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1.
Medicine (Baltimore) ; 99(10): e19365, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150081

RESUMO

OBJECTIVES: Preptin, irisin and adropin are 3 new players in energy regulation that are related body mass index, lipids, glucose and insulin levels which may affect incidence of cardiovascular diseases. The aim of the present study was to evaluate eight single nucleotide polymorphisms (SNPs) of preptin genes (rs1003483, rs1004446, rs2239681, rs680, and rs3741204), irisin (rs16835198 and rs3480) and adropin (rs2281997) gene in patients with coronary artery disease (CAD) and hypertension. METHODS: This case-control study was carried out on 372 volunteers, which were divided into 3 subgroups including: CAD patients with hypertension (CAD+H+), CAD patients with no hypertension (CAD+H-), and non-hypertensive non-CAD subjects as control group (CAD-H-) as health control. Genomic DNA from whole blood was extracted and eight SNPs were assessed using polymerase chain reaction- ligase detection reaction method. RESULTS: A significant difference was found in the genotype and allele frequency of preptin rs1003483 gene in CAD+H+ compared to CAD+H- groups (P = .019 and P = .018, respectively). Allele frequency of rs1003483 was significantly different between CAD+H- groups and healthy control groups (P = .043). There also existed a significant difference the genotype frequency of rs1004446 gene in CAD+H+ compared to CAD+H- groups (P = .027). CONCLUSIONS: The findings of present study revealed that the preptin rs1003483 and rs1004446 gene polymorphism might serve as predisposing factor in CAD and hypertension.


Assuntos
Doença da Artéria Coronariana/genética , Hipertensão/genética , Polimorfismo Genético/genética , Adulto , Estudos de Casos e Controles , China/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Feminino , Fibronectinas/análise , Fibronectinas/genética , Humanos , Hipertensão/epidemiologia , Fator de Crescimento Insulin-Like II , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos , Fatores de Risco
2.
Medicina (Kaunas) ; 55(9)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480453

RESUMO

Background and Objectives: The morphopathogenesis of adhesions is a complex process, characterized by the accumulation of an extracellular matrix, inflammation and hypoxia. The regulatory role between morphopathogenic factors in adhesions has not yet been defined. The aim was to investigate the appearance of transforming growth factor beta (TGFß), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor (VEGF), protein gene product 9.5 (PGP 9.5), chromogranin A (CgA), interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor alpha (TNFα), human beta defensine-2 (HBD-2), matrix metaloproteinase-2 (MMP-2) and matrix metaloproteinase-2 tissue inhibitor (TIMP-2) in intraabdominal adhesions. Materials and Methods: The study material was obtained from 49 patients under one year of age with total or partial bowel obstruction. All factors were detected using immunohistochemistry methods and their relative distribution was evaluated by means of the semiquantitative counting method. Results: Intraabdominal adhesions are characterized by increased TGFß, FGFR1, VEGF and decreased FGF-2, HGF, PGP 9.5, IL-1, IL-4, IL-8, TIMP-2 findings. The most significant changes observed were the remodulation of the extracellular matrix, promotion of neoangiogenesis and the maintenance of a prolonged inflammation. Conclusions: The increase in TGFß, relative to the decrease of HGF, as well as the disbalance between MMP-2 and TIMP-2 proves an increased fibrosis in intraabdominal adhesions. Less detected FGF-2 and more prominent FGR1 findings points out a compensatory receptor stimulation in response to the lacking same factor. The decrease in PGP 9.5 and the increase in VEGF-positive macrophages indicate hypoxic injury and proves the stimulation of neoangiogenesis. An unpronounced IL-1 and marked IL-10 finding indicate the local tissue protection reaction, the decrease in IL-4 could be the direct cause of giant cells, but the decrease of IL-8 could confirm a delayed chemotaxis of inflammatory cells.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Obstrução Intestinal/patologia , Aderências Teciduais/patologia , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intercelular/análise , Obstrução Intestinal/etiologia , Intestinos/química , Intestinos/patologia , Aderências Teciduais/etiologia
3.
Prostate ; 79(14): 1705-1714, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31433512

RESUMO

BACKGROUND: We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations. MATERIALS AND METHODS: We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real-time methylation-specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated. RESULTS: In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S-transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest-specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation. CONCLUSION: We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three-gene biomarker represents a promising basis for more accurate prostate cancer diagnosis.


Assuntos
Biomarcadores Tumorais , Metilação de DNA/genética , Neoplasias da Próstata/classificação , Neoplasias da Próstata/patologia , DNA/isolamento & purificação , Epigênese Genética , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/genética , Glutationa S-Transferase pi/análise , Glutationa S-Transferase pi/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Neoplasias da Próstata/química , Proteoglicanas/análise , Proteoglicanas/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
Nutrients ; 11(6)2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185620

RESUMO

Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milk.


Assuntos
Fatores Biológicos/análise , Doenças do Prematuro/metabolismo , Recém-Nascido Prematuro/metabolismo , Lactação/metabolismo , Leite Humano/química , Adipocinas/análise , Antioxidantes/análise , Colostro/química , Citocinas/análise , Humanos , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intercelular/análise
5.
J S Afr Vet Assoc ; 90(0): e1-e9, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31170778

RESUMO

Osteoarthritis is a common cause of lameness in horses, resulting in poor performance. Intra-articular platelet-rich plasma can deliver a collection of bioactive molecules, such as autologous growth factors and proteins involved in the quality of tissue repair. Horses (n=5) with osteoarthritis affecting antebrachiocarpal, middle carpal or metacarpophalangeal joints, and horses (n=5) without osteoarthritis of the corresponding joints (radiographically free of osteoarthritis), were used for the production of platelet-rich plasma which was subsequently injected into selected joints. Clinical and synovial fluid changes after intra-articular injection of platelet-rich plasma as well as synovial platelet-derived growth factor-BB and transforming growth factor-beta 1 concentration changes were evaluated in these joints and compared between normal joints and joints with osteoarthritis. A gravity filtration system produced a moderately concentrated platelet-rich plasma, representing a 4.7-fold increase in baseline platelet concentration. The synovial effusion score was significantly different between the control joints and joints with osteoarthritis on Day 0 with a higher score in the group with osteoarthritis. Within the control group, the synovial effusion score was significantly higher on Days 1 and 2 compared to Day 0. For both groups, the synovial fluid nucleated cell count, predominantly intact neutrophils, was significantly increased on Days 1 and 2, with no significant difference between groups. The mean synovial platelet-derived growth factor-BB and transforming growth factor-beta 1 concentrations were increased for both groups but significantly lowered in the group with osteoarthritis on Day 1 compared to normal joints. Concentrations for platelet-derived growth factor-BB remained unchanged on Day 5, compared to Day 1, with no significant difference between groups. In conclusion, intra-articular treatment with platelet-rich plasma resulted in increased synovial growth factor concentrations in joints but with lower concentrations in joints with osteoarthritis. A transient inflammatory reaction was seen both clinically as an increase in synovial effusion and cytologically in both normal joints and joints with osteoarthritis.


Assuntos
Doenças dos Cavalos/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/análise , Osteoartrite/veterinária , Plasma Rico em Plaquetas , Líquido Sinovial/citologia , Animais , Feminino , Doenças dos Cavalos/diagnóstico por imagem , Cavalos , Injeções Intra-Articulares/veterinária , Coxeadura Animal/complicações , Coxeadura Animal/diagnóstico por imagem , Masculino , Osteoartrite/complicações , Osteoartrite/tratamento farmacológico , Resultado do Tratamento
6.
BMC Cancer ; 19(1): 319, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953468

RESUMO

BACKGROUND: Despite the previously suggested role of Neudesin in tumorigenesis and its potential as a novel target for the treatment of cancers, its prognostic value has never been examined. Thus, the aim of the study was to evaluate Neudesin concentrations in primary brain tumor patients and make a comparison with non-tumoral individuals. METHODS: Cerebrospinal fluid (CSF) and serum Neudesin concentration was evaluated by means of the ELISA method. RESULTS: The total group of brain tumor patients had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.037). The meningeal tumor subgroup also had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.012). The Astrocytic brain tumor subgroup had significantly higher CSF Neudesin concentrations compared to the non-tumoral group (P = 0.046). Neudesin Quotient (CSF concentration divided by serum concentration) in the astrocytic brain tumor subgroup was statistically higher compared to the non-tumoral group (P = 0.023). Males had statistically lower concentrations of the serum Neudesin compared to females (P = 0.047). Univariate linear regression analysis revealed that for women the serum Neudesin concentration was 1.53 times higher than for men. In the model of multivariate linear regression analysis, predictor variables influencing serum Neudesin concentrations included CSF Neudesin concentration and the Neudesin Quotient, if other model parameters are fixed. The developed model explains 82% of the variance in serum Neudesin concentration. Both linear regression models, univariate and multivariate, pointed to fewer factors with a potential to influence the Neudesin Quotient compared to serum Neudesin concentration. CONCLUSIONS: In astrocytic brain tumor patients Neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum Neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum Neudesin concentration is clearly gender-dependent. Linear regression models pointed to fewer factors that may influence the Neudesin Quotient value, which suggests it is a better biomarker of astrocytic brain tumors than serum and CSF Neudesin concentrations alone.


Assuntos
Astrocitoma/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/análise , Modelos Biológicos , Proteínas do Tecido Nervoso/análise , Adulto , Idoso , Astrocitoma/sangue , Astrocitoma/líquido cefalorraquidiano , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/líquido cefalorraquidiano , Estudos de Casos e Controles , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores Sexuais
7.
Int J Mol Sci ; 20(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987106

RESUMO

Mesenchymal stem/stromal cells (MSC) remain a promising tool for regenerative medicine as the efficacy of MSC-based cell therapy has been demonstrated for a broad spectrum of indications. Their therapeutic potency is mainly associated with their ability to secrete multiple factors critical for tissue regeneration. Due to comparable effects along with superior safety MSC conditioned medium (MSC-CM) containing a complex of MSC-secreted products is considered a reasonable alternative to cell therapy. However, the lack of standards regulating bioprocessing, use of proper auxiliary materials, and quality control complicates the development of MSC secretome-based therapeutics. In this study, we suggested several approaches addressing these issues. We manufactured 36 MSC-CM samples based on different xeno-free serum-free chemically defined media (DMEM-LG or MSC NutriStem® XF) using original protocols and considered total concentrations of regeneration-associated paracrine factors secreted by human adipose-derived MSC at each time-point of conditioning. Using regression analysis, we retrospectively predicted associations between concentrations of several components of MSC-CM and its biological activity to stimulate human dermal fibroblast and endothelial cell migration in vitro as routine examples of potency assays for cell-based products. We also demonstrated that the cell culture medium might affect MSC-CM biological activity to varying degrees depending on the potency assay type. Furthermore, we showed that regression analysis might help to overcome donor variability. The suggested approaches might be successfully applied for other cell types if their secretome was shown to be promising for application in regenerative medicine.


Assuntos
Meios de Cultivo Condicionados/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pesquisa Médica Translacional , Movimento Celular , Sobrevivência Celular , Derme/citologia , Células Endoteliais/citologia , Fibroblastos/citologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Modelos Biológicos , Análise de Regressão
8.
Farm. hosp ; 43(2): 45-49, mar.-abr. 2019. ilus, graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182587

RESUMO

Objetivo: Evaluación galénica del proceso de obtención y almacenamiento del colirio de plasma rico en factores de crecimiento PRGF-Endoret(R). Método: Para evaluar la asepsia en la obtención del colirio de PRGFEndoret(R) se realizó un ensayo de esterilidad siguiendo las normas descritas en la Farmacopea Europea y se analizó la estanqueidad de los dispensadores de colirio de PRGF-Endoret(R). Asimismo, se estudiaron las propiedades químicas y biológicas del colirio tras su proceso de obtención y almacenamiento. Se incluyeron ensayos de filtración del colirio, de un ciclo de congelación a -20 ºC y descongelación, así como de estabilidad durante tres y seis meses almacenados a -20 ºC. Resultados: Los ensayos de esterilidad mostraron que no hubo crecimiento microbiano en ninguno de los dispensadores analizados y se observó que el 100% de los monodosis analizados y el 98,4% de los tapones mantenían el hermetismo. Todos los factores de crecimiento analizados permanecieron constantes tras el filtrado del colirio de PRGF-Endoret(R). Además, todos los estudios de estabilidad llevados a cabo con el colirio de PRGF-Endoret(R) en el presente estudio mostraron que no se produjeron cambios significativos en los niveles de factores de crecimiento, en la actividad proliferativa celular ni en las características químicas analizadas. Conclusiones: El presente trabajo muestra que el proceso de elaboración del colirio de PRGF-Endoret(R) se lleva a cabo de forma controlada, aséptica y segura, siguiendo las normas descritas en la Farmacopea Europea. Además, el colirio de PRGF-Endoret(R) obtenido mantiene sus propiedades físico-químicas y biológicas tras someterlo a diferentes tiempos y temperaturas de almacenamiento


Objective: Galenic evaluation of the process for obtaining and storing the platelet rich in growth factors PRGF-Endoret(R) eye drops. Method: To assess whether the PRGF-Endoret(R) eye drops process is aseptically obtained, a sterility test was carried out on the eye drops; the tightness of the PRGF-Endoret(R) eye drops containers was also analyzed. Likewise, the chemical and biological properties of the PRGF-Endoret(R) eye drops were evaluated after the obtaining process and storage. Eye drop filtration tests, one cycle of freezing at -20 °C and thawing, and eye drop stability for three and six months stored at -20 °C were included. Results: The results obtained in the sterility test showed no microbial contamination in any of the analyzed eyedropper; tightness test showed that 100% of the eyedrop containers and the 98.4% of the plugs analyzed remained hermetic. On the other hand, all the growth factors measured remained constant after filtering the PRGF-Endoret(R) eye drops. Furthermore, the different eye drop stability tests carried out in this study showed no significant changes in the growth factors levels, cell proliferative activity or in the chemical characteristics analyzed. Conclusions: The PRGF-Endoret(R) eye drops are obtained in a safety and aseptic manner following the guidelines issued by the Spanish Agency for Drugs and Health Products and the Ministry of Health to obtain medicines for human use. The PRGF-Endoret(R) eye drops maintain their physical-chemical and biological properties after being subjected to different storage times and temperatures


Assuntos
Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Soluções Oftálmicas/análise , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Estabilidade de Medicamentos , Embalagem de Medicamentos , Armazenamento de Medicamentos , Filtração , Congelamento , Esterilização
9.
J Anim Sci ; 97(5): 2258-2269, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-30869128

RESUMO

Nutrition and other external factors are known to have a marked effect on growth of skeletal muscle, modulated, at least in part, through effects on satellite cells. Satellite cells and their embryonic precursors play an integral role in both prenatal and postnatal skeletal muscle growth of mammals. Changes in maternal nutrition can impact embryonic muscle progenitor cells which ultimately impacts both prenatal and postnatal skeletal muscle development. Satellite cells are important in postnatal skeletal muscle growth as they support the hypertrophy of existing myofibers. Hypertrophy of existing fibers is the only mechanism of postnatal muscle growth because muscle fiber number is fixed at birth and fiber nuclei have exited the cell cycle. Because fiber nuclei do not divide, additional nuclei required for hypertrophy must be acquired from satellite cells. To date, little research has aimed at determining whether nutrition directly impacts satellite cell populations within skeletal muscle of livestock species. However, it is well established that nutrition alters circulating concentrations of various growth factors such as insulin-like growth factor 1, epidermal growth factor, hepatocyte growth factor, and fibroblast growth factor. Each of these different growth factors impacts satellite cell proliferation and/or activation, indicating that nutrition likely plays a large role in skeletal muscle growth through impacting the satellite cell pool in both prenatal and postnatal growth. The relationship among nutrition, growth factors, and satellite cells relative to skeletal muscle growth is an important area of research that warrants further consideration.


Assuntos
Diferenciação Celular , Proliferação de Células , Gado/fisiologia , Estado Nutricional , Células Satélites de Músculo Esquelético/fisiologia , Animais , Ciclo Celular , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/análise , Gado/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Materna , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Gravidez
10.
Int J Mol Sci ; 20(7)2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30925759

RESUMO

Hepatic intrasinusoidal (HI) natural killer (NK) cells from liver perfusate have unique features that are similar to those of liver-resident NK cells. Previously, we have reported that HI CD56bright NK cells effectively degranulate against SNU398 hepatocellular carcinoma (HCC) cells. Thus, the aim of this study was to further investigate the phenotype and function of HI NK cells. We found that HI CD56bright NK cells degranulated much less to Huh7 cells. HI CD56bright NK cells expressed NKG2D, NKp46, TNF-related apoptosis-inducing ligand (TRAIL), and FAS ligand (FASL) at higher levels than CD56dim cells. SNU398 cells expressed more NKG2D ligands and FAS and less PD-L1 than Huh7 cells. Blockade of NKG2D, TRAIL, and FASL significantly reduced the cytotoxicity of HI NK cells against SNU398 cells, but blockade of PD-L1 did not lead to any significant change. However, HI NK cells produced IFN-γ well in response to Huh7 cells. In conclusion, the cytotoxicity of HI CD56bright NK cells was attributed to the expression of NKG2D, TRAIL, and FASL. The results suggest the possible use of HI NK cells for cancer immunotherapy and prescreening of HCC cells to help identify the most effective NK cell therapy recipients.


Assuntos
Antígeno CD56/imunologia , Carcinoma Hepatocelular/imunologia , Células Matadoras Naturais/imunologia , Neoplasias Hepáticas/imunologia , Adulto , Antígeno CD56/análise , Linhagem Celular Tumoral , Proteína Ligante Fas/análise , Proteína Ligante Fas/imunologia , Feminino , Proteínas Ligadas por GPI/análise , Proteínas Ligadas por GPI/imunologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interferon gama/análise , Interferon gama/imunologia , Masculino , Ligante Indutor de Apoptose Relacionado a TNF/análise , Ligante Indutor de Apoptose Relacionado a TNF/imunologia
11.
Ginekol Pol ; 90(2): 86-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30860275

RESUMO

OBJECTIVES: This study Aims to explore the role of placental Cripto-1 in the incidence of an adherent placenta. MATERIAL AND METHODS: Ten pregnant women with placenta increta, 20 pregnant women with placenta previa and 30 women with normal pregnant were enrolled in this study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of Cripto-1 in the placenta while as the analysis of placental Cripto-1 was performed by Western blotting RESULTS: The placenta increta group showed higher levels of Cripto-1 in the center of the increta as compared to the non-implantation area. The level of placental Cripto-1 in the placenta increta was higher than that of the placenta accrete. The expression of placental Cripto-1 in the placenta increta and placenta previa groups was higher than that of control. CONCLUSIONS: Placental Cripto-1 is involved in the regulation of placental tissue invasion. Additionally, excessive placental growth or penetration into the myometrium are likely to be involved in the development of placenta increta.


Assuntos
Proteínas Ligadas por GPI/análise , Proteínas Ligadas por GPI/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Placenta Acreta/metabolismo , Placenta Prévia/metabolismo , Placenta/metabolismo , Adulto , Feminino , Proteínas Ligadas por GPI/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Neoplasias/genética , Placenta/química , Placenta/fisiopatologia , Placenta Acreta/epidemiologia , Placenta Acreta/fisiopatologia , Placenta Prévia/epidemiologia , Placenta Prévia/fisiopatologia , Gravidez
12.
Farm Hosp ; 43(2): 45-49, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30848175

RESUMO

OBJECTIVE: Galenic evaluation of the process for obtaining and storing the platelet rich in growth factors PRGF-Endoret® eye drops. METHOD: To assess whether the PRGF-Endoret® eye drops process is aseptically obtained, a sterility test was carried out on the eye drops; the tightness of the PRGF-Endoret® eye drops containers was also analyzed. Likewise, the chemical and biological properties of the PRGF- Endoret® eye drops were evaluated after the obtaining process and storage.  Eye drop filtration tests, one cycle of freezing at -20 °C and thawing, and  eye drop stability for three and six months stored at -20 °C were included. RESULTS: The results obtained in the sterility test showed no microbial  contamination in any of the analyzed eyedropper; tightness test showed that  100% of the eyedrop containers and the 98.4% of the plugs analyzed  remained hermetic. On the other hand, all the growth factors measured  remained constant after filtering the PRGF-Endoret® eye drops.  Furthermore, the different eye drop stability tests carried out in this study  showed no significant changes in the growth factors levels, cell proliferative  activity or in the chemical characteristics analyzed. Conclusions: The PRGF-Endoret® eye drops are obtained in a safety and aseptic manner following the guidelines issued by the Spanish Agency  for Drugs and Health Products and the Ministry of Health to obtain medicines for human use. The PRGF-Endoret® eye drops maintain their physical-chemical and biological properties after being subjected to different  storage times and temperatures.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/análise , Soluções Oftálmicas/análise , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Embalagem de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Filtração , Congelamento , Humanos , Esterilização
13.
Biosens Bioelectron ; 132: 47-54, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30852381

RESUMO

In precision medicine, clinical decisions and pharmaceutical evaluations tends to be made upon parallel analysis of multiple protein biomarkers. Currently, the growing needs of high-throughput multiplex immunoassay is partially satisfied by spectrally encoded bead flow suspension arrays and other platforms, yet there is still room for progress in terms of encoding capacity, decoding accuracy, ease-of-manufacture/operation, and cost-effectiveness, for which graphical suspension arrays could make substantial contributions. Here we described a suspension array system made up of graphically encoded silica particles, an automated microplate imager and an in-house data processing program. The micro-fabricated, highly uniform planar particles provide a code space of 128-plex with further extendibility. The derived multiplex immunoassay reaches sub-picogram per milliliter sensitivity level (lowest LoD = 80 fg/ml) with wide dynamic range, as well as high precision and accuracy. The potential of clinical diagnostics was demonstrated by parallel measurement of three serum biomarkers for type 1 diabetes patients. Importantly, use of standard microplates as assay vessel extends its power to high-throughput applications, such as disease screening or drug discovery.


Assuntos
Técnicas Biossensoriais/instrumentação , Citocinas/sangue , Diabetes Mellitus Tipo 1/sangue , Imunoensaio/instrumentação , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Anticorpos Imobilizados/química , Autoimunidade , Biomarcadores/sangue , Citocinas/análise , Desenho de Equipamento , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Limite de Detecção , Análise Serial de Proteínas/instrumentação
14.
Toxins (Basel) ; 11(3)2019 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-30857348

RESUMO

Comprehensive LC-MS and MS/MS analysis of the crude venom extract from the solitary eumenine wasp Eumenes micado revealed the component profile of this venom mostly consisted of small peptides. The major peptide components, eumenine mastoparan-EM1 (EMP-EM1: LKLMGIVKKVLGAL-NH2) and eumenine mastoparan-EM2 (EMP-EM2: LKLLGIVKKVLGAI-NH2), were purified and characterized by the conventional method. The sequences of these new peptides are homologous to mastoparans, the mast cell degranulating peptides from social wasp venoms; they are 14 amino acid residues in length, rich in hydrophobic and basic amino acids, and C-terminal amidated. Accordingly, these new peptides can belong to mastoparan peptides (in other words, linear cationic α-helical peptides). Indeed, the CD spectra of these new peptides showed predominantly α-helix conformation in TFE and SDS. In biological evaluation, both peptides exhibited potent antibacterial activity, moderate degranulation activity from rat peritoneal mast cells, and significant leishmanicidal activity, while they showed virtually no hemolytic activity on human or mouse erythrocytes. These results indicated that EMP-EM peptides rather strongly associated with bacterial cell membranes rather than mammalian cell membranes.


Assuntos
Anti-Infecciosos , Peptídeos e Proteínas de Sinalização Intercelular , Venenos de Vespas/química , Animais , Anti-Infecciosos/análise , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Eritrócitos/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Leishmania major/efeitos dos fármacos , Leishmania major/crescimento & desenvolvimento , Mastócitos/efeitos dos fármacos , Camundongos , Ratos Sprague-Dawley , Análise de Sequência de Proteína , Espectrometria de Massas em Tandem , Venenos de Vespas/análise , Venenos de Vespas/farmacologia , Vespas
15.
J Orthop Surg Res ; 14(1): 39, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728046

RESUMO

BACKGROUND: Platelet-rich plasma (PRP) is autologous in origin and contains a high concentration of platelets which is a source of various growth factors. Previous studies have suggested that PRP has a positive effect in accelerating fusion by an autologous bone graft in a lumbar fusion. The role of PRP on artificial bone grafts in spinal fusion remains controversial. In this study, positive effect on spinal fusion by PRP was hypothesized; in vitro and in vivo studies were designed to test this hypothesis. METHODS: PRP was produced from peripheral blood of Sprague-Dawley (SD) rats. A lumbar posterolateral arthrodesis model was used to test the efficacy of PRP on spinal fusion. Thirty SD rats were divided into three groups by different implants: the PRP group, PRP plus collagen-mineral carrier; the platelet-poor plasma (PPP) group, PPP plus collagen-mineral carrier; and the control group, collagen-mineral only. Spinal fusion was examined using plain radiographs, micro-computed tomography (micro-CT), manual palpation, and histological analysis. The fusion rate by micro-CT and that by manual palpation in groups were compared. RESULTS: In the micro-CT results, 16 fused segments were observed in the PRP group (80%, 16/20), 2 in the PPP group (10%, 2/20), and 2 in the control group (10%, 2/20). The fusion rate, determined by manual palpation, was 60% (6/10) in the PRP group, 0% (0/10) in the PPP group, and 0% (0/10) in the control group. Histology showed that the PRP group had more new bone and matured marrow formation. CONCLUSIONS: The results of this study demonstrated that PRP on an artificial bone carrier had positive effects on lumbar spinal fusion in rats. In the future, this composite could be potentially used as a bone graft in humans.


Assuntos
Vértebras Lombares/cirurgia , Plasma Rico em Plaquetas , Fusão Vertebral/métodos , Tecidos Suporte , Animais , Peptídeos e Proteínas de Sinalização Intercelular/análise , Vértebras Lombares/diagnóstico por imagem , Plasma Rico em Plaquetas/química , Ratos Sprague-Dawley
16.
Theranostics ; 9(2): 449-465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809286

RESUMO

The Wnt/ß-catenin pathway is constitutively active and promotes multiple tumor processes, including breast cancer metastasis. However, the underlying mechanism by which the Wnt/ß-catenin pathway is constitutively activated in breast cancer metastasis remains unclear. Inhibition of Wnt antagonists is important for Wnt/ß-catenin signaling activation, and post-transcriptional regulation of these antagonists by microRNAs (miRNAs) might be a possible mechanism underlying signaling activation. Regulation of nuclear pre-mRNA domain-containing 1A (RPRD1A) is a known inhibitor of cell growth and Wnt/ß-catenin signaling activity, but the function and regulatory mechanism of RPRD1A in breast cancer have not been clarified. The aim of this study was to understand how regulators of the Wnt/ß-catenin pathway may play a role in the metastasis of this cancer. Methods: RPRD1A expression and its association with multiple clinicopathological characteristics was analyzed immunohistochemically in human breast cancer specimens. miR-454-3p expression was analyzed using real-time PCR. RPRD1A or miR-454-3p knockdown and overexpression were used to determine the underlying mechanism of their functions in breast cancer cells. Xenografted tumor model, 3D invasive culture, cell migration and invasion assays and sphere formation assay were used to determine the biofunction of RPRD1A and miR-454-3p in breast cancer. Electrophoretic mobility shift assay (EMSA), luciferase reporter assay, and RNA immunoprecipitation (RIP) were performed to study the regulation and underlying mechanisms of RPRD1A and miR-454-3p expression and their correlation with the Wnt/ß-catenin pathway in breast cancer. Results: The Wnt/ß-catenin signaling antagonist RPRD1A was downregulated and its upstream regulator miR-454-3p was amplified and overexpressed in metastatic breast cancer, and both were correlated with overall and relapse-free survival in breast cancer patients. The suppression by miR-454-3p on RPRD1A was found to activate Wnt/ß-catenin signaling, thereby promoting metastasis. Simultaneously, three other negative regulators of the Wnt/ß-catenin pathway, namely, AXIN2, dickkopf WNT signaling pathway inhibitor (DKK) 3 and secreted frizzled related protein (SFRP) 1, were also found to be targets of miR-454-3p and were involved in the signaling activation. miR-454-3p was found to be involved in early metastatic processes and to promote the stemness of breast cancer cells and early relapse under both in vitro and in vivo conditions. Conclusions: The findings indicate that miR-454-3p-mediated suppression of Wnt/ß-catenin antagonist RPRD1A, as well as AXIN2, DKK3 and SFRP1, sustains the constitutive activation of Wnt/ß-catenin signaling; thus, miR-454-3p and RPRD1A might be potential diagnostic and therapeutic targets for breast cancer metastasis.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/análise , Regulação da Expressão Gênica , MicroRNAs/metabolismo , Metástase Neoplásica/patologia , Proteínas Repressoras/análise , Via de Sinalização Wnt , Animais , Proteína Axina/análise , Quimiocinas/análise , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/análise , Proteínas de Membrana/análise , Modelos Teóricos , Transplante de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Transplante Heterólogo
17.
Pathol Oncol Res ; 25(2): 447-453, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30712193

RESUMO

Whole saliva is mainly composed of fluid produced by major and minor salivary glands. Major salivary glands including parotid, submandibular, and sublingual glands, are known to secrete fluid transported from serum as well as surrounding glandular tissues [1]. Beside the secretions from salivary glands, oral mucosa, periodontium, as well as oral microflora also contribute to the final content of whole saliva [1]. Whole saliva therefore represents a complex balance among local and systemic sources [2]. This allows for the application of saliva in the diagnosis not only for salivary gland disorders but also for oral diseases and systemic conditions [2]. The role of saliva as a diagnostic tool in detecting Oral Squamous Cell Carcinoma. Articles published in PUBMED, EMBASE, COCHRANE, GOOGLE, manual search and back references of the articles for last 5 years extracted 77 articles. Studies which considered saliva as a diagnostic tool were included. Statistical analysis with Receivers Operating Curve to establish sensitivity and specificity of the salivary biomarkers as a diagnostic tool to detect Oral Squamous Cell Carcinoma were included for meta analysis. The measure of effect with 95% confidence interval were meta analysed for 9 articles in which 308 healthy individuals compared with 340 patients with Oral Squamous Cell Carcinoma. Highly sensitive salivary biomarkers for detecting Oral Squamous Cell Carcinoma were MMP-9, Chemerin, Choline + Betaine + Pipecolinic Acid + I - Carnitine(confidence interval ranges from 0.83-1.0). The narrow confidence interval of 0.95 + (0.88-1.00) was seen for MMP-9 followed by 1.00 + (0.78-1.00) for chemerin. Highly specific biomarkers for Oral Squamous Cell Carcinoma were MMP-9 (specificity -100%,), Chemerin(specificity-100%), over expressed mi RNA 136 with specificity of 0.88(0.69-0.97), under expressed mi RNA 27B with specificity of 1.0(0.66-1.00). Saliva can be used as a diagnostic tool with highly sensitive and specific markers namely MMP-9, Chemerin for early detection of Oral Squamous Cell Carcinoma.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Bucais/diagnóstico , Saliva/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Quimiocinas/análise , Quimiocinas/biossíntese , Detecção Precoce de Câncer/métodos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/biossíntese , Sensibilidade e Especificidade
18.
Int J Mol Sci ; 20(2)2019 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-30642068

RESUMO

Platelet rich plasma (PRP) is blood plasma with a platelet concentration above baseline. When activated, PRP releases growth factors involved in all stages of wound healing, potentially boosting the healing process. To expand our knowledge of the effectiveness of PRP, it is crucial to know the content and composition of PRP products. In this study, growth factor quantification measurements of PRP from burn patients and gender- and age-matched controls were performed. The PRP of burn patients showed levels of growth factors comparable to those of the PRP of healthy volunteers. Considerable intra-individual variation in growth factor content was found. However, a correlation was found between the platelet count of the PRP and most of the growth factors measured.


Assuntos
Queimaduras/terapia , Peptídeos e Proteínas de Sinalização Intercelular/análise , Plasma Rico em Plaquetas/química , Adulto , Idoso , Queimaduras/sangue , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Plasma Rico em Plaquetas/fisiologia , Cicatrização
19.
Biochem Biophys Res Commun ; 509(3): 687-693, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30616890

RESUMO

Atherosclerosis and cancer are the leading causes of mortality around the world that share common pathogenic pathways. The aim of this study is the investigation of the protein profile of atherosclerotic plaque in order to find similar biomarker between cancer and atherosclerosis. The small pieces of human coronary artery containing advanced atherosclerotic plaque is obtained from patients during bypass surgery. Structural characterization of type V plaque, including fibrous connective tissue, necrotic lipid core, cholesterol clefts and calcium deposits are performed using high resolution transmission electron microscopy (HR-TEM). The protein profile of atherosclerosis plaque is also analyzed using 2-dimensional electrophoresis and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF). TEM analysis shows that vascular smooth muscle cells (VSMCs) exhibit different and uncommon morphologies in atherosclerotic plaque which is correlated to the proliferative state of the cells. The proteomics analysis reveals proteins related to atherosclerosis formation including Mimecan, Ras Suppressor Protein-1 (RSUP-1) and Cathepsin D which identified as biomarker of cancerous tumors. The expression of Mimecan and RSUP-1 is down-regulated in atherosclerotic plaque while the expression of Cathepsin D is up-regulated. These data support that atherosclerotic plaque presents some degree of tumorgenesis with the significant activity of VSMCs as the key player in atherogenesis.


Assuntos
Catepsina D/análise , Peptídeos e Proteínas de Sinalização Intercelular/análise , Neoplasias/patologia , Placa Aterosclerótica/patologia , Fatores de Transcrição/análise , Biomarcadores Tumorais/análise , Eletroforese em Gel Bidimensional , Humanos , Neoplasias/química , Placa Aterosclerótica/química , Proteoma/análise , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
20.
J Am Acad Dermatol ; 80(3): 694-700, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30287324

RESUMO

BACKGROUND: Promising results with platelet-rich plasma (PRP) in androgenetic alopecia that could be associated with platelet number and growth factor levels were described. OBJECTIVE: Analyze the platelet countand growth factor levels in PRP and their correlation with hair growth parameters evaluated by using the TrichoScan (Tricholog GmbH, Freiburg, Germany). METHODS: A total of 26 patients were randomized to receive 4 subcutaneous injections of PRP or saline. Hair growth, hair density, and percentage of anagen hairs were evaluated by using the TrichoScan method before injection, 15 days after the last injection, and again 3 months after the last injection. Growth factors (platelet-derived growth factor, epidermal growth factor, and vascular endothelial growth factor) were measured by the Luminex method (Millipore, Bedford, MA). RESULTS: We demonstrated a significant increase in hair count (P = .0016), hair density (P = .012) and percentage of anagen hairs (P = .007) in the PRP group versus in the control group, without correlation with platelet counts or quantification of the growth factors in PRP. LIMITATIONS: Other growth factors that could be related to response to PRP were not evaluated. CONCLUSION: Our data favor the use of PRP as a therapeutic alternative in the treatment of androgenetic alopecia. The lack of association between platelet count, platelet-derived growth factor, epidermal growth factor, and vascular endothelial growth factor levels and clinical improvement suggest that other mechanisms could be involved in this response.


Assuntos
Alopecia/terapia , Cabelo/crescimento & desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/análise , Contagem de Plaquetas , Plasma Rico em Plaquetas/química , Plasma Rico em Plaquetas/citologia , Adulto , Dermoscopia , Método Duplo-Cego , Fator de Crescimento Epidérmico/análise , Cabelo/diagnóstico por imagem , Humanos , Masculino , Fator de Crescimento Derivado de Plaquetas/análise , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/análise , Adulto Jovem
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