Human embryonic stem cells (HESCs) are defined as self-renewing cells that retain their ability to differentiate into all cell types of the body. They have enormous potential in medical applications and as a model for early human development. There is a need for derivation of new HESC lines to meet emerging requirements for their use in cell replacement therapies, disease modeling, and basic research. Here, we describe a modified culture medium containing human recombinant leukemia inhibitory factor and human basic fibroblast growth factor that significantly increases the number of human blastocysts formed and their quality, as well as the efficiency of HESC derivation from poor-quality embryos. Culturing poor-quality embryos in modified medium resulted in a two-fold increase in the blastocyst formation rate and a seven-fold increase over the derivation efficiency in conventional medium. We derived 15 HESC lines from poor-quality embryos cultured in modified culture medium and two HESC lines from quality embryos cultured in conventional culture medium. All cell lines shared typical human pluripotent stem cell features including similar morphology, normal karyotypes, expression of alkaline phosphatase, pluripotency genes, such as Oct4, and cell surface markers (SSEA-4, TRA-1-60, TRA-1-81), the ability to form teratomas in SCID mice, and the ability to differentiate into cells of three embryonic germ layers in vitro. Our data suggest that poor-quality embryos that have reached the blastocyst stage in our modified culture medium are a robust source for normal HESC line derivation.
Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion–negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA / B , platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.
Objective In order to exam the effect of different temperature on spindle.Methods Mouse oocytes with or without polarbody were exposed to shifts from(37 ℃)(control),then to(38 ℃),(39 ℃),(40 ℃),(41 ℃) or(45 ℃);(35 ℃),(30 ℃) or(25 ℃) for(10 min) separately,the spindles were imaged with the LC-PolscopeTM.Results Spindles were intact at(37 ℃) during(20 min) of examination.The spindles in KM mouse oocytes were damaged at(45 ℃).The Retardance of Balb/C mouse MI oocytes which from(41 ℃) returened to(37 ℃) was significant different from those of other groups(P0.05).Cooling to(25 ℃),spindles were significant different from the spindles imaged before or after cooling(P0.05).Conclusion These results indicate that spindles in mouse oocytes are extremely sensitive to temperature changes. Moreover,maintenance of in vitro manipulation temperature at(37 ℃) is crucial for normal spindle function.
Glia maturation factor-beta: a potential therapeutic target in neurodegeneration and neuroinflammation Junsheng Fan,1,2,* Tszhei Fong,1,* Xinjie Chen,3,* Chuyun Chen,1 Peng Luo,1 Haiting Xie1 1Zhujiang Hospital of Southern Medical University, Guangzhou, China; 2Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China; 3Second School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China *These authors contributed equally to this work Abstract: Glia maturation factor-β (GMFB) is considered to be a growth and differentiation factor for both glia and neurons. GMFB has been found to be upregulated in several neuroinflammation and neurodegeneration conditions. It may function by mediating apoptosis and by modulating the expression of superoxide dismutase, granulocyte-macrophage colony-stimulating factor, and neurotrophin. In this review, we mainly discussed the role of GMFB in several neuroinflammatory and neurodegenerative diseases. On review of the literature, we propose that GMFB may be a promising therapeutic target for neuroinflammatory and neurodegenerative diseases. Keywords: glia maturation factor-β, neurodegeneration, neuroinflammation
Mesenchymal stem cell (MSC)-derived exosomes (Exos) enhanced new bone formation, coupled with positive effects on osteogenesis and angiogenesis. This study aims to define the role of microRNA (miR)-21-5p delivered by human umbilical MSC-derived Exos (hucMSC-Exos) in the osteonecrosis of the femoral head (ONFH). We first validated that miR-21-5p expression was downregulated in the cartilage tissues of ONFH patients. Besides, hucMSCs delivered miR-21-5p to hFOB1.19 cells and human umbilical vein endothelial cells (HUVECs) through the secreted Exos. Loss- and gain-of-function approaches were performed to clarify the effects of Exo-miR-21-5p, SOX5, and EZH2 on HUVEC angiogenesis and hFOB1.19 cell osteogenesis. It was established that Exo-miR-21-5p augments HUVEC angiogenesis and hFOB1.19 cell osteogenesis in vitro, as reflected by elevated alkaline phosphatase (ALP) activity and calcium deposition, and increased the expression of osteogenesis-related markers OCN, Runx2 and Collagen I. Mechanistically, miR-21-5p targeted SOX5 and negatively regulated its expression, while SOX5 subsequently promoted the transcription of EZH2. Ectopically expressed SOX5 or EZH2 could counterweigh the effect of Exo-miR-21-5p. Further, hucMSC-Exos containing miR-21-5p repressed the expression of SOX5 and EZH2 and augmented angiogenesis and osteogenesis in vivo. Altogether, our study uncovered the role of miR-21-5p shuttled by hucMSC-Exos, in promoting angiogenesis and osteogenesis, which may be a potential therapeutic target for ONFH.
To evaluate and compare the predictive value of Face, Arm, Speech Test (FAST) and Balance, Eyes, Face, Arm, Speech, Time (BEFAST) scale in the acute ischemic stroke (AIS).We searched Medline and Ovid databases for relevant literature in the English language. There were no limitations on the date. The sensitivity, specificity, likelihood ratio, and diagnostic odds ratio were pooled for meta-analysis. The symmetric receiver operator characteristic curve and Fagan's Nomogram were drawn, and meta-regression and subgroup analysis were used to explore the source of heterogeneity.A total of 9 studies, including 6,151 participants, were analyzed. The combined sensitivity of FAST was 0.77 [95% CI (0.64-0.86)], specificity was 0.60 [95% CI (0.38-0.78)], the area under the ROC curve was 0.76, and the diagnostic ratio was 1.57, while the sensitivity of BEFAST was 0.68 [95% CI (0.23-0.93)], specificity was 0.85 [95% CI (0.72-0.92)], the area under the ROC curve was 0.86, and the diagnostic odds ratio was 2.44. No publication bias was detected in Deeks' funnel plot. For FAST, meta-regression analysis showed that the prospective design, satisfactory description of the index test, and a broad spectrum of disease contributed to the heterogeneity in sensitivity, while no sources contributed to the heterogeneity in sensitivity. When the pretest probability was set as 20%, the posterior probability in Fagan's Nomogram was 32%; however, when the pretest probability was set as 20% in BEFAST, the posterior probability in Fagan's Nomogram was 52%.Our findings indicated that FAST and BEFAST might be useful in the diagnosis of acute ischemic stroke. The diagnostic value of BEFAST in acute ischemic stroke was higher than in FAST; thus, it might have an important role in the fast recognition of acute ischemic stroke.
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