Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Blood ; 137(24): 3339-3350, 2021 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-33881475

RESUMEN

Total body irradiation (TBI) is commonly used in host conditioning regimens for human hematopoietic stem cell (HSC) transplantation to treat various hematological disorders. Exposure to TBI not only induces acute myelosuppression and immunosuppression, but also injures the various components of the HSC niche in recipients. Our previous study demonstrated that radiation-induced bystander effects (RIBE) of irradiated recipients decreased the long-term repopulating ability of transplanted mouse HSCs. However, RIBE on transplanted human HSCs have not been studied. Here, we report that RIBE impaired the long-term hematopoietic reconstitution of human HSCs as well as the colony-forming ability of human hematopoietic progenitor cells (HPCs). Our further analyses revealed that the RIBE-affected human hematopoietic cells showed enhanced DNA damage responses, cell-cycle arrest, and p53-dependent apoptosis, mainly because of oxidative stress. Moreover, multiple antioxidants could mitigate these bystander effects, though at different efficacies in vitro and in vivo. Taken together, these findings suggest that RIBE impair human HSCs and HPCs by oxidative DNA damage. This study provides definitive evidence for RIBE on transplanted human HSCs and further justifies the necessity of conducting clinical trials to evaluate different antioxidants to improve the efficacy of HSC transplantation for the patients with hematological or nonhematological disorders.


Asunto(s)
Efecto Espectador/efectos de los fármacos , Daño del ADN , Rayos gamma/efectos adversos , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/metabolismo , Estrés Oxidativo/efectos de la radiación , Traumatismos Experimentales por Radiación/metabolismo , Animales , Femenino , Células Madre Hematopoyéticas/patología , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Traumatismos Experimentales por Radiación/patología
2.
Phys Chem Chem Phys ; 21(3): 1367-1374, 2019 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-30601508

RESUMEN

Understanding the atmospheric fate of hydrofluoroolefins (HFOs) is of great significance to assess their potential risk to the environment. As an important type of HFO, the comprehensive transformation mechanism and kinetics of Z(E)-CF3CH[double bond, length as m-dash]CHF initiated by OH radicals were investigated by performing quantum chemical calculations at the CCSD(T)/aug-cc-pVTZ//MP2/cc-pVDZ level. The results show that the OH-addition pathways are the most favorable for the title reaction. The rate constants are obtained by transition state theory with Wigner tunneling correction (TST/W). The calculated total rate constants are in good agreement with the experimental data. At 298 K, the computed rate constant and lifetime of Z(E)-CF3CH[double bond, length as m-dash]CHF are 9.66 × 10-13 (4.02 × 10-13) cm3 molecule-1 s-1 and 12.3 (29.7) days, respectively, which demonstrates that Z(E)-CF3CH[double bond, length as m-dash]CHF is atmospherically persistent.

3.
Molecules ; 24(19)2019 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-31546726

RESUMEN

Mature 'Hamlin' sweet oranges (Citrus sinensis (L.) Osbeck) were irradiated using light-emitting diodes (LEDs) and ultraviolet (UV) light for six days after harvest. Based on evaluation of the basic ripening parameters of fruits, the contents of soluble sugars, organic acids, and carotenoids were analyzed (in pulps) on the sixth day by high-performance liquid chromatography (HPLC). The results showed that LED and UV irradiation not only accelerated orange ripening but also caused significant changes in the soluble sugar, organic acid, and carotenoid content. Compared with fruit subjected to dark shade (DS) treatment, the total soluble sugar, fructose, and glucose contents increased significantly in UV-treated (UVA, UVB, and UVC) fruits, while the sucrose content increased remarkably in white light, UVB, and UVC-treated fruits (p < 0.05). UV treatment was associated with inducing the largest effect on the total soluble sugar content. Except for UVB, other types of light notably induced an accumulation of the total organic acid content, none but blue light and red light markedly induced citric acid accumulation (p < 0.05). Interestingly, only the red light and dark shade treatments had markedly positive effects in terms of inducing carotenoid accumulation, including the total carotenoid, isolutein, zeaxanthin, lutein, neoxanthin, all-trans-violaxanthin, phytofluene, cis-ζ-carotene, and ß-carotene concentrations. Other light treatments had significantly negative effects on carotenoid accumulation (p < 0.05). Therefore, soluble sugar, organic acid, and carotenoid accumulation in sweet oranges vary depending on the levels of UV and LED irradiation. Appropriate light irradiation is a potentially effective way to maintain or improve postharvest fruit quality.


Asunto(s)
Carotenoides/química , Citrus sinensis/química , Azúcares/metabolismo , Rayos Ultravioleta , Citrus sinensis/efectos de la radiación , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Proteínas de Plantas/metabolismo , Azúcares/química
4.
Molecules ; 24(9)2019 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-31064149

RESUMEN

To investigate the effect of post-harvest light irradiation on the accumulation of flavonoids and limonoids, harvested Newhall navel oranges were continuously exposed to light-emitting diode (LED) and ultraviolet (UV) light irradiation for 6 days, and the composition and content of flavonoids and limonoids in the segments were determined using UPLC-qTOF-MS at 0, 6, and 15 days after harvest. In total, six polymethoxylated flavonoids (PMFs), five flavone-O/C-glycosides, seven flavanone-O-glycosides, and three limonoids were identified in the segments. The accumulation of these components was altered by light irradiation. Red and blue light resulted in higher levels of PMFs during exposure periods. The accumulation of PMFs was also significantly induced after white light, UVB and UVC irradiation were removed. Red and UVC irradiation induced the accumulation of flavone and flavanone glycosides throughout the entire experimental period. Single light induced limonoid accumulation during exposure periods, but limonoid levels decreased significantly when irradiation was removed. Principal component analysis showed a clear correlation between PMFs and white light, between flavonoid glycosides and red light and UVC, and between limonoids and UVC. These results suggest that the accumulation of flavonoids and limonoids in citrus is regulated by light irradiation. White light, red light and UVC irradiation might be a good potential method for improving the nutrition and flavor quality of post-harvest citrus.


Asunto(s)
Citrus sinensis/metabolismo , Flavonoides/efectos de la radiación , Aromatizantes/efectos de la radiación , Limoninas/efectos de la radiación , Cromatografía Líquida de Alta Presión/métodos , Flavanonas/metabolismo , Flavonas/metabolismo , Flavonoides/metabolismo , Aromatizantes/metabolismo , Glicósidos/metabolismo , Luz , Limoninas/metabolismo , Análisis de Componente Principal/métodos , Espectrometría de Masas en Tándem/métodos , Factores de Tiempo , Rayos Ultravioleta
5.
Blood ; 124(20): e45-8, 2014 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-25287706

RESUMEN

Immunocompromised mice, such as the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, have been widely used to examine the self-renewal and differentiation potential of human hematopoietic stem cells (HSCs) in vivo. However, the efficiency of human HSC engraftment remains very low. Here, we report that NOD/SCID mice had higher levels of reactive oxygen species (ROS) in their bone marrow (BM) than other commonly used mouse strains (C57BL/6 and BALB/C). Treatment with the antioxidant N-acetyl-l-cysteine (NAC) decreased ROS levels in the BM of NOD/SCID mice. Furthermore, the NAC-treated mice displayed a significant increase in human HSC engraftment and multilineage hematopoietic differentiation in the mice. In comparison with the control mice, NAC-treated recipients displayed a 10.8-fold increase in hematopoietic engraftment in the injected tibiae. A beneficial effect of NAC for human hematopoietic engraftment was also observed in an additional immunodeficient mouse strain, namely NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NOD/SCID/γc(-/-) or NSG). Thus, this study uncovers a previously unappreciated negative effect of ROS on human stem cell engraftment in immunodeficient mice.


Asunto(s)
Acetilcisteína/uso terapéutico , Antioxidantes/uso terapéutico , Médula Ósea/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Médula Ósea/metabolismo , Femenino , Hematopoyesis/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/citología , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Trasplante Heterólogo
6.
Cancer Sci ; 106(5): 642-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25702787

RESUMEN

The epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway aberrations play significant roles in breast cancer occurrence and development. However, the status of EGFR and AKT1 gene copy numbers remains unclear. In this study, we showed that the rates of EGFR and AKT1 gene copy number alterations were associated with the prognosis of breast cancer. Among 205 patients, high EGFR and AKT1 gene copy numbers were observed in 34.6% and 27.8% of cases by multi-gene fluorescence in situ hybridization, respectively. Co-heightened EGFR/AKT1 gene copy numbers were identified in 11.7% cases. No changes were found in 49.3% of patients. Although changes in EGFR and AKT1 gene copy numbers had no correlation with patients' age, tumor stage, histological grade and the expression status of other molecular makers, high EGFR (P = 0.0002) but not AKT1 (P = 0.1177) gene copy numbers correlated with poor 5-year overall survival. The patients with co-heightened EGFR/AKT1 gene copy numbers displayed a poorer prognosis than those with tumors with only high EGFR gene copy numbers (P = 0.0383). Both Univariate (U) and COX multivariate (C) analyses revealed that high EGFR and AKT1 gene copy numbers (P = 0.000 [U], P = 0.0001 [C]), similar to histological grade (P = 0.001 [U], P = 0.012 [C]) and lymph node metastasis (P = 0.046 [U], P = 0.158 [C]), were independent prognostic indicators of 5-year overall survival. These results indicate that high EGFR and AKT1 gene copy numbers were relatively frequent in breast cancer. Co-heightened EGFR/AKT1 gene copy numbers had a worse outcome than those with only high EGFR gene copy numbers, suggesting that evaluation of these two genes together may be useful for selecting patients for anti-EGFR-targeted therapy or anti-EGFR/AKT1-targeted therapy and for predicting outcomes.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Receptores ErbB/genética , Dosificación de Gen , Proteínas Proto-Oncogénicas c-akt/genética , Anciano , Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia
7.
Tumour Biol ; 35(3): 1847-54, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24096545

RESUMEN

This study was conducted to analyze copy number alterations (CNAs) of the genes involved in the G1/S checkpoint signaling pathway of triple-negative breast cancer (TNBC) and to evaluate their clinical value in the prognosis of TNBC. Quantitative multi-gene fluorescence in situ hybridization was used to study CNAs of the genes involved in the G1/S checkpoint signaling pathway, including cyclin d1 (CCND1), c-Myc, p21, cell-cycle-checkpoint kinase 2 gene, p16, retinoblastoma (Rb1), murine double minute 2 (Mdm2) and p53, in 60 TNBC samples and 60 non-TNBC samples. In comparison with the non-TNBC samples, CNAs of the genes involved in the G1/S checkpoint signaling pathway were more frequently observed in the TNBC samples (p = 0.000). Out of a total of eight genes, six (CCND1, c-Myc, p16, Rb1, Mdm2, and p53) exhibited significantly different CNAs between the TNBC group and the non-TNBC group. Univariate survival analysis revealed that the gene amplification of c-Myc (p = 0.008), Mdm2 (p = 0.020) and the gene deletion of p21 (p = 0.004), p16 (p = 0.015), and Rb1 (p = 0.028) were the independent predictive factor of 5-year OS for patients with TNBC. Cox multivariate analysis revealed that the gene amplification of c-Myc (p = 0.026) and the gene deletion of p21 (p = 0.019) and p16 (p = 0.034) were independent prognostic factors affecting the 5-year OS for TNBC. CNAs of the genes involved in the G1/S checkpoint signaling pathway presented a higher rate of incidence in TNBC than in non-TNBC, which could indicate one of the molecular mechanisms for the specific biological characteristics of TNBC. The genes c-Myc, p21, and p16 were correlated with the prognosis of TNBC and therefore may have potential clinical application values in the prognostic prediction of TNBC.


Asunto(s)
Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Genes p16 , Proteínas Proto-Oncogénicas c-myc/genética , Transducción de Señal/genética , Neoplasias de la Mama Triple Negativas/genética , Femenino , Dosificación de Gen , Humanos , Procesamiento de Imagen Asistido por Computador , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Neoplasias de la Mama Triple Negativas/mortalidad
8.
Mol Ther ; 21(2): 423-32, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23295952

RESUMEN

High levels of reactive oxygen species (ROS) can exhaust hematopoietic stem cells (HSCs). Thus, maintaining a low state of redox in HSCs by modulating ROS-detoxifying enzymes may augment the regeneration potential of HSCs. Our results show that basal expression of manganese superoxide dismutase (MnSOD) and catalase were at low levels in long-term and short-term repopulating HSCs, and administration of a MnSOD plasmid and lipofectin complex (MnSOD-PL) conferred radiation protection on irradiated recipient mice. To assess the intrinsic role of elevated MnSOD or catalase in HSCs and hematopoietic progenitor cells, the MnSOD or catalase gene was overexpressed in mouse hematopoietic cells via retroviral transduction. The impact of MnSOD and catalase on hematopoietic progenitor cells was mild, as measured by colony-forming units (CFUs). However, overexpressed catalase had a significant beneficial effect on long-term engraftment of transplanted HSCs, and this effect was further enhanced after an insult of low-dose γ-irradiation in the transplant mice. In contrast, overexpressed MnSOD exhibited an insignificant effect on long-term engraftment of transplanted HSCs, but had a significant beneficial effect after an insult of sublethal irradiation. Taken together, these results demonstrate that HSC function can be enhanced by ectopic expression of ROS-detoxifying enzymes, especially after radiation exposure in vivo.


Asunto(s)
Catalasa/metabolismo , Células Madre Hematopoyéticas/citología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Western Blotting , Catalasa/genética , Femenino , Citometría de Flujo , Regulación de la Expresión Génica , Vectores Genéticos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de la radiación , Humanos , Ratones , Ratones Endogámicos C57BL , Oxidación-Reducción , Retroviridae/genética , Células Madre , Superóxido Dismutasa/genética , Transducción Genética
9.
Sci Immunol ; 8(81): eabn6429, 2023 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-36930730

RESUMEN

Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted HSPCs underwent rapid and measurable changes during the first 30 days after transplantation, characterized by a strong proliferative response on the first day. Transcriptomic analysis of HSPCs enabled us to observe that immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family were enriched in granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) infused fewer S100Ahigh immunoregulatory neutrophil progenitors, immunophenotyped as Lin-CD34+CD66b+CD177+, than those who did not develop aGVHD. Therefore, our study provides insights into the regenerative process of transplanted HSPCs in human patients and identifies a potential criterion for identifying patients at high risk for developing aGVHD early after transplant.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Factor Estimulante de Colonias de Granulocitos , Células Madre Hematopoyéticas , Antígenos CD34/análisis
10.
iScience ; 26(12): 108561, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38144459

RESUMEN

Hematopoietic stem cell (HSC) surface markers improve the understanding of cell identity and function. Here, we report that human HSCs can be distinguished by their expression of the CEA Cell Adhesion Molecule 5 (CEACAM5, CD66e), which serves as a marker and a regulator of HSC function. CD66e+ cells exhibited a 5.5-fold enrichment for functional long term HSCs compared to CD66e- cells. CD66e+CD34+CD90+CD45RA- cells displayed robust multi-lineage repopulation and serial reconstitution ability in immunodeficient mice compared to CD66e-CD34+CD90+CD45RA-cells. CD66e expression also identified almost all repopulating HSCs within the CD34+CD90+CD45RA- population. Together, these results indicated that CEACAM5 is a marker that enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

11.
Stem Cell Rev Rep ; 18(4): 1322-1336, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35318612

RESUMEN

Residing at the apex of the hematopoietic hierarchy, hematopoietic stem and progenitor cells (HSPCs) give rise to all mature blood cells. In the last decade, significant progress has been made in single-cell RNA sequencing as well as multi-omics technologies that have facilitated elucidation of the heterogeneity of previously defined human HSPCs. From the embryonic stage through the adult stage to aging, single-cell studies have enabled us to trace the origins of hematopoietic stem cells (HSCs), demonstrating different hematopoietic differentiation during development, as well as identifying novel cell populations. In both hematological benign diseases and malignancies, single-cell omics technologies have begun to reveal tissue heterogeneity and have permitted mapping of microenvironmental ecosystems and tracking of cell subclones, thereby greatly broadening our understanding of disease development. Furthermore, advances have also been made in elucidating the molecular mechanisms for relapse and identifying therapeutic targets of hematological disorders and other non-hematological diseases. Extensive exploration of hematopoiesis at the single-cell level may thus have great potential for broad clinical applications of HSPCs, as well as disease prognosis.


Asunto(s)
Ecosistema , Hematopoyesis , Adulto , Diferenciación Celular/genética , Hematopoyesis/genética , Células Madre Hematopoyéticas , Humanos
12.
Commun Biol ; 5(1): 303, 2022 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-35379890

RESUMEN

Light, a crucial environmental signal, is involved in the regulation of secondary metabolites. To understand the mechanism by which light influences carotenoid metabolism, grapefruits were bagged with four types of light-transmitting bags that altered the transmission of solar light. We show that light-transmitting bagging induced changes in carotenoid metabolism during fruit ripening. Compared with natural light, red light (RL)-transmittance treatment significantly increases the total carotenoid content by 62%. Based on weighted gene co-expression network analysis (WGCNA), 'blue' and 'turquoise' modules are remarkably associated with carotenoid metabolism under different light treatment (p < 0.05). Transcriptome analysis identifies transcription factors (TFs) bHLH128, NAC2-like/21/72, MYB-like, AGL11/AGL61, ERF023/062, WRKY20, SBPlike-7/13 as being involved in the regulation of carotenoid metabolism in response to RL. Under RL treatment, these TFs regulate the accumulation of carotenoids by directly modulating the expression of carotenogenic genes, including GGPPS2, PDS, Z-ISO, ZDS2/7, CRTISO3, CYP97A, CHYB, ZEP2, CCD1-2. Based on these results, a network of the regulation of carotenoid metabolism by light in citrus fruits is preliminarily proposed. These results show that RL treatments have great potential to improve coloration and nutritional quality of citrus fruits.


Asunto(s)
Citrus paradisi , Carotenoides/metabolismo , Citrus paradisi/metabolismo , Frutas/genética , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas , Luz
13.
Dev Cell ; 57(24): 2745-2760.e6, 2022 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-36493772

RESUMEN

Hematopoietic stem and progenitor cells (HSPCs) give rise to the blood system and maintain hematopoiesis throughout the human lifespan. Here, we report a transcriptional census of human bone-marrow-derived HSPCs from the neonate, infant, child, adult, and aging stages, showing two subpopulations of multipotent progenitors separated by CD52 expression. From birth to the adult stage, stem and multipotent progenitors shared similar transcriptional alterations, and erythroid potential was enhanced after the infant stage. By integrating transcriptome, chromatin accessibility, and functional data, we further showed that aging hematopoietic stem cells (HSCs) exhibited a bias toward megakaryocytic differentiation. Finally, in comparison with the HSCs from the cord blood, neonate bone-marrow-derived HSCs were more quiescent and had higher long-term regeneration capability and durable self-renewal. Taken together, this work provides an integral transcriptome landscape of HSPCs and identifies their dynamics in post-natal steady-state hemopoiesis, thereby helping explore hematopoiesis in development and diseases.


Asunto(s)
Hematopoyesis , Células Madre Hematopoyéticas , Niño , Humanos , Recién Nacido , Diferenciación Celular , Células Madre Hematopoyéticas/metabolismo , Lactante , Adulto , Anciano
14.
Blood Adv ; 6(2): 441-451, 2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34653241

RESUMEN

Single-cell analysis is of significant importance in delineating the exact phylogeny of the subclonal population and in discovering subtle diversification. So far, studies of intratumor heterogeneity and clonal evolution in multiple myeloma (MM) were largely focused on the bulk tumor population level. We performed quantitative multigene fluorescence in situ hybridization (QM-FISH) in 129 longitudinal samples of 57 MM patients. All the patients had newly diagnosed and relapsed paired samples. An expanded cohort of 188 MM patients underwent conventional FISH (cFISH) to validate the cytogenetic evolution in bulk tumor level. Forty-three of 57 patients (75.4%) harbored 3 or 4 cytogenetic clones at diagnosis. We delineated the phylogeny of the subclonal tumor population and derived the evolutionary architecture in each patient. Patients with clonal stabilization had a significantly improved overall survival (OS) than those with other evolutionary patterns (median OS, 71.2 months vs 39.7 months vs 35.2 months vs 25.5 months, for stable, differential, branching, and linear patterns, respectively; P = .001). A high degree of consistency and complementarity across QM-FISH and cFISH was observed in the evaluation of cytogenetic evolution patterns in MM. Survival after relapse was greater influenced by the presence of high-risk aberrations at relapse (hazard ratio = 2.07) rather than present at diagnosis (hazard ratio = 1.55). This study shows that QM-FISH is a valuable tool to elucidate the clonal architecture at the single-cell level. Clonal evolution pattern is of prognostic significance, highlighting the need for repeated cytogenetic evaluation in relapsed MM.


Asunto(s)
Mieloma Múltiple , Aberraciones Cromosómicas , Humanos , Hibridación Fluorescente in Situ , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia , Filogenia
15.
Natl Sci Rev ; 8(3): nwaa180, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34691592

RESUMEN

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors. With high sequencing depth and coverage, we constructed a single-cell transcriptional atlas of blood cells (ABC) on the basis of both protein-coding genes and long noncoding RNAs (lncRNAs), and showed a high consistence between them. Notably, putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified. While common transcription factor regulatory networks were activated in neutrophils and monocytes, lymphoid cells dramatically changed their regulatory networks during differentiation. Furthermore, we showed a subset of nucleated erythrocytes actively expressing immune signals, suggesting the existence of erythroid precursors with immune functions. Finally, a web portal offering transcriptome browsing and blood cell type prediction has been established. Thus, our work provides a transcriptional map of human blood cells at single-cell resolution, thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

16.
Artif Cells Nanomed Biotechnol ; 48(1): 336-344, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31884829

RESUMEN

Cytoplasmic p27 plays an important role in regulating the cell cycle. Recent studies have revealed p27 protein translocation from the nucleus to the cytoplasm in many tumour cells. The aim of this study was to investigate the role and molecular mechanisms of cytoplasmic p27 in the progression of nasopharyngeal carcinoma (NPC) and to explore its prognostic value. We found increased cytoplasmic p27 expression by immunohistochemistry in NPC tissues, and its expression level was significantly correlated with the T classification and TNM clinical stage of NPC. The survival rate was significantly lower for NPC patients with cytoplasmic p27 immunopositivity than for NPC patients with cytoplasmic p27 immunonegativity, and cytoplasmic p27 was an independent risk factor that affected the prognosis of patients with NPC. Cytoplasmic p27 promoted the proliferation, cell cycle progression, migration, and invasion of NPC cells, increased Bim-1 and Twist1 protein levels, and decreased RhoA-GTP level. Collectively, these findings suggest that cytoplasmic relocalization of p27 is involved in the pathogenesis of NPC and is closely related to the unfavourable prognosis of patients with NPC. Therefore, cytoplasmic p27 might be a useful prognostic factor and potential therapeutic target for patients with NPC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Citoplasma/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Adulto , Anciano , Línea Celular Tumoral , Citoplasma/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , Pronóstico
18.
Bone Marrow Transplant ; 55(6): 1029-1040, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31804621

RESUMEN

The bone marrow (BM) niche regulates multiple hematopoietic stem cell (HSC) processes. Clinical treatment for hematological malignancies by HSC transplantation often requires preconditioning via total body irradiation, which severely and irreversibly impairs the BM niche and HSC regeneration. Novel strategies are needed to enhance HSC regeneration in irradiated BM. We compared the effects of EGF, FGF2, and PDGFB on HSC regeneration using human mesenchymal stem cells (MSCs) that were transduced with these factors via lentiviral vectors. Among the above niche factors tested, MSCs transduced with PDGFB (PDGFB-MSCs) most significantly improved human HSC engraftment in immunodeficient mice. PDGFB-MSC-treated BM enhanced transplanted human HSC self-renewal in secondary transplantations more efficiently than GFP-transduced MSCs (GFP-MSCs). Gene set enrichment analysis showed increased antiapoptotic signaling in PDGFB-MSCs compared with GFP-MSCs. PDGFB-MSCs exhibited enhanced survival and expansion after transplantation, resulting in an enlarged humanized niche cell pool that provide a better humanized microenvironment to facilitate superior engraftment and proliferation of human hematopoietic cells. Our studies demonstrate the efficacy of PDGFB-MSCs in supporting human HSC engraftment.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Células Madre Mesenquimatosas , Animales , Médula Ósea , Células Madre Hematopoyéticas , Humanos , Ratones , Proteínas Proto-Oncogénicas c-sis
19.
Oxid Med Cell Longev ; 2019: 5153268, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31827678

RESUMEN

Hematopoietic stem cells (HSCs) are characterized by self-renewal and multilineage differentiation potentials. Although they play a central role in hematopoietic homeostasis and bone marrow (BM) transplantation, they are affected by multiple environmental factors in the BM. Here, we review the effects of reactive oxygen species (ROS) and Nrf2 on HSC function and BM transplantation. HSCs reside in the hypoxic microenvironment of BM, and ROS play an important role in HSPC regulation. Recently, an extraphysiologic oxygen shock/stress phenomenon was identified in human cord blood HSCs collected under ambient air conditions. Moreover, Nrf2 has been recently recognized as a master transcriptional factor that regulates multiple antioxidant enzymes. Since several years, the role of Nrf2 in hematopoiesis has been extensively studied, which has functional similarities of cellular oxygen sensor hypoxia-inducible factor-1 as transcriptional factors. Increasing evidence has revealed that abnormally elevated ROS production due to factors such as genetic defects, aging, and ionizing radiation unexceptionally resulted in lethal impairment of HSC function and hematopoiesis. Both experimental and clinical studies have identified elevated ROS levels as a major culprit of ineffective BM transplantation. Lastly, we discuss the possibility of using small molecule antioxidants, such as N-acetyl cysteine, resveratrol, and curcumin, to augment HSC function and improve the therapeutic efficacy of BM transplantation. Further research on the function of ROS levels and improving the efficacy of BM transplantation may have a great potential for broad clinical applications of HSCs.


Asunto(s)
Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Antioxidantes/química , Antioxidantes/metabolismo , Trasplante de Médula Ósea , Hematopoyesis , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , NADPH Oxidasas/metabolismo , Factor 2 Relacionado con NF-E2/genética , Oxidorreductasas/metabolismo , Especies Reactivas de Oxígeno/química
20.
Medicine (Baltimore) ; 97(4): e9680, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29369187

RESUMEN

The objective of the present study was to investigate the clinical application of magnetic resonance imaging (MRI)-respiratory gating technology for assessing illness severity in children with obstructive sleep apnea hypopnea syndrome (OSAHS).MRI-respiratory gating technology was used to scan the nasopharyngeal cavities of 51 children diagnosed with OSAHS during 6 respiratory phases. Correlations between the ratio of the area of the adenoid to the area of the nasopalatine pharyngeal cavity (Sa/Snp), with the main indexes of polysomnography (PSG), were analyzed. Receiver operator characteristic (ROC) curve and Kappa analysis were used to determine the diagnostic accuracy of Sa/Snp in pediatric OSAHS.The Sa/Snp was positively correlated with the apnea hypopnea index (AHI) (P < .001) and negatively correlated with the lowest oxygen saturation of blood during sleep (LaSO2) (P < .001). ROC analysis in the 6 respiratory phases showed that the area under the curve (AUC) of the Sa/Snp in the end-expiratory phase was the largest (0.992, P < .001), providing a threshold of 69.5% for the diagnosis of severe versus slight-moderate OSAHS in children. Consistency analysis with the AHI showed a diagnosis accordance rate of 96.0% in severe pediatric OSAHS and 96.2% in slight-moderate pediatric OSAHS (Kappa = 0.922, P < .001).Stenosis of the nasopalatine pharyngeal cavity in children with adenoidal hypertrophy was greatest at the end-expiration phase during sleep. The end-expiratory Sa/Snp obtained by a combination of MRI and respiratory gating technology has potential as an important imaging index for diagnosing and evaluating severity in pediatric OSAHS.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Técnicas de Imagen Sincronizada Respiratorias/métodos , Apnea Obstructiva del Sueño/diagnóstico por imagen , Tonsila Faríngea/diagnóstico por imagen , Tonsila Faríngea/fisiopatología , Adolescente , Área Bajo la Curva , Niño , Preescolar , Femenino , Humanos , Masculino , Nasofaringe/diagnóstico por imagen , Nasofaringe/fisiopatología , Polisomnografía , Curva ROC , Respiración , Índice de Severidad de la Enfermedad , Sueño
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA