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1.
Brain Pathol ; : e13261, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602336

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

2.
World J Gastroenterol ; 29(22): 3482-3496, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37389236

RESUMEN

BACKGROUND: Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC. AIM: To identify a novel biomarker for early detection of GC. METHODS: Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency. RESULTS: There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001). CONCLUSION: Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Detección Precoz del Cáncer , ARN Circular , Antígeno CA-19-9 , Biología Computacional
3.
J Nanosci Nanotechnol ; 21(3): 1462-1473, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33404409

RESUMEN

In this work, a novel N-doped magnetic mesoporous carbon (NMC) composite (Fe3O4/NMC) was synthesized by a two-step process. First, NMC was prepared by a template method using a melamine formaldehyde resin as nitrogen and carbon sources, and then, Fe3O4 nanoparticles were loaded into the as-prepared NMC via in-situ coprecipitation process. The morphology, structure, and magnetic properties of Fe3O4/NMC were characterized and its adsorption properties were investigated. It can be found that Fe3O4/NMC with saturation magnetization of 20 emu · g-1 features a mesoporous structure, and its specific surface area reaches 513 m² · g-1. These two excellent specificities are propitious to the adsorption and separation of Ag(I) from aqueous solution. The adsorption behavior of Fe3O4/NMC nanocomposite has been investigated by adsorption kinetics and isotherms adsorption analyses as well. The adsorption isotherm and the adsorption kinetics of Ag(I) onto Fe3O4/NMC agrees well with Langmuir model and pseudo-second-order model, respectively. Moreover, the Fe3O4/NMC was easily to recovery by applied magnetic field, the adsorption capacity of Fe3O4/NMC was about 90.3% of the initial saturation adsorption capacity after five continuous uses.

4.
Artículo en Inglés | MEDLINE | ID: mdl-32292777

RESUMEN

In recent years, there has been a noticeable increase in research interests on the Fusarium species, which includes prevalent plant pathogens and human pathogens, common microbial food contaminants and industrial microbes. Taken the advantage of gibberellin synthesis, Fusarium fujikuroi succeed in being a prevalent plant pathogen. At the meanwhile, F. fujikuroi was utilized for industrial production of gibberellins, a group of extensively applied phytohormone. F. fujikuroi has been known for its outstanding performance in gibberellin production for almost 100 years. Research activities relate to this species has lasted for a very long period. The slow development in biological investigation of F. fujikuroi is largely due to the lack of efficient research technologies and molecular tools. During the past decade, technologies to analyze the molecular basis of host-pathogen interactions and metabolic regulations have been developed rapidly, especially on the aspects of genetic manipulation. At the meanwhile, the industrial fermentation technologies kept sustained development. In this article, we reviewed the currently available research tools/methods for F. fujikuroi research, focusing on the topics about genetic engineering and gibberellin production.

5.
Yi Chuan ; 42(12): 1168-1177, 2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33509781

RESUMEN

Gene editing is a genetic engineering technology that can modify, delete, or insert a small piece of DNA at a specific point in the genome of cells and organisms. Gene editing technology holds great promises in the fields of disease treatment, gene function regulation, gene detection, drug research and development, and crop breeding. However, side effects, such as off-target editing, genotoxicity and other issues, have gradually emerged in the application. In the CRISPR (clustered regularly interspaced short palindromic repeats) system, the Cas9 nuclease can specifically recognize the target DNA by the base pairing of a guide RNA (gRNA) with the target DNA. Upon target recognition, the two DNA strands are cleaved by distinct domains of the Cas9 nuclease. Since both Cas9 nuclease and gRNA possess different characteristics in their own activities, recognition sites and binding ability to specific target, it is essential to precisely regulate the activity of Cas9 nuclease and gRNA in both time and space manners, thus preventing the risk of side effects and enhancing the precise regulation of the CRISPR/Cas9 gene editing technology. In this review, we summarize the advances in the precise control of gene editing, especially CRISPR/cas9 over several dimensions using fusion Cas9 proteins regulated by light, temperature and drugs, exploiting and screening anti-CRISPRs proteins, synthesizing and identifying small molecules- inhibitors, and developing other therapeutic agents, thereby providing a reference and research ideas for human disease treatment, crop and livestock improvement and prevention of biotechnology misuse.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , ARN Guía de Kinetoplastida/genética , Animales , Biotecnología , Productos Agrícolas , Humanos , Ganado
6.
Biopreserv Biobank ; 17(5): 444-451, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31194576

RESUMEN

Objectives: miR-200c-3p has been shown to serve as a tumor suppressor in various tumor types. However, the biological function of miR-200c-3p in nephroblastoma remains unknown. This study aims to investigate the biological function and regulatory mechanisms of miR-200c-3p in nephroblastoma development. Methods: The expression of miR-200c-3p in nephroblastoma tissues and cells was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-200c-3p on the proliferation and cell cycle of SK-NEP-1 nephroblastoma cell line were evaluated by CCK-8 assay, colony formation assay, and flow cytometry. The effects of miR-200c-3p on the migratory and invasive capacities of SK-NEP-1 cells were measured by wound healing assay and transwell assay. The ability of miR-200c-3p to target fibroblast growth factor receptor substrate 2 (FRS2) was detected by quantitative PCR, western blot, and luciferase reporter assay. Results: The expression of miR-200c-3p was significantly downregulated in nephroblastoma tissues and cells compared with that in normal renal tissues and cells. miR-200c-3p inhibited the proliferative, migratory, and invasive capacities of nephroblastoma cells by targeting FRS2. Conclusions: miR-200c-3p suppresses the malignant behaviors of nephroblastoma cells by downregulating the expression of FRS2.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Renales/genética , Proteínas de la Membrana/genética , MicroARNs/genética , Tumor de Wilms/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Invasividad Neoplásica , Tumor de Wilms/metabolismo
7.
Cell Commun Signal ; 16(1): 62, 2018 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-30241478

RESUMEN

BACKGROUND: TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown. RESULTS: Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation were found co-located on frozen cancer tissue sections. CONCLUSIONS: Taken together, our data provide evidence that TEM8 is a novel receptor for uPA, which may play a significant role in the regulation of tumor growth and metastasis.


Asunto(s)
Receptores ErbB/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Superficie Celular/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Secuencia de Aminoácidos , Animales , Línea Celular , Proliferación Celular , Humanos , Cinética , Proteínas de Microfilamentos , Metástasis de la Neoplasia , Fosforilación , Dominios Proteicos , Receptores del Activador de Plasminógeno Tipo Uroquinasa/química , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/química
8.
Clin Cancer Res ; 23(16): 4602-4616, 2017 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-28424201

RESUMEN

Purpose: Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC). However, the potential role of other genes downstream of the EGFR signaling pathway in conferring acquired resistance has not been extensively investigated.Experimental Design: Using circulating tumor DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we developed a targeted amplicon ultra-deep sequencing method to screen for low-abundance somatic mutations in a panel of genes that encode components of the EGFR signaling pathway. Mutations with significantly increased variant frequencies upon disease progression were selected by using quartile analysis. The functional consequences of the identified mutations were validated in cultured cells.Results: We analyzed 32 patients with acquired cetuximab resistance in a development cohort. Of them, seven (22%) carried five novel PIK3CA mutations, whereas eight (25%) carried previously reported KRAS mutations. Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. Only one novel PIK3CA mutation (p.K944N) was verified in one of the 27 patients with acquired resistance in a validation cohort, simultaneous KRAS and PIK3CA hotspot mutations were detected in two patients. Among the above 59 acquired resistance patients, those with PIK3CA or RAS mutations detected in ctDNA showed a pronounced decrease in progression-free survival than patients with no mutation.Conclusions: The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. Clin Cancer Res; 23(16); 4602-16. ©2017 AACR.


Asunto(s)
Cetuximab/uso terapéutico , Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/química , ADN Tumoral Circulante/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos
9.
Stem Cells Transl Med ; 5(9): 1162-70, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27381991

RESUMEN

UNLABELLED: : Adipose-derived mesenchymal stem cells (AD-MSCs) have been shown to ameliorate hyperglycemia in diabetic animals and individuals. However, little is known about whether AD-MSCs affect lipid metabolism. Here we have demonstrated for the first time that AD-MSC infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in db/db obese mice and diet-induced obesity mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia and associated cardiovascular diseases. SIGNIFICANCE: Mesenchymal stem cells (MSCs) are considered one of the most promising types of stem cells for translational application because of their rich tissue sources, multilineage differentiation capacity, and easy amplification in vitro and unique immunobiological properties. This study demonstrated that adipose-derived MSCs (AD-MSCs) infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in obese mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue were demonstrated to contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia.


Asunto(s)
Tejido Adiposo/citología , Dislipidemias/metabolismo , Trasplante de Células Madre Mesenquimatosas , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Glucemia , Western Blotting , Modelos Animales de Enfermedad , Inmunohistoquímica , Lípidos/sangre , Masculino , Células Madre Mesenquimatosas , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Reacción en Cadena en Tiempo Real de la Polimerasa , Esterol Esterasa/metabolismo
10.
Chin J Integr Med ; 22(5): 362-9, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26383159

RESUMEN

OBJECTIVE: To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo. METHODS: Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography (HPLC). Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract. RESULTS: HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration (IC50, 72 h) was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/(kg d)] and low-dose [0.138 mg/(kg d)] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced. CONCLUSIONS: Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Melia/química , Extractos Vegetales/uso terapéutico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/ultraestructura , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Femenino , Inmunohistoquímica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/ultraestructura , Masculino , Ratones Endogámicos BALB C , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Trasplante de Neoplasias , Estándares de Referencia , Proteína X Asociada a bcl-2/metabolismo , Receptor fas/metabolismo
11.
J Cell Biochem ; 117(7): 1649-57, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26639987

RESUMEN

Ribosomal protein S6 (rpS6) has long been regarded as one of the primary r-proteins that functions in the early stage of 40S subunit assembly, but its actual role is still obscure. The correct forming of 18S rRNA is a key step in the nuclear synthesis of 40S subunit. In this study, we demonstrate that rpS6 participates in the processing of 30S pre-rRNA to 18S rRNA only when its C-terminal five serines are phosphorylated, however, the process of entering the nucleus and then targeting the nucleolus does not dependent its phosphorylation. Remarkably, we also find that the aggregation of rpS6 at the nucleolus correlates to the phasing of cell cycle, beginning to concentrate in the nucleolus at later S phase and disaggregate at M phase. J. Cell. Biochem. 117: 1649-1657, 2016. © 2015 Wiley Periodicals, Inc.


Asunto(s)
Nucléolo Celular/metabolismo , Agregado de Proteínas/fisiología , Precursores del ARN/metabolismo , Procesamiento Postranscripcional del ARN/fisiología , ARN Ribosómico 18S/metabolismo , Proteína S6 Ribosómica/metabolismo , División Celular/fisiología , Células HEK293 , Humanos , Fosforilación/fisiología , Fase S/fisiología
12.
Nat Commun ; 4: 2544, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24149576

RESUMEN

Although PTEN/Akt signaling is frequently deregulated in human gastric cancers, the in vivo causal link between its dysregulation and gastric tumorigenesis has not been established. Here we show that inactivation of PTEN in mouse gastric epithelium initiates spontaneous carcinogenesis with complete penetrance by 2 months of age. Mechanistically, activation of Akt suppresses the abundance of p53, leading to decreased transcription of miR-365, thus causing upregulation of cyclin D1 and cdc25A, which promotes gastric cell proliferation. Importantly, genetic ablation of Akt1 restores miR-365 expression and effectively rescues gastric tumorigenesis in PTEN-mutant mice. Moreover, orthotopic restoration of miR-365 represses PTEN-deficient-induced hyperplasia. In human gastric cancer tissues, miR-365 reduction correlates with poorly differentiated histology, deep invasion and advanced stage, as well as the deregulation of PTEN, phosphorylated Akt, p53, cyclin D1 and cdc25A. These data demonstrate that the PTEN-Akt-p53-miR-365-cyclin D1/cdc25A axis serves as a new mechanism underlying gastric tumorigenesis, providing potential new therapeutic targets.


Asunto(s)
Ciclina D1/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas c-akt/genética , Neoplasias Gástricas/genética , Fosfatasas cdc25/genética , Anciano , Animales , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Ciclina D1/metabolismo , Femenino , Humanos , Masculino , Ratones , MicroARNs/administración & dosificación , MicroARNs/metabolismo , Persona de Mediana Edad , Fosfohidrolasa PTEN/deficiencia , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Fosfatasas cdc25/metabolismo
13.
Chem Commun (Camb) ; 48(65): 8132-4, 2012 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-22773035

RESUMEN

The palladium-catalysed heteroannulation of [60]fullerene with various N-benzyl sulfonamides via C-H bond activation affords [60]fullerene-fused tetrahydroisoquinolines. In the presence of a Brønsted acid [60]fullerene-fused tetrahydroisoquinolines are transformed to [60]fullerene-fused indanes, in which the sulfonamide group can be removed or replaced with an aryl group.

14.
Int J Biol Sci ; 7(5): 685-90, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21647251

RESUMEN

MicroRNAs involved in keratinocyte migration and wound healing are largely unknown. Here, we revealed the indispensable role of miR-21 in keratinocyte migration and in re-epithelialization during wound healing in mice. In HaCaT cell, miR-21 could be upregulated by TGF-ß1. Similar to the effect of TGF-ß1, miR-21 overexpression promoted keratinocyte migration. Conversely, miR-21 knockdown attenuated TGF-ß1-induced keratinocyte migration, suggesting that miR-21 was essential for TGF-ß-driven keratinocyte migration. Furthermore, we found that miR-21 was upregulated during wound healing, coincident with the temporal expression pattern of TGF-ß1. Consistently, knockdown of endogenous miR-21 using a specific antagomir dramatically delayed re-epithelialization possibly due to the reduced keratinocyte migration. TIMP3 and TIAM1, direct targets of miR-21, were verified to be regulated by miR-21 in vitro and in vivo, indicating that these two molecules might contribute to miR-21-induced keratinocyte migration. Taken together, our results demonstrate that miR-21 promotes keratinocyte migration and boosts re-epithelialization during skin wound healing.


Asunto(s)
Queratinocitos/citología , Queratinocitos/metabolismo , MicroARNs/fisiología , Cicatrización de Heridas/fisiología , Northern Blotting , Línea Celular , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Factores de Intercambio de Guanina Nucleótido/genética , Humanos , MicroARNs/genética , Reacción en Cadena de la Polimerasa , Proteína 1 de Invasión e Inducción de Metástasis del Linfoma-T , Inhibidor Tisular de Metaloproteinasa-3/genética , Factor de Crecimiento Transformador beta/farmacología , Cicatrización de Heridas/genética
15.
Int J Biol Sci ; 7(5): 567-74, 2011 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-21552422

RESUMEN

Accumulating evidence has shown that miRNAs are aberrantly expressed in human gastric cancer and crucial to tumorigenesis. Herein, we identified the role of miR-148a in gastric cell proliferation. miR-148a knockdown inhibited cell proliferation in gastric cancer cell lines. Conversely, miR-148a overexpression promoted cell proliferation and cell cycle progression. p27, a key inhibitor of cell cycle, was verified as the target of miR-148a, indicating miR-148a might downregulate p27 expression to promote gastric cell proliferation. Moreover, we confirmed that miR-148a expression was frequently and dramatically downregulated in human advanced gastric cancer tissues, and observed a good inverse correlation between miR-148a and p27 expression in tumor samples. Thus, our results demonstrated that miR-148a downregulation might exert some sort of antagonistic function in cell proliferation, rather than promote cell proliferation in gastric cancer.


Asunto(s)
Proliferación Celular , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , MicroARNs/metabolismo , Neoplasias Gástricas/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo , Humanos , Ratones
16.
Yi Chuan ; 32(3): 198-204, 2010 Mar.
Artículo en Chino | MEDLINE | ID: mdl-20233695

RESUMEN

Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.


Asunto(s)
Células Epidérmicas , Células Madre/citología , Células Madre/metabolismo , Animales , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Humanos , Transducción de Señal/genética , Transducción de Señal/fisiología
17.
Zhonghua Zhong Liu Za Zhi ; 28(2): 138-41, 2006 Feb.
Artículo en Chino | MEDLINE | ID: mdl-16750022

RESUMEN

OBJECTIVE: To investigate the response rate (RR), time to tumor progression (TTP), quality of life (QOL) and adverse reaction in the treatment of pretreated advanced non-small cell lung cancer (NSCLC) using escalated doses of rh-endostatin (YH-16), and to determine the optimal dose for clinical application. METHODS: In this phase II randomized, controlled, multicenter trial, the patients were randomly divided into two groups to receive daily 3 hours intravenous infusion of either 7.5 mg x m(-2) or 15 mg/m(2) YH-16 for 28 days. RESULTS: Totally, 68 patients were entered and 60 patients were evaluable. There were no differences in RR (3.0% in both groups, P > 0.05), median TTP (ITT: 60 days versus 71 days, P > 0.05), QOL and incidence rate of adverse reactions (48.6% versus 38.7%, P > 0.05). No significant unexpected adverse events were observed. CONCLUSION: Rh-endostatin may have anti-tumor activity with high clinical benefit rate and is well tolerated in pretreated advanced NSCLC patients. The dose of 7.5 mg x (m(2))(-1) x d(-1) is clinically recommended.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Endostatinas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Endostatinas/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Calidad de Vida , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Inducción de Remisión
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 14(2): 225-7, 2006 Apr.
Artículo en Chino | MEDLINE | ID: mdl-16638185

RESUMEN

To evaluate soluble GM-CSF-Ralpha expression in patients with acute myeloid leukemia (AML) and its clinic significance, plasma concentration of solGM-Ralpha in de novo 66 patients with AML was detected by enzyme-linked immuno-sorbent assay, and the relationship between solGM-Ralpha levels and various clinical parameters was analyzed. The result showed that the levels of solGM-Ralpha in plasma of patients with AML were significantly higher than that in plasma of normal controls; the lowest level of solGM-Ralpha was found in plasma of patients with AML-M3 (3897.75 +/- 2651.43 pg/ml), the highest level of solGM-Ralpha was observed in plasma of patients with AML-M5 (9990.92 +/- 6325.43 pg/ml). Patients with high level of solGM-Ralpha were generally accompanied with a distinct clinical picture, including higher counts of white blood cell and myeloid precursors, as well as higher expression of CD34, CD95 and CD116 antigen. It is concluded that the high level of solGM-Ralpha in plasma of patients may suggest AML poor prognosis and play a role in pathogenesis of leukemia, the GM-CSF and its receptor solGM-Ralpha needs further study.


Asunto(s)
Leucemia Mieloide Aguda/sangre , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Adolescente , Adulto , Anciano , Antígenos CD34/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Receptor fas/sangre
19.
Zhonghua Gan Zang Bing Za Zhi ; 12(3): 163-6, 2004 Mar.
Artículo en Chino | MEDLINE | ID: mdl-15059303

RESUMEN

OBJECTIVE: To construct a mouse that specifically expresses Cre recombinase in hepatocyte. METHODS: A hepatocyte specific transgenic construct containing mouse albumin promoter, the Cre recombinase gene and the poly (A) of human growth factor gene was generated. The linearized constructs were introduced into the fertilized eggs by microinjection to obtain the transgenic mice. The transcriptional specificity of Cre recombinase was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression and function of Cre recombinase were detected by PCR and Southern Blot after crossing the Alb-Cre transgenic mice with the Smad4 conditional knockout mice. RESULTS: The linearized constructs were microinjected into 837 fertilized eggs, and then the 797 effective eggs of microinjected eggs were implanted into the oviducts of 27 pseudo pregnant mice. In the 53 offspring, there were 6 mice carrying the transgene identified by polymerase chain reaction (PCR) and Southern Blot. Cre recombinase transcripts were detected in the livers and testis of the Alb-Cre transgenic mice using RT-PCR. The Cre recombinase was expressed in the livers of the double heterozygous for Alb-Cre and Smad4 floxed allele, and the exon 8 floxed by loxP site was deleted. CONCLUSION: A hepatocyte-specific Cre transgenic mouse was generated successfully. The Cre recombinase expressed specifically in liver and could mediate the recombination between loxP sites in vivo.


Asunto(s)
Hepatocitos/metabolismo , Integrasas/genética , Proteínas Virales/genética , Animales , Femenino , Humanos , Ratones , Ratones Transgénicos
20.
Eur J Hum Genet ; 11(9): 714-7, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12939660

RESUMEN

Osteoarthritis (OA) is the most common joint disease worldwide. Recent studies have shown that targeted disruption of Smad3 in mouse results in OA. To reveal the possible association between the Smad3 gene mutation and human OA, we employed polymerase chain reaction-single strand conformation polymorphism and sequencing to screen mutations in all nine exons of the Smad3 gene in 32 patients with knee OA and 50 patients with only bone fracture. A missense mutation of the Smad3 gene was found in one patient. The single base mutation located in the linker region of the SMAD3 protein was A --> T change in the position 2 of codon 197 and resulted in an asparagine to isoleucine amino-acid substitution. The expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 in sera of the patient carrying the mutation were higher than other OA patients and controls. This is the first report showing that the Smad3 gene mutations could be associated with the pathogenesis of human OA.


Asunto(s)
Proteínas de Unión al ADN/genética , Expresión Génica , Osteoartritis/genética , Transactivadores/genética , Análisis Mutacional de ADN , Electroforesis , Humanos , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 2 de la Matriz/genética , Mutación Missense/genética , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADN , Proteína smad3
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