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1.
Acta Histochem ; 121(8): 151450, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31672390

RESUMO

INTRODUCTION: Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is a rare oral ulcerated lesion of uncertain etiology, showing eosinophil-rich granulation tissue, with occasional large atypical CD30 positive mononuclear cells. It had been suggested that it may represent an oral counterpart of cutaneous lymphomatoid papulosis, with a potential to evolve into CD30 + T cell lymphoma OBJECTIVES: To compare TUGSE and non-specific oral ulcers (NSU) clinically, histopathologically and by clonality analysis for T-cell receptor re-arrangement, aiming to determine whether TGUSE with atypical cells is a lymphomatous premalignant condition, and whether therapeutic approach should be radical or conservative. MATERIALS AND METHODS: Retrospective archival analysis included 17 TUGSE and 8 NSU cases. Histopathological parameters included mean eosinophil number per high power field (HPF), presence of infiltration of deep soft tissues and presence of atypical cells. Immuno-morphometry comprised of the mean number of CD30+ atypical cells per HPF. T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR) was performed in all cases showing atypical cells. Clinical and follow up data were retrieved from files. RESULTS: TUGSE showed a significantly higher mean eosinophil number/HPF in comparison to NSU (7.0 + 4.2 cells and 2.3 + 1.72, respectively; p < 0.001). Atypical cells were found in 9 (53%) cases of TUGSE and in only 1 (11%) case of NSU. CD30+ atypical cells were found in 7 (41%) cases of TUGSE and only in 1 (11%) case of NSU. Mean number of CD30+ cells/HPF was 0.23 + 0.19 (range 0 - 0.54 cells/HPF) for TUGSE. In the only NSU case with CD30+ cells, their density was 0.52/HPF. All lesions with atypical cells were polyclonal for TCR. All cases were self-limiting, with no recurrences, after 3-9 years (mean 4.6 years) follow up. CONCLUSIONS: Analysis found no support to the suggestion that TUGSE with atypical cells represents the oral counterpart of lymphomatoid papulosis or predisposes the lesions for a hematolymphoid malignancy. Suggestions for radical therapeutic approach and long-term follow-up are probably unjustified, with no recurrences or malignancy recorded following conservative treatment alone for a period of up to 9 years of follow-up. Staining for CD30 and PCR for TCR gene rearrangement should be reserved only for rare cases with abundant large atypical cells and/or unusual clinical behavior.


Assuntos
Rearranjo Gênico do Linfócito T , Granuloma , Antígeno Ki-1 , Granulomatose Linfomatoide , Neoplasias Bucais , Proteínas de Neoplasias , Úlceras Orais , Ferimentos e Lesões , Idoso , Idoso de 80 Anos ou mais , Criança , Eosinofilia/genética , Eosinofilia/metabolismo , Eosinofilia/patologia , Feminino , Seguimentos , Granuloma/genética , Granuloma/metabolismo , Granuloma/patologia , Humanos , Antígeno Ki-1/genética , Antígeno Ki-1/metabolismo , Granulomatose Linfomatoide/genética , Granulomatose Linfomatoide/metabolismo , Granulomatose Linfomatoide/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Úlceras Orais/genética , Úlceras Orais/metabolismo , Úlceras Orais/patologia , Estudos Retrospectivos , Ferimentos e Lesões/genética , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia
2.
Nat Commun ; 10(1): 4042, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492871

RESUMO

Tissue injury induces changes in cellular identity, but the underlying molecular mechanisms remain obscure. Here, we show that upon damage in a mouse model, epidermal cells at the wound edge convert to an embryonic-like state, altering particularly the cytoskeletal/extracellular matrix (ECM) components and differentiation program. We show that SOX11 and its closest relative SOX4 dictate embryonic epidermal state, regulating genes involved in epidermal development as well as cytoskeletal/ECM organization. Correspondingly, postnatal induction of SOX11 represses epidermal terminal differentiation while deficiency of Sox11 and Sox4 accelerates differentiation and dramatically impairs cell motility and re-epithelialization. Amongst the embryonic genes reactivated at the wound edge, we identify fascin actin-bundling protein 1 (FSCN1) as a critical direct target of SOX11 and SOX4 regulating cell migration. Our study identifies the reactivated embryonic gene program during wound repair and demonstrates that SOX11 and SOX4 play a central role in this process.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Transcrição SOXC/genética , Cicatrização/genética , Ferimentos e Lesões/genética , Animais , Diferenciação Celular/genética , Movimento Celular/genética , Citoesqueleto/metabolismo , Células Epidérmicas/citologia , Células Epidérmicas/metabolismo , Epiderme/embriologia , Epiderme/metabolismo , Matriz Extracelular , Camundongos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Fatores de Transcrição SOXC/metabolismo , Ferimentos e Lesões/embriologia
3.
J Evid Based Integr Med ; 24: 2515690X19865166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31394920

RESUMO

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/fisiopatologia
4.
Int J Low Extrem Wounds ; 18(2): 143-152, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035807

RESUMO

This study focused on potential of vitamin C loaded human serum albumin (HSA) nanoparticles for treatment of wound. Nanocarrier were prepared and assessed for their effect on growth of 3T3 fibroblast cells, cell migration, wound healing rate and expression of miR-155, TGF-ß1 and SMAD 1,2 genes. Wound healing assay was done and wounds were treated with vitamin C loaded HSA nanoparticles. Nanoparticles were prepared with size and zeta potential of 180±6 and -29 mV, respectively. Vitamin C loaded HSA nanoparticles showed controlled release of vitamin C into the buffer solution. Also, yield and encapsulation efficacy of loaded nanoparticles were obtained as 70.6 and 52.1 %, respectively. MTT results showed that the growth of 3T3 fibroblast cells was promoted in culture medium with 20 µg/ml of vitamin C loaded HSA nanoparticles. Cell migration assay indicated the positive effect of loaded nanoparticles on wound healing. The in-vivo results showed that the rate of wound healing was increased after treatment with 20 µg/ml of vitamin C loaded HSA nanoparticles. The wounds were healed faster when treated with vitamin C loaded HSA nanoparticles in comparison with control group. The expression of miR-155 was downregulated after treatment. Furthermore, expression of TGF-ß1 and SMAD 1,2 were increased while the wounds were treated with these nanoparticles. In conclusion, these results showed for the first time that wounds were healed after treatment with albumin nanocarrier loaded with vitamin C. This nanocarrier changed expression of miR-155 and TGF-ß1 towards faster healing of wounds.


Assuntos
Ácido Ascórbico/uso terapêutico , MicroRNAs/genética , Nanopartículas/administração & dosagem , Albumina Sérica Humana/uso terapêutico , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/terapia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Valores de Referência , Pele/efeitos dos fármacos , Pele/lesões , Cicatrização/fisiologia , Ferimentos e Lesões/genética
5.
PLoS One ; 14(5): e0216249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31059533

RESUMO

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease resulting in non-healing wounds affecting body areas of high hair follicle and sweat gland density. The pathogenesis of HS is not well understood but appears to involve dysbiosis-driven aberrant activation of the innate immune system leading to excessive inflammation. Marked dysregulation of antimicrobial peptides and proteins (AMPs) in HS is observed, which may contribute to this sustained inflammation. Here, we analyzed HS skin transcriptomes from previously published studies and integrated these findings through a comparative analysis with a published wound healing data set and with immunofluorescence and qPCR analysis from new HS patient samples. Among the top differently expressed genes between lesional and non-lesional HS skin were members of the S100 family as well as dermcidin, the latter known as a sweat gland-associated AMP and one of the most downregulated genes in HS lesions. Interestingly, many genes associated with sweat gland function, such as secretoglobins and aquaporin 5, were decreased in HS lesional skin and we discovered that these genes demonstrated opposite expression profiles in healing skin. Conversely, HS lesional and wounded skin shared a common gene signature including genes encoding for S100 proteins, defensins, and genes encoding antiviral proteins. Overall, our results suggest that the pathogenesis of HS may be driven by changes in AMP expression and altered sweat gland function, and may share a similar pathology with chronic wounds.


Assuntos
Hidradenite Supurativa/genética , Pele , Glândulas Sudoríparas/metabolismo , Transcriptoma , Peptídeos Catiônicos Antimicrobianos/genética , Hidradenite Supurativa/patologia , Inflamação/etiologia , Proteínas S100/genética , Glândulas Sudoríparas/fisiopatologia , Ferimentos e Lesões/genética
6.
Gen Comp Endocrinol ; 280: 47-53, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981703

RESUMO

There is increasing evidence that one's risk for psychiatric disturbances and metabolic syndromes is influenced by their parents' own health history, lifestyle and living environment. For example, paternal high fat diet is strongly linked to neuroendocrine dysregulation in offspring and increased risk for diabetes. The potential intergenerational impact of paternal stress has only just begun to emerge, with the initial evidence suggestive of greater risk for anxiety-related disorders. The hypothalamic-pituitary-adrenal (HPA)-axis is a key neuroendocrine signalling system involved in physiological homeostasis and stress response. In individuals, dysregulation of this system is closely associated with behavioral deficits and mood disorders. Various preclinical models of paternal stress have demonstrated robust behavioral shifts but little is known about the intergenerational modification of HPA axis function. This review will present evidence drawn from a range of laboratory mouse and rat models that the intergenerational influence of paternal stress on offspring behavioral phenotypes involve some level of HPA axis dysregulation. It makes the case that further investigations to comprehensively profile HPA axis function in offspring generations is warranted.


Assuntos
Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Estresse Psicológico/metabolismo , Ferimentos e Lesões/psicologia , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Endogâmicos C57BL , Ratos , Estresse Psicológico/complicações , Ferimentos e Lesões/complicações , Ferimentos e Lesões/genética
7.
J Immunol ; 202(10): 3020-3032, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988118

RESUMO

The inflammatory response to infection or injury dramatically increases the hematopoietic demand on the bone marrow to replace effector leukocytes consumed in the inflammatory response. In the setting of infection, pathogen-associated molecular patterns induce emergency hematopoiesis, activating hematopoietic stem and progenitor cells to proliferate and produce progeny for accelerated myelopoiesis. Sterile tissue injury due to trauma also increases leukocyte demand; however, the effect of sterile tissue injury on hematopoiesis is not well described. We find that tissue injury alone induces emergency hematopoiesis in mice subjected to polytrauma. This process is driven by IL-1/MyD88-dependent production of G-CSF. G-CSF induces the expansion of hematopoietic progenitors, including hematopoietic stem cells and multipotent progenitors, and increases the frequency of myeloid-skewed progenitors. To our knowledge, these data provide the first comprehensive description of injury-induced emergency hematopoiesis and identify an IL-1/MyD88/G-CSF-dependent pathway as the key regulator of emergency hematopoiesis after injury.


Assuntos
Fator Estimulador de Colônias de Granulócitos/imunologia , Hematopoese/imunologia , Interleucina-1/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Ferimentos e Lesões/imunologia , Animais , Fator Estimulador de Colônias de Granulócitos/genética , Hematopoese/genética , Interleucina-1/genética , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia
8.
J Immunol ; 202(9): 2720-2727, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30910860

RESUMO

The aim of this study was to determine whether skin wounding induces monocyte (Mo) expansion in bone marrow and whether IL-1R1 signaling regulates this process. Our data show that skin wounding increases myeloid lineage-committed multipotent progenitors (MPP3 subset) and Mo in bone marrow, but this expansion is not impaired in Il1r1-/- mice. We also demonstrate that M-CSF-induced differentiation of myeloid progenitors into Mo is not impaired by the loss of IL-1R1 ex vivo, indicating that IL-R1 deficiency does not abrogate myeloid progenitor differentiation potential. In addition, we observed modestly delayed wound closure in Il1r1-/- mice associated with higher frequency of Ly6Clo Mo in the circulation at baseline and in wounds early after injury. Thus, in contrast to other models of inflammation that involve IL-1R1-dependent monopoiesis, our results demonstrate that skin wounding induces Mo progenitor and Mo expansion independently of IL-1R1 signaling.


Assuntos
Medula Óssea/imunologia , Monócitos/imunologia , Receptores Tipo I de Interleucina-1/deficiência , Pele/imunologia , Cicatrização/imunologia , Ferimentos e Lesões/imunologia , Animais , Medula Óssea/patologia , Camundongos , Camundongos Knockout , Monócitos/patologia , Receptores Tipo I de Interleucina-1/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Pele/patologia , Cicatrização/genética , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia
9.
Pigment Cell Melanoma Res ; 32(5): 643-656, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30849202

RESUMO

Although pigment synthesis is well understood, relevant mechanisms of psychologically debilitating dyspigmentation in nascent tissue after cutaneous injuries are still unknown. Here, differences in genomic transcription of hyper- and hypopigmented tissue relative to uninjured skin were investigated using a red Duroc swine scar model. Transcription profiles differed based on pigmentation phenotypes with a trend of more upregulation or downregulation in hyper- or hypopigmented scars, respectively. Ingenuity Pathway Analysis of significantly modulated genes in both pigmentation phenotypes showed pathways related to redox, metabolic, and inflammatory responses were more present in hypopigmented samples, while those related to stem cell development differentiation were found mainly in hyperpigmented samples. Cell-cell and cell-extracellular matrix interactions and inflammation responses were predicted (z-score) active in hyperpigmented and inactive in hypopigmented. The proinflammatory high-mobility group box 1 pathway showed the opposite trend. Analysis of differentially regulated mutually exclusive genes showed an extensive presence of metabolic, proinflammatory, and oxidative stress pathways in hypopigmented scars, while melanin synthesis, glycosaminoglycans biosynthesis, and cell differentiation pathways were predominant in hyperpigmented scar. Several potential therapeutic gene targets have been identified.


Assuntos
Biomarcadores/análise , Cicatriz Hipertrófica/patologia , Cor , Hiperpigmentação/patologia , Hipopigmentação/patologia , Pigmentação da Pele/genética , Ferimentos e Lesões/patologia , Animais , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/metabolismo , Modelos Animais de Doenças , Hiperpigmentação/genética , Hipopigmentação/genética , Masculino , Suínos , Transcriptoma , Cicatrização , Ferimentos e Lesões/genética
10.
Nat Commun ; 10(1): 424, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30723209

RESUMO

A major goal of regenerative medicine is to stimulate tissue regeneration after traumatic injury. We previously discovered that treating digit amputation wounds with BMP2 in neonatal mice stimulates endochondral ossification to regenerate the stump bone. Here we show that treating the amputation wound with BMP9 stimulates regeneration of a synovial joint that forms an articulation with the stump bone. Regenerated structures include a skeletal element lined with articular cartilage and a synovial cavity, and we demonstrate that this response requires the Prg4 gene. Combining BMP2 and BMP9 treatments in sequence stimulates the regeneration of bone and joint. These studies provide evidence that treatment of growth factors can be used to engineer a regeneration response from a non-regenerating amputation wound.


Assuntos
Dedos/cirurgia , Fator 2 de Diferenciação de Crescimento/metabolismo , Articulações/fisiopatologia , Ferimentos e Lesões/metabolismo , Amputação , Animais , Regeneração Óssea , Cartilagem Articular/metabolismo , Cartilagem Articular/fisiopatologia , Feminino , Fator 2 de Diferenciação de Crescimento/genética , Humanos , Articulações/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/metabolismo , Proteoglicanas/genética , Proteoglicanas/metabolismo , Cicatrização , Ferimentos e Lesões/genética , Ferimentos e Lesões/fisiopatologia
11.
J Invest Dermatol ; 139(5): 1171-1181.e6, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30684552

RESUMO

Cellular senescence can be broadly defined as a stable, but essentially irreversible, loss of proliferative capacity. Historically, senescence has been described as a negative outcome of advanced cellular age. It is now clear, however, that senescence represents a dynamic autonomous stress response, integral to long-term tumor suppression. Transient induction of a senescent phenotype has actually been suggested to promote regeneration in both liver and skin. Here, we explored the role of senescence in pathological aged and diabetic murine wound healing. Aged and diabetic wounds had greater numbers of senescent cells, and diabetic macrophages maintained altered retention of polarization and produced a CXCR2-enriched senescence-associated secretory phenotype (i.e., SASP). Of translational relevance, targeted expression of CXCR2 in primary human dermal fibroblasts led to paracrine induction of nuclear p21. Furthermore, a selective agonist to CXCR2 was able to reverse delayed healing in diabetic mice and accelerate ex vivo human skin wound healing. Collectively, these data suggest a hitherto unappreciated role for CXCR2 in mediating cellular senescence in pathological wound repair.


Assuntos
Envelhecimento/genética , Senescência Celular/genética , Receptores de Interleucina-8B/genética , Cicatrização/genética , Análise de Variância , Animais , Biópsia por Agulha , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Modelos Animais de Doenças , Fibroblastos/citologia , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina-8B/metabolismo , Valores de Referência , Úlcera Cutânea/genética , Úlcera Cutânea/patologia , Cicatrização/fisiologia , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia
12.
Matrix Biol ; 75-76: 12-26, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29330022

RESUMO

The ability of skin to act as a barrier is primarily determined by cells that maintain the continuity and integrity of skin and restore it after injury. Cutaneous wound healing in adult mammals is a complex multi-step process that involves overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodeling. Under favorable conditions, epidermal regeneration begins within hours after injury and takes several days until the epithelial surface is intact due to reorganization of the basement membrane. Regeneration relies on numerous signaling cues and on multiple cellular processes that take place both within the epidermis and in other participating tissues. A variety of modulators are involved, including growth factors, cytokines, matrix metalloproteinases, cellular receptors, and extracellular matrix components. Here we focus on the involvement of the extracellular matrix proteins that impact epidermal regeneration during wound healing.


Assuntos
Matriz Extracelular/genética , Pele/crescimento & desenvolvimento , Cicatrização/genética , Ferimentos e Lesões/genética , Membrana Basal/crescimento & desenvolvimento , Membrana Basal/metabolismo , Movimento Celular/genética , Células Epidérmicas , Matriz Extracelular/patologia , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Reepitelização , Transdução de Sinais/genética , Pele/lesões , Ferimentos e Lesões/patologia
13.
BMC Med Inform Decis Mak ; 18(Suppl 5): 115, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30526581

RESUMO

BACKGROUND: Feature selection and gene set analysis are of increasing interest in the field of bioinformatics. While these two approaches have been developed for different purposes, we describe how some gene set analysis methods can be utilized to conduct feature selection. METHODS: We adopted a gene set analysis method, the significance analysis of microarray gene set reduction (SAMGSR) algorithm, to carry out feature selection for longitudinal gene expression data. RESULTS: Using a real-world application and simulated data, it is demonstrated that the proposed SAMGSR extension outperforms other relevant methods. In this study, we illustrate that a gene's expression profiles over time can be regarded as a gene set and then a suitable gene set analysis method can be utilized directly to select relevant genes associated with the phenotype of interest over time. CONCLUSIONS: We believe this work will motivate more research to bridge feature selection and gene set analysis, with the development of novel algorithms capable of carrying out feature selection for longitudinal gene expression data.


Assuntos
Algoritmos , Biologia Computacional , Perfilação da Expressão Gênica , Análise em Microsséries , Ferimentos e Lesões/genética , Humanos
14.
Biomed Res Int ; 2018: 4210353, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519575

RESUMO

The pathogenesis of posttraumatic osteoarthritis (PTOA) remains unrevealed. We speculate that cartilage crack caused by joint trauma will induce local abnormal tensile stress, leading to change in extracellular matrix (ECM) expression of chondrocytes, cartilage degeneration, and initiation of osteoarthritis. Finite element model was used to examine whether the local tensile stress could be produced around the crack. Cell experiments were conducted to test the effect of tensile strain on chondrocyte ECM expression. Animal tests in rabbits were carried out to examine the change around the cartilage crack. The results indicated that the local tensile stress was generated around the crack and varied with the crack angles. The maximum principal tensile stress was 0.59 MPa around the 45° crack, and no tensile stress was found at 90°. 10% tensile strain could significantly promote type I collagen mRNA expression and inhibit type II collagen and aggrecan (the proteoglycan core protein) mRNA expression. Type I collagen was detected around the 45° crack region in the cartilage with no change in type II collagen and proteoglycan. We conclude that the local tensile stress produced around the cartilage crack can cause the change in cartilage matrix expression which might lead to cartilage degeneration and initiation of osteoarthritis. This study provides biomechanical-based insight into the pathogenesis of PTOA and potentially new intervention in prevention and treatment of PTOA.


Assuntos
Colágeno Tipo I/genética , Matriz Extracelular/genética , Osteoartrite/genética , Ferimentos e Lesões/genética , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Condrócitos/metabolismo , Condrócitos/patologia , Expressão Gênica/genética , Humanos , Articulações/fisiopatologia , Osteoartrite/etiologia , Osteoartrite/fisiopatologia , Coelhos , Estresse Mecânico , Ferimentos e Lesões/complicações , Ferimentos e Lesões/fisiopatologia
15.
Twin Res Hum Genet ; 21(6): 502-506, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30428952

RESUMO

The aim of this study was to examine the effects of genetic and environment influences and sex on injury involvement using two sets of Finnish twin data. The younger participants were 955 twins born between 1983 and 1987, aged 20 to 24 years. The older participants were 12,428 twins born between 1930 and 1957, aged 33 to 60 years. Within-twin correlations in monozygotic and dizygotic twins suggested that genetic effects play no role in injury involvement among young twins, but do have some effect at older ages. The results indicated that environmental factors have greater importance in injury involvement than genetic factors in the younger twin data set (FT12), whereas in a middle-aged (33-60 years) twin data set, genetic effects explained about quarter of the variance in injury involvement. Sex was a strong contributing factor, with males being generally more prone to injuries than females.


Assuntos
Doenças em Gêmeos/epidemiologia , Meio Ambiente , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Fatores Etários , Doenças em Gêmeos/genética , Feminino , Finlândia/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Ferimentos e Lesões/genética , Adulto Jovem
16.
Wounds ; 30(12): 353-362, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30304713

RESUMO

INTRODUCTION: The value of compression studies and applications in hypertrophic scar (HTS) treatment is often undermined due to the lack of ideal controls, patient compliance, and clear action mechanisms. OBJECTIVE: This study assesses the genome-wide compression effects on scars under well-controlled conditions. MATERIALS AND METHODS: An automated pressure delivery system (APDS) applied controlled doses of pressure to scars in a red Duroc swine HTS model. Full-thickness wounds were created by a skin grafting instrument on each animal's bilateral flanks and were observed through reepithelialization and scar development. On day 70, the APDSs were mounted on the developed scars; right flank scars received a pressure of 30 mm Hg, while left flank scars received APDSs with no pressure (sham) for 2 weeks. A genome-wide assessment of compression effect on transcription in scar specimens before (early), shortly after (mid), and long after (late) compression initiation were performed. RESULTS: Analysis of early-phase biopsies showed similar transcriptome profiles, which diverged thereafter in gene numbers and functions between compression- and sham-treated scars in the mid phase. The majority of these changes persisted in the late-phase scar samples. Canonical pathway analysis of differentially regulated genes resulted in an almost identical list of pathways during the early phase prior to compression. In the mid and late phases after compression, many of the identified pathways shifted in significance, and new pathways such as calcium signaling and cholesterol synthesis emerged. CONCLUSIONS: Compression modulates transcription and affects multiple biological functions associated with an improved scar appearance.


Assuntos
Cicatriz Hipertrófica/terapia , Regulação da Expressão Gênica , Pele/metabolismo , Ferimentos e Lesões/patologia , Animais , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/fisiopatologia , Colágeno/metabolismo , Modelos Animais de Doenças , Estudo de Associação Genômica Ampla , Masculino , Pressão , Transdução de Sinais , Pele/patologia , Suínos , Transcrição Genética , Ferimentos e Lesões/genética , Ferimentos e Lesões/terapia
17.
Ageing Res Rev ; 48: 32-39, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30316759

RESUMO

It is well established that numerous factors can affect the rate at which we age biologically. Diet, physical activity, lifestyle and our genes all play a major role in influencing the ageing trajectory and longevity. Major trauma affects millions globally, is the major cause of death in young adults and could influence ageing processes but has largely been ignored by biogenterologists. The long-term health consequences of physical trauma are well known in the medical community, how trauma effects the ageing process at a molecular level is not. It has long been difficult to assess ageing trajectories due to the absence of a biomarker of biological rather than chronological age. Recent advances in epigenetics have helped by identifying specific DNA methylation sites as good indicators of biological age. Recent investigations into the impact of psychological trauma and the associated physical stress on accelerating ageing as measured by epigenetic drift are promising. The physical and metabolic stress which is synonymous with physical trauma may also accelerate the ageing process. We suggest that long term epigenetic profiling is required to understand to what degree the ageing trajectory is altered by trauma, which will in turn add support for the development of novel therapies to improve health outcomes for survivors of traumatic injury.


Assuntos
Envelhecimento/genética , Envelhecimento/metabolismo , Epigênese Genética/fisiologia , Ferimentos e Lesões/genética , Ferimentos e Lesões/metabolismo , Envelhecimento/imunologia , Animais , Biomarcadores/metabolismo , Metilação de DNA/fisiologia , Exercício Físico/fisiologia , Humanos , Longevidade/fisiologia , Ferimentos e Lesões/imunologia
18.
BMC Biotechnol ; 18(1): 51, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157831

RESUMO

BACKGROUND: Fibroblast growth factor 9 (FGF9) is a heparin-binding growth factor, secreted by both mesothelial and epithelial cells, which participates in hair follicle regeneration, wound healing, and bone development. A suitable source of recombinant human FGF9 (rhFGF9) is needed for research into potential clinical applications. We present that expression of oleosin-rhFGF9 fusion protein in safflower (Carthamus tinctorius L.) seeds stimulates hair growth and wound healing. RESULTS: The oleosin-rhFGF9 expressed in safflower seeds, in which it localizes to the surface of oil bodies. The expression of oleosin-rhFGF9 was confirmed by polyacrylamide gel electrophoresis and western blotting. According to BCA and Enzyme-linked immunosorbent assay (ELISA) assay, the results show that the expression level of oleosin-rhFGF9 was 0.14% of oil body protein. The oil body bound oleosin-rhFGF9 showed mitogenic activity towards NIH3T3 cells in a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The efficacy of oil body bound oleosin-rhFGF9 in promoting hair growth and wound healing was investigated in C57BL/6 mice. In a hair regeneration experiment, 50 µg/µl oil body bound oleosin-rhFGF9 was applied to the dorsal skin of mice in the resting phase of the hair growth cycle. After 15 days, thicker hair and increased number of new hairs were seen compared with controls. Furthermore, the number of new hairs was greater compared with rhFGF9-treated mice. The hair follicles of mice treated with oil body bound oleosin-rhFGF9 expressed ß-catenin more abundantly. In a wound healing experiment, dorsal skin wounds were topically treated with 50 µg/µl oil body bound oleosin-rhFGF9. Wound healing was quicker compared with mice treated with rhFGF9 and controls, especially in the earlier stages of healing. CONCLUSIONS: The oil body bound oleosin-rhFGF9 promotes both hair growth and wound healing. It appears to promote hair growth, at least in part, by up-regulating ß-catenin expression. The potential of oil body bound oleosin-rhFGF9 as an external drug can treat the alopecia and wounds or use in further clinical application.


Assuntos
Carthamus tinctorius/genética , Fator 9 de Crescimento de Fibroblastos/administração & dosagem , Fator 9 de Crescimento de Fibroblastos/genética , Cabelo/crescimento & desenvolvimento , Gotículas Lipídicas/metabolismo , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/genética , Ferimentos e Lesões/tratamento farmacológico , Animais , Carthamus tinctorius/metabolismo , Fator 9 de Crescimento de Fibroblastos/metabolismo , Expressão Gênica , Cabelo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Proteínas de Plantas/metabolismo , Transporte Proteico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Cicatrização , Ferimentos e Lesões/genética , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/fisiopatologia , beta Catenina/genética , beta Catenina/metabolismo
19.
J Invest Dermatol ; 138(12): 2653-2665, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29906410

RESUMO

Wound healing is a dynamic process involving gene-expression changes that drive re-epithelialization. Here, we describe an essential role for polyamine regulator AMD1 in driving cell migration at the wound edge. The polyamines, putrescine, spermidine, and spermine are small cationic molecules that play essential roles in many cellular processes. We demonstrate that AMD1 is rapidly upregulated following wounding in human skin biopsies. Knockdown of AMD1 with small hairpin RNAs causes a delay in cell migration that is rescued by the addition of spermine. We further show that spermine can promote cell migration in keratinocytes and in human ex vivo wounds, where it significantly increases epithelial tongue migration. Knockdown of AMD1 prevents the upregulation of urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor on wounding and results in a failure in actin cytoskeletal reorganization at the wound edge. We demonstrate that keratinocytes respond to wounding by modulating polyamine regulator AMD1 in order to regulate downstream gene expression and promote cell migration. This article highlights a previously unreported role for the regulation of polyamine levels and ratios in cellular behavior and fate.


Assuntos
Adenosilmetionina Descarboxilase/metabolismo , Movimento Celular/genética , Epiderme/fisiologia , Queratinócitos/fisiologia , Cicatrização , Ferimentos e Lesões/metabolismo , Citoesqueleto de Actina/metabolismo , Adenosilmetionina Descarboxilase/genética , Biópsia , Sinalização do Cálcio , Células Cultivadas , Humanos , RNA Interferente Pequeno/genética , Reepitelização/genética , Espermina/metabolismo , Regulação para Cima , Ferimentos e Lesões/genética
20.
Dev Growth Differ ; 60(6): 306-315, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29873073

RESUMO

Inflammation at a wound site is essential for preventing infection. However, misregulated inflammation leads to pathologies of the healing process, including chronic non-healing wounds and scarring. MicroRNAs (miRNAs) are key regulators of the inflammatory response and tissue repair, acting by translational processing of target mRNAs. In the final step of miRNA processing, Argonaute 2 (Ago2)-bound mature miRNA complexes bind to target mRNAs and inhibit their translation. A variety of wound healing-related miRNAs have been identified and their misregulation likely contributes to wound pathologies, including scarring and chronic healing. Recently, we have developed an Ago2-bound mature miRNA purification system that uses Ago2 antibody to analyze the expression of miRNAs from wound tissues by microarray and next generation sequencing. We have identified several wound inflammation-related miRNAs via Ago2-target immunoprecipitation assays and next generation sequencing of wound tissues from wild-type and PU.1 knockout mice, which exhibit no inflammatory response because of a lack of immune cell lineages. We demonstrated that miR-142, an identified inflammation-related miRNA, is essential role for neutrophilic chemotaxis via inhibition of small GTPase translation; its misregulation leads to susceptibility to infection against Staphylococcus aureus at skin wound sites. In this review, we summarize recent advances of miRNA studies in skin wound healing, introduce our miRNA purification system using an immunoprecipitation assay method, and discuss the function of miR-142 in skin wound healing.


Assuntos
MicroRNAs/metabolismo , Pele/metabolismo , Infecções Cutâneas Estafilocócicas/metabolismo , Staphylococcus aureus , Cicatrização , Infecção dos Ferimentos/metabolismo , Ferimentos e Lesões/metabolismo , Animais , Proteínas Argonauta/genética , Proteínas Argonauta/metabolismo , Humanos , Camundongos , Camundongos Knockout , MicroRNAs/genética , Pele/lesões , Infecções Cutâneas Estafilocócicas/genética , Infecções Cutâneas Estafilocócicas/patologia , Infecção dos Ferimentos/genética , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia
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