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1.
Toxicol Lett ; 316: 73-84, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513886

RESUMO

In the liver microenvironment, interactions among diverse types of hepatic cells are involved in liver fibrosis. In fibrotic tissues, exosomes act as transporters in intercellular communication. Long non-coding RNAs (lncRNAs) are involved in the activation of hepatic stellate cells (HSCs), which are participants in liver fibrosis. However, the functions of exosomal lncRNAs in liver fibrosis induced by arsenite are undefined. The purposes of the present study were (a) to determine if lncRNAs secreted from human hepatic (L-02) cells exposed to arsenite are shuttled to hepatic stellate LX-2 cells and (b) to establish their effects on LX-2 cells. In mice, MALAT1 was overexpressed in the progression of liver fibrosis induced by arsenite as well as in L-02 cells exposed to arsenite. Co-cultures with arsenite-treated L-02 cells induced the activation of LX-2 cells and overexpression of MALAT1. Arsenite-treated L-02 cells transported MALAT1 into LX-2 cells. Downregulation of MALAT1, which reduced the MALAT1 levels in exosomes derived from arsenite-treated L-02 cells, inhibited the activation of LX-2 cells. Additionally, exosomal MALAT1 derived from arsenite-treated L-02 cells promoted the activation of LX-2 cells via microRNA-26b regulation of COL1A2. Furthermore, circulating exosomal MALAT1 was up-regulated in people exposed to arsenite. In sum, exosomes derived from arsenite-treated hepatic cells transferred MALAT1 to HSCs, which induced their activation. These findings support the concept that, during liver fibrosis induced by arsenite, exosomal lncRNAs are involved in cell-cell communication.


Assuntos
Arsenitos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Exossomos/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática Experimental/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Compostos de Sódio , Animais , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Técnicas de Cocultura , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Exossomos/genética , Exossomos/ultraestrutura , Regulação da Expressão Gênica , Células Estreladas do Fígado/ultraestrutura , Humanos , Fígado/ultraestrutura , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/patologia , Masculino , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , Transdução de Sinais
2.
Int J Nanomedicine ; 14: 5831-5848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534327

RESUMO

Purpose: In order to accelerate the tendon-bone healing processes and achieve the efficient osteointegration between the tendon graft and bone tunnel, we aim to design bioactive electrospun nanofiber membranes combined with tendon stem/progenitor cells (TSPCs) to promote osteogenic regeneration of the tendon and bone interface. Methods: In this study, nanofiber membranes of polycaprolactone (PCL), PCL/collagen I (COL-1) hybrid nanofiber membranes, poly(dopamine) (PDA)-coated PCL nanofiber membranes and PDA-coated PCL/COL-1 hybrid nanofiber membranes were successfully fabricated by electrospinning. The biochemical characteristics and nanofibrous morphology of the membranes, as well as the characterization of rat TSPCs, were defined in vitro. After co-culture with different types of electrospun nanofiber membranes in vitro, cell proliferation, viability, adhesion and osteogenic differentiation of TSPCs were evaluated at different time points. Results: Among all the membranes, the performance of the PCL/COL-1 (volume ratio: 2:1 v/v) group was superior in terms of its ability to support the adhesion, proliferation, and osteogenic differentiation of TSPCs. No benefit was found in this study to include PDA coating on cell adhesion, proliferation and osteogenic differentiation of TSPCs. Conclusion: The PCL/COL-1 hybrid electrospun nanofiber membranes are biocompatible, biomimetic, easily fabricated, and are capable of supporting cell adhesion, proliferation, and osteogenic differentiation of TSPCs. These bioactive electrospun nanofiber membranes may act as a suitable functional biomimetic scaffold in tendon-bone tissue engineering applications to enhance tendon-bone healing abilities.


Assuntos
Materiais Biocompatíveis/farmacologia , Osso e Ossos/fisiologia , Membranas Artificiais , Nanofibras/química , Células-Tronco/citologia , Tendões/citologia , Engenharia Tecidual/métodos , Animais , Osso e Ossos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Nanofibras/ultraestrutura , Osteogênese , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos
3.
Arch Endocrinol Metab ; 63(4): 394-401, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365627

RESUMO

OBJECTIVE: To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. SUBJECTS AND METHODS: 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. RESULTS: One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. CONCLUSION: PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.


Assuntos
Densidade Óssea , Colágeno Tipo I/metabolismo , Hiperparatireoidismo Primário/metabolismo , Paratireoidectomia/reabilitação , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Idoso , Biomarcadores/sangue , Cálcio/sangue , Feminino , Humanos , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Pró-Colágeno/sangue , Estudos Retrospectivos , Vitamina D/sangue
4.
Oncology ; 97(4): 236-244, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412345

RESUMO

INTRODUCTION: On a global scale, the malignant growth of mammary gland is the most common type of cancer in women. In the progress of mammary carcinoma, osseous metastatic invasion has a pivotal significance because it is a frequent complication occurring at an early stage of the disease. BACKGROUND: Bone metastases in breast cancer patients lead to increased mortality and decreased health-related quality of life. Therefore, early diagnostic assessment and treatment is requested. Meanwhile the progress of the disease should be monitored closely. Regarding health-related quality of life and lifetime prolongation, osseous metastases should be early diagnosed, therapied, and monitored. Up to date the gold standard is the whole-body scintigraphy. This kind of bone imaging features has high sensitivity but shows loss of specificity. AIM: This study aims to investigate the diagnostic versatility of bone markers in its resorption and formation function to detect bone metastases in patients with breast cancer. PATIENTS, MATERIALS, AND METHODS: For this purpose, the concentration of competing bone processing tumor markers in serums of 78 patients was detected and analyzed. Two groups of women with mammary carcinoma with and without osseous metastases were built to examine the presence (or absence) of statistically significant disparity of tumor marker concentration. The tumor markers employed in this study were the carboxyterminal collagen type I telopeptid (CTX), known as beta-crosslaps (ß-CTx), the alkaline phosphatase (AP), and its isoenzymes (especially the bone-specific AP [B-AP]). Additionally, the tumor markers for breast cancer (CA 15-3 and CEA) were analyzed in both groups. RESULTS: Our results provide evidence that in both groups, tumor markers such as ß-CTx and B-AP were a promising tool for the detection and exclusion of bone metastases in breast cancer. This comprehensive investigation shows both ß-CTx and B-AP are able to fulfill the conditions of a competent appliance to detect osseous metastases of patients with mammary carcinoma. CONCLUSION: Concerning the urgency of early and frequent detection, staging, and disease monitoring of mammary carcinoma with osseous metastases, this study renewed and underlined the importance of biochemical tumor markers - especially ß-CTx and B-AP - and laid a clinical-based cornerstone to build up on a prospective research.


Assuntos
Biomarcadores/metabolismo , Neoplasias Ósseas/metabolismo , Osso e Ossos/metabolismo , Neoplasias da Mama/metabolismo , Fosfatase Alcalina/metabolismo , Biomarcadores Tumorais , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Colágeno Tipo I/metabolismo , Feminino , Humanos , Mucina-1/metabolismo , Metástase Neoplásica , Qualidade de Vida , Curva ROC , Cintilografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Imagem Corporal Total
5.
Toxicol Lett ; 315: 87-95, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31425726

RESUMO

Prenatal alcohol exposure (PAE) is often associated with congenital heart defects, most commonly septal, valvular, and great vessel defects. However, there have been no known studies on whether PAE affects the resulting fibroblast population after development, and whether this has any consequences in the postnatal period. Our previous study focused on the effects of PAE on the postnatal fibroblast population, which translated into changes in cardiac extracellular matrix (ECM) composition and cardiac function in the neonatal heart. Moreover, our lab has previously demonstrated that alcohol-induced fibrosis is mediated by oxidative stress mechanisms in adult rat hearts following chronic alcohol exposure. Thus, we hypothesize that PAE alters cardiac ECM composition that persists into the postnatal period, leading to cardiac dysfunction, and these effects are prevented by antioxidant treatment. To investigate these effects, pregnant mice were intraperitoneally injected with 2.9 g EtOH/kg body weight on gestation days 6.75 and 7.25. Controls were injected with vehicle saline. Randomly selected dams in both groups were then treated with 100 mg/kg body weight of the antioxidant N-acetylcysteine (NAC) immediately after EtOH or vehicle administration. Left ventricular (LV) chamber dimension and function were assessed in sedated animals on neonatal day 5 using echocardiography. Ejection fraction decreased in the PAE group. NAC treatment prevented this depression of systolic function in PAE neonates. Hearts were analyzed for expression of fibroblast activation markers. Alpha smooth muscle actin (α-SMA) increased in PAE neonatal hearts, and this increase was prevented by NAC treatment. In PAE pups, collagen I decreased, but collagen III expression increased compared to saline animals; the overall collagen I/III ratio significantly decreased. When PAE mice were treated with NAC, collagen I/III ratio did not change. Overall, our data demonstrate that prenatal alcohol exposure produces changes in collagen subtype in neonatal cardiac ECM and a decline in systolic function, and these adverse effects were prevented by NAC treatment.


Assuntos
Acetilcisteína/farmacologia , Alcoolismo/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Vasos Coronários/química , Etanol/toxicidade , Fibroblastos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Camundongos , Gravidez
6.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(7): 475-480, 2019 Jul 09.
Artigo em Chinês | MEDLINE | ID: mdl-31288328

RESUMO

Objective: To observe the effect of adenosine triphosphate (ATP) phosphorylation on type Ⅰ collagen mineralization and explore the role of small molecule compound ATP in biomimetic mineralization. Methods: Fourier transform infrared spectroscopy (FT-IR) was used to analyze the phosphorylation of collagen molecules by different concentrations (0, 25, 50, 100 mmol/L) of ATP. The concentration of 50 mmol/L ATP was chosen to construct the phosphorylated collagen mineralization model. Transmission electron microscopy (TEM) was used to observed the ultrastructure of mineralized collagen and the collagen mineralization rate was further calculated by ImageJ software. The surface morphology of the collagen gel ATP group and the control group was observed by scanning electron microscopy (SEM) and the elemental analysis was performed by using an X-ray energy spectrometer. The artificial demineralized dentin samples were mineralized for 2 days and 4 days to compare the effect of ATP on dentin remineralization by SEM. Results: FT-IR analysis showed that the formation of new peaks at wavenumbers of 642, 818, and 902 cm(-1) indicated that ATP can phosphorylate type Ⅰ collagen. Through TEM and SEM observation, the mineralization degree of type Ⅰ collagen and demineralized dentin pretreated with 50 mmol/L ATP were significantly higher than that of the control group. Compared with the control group [(31.65±1.62)%], the mineralization rate of collagen in the ATP group [(100±0)%] was significantly increased after 2 days of mineralization (P<0.05). Conclusions: ATP phosphorylation can effectively promote the mineralization process of type Ⅰ collagen.


Assuntos
Trifosfato de Adenosina , Materiais Biomiméticos , Colágeno Tipo I , Trifosfato de Adenosina/farmacologia , Materiais Biomiméticos/química , Colágeno Tipo I/química , Colágeno Tipo I/metabolismo , Colágeno Tipo I/ultraestrutura , Dentina/química , Dentina/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Fosforilação , Espectroscopia de Infravermelho com Transformada de Fourier
7.
J Biol Regul Homeost Agents ; 33(4): 1105-1111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31332987

RESUMO

The adapter protein myeloid differentiation primary response gene 88 (MyD88) links the intracellular domains of interleukin receptors 1 and 18, and most Toll-like receptors (TLRs) to interleukin 1 receptor associated kinase (IRAK) signaling and subsequent NF-κB-mediated transcription. Previous work showed that mice with global deficiency of MyD88 (MyD88-/-) have osteopenic cancellous bone along with a reduction in osteoblastic but also osteoclastic surfaces. To further elucidate the role of MyD88 in bone, we utilized mice with osteoclast-restricted MyD88 expression in bone (MyD88OC). Bones of MyD88OC and wild type (wt) mice were examined by microCT analysis. Mechanical properties of bones were tested by three-point bending, and gene expression measured using quantitative real-time polymerase chain reaction. In MyD88OC mice, no osteopenic traits were observed, however, a drastic reduction in geometric parameters was detected. In trabecular bone a loss of connectivity density (-44%, p less than 0.0001) was measured and in cortical bone Imax (-31%, p less than 0.0001), Imin (-20%, p less than 0.001), J (-26%, p less than 0.0001) were reduced. Mechanical testing showed increased load to failure (77%, p less than 0.01) and decreased deflection at failure (-68%, p less than 0.01) of the femur. On the molecular level, relative gene expression analysis showed a (-29%, p less than 0.01) reduction in receptor activator of nuclear factor κ B ligand (RANKL) and no difference in osteoprotegerin (OPG) or RANK. Further, the bone resorption markers cathepsin K (CTSK) and tartrate-resistant acid phosphatase 5 (TRAP) were unchanged. In contrast, the bone formation markers collagen type 1 (COL1A1) and osteocalcin (OC) were decreased by -72% (p less than 0.0001) and -82% (p less than 0.0001), respectively. Together, our data suggests that the function of MyD88 in osteoclasts is sufficient to maintain bone mass, while it fails to preserve bone geometry, likely through dysfunctions in osteoblasts.


Assuntos
Reabsorção Óssea , Osso e Ossos/patologia , Fator 88 de Diferenciação Mieloide/metabolismo , Osteoclastos/citologia , Animais , Catepsina K/metabolismo , Diferenciação Celular , Colágeno Tipo I/metabolismo , Camundongos , Osteoblastos , Osteocalcina/metabolismo , Osteoclastos/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Fosfatase Ácida Resistente a Tartarato/metabolismo
9.
Life Sci ; 232: 116637, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288014

RESUMO

Keloid is characterized by overactive fibroblasts. Forkhead box M1 (FOXM1) is transcription factor that plays important roles in the progression of fibrosis. However, the role of FOXM1 in keloid has not been elucidated. In the present study, we examined the expression levels of FOXM1 in clinical keloid tissue specimens and primary keloid fibroblasts (KFs). The results showed that FOXM1 levels were significantly increased in both keloid tissues and KFs. To further investigate the biological functions of FOXM1, FOXM1 was knocked down in KFs by transfection with small interfering RNA targeting FOXM1 (si-FOXM1). Knockdown of FOXM1 inhibited transforming growth factor-ß1 (TGF-ß1)-induced cell proliferation and migration of KFs. Besides, the increased expressions of collagen (coll I), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in TGF-ß1-induced KFs were suppressed by si-FOXM1 transfection. Furthermore, TGF-ß1-induced increase in p-Smad2 and p-Smad3 expressions was attenuated by FOXM1 knockdown. These data indicated that knockdown of FOXM1 inhibited TGF-ß1-induced KFs activation and extracellular matrix (ECM) accumulation, which was attributed to the inhibition of TGF-ß1/Smad pathway.


Assuntos
Proteína Forkhead Box M1/deficiência , Queloide/metabolismo , Actinas/metabolismo , Adolescente , Adulto , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Técnicas de Silenciamento de Genes/métodos , Humanos , Queloide/genética , Masculino , Fosforilação , RNA Interferente Pequeno/genética , Transdução de Sinais , Proteína Smad2/antagonistas & inibidores , Proteína Smad2/metabolismo , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/metabolismo
10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(7): 883-888, 2019 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-31298008

RESUMO

Objective: To investigate the effect of transforming growth factor ß 1 (TGF-ß 1) induced proliferation of ligamentum flavum cells and ligamentum flavum hypertrophy and its effect on connective tissue growth factor (CTGF) expression. Methods: The ligamentum flavum tissue in lumbar intervertebral disc herniation was extracted and the ligamentum flavum cells were isolated and cultured by collagenase pre-digestion method. Morphological observation, immunofluorescence staining observation, and MTT assay were used for cell identification. The 3rd generation ligamentum flavum cells were divided into 5 groups. The cells of groups A, B, C, and D were respectively sealed with 3 ng/mL TGF-ß 1, 50 ng/mL CTGF, 3 ng/mL TGF-ß 1+CTGF neutralizing antibody, and 50 ng/mL CTGF+CTGF neutralizing antibody. Serum free DMEM was added to group E as the control. MTT assay was used to detect the effects of TGF-ß 1 and CTGF on the proliferation of ligamentum flavum cells. Western blot was used to detect the expression of CTGF protein. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of collagen type Ⅰ, collagen type Ⅲ, and CTGF genes. Results: The morphological diversity of cultured ligamentum flavum cells showed typical phenotype of ligamentum flavum fibroblasts; all cells expressed collagen type Ⅰ and vimentin, and some cells expressed collagen type Ⅲ; MTT identification showed that with the prolongation of culture time, the absorbance ( A) value of each generation of cells increased gradually, and the A value of the same generation of cells at each time point was significantly different ( P<0.05), there was no significant difference in A value between the cells of each generation at the same time point ( P>0.05). After cultured for 24 hours, MTT assay showed that the A value of cells in groups A and B was significantly higher than that of group E ( P<0.05). After adding CTGF neutralizing antibody, the A value of cells in groups C and D decreased, but it was still higher than that of group E ( P<0.05). There were also significant differences among groups A, C and groups B, D ( P<0.05). Western blot analysis showed that the relative expression of CTGF protein in groups A and B was significantly higher than that in group E ( P<0.05), while the relative expression of CTGF protein in groups C and D was significantly lower than that in group E ( P<0.05), and the difference between groups A, C and groups B, D was also significant ( P<0.05). qRT-PCR detection showed that the mRNA relative expression of CTGF, collagen type Ⅰ, and collagen type Ⅲ in group A was significantly higher than that in group E ( P<0.05). After adding neutralizing antibody, the mRNA relative expression of genes in group C was inhibited and were significantly lower than that in group A, but still significantly higher than that in group E ( P<0.05). The mRNA relative expressions of collagen type Ⅰ and collagen type Ⅲ in group B was significantly higher than that in group E ( P<0.05), but the mRNA relative expression of CTGF was not significantly different from that in group E ( P>0.05); after neutralizing antibody was added, the mRNA relative expression of collagen type Ⅰ and collagen type Ⅲ in group D was inhibited and was significantly lower than that in group B, but still significantly higher than that in group E ( P<0.05); there was no significant difference in the mRNA relative expression of CTGF between group D and groups B, E ( P>0.05). Conclusion: TGF-ß 1 can promote CTGF, collagen typeⅠ, collagen type Ⅲ gene level and protein expression in ligamentum flavum cells, and TGF-ß 1 can synergistically promote proliferation of ligamentum flavum cells through CTGF.


Assuntos
Proliferação de Células , Fator de Crescimento do Tecido Conjuntivo , Ligamento Amarelo , Fator de Crescimento Transformador beta1 , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Fator de Crescimento do Tecido Conjuntivo/fisiologia , Humanos , Ligamento Amarelo/fisiologia , Fator de Crescimento Transformador beta1/fisiologia
11.
Biomed Environ Sci ; 32(6): 419-426, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262387

RESUMO

OBJECTIVE: Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang II. METHODS: HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and α-smooth muscle actin (α-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type I, α-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang (1-7), and Ang II in serum were determined by ELISA. Co-localization of ACE2 and α-SMA in fibroblasts was detected by immunofluorescence. RESULTS: Ang (1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang (1-7) decreased the expressions of collagen type I and α-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang II. Ang (1-7) increased the levels of ACE2 and Ang (1-7) and decreased the level of Ang II in silicotic rat serum. A779 enhanced the protective effect of Ang (1-7) in fibroblasts stimulated by Ang II. CONCLUSION: Ang (1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang II by regulating ACE2-Ang (1-7)-Mas axis.


Assuntos
Angiotensina II/sangue , Angiotensina I/uso terapêutico , Pulmão/metabolismo , Miofibroblastos/efeitos dos fármacos , Fragmentos de Peptídeos/uso terapêutico , Silicose/prevenção & controle , Actinas/metabolismo , Angiotensina I/sangue , Angiotensina I/farmacologia , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Pulmão/patologia , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Ratos Wistar , Silicose/metabolismo , Silicose/patologia
12.
Toxicol Lett ; 313: 178-187, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284023

RESUMO

Long-term inhalation of crystalline silica particles leads to silicosis characterized by pulmonary inflammation and interstitial fibrosis. The growth arrest-specific protein 6 (Gas6) and its tyrosine receptor Mer have been implicated to involve in the regulation of inflammation, innate immunity and tissue repair. However, the role of Gas6 or Mer in silica-induced lung inflammation and fibrosis has not been investigated previously. In this study, we observed a remarkable increase of Gas6 in bronchoalveolar lavage fluid (BALF) from wild-type C57BL/6 mice after silica intratracheal administration. Then, we investigated whether genetic loss of Gas6 or Mer could attenuate silica-induced lung inflammation and fibrosis. Our results showed that Gas6-/- and Mer-/- mice exhibited reduced lung inflammation response from days 7 to 84 after silica exposure. We also uncovered an overexpression of the suppressor of cytokine signaling protein 1 in silica-treated deficient mice. Moreover, Gas6 or Mer deficiency attenuated silica-induced collagen deposition by inhibiting the expression of transforming growth factor-ß. We conclude that gene absence of Gas6 or Mer is protective against silica-induced lung inflammation and fibrosis in mice. Targeting Gas6/Mer pathway may be a potential therapeutic approach to treat pulmonary fibrosis in patients with silicosis.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Pulmão/enzimologia , Pneumonia/prevenção & controle , Fibrose Pulmonar/prevenção & controle , Silicose/prevenção & controle , c-Mer Tirosina Quinase/deficiência , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular/genética , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/enzimologia , Pneumonia/genética , Pneumonia/patologia , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Transdução de Sinais , Silicose/enzimologia , Silicose/genética , Silicose/patologia , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , c-Mer Tirosina Quinase/genética
13.
Int J Nanomedicine ; 14: 4133-4144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239672

RESUMO

Background: Although titanium dioxide nanotubes (TNTs) had great potential to promote osteogenesis, their weak bonding strength with titanium substrates greatly limited their clinical application. Purpose: The objective of this study was to maintain porosity and improve the stability of TNT coatings by preparing some micro-patterned mesoporous/nanotube (MP/TNT) structures via a photolithography-assisted anodization technology. Methods: The adhesion strength of different coatings was studied by ultrasonic cleaning machine and scratch tester. The early adhesion, spreading, proliferation and differentiation of MC3T3-E1 cells on different substrates were investigated in vitro by fluorescent staining, CCK8, alkaline phosphatase activity, mineralization and polymerase chain reaction assays, respectively. Results: Results of ultrasonic and scratch assays showed that the stability of TNTs (especially 125 nm) was significantly improved after being patterned with MP structures. In vitro cell assays further demonstrated that the insertion of MP structure into 125 nm TNT coating, which was denoted as MP125, could effectively improve the early adhesion, spreading and proliferation of surface MC3T3-E1 cells without damaging their osteogenic differentiation. Conclusion: We determined that the MP/TNT patterned samples (especially MP125) have excellent stability and osteogenesis properties, and may have better clinical application prospects.


Assuntos
Nanotubos/química , Osteogênese , Titânio/química , Adsorção , Fosfatase Alcalina/metabolismo , Animais , Adesão Celular/genética , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/genética , Forma Celular/genética , Sobrevivência Celular/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fluorescência , Regulação da Expressão Gênica , Humanos , Camundongos , Minerais/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/genética , Osteopontina/metabolismo , Porosidade , Água/química
14.
J Photochem Photobiol B ; 197: 111504, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31228687

RESUMO

High disappointment rate of the ligament to hard tissue mending after the medical procedure has dependably been a testing issue in rotator cuff repair. Considering the elasticity of carbon dot decorated polyethylene (f-CDs-PE) and osteogenic movement of gold substituted hydroxyapatite (Au@HA) bioceramic, f-CDs-PE-Au@HA biocomposite coatings were created by an electrophoretic deposition method (EPD), the in vivo and in vitro bioactivity and cytocompatibility were researched. The physico-chemical properties of f-CDs-PE-Au@HA biocomposite coatings were characterized using fourier transform infra-red (FTIR) and X-Ray diffractometery (XRD). The morphology of the fabricated biocomposites was analyses via scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. With a gamma-irradiation of f-CDs-PE-Au@HA biocomposite coating (BC2), the bond and multiplication of cells on biocomposite coating were improved. The specimen with a f-CDs-PE-Au@HA biocomposite (BC2) demonstrated a most noteworthy alkaline phosphatase activity articulation. The animal model consequences additionally show that the f-CDs-PE-Au@HA biocomposite (BC2) had great bioactive and cytocompatibility, which could develop the association of collagen and the arrangement of ligament and hard tissue. Expansion of the gamma-ray irradiation with f-CDs-PE-Au@HA biocomposite coating (BC2) at the tendon- hard tissue crossing point was exhibited to reinforce the mending entheses, increment hard tissue and tendon development and progress collagen association contrasted and control. The above outcomes have recommended that the progressive, implantable and solid stringy platforms built utilizing EPD extraordinary potential for enlargement of rotator cuff tears-recuperating.


Assuntos
Materiais Revestidos Biocompatíveis/química , Durapatita/química , Raios gama , Pontos Quânticos/química , Articulação do Ombro/patologia , Titânio/química , Artroplastia de Substituição , Densidade Óssea/efeitos da radiação , Carbono/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Materiais Revestidos Biocompatíveis/farmacologia , Colágeno Tipo I/metabolismo , Ouro/química , Humanos , Polietileno/química , Próteses e Implantes , Articulação do Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X
15.
Mol Med Rep ; 19(6): 4553-4560, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059021

RESUMO

Cardiac fibrosis secondary to long­term hypertension is known to promote cardiac dysfunction; however, few therapeutic agents are available for the treatment of this condition in clinical practice. The heptapeptide alamandine (Ala) has recently been identified as a component of the renin­angiotensin system (RAS), which exerts a protective effect against cardiac hypertrophy; however, it is unknown whether Ala may also be useful for the treatment of cardiac fibrosis. In the present study, the potential therapeutic effects of Ala on long­term hypertension­induced cardiac fibrosis were investigated in an aged, spontaneous hypertensive rat model. Weekly blood pressure (BP) measurements revealed that daily Ala treatment significantly decreased the systolic, diastolic and mean arterial BP compared with the control. Of note, the observed reduction in BP in Ala­treated animals markedly differed to that observed in rats treated with hydralazine (Hyd). Echocardiography further demonstrated that Ala treatment decreased the ratio of left ventricle mass to body weight, and alleviated structural and functional parameters associated with cardiac fibrosis, including left ventricular volume, ejection fraction and fractional shortening compared with the control and Hyd­treated groups. Furthermore, Ala deceased the density of cardiac fibrosis, as assessed by Masson and Sirius red staining; reduced expression of fibrotic proteins, including connective tissue growth factor, collagen I (COL1A1) and matrix metalloproteinase 9, was also observed. In addition, Ala treatment further decreased the expression of angiotensin II­induced fibrotic markers at the mRNA and protein levels in cultured cardiac fibroblasts; Ala­mediated inhibition of COL1A1 expression and Akt phosphorylation was inhibited via the Mas­related G protein receptor antagonist, PD123319. Collectively, the findings of the present study suggest that Ala is an effective anti­hypertensive peptide that can attenuate cardiac dysfunction and fibrosis induced by chronic hypertension, independent of BP.


Assuntos
Cardiomegalia/tratamento farmacológico , Fibrose/tratamento farmacológico , Hipertensão/tratamento farmacológico , Oligopeptídeos/farmacologia , Angiotensina II/genética , Angiotensina II/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Cardiomegalia/etiologia , Colágeno Tipo I/antagonistas & inibidores , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibrose/etiologia , Ventrículos do Coração/metabolismo , Hipertensão/complicações , Imidazóis/farmacologia , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Sistema Renina-Angiotensina
16.
Life Sci ; 231: 116422, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31059689

RESUMO

This study was performed to evaluate the antidiabetic and wound healing activity of plumbagin in diabetic rats by macroscopical, biochemical, histological, immunohistochemical and molecular methods. Percentage of wound closure and contraction was delayed in diabetic rats when compared to non-diabetic group. There was significant reduction in period of epithelialization, collagen and protein content. Serum insulin level was significantly lowered together with increase in glucose level in diabetic rats. Lipid levels were increased significantly with concomitant decrease in HDL level. The mRNA levels of Nrf2, collagen-1, TGF-ß and α-SMA were significantly lowered whereas Keap-1 levels were increased in diabetic rats. The level of lipid peroxides was increased while the levels of antioxidants were lowered significantly. ELISA results reveal upregulated levels of inflammatory markers. Western blot result shows upregulated levels of CD68 and CD163 proteins in wound area of diabetic rats. Histopathological observation revealed increased inflammatory cells infiltration in diabetic control. Immunofluorescent staining and immunohistochemical analysis also displayed delayed wound healing in diabetic groups. Diabetic rats treated with 10% and 20% plumbagin showed increased epithelialization, collagen deposition, increased serum insulin level and increased antioxidant status. Lipid peroxides and lipid levels were lowered significantly with increase in HDL level. Inflammatory markers were lowered, and growth factors expressions were increased markedly. Thus, the results of the study indicated that plumbagin administration could improve wound healing activity and could serve as a potent antidiabetic and anti-inflammatory agent.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Naftoquinonas/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Insulina/sangue , Masculino , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo
17.
Mol Med Rep ; 19(6): 5440-5452, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059099

RESUMO

The aim of the present study was to investigate the effects of advanced glycation end products (AGEs) and berberine hydrochloride (BBR) on the osteogenic differentiation ability of human periodontal ligament stem cells (hPDLSCs) in vitro, and their underlying mechanisms. hPDLSCs were subjected to osteogenic induction and were treated with AGEs or AGEs + BBR. Following varying numbers of days in culture, alkaline phosphatase (ALP) activity assays, ALP staining, alizarin red staining, ELISAs, and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analyses were performed to determine the osteogenic differentiation ability of hPDLSCs; RT­qPCR, western blot analysis, and immunofluorescence staining were conducted to investigate the underlying mechanisms. The canonical Wnt/ß­catenin pathway inhibitor XAV­939 and agonist CHIR­99021 were used to determine the contribution of the canonical Wnt/ß­catenin pathway to differentiation. Treatment with AGEs resulted in reduced ALP activity and Collagen I protein levels, decreased ALP staining, fewer mineralized nodules, and downregulated expression of osteogenic­specific genes [Runt­related transcription factor 2 (Runx2), Osterix, ALP, osteopontin (OPN), Collagen I and osteocalcin (OCN)] and proteins (Runx2, OPN, BSP and OCN); however, BBR partially rescued the AGE­induced decrease in the osteogenic potential of hPDLSCs. Furthermore, AGEs activated the canonical Wnt/ß­catenin signaling pathway and promoted the nuclear translocation of ß­catenin; BBR partially attenuated this effect. In addition, XAV­939 partially rescued the AGE­induced reduction in the osteogenic potential of hPDLSCs, whereas CHIR­99021 suppressed the BBR­induced increase in the osteogenic potential of hPDLSCs. The present study indicated that AGEs attenuated the osteogenic differentiation ability of hPDLSCs, in part by activating the canonical Wnt/ß­catenin pathway; however, BBR attenuated these effects by inhibiting the canonical Wnt/ß­catenin pathway. These findings suggest a role for BBR in periodontal regeneration induced by hPDLSCs in patients with diabetes mellitus.


Assuntos
Berberina/farmacologia , Osteogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação para Baixo/efeitos dos fármacos , Produtos Finais de Glicação Avançada/farmacologia , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Queratina-19/metabolismo , Ligamento Periodontal/citologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Fator de Transcrição Sp7/genética , Fator de Transcrição Sp7/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
18.
Mol Med Rep ; 19(6): 4727-4734, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059065

RESUMO

The aim of the present study was to investigate the protective effect of integrin ß1 in the treatment of stress urinary incontinence (SUI) by electrical stimulation, and the underlying mechanisms by which electrical stimulation regulates the collagen metabolism of female vaginal wall fibroblasts (FVWFs). FVWFs obtained from the vaginal wall tissue of patients with (Ingelman­Sundberg scale; grade II, n=8; grade III, n=10) or without (n=8) SUI during gynecological operations were isolated by enzymatic digestion and subsequently identified by immunocytochemistry. Following this, cultured FVWFs were treated with an inhibitor of integrin ß1, recombinant human integrin ß1 and electrical stimulation (100 mv/mm, 2 h, 20 Hz), followed by total mRNA and protein extraction. mRNA and protein expression levels of integrin ß1, transforming growth factor (TGF)­ß1 and collagen (COL) I and III in FVWFs were quantified by reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis respectively. Integrin ß1, TGF­ß1 and COL I and III expression levels were decreased in patients with SUI compared with healthy controls, and the grade III group had lower levels than the grade II group. Following electrical stimulation treatment, the expression levels of TGF­ß1, COL I and III were enhanced in the grade II group, but not in the grade III group. Nevertheless, the inhibitor of integrin ß1 reduced the protective effect of electrical stimulation in the grade II group. In addition, electrical stimulation combined with recombinant human integrin ß1 could also protect cells from SUI in the grade III group. The present study provides evidence for the increased degradation of the extracellular matrix and integrin ß1 in the vaginal wall tissues of patients with SUI, and the protective effect of electrical stimulation against SUI via integrin ß1. These results provide a novel mechanism for the treatment of SUI using electrical stimulation.


Assuntos
Estimulação Elétrica/métodos , Integrina beta1/farmacologia , Integrina beta1/uso terapêutico , Incontinência Urinária por Estresse/tratamento farmacológico , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Fator de Crescimento Transformador beta1 , Incontinência Urinária , Vagina/metabolismo , Vagina/patologia
19.
Toxicol Ind Health ; 35(4): 277-293, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30983556

RESUMO

The aim of the study was to investigate the effect of physical training on bone parameters of rats exposed to alcohol (Al) and/or cadmium (Cd). Young female rats were divided into one control group and six groups exposed to Cd and/or Al. Al (36% calories of diet) and Cd (20 mg Cd/kg feed) were administered with liquid diet. Half of the rats from the treated groups were subjected to treadmill training (20 m/min for 0.5 h, 4 days a week). The experiment was carried out for 5 months. Al decreased the concentration of calcium (Ca) and iron (Fe) in the femur, whereas Cd and Cd + Al intake reduced the contents of Ca, Fe and zinc. Al and/or Cd caused an increase in both C-terminal telopeptide of type I collagen (CTX1; bone resorption marker) and osteocalcin (OC; formation indicator) and enhanced the degree of porosity and flexural strength of the femur. Al partially prevented the loss of Fe from the bone caused by Cd, but intensified the inhibition of growth of body weight in comparison with separate exposure to Cd. In rats co-exposed to Cd + Al, the levels of CTX1 were greater compared with those treated with Al or Cd separately, and the density was less than that in rats exposed to Al separately. The training caused increases of magnesium and Ca contents, decreases in CTX1, as well as increases in OC and bone density, decreasing their porosity. The effect of training on the bone status, however, was limited (especially in rats co-exposed to Cd and Al) because of the increase in their mineralization, stimulated by exercises, was insufficient in relation to collagen production intensity. In conclusion, training had favourable effects on some bone parameters, but did not compensate for the negative effects of Al and/or Cd exposure on the poor mineralization and histopathological and morphological changes in the femur.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Cádmio/farmacologia , Etanol/farmacologia , Condicionamento Físico Animal/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Reabsorção Óssea , Cálcio/metabolismo , Colágeno Tipo I/metabolismo , Feminino , Fêmur/efeitos dos fármacos , Ferro/metabolismo , Magnésio/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Zinco/metabolismo
20.
Mol Med Rep ; 19(6): 4841-4851, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942423

RESUMO

Anastomotic fibrosis is highly likely to lead to reoperation in Crohn's disease (CD) patients. Triptolide (TPL) is considered to have anti­inflammatory and antifibrotic effects in a variety of autoimmune diseases, including CD. The present study aimed to investigate the effects of TPL on fibroblasts from strictured ileocolonic anastomosis of patients with CD and its underlying mechanism. Primary fibroblasts were obtained from strictured anastomosis tissue (SAT) samples and matched anastomosis­adjacent normal tissue (NT) samples which were collected from 10 CD patients who underwent reoperation because of anastomotic stricture. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to measure miR­16­1 and heat shock protein 70 (HSP70) levels. Western blotting was conducted to determine expression of HSP70, collagen I (Col­I), collagen III (Col­III) and α­smooth muscle actin (α­SMA) proteins. Agomir­16­1 and antagomir­16­1 were used to up and downregulate the expression of miR­16­1, respectively. Small interfering RNA (siRNA) was employed to inhibit the expression of HSP70. A wound healing assay was performed to measure the migration of fibroblasts. Cell proliferation was evaluated by MTT and 5­bromo­2­deoxyrudidine assays. Cell apoptosis was determined by caspase­3 activity and TUNEL assays. The results demonstrated that the levels of Col­I, Col­III and α­SMA were all significantly upregulated in SAT compared with NT. miR­16­1 levels in the SAT group were significantly compared with the NT group; conversely, the expression levels of HSP70 mRNA and protein in the SAT group were significantly lower compared with the NT group. Next, fibroblasts were treated with TPL to examine its effect on the miR­16­1/HSP70 pathway. The results demonstrated that the elevated expression of miR­16­1 in the SAT group was effectively inhibited by TPL treatment. Compared with the NT group, both the mRNA and protein levels of HSP70 were significantly downregulated in the SAT group cells, while TPL exhibited a strong promoting effect on HSP70 synthesis. Furthermore, upregulation of miR­16­1 reversed the effect of TPL on the miR­16­1/HSP70 pathway in fibroblasts from SAT. Overexpression of miR­16­1 significantly reversed the inhibitory effects of TPL treatment on migration, proliferation and extracellular matrix (ECM)­associated protein expression of fibroblasts from SAT. Finally, downregulation of miR­16­1 caused similar effects to the fibroblasts as the TPL treatment; however, the inhibitory effects on cell biological functions induced by antagomir­16­1 were all significantly reversed by HSP70 silencing. The present findings indicated that TPL may be a potential therapeutic option for postoperative anastomosis fibrosis of patients with CD. The miR­16­1/HSP70 pathway had a substantial role in the inhibitory effects of TPL on migration, proliferation and ECM synthesis rate of fibroblasts from strictured anastomosis tissues.


Assuntos
Anastomose Cirúrgica , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doença de Crohn/tratamento farmacológico , Diterpenos/antagonistas & inibidores , Fibroblastos/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , MicroRNAs/metabolismo , Fenantrenos/antagonistas & inibidores , Actinas/metabolismo , Adulto , Antagomirs/farmacologia , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , China , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Regulação para Baixo/efeitos dos fármacos , Compostos de Epóxi/antagonistas & inibidores , Feminino , Fibroblastos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
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