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1.
Nat Commun ; 14(1): 2829, 2023 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-37198156

RESUMEN

Human cellular reprogramming to induced pluripotency is still an inefficient process, which has hindered studying the role of critical intermediate stages. Here we take advantage of high efficiency reprogramming in microfluidics and temporal multi-omics to identify and resolve distinct sub-populations and their interactions. We perform secretome analysis and single-cell transcriptomics to show functional extrinsic pathways of protein communication between reprogramming sub-populations and the re-shaping of a permissive extracellular environment. We pinpoint the HGF/MET/STAT3 axis as a potent enhancer of reprogramming, which acts via HGF accumulation within the confined system of microfluidics, and in conventional dishes needs to be supplied exogenously to enhance efficiency. Our data suggest that human cellular reprogramming is a transcription factor-driven process that it is deeply dependent on extracellular context and cell population determinants.


Asunto(s)
Células Madre Pluripotentes Inducidas , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Reprogramación Celular , Regulación de la Expresión Génica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Células Cultivadas
2.
Cell Stem Cell ; 29(12): 1703-1717.e7, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36459970

RESUMEN

The establishment of in vitro naive human pluripotent stem cell cultures opened new perspectives for the study of early events in human development. The role of several transcription factors and signaling pathways have been characterized during maintenance of human naive pluripotency. However, little is known about the role exerted by the extracellular matrix (ECM) and its three-dimensional (3D) organization. Here, using an unbiased and integrated approach combining microfluidic cultures with transcriptional, proteomic, and secretome analyses, we found that naive, but not primed, hiPSC colonies are characterized by a self-organized ECM-rich microenvironment. Based on this, we developed a 3D culture system that supports robust long-term feeder-free self-renewal of naive hiPSCs and also allows direct and timely developmental morphogenesis simply by modulating the signaling environment. Our study opens new perspectives for future applications of naive hiPSCs to study critical stages of human development in 3D starting from a single cell.


Asunto(s)
Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Humanos , Proteómica , Matriz Extracelular , Morfogénesis
3.
World J Clin Cases ; 10(12): 3866-3871, 2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35647139

RESUMEN

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has been the most important clinical challenge worldwide since January 2020. COVID-19 inactivated vaccines play a crucial role in reducing the rates of morbidity and mortality. CASE SUMMARY: We presented a 48-year-old woman from Haidian District, Beijing, China who developed ischemic colitis after receiving the second dose of COVID-19 inactivated vaccine. Computed tomography of the abdomen showed edema and bowel wall thickening with hypodensity in the sigmoid colon and descending colon. Colonoscopy revealed hyperemia, edema and erosion of the mucosa with superficial ulceration and a yellow-white coating at the descending colon and sigmoid colon. The symptoms were relieved after 1 wk of receiving pinaverium bromide (50 mg, tid) and aspirin enteric-coated tablets (0.1 g, qd). CONCLUSION: The possible occurrence of ischemic colitis should be considered after administration of the COVID-19 inactivated vaccines.

4.
Biochim Biophys Acta Gen Subj ; 1866(8): 130165, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35513203

RESUMEN

BACKGROUND: Phosphorylated proteins are known to be present in multiple body fluids in normal conditions, and abnormally accumulated under some pathological conditions. The biological significance of their role in the extracellular space has started being elucidated only recently, for example in bone mineralization, neural development, and coagulation. Here, we address some criticalities of conventional culture systems for the study of the extracellular regulation of phosphorylation. METHODS: We make use of microfluidics to scale-down the culture volume to a size comparable to the interstitial spaces occurring in vivo. The phosphoprotein content of conditioned media was analyzed by a colorimetric assay that detects global phosphorylation. RESULTS: We found that miniaturization of the culture system increases phosphoprotein accumulation. Moreover, we demonstrated that in conventional culture systems dilution affects the extent of the phosphorylation reactions occurring within the extracellular space. On the other hand, in microfluidics the phosphorylation status was not affected by addition of adenosine triphosphate (ATP) and FAM20C Golgi Associated Secretory Pathway Kinase (FAM20C) ectokinase, as if their concentration was already not limiting for the phosphorylation reaction to occur. CONCLUSIONS: The volume of the extracellular environment plays a role in the process of extracellular phosphorylation due to its effect on the concentration of substrates, enzymes and co-factors. GENERAL SIGNIFICANCE: Thus, the biological role of extracellular phosphoregulation may be better appreciated within a microfluidic culture system.


Asunto(s)
Calcificación Fisiológica , Fosfoproteínas , Adenosina Trifosfato/metabolismo , Aparato de Golgi/metabolismo , Fosfoproteínas/metabolismo , Fosforilación
5.
Biomaterials ; 286: 121564, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35576810

RESUMEN

Nuclear deformation is an essential phenomenon allowing cell migration and can be observed in association with pathological conditions such as laminopathies, neurodegenerative disorders and diabetes. Abnormal nuclear morphologies are a hallmark of cancer progression and nuclear deformability is a necessary feature for metastatic progression. Nevertheless, the cellular processes and the key molecular components controlling nuclear shape are poorly understood, in part due to a limited availability of assays that allow high-throughput screening of nuclear morphology-phenotypes. In this study, we explore the application of micropillared substrates as the basis for a phenotypic screening platform aimed at identifying novel determinants of nuclear morphology. We designed PDMS substrates to maximize simplicity in image acquisition and analyses, and in a small-scale screening of inhibitors targeting chromatin-modifying enzymes, we identify histone deacetylation as cellular process involved in nuclear deformation. With increasingly specific targeting approaches, we identify HDAC2 as a novel player in controlling nuclear morphology through gene transcription repression. This study shows the effectiveness of micropillar-based substrates to act as phenotypic drug screening platforms and opens a new avenue in the identification of genes involved in determining the nuclear shape.


Asunto(s)
Histona Desacetilasa 2 , Neoplasias , Cromatina/genética , Cromatina/metabolismo , Evaluación Preclínica de Medicamentos , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/metabolismo , Humanos , Fenotipo
6.
Cells ; 9(11)2020 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-33233551

RESUMEN

Nuclear shape modulates cell behavior and function, while aberrant nuclear morphologies correlate with pathological phenotype severity. Nevertheless, functions of specific nuclear morphological features and underlying molecular mechanisms remain poorly understood. Here, we investigate a nucleus-intrinsic mechanism driving nuclear lobulation and segmentation concurrent with granulocyte specification, independently from extracellular forces and cytosolic cytoskeleton contributions. Transcriptomic regulation of cholesterol biosynthesis is equally concurrent with nuclear remodeling. Its putative role as a regulatory element is supported by morphological aberrations observed upon pharmacological impairment of several enzymatic steps of the pathway, most prominently the sterol ∆14-reductase activity of laminB-receptor and protein prenylation. Thus, we support the hypothesis of a nuclear-intrinsic mechanism for nuclear shape control with the putative involvement of the recently discovered GGTase III complex. Such process could be independent from or complementary to the better studied cytoskeleton-based nuclear remodeling essential for cell migration in both physiological and pathological contexts such as immune system function and cancer metastasis.


Asunto(s)
Citoesqueleto/metabolismo , Granulocitos/metabolismo , Prenilación de Proteína/genética , Células HL-60 , Humanos , Modelos Moleculares
7.
Biomed Res Int ; 2020: 7196782, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33062694

RESUMEN

OBJECTIVE: To contrast the effect of rebamipide with proton pump inhibitors (PPIs) versus PPIs alone for the treatment of endoscopic submucosal dissection (ESD-) induced ulcers. METHODS: PubMed, Embase, the Cochrane library, the WanFang database, and China National Knowledge Infrastructure (CNKI) were searched to identify studies that met the inclusion criteria. RESULTS: Nine randomized controlled trials (RCTs) were recognized, including 1170 patients. In general, rebamipide plus PPIs acted better than PPIs alone against ESD-induced ulcers at four weeks (RR = 1.42, 95% CI: 1.13-1.78, P = 0.003) but showed no significant differences at eight weeks (RR = 1.03, 95% CI: 0.97-1.10, P = 0.315). The use of rebamipide plus PPIs was superior to PPIs alone for ESD-induced ulcers greater than 20 mm in size (20-40 mm: RR = 1.98, 95% CI: 1.22-3.23, P = 0.006; >40 mm: RR = 5.14, 95% CI: 1.49-17.74, P = 0.010). In addition, rebamipide plus PPI therapy was discovered to be significantly more effective than PPIs alone for lower ESD-induced ulcers (RR = 1.82, 95% CI: 1.04-3.20, P = 0.037). There were no significant differences between the treatment groups with the ulcer reduction rate. CONCLUSION: Evidences now available show rebamipide plus PPIs is practical for protecting against ESD-induced ulcers at four weeks but not at eight weeks, especially large ulcers (>20 mm). However, we still need more high-quality RCTs in the future to supplement our conclusions.


Asunto(s)
Alanina/análogos & derivados , Antiulcerosos/uso terapéutico , Resección Endoscópica de la Mucosa/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Quinolonas/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Alanina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Úlcera Gástrica/etiología
8.
J Plant Physiol ; 255: 153292, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33069038

RESUMEN

Osmotic stress, caused by drought, salinity, or PEG (polyethylene glycol), is one of the most important abiotic factors that hinder plant growth and development. In Arabidopsis, more than 100 R2R3-MYB transcription factors (TFs) have been identified, and many of them are involved in the transcriptional regulation of a variety of biological processes related to growth and development, as well as responses to biotic and abiotic stresses. However, the MYB TF involving in both plant development and stress response has rarely been reported. We report here that Arabidopsis AtMYB109, a R2R3-MYB TF, functions as a negative regulator of stomatal closure under osmotic stress as well as of pollen tube elongation. Under PEG-induced osmotic stress, whole leaves of AtMYB109-OXs were intensely wilted, while leaves of the wild-type (WT) and myb109 were weakly affected. Moreover, we confirmed that the wilting in AtMYB109-OXs was more severe than in WT and myb109 under drought conditions, and that after re-watering, WT and myb109 plants promptly recovered, while AtMYB109-OXs failed to survive. In addition, stomatal closure was delayed in the AtMYB109-OXs compared to the WT and myb109. However, proline content and the expression of stress-induced and proline synthesis genes were higher in the overexpression lines than in WT and myb109. Then, we observed that the expression of ICS1, a key gene in SA biosynthesis, was greatly suppressed in AtMYB109-OXs. In addition, we found that AtMYB109 expression gradually increased until the flowers were fully opened and thereafter dramatically decreased during silique development. The pollen tube growth was significantly suppressed in AtMYB109-OXs compared to the WT and myb109. Using EMSA and ChIP-qPCR, we confirmed that AtMYB109 bound to the promoter of RABA4D, a gene encoding a pollen development regulator. Taken together, we suggest the delayed stomatal closing and vulnerable phenotypes in the AtMYB109-OXs under osmotic stress are possibly directly or indirectly associated with a SA-mediated mechanism, and that AtMYB109 suppresses RABA4D that modulates pollen tube growth.


Asunto(s)
Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Estomas de Plantas/genética , Estomas de Plantas/fisiología , Estrés Fisiológico/fisiología , Flores/crecimiento & desarrollo , Flores/metabolismo , Genes de Plantas , Presión Osmótica/fisiología , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo
9.
BMC Gastroenterol ; 20(1): 294, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32891125

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients. METHODS: A total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses. RESULTS: A total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49-73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05-119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively. CONCLUSIONS: High-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.


Asunto(s)
Colitis Ulcerosa , Infecciones por Citomegalovirus , Albúminas , China/epidemiología , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Citomegalovirus , Infecciones por Citomegalovirus/complicaciones , ADN Viral , Humanos , Inmunoglobulina A , Masculino
10.
Stem Cells Transl Med ; 9(10): 1233-1243, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32578968

RESUMEN

Skeletal muscle decellularization allows the generation of natural scaffolds that retain the extracellular matrix (ECM) mechanical integrity, biological activity, and three-dimensional (3D) architecture of the native tissue. Recent reports showed that in vivo implantation of decellularized muscles supports muscle regeneration in volumetric muscle loss models, including nervous system and neuromuscular junctional homing. Since the nervous system plays pivotal roles during skeletal muscle regeneration and in tissue homeostasis, support of reinnervation is a crucial aspect to be considered. However, the effect of decellularized muscles on reinnervation and on neuronal axon growth has been poorly investigated. Here, we characterized residual protein composition of decellularized muscles by mass spectrometry and we show that scaffolds preserve structural proteins of the ECM of both skeletal muscle and peripheral nervous system. To investigate whether decellularized scaffolds could per se attract neural axons, organotypic sections of spinal cord were cultured three dimensionally in vitro, in presence or in absence of decellularized muscles. We found that neural axons extended from the spinal cord are attracted by the decellularized muscles and penetrate inside the scaffolds upon 3D coculture. These results demonstrate that decellularized scaffolds possess intrinsic neurotrophic properties, supporting their potential use for the treatment of clinical cases where extensive functional regeneration of the muscle is required.


Asunto(s)
Matriz Extracelular/metabolismo , Imagenología Tridimensional/métodos , Músculo Esquelético/metabolismo , Proteómica/métodos , Ingeniería de Tejidos/métodos , Animales , Femenino , Humanos , Masculino , Ratas
11.
Acta Biomater ; 108: 56-66, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32251786

RESUMEN

Injury to the skin from severe burns can cause debilitating physical and psychosocial distress to the patients. Upon healing, deep dermal burns often result in devastating hypertrophic scar formation. For many decades, stem cell-based therapies have shown significant potential in improving wound healing. However, current cell delivery methods are often insufficient to maintain cell viability in a harmful burn wound environment to promote skin regeneration. In this study, we developed an enhanced approach to deliver adipose-derived stem cells (ASCs) for the treatment of burn wounds, using an in-situ-formed hydrogel system comprised of a hyperbranched poly(ethylene glycol) diacrylate (HB-PEGDA) polymer, a commercially available thiol-functionalized hyaluronic acid (HA-SH) and a short RGD peptide. Stable hydrogels with tunable swelling and mechanical properties form within five minutes under physiological conditions via the Michael-type addition reaction. Combining with RGD peptide, as a cell adhesion motif, significantly alters the cellular morphology, enhances cell proliferation, and increases the paracrine activity of angiogenesis and tissue remodeling growth factors and cytokines. Bioluminescence imaging of luciferase+ ASCs indicated that the hydrogel protected the implanted cells from the harmful wound environment in burns. Hydrogel-ASC treatment significantly enhanced neovascularization, accelerated wound closure and reduced the scar formation. Our findings suggest that PEG-HA-RGD-based hydrogel provides an effective niche capable of augmenting the regenerative potential of ASCs and promoting burn wound healing. STATEMENT OF SIGNIFICANCE: Burn injury is one of the most devastating injures, and patients suffer from many complications and post-burn scar formation despite modern therapies. Here, we designed a conformable hydrogel-based stem cell delivery platform that allows rapid in-situ gelation upon contact with wounds. Adipose-derived stem cells were encapsulated into a PEG-HA-RGD hydrogels. Introducing of RGD motif significantly improved the cellular morphology, proliferation, and secretion of angiogenesis and remodeling cytokines. A deep second-degree burn murine model was utilized to evaluate in-vivo cell retention and therapeutic effect of the hydrogel-ASC-based therapy on burn wound healing. Our hydrogel remarkably improved ASCs viability in burn wounds and the hydrogel-ASC treatment enhanced the neovascularization, promoted wound closure, and reduced scar formation.


Asunto(s)
Ácido Hialurónico , Hidrogeles , Adipocitos , Tejido Adiposo , Animales , Humanos , Ratones , Células Madre
12.
Zhonghua Yi Xue Za Zhi ; 96(4): 260-4, 2016 Jan 26.
Artículo en Chino | MEDLINE | ID: mdl-26879784

RESUMEN

OBJECTIVE: To observe the effects and safety of quadruple regimens including domestically manufactured rabeprazole used as first line/initial therapy for Helicobacter pylori(H.pylori) eradication in gastritis and duodenal ulcer patients, and to investigate the effects of extended use of bismuth after the quadruple therapy on eradication of H. pylori. METHODS: From January to August 2013, 430 patients with chronic gastritis or duodenal ulcer who were confirmed as H. pylori positive in gastroscopy for upper gastrointestinal symptoms were enrolled from 12 centers in China for initial treatment using quadruple regimens for H. pylori eradication. The study was a prospective, multicenter, randomized double-blinded double-dummy parallel-controlled clinical trial. The 310 chronic gastritis patients were divided into 2 groups: group A1 was given quadruple regime (rabeprazole+ amoxicillin+ clarithromycin+ bismuth potassium citrate) for 10 days followed by bismuth-placebo for 21 days; group A2 was given the quadruple regimen for 10 days and then bismuth potassium citrate for 21 days. The duodenal ulcer patients were given the quadruple for 10 days, then rabeprazole for 14 days. All the patients took (13)C urea breath test to detect H. pylori 28 days after medicine withdrawal. RESULTS: Altogether 428 cases were enrolled and 404 completed the trial. The total eradication rate in the chronic gastritis patients was 85.1% (262/308, intention-to-treat (ITT)analysis), which was 81.7% (125/153, ITT) in the A1 group and 88.4% (137/155, ITT) in the A2 group; the eradication rate in the duodenal ulcer patients was 85.8% (103/120, ITT). No severe adverse effects were reported. The symptoms (pain, burning sensation, reflux, belching, nausea, and vomiting) improvement status was similar among A1 and A2 groups. CONCLUSIONS: The quadruple regimen using rabeprazole manufactured in China and administered for 10 days as first line/initial therapy in chronic gastritis and duodenal ulcer patients could achieve good H. pylori eradication rate. The extended use of bismuth after 10-day quadruple regimen might further improve the eradication rate. The regimens containing proton-pump inhibitor and bismuth may be well tolerated and safe in clinical application.


Asunto(s)
Úlcera Duodenal , Helicobacter pylori , Amoxicilina , Antiácidos , Bismuto , Pruebas Respiratorias , Quimioterapia Combinada , Gastritis , Reflujo Gastroesofágico , Gastroscopía , Infecciones por Helicobacter , Humanos , Compuestos Organometálicos , Estudios Prospectivos , Inhibidores de la Bomba de Protones , Urea
13.
Trends Plant Sci ; 20(11): 741-753, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26442683

RESUMEN

The pollen wall is a specialized extracellular cell wall matrix that surrounds male gametophytes and plays an essential role in plant reproduction. Uncovering the mechanisms that control the synthesis and polymerization of the precursors of pollen wall components has been a major research focus in plant biology. We review current knowledge on the genetic and biochemical mechanisms underlying pollen wall development in eudicot model Arabidopsis thaliana and monocot model rice (Oryza sativa), focusing on the genes involved in the biosynthesis, transport, and assembly of various precursors of pollen wall components. The conserved and divergent aspects of the genes involved as well as their regulation are addressed. Current challenges and future perspectives are also highlighted.


Asunto(s)
Arabidopsis/crecimiento & desarrollo , Oryza/crecimiento & desarrollo , Polen/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/metabolismo , Oryza/genética , Oryza/metabolismo , Polen/genética , Polen/metabolismo
14.
Hepatogastroenterology ; 62(138): 503-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25916090

RESUMEN

BACKGROUND/AIMS: We aimed to observe the changes in the anti-Helicobacter pylori (Hp) serum antibodies to Hp virulence factors after eradication therapy and evaluate the potential application value of protein microarray in detecting Hp antibodies after eradication therapy. METHODOLOGY: A total of 107 Hp-positive patients with peptic ulcers (55) and chronic gastritis (52) were recruited. Serum antibodies to Hp urease (Ure), cytotoxin-associated protein (CagA), vacuolating cytotoxin (VacA), heat shock protein 60 (Hsp60), and anti-RdxA nitroreductase were measured. Four weeks after treatment, a 13C-urea breath test (13C- UBT) was applied to assess the Hp eradication state and to analyze correlations between the Hp eradication rate and the five antibodies. Six months after the therapy, protein microarray analysis was used to study the changes in these five serum antibodies. RESULTS: The overall Hp eradication rate was 86.0%There was no significant difference in the rate among the groups that tested positive and negative for the remaining four virulence factors. CONCLUSION: The disease type and serum anti-CagA antibody levels affect the therapeutic outcome of Hp eradication therapy. Protein microarray detection of Hp-related antibodies did not have significant application value for the long-term follow-up of Hp infection after eradication therapy.


Asunto(s)
Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/sangre , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Análisis por Matrices de Proteínas , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de Virulencia/inmunología , Adulto , Anciano , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Pruebas Respiratorias , Enfermedad Crónica , Úlcera Duodenal/tratamiento farmacológico , Úlcera Duodenal/microbiología , Femenino , Estudios de Seguimiento , Gastritis/tratamiento farmacológico , Gastritis/microbiología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/microbiología , Factores de Tiempo , Resultado del Tratamiento , Ureasa/inmunología , Virulencia
15.
Leuk Lymphoma ; 56(7): 2170-81, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25363403

RESUMEN

Tyrosine 177 and the Src homology 2 (SH2) domain play important roles in linking p185Bcr-Abl to downstream pathways critical for cell growth and survival. However, a mutant p185(Y177FR552L) (p185(YR)), in which tyrosine 177 and arginine 552 in the SH2 domain are mutated, is still capable of transforming hematopoietic cells in vitro. Transplant of these cells into syngeneic mice also leads to leukemogenesis, albeit with a phenotype distinct from that produced by wild-type p185Bcr-Abl (p185(wt))-transformed cells. Here we show that G-protein coupled receptor 34 (Gpr34) expression is markedly up-regulated in p185(YR)-transformed cells compared to those transformed by p185(wt). Knockdown of Gpr34 in p185(YR) cells is sufficient to suppress growth factor-independent proliferation and survival in vitro and attenuate leukemogenesis in vivo. The Erk and phosphatidylinositol 3-kinase/Akt pathways are activated in p185(YR) cells and the activation is dependent on Gpr34 expression. These studies identify Gpr34 as an alternative pathway that may mediate p185Bcr-Abl-induced transformation and leukemogenesis.


Asunto(s)
Transformación Celular Neoplásica/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas de Fusión bcr-abl/metabolismo , Leucemia/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Lisofosfolípidos/metabolismo , Adulto , Animales , Apoptosis , Western Blotting , Ciclo Celular , Proliferación Celular , Transformación Celular Neoplásica/genética , Resistencia a Antineoplásicos , Quinasas MAP Reguladas por Señal Extracelular/genética , Femenino , Proteínas de Fusión bcr-abl/genética , Humanos , Técnicas para Inmunoenzimas , Leucemia/genética , Leucemia/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Mutación/genética , Fosfatidilinositol 3-Quinasa/genética , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Lisofosfolípidos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Células Tumorales Cultivadas
16.
Asian Pac J Cancer Prev ; 14(5): 3063-6, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23803080

RESUMEN

OBJECTIVE: To test the microRNA-181c (miR-181c) expression in tissues and plasma of gastric cancer (GC) cases, analyze any correlations, and explore the possibility of miR-181c as a potential molecular marker for GC diagnosis. MATERIALS AND METHODS: Relative miR-181c expression levels in cancers and plasma from 30 GC patients was tested using reverse transcription?real-time fluorescent quantitation PCR and compared to that in samples from 30 gastric ulcer and 30 chronic gastritis patients. RESULTS: The miR-181c expression level in the GC tissues was significantly higher than that in the gastric ulcer and chronic gastritis tissues (P = 0.000), as was the miR-181c expression level in the GC plasma (P = 0.000). We determined that miR-181c expression in GC plasma was positively correlated to its expression in the GC tissues (P = 0.000). CONCLUSIONS: The expression of miR-181c is upregulated in GC tissues and plasma, and the miR-181c expression level in GC plasma is positively correlated to that in the corresponding cancer tissues. Plasma miR-181c is possibly a new serological marker for GC diagnosis.


Asunto(s)
Adenocarcinoma/genética , Gastritis/genética , MicroARNs/sangre , MicroARNs/genética , Neoplasias Gástricas/sangre , Neoplasias Gástricas/genética , Úlcera Gástrica/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Gastritis/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias Gástricas/patología , Úlcera Gástrica/patología
17.
Hepatogastroenterology ; 60(125): 961-4, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23425811

RESUMEN

BACKGROUND/AIMS: The relationship of miR-181c, a potential tumor regulatory factor, with gastric cancer is not well studied. We have investigated this relationship in our study. METHODOLOGY: Paraffin-embedded tissue specimens from 103 gastric cancer patients were subjected to total RNA extraction. Reverse transcription real-time fluorescence quantitative PCR was used to detect miR-181c expression. Its relative expression was correlated with the patients' clinicopathological features. Also, the 5-year survival rate and median survival time were correlated with the miR-181c expression level. RESULTS: miR-181c expression was significantly and directly correlated with the degree of tumor differentiation, invasive depth and clinical stage. Moreover, lymph node metastasis was significantly related with higher miR-181c expression. However, miR-181c expression was not significantly correlated with gender, age, tumor location and distant metastasis. The 5-year overall survival rate and median survival time were significantly greater in patients with low expression of miR-181c. CONCLUSIONS: miR-181c expression level was significantly related to several clinicopathological features of gastric cancer; therefore, miR-181c probably plays a role in its development and progression. This relationship needs to be studied in detail, so that the potential use of miR-181c as a marker for gastric cancer and therapeutic target can be explored.


Asunto(s)
MicroARNs/fisiología , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Metástasis Linfática , Masculino , MicroARNs/análisis , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad
19.
Zhonghua Yi Xue Za Zhi ; 92(30): 2108-12, 2012 Aug 14.
Artículo en Chino | MEDLINE | ID: mdl-23158273

RESUMEN

OBJECTIVE: To explore the effects of 7-day quadruple regimen as the first-line therapy strategy for Helicobacter pylori(H. pylori)infection and compare the eradication rate of ilaprazole versus esoprazole-based regimen. METHODS: A total of 440 patients with H. pylori infection, who had never received H. pylori eradication treatment, were enrolled from 10 domestic hospitals from October 2010 to July 2011. Diagnosed as chronic gastritis or duodenal ulcer according to their endoscopic examination results, they were randomized into ilaprazole and(or) esoprazole-based bismuth-containing quadruple regimen group with amoxicillin and clarithromycin (n = 110 each). After a 7-day eradication treatment, all patients with duodenal ulcer received PPI (ilaprazole and(or) esoprazole) treatment for 14 days and (13)C urea breath test was performed at least 28 days after the end of therapy. The patients with failed eradication treatment underwent endoscopy examination and biopsy. H. pylori culture and detection of antibiotic-resistant genes were also performed. RESULTS: In gastritis patients, the eradication rate (per-protocol, PP value) were 78.2% (79/101) and 82.0% (82/100) in ilaprazole and esoprazole groups (P = 0.50) while the (intention-to-treat) ITT value of eradication rate were 71.8% (79/110) and 74.5% (82/110) in ilaprazole and esoprazole groups respectively (P = 0.65). And there was no statistical difference (P > 0.05). In duodenal patients, the eradication rate (PP) were 92.1% (93/101) and 91.4% (96/105) in ilaprazole and esoprazole group (P = 0.86) while the ITT value of eradication rate were 84.5% (93/110) and 87.3% (96/110) in ilaprazole and esoprazole groups respectively (P = 0.56). And no significant difference existed between two groups in gastritis and duodenal ulcer patients (P > 0.05). In total, the eradication rate was 80.1% (161/201) (PP) and 73.2% (161/220) (ITT), 91.7% (189/206) (PP) and 85.9% (189/220) (ITT) in chronic gastritis and duodenal ulcer patients respectively. The symptomatic improvements of stomachache, burning, belching and nausea remained almost unchanged. No severe side effect was observed. The point mutations for clarithromycin resistance were detected in all 53 H. pylori strains (100%) isolated from the patients with failed eradication treatment. CONCLUSIONS: The eradication rate of PPI based bismuth-containing quadruple regimen as the first-line treatment is satisfactory in chronic gastritis and duodenal ulcer patients. No significant difference exists between the effects of ilaprazole and esoprazole-based groups. And the treatment failure may be attributed mainly to the clarithromycin resistance of H. pylori.


Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/uso terapéutico , Antiulcerosos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Omeprazol/uso terapéutico , 2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Adolescente , Adulto , Anciano , Antiulcerosos/administración & dosificación , China , Quimioterapia Combinada , Femenino , Helicobacter pylori , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Adulto Joven
20.
Bioresour Technol ; 125: 300-4, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23063747

RESUMEN

The objective of this research was to seek a cost effective solution to prepare adsorbents for nitrogen oxide from surplus sludge. Leaf litter and powder coal ash were used as cheap and easily available additives. An adsorbent for nitrogen oxide was prepared by pyrolysis of dried sludge mixed with zinc chloride. Under optimum pyrolysis conditions of 375°C for 90 min and a zinc chloride content of 30%, the surface area of the adsorbent with leaf litter was 514.41 m(2)/g, the surface area of the adsorbent with powder coal ash was 432.34 m(2)/g, respectively, corresponding to an increase of 90.70% and 60.27% when compared to the adsorbent without the additives. The saturated adsorption quantity of the adsorbent with leaf litter reached 271 mg/g at 20°C. The results indicated that the sludge-derived adsorbent was quite promising for nitrogen oxide removal.


Asunto(s)
Ceniza del Carbón/química , Incineración/métodos , Dióxido de Nitrógeno/química , Dióxido de Nitrógeno/aislamiento & purificación , Hojas de la Planta/química , Aguas del Alcantarillado/química , Ultrafiltración/métodos , Adsorción , Calor , Polvos
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