RESUMO
Some studies report neurological lesions in patients with genetic skeletal disorders (GSDs). However, none of them describe the frequency of neurological lesions in a large sample of patients or investigate the associations between clinical and/or radiological central nervous system (CNS) injury and clinical, anthropometric and imaging parameters. The project was approved by the institution's ethics committee (CAAE 49433215.5.0000.0022). In this cross-sectional observational analysis study, 272 patients aged four or more years with clinically and radiologically confirmed GSDs were prospectively included. Genetic testing confirmed the diagnosis in the FGFR3 chondrodysplasias group. All patients underwent blinded and independent clinical, anthropometric and neuroaxis imaging evaluations. Information on the presence of headache, neuropsychomotor development (NPMD), low back pain, joint deformity, ligament laxity and lower limb discrepancy was collected. Imaging abnormalities of the axial skeleton and CNS were investigated by whole spine digital radiography, craniocervical junction CT and brain and spine MRI. The diagnostic criteria for CNS injury were abnormal clinical and/or radiographic examination of the CNS. Brain injury included malacia, encephalopathies and malformation. Spinal cord injury included malacia, hydrosyringomyelia and spinal cord injury without radiographic abnormalities. CNS injury was diagnosed in more than 25% of GSD patients. Spinal cord injury was found in 21.7% of patients, and brain injury was found in 5.9%. The presence of low back pain, os odontoideum and abnormal NPMD remained independently associated with CNS injury in the multivariable analysis. Early identification of these abnormalities may have some role in preventing compressive CNS injury, which is a priority in GSD patients.
Assuntos
Doenças Ósseas/genética , Sistema Nervoso Central/lesões , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ferimentos e Lesões/diagnóstico por imagem , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia , Adulto JovemRESUMO
Wound healing involves the interaction of blood cells, proteins, proteases, growth factors, and extracellular matrix components. Inflammation is one of the first events occurring during this process. Previously, we showed that the N-Methyl-(2S,4R)-trans-4-Hydroxy-L-Proline (NMP) from Sideroxylon obtusifolium leaves (a Brazilian medicinal species) presents an anti-inflammatory action. Considering inflammation as an important event in the wound healing process, the objectives were to investigate the topical effects of the NMP gel on a mice wound-induced model. Male Swiss mice were divided into 4 groups: Sham (surgical procedure only), Control (gel-base treated), and 3% or 10% NMP gel-treated groups. Measurements of wound areas and microscopic analyses (HE [hematoxylin-eosin] and PSR [picrosirius red] stainings) were carried out, at the 7th and 12th, days after the wound induction. Furthermore, immunohistochemical assays for iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) and biochemical measurements for TBARS (thiobarbituric acid reactive substances), GSH (glutathione), and myeloperoxidase (MPO) were also performed, at the second day after the wound induction. The work showed that NMP decreases the wound areas, after topical application, relatively to the Sham and Control groups. In addition, microscopic alterations were reduced and collagen deposition was increased, at the 7th and 12th days, in the 10% NMP group. While iNOS and COX-2 immunostainings and GSH contents increased, in relation to the Sham and Control groups, TBARS and MPO decreased. Altogether, the results showed NMP to improve the wound healing process, by upregulating iNOS and COX-2 activities, reducing lipid peroxidation and MPO activity, and increasing GSH contents. In addition, NMP certainly contributes to the increased collagen deposition. These data may stimulate translational studies dealing with the possible use of NMP from Sideroxylon obtusifolium or from other sources for the management of wound healing.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Prolina/administração & dosagem , Sapotaceae/química , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Colágeno/genética , Colágeno/imunologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Glutationa/imunologia , Humanos , Masculino , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Peroxidase/genética , Peroxidase/imunologia , Extratos Vegetais/química , Prolina/análogos & derivados , Ferimentos e Lesões/genética , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/fisiopatologiaRESUMO
The present study investigated the moment of peak NF-kB activation and its dissipation in the cortical bone in the femur of Wistar rat stimulated by surgical trauma. Sixty-five Wistar rats were divided into 13 groups (n = 5 per group): eight experimental groups (expG 1-8) divided based on the euthanasia time point (zero, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h) and five sham control groups (conG 1-5) killed at zero, 1 h, 2 h, 4 h and 6 h, respectively. A 1.8-mm-diameter defect was generated 0.5 mm from the femur proximal joint using a round bur to induce the surgical trauma. Overall, the activation peak of NF-κB in the cortical bone was 6 h (expG5 group) independent of the evaluated position; this peak was significantly different compared to those in the other groups (p < 0.05). The surgical trauma resulted in a spread of immune markings throughout the cortical bone with an accentuation in the knee region. The present study provides the first evidence that the NF-κB activation peak was established after 6 hours in the cortical bone of Wistar rats. The signs from a surgical trauma can span the entire cortical bone and are not limited to the damaged region.
Assuntos
Osso e Ossos/metabolismo , Traumatismos do Joelho/genética , NF-kappa B/biossíntese , Ferimentos e Lesões/genética , Animais , Osso e Ossos/lesões , Osso e Ossos/patologia , Fêmur/lesões , Fêmur/metabolismo , Fêmur/patologia , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/patologia , Traumatismos do Joelho/patologia , NF-kappa B/genética , Ratos , Ratos Wistar , Ferimentos e Lesões/patologiaRESUMO
Despite years of effort, current therapies for diabetic wounds are still not fully efficacious. Emerging evidence has suggested that microRNAs (miRNAs) play key roles in multiple physiological and pathological processes in eukaryotes, and could potentially be powerful therapeutic tools. This study investigated the differential expression profiling of miRNAs in cutaneous wounds in streptozotocin-induced diabetic rats and normal rats, and its significance in diabetic wound healing. Using microarrays, 18 miRNAs were identified as being upregulated and 65 as being downregulated in the diabetic group. The miRNA profiling results were validated by quantitative reverse transcriptase polymerase chain reaction. Finally, functional annotation analysis using the DAVID and miR2Subpath databases revealed that the differentially expressed miRNAs were involved in MAPK signaling pathways, the Wnt signaling pathway, and other signaling pathways that may be closely linked to wound healing. This study provides an experimental foundation for further investigation of mechanisms that underlie poor diabetic wound healing, and of miRNA-based therapies that are associated with wound healing.
Assuntos
Complicações do Diabetes , Diabetes Mellitus Experimental , MicroRNAs/genética , Transcriptoma , Ferimentos e Lesões/etiologia , Animais , Biologia Computacional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Masculino , Anotação de Sequência Molecular , Fenótipo , Ratos , Reprodutibilidade dos Testes , Transdução de Sinais , Úlcera Cutânea/etiologia , Úlcera Cutânea/genética , Úlcera Cutânea/metabolismo , Cicatrização/genética , Ferimentos e Lesões/genética , Ferimentos e Lesões/metabolismoRESUMO
This study aimed to identify marker genes in diabetic wounds using a dataset based on a DNA microarray of dermal lymphatic endothelial cells, and our results provide a basic understanding of diabetic wounds through further study of these differentially expressed genes (DEGs). From the Gene Expression Omnibus database, we downloaded a gene expression microarray (GSE38396) that includes 8 samples: 4 normal controls and 4 disease samples (type II diabetes). We then identified genes that were differentially expressed between normal and disease samples using packages in R language, constructed a protein-protein interaction (PPI) network and analyzed modules in the network. In addition, phylogenetic analysis was performed by MEGA to find the most conserved genes. Two hundred and thirteen genes were identified as being differentially expressed between normal and disease samples, and we constructed a PPI network that included 213 pairs of proteins. We then identified a module including 20 genes, the function of which was significantly enriched in wounding response. Lastly, the most conserved genes, CD44 and CCL5, were identified through phylogenetic analysis. In summary, we found differentially expressed marker genes, a wounding response-related module, and the most important genes CD44 and CCL5. Our findings suggest new approaches to therapies for diabetic wounds.