding and should be used carefully.

10.
Clin Cancer Res ; 24(12): 2873-2885, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29549161

RESUMO

Purpose: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies.Experimental Design: Growth factor screening in pancreatic cancer cell lines was performed to identify activators of prosurvival PI3K/AKT signaling. The prevalence of activating growth factors and their receptors was assessed in pancreatic cancer patient samples. Effects of a bispecific IGF-1R and ErbB3 targeting antibody on receptor expression, signaling, cancer cell viability and apoptosis, spheroid growth, and in vivo chemotherapy activity in pancreatic cancer xenograft models were determined.Results: Growth factor screening in pancreatic cancer cells revealed insulin-like growth factor 1 (IGF-1) and heregulin (HRG) as the most potent AKT activators. Both growth factors reduced pancreatic cancer cell sensitivity to gemcitabine or paclitaxel in spheroid growth assays. Istiratumab (MM-141), a novel bispecific antibody that blocks IGF-1R and ErbB3, restored the activity of paclitaxel and gemcitabine in the presence of IGF-1 and HRG in vitro Dual IGF-1R/ErbB3 blocking enhanced chemosensitivity through inhibition of AKT phosphorylation and promotion of IGF-1R and ErbB3 degradation. Addition of istiratumab to gemcitabine and nab-paclitaxel improved chemotherapy activity in vivoConclusions: Our findings suggest a critical role for the HRG/ErbB3 axis and support the clinical exploration of dual IGF-1R/ErbB3 blocking in pancreatic cancer. Clin Cancer Res; 24(12); 2873-85. ©2018 AACR.

11.
Sci Rep ; 8(1): 5197, 2018 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-29581461

RESUMO

WRKY, a plant-specific transcription factor family, plays important roles in pathogen defense, abiotic cues, phytohormone signaling, and regulation of plant secondary metabolism. However, little is known about the roles, functions, and mechanisms of WRKY in taxane biosynthesis in Taxus spp. In this study, 61 transcripts were identified from Taxus chinensis transcriptome datasets by using hidden Markov model search. All of these transcripts encoded proteins containing WRKY domains, which were designated as TcWRKY1-61. After phylogenetic analysis of the WRKY domains of TcWRKYs and AtWRKYs, 16, 8, 10, 14, 5, 7, and 1 TcWRKYs were cladded into Group I, IIa-IIe, and III, respectively. Then, six representative TcWRKYs were selected to classify their effects on taxol biosynthesis. After MeJA (methyl jasmonate acid) and SA (salicylic acid) treatments, all of the six TcWRKYs were upregulated by MeJA treatment. TcWRKY44 (IId) and TcWRKY47 (IIa) were upregulated, whereas TcWRKY8 (IIc), TcWRKY20 (III), TcWRKY26 (I), TcWRKY41 (IIe), and TcWRKY52 (IIb) were downregulated by SA treatment. Overexpression experiments showed that the six selected TcWRKYs exerted different effects on taxol biosynthesis. In specific, TcWRKY8 and TcWRKY47 significantly improved the expression levels of taxol-biosynthesis-related genes. Transcriptome-wide identification of WRKY factors in Taxus not only enhances our understanding of plant WRKY factors but also identifies candidate regulators of taxol biosynthesis.

12.
J Theor Biol ; 443: 82-91, 2018 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-29355543

RESUMO

In this paper, a mathematical model describing the transmission of two-strain Dengue virus between mosquitoes and humans, incorporating vector control and awareness of susceptible humans, is proposed. By using the next generation matrix method, we obtain the threshold values to identify the existence and stability of three equilibria states, that is, a disease-free state, a state where only one serotype is present and another state where both serotypes coexist. Further, explicit conditions determining the persistence of this disease are also obtained. In addition, we investigate the sensitivity analysis of threshold conditions and the optimal control strategy for this disease. Theoretical results and numerical simulations suggest that the measures of enhancing awareness of the infected and susceptible human self-protection should be taken and the mosquito control measure is necessary in order to prevent the transmission of Dengue virus from mosquitoes to humans.

13.
Mol Med Rep ; 16(4): 5667-5674, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849008

RESUMO

Previous reports have indicated that microRNAs (miRNAs) have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte apoptosis induced by high glucose (HG) is characteristic of DN. However, the role of miRNAs in HG­induced podocyte apoptosis remains poorly understood. The present study investigated the role and potential underlying mechanism of miRNA­20b (miR­20b) in podocyte apoptosis induced by HG. The results demonstrated that miR­20b was significantly upregulated in HG­treated podocytes, as determined by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Caspase­3 activity and TUNEL assays indicated that suppression of miR­20b using miR­20b inhibitors significantly inhibited the podocyte apoptosis induced by HG. Sirtuin 7 (SIRT7) was identified as a functional target of miR­20b by a Dual­Luciferase activity reporter assay, RT­qPCR and western blot analysis. Silencing SIRT7 promoted HG­induced podocyte apoptosis, as determined by the caspase­3 activity, while SIRT7 overexpression attenuated HG­induced podocyte apoptosis. However, SIRT7 silencing significantly blocked the protective effect of miR­20b suppression against HG­induced apoptosis. In conclusion, these results indicate that miR­20b may contribute to HG­induced podocyte apoptosis by targeting SIRT7, providing a potential therapeutic target for the treatment of DN.


Assuntos
Apoptose/genética , Regulação da Expressão Gênica , Glucose/metabolismo , MicroRNAs/genética , Podócitos/metabolismo , Interferência de RNA , Sirtuínas/genética , Regiões 3' não Traduzidas , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Transformada , Técnicas de Silenciamento de Genes , Glucose/farmacologia , Humanos , Camundongos
14.
Am J Transl Res ; 9(4): 1856-1865, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28469790

RESUMO

MicroRNAs (miRNAs) have been involved in some human malignancies and correlated with tumor progression. The dysregulation of miR-130 is found in various cancers and correlated with tumor proliferation and apoptosis. However, its expression and function in non-small cell lung cancer (NSCLC) have not been investigated yet. In this study, we demonstrated that miR-130 is significantly down-regulated in NSCLC tissue samples and cell lines. Low miR-130 expression was closely associated with lymph node metastasis, late stages of disease progression and diminished survival in NSCLC patients. The up-regulation of miR-130 could significantly inhibit NSCLC cell growth and enhance cell apoptosis both in vitro and in vivo. Whereas inhibition of miR-130 exerted opposite effects. Furthermore, dual-luciferase reporter assay confirmed that PTEN was regulated by miR-130 directly, and the knockdown of PTEN markedly abrogated the anti-growth effect of miR-130. Additionally, miR-130 was found positively correlated with PTEN in NSCLC specimens. In conclusion, our results suggested that the expression of miR-130 is significantly associated with the growth and apoptosis of NSCLS cells by targeting PTEN, whilst miR-130 may be a potential therapeutic target for NSCLC treatment.

15.
Oncotarget ; 8(26): 43023-43034, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28498809

RESUMO

OBJECTIVE: Follistatin-like protein 1 (FSTL1) is a well-known mediator of inflammation. Intervertebral disc disease is an inflammatory disorder. Here, we investigated the role of FSTL1 in the intervertebral discs inflammation. METHODS: Expression of FSTL1 in nucleus pulposus tissues from rats and human was determined by immunohistochemistry staining and western blot analysis. The expression levels of tumor necrosis factor-α (TNF-α), interleukin1-ß (IL-1ß) and matrix metalloproteinase 13 (MMP-13) in human and rat nucleus pulposus tissues were measured by immunohistochemistry staining. The mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NFκB) signaling pathways were detected by western blotting. RESULTS: FSTL1 serum levels were significantly increased in lumbar disc herniation patients and had a positive correlation with Visual Analogue Scores. Additionally, FSTL1 expression was significantly increased in extrusion group compared with protrusion and control groups. Furthermore, FSTL1 expression was significantly increased in intervertebral disc degeneration models of rats. Immunohistochemistry staining demonstrated that the levels of TNF-α, IL-1ß and MMP-13 were increased in the pathogenesis of intervertebral disc disease. Recombinant human FSTL1 significantly increased the production of proinflammatory cytokines in vitro. In addition, FSTL1 promoted inflammation by activating c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases 1/2(ERK1/2) and NFκB signaling. CONCLUSIONS: These data imply that FSTL1 expression was increased in the pathogenesis of intervertebral disc disease. Importantly, FSTL1 promoted inflammatory catabolism in the nucleus pulposus by activating JNK, ERK 1/2/MAPK and NFκB signaling.


Assuntos
Proteínas Relacionadas à Folistatina/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Núcleo Pulposo/citologia , Transdução de Sinais , Animais , Biomarcadores , Citocinas/sangue , Citocinas/metabolismo , Feminino , Proteínas Relacionadas à Folistatina/sangue , Proteínas Relacionadas à Folistatina/genética , Expressão Gênica , Humanos , Inflamação/patologia , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Degeneração do Disco Intervertebral/etiologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/etiologia , Deslocamento do Disco Intervertebral/metabolismo , Deslocamento do Disco Intervertebral/patologia , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
16.
Gene ; 620: 66-74, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28390989

RESUMO

Taxus spp. are ancient gymnosperms that produce a unique secondary metabolite, namely, taxol, an anticancer drug. JAZ proteins are key regulators of the JA signaling pathway, which control taxol biosynthesis. However, the JAZ proteins of Taxus spp. are poorly studied. In this work, nine JAZ genes from Taxus chinensis were identified using our previous transcriptome data and named as TcJAZ1-TcJAZ9. Of these nine TcJAZ proteins, eight contain Jas and TIFY domains, and the Jas domain of TcJAZ6 is incomplete. Most TcJAZs and PsJAZs are not related to AtJAZs and OsJAZs. Phylogenetic analysis divided all JAZ proteins from Arabidopsis thaliana, Oryza sativa, Picea sitchensis, and T. chinensis into eight subgroups; gymnosperms JAZs were classified into subgroups V-VIII, and angiosperm JAZs were categorized into subgroups I-V. Three motifs of subgroups VI-VIII were identified in gymnosperm JAZs, indicating that gymnosperm JAZ proteins exhibit a different evolutionary process from those of angiosperms. The expression patterns of nine TcJAZs showed that TcJAZ2/3/8 was a key regulator, indicating their important roles in T. chinensis. Results revealed that gymnosperm JAZs differ from angiosperm JAZs in terms of molecular structure. Three novel conserved motifs were found in TcJAZs and PsJAZs. This study provides a basis for research on JA regulatory system in Taxus spp. and for elucidating the significance of JA signaling pathway to land plants.


Assuntos
Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Filogenia , Proteínas de Plantas/genética , Taxus/genética , Fatores de Transcrição/genética , Motivos de Aminoácidos , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/química , Taxus/classificação , Taxus/efeitos dos fármacos , Fatores de Transcrição/química
17.
Inflammation ; 40(3): 946-955, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28247166

RESUMO

The aim of this study was to investigate progranulin (PGRN) expression and its effect in cartilage degradation and in the pathogenesis of osteonecrosis of the femoral head (ONFH). Cartilage specimens were obtained from ONFH and FNF patients and PGRN expression was analyzed by immunohistochemistry, western blot analysis, and RT-PCR. Peripheral blood PGRN level was detected by ELISA. Additionally, primary chondrocytes were cultured and treated with PGRN. Next, the expression of aggrecan and collagen II and the activation of ERK1/2 were detected. We observed that the expression of PGRN was significantly upregulated in ONFH patients' articular cartilage, and recombinant PGRN could promote expression of aggrecan and collagen II and the activation of ERK1/2. Collectively, PGRN can improve chondrocyte anabolism and perform a therapeutic role in the pathogenesis of ONFH. This study helps to elucidate the pathogenesis of ONFH and presents PGRN as a potential target for the treatment of ONFH.


Assuntos
Cabeça do Fêmur/patologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteonecrose/prevenção & controle , Agrecanas/metabolismo , Cartilagem Articular , Células Cultivadas , Condrócitos/metabolismo , Colágeno/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Progranulinas , Substâncias Protetoras/farmacologia
18.
J Mol Histol ; 48(2): 63-72, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27913976

RESUMO

Follistain-like protein 1 (FSTL1), has been recently demonstrated to be involved in the embryo development of nervous system and glioblastoma. However, the role of FSTL1 in neuroinflammation remains unexplored. In this study, the expression of FSTL1 in astrocytes was verified and its role was studied in neuroinflammation induced by in vivo intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) or LPS treatment to astrocytes in vitro. FSTL1 was significantly induced after ICV LPS injection or LPS treatment. FSTL1 suppressed upregulation of pro-inflammatory cytokines in astrocytes after LPS treatment. Moreover, FSTL1 downregulated expression of pro-inflammatory cytokines through suppressing MAPK/p-ERK1/2 pathway in astrocytes. Our results suggest that FSTL1 may play an anti-inflammatory role in neuroinflammation mediated by astrocytes.


Assuntos
Astrócitos/patologia , Citocinas/metabolismo , Proteínas Relacionadas à Folistatina/fisiologia , Inflamação/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Astrócitos/metabolismo , Proteínas Relacionadas à Folistatina/genética , Proteínas Relacionadas à Folistatina/farmacologia , Regulação da Expressão Gênica , Humanos , Inflamação/induzido quimicamente , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo
19.
Spine (Phila Pa 1976) ; 41(21): 1631-1640, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27802252

RESUMO

STUDY DESIGN: Based on human disc surgical samples and isolated cells in vitro, we undertook a descriptive and mechanistic investigation of proinflammatory effects of interleukin (IL)-9 in intervertebral disc (IVD) degeneration. OBJECTIVE: To investigate the proinflammatory role of IL-9 in the pathological process of IVD degeneration. SUMMARY OF BACKGROUND DATA: IL-9 is known as a pleiotropic cytokine that regulates the human pathogenesis of inflammatory and autoimmune diseases. However, whether IL-9 cytokine is involved in the immuno-inflammatory pathogenesis of IVD degeneration is unclear. METHODS: The IVD samples were obtained from 45 patients. Immunohistochemistry, western blot, and real-time Polymerase Chain Reaction (PCR) were performed to detect the expression of IL-9 and tumor necrosis factor alpha (TNF-α) in the degenerated IVDs. Moreover, nucleus pulposus (NP) cells were treated with 0, 1, 10, and 100 ng/mL IL-9 cytokine and stimulated with IL-9 alone at 100 ng/mL for 0, 12, 24, and 48 hours. TNF-α expression was determined by immunofluorescence staining, western blot, and real-time PCR, respectively. The amounts of TNF-α and prostaglandin E2 (PGE2) in the supernatant were quantified by enzyme-linked immunosorbent assay. Additionally, Spearman correlation analyses were performed to analyze the correlation between Pfirrmann grading score of the involved degenerated IVDs and serum levels of IL-9. RESULTS: The expressions of IL-9 and TNF-α in degenerated IVD tissues were dramatically elevated in comparison with the control. IL-9 significantly up-regulated the TNF-α and PGE2 secretion of NP cells in dose- and time-dependent manner. Moreover, there is a positive correlation between IL-9 serum level and severity of involved IVD degeneration. CONCLUSION: Our findings suggest that IL-9 may play a potential role in the inflammatory processes of IVD degeneration. IL-9 may be involved in the IVD degeneration, at least in part, though stimulating the release of TNF-α and PGE2 in NP cells. LEVEL OF EVIDENCE: N/A.


Assuntos
Dinoprostona/metabolismo , Interleucina-9/farmacologia , Degeneração do Disco Intervertebral/metabolismo , Disco Intervertebral/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Feminino , Humanos , Inflamação/metabolismo , Interleucina-9/metabolismo , Disco Intervertebral/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Mol Med Rep ; 14(5): 4271-4278, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27633853

RESUMO

MicroRNA-181a (miR-181a) is upregulated in osteosarcoma, and its overexpression promotes the proliferation and inhibits the apoptosis of osteosarcoma cells. However, the mechanism of miR­181a as an oncogene remains to be fully elucidated in osteosarcoma. Cleavage factor (CF) Im25 links alternative polyadenylation to glioblastoma tumor suppression, however, its role in osteosarcoma has not been reported. In the present study, it was confirmed that the expression of miR­181a was upregulated in osteosarcoma, and that silencing miR­181a inhibited the proliferation and promoted the apoptosis of osteosarcoma cells. miRNAs are short non­coding RNAs, which regulate target mRNAs by binding predominantly to the 3'untranslated region (3'UTR), inducing either translational repression or degradation of the target. In the present study, target genes of miR­181a were screened using miRanda, which is a commonly used prediction algorithm. It was found that miR­181a targeted the 3'UTR of CFIm25 mRNA. Subsequent experiments confirmed that miR­181a downregulated the expression of CFIm25 in osteosarcoma cells. Finally, it was demonstrated that the CFIm25 protein was also downregulated in osteosarcoma tissues, and inhibited the proliferation and promoted the apoptosis of the cells. Elucidating the roles of miR­181a and CFIm25 in osteosarcoma not only assists in further understanding the pathogenesis and progression of this disease, but also offers novel targets for effective therapies.


Assuntos
Proliferação de Células/genética , MicroRNAs/genética , Osteossarcoma/genética , Fatores de Poliadenilação e Clivagem de mRNA/biossíntese , Apoptose/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Osteossarcoma/patologia , RNA Mensageiro/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética
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