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This work reports a dual heterojunction of etched MIL-68(In)-NH2 (MN) supported heptazine-/triazine-based carbon nitride (HTCN) via a facile hydrothermal process for photocatalytic ammonia (NH3 ) synthesis. By applying the hydrothermal treatment, MN microrods are chemically etched into hollow microtubes, and HTCN with nanorod array structures are simultaneously tightly anchored on the outside surface of the microtubes. With the addition of 9 wt% HTCN, the resulting dual heterojunction presents an enhanced photocatalytic ammonia yield rate of 5.57 mm gcat -1 h-1 with an apparent quantum efficiency of 10.89% at 420 nm. Moreover, stable ammonia generation using seawater, tap water, lake water, and turbid water in the absence of sacrificial reagents verifies the potential of the dual-heterojunction composites as a commercially viable photosystem. The obtained one-dimensional (1D) microtubes and coating of HTCN confers this unique composite with extended visible-light harvesting and accelerated charge carrier migration via a multi-stepwise charge transfer pathway. This work provides a new strategy for optimizing nitrogen (N2 )-into-ammonia conversion efficiency by designing novel dual-heterojunction catalysts.
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In this work, an intramolecular carbon nitride (CN)-based quaternary homojunction functionalized with pyridine rings is prepared via an in situ alkali-assisted copolymerization strategy of bulk CN and 2-aminopyridine for efficient visible light hydrogen generation. In the obtained structure, triazine-based CN (TCN), heptazine-based CN (HCN), pyridine unit incorporated TCN, and pyridine ring inserted HCN constitute a special multicomponent system and form a built-in electric field between the crystalline semiconductors by the arrangement of energy band levels. The electron-withdrawing function of the conjugated heterocycle can trigger the skeleton delocalization and edge induction effect. Highly accelerated photoelectron-hole transfer rates via multi-stepwise charge migration pathways are achieved by the synergistic effect of the functional group modification and molecular quaternary homojunction. Under the addition of 5 mg 2-aminopyridine, the resulting homojunction framework exhibits a significantly improved hydrogen evolution rate of 6.64 mmol g-1 h-1 with an apparent quantum efficiency of 12.27% at 420 nm. Further, the catalyst verifies its potential commercial value since it can produce hydrogen from various real water environments. This study provides a reliable way for the rational design and fabrication of intramolecular multi-homojunction to obtain high-efficient photocatalytic reactions.
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Metal-organic framework derived materials received a lot of attention due to their significant benefits in photocatalytic reactions. In this work, a Z-scheme ZnIn2S4/Bi2S3 hierarchical heterojunction is first developed by a one-pot method using CAU-17 as a template. The specific preparation method endows an intimate interface contact between these two monomers, and CAU-17-derived Bi2S3 possesses a high surface area and porosity, resulting in an efficient charge separation and O2 capture. Thus, for photocatalytic H2O2 production from the O2 reduction reaction, the ZnIn2S4/Bi2S3 heterojunction can achieve an H2O2 yield of 995 µmol L-1 in pure water and ambient air under visible light, 4.5 and 4 times that of ZnIn2S4 and Bi2S3, respectively. In addition, in tetracycline solution, ZnIn2S4/Bi2S3 can degrade tetracycline with a degradation rate of 95% by photocatalysis, and at the same time, a final H2O2 production yield of 1223 µmol L-1 is reached. Similarly, high yields of H2O2 are also obtained from wastewater containing o-nitrophenol, acid golden yellow, or acid red, and these pollutants are effectively degraded. This work reveals the potential of metal-organic framework-derived materials in photocatalysis, as well as provides insights into H2O2 green synthesis and wastewater treatment.
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A kind of ionic conductive gel (also named eutectogel) is developed from an inorganic salt (ZnCl2)-based deep eutectic solvent (DES). The ternary DES consists of ZnCl2, acrylic acid, and water, and cotton linter cellulose is introduced into the DES system to tailor its mechanical and conductive properties. Enabled by the extensive hydrogen bonds and ion-dipole interactions, the obtained eutectogel displays superior ionic conductivity (0.33 S/m), high stretchability (up to 2050%), large tensile strength (1.82 MPa), and wide temperature tolerance (-40 to 60 °C). In particular, the water-induced coordination interactions can tune the strength of hydrogen/ionic bonds in the eutectogels, imparting them with appealing humidity sensing ability in complex and extreme conditions.
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OBJECTIVE: Ulcerative colitis (UC), a chronic and refractory nonspecific inflammatory bowel disease, affects millions of patients worldwide and increases the risk of colorectal cancer. Teprenone is an acylic polyisoprenoid that exerts anti-inflammatory properties in rat models of peptic ulcer disease. This in vitro and in vivo study was designed to investigate the effects of teprenone on UC and to explore the underlying mechanisms. METHODS: Human intestinal epithelial cells (Caco-2 cells) serve as the in vitro experimental model. Lipopolysaccharide (LPS, 1 µg/mL) was employed to stimulate the production of pro-inflammatory cytokines (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α), Toll-like receptor-4 (TLR4), MyD88 expression, and NF-κB activation. A trinitrobenzene sulfonic acid (TNBS)-induced chronic UC rat model was employed for the in vivo assay. RESULTS: Pro-inflammatory cytokine stimulation by LPS in Caco-2 cells was inhibited by teprenone at 40 µg/mL through the TLR4/NF-κB signaling pathway. Teprenone attenuated TNBS-induced UC, decreased myeloperoxidase and malondialdehyde, induced TLR4 expression and NF-κB activation, and increased glutathione and zonula occludens-1 level in the rat colonic tissue. Moreover, Fusobacterium, Escherichia coli, Porphyromonas gingivalis elevation, and Mogibacterium timidum decline in UC rats were inhibited by teprenone. CONCLUSION: Based on our results, the protective effects of teprenone for UC may be related to its ability to modulate the gut microbiota and reduce the inflammatory response.
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Colitis Ulcerosa , Colitis , Diterpenos , Microbioma Gastrointestinal , Ratas , Humanos , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/prevención & control , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Células CACO-2 , Lipopolisacáridos/toxicidad , Citocinas/metabolismo , Trinitrobencenos , Factor de Necrosis Tumoral alfa , Colitis/inducido químicamente , Modelos Animales de EnfermedadRESUMEN
Inference of population structure from genetic data plays an important role in population and medical genetics studies. With the advancement and decreasing cost of sequencing technology, the increasingly available whole genome sequencing data provide much richer information about the underlying population structure. The traditional method originally developed for array-based genotype data for computing and selecting top principal components (PCs) that capture population structure may not perform well on sequencing data for two reasons. First, the number of genetic variants p is much larger than the sample size n in sequencing data such that the sample-to-marker ratio n / p $n/p$ is nearly zero, violating the assumption of the Tracy-Widom test used in their method. Second, their method might not be able to handle the linkage disequilibrium well in sequencing data. To resolve those two practical issues, we propose a new method called ERStruct to determine the number of top informative PCs based on sequencing data. More specifically, we propose to use the ratio of consecutive eigenvalues as a more robust test statistic, and then we approximate its null distribution using modern random matrix theory. Both simulation studies and applications to two public data sets from the HapMap 3 and the 1000 Genomes Projects demonstrate the empirical performance of our ERStruct method.
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Genética de Población , Polimorfismo de Nucleótido Simple , Genotipo , Simulación por Computador , Secuenciación Completa del GenomaRESUMEN
This work for the first time reports bimetallic Ni-Co and monometallic (Ni and Co) nanoparticles (NPs)-engineered carbon nitride nanotubes with nitrogen vacancies (V-CNNTs) for visible-light photocatalytic H2 generation application. The bimetallic Ni-Co NPs have an average size of less than 5 nm and are homogenously dispersed along the nanochannels of V-CNNTs. The composition of the bimetallic NPs plays an essential role to maximize photocatalytic activity. With the optimal Ni/Co atom ratio of 3:1, Ni-Co/V-CNNTs nanohybrids yielded a H2 production rate of 4.19 µmol/h, which is higher than those of monometallic counterparts and V-CNNTs. The intimately loaded Ni-Co NPs and incorporated nitrogen vacancies enhance the photocatalytic performance through extended light absorption, abundant active sites, strong metal-support interaction, and efficient charge carrier transfer along the axial direction. This study presents a stable and highly efficient hybrid as a promising photocatalyst for visible light photocatalytic H2 production through water splitting.
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Nanopartículas , Nanotubos , Catálisis , Hidrógeno , Nitrilos , NitrógenoRESUMEN
Embryo quality determines the success of in vitro fertilization and embryo transfer (IVF-ET) treatment. Biomarkers for the evaluation of embryo quality have some limitations. Apoptosis in cumulus cells (CCs) is important for ovarian function. PTEN (phosphatase and tensin homolog) is a well known tumour suppressor gene that functions as a mediator of apoptosis and is crucial for mammalian reproduction. In the present study, we analyzed the expression level of PTEN in human CCs and aimed to investigate its association with embryo developmental competence in IVF treatment cycles. The PTEN mRNA level in CCs was measured using real-time fluorescence quantitative PCR. The association of the differential expression of PTEN with embryo quality was analyzed. Our data showed that PTEN mRNA levels were significantly decreased in CCs surrounding mature oocytes compared with immature oocytes. Similar changes were found in the analysis of fertilization and blastocyst formation. The speculation that the measurement of PTEN mRNA levels in human CCs would provide a useful tool for selecting oocytes with greater chances to implant into the uterus needs to be further verified through single-embryo transfer in the future. The proapoptotic mechanism of PTEN in human reproduction needs to be further studied.
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Células del Cúmulo , Oocitos , Animales , Biomarcadores/metabolismo , Células del Cúmulo/metabolismo , Desarrollo Embrionario , Femenino , Fertilización In Vitro , Humanos , Mamíferos , Oocitos/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Tensinas/metabolismoRESUMEN
Zeolite ZIF-8 has been etched with acid to form microporous ZIF-8-E crystals. These were then introduced into a polyethersulfone (PES) membrane matrix to enhance its CO2 /N2 separation performance. Open through pores of size about 100â nm formed in the ZIF-8 crystals allow the ingrowth of polyethersulfone chains, ensuring a reduction in the number of nonselective voids, thereby achieving better interaction between ZIF-8-E and PES. As a result, the CO2 /N2 separation performance of the ZIF-8-E/PES membrane increased significantly, showing a CO2 permeability of 15.7â Barrer and a CO2 /N2 ideal selectivity of 6.5.
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BACKGROUND: YKL-40, a chitinase-like glycoprotein has been identified as a candidate tumor marker. The current study evaluated the clinical significance of plasma YKL-40 in esophageal cancer patients. METHODS: We enrolled 127 esophageal cancer patients, 29 healthy controls. Plasma YKL-40 levels were measured through enzyme linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficiency of plasma YKL-40 in esophageal cancer patients. The correlations between plasma YKL-40 and clinicopathological characteristics of esophageal were analyzed. RESULTS: Plasma YKL-40 levels were significantly higher in patients with lymph node metastasis than those that were non-metastatic (p = 0.005). Patients with tumor thrombus formation presented with significantly higher YKL-40 levels than those without thrombus formation (160.3 vs. 74.7 ng/mL, p = 0.012). YKL-40 levels in patients with advanced stage (III and IV) were significantly higher than those in the early stages (I and II, p = 0.016). ROC curve analysis showed that the area under curve was 0.909, and the best diagnostic threshold of YKL-40 for esophageal cancer was 80.6 ng/mL with 68.9% sensitivity and 96.6% specificity. CONCLUSIONS: This study indicated that YKL-40 may be a biomarker for esophageal cancer and potential biomarker for identification of invasive esophageal cancer.
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Biomarcadores de Tumor/sangre , Proteína 1 Similar a Quitinasa-3/sangre , Neoplasias Esofágicas , Adulto , Anciano , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: This prospective, randomized, controlled study aimed to evaluate the effects of flaxseed supplementation on functional constipation and quality of life in adult men and women in China. METHODS AND STUDY DESIGN: 90 subjects with functional constipation diagnosed by the Rome IV criteria were enrolled. Subjects were randomly assigned to receive either 50 g/day flaxseed flour with meals (n=60) or 15 mL/day of a lactulose solution on an empty stomach (n=30) every morning for 4 weeks. Wexner constipation scores, stool consistency according to the Bristol Stool Form Scale, and bowel habits (frequency of bowel movements/week, the time spent on defecation) were the primary outcomes. The change in Patient Assessment of Constipation Quality of Life score was the secondary outcome. RESULTS: After 4 weeks, the bowel habits in both groups were significantly improved. The median Wexner constipation score decreased from 14 to 6.5 in the flaxseed group (p<0.001) and from 15 to 9 in the lactulose group (p<0.001). The median defecation frequency per week increased significantly (2 to 7 for flaxseed and 2 to 6 for lactulose, p<0.001 for both groups). The Patient Assessment of Constipation Quality of Life score decreased significantly (-1.34 and -0.66 for flaxseed and lactulose, respectively; p<0.001 for both groups). CONCLUSIONS: Flaxseed flour is somewhat more effective at increasing defecation frequency than lactulose, improving bowel movements and promoting life quality of subjects with chronic functional constipation in the Chinese population.
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Estreñimiento/prevención & control , Defecación/efectos de los fármacos , Suplementos Dietéticos , Lino , Semillas , Adulto , China/epidemiología , Femenino , Humanos , Lactulosa/administración & dosificación , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
As a novel type of mesenchymal stem cell, induced pluripotent stem cell-derived mesenchymal stem cells (iPMSCs) have huge potential for cell therapy. iPMSCs exhibited the typical characteristics of MSCs, whereas the tri-lineage differentiation potential is limited, especially the adipogenic propensity. Here, to reveal the molecular mechanism we carried out the epigenetic comparisons between the iPMSCs and the bone marrow-derived mesenchymal stem cells (BMSCs) and embryonic stem cell-derived mesenchymal stem cells (EMSCs). We found that the iPMSCs was significantly higher than the BMSCs in terms of genome-wide DNA methylation. Meanwhile, the adipogenic gene PPARγ promoter region existed hypermethylation. In addition, compared with EMSCs and BMSCs, iPMSCs had significant differences in the histones epigenetic modification of methylation and acetylation, especially high levels of histone 27 lysine trimethylation (H3K27me3). Furthermore, the epigenetic modifiers Decitabine and EPZ6438 effectively upregulated the gene expression of PPARγ and promoted the adipogenic differentiation of iPMSCs via chromatin remodeling. Taken together, our findings set new metrics to the applications for improving the efficiency and the therapeutic potential of iPMSCs.
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Adipogénesis/efectos de los fármacos , Benzamidas/farmacología , Decitabina/farmacología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Piridonas/farmacología , Animales , Compuestos de Bifenilo , Células Cultivadas , Metilación de ADN/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Células Madre Pluripotentes Inducidas/citología , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos C57BL , MorfolinasRESUMEN
BACKGROUND: Liver injury associated with acute graft-versus-host disease (aGVHD) is a frequent and severe complication of hematopoietic stem cell transplantation and remains a major cause of transplant-related mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) has been proposed as a potential therapeutic approach for aGVHD. However, the therapeutic effects are not always achieved. In this study, we genetically engineered C57BL/6 mouse BM-MSCs with AKT1 gene and tested whether AKT1-MSCs was superior to control MSCs (Null-MSCs) for cell therapy of liver aGVHD. RESULTS: In vitro apoptosis analyses showed that, under both routine culture condition and high concentration interferon-γ (IFN-γ) (100ng/mL) stimulation condition, AKT1-MSCs had a survival (anti-apoptotic) advantage compared to Null-MSCs. In vivo imaging showed that AKT1-MSCs had better homing capacity and longer persistence in injured liver compared to Null-MSCs. Most importantly, AKT1-MSCs demonstrated an enhanced immunomodulatory function by releasing more immunosuppressive cytokines, such as IL-10. Adoptive transfer of AKT1-MSCs mitigated the histopathological abnormalities of concanavalin A(ConA)-induced liver injury along with significantly lowered serum levels of ALT and AST. The attenuation of liver injury correlated with the decrease of TNF-α and IFN-γ both in liver tissue and in the serum. CONCLUSIONS: In summary, BM-MSCs genetically modified with AKT1 has a survival advantage and an enhanced immunomodulatory function both in vitro and in vivo and thus demonstrates the therapeutic potential for prevention and amelioration of liver GVHD and other immunity-associated liver injuries.
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The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c-Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c-Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c-Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c-Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c-Met expression with tumor stages of CRC liver metastasis, as well as c-Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c-Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c-Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.
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Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Factor de Crecimiento de Hepatocito/biosíntesis , Neoplasias Hepáticas , Hígado/metabolismo , Proteínas Proto-Oncogénicas c-met/biosíntesis , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Humanos , Hígado/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad NeoplásicaRESUMEN
Inspired by the anti-freezing mechanisms found in nature, ionic compounds (ZnCl2 /CaCl2 ) are integrated into cellulose hydrogel networks to enhance the freezing resistance. In this work, cotton cellulose is dissolved by a specially designed ZnCl2 /CaCl2 system, which endows the cellulose hydrogels specific properties such as excellent freeze-tolerance, good ion conductivity, and superior thermal reversibility. Interestingly, the rate of cellulose coagulation could be promoted by the addition of extra water or glycerol. This new type of cellulose-based hydrogel may be suitable for the construction of flexible devices used at temperature as low as -70 °C.
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We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7% ± 5.3% versus 43.4% ± 7.0%, P = .015) and chronic graft-versus- host disease (GVHD; 20.1% ± 5.8% versus 46.0% ± 7.9%, P = .003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1% ± 3.3% versus 84.4% ± 5.7%, P = .235), grades III to IV acute GVHD (3.4% ± 2.4% versus 12.3% ± 4.7%, P = .098), moderate to severe chronic GVHD (12.6% ± 4.9% versus 11.5% ± 4.9%, P = .905), or graft rejection (7.4% ± 3.6% versus 5.5% ± 3.1%, P = .852). There was also no significant difference with regard to the incidence of severe bacterial infection (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P = .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.
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Anemia Aplásica/terapia , Suero Antilinfocítico/farmacología , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Adulto , Anemia Aplásica/mortalidad , Animales , Suero Antilinfocítico/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA , Histocompatibilidad , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Conejos , Estudios Retrospectivos , Hermanos , Análisis de Supervivencia , Porcinos , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Prolonged isolated thrombocytopenia (PT) is a severe complication in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether the megakaryoctic potential of hematopoietic stem cells (HSCs) in bone marrow is intact and what factors drive the pathological process of PT remain elusive. A retrospective study in patients (n = 285) receiving HSCT revealed that the occurrence of PT was approximately 8% and the number of platelets and megakaryocytes in PT patients is much lower compared with control subjects. To test whether the deficiency of thrombopoiesis was caused by the activities of HSCs, the megakaryocytic differentiation potential of HSCs before or after transplantation was assessed. Interestingly, a substantial decrease of megakaryocytic differentiation was observed 2 weeks after transplantation of HSCs in all of the allo-HSCT recipients. However, 4 weeks after transplantation, the ability of HSCs to generate CD41+CD42b+ megakaryocytes in successful platelet engraftment patients recovered to the same level as those of HSCs before implantation. In contrast, HSCs derived from PT patients throughout the postimplantation period exhibited poor survival and failed to differentiate properly. A protein array analysis demonstrated that multiple inflammation-associated cytokines were elevated in allo-HSCT recipients with PT. Among them, insulin-like growth factor-binding protein 1 and regulated on activation, normal T cell expressed and secreted were found to significantly suppress the proliferation and megakaryocytic differentiation of HSCs in vitro. Our results suggested that the occurrence of PT may be attributed, at least partially, to the damage to HSC function caused by inflammation-associated cytokines after HSCT. These findings shed light on the mechanism underlying HSC megakaryocytic differentiation in PT patients and may provide potential new strategies for treating PT patients after HSCT.
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Quimiocina CCL5/farmacología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células Madre Hematopoyéticas/citología , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/farmacología , Megacariocitos/citología , Trombocitopenia/etiología , Adulto , Diferenciación Celular , Citocinas , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombocitopenia/patología , Trasplante Homólogo/efectos adversosRESUMEN
INTRODUCTION: Certain procaspase-8 mutations are reported to be associated with the progression and prognosis of multiple tumors. However, it remains unclear whether the poor chemotherapy response and frequent relapse after complete remission of patients with acute myeloid leukemia (AML) is also related to procaspase-8 abnormalities. METHODS: Polymerase chain reaction (PCR) amplification and Sanger sequencing of the procaspase-8 gene (CASP8) were performed. Apoptotic rates were analyzed with Annexin V-FITC staining in cells expressing wild-type (WT) procaspase-8, the Q482H or C360S mutant, or control vector after treatment with or without tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Western blot analysis was performed to detect activation of procaspase-8 and downstream apoptotic signaling pathway components in those cells. The Co-immunoprecipitation (Co-IP) assays were performed to detect interaction between WT and mutant procaspase-8 proteins. RESULTS: AML patients carrying the Q482H mutation were likely to develop chemotherapy resistance. Similar to C360S, The Q482H mutation abolished caspase-8-mediated apoptotic signaling and inhibited TRAIL-induced apoptosis. The Q482H mutation impaired procaspase-8 dimerization, thus preventing the self-activation of procaspase-8. CONCLUSION: The procaspase-8 Q482H mutation in AML patients abolishes caspase-8-mediated apoptosis by impairing procaspase-8 dimerization.
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Apoptosis/genética , Caspasa 8/genética , Resistencia a Antineoplásicos/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Anciano , Anciano de 80 o más Años , Dimerización , Femenino , Regulación Enzimológica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación/genética , Células Tumorales CultivadasRESUMEN
Ghrelin is a gastric acyl-peptide that plays an important role in cell proliferation. In the present study, we explored the role of ghrelin in A549â¯cell proliferation and the possible molecular mechanisms. We found that ghrelin promotes A549â¯cell proliferation, knockdown of the growth hormone secretagogue receptor (GHSR) attenuated A549â¯cell proliferation caused by ghrelin. Ghrelin induced the rapid phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, ERK, mammalian target of rapamycin (mTOR) and P70S6K. PI3K inhibitor (LY 294002), ERK inhibitor (PD98059) and mTOR inhibitor (Rapamycin) inhibited ghrelin-induced A549â¯cell proliferation. Moreover, GHSR siRNA inhibited phosphorylation of PI3K, Akt, ERK, mTOR and P70S6K induced by ghrelin. Akt and mTOR/P70S6K phosphorylation was inhibited by LY 294002 but not by PD98059. These results indicate that ghrelin promotes A549â¯cell proliferation via GHSR-dependent PI3K/Akt/mTOR/P70S6K and ERK signaling pathways.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular , Ghrelina/metabolismo , Neoplasias Pulmonares/metabolismo , Transducción de Señal , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Ghrelina/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
High-precision measurement of X-ray spectra is affected by the statistical fluctuation of the X-ray beam under low-counting-rate conditions. It is also limited by counting loss resulting from the dead-time of the system and pile-up pulse effects, especially in a high-counting-rate environment. In this paper a detection system based on a FAST-SDD detector and a new kind of unit impulse pulse-shaping method is presented, for counting-loss correction in X-ray spectroscopy. The unit impulse pulse-shaping method is evolved by inverse deviation of the pulse from a reset-type preamplifier and a C-R shaper. It is applied to obtain the true incoming rate of the system based on a general fast-slow channel processing model. The pulses in the fast channel are shaped to unit impulse pulse shape which possesses small width and no undershoot. The counting rate in the fast channel is corrected by evaluating the dead-time of the fast channel before it is used to correct the counting loss in the slow channel.