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1.
BMJ Open ; 12(9): e064264, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36137624

RESUMO

INTRODUCTION: Primary congenital glaucoma (PCG), a type of childhood glaucoma, is primarily treated surgically to lower intraocular pressure (IOP). Failure to intervene could result in partial, or even total, blindness. Various surgical intervention types have been proposed for PCG, though the evidence on comparative effectiveness remains limited. The current protocol is an ongoing network meta-analysis enabling comparative investigation of surgical interventions for which randomised controlled trials (RCTs) are available. Our aim is to systematically compare the efficacy of various types of surgical intervention for patients with PCG. METHODS AND ANALYSIS: Studies of interest will assess the effects of those surgical interventions on surgery-naïve children (age <18 years) suffering PCG. RCTs regardless of language or publication date will be searched from three electronic databases (Cochrane Central Register of Controlled Trials, Embase and MEDLINE) from 4 April 2022. Two reviewers will screen, first, titles and abstracts, followed by full-text papers, for useful data that they will extract. The primary outcome measure will be the IOP-lowering effect of a given surgical intervention. The two reviewers also will assess the internal validity of studies using the relevant and domain-based risk-of-bias assessment tool. Overall evidence quality will be assessed according to the Confidence in Network Meta-Analysis approach and will be presented in summarised form with network diagrams. For enhanced visualisation of the included interventions' effects, forest plots will be constructed. Pairwise effect sizes also will be calculated based on the evidence that is available in the network. ETHICS AND DISSEMINATION: This work will synthesise evidence obtained from published studies, and as such, no ethics review or approval will be required. A paper presenting the findings will be submitted to a peer-reviewed scientific journal for publication. PROSPERO REGISTRATION NUMBER: CRD42022313954.


Assuntos
Glaucoma , Envio de Mensagens de Texto , Adolescente , Criança , Glaucoma/congênito , Glaucoma/cirurgia , Humanos , Pressão Intraocular , Metanálise como Assunto , Metanálise em Rede , Revisões Sistemáticas como Assunto
2.
Int J Mol Sci ; 21(17)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32883029

RESUMO

YKL-40, also known as chitinase-3-like 1 (CHI3L1), is a glycoprotein that is expressed and secreted by various cell types, including cancers and macrophages. Due to its implications for and upregulation in a variety of diseases, including inflammatory conditions, fibrotic disorders, and tumor growth, YKL-40 has been considered as a significant therapeutic biomarker. Here, we used a phage display to develop novel monoclonal antibodies (mAbs) targeting human YKL-40 (hYKL-40). Human synthetic antibody phage display libraries were panned against a recombinant hYKL-40 protein, yielding seven unique Fabs (Antigen-binding fragment), of which two Fabs (H1 and H2) were non-aggregating and thermally stable (75.5 °C and 76.5 °C, respectively) and had high apparent affinities (KD = 2.3 nM and 4.0 nM, respectively). Reformatting the Fabs into IgGs (Immunoglobulin Gs) increased their apparent affinities (notably, for H1 and H2, KD = 0.5 nM and 0.3 nM, respectively), presumably due to the effects of avidity, with little change to their non-aggregation property. The six anti-hYKL-40 IgGs were analyzed using a trans-well migration assay in vitro, revealing that three clones (H1, H2, and H4) were notably effective in reducing cell migration from both A549 and H460 lung cancer cell lines. The three clones were further analyzed in an in vivo animal test that assessed their anti-cancer activities, demonstrating that the tumor area and the number of tumor nodules were significantly reduced in the lung tissues treated with H1 (IgG). Given its high affinity and desirable properties, we expect that the H1 anti-hYKL-40 mAb will be a suitable candidate for developing anti-cancer therapeutics.


Assuntos
Anticorpos Monoclonais/isolamento & purificação , Anticorpos Monoclonais/farmacologia , Proteína 1 Semelhante à Quitinase-3/antagonistas & inibidores , Fragmentos Fab das Imunoglobulinas/imunologia , Neoplasias/tratamento farmacológico , Biblioteca de Peptídeos , Animais , Anticorpos Monoclonais/imunologia , Afinidade de Anticorpos , Especificidade de Anticorpos , Apoptose , Movimento Celular , Proliferação de Células , Proteína 1 Semelhante à Quitinase-3/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Sci Rep ; 9(1): 16757, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727938

RESUMO

Cancer stem-like cells (CSCs) can generate solid tumors through the properties of stem cells such as self-renewal and differentiation and they cause drug resistance, metastasis and recurrence. Therefore, establishing CSC lines is necessary to conduct various studies such as on the identification of CSC origin and specific targeted therapies. In this study, we stimulated NIH3T3 fibroblasts to exhibit the characteristics of CSCs using the whole protein lysates of B16F10 melanoma cells. As a result, we induced colony formation that displayed self-renewal and differentiation capacities through anchorage-independent culture and re-attached culture. Moreover, colonies showed drug resistance by being maintained in the G0/G1 state. Colonies expressed various CSC markers and displayed high-level drug efflux capacity. Additionally, colonies clearly demonstrated tumorigenic ability by forming a solid tumor in vivo. These results show that proteins of cancer cells could transform normal cells into CSCs by increasing expression of CSC markers. This study argues the tremendous importance of the extracellular microenvironmental effect on the generation of CSCs. It also provides a simple experimental method for deriving CSCs that could be based on the development of targeted therapy techniques.


Assuntos
Fibroblastos/citologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Células-Tronco Neoplásicas/citologia , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Fibroblastos/metabolismo , Fibroblastos/patologia , Camundongos , Células NIH 3T3 , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células Tumorais Cultivadas , Microambiente Tumoral
4.
J Med Food ; 22(6): 639-643, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31017501

RESUMO

Lizards are the evolutionarily closest animals to humans among the self-renewable species. Recent reports show that lizard tail extracts (LTE) inhibit the proliferation and angiogenesis of cancer cells but do not show any toxicity against human fibroblast cells. Nevertheless, few scientific studies investigated the effects of LTE on the treatment of skin diseases, especially oxidative stress aging. Therefore, we explored the effect of LTE on the anti-aging activity of human fibroblasts. We confirmed the anti-aging effect of LTE by SA-ß-galactosidase staining. In addition, the hydrogen peroxide-induced reactive oxygen species (ROS) were decreased by the LTE, as measured by staining with the 2',7'-dichlorofluorescein diacetate reagent. We performed Western blot analysis to examine the signaling pathways. In conclusion, the LTE can prevent cellular senescence through the suppression of ROS and the downregulation of p21.


Assuntos
Fibroblastos/citologia , Lagartos , Cauda/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
5.
J Microbiol Biotechnol ; 27(10): 1877-1884, 2017 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-28870012

RESUMO

Mesenchymal stem cells (MSCs) have been suggested as a primary candidate for cell therapy applications because they have self-renewal and differentiation capabilities. Although they can be expanded in ex vivo system, clinical application of these cells is still limited because they survive poorly and undergo senescence or apoptosis when transplanted and exposed to environmental factors such as oxidative stress. Thus, reducing oxidative stress is expected to improve the efficacy of MSC therapy. The milk protein lactoferrin is a multifunctional iron-binding glycoprotein that plays various roles, including reduction of oxidative stress. Thus, we explored the effect of lactoferrin on oxidative stress-induced senescence and apoptosis of human MSCs (hMSCs). Measurement of reactive oxygen species (ROS) revealed that lactoferrin inhibited the production of hydrogen peroxide-induced intracellular ROS, suggesting lactoferrin as a good candidate as an antioxidant in hMSCs. Pretreatment of lactoferrin suppressed hydrogen peroxide-induced senescence of hMSCs. In addition, lactoferrin reduced hydrogen peroxide-induced apoptosis via inhibition of caspase-3 and Akt activation. These results demonstrate that lactoferrin can be a promising factor to protect hMSCs from oxidative stress-induced senescence and apoptosis, thus increasing the efficacy of MSC therapy.


Assuntos
Apoptose/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Lactoferrina/farmacologia , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/metabolismo , Caspase 3/efeitos dos fármacos , Sobrevivência Celular , Humanos , Peróxido de Hidrogênio/farmacologia , Proteínas de Ligação ao Ferro/fisiologia , Proteína Oncogênica v-akt/efeitos dos fármacos , Substâncias Protetoras , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
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