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Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes , Dexametasona , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sulfonamidas , Humanos , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Anciano , Resultado del TratamientoRESUMEN
Abstract@#Early rehabilitation activity is an important way to improve functional impairment in stroke patients. However, there are no clear standards and opinions on the optimal start time, dosage and frequency of early rehabilitation activity. It is generally believed that early rehabilitation activity should start at 24 to 48 hours after stroke, and individual programs should be developed according to the assessment of stroke type, severity of disease, tolerance degree and other factors. This review searches domestic and international literature related to early rehabilitation activity and summarizes the start time, dose, frequency and content of early rehabilitation activity, as well as the cognition and attitude of medical workers towards it, so as to provide insights into studies and clinical applications of early rehabilitation activity.
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BACKGROUND AND AIMS: DILI accounts for more than half of acute liver failure cases in the United States and is a major health care issue for the public worldwide. As investigative toxicology is playing an evolving role in the pharmaceutical industry, mechanistic insights into drug hepatotoxicity can facilitate drug development and clinical medication. METHODS: By integrating multisource datasets including gene expression profiles of rat livers from open TG-GATE database and DrugMatrix, drug labels from FDA Liver Toxicity Knowledge Base, and clinical reports from LiverTox, and with the employment of bioinformatic and computational tools, this study developed an approach to characterize and predict DILI based on the molecular understanding of the processes (toxicity pathways). RESULTS: A panel of 11 pathways widely covering biological processes and stress responses was established using a training set of six positive and one negative DILI drugs from open TG-GATEs. An entropy weight method-based model was developed to weight responsive genes within a pathway, and an interpretable machine-learning (ML) model XGBoot-SHAP was trained to rank the importance of pathways to the panel activity. The panel activity was proven to differentiate between injured and noninjured sample points and characterize DILI manifestation using six training drugs. Next, the model was tested using an additional 89 drugs (61 positives + 28 negatives), and a precision of 86% and higher can be achieved. CONCLUSIONS: This study provides a novel approach to mechanisms-driven prediction modeling, as well as big data integration for insights into pharmacology and other human biology areas.
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Few studies have examined the role of cognitive control in processing ambiguity, let alone the roles of different components of cognitive control. In the current study, the English (L2) Sentence Processing Task and a series of cognitive control tasks were administered among 111 young adult Chinese-English bilinguals to investigate the influence of different components of cognitive control on garden path sentence comprehension, with other factors such as age, socio-economic status, and language proficiency strictly matched. Data analysis results showed a significant garden path effect on response times (RTs) and accuracy among all the participants. The results of independent t-test analyses revealed that the high working memory (WM) group was faster in ambiguity resolution, and so was the high monitoring group. However, there were no differences between the high and low inhibition and shifting groups in ambiguity resolution. These findings reveal that only certain aspects of cognitive control influence garden path sentence comprehension.
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The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly around the world and has led to millions of infections and deaths. Growing evidence indicates that iron metabolism is associated with COVID-19 progression, and iron-related biomarkers have great potential for detecting these diseases. However, the results of previous studies are conflicting, and there is not consistent numerical magnitude relationship between those biomarkers and COVID-19. Thereby, we aimed to integrate the results of current studies and to further explore their relationships through a meta-analysis. We searched peer-reviewed literature in PubMed, Scopus and Web of Science up to 31 May 2022. A random effects model was used for pooling standard mean difference (SMD) and the calculation of the corresponding 95% confidence interval (CI). I2 was used to evaluate heterogeneity among studies. A total of 72 eligible articles were included in the meta-analysis. It was found that the ferritin levels of patients increased with the severity of the disease, whereas their serum iron levels and hemoglobin levels showed opposite trends. In addition, non-survivors had higher ferritin levels (SMD (95%CI): 1.121 (0.854, 1.388); Z = 8.22 p for Z < 0.001; I2 = 95.7%, p for I2 < 0.001), lower serum iron levels (SMD (95%CI): −0.483 (−0.597, −0.368), Z = 8.27, p for Z < 0.001; I2 = 0.9%, p for I2 =0.423) and significantly lower TIBC levels (SMD (95%CI): −0.612 (−0.900, −0.324), Z = 4.16, p for Z < 0.001; I2 = 71%, p for I2 = 0.016) than survivors. This meta-analysis demonstrates that ferritin, serum iron, hemoglobin and total iron banding capacity (TIBC) levels are strongly associated with the risk, severity and mortality of COVID-19, providing strong evidence for their potential in predicting disease occurrence and progression.
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COVID-19 , SARS-CoV-2 , Biomarcadores , COVID-19/mortalidad , Ferritinas , Hemoglobinas/metabolismo , Humanos , HierroRESUMEN
With the increasingly prominent energy and environmental problems, environmental innovation has become a critical path to achieving the goal of coordinating economic development and environmental protection fundamentally. This study aims to examine the impacts of executive overconfidence on environmental innovation and the mediating role of digital transformation. We conduct empirical tests based on the panel data of Chinese publicly listed enterprises during the period of 2007-2019. The results exhibit that (a) executive overconfidence can significantly promote environmental technology innovation but has no obvious effect on environmental management innovation; (b) executive overconfidence can significantly enhance digital transformation, and, accordingly, digital transformation can significantly promote environmental technology innovation and environmental management innovation; (c) industry competition and economic policy uncertainty can enhance the positive effect of executive overconfidence on digital transformation; and (d) a firms' asset size can enhance the impact of digital transformation on environmental technology innovation; internal control positively moderates the impact of digital transformation on environmental technology innovation and negatively moderates the impact on environmental management innovation. This study not only breaks the stereotype about overconfidence and confirms its positive impact on digital transformation and environmental innovation but also provides insights for enterprises to improve environmental innovation through digital transformation.
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Desarrollo Económico , Invenciones , Conservación de los Recursos Naturales , IndustriasRESUMEN
Although a firm's exposure to air pollution-related risk has become an important factor that creditors cannot ignore in the procedure of lending decision making with the aggravation of air pollution, empirical evidence on whether and how air pollution affects the cost of debt has been relatively scarce. Employing a series of Chinese listed firms from the main board of the Shanghai and Shenzhen Stock Exchanges covering 2014 to 2018, our research responds to this research gap by exploring how air pollution-induced environmental violation risk affects the cost of debt by constructing an assessment system of firms' environmental violation risk. The results shed light on an issue that firms exposed to higher concentrations of air pollution may suffer a higher environmental violation risk, resulting in a higher debt cost. In addition, a further analysis shows that environmental regulatory pressure and heavily polluting firms enhance the influence of air pollution on the cost of debt, while state-owned firms and firms' economic contributions weaken the influence of air pollution on the cost of debt. Our research is conducive to highlighting not only the importance of environmental governance for mitigating the cost of debt to the firms exposed to air pollution, but also its importance to creditors exposed to their clients' environmental violation risk and default risk.
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Contaminación del Aire , Política Ambiental , Contaminación del Aire/efectos adversos , China , Conservación de los Recursos Naturales , Contaminación Ambiental/efectos adversos , HumanosRESUMEN
Previous studies have suggested a bilingual advantage in cognitive control as a result of the bilinguals' language experience. However, the results are controversial as there are various factors (language proficiency, SES, culture, and intelligence, etc.) affecting cognitive control. In the current study, after between-group comparisons, we adopted a within-group approach by multiple regressions to investigate whether the performance by 10-to-75-year-old participants (N = 91) of tasks measuring inhibition, monitoring, and mental set shifting could be predicted by bilingualism, or demographic factors, or both. The results of multiple stepwise regression analyses showed that L2 proficiency was a significant predictor for conflict monitoring and inhibition, education and age were significant predictors for mental set shifting, and SES was a minor predictor for inhibition. These findings provide evidence that cognitive control is affected by both bilingualism and demographic factors. Future studies are encouraged to further identify the relationship between bilingualism and cognitive control from specific bilingual experience.
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Enterovirus A71 (EV-A71) is a major etiological agent of human hand, foot and mouth disease, and it can cause severe neurological complications. Although several genotypes of EV-A71 strains are prevalent in different regions of the world, the genotype C4 has circulated in mainland China for more than 20 years. The pathogenicity of different EV-A71 clinical isolates varies and needs to be explored. In this study, hSCARB2 knock-in mice (N = 181) with a wide range of ages were tested for their susceptibility to two EV-A71 strains with the subgenotypes C4 and C2, and two infection routes (intracranial and venous) were compared. The clinical manifestations and pathology and their relationship to the measured viral loads in different tissues were monitored. We observed that 3 weeks is a crucial age, as mice younger than 3-week-old that were infected became extremely ill. However, mice older than 3 weeks displayed diverse clinical symptoms. Significant differences were observed in the pathogenicity of the two strains with respect to clinical signs, disease incidence, survival rate, and body weight change. We concluded that hSCARB2 knock-in mice are a sensitive model for investigating the clinical outcomes resulting from infection by different EV-A71 strains. The intracranial infection model appears to be suitable for evaluating EV-A71 neurovirulence, whereas the venous infection model is appropriate for studying the pathogenicity of EV-A71.
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Encéfalo/virología , Modelos Animales de Enfermedad , Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/virología , Proteínas de Membrana de los Lisosomas/genética , Receptores Depuradores/genética , Administración Intravenosa , Factores de Edad , Animales , Antígenos Virales/genética , Enterovirus Humano A/genética , Infecciones por Enterovirus/sangre , Técnicas de Sustitución del Gen , Genotipo , Humanos , Ratones , Cráneo/virología , Carga Viral , VirulenciaRESUMEN
BACKGROUND: Real-time polymerase chain reaction (PCR) has become an increasingly important technique for gene expression profiling because it can provide insights into complex biological and pathological processes and be used to predict disease or treatment outcomes. Although normalized data are necessary for an accurate estimation of mRNA expression levels, several pieces of evidence suggest that the expression of so-called housekeeping genes is not stable. This study aimed to validate reference genes for the normalization of real-time PCR in an N-methyl-N-nitrosourea (MNU)-induced T-cell lymphoma mouse model. METHODS: T-cell lymphomas were generated in p53-deficient mice by treatment with 37.5 mg/kg MNU. Thymus and spleen were identified as the primary target organs with the highest incidences of lymphomas. We analyzed the RNA expression levels of eight potential endogenous reference genes (Gapdh, Rn18s, Actb, Hprt, B2M, Rplp0, Gusb, Ctbp1). The expression stabilities of these reference genes were tested at different time points after MNU treatment using geNorm and NormFinder algorithms. RESULTS: A total of 65% of MNU-treated mice developed T-cell lymphomas, with the spleen and thymus as the major target organs. All candidate reference genes were amplified efficiently by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Gene stability evaluation after MNU treatment and during lymphomagenesis revealed that Ctbp1 and Rplp0 were the most stably expressed genes in the thymus and spleen, respectively. RT-PCR of thymus RNA using two additional sets of primer confirmed that Ctbp1 was the most stable of all the candidate reference genes. CONCLUSIONS: We provided suitable endogenous controls for gene expression studies in the T-cell lymphoma model.
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Oxidorreductasas de Alcohol/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Genes Esenciales , Linfoma de Células T/genética , Metilnitrosourea/toxicidad , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Proteínas Ribosómicas/genética , Animales , Modelos Animales de Enfermedad , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/metabolismo , Ratones , Ratones Noqueados , Proteína p53 Supresora de Tumor/genéticaRESUMEN
As concerns increase about adenovirus type 5 (Ad5) being a safe gene transfer vector, it is important to evaluate its distribution, residence time, and possible toxicity in immunodeficient populations. To characterize the potential risk associated with different Ad5 vector delivery modes, we used immunocompetent and immunodeficient Rag2 -/- animals to establish mouse and rat models that could be monitored with bioluminescent imaging following intramuscular or intravascular infection with an engineered replication-incompetent Ad5 virus carrying the firefly luciferase gene (Ad5-Fluc). The Ad5 vector was less well-tolerated by Rag2 -/- animals than by wildtype ones, with delayed residence time, wider virus dissemination, less weight gain, and relatively severe pathological changes. In intravascularly Ad5-Fluc-infected Rag2 -/- mice, systemic virus dissemination extended from the abdomen to the limbs and head on day 9 post-infection. Additionally, significant increases in plasma TNF-α and IFN-γ, which may be important factors in the heightened immunopathology in the liver and brain, were detected in the Rag2 -/- mice 30 days after intravascular delivery. The Ad5 vector was better tolerated after intramuscular delivery than after intravascular delivery. Ad5-Fluc/Rag2 -/- mice and rats can be used as reliable models of an immunodeficient population in which to evaluate the safety of Ad5-vectored vaccines or gene therapy products.
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Adenovirus Humanos/genética , Portadores de Fármacos/farmacocinética , Vectores Genéticos/farmacocinética , Mediciones Luminiscentes , Administración Intravenosa , Animales , Portadores de Fármacos/administración & dosificación , Genes Reporteros , Vectores Genéticos/administración & dosificación , Inyecciones Intramusculares , Luciferasas de Luciérnaga/análisis , Ratones , Ratas , Coloración y Etiquetado , Factores de Tiempo , Imagen de Cuerpo EnteroRESUMEN
The inclusion complexation behavior, characterization, and inclusion mode of podophyllotoxin (POD) with hydroxypropyl-ß-cyclodextrin (HPßCD) were investigated in both solution and the solid state by means of XRD, DSC, SEM, 1H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and thermal stability of POD were obviously increased in the inclusion complex with HPßCD. The cytotoxicity of POD/HPßCD inclusion complex against all the human tumor cell lines investigated still remains. This satisfactory water solubility and high thermal stability of the POD/HPßCD complex will be potentially useful for their application as herbal medicines or healthcare products.
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2-Hidroxipropil-beta-Ciclodextrina/química , Podofilotoxina/química , Rastreo Diferencial de Calorimetría , Línea Celular Tumoral , Humanos , SolubilidadRESUMEN
Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. The in vivo treatment efficiencies of three novel anti-EBOV mAbs at 12 h post-infection correlated with their in vitro anti-EBOV ADCC activities, without neutralizing activity. When they were treated with these mAbs, natural killer cell (NK)-deficient mice had lower viral clearance than WT mice, indicating that the anti-EBOV mechanism of the ADCC activity of these mAbs is predominantly mediated by NK cells. One potent anti-EBOV mAb (M318) displayed unprecedented neutralizing and ADCC activities (neutralization IC50, 0.018 µg/ml; ADCC EC50, 0.095 µg/ml). These results have important implications for the efficacy of antiviral drugs and vaccines as well as for pathogenicity studies of EBOV.
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Anticuerpos Monoclonales/inmunología , Citotoxicidad Celular Dependiente de Anticuerpos , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Fiebre Hemorrágica Ebola/inmunología , Animales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Antivirales/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Humanos , Células Asesinas Naturales/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
Enterovirus A71 infection has become a severe threat for global public health. Vaccines for controlling and preventing Enterovirus A71 epidemics are highly demanded, however, vaccine evaluation has been hindered by the lack of suitable Enterovirus A71 infection animal models. Here we established an hSCARB2 knockin mouse model for real-time monitoring of enterovirus A71 infection in vivo. This model was sensitive to the infection of both replication-competent virus rEV71(FY)-EGFP and single round pseudotype virus pEV71(FY)-Luc. The intensity of bioluminescence correlated well with viral loads in infected tissues (R=0.86, P<0.01). Pathological changes recapitulated human infectious and clinical features of enterovirus A71, including both general characteristics of "hand foot and mouth" and the severe symptoms in the CNS. A formalin-inactivated enterovirus A71 vaccine can elicit antibodies in R26-hSCARB2 mice, which play effective roles in protecting knockin mice against enterovirus A71 infection as indicated by bioluminescence. Therefore, this work provides a safe, sensitive and visualizing model for exploring mechanisms of enterovirus A71 infection and examining human enterovirus A71 vaccines and antiviral therapies.
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Modelos Animales de Enfermedad , Enfermedad de Boca, Mano y Pie/inmunología , Enfermedad de Boca, Mano y Pie/patología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Enterovirus Humano A , Femenino , Técnicas de Sustitución del Gen , Humanos , Mediciones Luminiscentes , Proteínas de Membrana de los Lisosomas/genética , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutagénesis Insercional , Receptores Depuradores/genética , Vacunas de Productos Inactivados/inmunología , Carga Viral , Vacunas Virales/inmunologíaRESUMEN
The inclusion complexation behavior, characterization and binding ability of hesperetin with ß-cyclodextrin and its derivatives were investigated in both the solution and solid state by means of XRD, DSC, SEM, (1)H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and stability of hesperetin were obviously increased in the inclusion complex with cyclodextrins. This satisfactory water solubility and high stability of the hesperetin/CD complexes will be potentially useful for their application as herbal medicines or healthcare products.
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Ciclodextrinas/química , Hesperidina/química , Estabilidad de Medicamentos , Resonancia Magnética Nuclear Biomolecular , SolubilidadRESUMEN
Due to the increasing concern of using smallpox virus as biological weapons for terrorist attack, there is renewed interest in studying the pathogenesis of human smallpox and development of new therapies. Animal models are highly demanded for efficacy and safety examination of new vaccines and therapeutic drugs. Here, we demonstrated that both wild type and immunodeficient rats infected with an engineered vaccinia virus carrying Firefly luciferase reporter gene (rTV-Fluc) could recapitulate infectious and clinical features of human smallpox. Vaccinia viral infection in wild type Sprague-Dawley (SD) rats displayed a diffusible pattern in various organs, including liver, head and limbs. The intensity of bioluminescence generated from rTV-Fluc correlated well with viral loads in tissues. Moreover, neutralizing antibodies had a protective effect against virus reinfection. The recombination activating gene 2 (Rag2) knockout rats generated by transcription activator-like effector nucleases (TALENs) technology were further used to examine the infectivity of the rTV-Fluc in immunodeficient populations. Here we demonstrated that Rag2-/- rats were more susceptible to rTV-Fluc than SD rats with a slower virus clearance rate. Therefore, the rTV-Fluc/SD rats and rTV-Fluc/Rag2-/- rats are suitable visualization models, which recapitulate wild type or immunodeficient populations respectively, for testing human smallpox vaccine and antiviral drugs.
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Viruela/patología , Virus Vaccinia/patogenicidad , Animales , Animales Modificados Genéticamente/genética , Animales Modificados Genéticamente/metabolismo , Anticuerpos Neutralizantes/uso terapéutico , Linfocitos B/citología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Secuencia de Bases , Chlorocebus aethiops , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Femenino , Genes Reporteros , Genotipo , Humanos , Huésped Inmunocomprometido , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Imagen Óptica , Ratas , Ratas Sprague-Dawley , Viruela/prevención & control , Viruela/virología , Linfocitos T/citología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Virus Vaccinia/genética , Células VeroRESUMEN
The inclusion complexation behavior, characterization and binding ability of naringenin with ß-cyclodextrin and its derivatives were investigated in both solution and the solid state by means of XRD, DSC, SEM, (1)H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and thermal stability of naringenin were obviously increased in the inclusion complex with cyclodextrins. This satisfactory water solubility and high thermal stability of the naringenin/CD complexes will be potentially useful for their application as herbal medicines or healthcare products.
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Flavanonas/química , Agua/química , beta-Ciclodextrinas/química , Disponibilidad Biológica , Flavanonas/farmacocinética , SolubilidadRESUMEN
Several research groups have suggested that the embryonic-abembryonic (Em-Ab) axis in the mouse can be predicted by the first cleavage plane of the early embryo. Currently, it is not known whether this early patterning occurs in cloned embryos produced by nuclear transfer and whether it affects development to term. In this work, the relationship between the first cleavage plane and the Em-Ab axis was determined by the labeling of one blastomere in cloned mouse embryos at the 2-cell stage, followed by ex-vivo tracking until the blastocyst stage. The results demonstrate that approximately half of the cloned blastocysts had an Em-Ab axis perpendicular to the initial cleavage plane of the 2-cell stage. These embryos were classified as "orthogonal" and the remainder as "deviant". Additionally, we report here that cloned embryos were significantly more often orthogonal than their naturally fertilized counterparts and overexpressed Sox2. Orthogonal cloned embryos demonstrated a higher rate of post-implantation embryonic development than deviant embryos, but cloned pups did not all survive. These results reveal that the angular relationship between the Em-Ab axis and the first cleavage plane can influence later development and they support the hypothesis that proper early patterning of mammalian embryos is required after nuclear transfer.
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Blastocisto/citología , Embrión de Mamíferos/citología , Embrión de Mamíferos/embriología , Desarrollo Embrionario , Animales , Blastocisto/metabolismo , Clonación de Organismos , Transferencia de Embrión , Embrión de Mamíferos/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Microscopía Confocal , Proteína Homeótica Nanog , Técnicas de Transferencia Nuclear , Factor 3 de Transcripción de Unión a Octámeros/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción SOXB1/genéticaRESUMEN
Recently, reprogramming of somatic cells from a differentiated to pluripotent state by overexpression of specific external transcription factors has been accomplished. It has been widely speculated that an undifferentiated state may make donor cells more efficient for nuclear transfer. To test this hypothesis, we derived induced pluripotent stem cells (iPS cells) from several somatic cell lines: mouse embryonic fibroblast (MEF), adult tail tip fibroblast (TTF), and brain neural stem cells (NSCs). Three dimensional (3D)-fluorescent in situ hybridization (FISH) and quantitative-FISH (Q-FISH) were then used to evaluate constitutive (pericentric and telomeric) heterochromatin organization in these iPS cells and in their parental differentiated cells. Here, we show that important nuclear remodeling and telomeres rejuvenation occur in these iPS cells regardless of their parental origin. When we used these cells as donors for nuclear transfer, we produced live-born cloned mice at much higher rates with the iPS-induced cells than with the parental cell lines. Interestingly, we noticed that developmental potential after nuclear transfer could be correlated with telomere length of the donor cells. Altogether, our findings suggest that constitutive heterochromatin organization from differentiated somatic cells can be reprogrammed to the pluripotent state by induction of iPS cells, which in turn support nuclear transfer procedure quite efficiently.