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1.
Rev Med Virol ; 31(1): 1-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32845042

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors-including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings-that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.


Assuntos
COVID-19 , Índice de Gravidade de Doença , Adulto , Envelhecimento , Biomarcadores , COVID-19/mortalidade , COVID-19/patologia , COVID-19/transmissão , Criança , Comorbidade , Humanos , Hipóxia/patologia , Prognóstico , SARS-CoV-2/patogenicidade
2.
Mol Cell Biochem ; 474(1-2): 263-275, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32737772

RESUMO

Osteoarthritis (OA) is an age-related chronic joint degenerative disease. Interleukin 1 beta (IL-1ß) is considered a marker for the progression of OA. In this study, we found that Ubiquitin-Specific Peptidase 49 (USP49) was significantly less expressed in OA patients compared with healthy individuals. Treating primary rat chondrocytes with different concentrations of IL-1ß resulted in decreased Usp49 expression, while Usp49 overexpression could attenuate IL-1ß-induced chondrocyte apoptosis by promoting Axin deubiquitination. The deubiquitination of Axin led to the accumulation of the protein, which in turn resulted in ß-catenin degradation and Wnt/ß-catenin signaling cascade inhibition. Interestingly, we also found that [6]-gingerol, an anti-OA drug, could upregulate the protein level of Usp49 and suppress the Wnt/ß-catenin signaling cascade in primary rat chondrocytes. Taken together, our study not only demonstrates that Usp49 can negatively regulate the progression of OA by inhibiting the Wnt/ß-catenin signaling cascade, but also elucidates the underlying molecular mechanisms.


Assuntos
Apoptose , Proteína Axina/metabolismo , Condrócitos/patologia , Interleucina-1beta/farmacologia , Osteoartrite/patologia , Ubiquitina Tiolesterase/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Proteína Axina/genética , Estudos de Casos e Controles , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Humanos , Osteoartrite/genética , Osteoartrite/metabolismo , Ratos , Ratos Sprague-Dawley , Ubiquitina Tiolesterase/genética , Ubiquitinação , Proteínas Wnt/genética , beta Catenina/genética
3.
Injury ; 51(7): 1468-1476, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32409189

RESUMO

BACKGROUND: Worldwide, injuries account for approximately five million mortalities annually, with 90% occurring in low- and middle-income countries (LMICs). Although guidelines characterizing data for blood product transfusion in injury resuscitation have been established for high-income countries (HICs), no such information on use of blood products in LMICs exists. This systematic review evaluated the available literature on the use and associated outcomes of blood product transfusion therapies in LMICs for acute care of patients with injuries. METHODS: A systematic search of PubMed, EMBASE, Global Health, CINAHL and Cochrane databases through November 2018 was performed by a health sciences medical librarian. Prospective and cross-sectional reports of injured patients from LMICs involving data on blood product transfusion therapies were included. Two reviewers identified eligible records (κ=0.92); quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Report elements, patient characteristics, injury information, blood transfusion therapies provided and mortality outcomes were extracted and analyzed. RESULTS: Of 3411 records, 150 full-text reports were reviewed and 17 met inclusion criteria. Identified reports came from the World Health Organization regions of Africa, the Eastern Mediterranean, and South-East Asia. A total of 6535 patients were studied, with the majority from exclusively inpatient hospital settings (52.9%). Data on transfusion therapies demonstrated that packed red blood cells were given to 27.0% of patients, fresh frozen plasma to 13.8%, and unspecified product types to 50.1%. Among patients with blunt and penetrating injuries, 5.8% and 15.7% were treated with blood product transfusions, respectively. Four reports provided data on comparative mortality outcomes, of which two found higher mortality in blood transfusion-treated patients than in untreated patients at 17.4% and 30.4%. The overall quality of evidence was either low (52.9%) or very low (41.2%), with one report of moderate quality by GRADE criteria. CONCLUSION: There is a paucity of high-quality data to inform appropriate use of blood transfusion therapies in LMIC injury care. Studies were geographically limited and did not include sufficient data on types of therapies and specific injury patterns treated. Future research in more diverse LMIC settings with improved data collection methods is needed to inform injury care globally.


Assuntos
Transfusão de Sangue , Hemorragia/terapia , Ferimentos e Lesões/complicações , Doença Aguda , Países em Desenvolvimento , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ferimentos e Lesões/cirurgia
4.
J Mech Behav Biomed Mater ; 106: 103738, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32250947

RESUMO

There is no ideal implant for mechanical strut on early-stage osteonecrosis of the femoral head (ONFH) after core decompression. In this study, a biogenic trabecular porous titanium rod with lamellar configuration was designed and fabricated using selective laser melting technique. Early-stage ONFH of sheep induced by cryo-insult were dealt with core decompression combined with rod insertion (Rod group) and core decompression alone (CD group) after X-ray evaluation was used to assess the necrotic region one months after cryo-intervention. Bone integration and ingrowth of the two groups were investigated and compared. Early-stage ONFH intervened with the rod gained better bone ingrowth than CD 3 and 6 months after the intervention, as evidenced by radiographic, micro-CT and histological evaluation. X-ray images showed compact integration between rods and peripheral bone, evidenced by no radiolucent lines encircling the rods at 3 and 6 months. Micro-CT and histological images showed that the new bone had grown into the centre of rods along the metal at 3 months, whereas the new bone grew mainly at the periphery of the decompressive channel. Micro-CT analysis show that the ratios of bone volume to total volume (BV/TV) of volume of interest (VOI) in Rod group was 890.0% and 438.1% higher than CD group at 3 (0.198 ± 0.0094 VS 0.020 ± 0.0058, p < 0.05, n = 3) and 6 (0.226 ± 0.0166 VS 0.042 ± 0.0061, p < 0.05, n = 3) months respectively. Histological analysis showed that the BV/TV of VOI in Rod group was 881.0% and 413.3% higher than CD group at 3 (0.206 ± 0.0102 VS 0.021 ± 0.0061, p < 0.05, n = 3) and 6 (0.231 ± 0.0156 VS 0.045 ± 0.0059, p < 0.05, n = 3) months respectively. The mechanical tests revealed that the maximum load of Rod group was 57.6% larger than CD group at 6 months (4505.25 ± 443.86 N VS 2858.25 ± 512.91 N, p < 0.05, n = 3). These favourable short-term results can provide insight on treatment of early-stage ONFH.


Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Titânio , Ligas , Animais , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Porosidade , Impressão Tridimensional , Próteses e Implantes , Ovinos
5.
Invest Ophthalmol Vis Sci ; 60(13): 4196-4204, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618423

RESUMO

Purpose: Clinical manifestations of photoreceptor degeneration include gradual thinning of the outer nuclear layer (ONL) and progressive reduction of electroretinogram (ERG) amplitudes and vision loss. Although preclinical evaluations of treatment strategies greatly depend on rodent models, the courses of these changes in mice remain unclear. We thus sought to investigate the temporal correlations in changes of spatial vision, ERG response, and ONL thickness in mice with progressive photoreceptor degeneration. Methods: Adult wild-type (WT) mice and mice carrying rhodopsin deficiency (Rho-/-), a frequently used mouse model of human retinitis pigmentosa, were selected for investigation. Mouse spatial vision, including visual acuity (VA) and contrast sensitivity (CS), was determined using optomotor response (OMR) assays; ONL thickness was quantified by spectral-domain optical coherence tomography (SD-OCT), and ERG was performed to evaluate retinal functions. The mice were killed when they were 14 weeks old, and the cone photoreceptors in retinal sections were counted. Results: Spatial vision, ONL thickness, and ERG amplitudes remained stable in WT mice at all examined time points. While 6-week-old Rho-/- mice had VA, CS, as well as ERG responses similar to those of WT mice, progressive reductions in the spatial vision and retinal functions were recorded thereafter. Most tested 12-week-old Rho-/- mice had no visual-evoked OMR and ERG responses. Moreover, CS, but not VA, displayed a linear decline that was closely associated with ONL thinning, reduction of ERG amplitudes, and loss of cones. Conclusions: We presented a comprehensive study of the relation between the changes of spatial vision, retinal function, and ONL thickness in postnatal week (PW)6 to PW12 Rho-/- mice. CS is a more sensitive indicator of spatial vision compared to VA, although both are required as separate parameters for monitoring the visual changes in retina undergoing photoreceptor degeneration.


Assuntos
Sensibilidades de Contraste/fisiologia , Degeneração Retiniana/fisiopatologia , Rodopsina/deficiência , Transtornos da Visão/fisiopatologia , Animais , Modelos Animais de Doenças , Eletrorretinografia , Camundongos , Camundongos Knockout , Campos Visuais/fisiologia
6.
Nat Commun ; 9(1): 3914, 2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30237502

RESUMO

The originally published version of this Article contained an error in Figure 4. The bar chart in panel f was inadvertently replaced with a duplicate of the bar chart in panel e. This error has now corrected in both the PDF and HTML versions of the Article.

7.
Nat Commun ; 9(1): 3209, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-30097565

RESUMO

Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora.


Assuntos
Glaucoma/imunologia , Microbiota , Degeneração Neural/imunologia , Linfócitos T/imunologia , Animais , Axônios/patologia , Feminino , Vida Livre de Germes , Glaucoma/complicações , Glaucoma/patologia , Glaucoma/fisiopatologia , Proteínas de Choque Térmico/metabolismo , Humanos , Pressão Intraocular , Masculino , Camundongos Endogâmicos C57BL , Degeneração Neural/complicações , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Células Ganglionares da Retina/patologia
8.
Psychiatry Res Neuroimaging ; 266: 53-58, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28605662

RESUMO

In this pilot study, we examined training effects of a computerized working memory program on resting state functional magnetic resonance imaging (fMRI) measures in children with neurofibromatosis type 1 (NF1). We contrasted pre- with post-training resting state fMRI and cognitive measures from 16 participants (nine males; 11.1 ± 2.3 years) with NF1 and documented working memory difficulties. Using non-parametric permutation test inference, we found significant regionally specific differences (family-wise error corrected) in two of four voxel-wise resting state measures: fractional amplitude of low frequency fluctuations (indexing peak-to-trough intensity of spontaneous oscillations) and regional homogeneity (indexing local intrinsic synchrony). Some cognitive task improvement was observed as well. These preliminary findings suggest that regionally specific changes in resting state fMRI indices may be associated with treatment-related cognitive amelioration in NF1. Nevertheless, current results must be interpreted with caution pending independent controlled replication.


Assuntos
Encéfalo/fisiopatologia , Remediação Cognitiva/métodos , Neuroimagem Funcional/métodos , Memória de Curto Prazo/fisiologia , Neurofibromatose 1/reabilitação , Adolescente , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Projetos Piloto
9.
Hum Gene Ther ; 27(8): 609-20, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27466076

RESUMO

Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons. Here, recent findings concerning the intrinsic and extrinsic factors that regulate retinal progenitor cell maintenance and differentiation are summarized, especially transcriptional factors and extrinsic signals. Understanding these mechanisms is indispensable because they have potential clinical applications, chiefly the generation of specific retinal cells such as retinal ganglion cells to treat glaucoma and other optic neuropathy diseases.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Degeneração Retiniana/terapia , Células Ganglionares da Retina/citologia , Transdução de Sinais , Transplante de Células-Tronco , Células-Tronco/citologia , Animais , Diferenciação Celular , Humanos
10.
Contemp Oncol (Pozn) ; 18(3): 165-70, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25520575

RESUMO

AIM OF THE STUDY: Tumour endothelial cells have been proven to have molecular markers distinct from normal endothelial cells. These specific molecular markers allow for targeting of the tumour vasculature with specific pharmacological vehicles to direct diagnostic or therapeutic modalities at the endothelial cells. By performing a phage display-based screening, this study aimed to identify a certain short peptide that could specifically bind to osteosarcoma vasculature. MATERIAL AND METHODS: We performed in vivo screening in the murine models of osteosarcoma with annular Ph.D.-C7C library in the present study. To explore the in vivo binding specificity of the retrieved peptide, we conjugated the peptide with fluorescein isothiocyanate (FITC) and injected it intravenously into osteosarcoma-bearing BALB-c mice. RESULTS: CTKPDKGYC was the dominant sequence isolated from in vivo screening and was named as NF-1. Fluorescence staining found that FITC-NF-1 peptide could be specifically homed to osteosarcoma vasculature while being almost undetectable in the heart, brain, lung and liver. Simultaneously, a small amount of fluorescence could also be detected in the renal glomerulus and renal tubule but not in renal vascular endothelium, indicating that FITC-NF-1 peptide might be excreted mainly through the renal-urinary route. CONCLUSIONS: Our data suggest that, with high binding specificity to osteosarcoma vasculature, peptide NF-1 may have potential value in early diagnosis or targeted therapy for osteosarcoma.

11.
J Orthop Res ; 28(12): 1569-75, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20973059

RESUMO

Alternations in cartilage chondrocyte phenotype characteristic by the decreased type II collagen and aggrecan together with increased type X collagen synthesis serve as a beacon for osteoarthritis progression. However, little is known about the underlying molecular mechanisms. The current study seeks to discover molecules that involved in osteoarthritic chondrocytes phenotype regulation. Differential proteomics was generated with two-dimensional gel electrophoresis between normal articular cartilage (NAC) and advanced osteoarthritic cartilage (AOC). Those differentially expressed proteins were identified by mass spectrometry. The down-regulation of a neuronal silencer, the REST corepressor (CoREST) in AOC, was verified by Western blot. CoREST silencing was performed in primarily cultured NAC chondrocytes with specific siRNA to reveal the possible involvement of CoREST repression in chondrocyte phenotypic genes modulation. Ninteen differentially expressed proteins were screened and identified. Among these proteins, CoREST, HHL, and zinc finger protein 155 were estimated to be possible gene modulators. CoREST protein level was verified to be down-regulated by 69.5% (p < 0.001) in AOC. In response to CoREST knock-down by 64.8% (p < 0.001) in NAC chondrocytes, the gene expression level of the chondrocyte terminal differentiation marker gene, collagen X was found to be up-regulated by 40.0% (p = 0.017), whereas the chondrocyte differentiation phenotypic genes, collagen II and aggrecan were down-regulated by 71.4% (p < 0.001) and 57.6% (p < 0.001), respectively. The results indicate that the silencing of CoREST by siRNA transfection in NAC may reflect CoREST repression in AOC, which results in phenotypic genes modulation and suggests a homeostatic role of this transcription factor in articular chondrocyte.


Assuntos
Condrócitos/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Osteoartrite/genética , Osteoartrite/metabolismo , Proteínas Repressoras/fisiologia , Adulto , Idoso , Agrecanas/biossíntese , Cartilagem Articular/metabolismo , Proteínas Correpressoras , Colágeno Tipo II/biossíntese , Colágeno Tipo X/biossíntese , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Regulação para Cima
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 28(11): 1960-3, 2008 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19033102

RESUMO

OBJECTIVE: To compare two different methods, namely orthotopic implantation and armpit implantation, for establishing nude mouse model bearing osteosarcoma in light of the tumor formation rate and time, tumor growth changes and lung metastasis. METHODS: Osteosarcoma cells were inoculated in the left armpit or the femoral medullary canal of nude mice, and the tumor growth was observed 6 weeks later. The differences in the pulmonary metastasis were examined macroscopically and microscopically. RESULTS: Armpit implantation allowed easy operation and fast tumor growth, but tumors often sustained damages by frictions on the surface (P<0.05), and avascular necrosis occurred earlier in the tumors (P<0.05). With this approach, the pulmonary metastasis rate was only 40% (P<0.05), and the metastases in the lungs were sparser (P<0.05) and small. Orthotopic transplantation could well simulate the original growth environment of osteosarcoma, and resulted in milder avascular necrosis and greater pulmonary metastasis rate (100%) with larger and denser metastatic foci. But orthotopic transplantation required more complicated operation for establishing osteosarcoma-bearing models. CONCLUSION: The two methods both result in high tumor growth rate, but orthotopic transplantation is superior in inducing pulmonary metastasis of osteosarcoma and reducing friction injury of the tumor and avascular necrosis in the tumor.


Assuntos
Neoplasias Ósseas , Modelos Animais de Doenças , Transplante de Neoplasias/métodos , Osteossarcoma , Animais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
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