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Objetivo: Determinar la efectividad del suero autólogo rico en factores de crecimiento en la reparación de lesiones de la superficie ocular de evolución incierta con el tratamiento convencional. Materiales y métodos: Se trataron 46 unidades oculares con afecciones de la superficie ocular agrupadas en queratopatías por exposición, queratopatías por síndrome de ojo seco / neurotróficas, y traumas oculares. Las partes oculares afectadas fueron: conjuntiva, cornea (epitelio, estroma) y esclera. Se evaluaron de manera anatómica y funcional con la prueba de Schirmer, tinción con Fluoresceína y tomografía de coherencia óptica (TCO) entre marzo y diciembre del 2020. Resultados: Los síntomas mejoraron en el siguiente orden: dolor ocular, sensación de cuerpo extraño, blefaroespasmo, hiperemia y lagrimeo. Las lesiones evolucionaron favorablemente de la siguiente manera: en primer lugar las conjuntivales y del epitelio corneal, luego las del estroma corneal y finalmente las lesiones en la esclera. Se obtuvo una media de 15 días para recuperación inmediata de la superficie y de 21 días para recuperación tardía. Las lesiones con adelgazamiento parcial profundo de esclera tomaron alrededor de 2 meses. Conclusiones: Los hallazgos relacionados al umbral del dolor, tiempo de recuperación, remodelación cicatrizal del tejido afectado y recuperación de la agudeza visual son prometedores e importantes. La utilización de suero autólogo rico en factores de crecimiento puede ser una alternativa terapéutica para las lesiones de difícil resolución con el tratamiento convencional.
Objective: To determine the effectiveness of autologous serum rich in growth factors to repair ocular surface lesions which have uncertain progression with conventional treatment. Materials and methods: AForty-six (46) eyes with ocular surface disorders such as exposure keratopathy, keratopathy caused by dry eye syndrome, neurotrophic keratopathy and blunt eye injury were treated. The affected areas were the conjunctiva, cornea (epithelium, stroma) and sclera. Anatomical and functional evaluations were performed between March and December 2020 using Schirmer's test, fluorescein eye stain and optical coherence tomography (OCT). Results: The symptoms improved in the following order: eye pain, foreign body sensation, blepharospasm, hyperemia and epiphora. Additionally, the lesions progressed favorably as follows: first, those of the conjunctiva and corneal epithelium; then, those of the corneal stroma; and, finally, those of the sclera. An average of 15 days was required for immediate ocular surface recovery and 21 days for late recovery. The lesions with total scleral thinning healed in about two months. Conclusions: The findings related to pain threshold, recovery time, scar tissue remodeling of the affected tissue and visual acuity improvement are promising and important. Using autologous serum rich in growth factors may be a therapeutic alternative for those lesions that are difficult to resolve with conventional treatment.
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Objective:To investigate the relationship between plasma Dickkopf-1 and early neurological deterioration (END) and outcome in patients with acute ischemic stroke.Methods:From January 2020 to December 2020, consecutive patients with first-ever ischemic stroke form the Department of Neurology, Nanjing Jiangbei Hospital were included. All patients were hospitalized within 24 h after onset. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d after admission increased by ≥2 or motor function score increased by ≥1 compared with the baseline. Poor outcome was defined as the modified Rankin Scale score >2 at 90 d after onset. Multivariate logistic regression analysis was used to determine the independent correlation between plasma Dickkopf-1 and END and outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of plasma Dickkopf-1 for END and poor outcome. Results:A total of 176 patients were enrolled, including 92 males (52.3%), aged 66.7±9.6 years. The median Dickkopf-1 was 4.30 μg/L, 52 patients (29.5%) developed END, and 81 (46.0%) had poor outcome. Multivariate logistic regression analysis showed that the higher Dickkopf-1 was an independent predictor of END (odds ratio [ OR] 1.696, 95% confidence interval [ CI] 1.223-2.351; P=0.002) and poor outcome ( OR 1.566, 95% CI 1.156-2.121; P=0.004). ROC curve analysis showed that plasma Dickkopf-1 had good predictive value for END, and its area under the curve was 0.717 (95% CI 0.634-0.801); the optimal cut-off value was 4.40 μg/L, and the corresponding predictive sensitivity and specificity were 71.2% and 60.5%, respectively. Dickkopf-1 also had good predictive value for poor outcome, and its area under the curve was 0.701 (95% CI 0.624-0.778); the optimal cut-off value was 4.25 μg/L, and the corresponding predictive sensitivity and specificity were 65.4% and 61.1%, respectively. Conclusion:Plasma Dickkopf-1 has good predictive value for END and poor outcome in patients with acute ischemic stroke.
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RESUMEN Introducción: los avances científico-técnicos en el campo de la Biología celular y molecular han permitido restaurar y mejorar la función de órganos y tejidos lesionados por ciertas enfermedades y traumatismos. La Ingeniería de tejido se define como el uso de los principios y métodos de la Ingeniería, la Biología y la Bioquímica, los cuales están orientados a la comprensión de la estructura y la función de los tejidos normales y patológicos, y al consecuente desarrollo de sustitutos biológicos para restaurar, mantener o mejorar su función. Objetivo: realizar un acercamiento a algunos aspectos de la Biología celular y molecular vinculada con la Ingeniería tisular ósea. Métodos: se realizó una búsqueda bibliográfica en SciELO Cuba y en Google académico durante el período de 1 de marzo al 28 de abril de 2018. Se evaluaron 134 artículos y el estudio se circunscribió a los 25 artículos que se enfocaban en estas temáticas de manera integral. Conclusiones: se ofreció una visión general de los avances que se han obtenido en la Biología celular y molecular, y en particular a: la aplicación de los factores de crecimiento en la Ingeniería del tejido óseo, así como sus futuras perspectivas. Se concluyó que es fundamental consolidar una base apropiada de conocimientos sobre la Biología celular y molecular y el desarrollo actual de la Ingeniería del tejido óseo.
ABSTRACT Introduction: scientific and technical advances in the field of cellular and molecular biology have allowed restoring and improving the function of organs and tissues injured by certain diseases and trauma. Tissue engineering is defined as the use of the principles and methods of Engineering, Biology and Biochemistry, which are aimed at understanding the structure and function of normal and pathological tissues, and the consequent development of biological substitutes to restore, maintain or improve their function. Objective: to carry out an approach to some aspects of cellular and molecular biology related to bone tissue engineering. Methods: a bibliographic review was carried out in SciELO Cuba and Google Scholar from March 1 to April 28, 2018. A number of 134 articles were evaluated and the study was limited to 25 articles that focused on these topics in an integral way. Conclusions: an overview of the advances that have been obtained in cellular and molecular biology was offered, particularly to the application of growth factors in bone tissue engineering, as well as its future perspectives. We concluded that it is essential to consolidate an appropriate knowledge base on cellular and molecular biology and the current development of bone tissue engineering.
Subject(s)
Tissue Engineering , Intercellular Signaling Peptides and Proteins , Regenerative Medicine , Placenta Growth FactorABSTRACT
ABSTRACT Objective: To identify evidence about the effects of growth factor application on venous ulcer healing. Method: Systematic review and meta-analysis, including Randomized Clinical Trials. Searches: Ovid MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, LILACS, Web of Science, Digital Library of Theses and Dissertations; Google Scholar and list of references. Results: 802 participants were recruited from the 10 included studies: 472 in the intervention group (growth factors) and 330 as control. The relative risk for the complete healing outcome was 1.06 [95% CI 0.92-1.22], p = 0.41. Participants who received Platelet-Rich Plasma and Epidermal Growth Factor showed a slight tendency to achieve complete healing, but without statistical relevance (p <0.05). Most of the studies were classified as moderate risk of bias. Conclusion: The effect of the application of growth factors for complete healing in venous ulcers is not clear, and clinical trials with methodological quality are required for more accurate recommendations.
RESUMEN Objetivo: Identificar evidencias acerca de los efectos de la aplicación de factores de crecimientoenlacicatrización de úlceras venosas. Método: Revisión sistemática y metanálisis, incluyendo Ensayos Clínicos aleatorizados. Búsquedas: Ovid MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, LILACS, Web of Science, Biblioteca Digital de Tesis y Disertaciones; Google Académico y lista de referencias Resultados: 802 participantes fueron reclutados por los 10 estudios incluidos: 472 en el grupo intervención (factores de crecimiento) y 330 como control. El riesgo relativo para el desenlace de cicatrización completa fue de 1,06 [IC95% 0,92-1,22], p = 0.41. Los participantes que recibieron Plasma Rico en Plaquetas y Factor de Crecimiento Epidérmico presentaron una ligera tendencia a alcanzar una cicatrización completa, pero sin relevancia estadística (p <0.05). La mayoría de los estudios se clasificaron como moderado riesgo de sesgo. Conclusión: El efecto de la aplicación de factores de crecimiento para cicatrización completa en úlceras venosas no está claro, siendo necesarios ensayos clínicos con calidad metodológica para recomendaciones más precisas.
RESUMO Objetivo: Identificar evidências acerca dos efeitos da aplicação de fatores de crescimento na cicatrização de úlceras venosas. Método: Revisão sistemática e metanálise, incluindo Ensaios Clínicos Randomizados. Buscas: Ovid MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, LILACS, Web of Science, Biblioteca Digital de Teses e Dissertações; Google Acadêmico e lista de referências. Resultados: 802 participantes foram recrutados pelos 10 estudos incluídos: 472 no grupo intervenção (fatores de crescimento) e 330 como controle. O risco relativo para o desfecho de cicatrização completa foi de 1,06 [IC95% 0,92-1,22], p=0.41. Os participantes que receberam Plasma Rico em Plaquetas e Fator de Crescimento Epidérmico apresentaram uma ligeira tendência a alcançar cicatrização completa, porém sem relevância estatística (p<0.05). A maioria dos estudos foi classificada como moderado risco de viés. Conclusão: O efeito da aplicação de fatores de crescimento para cicatrização completa em úlceras venosas não está claro, sendo necessários ensaios clínicos com qualidade metodológica para recomendações mais precisas.
Subject(s)
Humans , Varicose Ulcer/drug therapy , Wound Healing/drug effects , Intercellular Signaling Peptides and Proteins/pharmacology , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Programmed death-1 (PD-1) is an important immunosuppressive molecule which interacts with its ligand programmed death-ligand 1 (PD-L1) and plays an important role in central/peripheral immune tolerance, transplantation immunity, tumor immune escape, and autoimmune disease. At present, there is still no systematic understanding of the role of the PD-1/PD-L1 pathway in the development and progression of liver diseases. This article summarizes related studies on the role of the PD-1/PD-L1 pathway in the progression of liver diseases and reviews the immunoregulatory function of the PD-1/PD-L1 pathway and its role in liver diseases. It is pointed out that the PD-1/PD-L1 pathway is involved in immunoregulatory function of the liver and plays an important role in the development and progression of liver inflammation, autoimmune liver diseases, viral liver diseases, tumor immune escape, transplantation rejection reaction, induced immune response, and autoimmune tolerance. Intervention of the PD-1/PD-L1 pathway may provide new strategies and directions for the prevention and treatment of liver disease.
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Programmed death-1 (PD-1) is an important immunosuppressive molecule which interacts with its ligand programmed death-ligand 1 (PD-L1) and plays an important role in central/peripheral immune tolerance, transplantation immunity, tumor immune escape, and autoimmune disease. At present, there is still no systematic understanding of the role of the PD-1/PD-L1 pathway in the development and progression of liver diseases. This article summarizes related studies on the role of the PD-1/PD-L1 pathway in the progression of liver diseases and reviews the immunoregulatory function of the PD-1/PD-L1 pathway and its role in liver diseases. It is pointed out that the PD-1/PD-L1 pathway is involved in immunoregulatory function of the liver and plays an important role in the development and progression of liver inflammation, autoimmune liver diseases, viral liver diseases, tumor immune escape, transplantation rejection reaction, induced immune response, and autoimmune tolerance. Intervention of the PD-1/PD-L1 pathway may provide new strategies and directions for the prevention and treatment of liver disease.
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Abstract Objective: To demonstrate the underlying mechanisms of aortic dissection compared to those of coronary artery disease in terms of the transforming growth factor-beta (TGF-β) signaling pathway. Methods: Twenty consecutive aortic dissection patients and 20 consecutive coronary artery disease patients undergoing a surgical treatment in this hospital were enrolled into this study. The aortic tissues were sampled and the TGF-β1 and its receptor TGF-β receptor I (TβRI) were detected by Western blotting assay. Results: TGF-β1 and TβRI were positively expressed in the aortic tissues in both groups by Western blotting assay. The expressions of the two proteins were significantly higher in the aortic tissue of patients with aortic dissection than in those with coronary artery disease. The quantitative analyses of the relative gray scales of the proteins disclosed close correlations between the expressions of TGF-β1 and TβRI in both the study and control group patients. Conclusions: The aortic remodeling of aortic dissection might differ from that of coronary artery atherosclerosis concerning the nature, mechanism, mode, and activities of TGF-β signaling pathway. The development of aortic dissection could be associated with a significantly enhanced function of TGF-β1/Smad signaling transduction as a result of aortic remodeling incorporating both vascular injury and repair.
Subject(s)
Humans , Male , Female , Middle Aged , Coronary Artery Disease/metabolism , Transforming Growth Factor beta1/metabolism , Aortic Dissection/metabolism , Biomarkers/metabolismABSTRACT
ABSTRACT Objective: To evaluate the neurotrophin mRNA expression and axon count in the median nerve of Wistar rats submitted to neural mobilization (NM) after nerve compression. Methods: Eighteen animals were randomly divided into G1 (nerve compression only), G2 (NM for 1 min), and G3 (NM for 3 min). For NM, the animals were anesthetized and the right scapula received the mobilization, adapted as indicated for humans, on alternate days, from the third to the 13th postoperative (PO) day, totaling six days of therapy. On the 14th PO day, animals were anesthetized and euthanized. Fragments of the median nerve, distal to the compression procedure, were removed for histomorphometric analysis and expression of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) by RT-PCR. Results: Histomorphometric analysis revealed differences in the number of axons in the injured side, which was significantly lower in the injured limb nerve compared to the control limb, whereas the RT-PCR analysis showed no significant differences in the expression of NGF or BDNF. Conclusion: NM treatment did not affect median nerve regeneration, which maintained normal recovery rates.
RESUMO Objetivo: Avaliar a expressão de RNAm de neurotrofinas e a contagem de axônios no nervo mediano de ratos Wistar submetidos à mobilização neural (MN) após compressão nervosa. Métodos: Foram divididos aleatoriamente 18 animais em G1 (apenas compressão nervosa), G2 (MN por 1 minuto) e G3 (MN por 3 minutos). Para a MN, os animais foram anestesiados e o membro escapular direito recebeu a mobilização, adaptada da forma indicada para humanos, em dias alternados, do terceiro ao 13° dia de pós-operatório (PO), em seis dias de terapia. No 14° dia PO, os animais foram anestesiados e eutanasiados. Fragmentos do nervo mediano, distais ao procedimento de compressão, foram retirados para análise histomorfométrica e de expressão das neutrotrofinas, fator de crescimento do nervo (NGF) e fator de crescimento derivado do cérebro (BNDF) por RT-PCR. Resultados: A análise histomorfométrica evidenciou diferenças no número de axônios nos lados lesionados, que foi significativamente menor no nervo do membro lesado comparado com o membro controle; por sua vez, a análise por RT-PCR não apontou diferenças significativas na expressão de NGF e nem de BNDF. Conclusão: O tratamento de MN não afetou a regeneração do nervo mediano, que manteve índices normais de recuperação.
Subject(s)
Animals , Rats , Exercise , Rats, Wistar , Intercellular Signaling Peptides and Proteins , Histology , Median Nerve , Nerve RegenerationABSTRACT
Primary liver cancer is a common malignant tumor in clinical practice,and secreted protein acidic and rich in cysteine (SPARC) plays a very important role in the progression and metastasis of liver cancer.This article introduces the structure and biological function of SPARC and analyzes its mechanism of action in malignant tumors and its association with the progression and metastasis of liver cancer,as well as the perspectives of its application in the diagnosis and treatment of liver cancer.
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Abstract Periodontal regeneration is still a challenge in terms of predictability and magnitude of effect. In this study we assess the biological effects of combining chemical root conditioning and biological mediators on three relevant cell types for periodontal regeneration. Material and Methods: Bovine dentin slices were conditioned with 25% citric acid followed by topical application of basic fibroblast growth factor (bFGF, 10 and 50 ng). We used ELISA to assess the dynamics of bFGF release from the dentin surface and RT-qPCR to study the expression of Runx2, Col1a1, Bglap and fibronectin by periodontal ligament (PDL) fibroblasts, cementoblasts and bone marrow stromal cells (BMSC) grown onto these dentin slices. We also assessed the effects of topical application of bFGF on cell proliferation by quantification of genomic DNA. Results: Acid conditioning significantly increased the release of bFGF from dentin slices. Overall, bFGF application significantly (p<0.05) increased cell proliferation, except for BMSC grown on non-conditioned dentin slices. Dentin substrate discretely increased expression of Col1a1 in all cell types. Expression of Runx2, Col1a1 and Fn was either unaffected or inhibited by bFGF application in all cell types. We could not detect expression of the target genes on BMSC grown onto conditioned dentin. Conclusion: Acid conditioning of dentin improves the release of topically-applied bFGF. Topical application of bFGF had a stimulatory effect on proliferation of PDL fibroblasts, cementoblasts and BMSC, but did not affect expression of Runx2, Col1a1, Bglap and fibronectin by these cells.
Subject(s)
Animals , Cattle , Periodontal Ligament/drug effects , Regeneration/drug effects , Fibroblast Growth Factor 2/pharmacology , Dentin/drug effects , Cell Proliferation/drug effects , Periodontal Ligament/metabolism , Gene Expression , Fibroblast Growth Factor 2/administration & dosageABSTRACT
O PRF líquido pode facilitar o posicionamento e a escultura de enxertos ósseos particulados, além dos possíveis benefícios relacionados ao reparo ósseo e fibromucosa. Para tanto, é necessário que o profissional conheça os aspectos práticos e teóricos envolvidos no seu uso. Um paciente com 45 anos de idade, apresentava perda dos incisivos maxilares e de espessura da crista óssea na região, impossibilitando a colocação de implantes de diâmetro convencional. Para a regeneração óssea, foi utilizado enxerto com substituto ósseo associado a coágulos de PRF, PRF líquido e tela de titânio. Após o reparo ósseo, foram instalados dois implantes na região dos incisivos laterais como pilares de uma prótese parcial fixa de quatro elementos. O PRF líquido pode facilitar procedimentos de enxertia óssea e diminuir o risco de iatrogenia sem, contudo, aumentar significativamente o custo e o tempo do tratamento.
The liquid PRF can facilitate the positioning and carving of particulate bone grafts, in addition to possible benefi ts related to bone and soft tissue repair. Therefore, it is necessary that the professional knows the practical and theoretical aspects involved in its use. A 45-year-old patient presented loss of maxillary incisors and thickness of the bone crest in the region, making it impossible to place implants of conventional diameter. For bone regeneration, graft was used with bone substitute associated with PRF clots, liquid PRF and titanium mesh. After bone repair, two implants were installed in the region of the lateral incisors as pillars of a fixed partial denture of four elements. The liquid PRF can facilitate bone graft procedures and reduce the risk of iatrogenic, without, however, significantly increasing the cost and time of treatment.
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Humans , Female , Middle Aged , Biocompatible Materials , Bone Substitutes/therapeutic use , Bone Transplantation/methods , Dental Implantation , Dental Prosthesis, Implant-Supported , Platelet-Rich PlasmaABSTRACT
Objective To observe the expression of cysteine-rich protein 61 (Cyr61) in transforming growth factor-β1 (TGF-β1)-activated renal fibroblasts (NRK-49F),and to explore its effect and mechanism.Methods (1) NRK-49F cells were activated by TGF-β1 with different concentrations (0.0,0.5,1.0,2.0,5.0 μg/L).Western blotting was used to detect the expression of Cyr61 protein,and CCK-8 assay was used to test the proliferative activity of NRK-49F cells.(2) NRK-49F cells with low expression and over expression of Cyr61 were established by plasmid transfection.The cells were divided into control group (null vector transfection),over-expression group and lowexpression group.The proliferation was discovered by CCK-8 assay after 24,48 and 72 h.Further,5.0 μg/L TGF-β1 activated these three groups.The proliferation was also discovered by CCK-8 assay and the cell cycle was analyzed by flow cytometry.The mRNA expressions of fibrosis markers (Collα1,Col3αl,MMP9,MMP13) and factors of cell senescence signal pathway (p53,p21,Rb,p16) were ascertained by real time PCR,and the protein expressions of Col3 and MMP9 were detected by Western blotting.Results (1) Compared with 0.0 μg/L TGF-β1 group,the proliferation of NRK-49F cells was enhanced in 0.5,1.0,2.0 and 5.0 μg/L TGF-β1 groups (all P ＜ 0.05),while the expression of Cyr61 protein was decreased in 1.0 μg/L group and increased in 5.0 μg/L group (all P ＜0.05).(2) The proliferation of over-expression group was lower than that of control group after 24,48and 72 h (all P＜ 0.05),which was in a time-dependent manner.(3) Compared with control group activated by TGF-β1,the over-expression group expressed less fibrosis factors (Col1α1 and Col3α1)and more anti-fibrosis factors (MMP9 and MMP13) with decreased proliferation (all P ＜ 0.05).Simultaneously,the proportion of cells bogged down in G1 phases,as well as the expressions of p53,p21 and Rb mRNA increased (all P ＜ 0.05).The above effects of low-expression group were just opposite to over-expression group.Moreover,there was no significant difference in the expression of p16 gene among the three groups (P ＞ 0.05).Conclusions Cyr61 can curb the proliferation and fibrotic phenotypes of fibroblasts,thereafter slowing down the process of renal fibrosis.The p53/p21/Rb interrelated cell senescence signal pathway may be involved in the anti-fibrosis process.
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The incidence of spinal cord injury is increasing year by year, and more and more attentions have been paid. Growth factors can promote the regeneration of nerve fibers and synapses, and they also play an important role in the treatment of spinal cord injury and the recovery of neurological function. The growth factor itself has a short half-life, so it is necessary to use growth factor gene vectors to transfect stem cells and nanoparticles to deliver growth factors or biocompatible scaffolds to support growth factors to treat spinal cord injuries. With the development of the research on growth factors, the application of single growth factor is difficult to meet the need of treatment to spinal cord injury. To explore the synergistic effect of various growth factors in order to achieve a better therapeutic effect is a promising research direction in the future. The purpose of this review is to summarize the therapeutic effects of growth factors on spinal cord injury including brain-derived neurotrophic factor, neurotrophic factor 3, nerve growth factor, basic fibroblast growth factor and synergy therapy of growth factors.
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Objective To observe the expression of cysteine-rich protein 61 (Cyr61) in transforming growth factor-β1 (TGF-β1)-activated renal fibroblasts (NRK-49F),and to explore its effect and mechanism.Methods (1) NRK-49F cells were activated by TGF-β1 with different concentrations (0.0,0.5,1.0,2.0,5.0 μg/L).Western blotting was used to detect the expression of Cyr61 protein,and CCK-8 assay was used to test the proliferative activity of NRK-49F cells.(2) NRK-49F cells with low expression and over expression of Cyr61 were established by plasmid transfection.The cells were divided into control group (null vector transfection),over-expression group and lowexpression group.The proliferation was discovered by CCK-8 assay after 24,48 and 72 h.Further,5.0 μg/L TGF-β1 activated these three groups.The proliferation was also discovered by CCK-8 assay and the cell cycle was analyzed by flow cytometry.The mRNA expressions of fibrosis markers (Collα1,Col3αl,MMP9,MMP13) and factors of cell senescence signal pathway (p53,p21,Rb,p16) were ascertained by real time PCR,and the protein expressions of Col3 and MMP9 were detected by Western blotting.Results (1) Compared with 0.0 μg/L TGF-β1 group,the proliferation of NRK-49F cells was enhanced in 0.5,1.0,2.0 and 5.0 μg/L TGF-β1 groups (all P ＜ 0.05),while the expression of Cyr61 protein was decreased in 1.0 μg/L group and increased in 5.0 μg/L group (all P ＜0.05).(2) The proliferation of over-expression group was lower than that of control group after 24,48and 72 h (all P＜ 0.05),which was in a time-dependent manner.(3) Compared with control group activated by TGF-β1,the over-expression group expressed less fibrosis factors (Col1α1 and Col3α1)and more anti-fibrosis factors (MMP9 and MMP13) with decreased proliferation (all P ＜ 0.05).Simultaneously,the proportion of cells bogged down in G1 phases,as well as the expressions of p53,p21 and Rb mRNA increased (all P ＜ 0.05).The above effects of low-expression group were just opposite to over-expression group.Moreover,there was no significant difference in the expression of p16 gene among the three groups (P ＞ 0.05).Conclusions Cyr61 can curb the proliferation and fibrotic phenotypes of fibroblasts,thereafter slowing down the process of renal fibrosis.The p53/p21/Rb interrelated cell senescence signal pathway may be involved in the anti-fibrosis process.
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Objective To investigate the specific growth factor tumor (TSGF) in the treatment of chemoembolization (transcatheter) in the treatment of primary hepatic carcinoma (HCC) with the change of the level of arterial and transcatheter arterial chemoembolization (TACE),and the evaluation of the value in the treatment.Methods From January 2012 to December 2014 in Inner Mongolia Medical University affiliated Hospital,75 patients with primary liver cancer were treated by TACE,and all patients were treated with TACE.Then the changes of liver function,blood routine,alpha-fetoprotein (AFP),and TSGF levels were monitored at the preoperative,postoperative 1 week,1 month,and 3 months.The curative effect was evaluated.Results At 1 week after operation,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly higher than those before operation,but no differences were compared to the preoperative 1 month after operation.There was no significant difference in the level of WBC before and after operation.At 1 week after operation,the averaged AFP and TSGF water were significantly increased,but the 1 week after operation was significantly decreased.At 1 month after operation,there was no difference in the levels of TSGF and AFP between complete remission + partial remission + stable disease (CR + PR + SD) and progress disease (PD),and the levels of AFP and CR + PR + SD in PD patients were significantly lower than those in patients with TSGF at 3 months after operation.The levels of TSGF and AFP were lower in PD patients after 3 months,and there was no difference between TSGF and AFP levels at the different time after treatment in patients with CR + PR + SD.There was no significant difference in AFP levels before and after AFP treatment,and the average water level of TSGF before treatment was significantly higher than that of TACE before and after treatment.The difference was statistically significant (P ＜ 0.05).Conclusions TSGF level in patients with primary liver cancer patients with TACE treatment increased after the first rise,especially in the treatment of 1 month after the deterioration of the situation and the tumor has a significant correlation.In the evaluation of curative effect,it has a high value.Combined with AFP,CT examination can increase the long-term efficacy of TACE treatment of primary liver cancer.
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The incidence of spinal cord injury is increasing year by year, and more and more attentions have been paid. Growth factors can promote the regeneration of nerve fibers and synapses, and they also play an important role in the treatment of spinal cord injury and the recovery of neurological function. The growth factor itself has a short half-life, so it is necessary to use growth factor gene vectors to transfect stem cells and nanoparticles to deliver growth factors or biocompatible scaffolds to support growth factors to treat spinal cord injuries. With the development of the research on growth factors, the application of single growth factor is difficult to meet the need of treatment to spinal cord injury. To explore the synergistic effect of various growth factors in order to achieve a better therapeutic effect is a promising research direction in the future. The purpose of this review is to summarize the therapeutic effects of growth factors on spinal cord injury including brain-derived neurotrophic factor, neurotrophic factor 3, nerve growth factor, basic fibroblast growth factor and synergy therapy of growth factors.
ABSTRACT
ABSTRACT Objective: To evaluate growth factors and cytokines in samples of platelet-rich plasma obtained by three different centrifugation methods. Methods: Peripheral blood of six individuals with no hematological diseases, aged 18 to 68 years, was drawn to obtain platelet-rich plasma, using the open method and commercial columns by Medtronic and Biomet. The products obtained with the different types of centrifugation were submitted to laboratory analysis, including pro-inflammatory cytokines and chemokines by flow cytometry assays, the concentration of fibroblast growth factors-2 (FGF-2) and transforming growth factor-beta1 (TGF-β1). Results: The diverse separation methods generated systematically different profiles regarding number of platelets and leukocytes. The Medtronic system yielded a product with the highest concentration of platelets, and the open method, with the lowest concentration of platelets. The results of cytokine analysis showed that the different types of centrifugation yielded products with high concentrations of interleukin 8, interleukin 1β. The open system resulted in a product with high levels of interleukin 6. Other cytokines and chemokines measured were similar between systems. The product obtained with the open method showed higher levels of TGF-β1 in relation to other systems and low FGF-2 levels. Conclusion: The formed elements, growth factors and cytokines in samples of platelet-rich plasma varied according to the centrifugation technique used.
RESUMO Objetivo: Avaliar fatores de crescimento e citocinas em amostras de plasma rico em plaquetas obtidas por três diferentes métodos de centrifugação. Métodos: Foi coletado sangue periférico de seis indivíduos, sem doença hematológica, com idades entre 18 e 68 anos, para obtenção de plasma rico em plaquetas, utilizando o método aberto e sistemas comerciais das empresas Medtronic e Biomet. Os produtos obtidos com os diferentes tipos de centrifugação foram submetidos às análises laboratoriais, incluindo citocinas próinflamatórias e quimiocinas, por meio de ensaios de citometria de fluxo, concentração do fator de crescimento fibroblástico-2 (FGF-2) e fator de crescimento transformador-beta1 (TGF-β1). Resultados: As diferentes centrifugações geraram perfis sistematicamente diferentes referentes ao número de plaquetas e de leucócitos. O sistema da Medtronic originou produto com a maior concentração de plaquetas, e o método aberto com a menor concentração de plaquetas. Os resultados da análise de citocinas demonstraram que os diferentes tipos de centrifugação originaram produtos com elevadas concentrações de interleucina 8 e interleucina 1β. O sistema aberto resultou em produto com elevados níveis de interleucina 6. As demais citocinas e quimiocinas mensuradas foram similares entre os sistemas. O produto obtido com o método aberto apresentou níveis superiores de TGF-β1 em relação aos demais sistemas e reduzidos níveis de FGF-2. Conclusão: Os elementos figurados, fatores de crescimento e citocinas, em amostras de plasma rico em plaquetas, variaram conforme a técnica de centrifugação utilizada.
Subject(s)
Humans , Adolescent , Adult , Middle Aged , Aged , Young Adult , Cytokines/analysis , Intercellular Signaling Peptides and Proteins/analysis , Platelet-Rich Plasma/chemistry , Centrifugation/methods , Cytokines/blood , Interleukins/analysis , Interleukins/blood , Chemokines/analysis , Chemokines/blood , Intercellular Signaling Peptides and Proteins/blood , Rotator Cuff Injuries/surgeryABSTRACT
Abstract Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine.
Resumo O infarto do miocárdio representa a manifestação mais significativa da cardiopatia isquêmica e está associado a elevada morbimortalidade. Novas estratégias vêm sendo investigadas com o intuito de regenerar o miocárdio lesionado, incluindo a terapia gênica, a terapia celular e a utilização de fatores de crescimento. A terapia com fatores de crescimento despertou interesse em medicina cardiovascular, devido aos mecanismos de regeneração induzidos por essas biomoléculas, incluindo angiogênese, remodelamento da matriz extracelular, proliferação de cardiomiócitos e recrutamento de células-tronco, dentre outros. Em conjunto, tais mecanismos promovem a reparação do miocárdio e a melhora da função cardíaca. Esta revisão pretende abordar o papel estratégico da terapia, com fatores de crescimento, para a regeneração cardíaca, considerando seu caráter inovador e multifatorial sobre o reparo do miocárdio após dano isquêmico. Diferentes questões serão discutidas, destacando-se os mecanismos de regeneração como recurso terapêutico potencial mediado por fatores de crescimento e os desafios para tornar essas proteínas terapeuticamente viáveis no âmbito da cardiologia e da medicina regenerativa.
Subject(s)
Humans , Regeneration/physiology , Myocardial Ischemia/physiopathology , Myocardial Ischemia/therapy , Intercellular Signaling Peptides and Proteins/therapeutic use , Regenerative Medicine/methods , Neovascularization, Physiologic/physiology , Myocytes, Cardiac/physiology , Regenerative Medicine/trends , Heart/physiologyABSTRACT
Contextualização: Os fatores de crescimento atuam no reparo tecidual emitindo sinais modulatórios estimulando ou inibindo os processos celulares. Objetivo: Analisar a eficácia dos fatores de crescimento no processo cicatricial de úlceras venosas através da busca de evidência na literatura científica. Método: Revisão sistemática segundo as recomendações da Colaboração Cochrane. Critérios de inclusão: Ensaios clínicos randomizados sobre o uso dos fatores de crescimento no tratamento de úlceras venosas; abordando o número total de úlceras cicatrizadas, redução da área e/ou tempo de cicatrização. Exclusão: estudos em andamento, protocolos de pesquisa; artigos que associam fatores de crescimento ao enxerto de pele e estudos que incluíram úlceras de múltiplas etiologias sem análise por subgrupo. Bases de dados consultadas: Ovid MEDLINE(R); Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations; Ovid MEDLINE(R) Epub Ahead of Print; EMBASE; CINAHL Plus with Full Text, Cochrane CENTRAL, LILACS e Web of Science. Também foram consultados a Biblioteca Digital Brasileira de Teses e Dissertações e Google Acadêmico, além da busca manual através da lista de referências dos estudos incluídos. Não houve restrição temporal ou de idioma. A análise estatística foi realizada através do programa Review Manager 5.3 (Colaboração Cochrane). Para variáveis dicotômicas, foram calculados o risco relativo considerando um intervalo de confiança de 95%. A metanálise foi realizada utilizado o modelo de efeito fixo de Mantel-Haenszel quando I2 < 50% e modelo randômico para I2 > 50%. Resultados: A aplicação de fatores de crescimento para tratamento de úlceras venosas não acelerou o reparo tecidual comparado como tratamento padrão/placebo (RR 1,01 [IC 95%: 0,88-1,16]). Resultados semelhantes foram encontrados ao analisar os subgrupos PRP (RR 1,01 [IC 95%: 0,80-1,28]); KGF (RR 0,93 [IC 95%:0,78-1,11]); PDGF (RR 1,17 [IC 95%: 0,78-1,74]); EGF (RR 2,87 [IC 95%: 0,65-12,73; p=0,17]); TGF (RR 1,14 [IC 95%: 0,41-3,15]). Conclusão: Os resultados dessa revisão foram baseados em estudos classificados como moderado a alto risco de viés, portanto, precisam ser interpretados com cautela. Portanto, não há evidências para afirmar que os fatores de crescimento influenciam positivamente na cicatrização de úlceras venosas. Estudos mais robustos, com maior poder e melhor qualidade metodológica são necessários para de determinar melhores recomendações sobre o uso dos fatores de crescimento no tratamento de úlceras venosas. (Registro PROSPERO: CRD42016038390)
Background: Growth factors act in tissue repair by sending modulated signals stimulating or inhibiting cellular processes. Aim: To analyze the efficacy of growth factors in the healing process of venous ulcers by seeking evidence in the scientific literature. Method: Systematic review according to Cochrane Collaboration. Inclusion criteria: Randomized controlled trials using growth factors in the treatment of venous leg ulcers; approaching the total number of healed ulcers, wound area reduction and healing time. Exclusion: ongoing studies, research protocols; articles linking growth factors to the skin graft and studies that included ulcers of multiple etiologies without subgroup analysis. Databases consulted: Ovid MEDLINE (R); Ovid MEDLINE (R) In-Process & Other Non-Indexed Citations; Ovid MEDLINE (R) Epub Ahead of Print; EMBASE; CINAHL Plus with Full Text, Cochrane CENTRAL, LILACS and Web of Science. Also, the Brazilian Digital Library of Theses and Dissertations and Google Scholar were consulted, as well as hand search through the list of references of included studies. There was no time or language restrictions. Statistical analysis was performed using Review Manager 5.3 software (Cochrane Collaboration). For dichotomous variables, the relative risk was calculated considering a 95% confidence interval. The meta-analysis was performed using the fixed-effect model of Mantel-Haenszel when I2 <50% and a random model for I2> 50%. Results: The application of growth factors for the treatment of venous ulcers did not accelerate the healing process compared to standard treatment/placebo (RR 1.01 [95% CI: 0.88 to 1.16]). Similar results were found when analyzing the following subgroups: PRP (RR 1.01 [95% CI: 0.80 to 1.28]); KGF (RR 0.93 [95% CI: 0.78 to 1.11]); PDGF (RR 1.17 [95% CI: 0.78 to 1.74]); EGF (RR 2.87 [95% CI: 0.65 to 12.73, p = 0.17]); TGF (RR 1.14 [95% CI: 0.41 to 3.15]). Conclusion: The results of this review were based on studies classified as moderate to high risk of bias, therefore need to be interpreted with caution. So there is no evidence that the growth factors positively influence the healing of venous leg ulcers. More robust studies, more power and better methodological quality are needed to determine the best recommendations on the use of growth factors in the treatment of venous leg ulcers. (PROSPERO Registration: CRD42016038390)
Subject(s)
Evidence-Based Nursing , Intercellular Signaling Peptides and Proteins , Varicose UlcerABSTRACT
Objective To explore the serum levels of growth differentiation factor-15 (GDF-15) in patients with acute exacerbation of chronic heart failure (CHF) and its correlation with other common indexes,to provide reference for its clinical diagnosis,treatment and prognosis.Methods Two hundred patients with acute exacerbation of CHF were selected as CHF group,and 100 matched healthy volunteers were selected as control group.Serum levels of GDF-15 and N-terminal pronatriuretic peptide (NT-proBNP) were detected,and left ventricular end diastolic diameter (LVESD),left ventricular end diastolic diameter (LVEDD),and left ventricular ejection fraction (LVEF) were measured by echocardiography within 2 hours after admitted to hospital,and after the symptoms improved of CHF group,and on health examination day of control group.Patients in CHF group were followed up to record CHF related adverse events.Correlations between GDF-15 and other indicators were analyzed by Spearman correlation analysis,and the clinical value of serum GDF-15 on diagnosing CHF was analyzed by the receiver operating characteristic curve (ROC) and the area under the curve (AUC).Results The serum levels of GDF-15 and NT-proBNP in each time-point of CHF group were all higher than those of control group (t =4.70 ～ 7.11,P ＜ 0.05 orP ＜ 0.01).The serum levels of GDF-15 and NT-proBNP had negative correlation with LVEF (r =-0.539,-0.572,P ＜ 0.01),and had positive correlation with LVESD,LVEDD,and NYHA cardiac functional grading (r =0.505 ～ 0.861,P ＜ 0.01).Serum GDF-15 had positive correlation with serum NT-proBNP (r =0.528,P ＜0.01).With the increase of serum GDF-15 level,CHF group's readmission (rate) and death (rate) were both increased (x2 =36.86,26.59,P ＜0.01).AUC of predicting readmission risk by serum GDF-15 was 0.822 (95％ CI:0.719 ～0.890,P ＜0.01),and the best predictive cutoff point was 2 876.30 ng/L (sensitivity was 91.86％,specificity was 73.27％).AUC of predicting mortality risk was 0.816 (95％ CI:0.715 ～ 0.885,P ＜ 0.01),and the best predictive cutoff point was 3 487.05 ng/L (sensitivity was 91.72％,specificity was 69.05％).Conclusions Serum GDF-15 level in patients with acute exacerbation of CHF is higher,decreases with symptoms improvement,has positive correlation with LVESD,LVEDD,and NYHA cardiac functional grading,and has negative correlation with LVEF,has higher sensitivity on predicting CHF-related adverse events,and the mechanism may be related to the activation of SMAD pathway.Therefore,it may be a promising biomarker for clinical diagnosis and prognosis of cardiovascular diseases.