We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro.The capacities for mammosphere formation and STAT3 expression of CD44+CD24-/low MCF-7 and MCF-7 were observed.Th...We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro.The capacities for mammosphere formation and STAT3 expression of CD44+CD24-/low MCF-7 and MCF-7 were observed.The CD44+CD24-/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant(TAM-R) cells.Cell cycle,apoptosis,STAT3 and phospho-STAT3 changes were observed af-ter treatment with tamoxifen.Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed.CD44+CD24-/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7.The CD44+CD24-/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7.Cell cycle changes,anti-apoptotic effects and STAT3 changes were also found.Mean-while,the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen.It is concluded that STAT3 plays an essential role in breast cancer stem cells,which correlated with tamoxifen resistance.展开更多
Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells (GM-CSF-BMSCs) into the ischemic boundary zone at 24 hours after onset of mi...Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells (GM-CSF-BMSCs) into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion. Results showed reduced infarct volume, decreased number of apoptotic cells, improved neurological functions, increased angiogenic factor expression, and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group. Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.展开更多
Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Mel...Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma(SKCM)were downloaded from the UCSC XENA website(http://xena.ucsc.edu/).Subsequently,transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus(GEO),a large global public database.All the transcriptome expression data matrices were log2 transformed for subsequent analysis.GEPIA,TIMER,and IMMPORT databases are also used for analysis.Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375.Results:Our study provides potential tumor antigens for vaccine development in melanoma patients:GZMB,GBP4,CD79A,APOBEC3F,IDO1,JCHAIN,LAG3,PLA2G2D,XCL2.In addition,we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination.In view of the unclear role of IDO1 in melanoma,we selected IDO1 for cell assay validation.Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line.After IDO1 knockdown,the activity,invasion,migration and healing ability of A375 cell lines were significantly decreased.Conclusion:Our study could provide a reference for the development of vaccines for melanoma patients.展开更多
Academic procrastination among adolescents is an increasingly prominent problem. It is important to look forinfluences behind academic procrastination in the adolescent population. The present study aimed to revealthe...Academic procrastination among adolescents is an increasingly prominent problem. It is important to look forinfluences behind academic procrastination in the adolescent population. The present study aimed to revealthe explanatory mechanisms underlying the association between hope and academic procrastination behaviorsamong Chinese adolescents by testing the mediating role of attentional control and the moderating role of traitmindfulness. Participants in the current study were 1156 Chinese adolescents who completed self-report questionnaireson hope, attentional control, academic procrastination, and trait mindfulness. The results indicatedthat adolescent hope was negatively related to academic procrastination and that attentional control partiallymediated this association. In addition, trait mindfulness moderated the direct association between hope and academicprocrastination in the mediated model. In conclusion, identifying the mechanisms by which hope is associatedwith academic procrastination in adolescent populations is of potential value for the prevention of andintervention in this undesirable study habit.展开更多
Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progr...Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.展开更多
文摘We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro.The capacities for mammosphere formation and STAT3 expression of CD44+CD24-/low MCF-7 and MCF-7 were observed.The CD44+CD24-/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant(TAM-R) cells.Cell cycle,apoptosis,STAT3 and phospho-STAT3 changes were observed af-ter treatment with tamoxifen.Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed.CD44+CD24-/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7.The CD44+CD24-/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7.Cell cycle changes,anti-apoptotic effects and STAT3 changes were also found.Mean-while,the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen.It is concluded that STAT3 plays an essential role in breast cancer stem cells,which correlated with tamoxifen resistance.
基金supported by a grant from "135 Project" Foundation of the Public Health Department of Jiangsu Province,ChinaNanjing Medical Science and Technique Development Foundation
文摘Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells (GM-CSF-BMSCs) into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion. Results showed reduced infarct volume, decreased number of apoptotic cells, improved neurological functions, increased angiogenic factor expression, and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group. Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.
基金supported by the Top Talent Project of Jiangsu Provincial People’s Hospital(No.YNRCZN0310).
文摘Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma(SKCM)were downloaded from the UCSC XENA website(http://xena.ucsc.edu/).Subsequently,transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus(GEO),a large global public database.All the transcriptome expression data matrices were log2 transformed for subsequent analysis.GEPIA,TIMER,and IMMPORT databases are also used for analysis.Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375.Results:Our study provides potential tumor antigens for vaccine development in melanoma patients:GZMB,GBP4,CD79A,APOBEC3F,IDO1,JCHAIN,LAG3,PLA2G2D,XCL2.In addition,we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination.In view of the unclear role of IDO1 in melanoma,we selected IDO1 for cell assay validation.Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line.After IDO1 knockdown,the activity,invasion,migration and healing ability of A375 cell lines were significantly decreased.Conclusion:Our study could provide a reference for the development of vaccines for melanoma patients.
文摘Academic procrastination among adolescents is an increasingly prominent problem. It is important to look forinfluences behind academic procrastination in the adolescent population. The present study aimed to revealthe explanatory mechanisms underlying the association between hope and academic procrastination behaviorsamong Chinese adolescents by testing the mediating role of attentional control and the moderating role of traitmindfulness. Participants in the current study were 1156 Chinese adolescents who completed self-report questionnaireson hope, attentional control, academic procrastination, and trait mindfulness. The results indicatedthat adolescent hope was negatively related to academic procrastination and that attentional control partiallymediated this association. In addition, trait mindfulness moderated the direct association between hope and academicprocrastination in the mediated model. In conclusion, identifying the mechanisms by which hope is associatedwith academic procrastination in adolescent populations is of potential value for the prevention of andintervention in this undesirable study habit.
基金funded by the National Natural Science Foundation of China(81270408,81570666,81730041,and 81671447)the International Society of Nephrology(ISN)Clinical Research Program(18-01-0247)+7 种基金Construction Program of Jiangsu Provincial Clinical Research Center Support System(BL2014084)Jiangsu Province Key Medical Personnel Project(ZDRCA2016002)CKD Anemia Research Foundation from China International Medical Foundation(Z-2017-24-2037)Outstanding Young and Middle-Aged Talents Support Program of The First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital)the National Key Research and Development Program of China(2017YFC1001303)the Program of Jiangsu Province Clinical Medical Center(YXZXB2016001,BL2012009)the State Key Laboratory of Reproductive Medicine Program(SKLRM-GC201803)the Program of Jiangsu Commission of Health(H201605).
文摘Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.