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1.
Int J Cancer ; 145(3): 662-670, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30653265

RESUMO

Early tumor recurrence after curative surgical resection poses a great challenge to the clinical management of hepatocellular carcinoma (HCC). We conducted whole genome expression microarrays on 64 primary HCC tumors with clinically defined recurrence status and cross-referenced with RNA-seq data from 18 HCC tumors in the Cancer Genome Atlas project. We identified a 77-gene signature, which is significantly associated with early recurrent (ER) HCC tumors. This ER-associated signature shows significant enrichment in genes involved in cell cycle pathway. We performed receiver operating characteristic (ROC) analysis to evaluate the prognostic biomarker potential of these 77 genes and Pearson correlation analysis to identify 11 close clusters. The one gene with the best area under the ROC curve in each of the 11 clusters was selected for validation using reverse-transcription quantitative PCR in an independent cohort of 24 HCC tumors. NUF2 was identified to be the minimal biomarker sufficient to discriminate ER tumors from LR tumors. NUF2 in combination with liver cirrhosis could significantly improve the detection of ER tumors with an AUROC of 0.82 and 0.85 in the test and validation cohort, respectively. In conclusion, NUF2 in combination with liver cirrhosis is a promising prognostic biomarker for early HCC recurrence.


Assuntos
Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Hepáticas/metabolismo , Recidiva Local de Neoplasia/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Feminino , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Taxa de Sobrevida , Transcriptoma
2.
Eur Arch Otorhinolaryngol ; 275(9): 2297-2302, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30078130

RESUMO

PURPOSE: This study aims to determine the indications and effectiveness of transnasal endoscopic prelacrimal recess approach (PLRA) in patients with maxillary sinus inverted papilloma (IP). METHODS: We retrospectively analyzed 71 patients treated in our institution for maxillary sinus IP between August 2008 and April 2015. 20 patients underwent endoscopic surgery via PLRA. All the patients who had postoperative follow-up for 3 years were enrolled. Demographic data, surgical technique, location of IP attachment, intra- and postoperative complications, follow-up duration and recurrence were recorded. RESULTS: The outpatient follow-up period was 3-10 years after surgery. Recurrence of IP was seen in 6 (8.5%) of 71 patients, including 1 patient in the PLRA group. The recurrence rate was 5% in the PLRA group. Six of 71 patients experienced postoperative complications, but none was observed in the PLRA group. CONCLUSION: Transnasal endoscopic PLRA is a minimally invasive, safe and effective method for maxillary sinus IP. The indication for PLRA is tumor pedicle located on the antero-inferior or infero-lateral wall or at multiple attachment sites of the maxillary sinus.


Assuntos
Neoplasias do Seio Maxilar/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Recidiva Local de Neoplasia/epidemiologia , Papiloma Invertido/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento
3.
Int J Ophthalmol ; 17(8): 1396-1402, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39156779

RESUMO

AIM: To investigate the therapeutic effects of hydrogel dressings on neurotrophic keratitis in rats. METHODS: Male Wistar rats, aged 42-56d, were randomly divided into control, experimental, and treatment groups, each consisting of five rats. The experimental and treatment groups underwent neurotrophic keratitis modeling in both eyes. After successful modeling, biomedical hydrogels formed with polyvinyl alcohol and polyvinyl pyrrolidone were used in treatment group for 7d. Ocular irritation response and keratitis index scores, Schirmer's test, tear film break-up time (BUT), sodium fluorescein staining, and hematoxylin and eosin (HE) staining were used to evaluate the effectiveness of the treatment. RESULTS: The neurotrophic keratitis model was successfully established in rats with severe ophthalmic nerve injury, characterized by keratitis, ocular irritation, reduced tear secretion measured by decreased BUT and Schirmer test values, corneal epithelial loss, and disorganized collagen fibers in the stromal layer. Following treatment with hydrogel dressings, significant improvements were observed in keratitis scores and ocular irritation symptoms in model eyes. Although the recovery of tear secretion, as measured by the Schirmer's test, did not show statistical differences, BUT was significantly prolonged. Fluorescein staining confirmed a reduction in the extent of corneal epithelial loss after treatment. HE staining revealed the restoration of the structural disorder in both the epithelial and stromal layers to a certain extent. CONCLUSION: Hydrogel dressing reduces ocular surface irritation, improves tear film stability, and promotes the repair and restoration of damaged epithelial cells by maintaining a moist and clean environment on the ocular surface in the rat model.

4.
J Neuroinflammation ; 10: 106, 2013 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-23971414

RESUMO

BACKGROUND: Previous studies have shown beneficial effects of mesenchymal stem cell (MSC) transplantation in central nervous system (CNS) injuries, including traumatic brain injury (TBI). Potential repair mechanisms involve transdifferentiation to replace damaged neural cells and production of growth factors by MSCs. However, few studies have simultaneously focused on the effects of MSCs on immune cells and inflammation-associated cytokines in CNS injury, especially in an experimental TBI model. In this study, we investigated the anti-inflammatory and immunomodulatory properties of MSCs in TBI-induced neuroinflammation by systemic transplantation of MSCs into a rat TBI model. METHODS/RESULTS: MSCs were transplanted intravenously into rats 2 h after TBI. Modified neurologic severity score (mNSS) tests were performed to measure behavioral outcomes. The effect of MSC treatment on neuroinflammation was analyzed by immunohistochemical analysis of astrocytes, microglia/macrophages, neutrophils and T lymphocytes and by measuring cytokine levels [interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, interferon-γ, RANTES, macrophage chemotactic protein-1, macrophage inflammatory protein 2 and transforming growth factor-ß1] in brain homogenates. The immunosuppression-related factors TNF-α stimulated gene/protein 6 (TSG-6) and nuclear factor-κB (NF-κB) were examined by reverse transcription-polymerase chain reaction and Western blotting. Intravenous MSC transplantation after TBI was associated with a lower density of microglia/macrophages and peripheral infiltrating leukocytes at the injury site, reduced levels of proinflammatory cytokines and increased anti-inflammatory cytokines, possibly mediated by enhanced expression of TSG-6, which may suppress activation of the NF-κB signaling pathway. CONCLUSIONS: The results of this study suggest that MSCs have the ability to modulate inflammation-associated immune cells and cytokines in TBI-induced cerebral inflammatory responses. This study thus offers a new insight into the mechanisms responsible for the immunomodulatory effect of MSC transplantation, with implications for functional neurological recovery after TBI.


Assuntos
Lesões Encefálicas/imunologia , Lesões Encefálicas/cirurgia , Imunomodulação/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/prevenção & controle , Inflamação/cirurgia , Ratos , Ratos Sprague-Dawley
5.
Cell Mol Neurobiol ; 33(5): 651-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23572380

RESUMO

Glioma stem cells (GSCs) are thought to be critical for resistance to radiotherapy and chemotherapy and for tumor recurrence after surgery in glioma patients. Identification of new therapeutic strategies that can target GSCs may thus be critical for improving patient survival. MicroRNAs (miRNAs) are small non-coding RNAs that function as tumor suppressors or oncogenes. In this study, we confirmed that miR-107 was down-regulated in GSCs. To investigate the role of miR-107 in tumorigenesis of GSCs, a lentiviral vector over-expressing miR-107 in U87GSCs was constructed. We found that over-expression of miR-107 suppressed proliferation and down-regulated Notch2 protein and stem cell marker (CD133 and Nestin) expression in U87GSCs. Furthermore, enhanced miR-107 expression significantly inhibited U87GSC invasion and reduced matrix metalloproteinase-12 expression. miR-107 also suppressed U87GSCs xenograft growth in vivo. These findings suggest that miR-107 is involved in U87GSCs growth and invasion and may provide a potential therapeutic target for glioma treatment.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Sequência de Bases , Neoplasias Encefálicas/enzimologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Glioma/enzimologia , Glicoproteínas/metabolismo , Humanos , Lentivirus/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/genética , Dados de Sequência Molecular , Invasividade Neoplásica , Células-Tronco Neoplásicas/enzimologia , Nestina/genética , Nestina/metabolismo , Peptídeos/metabolismo , Receptor Notch2/genética , Receptor Notch2/metabolismo , Transdução Genética , Regulação para Cima/genética , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Neurooncol ; 112(1): 59-66, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23299462

RESUMO

MicroRNAs (miRNAs), small non-protein-coding RNA molecules, modulate target gene expression by binding to 3'untranslated regions (UTR) of target mRNA. These molecules are aberrantly expressed in many human cancers, and can function either as tumor suppressors or oncogenes. In the current study, we show that miR-107 is down-regulated in glioma tissues and cell lines, and its overexpression leads to inhibition of the migratory and invasive ability of glioma cells via direct targeting of Notch2, which is known to transactivate Tenascin-C and Cox-2. Experiments with Notch2 siRNA further suggest that miR-107 may exerts its anti-invasive activity through Notch2 signaling pathways. Our findings collectively indicate that miR-107 is involved in glioma cell migration and invasion, and support its utility as a potential target for glioma treatment.


Assuntos
Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Receptor Notch2/metabolismo , Análise de Variância , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/patologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Técnicas In Vitro , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor Notch2/genética , Tenascina/metabolismo , Transfecção , Cicatrização/efeitos dos fármacos , Cicatrização/genética
7.
J Neurooncol ; 112(3): 339-45, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23417321

RESUMO

A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.


Assuntos
Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Glioblastoma/irrigação sanguínea , Glioblastoma/patologia , Adolescente , Adulto , Idoso , Antígenos CD34/análise , Antígenos CD34/biossíntese , Neoplasias Encefálicas/mortalidade , Feminino , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Adulto Jovem
8.
Br J Neurosurg ; 27(2): 187-93, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22984981

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of transorbital puncture for the retreatment of previously embolized cavernous sinus dural arteriovenous fistulas (DAVFs) via a superior ophthalmic vein (SOV) approach. MATERIALS AND METHODS: During a 12-year period, 9 consecutive patients with previously embolized cavernous sinus DAVFs underwent retreatment via the transorbital SOV approach. RESULTS: All of the nine cases of previously embolized cavernous sinus DAVFs were successfully embolized. Clinical follow-ups were conducted in all nine cases at the duration of 17-141 months (61.22 ± 39.13 months). No recanalization occurred during the follow-up period. A subtle ptosis appeared in two patients and disappeared in one of the two cases after a 4-year follow-up. One patient suffered from paroxysmal positional vertigo and bruit for nearly 2 years after the treatment, but the follow-up angiography demonstrated no recurrence. One patient had persistent visual impairment caused by the initial venous stasis retinopathy. One patient with a history of a procedure-related transient decrease in visual acuity had it return to the normal level. The remaining four cases had clear improvement in the ocular symptoms and became completely asymptomatic during the follow-up period. No patient worsened or developed new symptoms. CONCLUSION: The approach of surgical cannulation of the SOV for the retreatment of previously embolized cavernous sinus DAVFs was proved feasible and efficient, especially when the transarterial and transfemoral venous approaches were inaccessible. However, if the SOV is not dilated enough or is located deeply in the orbit, transorbital venous puncture access may not be possible.


Assuntos
Cateterismo/métodos , Seio Cavernoso/anormalidades , Malformações Vasculares do Sistema Nervoso Central/terapia , Olho/irrigação sanguínea , Veias/cirurgia , Adulto , Idoso , Seio Cavernoso/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Embolização Terapêutica , Procedimentos Endovasculares/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Radiografia , Retratamento , Estudos Retrospectivos , Trombose Venosa/cirurgia , Adulto Jovem
9.
Cell Mol Neurobiol ; 32(1): 67-75, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21833552

RESUMO

Microglia, implicating in such neuro-pathologies as brain inflammation, neurodegeneration, glioma, and neurogenesis, play an important role in central nervous system. Advanced research on microglia is crucial in exploring the neuro-pathology and neuro-physiology of these diseases, so how to culture large numbers of microglia in vitro becomes the base of a research. The wildly used method, at present, obtaining microglia from murine cannot fulfill the requirement of research, costing too much time and needing too many rats. We intend to introduce an optimized method that can harvest large quantities of microglia with high purity. Neonatal 2-3 days old Wistar rats were sacrificed and the cerebral cortices were trypsinized. We primarily cultured mixed cortical cells for 8-10 days. The microglia were harvested from the liquid supernatant; the left cells in the mixed cortical glial culture were passaged at a 1:2 density. After another 8-10 days of culture, microglia were collected again. And then, we passaged the left cells again for acquiring microglia from the third collection. We did not add additional mitogens in the experiment. At last, on average, 7.0 × 10(6) microglia were collected from one neonatal rat. By this modified method, much more microglia can be effectively and easily harvested comparing with the usual protocol before. We compared the characteristics of microglia harvested from these three passages, such as morphology, phenotype, purity, and abilities on proliferation, secretion, and phagocytosis. The cells presented typical microglia morphology, having phenotype markers of CD11b/c and CD45. The microglia from these three passages retained similar phagocytosis and secretion functions. Expanded population of microglia for investigation can be provided by this easy method in a short time with little cost and few rats.


Assuntos
Técnicas de Cultura de Células/economia , Técnicas de Cultura de Células/métodos , Microglia/citologia , Animais , Animais Recém-Nascidos , Proliferação de Células , Separação Celular/economia , Separação Celular/métodos , Células Cultivadas , Análise Custo-Benefício , Eficiência , Citometria de Fluxo/economia , Citometria de Fluxo/métodos , Microglia/fisiologia , Microglia/ultraestrutura , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Fagocitose/fisiologia , Ratos , Ratos Wistar
10.
Front Pharmacol ; 13: 942032, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160423

RESUMO

CKD is a clinical syndrome with slow development and gradual deterioration of renal function. At present, modern medicine still lacks an ideal treatment method for this disease, while TCM has accumulated rich clinical experience in the treatment of CKD, which can effectively improve renal function and delay renal failure, and has unique advantages. RC is widely used in clinical practice to treat CKD, especially the "Kidney-Yin" deficiency syndrome. However, the compatibility mechanisms responsible for its effects in experimental studies, including preclinical and clinical research studies, are still not fully understood. Adenine-induced CKD rats were used to investigate the preventive effect of RC on CKD rats. Based on the high-throughput 16S rRNA gene sequencing results from Illumina, we discussed the intestinal flora abundance in rats in different treatment groups. According to a PCA and a PCoA based on a distance matrix, there was a clear separation of gut microbiome profiles between normal rats and model rats in terms of beta diversity. The abundance of Firmicutes in CKD rats was relatively increased, while that of Bacteroidetes was decreased. It is clear that the plot for the RC group was closer to that of the normal group, suggesting that the RC group had higher similarities among bacterial members with N rats. Ussing chamber, Western blot, and PCR assays were used to investigate the effects of RC on intestinal barrier function and its molecular mechanism in model animals. The results indicated that the protein expressions of ZO-1, claudin-1, and occludin-1 were decreased significantly in chronic kidney disease rats with the induction of adenine. With the treatment of RG, CO, and RC, the intestinal barrier was repaired due to the upregulated expressions of the aforementioned proteins in CKD rats. Based on our findings, RC appears to strengthen the intestinal barrier and modulate gut microbiota in adenine-induced CKD rats. This project revealed the compatibility mechanism of RC in regulating the intestinal microecology and barrier function to intervene in CKD and provided the basis and ideas for the clinical application of RC and the development of innovative drugs for CKD.

11.
Cytotherapy ; 13(1): 46-53, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20735164

RESUMO

BACKGROUND AIMS: This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-ß (TGF-ß), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). METHODS: Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-ß, PDGF-BB, BDNF, GDNF and NGF. RESULTS: The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. CONCLUSIONS: The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.


Assuntos
Células da Medula Óssea/citologia , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo , Células Endoteliais/transplante , Transplante de Células-Tronco , Animais , Comportamento Animal , Células da Medula Óssea/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Células Endoteliais/citologia , Microvasos/patologia , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Ratos , Ratos Wistar , Células-Tronco/citologia , Células-Tronco/metabolismo , Células Estromais/citologia , Células Estromais/transplante
12.
Neurochem Res ; 36(12): 2391-400, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21877237

RESUMO

Transdifferentiated and untransdifferentiated mesenchymal stem cells (MSCs) have shown therapeutic benefits in central nervous system (CNS) injury. However, it is unclear which would be more appropriate for transplantation. To address this question, we transplanted untransdifferentiated human umbilical mesenchymal stem cells (HUMSCs) and transdifferentiated HUMSCs (HUMSC-derived neurospheres, HUMSC-NSs) into a rat model of traumatic brain injury. Cognitive function, cell survival and differentiation, brain tissue morphology and neurotrophin expression were compared between groups. Significant improvements in cognitive function and brain tissue morphology were seen in the HUMSCs group compared with HUMSC-NSs group, which was accompanied by increased neurotrophin expression. Moreover, only few grafted cells survived in both the HUMSCs and HUMSC-NSs groups, with very few of the cells differentiating into neural-like cells. These findings indicate that HUMSCs are more appropriate for transplantation and their therapeutic benefits may be associated with neuroprotection rather than cell replacement.


Assuntos
Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/cirurgia , Diferenciação Celular , Transdiferenciação Celular , Transplante de Células-Tronco Mesenquimais , Animais , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Sobrevivência Celular , Cognição , Humanos , Aprendizagem em Labirinto , Células-Tronco Mesenquimais/fisiologia , Fatores de Crescimento Neural/biossíntese , Neurônios/citologia , Ratos , Ratos Sprague-Dawley
13.
Differentiation ; 79(1): 15-20, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19800163

RESUMO

Human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) are capable of differentiating into neural and astroglia-like cell types. However, a reliable means of inducing the selective differentiation of hWJ-MSCs into oligodendrocyte progenitor cells (OPCs) in vitro has not yet been established. In this study, the OPC-like differentiation of hWJ-MSCs was characterized using and immunoblotting. The hWJ-MSC-derived OPC-like cells were able to secrete nerve growth factors and promote neurite outgrowth in vitro. These results show that hWJ-MSCs can be induced to differentiate into cells with the morphologic, phenotypic and functional characteristics of OPC-like cells.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Fator de Crescimento Neural/metabolismo , Neurônios/citologia , Oligodendroglia/citologia , Células-Tronco/citologia , Cordão Umbilical/citologia , Separação Celular , Células Cultivadas , Feminino , Humanos , Imunofenotipagem , Neurônios/metabolismo , Oligodendroglia/metabolismo , Gravidez , Células-Tronco/metabolismo , Células Estromais/metabolismo
14.
Int J Cancer ; 127(9): 2222-9, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20127864

RESUMO

Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165-PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38-IRES2-EGFP plasmid. ELISA was used to confirm the expression of VEGF165-PE38 in the transfected cells. These cells released 1396 + or - 131.9 pg VEGF165-PE38/1x10(4) cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary-like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38-IRES2-EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. Quantitative analysis of microvessel density in the treated group was 1.99 + or - 0.69/0.74 mm(2), and was significantly lower than that in the control groups (9.33 + or - 1.99/0.74 mm(2), 8.09 + or - 1.39/0.74 mm(2) and 8.49 + or - 1.69/0.74 mm(2)). Immunohistochemistry analysis indicated that immunotoxin VEGF165-PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165-PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Terapia Genética , Glioma/terapia , Imunotoxinas/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , ADP Ribose Transferases/uso terapêutico , Animais , Toxinas Bacterianas/uso terapêutico , Linhagem Celular Tumoral , Exotoxinas/uso terapêutico , Estudos de Viabilidade , Glioma/irrigação sanguínea , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Plasmídeos , Pseudomonas/metabolismo , Transfecção , Fatores de Virulência/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Exotoxina A de Pseudomonas aeruginosa
15.
Cell Mol Neurobiol ; 30(2): 275-82, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19757023

RESUMO

Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and Nogo-A, inhibit the central nervous system regeneration. In this study, the DNA vaccine encoding for oligodendrocyte and myelin-related antigens was employed to attenuate the axonal growth inhibitory properties of myelin in the setting of spinal cord injury. Using a rat spinal cord dorsal hemisection model, the vaccine directed against the inhibitory epitopes of Nogo-A, MAG, OMgp, and TN-R was administered intramuscularly once a week following spinal cord injury, supplemented with local application of specific anti-sera against the four antigens. Anterograde labeling of dorsal column fibers showed active axonal regeneration through the lesion site at the eighth week following the treatment in experimental group but not in control groups. Light microscopic and ultrastructural analysis revealed that vaccination with these myelin-related antigens did not lead to demyelinating disease. OMgp and TN-R levels were down-regulated at the lesion site together with a parallel increase in growth-associated protein 43 levels in the treatment groups. This study reveals the effective approach of a DNA vaccine strategy by attaining the special antibody to direct neutralization of the myelin inhibitors during spinal cord injury.


Assuntos
Axônios/fisiologia , Traumatismos da Medula Espinal/terapia , Vacinas de DNA/uso terapêutico , Animais , Axônios/ultraestrutura , Encefalomielite Autoimune Experimental/patologia , Epitopos/genética , Feminino , Proteínas Ligadas por GPI , Imunização Passiva , Atividade Motora , Proteínas da Mielina/genética , Proteínas da Mielina/imunologia , Glicoproteína Associada a Mielina/genética , Glicoproteína Associada a Mielina/imunologia , Glicoproteína Associada a Mielina/metabolismo , Glicoproteína Mielina-Oligodendrócito , Regeneração Nervosa , Proteínas Nogo , Ratos , Ratos Endogâmicos Lew , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Tenascina/genética , Tenascina/imunologia , Tenascina/metabolismo
16.
Neurochem Res ; 35(4): 572-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19960248

RESUMO

The aim of this study was to compare the neural differentiation potential and the expression of neurotrophic factors (NTFs) in differentiated adipose-derived stem cells (ADSCs) using three established induction protocols, serum free (Protocol 1), chemical reagents (Protocol 2), and spontaneous (Protocol 3) protocols. Protocol 1 produced the highest percentage of mature neural-like cells (MAP2ab(+)). Protocol 2 showed the highest percentage of immature neural-like cells (beta-tubulin III(+)), but the neural-like state was transient and reversible. Protocol 3 caused ADSCs to differentiate spontaneously into immature neural-like cells, but not into mature neural cell types. The neural-like cells produced by Protocol 1 lived the longest in culture with little cell death, but Protocol 2 and 3 led to the significant cell death. Therefore, Protocol 1 is the most efficient among these protocols. Additionally, soon after differentiation, the mRNA levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in dADSCs were sharply decreased by Protocol 1 and 2 (acute induction protocol), but not by Protocol 3 (chronic induction protocol). The results indicate that NTFs played an important role in neural differentiation via acute responses to NGF and BDNF, but not chronically during the transdifferentiation process.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular , Neurônios/citologia , Células Estromais/citologia , Tecido Adiposo/metabolismo , Animais , Sequência de Bases , Biomarcadores , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Meios de Cultura Livres de Soro , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Fator de Crescimento Neural/metabolismo , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/metabolismo
17.
Neurochem Res ; 35(10): 1522-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20658188

RESUMO

Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.


Assuntos
Dopamina/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Atividade Motora , Fator de Crescimento Neural/uso terapêutico , Doença de Parkinson/terapia , Veias Umbilicais/citologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/citologia , Doença de Parkinson/metabolismo , Doença de Parkinson/psicologia , Ratos , Ratos Sprague-Dawley
18.
Neuroimmunomodulation ; 17(4): 270-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20203533

RESUMO

LINGO-1 (leucine-rich repeat and Ig domain-containing, Nogo receptor-interacting protein) is an important component of the NgR receptor complex involved in RhoA activation and axon regeneration. The authors report on passive immunization with LINGO-1 polyclonal antiserum, a therapeutic approach to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). The intrathecally administered high-titer rabbit-derived antiserum can be detected around the injury site within a wide time window; it blocks LINGO-1 in vivo with high molecular specificity. In this animal model, passive immunization with LINGO-1 antiserum significantly decreased RhoA activation and increased neuronal survival. Adult rats immunized in this manner show recovery of certain hindlimb motor functions after dorsal hemisection of the spinal cord. Thus, passive immunotherapy with LINGO-1 polyclonal antiserum may represent a promising repair strategy following acute SCI.


Assuntos
Citoproteção/efeitos dos fármacos , Imunização Passiva/métodos , Proteínas de Membrana/antagonistas & inibidores , Proteínas do Tecido Nervoso/antagonistas & inibidores , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Citoproteção/imunologia , Modelos Animais de Doenças , Feminino , Soros Imunes/imunologia , Soros Imunes/farmacologia , Injeções Espinhais , Proteínas de Membrana/imunologia , Degeneração Neural/tratamento farmacológico , Degeneração Neural/imunologia , Degeneração Neural/fisiopatologia , Proteínas do Tecido Nervoso/imunologia , Paralisia/tratamento farmacológico , Paralisia/imunologia , Paralisia/fisiopatologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/imunologia , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/fisiopatologia , Resultado do Tratamento , Proteína rhoA de Ligação ao GTP/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/metabolismo
19.
Cell Mol Neurobiol ; 29(1): 81-5, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18709454

RESUMO

Neuroinflammation has been implicated in the etiology of Alzheimer's disease (AD). Many studies have suggested that C(-889) T promoter polymorphism in one of the proinflammatory cytokine interleukin-1 (IL-1) encoding gene IL-1A may be associated with AD pathogenesis. To determine whether the polymorphism contributes to the risk for late-onset AD (LOAD) in Chinese, we carried out our investigation in 344 sporadic LOAD patients and 224 healthy controls. No statistical significant association was obtained between IL-1A C(-889) T polymorphism and LOAD and no statistical difference was found between cases and controls after stratification for apolipoprotein E allele 4 (APOE epsilon4) status. The results reveal that it is not likely that the IL-1A C(-889) T polymorphism is involved in AD pathogenesis in the Chinese population. Further studies of the associations between other IL-1A genetic polymorphisms and AD should be performed in a larger population and biologic functional analysis of IL-1A gene is required to verify the underlying roles of IL-IA in LOAD.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Interleucina-1alfa/genética , Polimorfismo de Nucleotídeo Único/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Heterozigoto , Humanos , Masculino
20.
Cell Mol Neurobiol ; 29(8): 1283-92, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19533335

RESUMO

Controversies exist concerning the need for mesenchymal stromal cells (MSCs) to be transdifferentiated prior to their transplantation. In the present study, we compared the results of grafting into the rat contused spinal cord undifferentiated, adipose tissue-derived stromal cells (uADSCs) versus ADSCs induced by two different protocols to form differentiated nervous tissue. Using Basso, Beattie, and Bresnahan scores and grid tests, we found that three cell-treated groups, including uADSCs-treated, dADSCs induced by Protocol 1 (dADSC-P1)-treated, and dADSCs induced by Protocol 2 (dADSC-P2)-treated groups, significantly improved locomotor functional recovery in SCI rats, compared with the saline-treated group. Furthermore, functional recovery was better in the uADSC-treated and dADSC-P2-treated groups than in the dADSC-P1-treated group at week 12 postinjury (P < 0.05 for dADSC-P1 group vs. uADSCs or dADSC-P2 groups). Although both protocols could induce high percentages of cells expressing neural markers in vitro, few BrdU-labeled cells survived at the injury sites in the three cell-treated groups, and only a small percentage of BrdU-positive cells expressed neural markers. On the other hand, the number of NF200-positive axons in the uADSC-treated and dADSC-P2-treated groups was significantly larger than those in the dADSC-P1-treated and saline-treated control groups. Our results indicate that ADSCs are able to differentiate into neural-like cells in vitro and in vivo. However, neural differentiated ADSCs did not result in better functional recovery than undifferentiated ones, following SCI. In vitro neural transdifferentiation of ADSCs might therefore not be a necessary pretransplantation step. Furthermore, cellular replacement or integration might not contribute to the functional recovery of the injured spinal cord.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Células Estromais/citologia , Células Estromais/transplante , Animais , Axônios/fisiologia , Comportamento Animal , Biomarcadores/metabolismo , Forma Celular , Células Cultivadas , Proteínas de Filamentos Intermediários/metabolismo , Locomoção , Proteínas do Tecido Nervoso/metabolismo , Nestina , Neurônios/citologia , Neurônios/metabolismo , Ratos , Regeneração/fisiologia , Tubulina (Proteína)/metabolismo
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