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1.
Sheng Li Xue Bao ; 73(4): 584-596, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34405215

RESUMO

Heart failure (HF), a clinical syndrome with high morbidity and mortality, is becoming a growing public health problem. Dilated cardiomyopathy (DCM) is one of the major causes of HF, yet the molecular mechanisms underlying DCM-mediated HF are not completely understood. Previous studies have shown that dysregulation of arachidonic acid (AA) metabolism could contribute to the development of HF. To explore the roles of microRNAs (miRNAs) in regulating AA metabolism in HF, we used two public datasets to analyze the expression changes of miRNAs in the patients of DCM-mediated HF. A total of 101 and 88 miRNAs with significant abundance alterations in the two dataset were obtained, respectively. Around 1/3 of these miRNAs were predicted to target AA metabolic pathway genes. We also investigated the distribution of known single nucleotide polymorphisms (SNPs) within the sequences of miRNAs dysregulated in DCM-mediated HF patients, and identified miRNAs harboring high number of SNPs in either the seed regions or the entire sequences. These information could provide clues for further functional studies of miRNAs in the pathogeny of DCM-mediated HF.


Assuntos
Cardiomiopatia Dilatada , Insuficiência Cardíaca , MicroRNAs , Ácido Araquidônico , Cardiomiopatia Dilatada/genética , Insuficiência Cardíaca/genética , Humanos , MicroRNAs/genética
2.
Med Sci Monit ; 27: e933601, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34456330

RESUMO

BACKGROUND The aim of this study was to investigate distribution rules of radial peripapillary capillaries (RPCs) density and correlations with retinal nerve fiber layers (RNFL) thickness in normal subjects. MATERIAL AND METHODS We included 78 eyes of 78 healthy subjects examined by optical coherence tomography angiography (OCTA). RPCs density and RNFL thickness were measured automatically. Distributions of RPCs density and RNFL thickness were analyzed at different locations. Correlations of these 2 parameters and relationship with large vessels were evaluated by Spearman test. RESULTS Average density for overall, peripapillary, and inside disc RCPs was 56.12±2.51%, 58.56±2.84%, and 60.16±4.01%, respectively. Overall and peripapillary RCPs density were positively correlated with RNFL thickness (r=0.595, P.


Assuntos
Capilares/citologia , Fibras Nervosas/fisiologia , Disco Óptico/irrigação sanguínea , Vasos Retinianos/citologia , Adulto , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Campos Visuais , Adulto Jovem
3.
Biochim Biophys Acta Gen Subj ; 1865(10): 129955, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34229069

RESUMO

BACKGROUND: Despite advances in the treatments of diabetic complications, proliferative diabetic retinopathy (PDR) still remains a major cause leading to visual loss, mainly because of the lack of pathological mechanisms and complicated protein expressions in vivo. Current study aimed to investigate the patterns of connexin43 (Cx43) changes and the possible interactions with O-GlcNAcylation in DR. METHODS: Clinical samples of vitreous and fibrovascular membranes were acquired from PDR patients during pars plana vitrectomy. Brown Norway rats were used to build diabetic animal models; to investigate the effects of O-GlcNAcylation on Cx43 expressions, total retinal O-GlcNAcylation was changed by intravitreal injections. Levels of protein expressions were examined by immunofluorescence staining and western blot. RESULTS: Our results revealed increased Cx43 expressions in a vessel-shape pattern followed by the distribution of glial fibrillary acidic protein (GFAP) in diabetic fibrovascular membranes. Similarly, Cx43 and GFAP expressions were elevated in PDR vitreous and diabetic animal retinas. Retinal O-GlcNAcylation was effectively regulated by intravitreal injections, and the increase of Cx43 and GFAP was significantly suppressed by O-GlcNAcylation inhibition under hyperglycemia conditions. CONCLUSIONS: We systemically proved the changes of Cx43 with different retinal cells, and reported the effective methods to regulate retinal O-GlcNAcylation by intravitreal injections, and clearly illustrated the downregulated effects of O-GlcNAcylation inhibition on Cx43 and GFAP expressions. GENERAL SIGNIFICANCE: Targeting connexin43 in glial cells reveals a novel mechanism to understand the formation of diabetic fibrovascular membranes and offers a potential therapeutic strategy to interfere the development of PDR.

4.
J Clin Invest ; 131(15)2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34156976

RESUMO

Clear cell sarcoma (CCS) is a deadly malignancy affecting adolescents and young adults. It is characterized by reciprocal translocations resulting in expression of the chimeric EWSR1-ATF1 or EWSR1-CREB1 fusion proteins, driving sarcomagenesis. Besides these characteristics, CCS has remained genomically uncharacterized. Copy number analysis of human CCSs showed frequent amplifications of the MITF locus and chromosomes 7 and 8. Few alterations were shared with Ewing sarcoma or desmoplastic, small round cell tumors, which are other EWSR1-rearranged tumors. Exome sequencing in mouse tumors generated by expression of EWSR1-ATF1 from the Rosa26 locus demonstrated no other repeated pathogenic variants. Additionally, we generated a new CCS mouse by Cre-loxP-induced chromosomal translocation between Ewsr1 and Atf1, resulting in copy number loss of chromosome 6 and chromosome 15 instability, including amplification of a portion syntenic to human chromosome 8, surrounding Myc. Additional experiments in the Rosa26 conditional model demonstrated that Mitf or Myc can contribute to sarcomagenesis. Copy number observations in human tumors and genetic experiments in mice rendered, for the first time to our knowledge, a functional landscape of the CCS genome. These data advance efforts to understand the biology of CCS using innovative models that will eventually allow us to validate preclinical therapies necessary to achieve longer and better survival for young patients with this disease.

5.
Medicine (Baltimore) ; 100(18): e25545, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950928

RESUMO

BACKGROUND: Breast cancer is a common malignant tumor in women. In recent years, its incidence is increasing year by year, and its morbidity and mortality rank the first place among female malignant tumors. Some key enzymes and intermediates in glycolysis are closely related to tumor development. Pyruvate kinase M2 (PKM2) is an important rate-limiting enzyme in glycolysis pathway. Meanwhile, it is highly expressed in proliferative cells, especially in tumor cells, and plays an important role in the formation of Warburg effect and tumorigenesis. Previous studies have explored the effects of PKM2 expression on the prognosis and clinical significance of breast cancer patients, while the results are contradictory and uncertain. This study uses controversial data for meta-analysis to accurately evaluate the problem. We collected relevant Oncomine and The Cancer Genome Atlas (TCGA) data to further verify the results. Through bioinformatics analysis, the mechanism and related pathways of PKM2 in breast cancer are explored. METHODS: We searched Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases from inception to March 2021. The language restrictions are Chinese and English. The published literatures on PKM2 expression and prognosis or clinicopathological characteristics of breast cancer patients were statistically analyzed. Combined hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (95% CIs) were used to evaluate the effects of PKM2 on the prognosis and clinicopathological features of breast cancer. Stata 14.0 software was applied for meta-analysis. Oncomine and TCGA databases were used to meta-analyze the differences of PKM2 mRNA expression between breast cancer and normal breast tissues. The expression of PKM2 protein was verified by Human Protein Atlas (HPA) database. The relationship between the gene and the survival of breast cancer patients was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). The relationship between PKM2 gene and clinicopathological characteristics was analyzed by using LinkedOmics, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis was performed by using Metascape. Protein-protein interaction (PPI) network was constructed by String website. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study provides high-quality medical evidence for the correlation between the expression of PKM2 and the prognosis and clinicopathological features of breast cancer. Through bioinformatics analysis, this study further deepens the understanding of the mechanism and related pathways of PKM2 in breast cancer. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W52HB.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Mama/patologia , Carcinogênese/patologia , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Proteínas de Transporte/análise , Biologia Computacional , Intervalo Livre de Doença , Feminino , Humanos , Proteínas de Membrana/análise , Metanálise como Assunto , Prognóstico , Medição de Risco/métodos , Hormônios Tireóideos/análise , Efeito Warburg em Oncologia
6.
Fluids Barriers CNS ; 18(1): 21, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952281

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is the leading cause of cerebral small vessel disease (CSVD). CCH is strongly associated with blood-brain barrier (BBB) dysfunction and white matter lesions (WMLs) in CSVD. However, the effects of CCH on BBB integrity and components and the cellular and molecular mechanisms underlying the effects of BBB dysfunction remain elusive. Whether maintaining BBB integrity can reverse CCH-induced brain damage has also not been explored. METHODS: In this study, we established a rat model of CSVD via permanent bilateral common carotid artery occlusion (2VO) to mimic the chronic hypoperfusive state of CSVD. The progression of BBB dysfunction and components of the BBB were assessed using immunostaining, Western blotting, transmission electron microscopy (TEM) and RNA sequencing. We also observed the protective role of imatinib, a tyrosine kinase inhibitor, on BBB integrity and neuroprotective function following CCH. The data were analyzed using one-way or two-way ANOVA. RESULTS: We noted transient yet severe breakdown of the BBB in the corpus callosum (CC) following CCH. The BBB was severely impaired as early as 1 day postoperation and most severely impaired 3 days postoperation. BBB breakdown preceded neuroinflammatory responses and the formation of WMLs. Moreover, pericyte loss was associated with BBB impairment, and the accumulation of serum protein was mediated by increased endothelial transcytosis in the CC. RNA sequencing also revealed increased transcytosis genes expression. BBB dysfunction led to brain damage through regulation of TGF-ß/Smad2 signaling. Furthermore, imatinib treatment ameliorated serum protein leakage, oligodendrocyte progenitor cell (OPC) activation, endothelial transcytosis, microglial activation, and aberrant TGF-ß/Smad2 signaling activation. CONCLUSIONS: Our results indicate that reduced pericyte coverage leads to increased BBB permeability via endothelial transcytosis. Imatinib executes a protective role on the BBB integrity via inhibition of endothelial transcytosis. Maintenance of BBB integrity ameliorates brain damage through regulation of TGF-ß/Smad2 signaling following CCH; therefore, reversal of BBB dysfunction may be a promising strategy for CSVD treatment.

7.
Int Immunopharmacol ; 88: 106891, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32853927

RESUMO

BACKGROUND: The therapeutic approaches guided toward microRNAs (miRNAs) have been extensively explored in lupus nephritis (LN), but the precise position of miR-10a-3p posted in disease is not translated thoroughly. Therein, this work pivoting on miR-10a-3p was launched with the involvement of regenerating islet-derived 3 α (REG3A). METHODS: Peripheral blood samples from LN patients and healthy controls (n = 132) were collected. miR-10a-3p and REG3A expression in peripheral blood mononuclear cells were tested. Mice were injected with miR-10a-3p agomir, miR-10a-3p antagomir and/or REG3A low expression vector for presentation of their roles in renal function, T helper cell 17 (Th17)/regulatory cell (Treg) balance, renal pathological damage, JAK2/STAT3 pathway activation and renal injury in LN. The relation between miR-10a-3p and REG3A was tested. RESULTS: MiR-10a-3p was down-regulated while REG3A was up-regulated in LN. Restoring miR-10a-3p or silencing REG3A decreased Th17/Treg ratio in CD4+ T cells, inhibited JAK2/STAT3 pathway activation, ameliorated renal function, improved renal pathological damage and alleviated renal injury in LN. REG3A depletion negated the effects of down-regulated miR-10a-3p on LN. MiR-10a-3p targeted REG3A. CONCLUSION: The work elucidates that miR-10a-3p restoration decreases Th17/Treg ratio and attenuates renal injury in LN via inhibiting REG3A and the activation of JAK2/STAT3 pathway, which renews the therapeutic reference for LN management.


Assuntos
Nefrite Lúpica/imunologia , MicroRNAs , Proteínas Associadas a Pancreatite/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto , Animais , Feminino , Humanos , Janus Quinase 2/imunologia , Rim/imunologia , Nefrite Lúpica/sangue , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Proteínas Associadas a Pancreatite/genética , Fator de Transcrição STAT3/imunologia , Baço/citologia
8.
Stem Cell Reports ; 15(2): 529-545, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32679066

RESUMO

The pluripotency of stem cells determines their developmental potential. While the pluripotency states of pluripotent stem cells are variable and interconvertible, the mechanisms underlying the acquisition and maintenance of pluripotency remain largely elusive. Here, we identified that methylenetetrahydrofolate dehydrogenase (NAD+-dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2) plays an essential role in maintaining embryonic stem cell pluripotency and promoting complete reprogramming of induced pluripotent stem cells. Mechanistically, in mitochondria, Mthfd2 maintains the integrity of the mitochondrial respiratory chain and prevents mitochondrial dysfunction. In the nucleus, Mthfd2 stabilizes the phosphorylation of EXO1 to support DNA end resection and promote homologous recombination repair. Our results revealed that Mthfd2 is a dual-function factor in determining the pluripotency of pluripotent stem cells through both mitochondrial and nuclear pathways, ultimately ensuring safe application of pluripotent stem cells.


Assuntos
Aminoidrolases/metabolismo , Reparo do DNA , Células-Tronco Pluripotentes Induzidas/metabolismo , Meteniltetra-Hidrofolato Cicloidrolase/metabolismo , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Mitocôndrias/metabolismo , Complexos Multienzimáticos/metabolismo , Animais , Proteína Quinase CDC2/metabolismo , Núcleo Celular/metabolismo , Autorrenovação Celular/genética , Dano ao DNA , Enzimas Reparadoras do DNA/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Exodesoxirribonucleases/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Glicólise , Meteniltetra-Hidrofolato Cicloidrolase/deficiência , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Fosforilação Oxidativa , Fosforilação , Ligação Proteica
9.
Acad Radiol ; 27(3): 354-360, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31151900

RESUMO

OBJECTIVE: To investigate the correlation between dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) parameters and angiogenesis and to explore prospectively the feasibility of using DSC-MRI to differentiate malignant from benign soft tissue tumors (STTs) in limbs. METHODS: This prospective study included 33 patients with STTs in limbs who underwent DSC-MRI after bolus Gd-DTPA infusion. All STTs were confirmed by pathological examination after surgery and microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, were evaluated by immune-histochemical analysis. Semiquantitative DSC-MRI parameters, including negative enhancement integral (NEI), maximum slopes of decrease (MSD) and increase (MSI), and mean time to enhancement were calculated by postprocessing in workstation. The correlation was analyzed between DSC-MRI parameters and angiogenesis factors. Then, the DSC-MRI parameters were compared between benign and malignant STTs and evaluated for diagnostic efficiency by receiver operating characteristic. RESULTS: The 33 evaluated tumors were consisted of 13 benign and 20 malignant STTs in limbs. Significant positive correlations were observed between NEI, MSD, MSI and MVD, VEGF (p < 0.05). However, mean time to enhancement had no correlation with MVD and VEGF. The benign and malignant STTs differed significantly in terms of NEI, MSD, and MSI (p < 0.05). The areas under the curve (AUC) of NEI, MSD, and MSI were 0.915, 0.862, and 0.815 for discriminating between benign and malignant STTs, respectively. CONCLUSION: DSC-MRI parameters are positively correlated with MVD and VEGF, which can evaluate angiogenesis indirectly. Furthermore, DSC-MRI can be considered as one of assistant noninvasive MR imaging technique in differentiation between benign and malignant STTs in limbs.


Assuntos
Neoplasias de Tecidos Moles , Fator A de Crescimento do Endotélio Vascular , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Neoplasias de Tecidos Moles/diagnóstico por imagem
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117908, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31841672

RESUMO

A new probe (SRh) which based on dual-binding benzene and rhodamine B conjugate derivatives for hypochlorite detection was developed. By desulfurization effect, probe SRh displayed"Off-On" switching in its fluorogenic and chromogenic responses to hypochlorite. The detection limit of ClO- was at a low level (up to 2.43 nM). Moreover, probe SRh has been applied in bioimaging with good biocompatibility and low cytotoxicity.


Assuntos
Benzeno/química , Corantes Fluorescentes , Ácido Hipocloroso/metabolismo , Imagem Óptica , Rodaminas/química , Linhagem Celular , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Humanos
11.
Front Vet Sci ; 6: 136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31157244

RESUMO

To meet increasing demand for animal protein, swine have been raised in large Chinese farms widely, using antibiotics as growth promoter. However, improper use of antibiotics has caused serious environmental and health risks, in particular Antimicrobial resistance (AMR). This paper reviews the consumption of antibiotics in swine production as well as AMR and the development of novel antibiotics or alternatives in China. The estimated application of antibiotics in animal production in China accounted for about 84240 tons in 2013. Overuse and abuse of antibiotics pose a great health risk to people through food-borne antibiotic residues and selection for antibiotic resistance. China unveiled a national plan to tackle antibiotic resistance in August 2016, but more support is needed for the development of new antibiotics or alternatives like plant extracts. Antibiotic resistance has been a major global challenge, so international collaboration between China and Europe is needed.

12.
Biochem J ; 476(11): 1585-1604, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31036718

RESUMO

Mitochondria play a central role in the maintenance of the naive state of embryonic stem cells. Many details of the mechanism remain to be fully elucidated. Solute carrier family 25 member 36 (Slc25a36) might regulate mitochondrial function through transporting pyrimidine nucleotides for mtDNA/RNA synthesis. Its physical role in this process remains unknown; however, Slc25a36 was recently found to be highly expressed in naive mouse embryonic stem cells (mESCs). Here, the function of Slc25a36 was characterized as a maintenance factor of mESCs pluripotency. Slc25a36 deficiency (via knockdown) has been demonstrated to result in mitochondrial dysfunction, which induces the differentiation of mESCs. The expression of key pluripotency markers (Pou5f1, Sox2, Nanog, and Utf1) decreased, while that of key TE genes (Cdx2, Gata3, and Hand1) increased. Cdx2-positive cells emerged in Slc25a36-deficient colonies under trophoblast stem cell culture conditions. As a result of Slc25a36 deficiency, mtDNA of knockdown cells declined, leading to impaired mitochondria with swollen morphology, decreased mitochondrial membrane potential, and low numbers. The key transcription regulators of mitochondrial biogenesis also decreased. These results indicate that mitochondrial dysfunction leads to an inability to support the pluripotency maintenance. Moreover, down-regulated glutathione metabolism and up-regulated focal adhesion reinforced and stabilized the process of differentiation by separately enhancing OCT4 degradation and promoting cell spread. This study improves the understanding of the function of Slc25a36, as well as the relationship of mitochondrial function with naive pluripotency maintenance and stem cell fate decision.


Assuntos
Glutationa/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas Mitocondriais/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Proteínas de Transporte de Nucleotídeos/metabolismo , Animais , Fator de Transcrição CDX2/metabolismo , Diferenciação Celular/genética , Células Cultivadas , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Adesões Focais , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/genética , Proteínas de Transporte de Nucleotídeos/antagonistas & inibidores , Proteínas de Transporte de Nucleotídeos/genética , Fator 3 de Transcrição de Octâmero/metabolismo
13.
J Exp Bot ; 69(15): 3759-3771, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29757407

RESUMO

Roots and root-released organic anions play important roles in uptake of phosphorus (P), an essential macronutrient for food production. Oat, ranking sixth in the world's cereal production, contains valuable nutritional compounds and can withstand poor soil conditions. Our aim was to investigate root transcriptional and metabolic responses of oat grown under P-deficient and P-sufficient conditions. We conducted a hydroponic experiment and measured root morphology and organic anion exudation, and analysed changes in the transcriptome and metabolome. Oat roots showed enhanced citrate and malate exudation after 4 weeks of P deficiency. After 10 d of P deficiency, we identified 9371 differentially expressed transcripts with a 2-fold or greater change (P<0.05): 48 sequences predicted to be involved in organic anion biosynthesis and efflux were consistently up-regulated; 24 up-regulated transcripts in oat were also found to be up-regulated upon P starvation in rice and wheat under similar conditions. Phosphorylated metabolites (i.e. glucose-6-phosphate, myo-inositol phosphate) were reduced dramatically, while citrate and malate, some sugars and amino acids increased slightly in P-deficient oat roots. Our data are consistent with a strategy of increased organic anion efflux and a shift in primary metabolism in response to P deficiency in oat.


Assuntos
Avena/genética , Metaboloma , Fósforo/deficiência , Transcriptoma , Ânions/metabolismo , Avena/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
14.
Int J Mol Sci ; 19(2)2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29419748

RESUMO

Large numbers of lipids exist in the porcine oocytes and early embryos and have the positive effects on their development, suggesting that the lipids may play an important role in pluripotency establishment and maintenance in pigs. However, the effects of lipids and their metabolites, such as fatty acids on reprogramming and the pluripotency gene expression of porcine-induced pluripotent stem cells (iPSCs), are unclear. Here, we generated the porcine iPSCs that resemble the mouse embryonic stem cells (ESCs) under lipid and fatty-acid-enriched cultural conditions (supplement of AlbuMAX). These porcine iPSCs show positive for the ESCs pluripotency markers and have the differentiation abilities to all three germ layers, and importantly, have the capability of aggregation into the inner cell mass (ICM) of porcine blastocysts. We further confirmed that lipid and fatty acid enriched condition can promote the cell proliferation and improve reprogramming efficiency by elevating cAMP levels. Interestingly, this lipids supplement promotes mesenchymal-epithelial transition (MET) through the cAMP/PKA/CREB signal pathway and upregulates the E-cadherin expression during porcine somatic cell reprogramming. The lipids supplement also makes a contribution to lipid droplets accumulation in the porcine iPSCs that resemble porcine preimplantation embryos. These findings may facilitate understanding of the lipid metabolism in porcine iPSCs and lay the foundation of bona fide porcine embryonic stem cell derivation.


Assuntos
Proteína de Ligação a CREB/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Suplementos Nutricionais , Células-Tronco Pluripotentes Induzidas/metabolismo , Metabolismo dos Lipídeos , Lipídeos , Transdução de Sinais , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Reprogramação Celular , Ácidos Graxos/metabolismo , Fibroblastos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Lipídeos/farmacologia , Modelos Biológicos , Proteínas Proto-Oncogênicas c-met/genética , Suínos
15.
J Clin Invest ; 128(1): 207-218, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29202462

RESUMO

Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma that is often discovered during adolescence and young adulthood. Despite the name, synovial sarcoma does not typically arise from a synoviocyte but instead arises in close proximity to bones. Previous work demonstrated that mice expressing the characteristic SS18-SSX fusion oncogene in myogenic factor 5-expressing (Myf5-expressing) cells develop fully penetrant sarcomagenesis, suggesting skeletal muscle progenitor cell origin. However, Myf5 is not restricted to committed myoblasts in embryos but is also expressed in multipotent mesenchymal progenitors. Here, we demonstrated that human SS and mouse tumors arising from SS18-SSX expression in the embryonic, but not postnatal, Myf5 lineage share an anatomic location that is frequently adjacent to bone. Additionally, we showed that SS can originate from periosteal cells expressing SS18-SSX alone and from preosteoblasts expressing the fusion oncogene accompanied by the added stabilization of ß-catenin, which is a common secondary change in SS. Expression and secretion of the osteoclastogenesis inhibitory factor osteoprotegerin enabled early growth of SS18-SSX2-transformed cells, indicating a paracrine link between the bone and synovial sarcomagenesis. These findings explain the skeletal contact frequently observed in human SS and may provide alternate means of enabling SS18-SSX-driven oncogenesis in cells as differentiated as preosteoblasts.


Assuntos
Neoplasias Ósseas/metabolismo , Transformação Celular Neoplásica/metabolismo , Osteoprotegerina/metabolismo , Comunicação Parácrina , Periósteo/metabolismo , Sarcoma Sinovial/metabolismo , beta Catenina/metabolismo , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Humanos , Camundongos , Camundongos Knockout , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoprotegerina/genética , Periósteo/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologia , beta Catenina/genética
16.
Waste Manag ; 78: 992-1000, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32559995

RESUMO

Recovery of secondary resources including waste SmCo magnets contributes to easing the natural resources and environmental issues. For the development of recovery technologies, an ionic liquid (IL)-based precipitation route based on [trihexyl(tetradecyl)phosphonium]2[benzene-1,4-dioxydiacetate] ([P6,6,6,14]2[BDOAC]) is presented. The slow release of [BDOAC]2- from [P6,6,6,14]2[BDOAC] increases the kinetics difference in the formations of precipitates, and makes the precipitates contain less impurity. While cobalt-rich solution is obtained with no loss, precipitation efficiency of Sm(III) and Cu(II) reaches 96.8% and 100% respectively. Afterwards, Cu(II) is removed using aqueous ammonia and pure Cu(II) (96.4% precipitation efficiency) is obtained by adjusting the pH of cuprammonium complex solution. The proposed process without volatile diluent reveals higher separation factors of Sm/Co, Cu/Co and Sm/Cu. Lower acidities are efficient for the complete stripping of Sm(III) and Cu(II) from their precipitates. SmCl3 and CuCl2 solutions are obtained both with the high purities. Moreover, the IL-based precipitant can be regenerative. It is shown that the strategy is efficient for recovering and separating Sm, Co and Cu from the simulated leaching solution of waste SmCo magnets.

17.
Sci Rep ; 7(1): 3030, 2017 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-28596585

RESUMO

Our study examined the in vivo chimeric and survival capacities of chimeras created by injecting tetraploid embryonic stem cells (ESCs) expressing green fluorescent protein (GFP) into diploid embryos. At 3.5 days post-coitum (dpc) and 4.5 dpc, the tetraploid ESCs were able to contribute to the inner cell mass (ICM) just as diploid ESCs tagged with GFP. At 6.5 dpc, 8.0 dpc and 10.5 dpc, the tetraploid ESCs manifested in the same location as the diploid ESCs. The GFP cells in the extraembryonic tissues and fetuses of tetraploid ESC chimeras were tetraploid as determined by fluorescence activated cell sorting (FACS). Furthermore, tetraploid ESCs contributed to the development of the placenta, embryolemma and umbilical cord at 13.5 dpc and 16.5 dpc; however, very less GFP cells were found in the fetuses of tetraploid ESC chimeras. We further found that the proliferation of tetraploid ESCs was slower than that of diploid ESCs. In addition, the relative mRNA expression in the three germ layers and the trophoblast was abnormal in the EBs of tetraploid ESCs compared with diploid ESCs. In short, slower proliferation and abnormal differentiation potential of tetraploid ESCs might be two of the reasons for their poor survival and chimeric capacities.


Assuntos
Quimerismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Desenvolvimento Fetal/genética , Organogênese/genética , Tetraploidia , Blastômeros/citologia , Blastômeros/metabolismo , Diferenciação Celular , Linhagem Celular , Proliferação de Células/genética , Diploide , Expressão Gênica , Genes Reporter , Cariótipo
18.
Plant Biotechnol J ; 15(12): 1611-1621, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28419665

RESUMO

The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500 000 die yearly from HCV-related liver pathologies. To date, there is no licensed vaccine available to prevent HCV infection and production of a HCV vaccine remains a major challenge. Here, we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium-mediated transient expression technology. The wild-type dimer (E1E2) and a variant without an N-glycosylation site in the E2 polypeptide (E1E2∆N6) were expressed, and appropriate N-glycosylation pattern and functionality of the E1E2 dimers were demonstrated. The humoral immune response induced by the HCV proteins was investigated in mice following oral administration of lettuce antigens with or without previous intramuscular prime with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding only resulted in development of weak serum levels of anti-HCV IgM for both antigens; however, the E1E2∆N6 proteins produced higher amounts of secretory IgA, suggesting improved immunogenic properties of the N-glycosylation mutant. The mice group receiving the intramuscular injection followed by two oral boosts with the lettuce E1E2 dimer developed a systemic but also a mucosal immune response, as demonstrated by the presence of anti-HCV secretory IgA in faeces extracts. In summary, our study demonstrates the feasibility of producing complex viral antigens in lettuce, using plant transient expression technology, with great potential for future low-cost oral vaccine development.


Assuntos
Alface/genética , Proteínas do Envelope Viral/imunologia , Vacinas contra Hepatite Viral/administração & dosagem , Vacinas contra Hepatite Viral/imunologia , Administração Oral , Animais , Feminino , Células HEK293 , Humanos , Imunidade Humoral , Camundongos Endogâmicos BALB C , Plantas Geneticamente Modificadas , Engenharia de Proteínas/métodos , Multimerização Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas do Envelope Viral/genética , Vacinas contra Hepatite Viral/genética
19.
Chest ; 152(4): 810-820, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28427968

RESUMO

BACKGROUND: Our previous review reported great variability in the incidence and prevalence of atrial fibrillation (AF) in non-Western cohorts, especially from Asian countries; in recent years, epidemiologic studies on AF have been increasingly reported from Asia. METHODS: The goal of this updated systematic review was to present the current knowledge base of AF epidemiology in Asian countries since our previous review. We also explored AF incidence and the risk of stroke in AF by using a meta-analysis, with I2 testing the heterogeneity. Third, "real-world" antithrombotic drug use for ischemic stroke (IS) prevention associated with AF was studied. RESULTS: A total of 58 articles from eight countries in Asia were included in the analysis. The summary annual incidence of AF was 5.38 (95% CI, 4.53-6.24; I2 = 99.5%; n = 10) per 1,000 person-years, and the IS annual risk in AF was 3.0% (1.60%-4.95%; I2 = 99.8%; n = 8) when meta-analysis was performed on hospital- and community-based studies. Hospital- and community-based AF prevalence ranged from 0.37% to 3.56% and 2.8% to 15.8%, respectively. IS prevalence in AF ranged from 1.9% to 6.0% and 0.36% to 28.3% in community- and hospital-based studies. Warfarin use in Chinese subjects is relatively low (1.0%-4.1%) compared with Japanese subjects (49.1%-70.0%) in community-based studies. The rate of warfarin use was < 50% in hospital-based studies. CONCLUSIONS: The incidence and prevalence of AF have increased in recent years, although great variability still exists in Asian countries. Variability in annual IS risk in patients with AF was apparent between hospital- and community-based studies. However, the rate of warfarin use was < 50% in hospital studies from Asian countries.


Assuntos
Fibrilação Atrial/epidemiologia , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Ásia/epidemiologia , Fibrilação Atrial/complicações , Humanos , Incidência , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/etiologia
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