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1.
Bratisl Lek Listy ; 121(1): 14-21, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31950835

RESUMO

AIM: Apelin is an active endogenous peptide, which affects blood vessels. Also exercise increases angiogenesis after myocardial infarction and exerts cardio protective effects. The aim of the present study was to investigate the effect of Apelin and aerobic exercise on reducing the severity of Ischemia-reperfusion injury in rats. METHODS: The rats were divided into the following 4 groups 8 weeks before surgery (Langendorff model of perfusion): I) Ischemia-reperfusion (I/R), II: Exercise Ischemia- reperfusion (EX+I/R), III: Apelin+Ischemia-reperfusion (APE+I/R) (Apelin 10 nmol/kg/day, i.p), and IV: Exercise+Apelin+Ischemia-reperfusion (EX+APE+I/R). Exercise was performed on a treadmill 8 weeks before the surgery at a speed of 17 m/min for 10 to 50 min/day. The ventricular function was evaluated after I/R injury, histopathological and immunohistopathology indices were then measured at the scar tissue. RESULTS: The results of H(et)E, Masson's trichrome staining indicated that APE+EX pre-treatment reduced cardiac fibrosis and the percentage of collagen deposition. It also enhanced the microvessels density (MVD) and decreased the number of inflammatory cells and apoptosis rate. CONCLUSION: According to our study, Apelin and exercise preconditioning had anti-fibrotic and anti-apoptotic effects on the ischemia-reperfusion myocardium cells, which could lead to the protection of cardiac cells (Tab. 5, Fig. 3, Ref. 33).


Assuntos
Apelina , Infarto do Miocárdio , Traumatismo por Reperfusão , Animais , Apelina/farmacologia , Apelina/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular , Infarto do Miocárdio/complicações , Miócitos Cardíacos , Ratos , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/terapia
2.
Eur J Ophthalmol ; 30(1): 94-103, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30585084

RESUMO

PURPOSE: To evaluate the efficacy and safety of plasma rich in growth factors eye drops for the treatment of corneal and ocular surface disorders in patients with graft versus host disease. METHODS: This retrospective and longitudinal study included graft versus host disease patients with ocular disorders. The resolution of corneal ulcers (area and density staining) was evaluated as primary outcome. Best corrected visual acuity, intraocular pressure, tear film breakup time, Schirmer test, ocular surface disease index, and visual analog score were evaluated as secondary outcomes. All variables were analyzed before and after plasma rich in growth factors treatment. The safety of plasma rich in growth factors treatment was also assessed. RESULTS: Twelve patients (23 eyes) with ocular graft versus host disease were evaluated. Statistically significant improvement in the area (75.7%) and density (73.3%) of the corneal staining, in best corrected visual acuity (74.7%), in ocular surface disease index scale (75.4%), visual analog score frequency (81.4%) and visual analog score severity (81.9%), and an increase of 3.8 s in tear film breakup time and 6 mm in Schirmer test was observed after plasma rich in growth factors treatment (p < 0.001). Some potential modifiers of the therapeutic effect were identified. All patients achieved corneal stability without perforation risk. No adverse events associated with the plasma rich in growth factors were observed. CONCLUSION: Immunosafe plasma rich in growth factors eye drops for the treatment of patients with ocular graft versus host disease could be safe and effective, showing a high rate of corneal ulcer resolution and dry eye disease control. Plasma rich in growth factors eye drops may help to maintain corneal stability and prevent it against higher ocular complications.


Assuntos
Síndromes do Olho Seco/terapia , Doença Enxerto-Hospedeiro/complicações , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Plasma Rico em Plaquetas , Adulto , Idoso , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/metabolismo , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Estudos Retrospectivos , Lágrimas/metabolismo
3.
Gene ; 722: 144057, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31430519

RESUMO

OBJECTIVE: Fork head domain-containing transcription factor family (FOX), is comprised of >20 members. Members of FOX family have been implicated in a wide range of physiological and/or diseased conditions. Many of FOX members have been shown to be involved in tumorigenesis and progression. The potential roles in carcinogenesis of FOXN4, a member as one of the vast FOX family, remains relatively unknown. METHOD: Here, we explored the potential involvement of FOXN4 in breast cancer. RESULTS: First, observed that a higher FOXN4 was identified in the normal adjacent breast tissue as compared to that in the breast cancer samples; an increased FOXN4 level was associated with a better prognosis in patients with breast cancer. In addition, ectopically expression of FOXN4 led to the decreased cell proliferation, reduced colony formation and metastatic abilities (EMT, migration and invasion) in breast cancer cell lines. Furthermore, we showed the direct interaction between FOXN4 and TP53 and FOXN4 binding led to the increased activity of TP53. Silencing FOXN4 led to reduced TP53 and increased expression of Dll4, Notch and survivin, providing a link between FOXN4 and Notch signaling. Finally, we used patient-derived xenograft mouse model to demonstrate the tumor inhibitory effects of Notch-inhibitor, PF-3084014. We found that PF-3084014 treatment led to a significantly smaller tumor burden and higher survival ratio in patient-derived xenograft mice as compared to the vehicle. This tumor suppressive effect was accompanied by the increased expression of TP53, FOXN4 and decreased Dll4 and Notch. CONCLUSION: Collectively, our data strongly suggested the tumor suppressive roles of FOXN4 in breast tumorigenesis via the activation of TP53 while suppressing Notch signaling. Future studies are warranted to explore the clinical application of PF-3084104 (Notch inhibitor) for the treatment of breast cancer patients.


Assuntos
Neoplasias da Mama/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Metástase Neoplásica , Prognóstico , Receptores Notch/antagonistas & inibidores , Receptores Notch/metabolismo , Transdução de Sinais , Tetra-Hidronaftalenos/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética , Valina/análogos & derivados , Valina/uso terapêutico
4.
Life Sci ; 241: 117174, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843531

RESUMO

Hypertrophic scar is a dermal fibroproliferative disorder characterized by excess collagen deposition. There are many existing treatment modalities, but none works perfectly in all individuals. Recently, evidence is increasing that peptides can play crucial roles in the prevention or treatment of hypertrophic scar. The peptides may be derived from growth factors, hormones, and intracellular products of proteolysis. In vitro and in vivo studies have revealed that a number of peptides, usually topically applied, have beneficial effects on fibroblasts in rat, mouse, hamster, pig and rabbit scar models. The length of such peptides typically ranges between 10 and 15 amino acids (aa). Peptides may reduce scar progenitors, prevent excessive scarring, decrease scar growth, speed re-epithelialization and promote scar maturation through multiple mechanisms. They may target TGF-ß signaling, fibroblast function or collagen modulation, inflammation, renin angiotensin system, gap junction and other pathways. However, there is a paucity of evidence regarding specific binding sites for these peptides in scar models. Here, we review current research progress on the roles of peptides and underlying mechanisms in hypertrophic scar. We also discuss the clinical potential of peptides as therapeutic agents in scarring. Finally, the functions of several peptide-related compounds in hypertrophic scar are summarized.


Assuntos
Cicatriz Hipertrófica/prevenção & controle , Hormônios/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fragmentos de Peptídeos/uso terapêutico , Animais , Cicatriz Hipertrófica/metabolismo , Humanos
5.
J Cancer Res Clin Oncol ; 146(2): 315-327, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865530

RESUMO

PURPOSE: To investigate the interaction between Wnt/ß-catenin and estrogen signaling pathways in endometrial cancer (EC). METHODS: 119 women were involved in this study, including 65 women with histologically confirmed EC and 54 healthy women as a control group. Serum protein levels of Dkk1 were measured using ELISA. Protein expression levels of Dkk1, ß-catenin, ER-ß isoforms (ß1, ß2, ß5), and ER-α were tested in paraffin-embedded tissues using IHC. Gene expression levels of Dkk1, CTNNB, ESR1, and ESR2 were tested in fresh tumorous and normal endometrium tissues using RT-PCR. RESULTS: EC patients had significantly higher serum levels of Dkk1 protein compared with healthy women. Dkk1 and ß-catenin showed different expression pattern in tumor cells compared to it in normal cells at the protein level but not at the gene level. Protein expression levels of ERß2 and ERα were significantly lower in tumor cells compared with tumor-adjacent normal cells. Increased protein expression levels of ERα were associated with favorable clinicopathological features and better overall survival rate (OS). Protein expression levels of ERα were correlated with protein expression levels of Dkk1 and cytoplasmic ß-catenin. The association between ERα expression levels and OS was no more significant when tested in regard to Dkk1- and cytoplasmic ß-catenin expression levels. CONCLUSIONS: Our data demonstrated that Wnt/ß-catenin and estrogen signaling systems are dysregulated in EC showing; for the first time, a potential crosstalk between certain components of these two pathways, which in turn has affected the specificity of these molecules in disease characteristics. Understanding the signaling networks in EC is crucial in designing clinical trials to evaluate the efficacy of molecular-targeted agents and providing more successful therapies in the future.


Assuntos
Neoplasias do Endométrio/metabolismo , Receptores Estrogênicos/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pessoa de Meia-Idade
6.
J Surg Res ; 245: 1-12, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31394402

RESUMO

BACKGROUND: The process of aortic injury, repair, and remodeling during aortic aneurysm and dissection is poorly understood. We examined the activation of bone marrow (BM)-derived and resident aortic cells in response to aortic injury in a mouse model of sporadic aortic aneurysm and dissection. MATERIALS AND METHODS: Wild-type C57BL/6 mice were transplanted with green fluorescent protein (GFP)+ BM cells. For 4 wk, these mice were either unchallenged with chow diet and saline infusion or challenged with high-fat diet and angiotensin II infusion. We then examined the aortic recruitment of GFP+ BM-derived cells, growth factor production, and the differentiation potential of GFP+ BM-derived and GFP- resident aortic cells. RESULTS: Aortic challenge induced recruitment of GFP+ BM cells and activation of GFP- resident aortic cells, both of which produced growth factors. Although BM cells and resident aortic cells equally contributed to the fibroblast populations, we did not detect the differentiation of BM cells into smooth muscle cells. Interestingly, aortic macrophages were both of BM-derived (45%) and of non-BM-derived (55%) origin. We also observed a significant increase in stem cell antigen-1 (Sca-1)+ stem/progenitor cells and neural/glial antigen 2 (NG2+) cells in the aortic wall of challenged mice. Although some of the Sca-1+ cells and NG2+ cells were BM derived, most of these cells were resident aortic cells. Sca-1+ cells produced growth factors and differentiated into fibroblasts and NG2+ cells. CONCLUSIONS: BM-derived and resident aortic cells are activated in response to aortic injury and contribute to aortic inflammation, repair, and remodeling by producing growth factors and differentiating into fibroblasts and inflammatory cells.


Assuntos
Aneurisma Dissecante/patologia , Aorta/patologia , Aneurisma Aórtico/patologia , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/imunologia , Animais , Aorta/citologia , Aorta/imunologia , Aneurisma Aórtico/complicações , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Fibroblastos/imunologia , Fibroblastos/metabolismo , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1253-1259, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801721

RESUMO

OBJECTIVE: To investigate the expression profile of long non-coding RNAs (lncRNA) and identify potential lncRNA-related competing endogenous RNAs (ceRNA) in placenta accrete spectrum disorders (PAS). METHODS: Five tissue specimens of placental implantation and 5 adjacent normal placental tissues were collected from cesarean section deliveries complicated by PAS in our hospital between December, 2017 and June, 2018. Human microarrays were used to identify the lncRNAs that were differentially expressed in PAS, and 5 of the identified lncRNAs were further validated using qRT-PCR. GO and KEGG pathway analyses were performed to indentify the most significant enrichment functions. A ceRNA network was constructed based on ENST00000511361 (RP5-875H18.4), NR_027457 (LINC00221) and NR_126415 (FOXP4-AS1) to pinpoint the potential lncRNAs-related ceRNA. RESULTS: A total of 329 lncRNAs and 179 mRNAs were identified to have differential expression in PAS. The results of qRT-PCR were consistent with the human microarrays results. Transforming growth factor-ß (TGF-ß) signaling pathway was the most significantly enriched pathway. The constructed ceRNA network suggested that RP5-875H18.4--miRNA-218--SLIT2 had a potential ceRNA regulatory mechanism in PAS. CONCLUSIONS: The differentially expressed lncRNAs are involved in the occurrence and progression of PAS possibly by regulating the TGF-ß signaling pathway. The ceRNA network of RP5-875H18.4--miRNA-218--SLIT2 may play a role in the occurrence of PAS.


Assuntos
Placenta Acreta/patologia , RNA Longo não Codificante/genética , Cesárea , Feminino , Redes Reguladoras de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Placenta Acreta/genética , Gravidez , Transdução de Sinais , Fator de Crescimento Transformador beta
9.
Adv Exp Med Biol ; 1185: 233-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884617

RESUMO

The specific association of Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (LCA-like) with sensorineural hearing loss (SHL) is uncommon. Recently, we ascribed some of these distinctive associations to dominant and de novo mutations in the ß-tubulin 4B isotype-encoding gene (TUBB4B), providing a link between a sensorineural disease and anomalies in microtubules behavior. Here, we report 12 sporadic cases with LCA/SHL or LCA-like/SHL and no TUBB4B mutation. Trio-based whole exome sequencing (WES) identified disease-causing mutations in 5/12 cases. Four out of five carried biallelic mutations in PEX1 (1/4) or PEX6 (3/4), involved in peroxisome biogenesis disorders from Zellweger syndrome characterized by severe neurologic and neurosensory dysfunctions, craniofacial abnormalities, and liver dysfunction to Heimler syndrome associating SHL, enamel hypoplasia of the secondary dentition, nail abnormalities, and occasional retinal disease. Upon reexamination, the index case carrying PEX1 mutations, a 4-year-old girl, presented additional symptoms consistent with Zellweger syndrome. Reexamination of individuals with PEX6 mutations (1/3 unavailable) revealed normal nails but enamel hypoplasia affecting one primary teeth in a 4-year-old girl and severe enamel hypoplasia of primary teeth hidden by dental prosthesis in a 50-year-old male, describing a novel PEX6-associated disease of the Zellweger/Heimler spectrum. Finally, hemizygosity for a CACNA1F mutation was identified in an 18-year-old male addressed for LCA/SHL, redirecting the retinal diagnosis to congenital stationary night blindness (CSNB2A). Consistent with the pure CSNB2A retinal involvement, SHL was ascribed to biallelic mutations in another gene, STRC, involved in nonprogressive DFNB16 deafness.


Assuntos
Perda Auditiva Neurossensorial/genética , Amaurose Congênita de Leber/genética , Distrofias Retinianas/genética , ATPases Associadas a Diversas Atividades Celulares/genética , Adolescente , Canais de Cálcio Tipo L/genética , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Unhas Malformadas , Linhagem
10.
Clin Exp Rheumatol ; 37 Suppl 121(6): 142-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856934

RESUMO

OBJECTIVES: To describe phenotypic and functional characteristics of patients with the homozygous c.973-2A>G splice site mutation in the adenosine deaminase 2 (ADA2) gene (rs139750129), resulting in deficiency of ADA2 (DADA2). METHODS: We present case synopses of six patients from three unrelated families. Clinical data were analysed and next-generation sequencing (NGS) was performed. We also tested for aberrant RNA splicing and measured ADA2 enzyme activity. RESULTS: One family had common DADA2 symptoms, whereas Behçet's disease-like manifestations were observed in the other two families. We detected the homozygous c.973-2A>G splice site mutation in ADA2 in all patients tested. ADA2 enzyme activity was significantly lower in patients than in healthy controls, but no correlation between ADA2 activity levels and disease severity was observed. Aberrant splicing was detected in a minority of mRNA transcripts, but the formation of other, undetected, aberrant splicing products could not be excluded. Patients were treated with TNF-α inhibitors to prevent recurrence of inflammatory findings including cerebral vasculitis-associated stroke. CONCLUSIONS: We describe three families with the same homozygous splice site mutation in ADA2 and observed a novel combination of manifestations resembling Behçet's disease. This further expands the range of phenotypes caused by ADA2 mutations, although no complete genotype-phenotype association could be determined. Even without active disease, the risk of stroke should be addressed in making decisions regarding treatment of DADA2 patients.


Assuntos
Adenosina Desaminase , Síndrome de Behçet/genética , Peptídeos e Proteínas de Sinalização Intercelular , Mutação/genética , Adenosina Desaminase/deficiência , Adenosina Desaminase/genética , Variação Biológica da População , Estudos de Associação Genética , Homozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Peptídeos e Proteínas de Sinalização Intercelular/genética
11.
Adv Clin Exp Med ; 28(11): 1571-1575, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31756066

RESUMO

Despite great advances in medicine, the proper treatment of arterial hypertension (AH), diabetes mellitus (DM) and chronic kidney disease (CKD) remains a major challenge. Untreated, undiagnosed AH or DM may lead to the development of CKD and consequently to the occurrence of cardiovascular events. Adropin and irisin are newly discovered proteins which may play a role in the development and progression of the chronic diseases mentioned above. Endothelium dysfunction could be a bonding point. The following review paper focuses on adropin and irisin concentrations and their correlations in AH, DM and CKD. Lower adropin concentrations have been measured in patients with primary AH when compared to healthy volunteers. Irisin has reduced blood pressure on nitric oxide (NO)-dependent pathways in experimental studies; a negative correlation between irisin and blood pressure values has also been observed in preeclamptic women. Irisin also plays a role in insulin sensitivity and metabolic disorders. Lower irisin levels have been observed in patients with DM type 2 in comparison to a nondiabetic control group. It is also lower in the serum of pregnant women with gestational DM. A negative correlation between irisin and estimated glomerular filtration rate (EGFR) has also been noted. Adropin and irisin are newly described myokines measured in human plasma in healthy and disease status. Their exact function has not been specified yet and requires further studies.


Assuntos
Diabetes Mellitus/fisiopatologia , Fibronectinas/sangue , Hipertensão/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos/sangue , Insuficiência Renal Crônica/fisiopatologia , Biomarcadores/sangue , Proteínas Sanguíneas , Diabetes Mellitus/sangue , Diabetes Mellitus/metabolismo , Fibronectinas/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/metabolismo
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 769-775, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750816

RESUMO

Objective To explore the functions and mechanisms of macrophages derived from PGRN gene knockout (PGRN-/- ) C57BL/6 mice in the invasion and migration of breast cancer cells. Methods Breast cancer cells were cultured in conditioned medium of macrophages derived from WT and PGRN-/- mice. TranswellTM assay and scratch assay were used to detect the invasion and migration ability of cancer cells. Western blot analysis was used to detect the expression of E-cadherin and N-cadherin in cancer cells. Cytokine array, real-time quantitative PCR and ELISA were performed to investigate the differences of cytokines secreted by macrophages derived from WT and PGRN-/- mice. Breast cancer cells were treated by the differentially expressed cytokine interleukin-6 (IL-6), and then the above methods were used to investigate its effect on cancer cells. Western blot analysis was used to verify the roles of NF-κB and JAK/STAT3 signaling pathways. Results The macrophages derived from PGRN-/- mice blocked NF-κB signaling pathway, reduced IL-6 secretion, and inhibited the invasion and migration of breast cancer cells. IL-6 activated JAK/STAT3 signaling pathway to promote the invasion and migration of breast cancer cells. Conclusion The macrophages derived from PGRN-/- mice can block the NF-κB and JAK/STAT3 signaling pathways, down-regulate IL-6 expression, and inhibit the invasion and migration of breast cancer cells.


Assuntos
Neoplasias da Mama/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interleucina-6/imunologia , Macrófagos/imunologia , Transdução de Sinais , Animais , Neoplasias da Mama/imunologia , Caderinas , Movimento Celular , Meios de Cultivo Condicionados , Granulinas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Invasividade Neoplásica , Fator de Transcrição STAT3/metabolismo , Células Tumorais Cultivadas
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1115-1119, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703139

RESUMO

OBJECTIVE: To explore the genetic basis for a boy with mental retardation. METHODS: Clinical data and peripheral blood samples of the family were collected. Potential variants were screened by using a panel for genes associated with intellectual impairment. Suspected variants were verified by PCR and Sanger sequencing. RESULTS: The child presented with mental retardation, language delay and poor self-care. Imaging analysis showed widening of brain fissures and subarachnoid space, and dysplasia of corpus callosum. Three novel heterozygous variants, namely c.1705T to C (p.S569P), c.1708dupC (p.R570Pfs*80) and c.2273delA (p.N758Tfs*22), were identified in the TRAPPC9 gene. The mother of the proband has carried the c.1708dupC (p.R570Pfs*80) and c.1705T to C (p.S569P) variants, while his father has carried the c.2273delA (p.N758Tfs*22) variant. CONCLUSION: The compound heterozygous variants of the TRAPPC9 gene probably underlie the disease in this family. Considering the clinical and genetic heterogeneity of mental retardation, genetic testing is essential for attaining diagnosis for patients with the relevant phenotype.


Assuntos
Proteínas de Transporte/genética , Deficiência Intelectual/genética , Criança , Testes Genéticos , Heterozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Mutação , Fenótipo
14.
J Biol Regul Homeost Agents ; 33(5): 1369-1376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637897

RESUMO

The objective of this paper was to study the effects of PYR-ARG-PRO-ARG-LEU-SER-HIS-YSGLY-PRO-MET-PRO-PHE-OH (APELIN-13) on the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in rats with experimental autoimmune neuritis (EAN). A total of 30 rats were divided into a control group, an EAN group, and an APELIN-13 group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-6, TNF-α, and IFN-γ in rat plasma. Real-time quantitative Polymerase Chain Reaction (PCR) and Western blot were used to detect the protein and mRNA expression of IL-6, TNF-α, and IFN-γ in rat lymph nodes. In the EAN group, the infiltration of various types of inflammatory cells and focal demyelination were observed near the nerve fascicles of sciatic nerves. Compared with the EAN group, the infiltration of inflammatory cells and demyelination in the APELIN-13 group decreased significantly. The levels of plasma IL-6, TNF-α, and IFN-γ in the EAN group were significantly higher than those in the control group (P < 0.05) but significantly lower than those in the APELIN-13 group (P < 0.05). Compared with the control group, the mRNA and protein expression of IL-6, TNF-α, and IFN-γ increased significantly (P < 0.05) in the EAN group but decreased significantly in the APELIN-13 group (P < 0.05). In conclusion, APELIN-13 exerted a protective effect against EAN in rats.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Interferon gama/metabolismo , Interleucina-6/metabolismo , Neurite Autoimune Experimental/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Ratos
15.
Medicine (Baltimore) ; 98(43): e17432, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651846

RESUMO

BACKGROUND: Several studies have explored the prognostic value of stanniocalcin 2 (STC2) in various cancers, but obtained inconsistent results. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathologic significance of STC2 in various cancers. METHODS: Eligible studies were identified by searching the online databases PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure up to March 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) and were calculated to clarify the correlation between STC2 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between STC2 with clinicopathologic characteristics of patients with cancer. RESULTS: A total of 16 eligible studies with 4074 patients with cancer were included in our meta-analysis. The results showed that high STC2 expression can predict poor overall survival (OS) for cancer (HR = 1.48, 95% CI: 1.15-1.90, P = .002). Subgroup analysis found that high STC2 expression was associated with worse OS in Asian (HR = 1.85, 95% CI: 1.35-2.55), the reported directly from articles group (HR = 1.39, 95% CI: 1.05-1.84), survival curves group (HR = 1.93, 95% CI: 1.36-2.74), and gastric cancer (HR = 1.43, 95% CI: 1.04-1.95). Furthermore, high STC2 expression was significantly related to advanced T stage (OR = 1.83, 95% CI: 1.17-2.86, P = .008), lymph node metastasis (OR = 2.29, 95% CI: 1.51-3.45, P < .001), lymphatic invasion (OR = 2.15, 95% CI: 1.53-3.02, P < .001), venous invasion (OR = 1.97, 95% CI: 1.30-2.99, P = .001), and more advanced clinical stage (OR = 2.36, 95% CI: 1.74-3.19, P < .001) CONCLUSION:: Elevated expression of STC2 suggested a poor prognosis in patients with cancer and may serve as a new tumor marker to monitor cancer development and progression.


Assuntos
Glicoproteínas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/sangue , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Neoplasias/patologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
16.
Zhonghua Yan Ke Za Zhi ; 55(10): 769-776, 2019 Oct 11.
Artigo em Chinês | MEDLINE | ID: mdl-31607066

RESUMO

Objective: To identify differentially expressed proteins between the patients with proliferative diabetic retinopathy (PDR) and vitreous floaters, and explore treatment target for PDR based on isobaric tags for relative and absolute quantification (iTRAQ) LC-MS/MS Proteomics. Method: Vitreous samples were collected from 28 eyes of patients with PDR and 4 eyes with vitreous floaters, which served as controls. For quantitative proteomics, vitreous samples were combined and proteins extracted and labeled with iTRAQ peptide-tagging reagents. Samples were fractionated by liquid chromatography (LC), analyzed by tandem mass spectrometry (MS/MS) and Gene Ontology (GO) analyses performed on differentially expressed proteins identified in the PDR samples. Results: In the PDR vitreous, 26 proteins were identified that were differentially expressed when compared to the controls. Of these, 7 showed a significant increase (P<0.05) and 19 a significant decrease (P<0.05)in expression in PDR patients. These included some high abundance proteins including Retinoic acid receptor reactive protein 2 (PDR 1=85.0, PDR 2=83.0, Control 1=119.6, Control 2=120.2, FC=0.710, P=0.001), Semaphorin-4B(PDR 1=64.4, PDR 2=68.8, Control 1=135.4, Control 2=146.0, FC=0.473, P=0.023), Apolipoprotein B (PDR 1=104.4, PDR 2=106.6, Control 1=89.0, Control 2=85.3, FC=1.211, P=0.024), and Heat shock protein 70 (PDR 1=69.3, PDR 2=75.0, Control 1=137.7, Control 2=138.3, FC=0.523, P=0.026), which are closely related to the pathological mechanism of PDR. GO analysis clustered the differentially expressed genes into three major functional domains: Biological Processes, Molecular Function and Cellular Component. Differential gene expression was found in the categories of cellular metabolism, organonitrogen compound and carbohydrate derivative metabolic processes, transferase activity and transmembrane signaling receptor activity. KEGG Pathway analysis indicate that Chemerin signaling through Akt, Sema4B signaling via PI3K, and HIF-1α signal pathways were all altered in the PDR samples. Conclusions: In this study we identified variations in expression of genes extensively involved in key biological processes in the retina including neovascularization, cellular metabolism and transmembrane signaling, which provide new insights into the pathophysiology of PDR. Extracellular matrix was degraded and endothelial cell migration was induced by Chemerin, in addition, the destruction of blood-retinal barrier and neuronal apoptosis were induced by ApoB. Chemerin and ApoB accelerated the development of PDR. Sema 4B participated in vascular protection, HSP70 conducted anti-apoptosis. These two cytokines protected the retinal neurovascular in PDR patients. Therefore, Chemerin, Sema 4B, ApoB and HSP70 may be the treatment target for PDR. (Chin J Ophthalmol, 2019, 55:769-776).


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Corpo Vítreo/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Quimiocinas/metabolismo , Cromatografia Líquida/métodos , Diabetes Mellitus Tipo 2/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Proteoma/análise , Espectrometria de Massas em Tandem/métodos , Corpo Vítreo/química
17.
Cell Physiol Biochem ; 53(4): 687-700, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31577078

RESUMO

BACKGROUND/AIMS: Apelin and its G protein-coupled receptor APJ (gene symbol Aplnr) are strongly expressed in magnocellular vasopressinergic neurons suggesting that the apelin/APJ system plays a key role at the central level in regulating salt and water balance by counteracting the antiduretic action of vasopressin (AVP). Likewise, recent studies revealed that apelin exerts opposite effects to those of vasopressin induced on water reabsorption via a direct action on the kidney collecting duct. However, the underlying mechanisms of the peripheral action of apelin are not clearly understood. Here, we thus investigated the role of the apelin/APJ system in the regulation of water balance in the kidney, and more specifically its involvement in modulating the function of aquaporin-2 (AQP2) in the collecting duct. METHODS: Mouse cortical collecting duct cells (mpkCCD) were incubated in the presence of dDAVP and treated with or without apelin-13. Changes in AQP2 expression and localization were determined by immunoblotting and confocal immunofluorescence staining. RESULTS: Herein, we showed that the APJ was present in mpkCCD cells. Treatment of mpkCCD with apelin-13 reduced the cAMP production and antagonized the AVP-induced increase in AQP2 mRNA and protein expressions. Immunofluorescent experiments also revealed that the AVP-induced apical cell surface expression of AQP2, and notably its phosphorylated isoform AQP2-pS269, was considerably reduced following apelin-13 application to mpkCCD cells. CONCLUSION: Our data reinforce the aquaretic role of the apelin/APJ system in the fine regulation of body fluid homeostasis at the kidney level and its physiological opposite action to the antiduretic activity of AVP.


Assuntos
Aquaporina 2/metabolismo , Desamino Arginina Vasopressina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Transporte Proteico/efeitos dos fármacos , Animais , Receptores de Apelina/metabolismo , Aquaporina 2/genética , Linhagem Celular , AMP Cíclico/metabolismo , Células HEK293 , Humanos , Túbulos Renais Coletores/citologia , Túbulos Renais Coletores/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos
18.
Medicine (Baltimore) ; 98(38): e17208, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567972

RESUMO

Ulcerative colitis (UC) and Crohn disease (CD) are the most common forms of inflammatory bowel disease (IBD). Because these subtypes of IBD are characterized by periods of activity and remission, an understanding of the modulation of biochemical markers with the clinical features of IBD or its treatment, may be useful for determining the correct treatment protocol.This study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with IBD, correlation with clinical findings of disease, and modulation according to the pharmacologic therapy.A case-control study was carried out in Zacatecas, Mexico. The 27 protein profiles of serum from 53 participants (23 UC, 11 CD, and 19 controls) were evaluated using the Pro Human Cytokine 27-Plex immunoassay (Bio-Rad).Considering the controls as a reference, the group with IBD endoscopic activity showed higher serum levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1 receptor antagonist (IL-1Ra), and platelet-derived growth factor BB (PDGF-BB) (P < .05). Interferon-induced protein 10 (IP-10) was associated with extraintestinal symptoms of disease (P = .041). Both PDGF-BB and interleukin 6 (IL-6) showed the strongest correlations with clinical features of IBD. Levels of IL-6, IL-7, and monocyte chemoattractant protein 1 were higher with 5-aminosalicylic acid (5-ASA) + Azathioprine therapy than controls (P < .05). Combined therapy with 5-ASA + Adalimumab led to the strongest changes in marker modulation: IL-4, IL-5, IL-15, and PDGF-BB, were upregulated (P < .05).Elevated serum levels of G-CSF, IL-1Ra, and PDGF-BB were associated with IBD endoscopic activity, and of IP-10 with extraintestinal manifestations of IBD. Combined therapy of 5-ASA + Adalimumab produced significant upregulation of IL-4, IL-5, IL-15, and PDGF-BB. This information may be useful for deciding on the course of pharmacologic therapy for patients with IBD and for generating new therapy alternatives to improve the outcome of patients with IBD.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Doenças Inflamatórias Intestinais/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Adalimumab/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Becaplermina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CXCL10/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-6/sangue , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Receptores de Interleucina-1/sangue
19.
Med Oral Patol Oral Cir Bucal ; 24(6): e704-e711, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655828

RESUMO

BACKGROUND: The main aim of this systematic review was to assess the dry socket management using plasma rich in growth factor (PRGF) in terms of pain relief, alveolar fossa healing, inflammation, the incidence of dry socket. MATERIAL AND METHODS: PubMed, Cochrane Library, Elsevier Science Direct, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI) and VIP database were searched for the related articles without language limitation. Two reviewers independently searched and evaluated relevant studies. This review has been registered in the website PROSPERO (CRD42018087252). RESULTS: 28 articles were retrieved on PubMed and 98 on other electronic databases in the initial search. In the end, 4 randomized controlled trials (RCTs) were included, with a total of 139 patients enrolled. The descriptive results indicated that the use of PRGF may help reduce pain and inflammation after tooth extraction. To some extent, it is beneficial to the management of dry socket after extraction. CONCLUSIONS: Quality assessment indicated all the included studies were judged to be at high risk of bias with low quality. Hence, it was impossible to make a recommendation for clinical use of PRGF based on the current evidence. Clearly, a multicenter clinical randomized controlled trial is needed urgent to evaluate the safety and efficacy of PRGF for dry socket management.


Assuntos
Alvéolo Seco , China , Assistência Odontológica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Extração Dentária
20.
Plast Reconstr Surg ; 144(4): 639e-647e, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568303

RESUMO

Management of flexor tendon injuries of the hand remains a major clinical problem. Even with intricate repair, adhesion formation remains a common complication. Significant progress has been made to better understand the mechanisms of healing and adhesion formation. However, there has been slow progress in the clinical prevention and reversal of flexor tendon adhesions. The goal of this article is to discuss recent literature relating to tendon development, tendon healing, and adhesion formation to identify areas in need of further research. Additional research is needed to understand and compare the molecular, cellular, and genetic mechanisms involved in flexor tendon morphogenesis, postoperative healing, and mechanical loading. Such knowledge is critical to determine how to improve repair outcomes and identify new therapeutic strategies to promote tissue regeneration and prevent adhesion formation.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Traumatismos dos Tendões/cirurgia , Tendões/crescimento & desenvolvimento , Tendões/cirurgia , Aderências Teciduais , Cicatrização , Animais , Humanos , Aderências Teciduais/etiologia
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