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OBJECTIVE: Enteral nutrition (EN) is the first-choice nutritional support, as it is more in line with normal physiological processes. During EN, the major goals to achieve include accurate confirmation of the feeding tube position, monitoring the gastric residual volume, assessing gastrointestinal motility, and monitoring the nutritional status of patients. With rapid development in technology, point-of-care ultrasound (POCUS) has become a more convenient and effective technical tool for monitoring critically ill patients receiving EN. In this review, we have summarized and discussed the value of POCUS in the implementation, monitoring, and evaluation of EN therapy to provide a reference for nutritional support of critically ill patients in critical care settings. MATERIALS AND METHODS: This is a narrative review. A literature search for Scopus-indexed articles was performed randomly using PubMed and MEDLINE databases as the primary sources. No specific term was used for the search. RESULTS: POCUS can be used for positioning of nasogastric and nasointestinal tubes, evaluation of gastric residuals and gastrointestinal motility as well as monitoring of nutritional status. CONCLUSIONS: POCUS is a real-time, highly repeatable, radiation-free, and non-invasive visual inspection technique, with high application value in assessing the nutritional status of patients receiving EN and guiding the development of further nutritional treatment plans. It is an important diagnostic and monitoring tool that can be used by the clinicians in the ICU.
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Estado Terminal , Nutrição Enteral , Cuidados Críticos/métodos , Estado Terminal/terapia , Nutrição Enteral/métodos , Humanos , Unidades de Terapia Intensiva , Intubação Gastrointestinal , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
OBJECTIVE: This study aims to investigate the biological function of circular RNA ABCB10 (circ-ABCB10) in regulating the progression of glioma and to study the possible underlying mechanisms. PATIENTS AND METHODS: The expression levels of circ-ABCB10, miR-620 and FABP5 mRNA in glioma tissues, normal surrounding tissues and glioma cell lines were measured by Real-time PCR (RT-PCR). Circ-ABCB10 was silenced by siRNA in glioma cell lines (U87, T98G). The proliferation, migration and invasion of glioma cells were measured by MTT, wound healing and transwell assays, respectively. The relationship between circ-ABCB10, miR-620 and FABP5 was tested by Dual-Luciferase assay. The expression of proteins was measured by Western blot. The cell cycle distribution and apoptosis were measured by flow cytometry. RESULTS: The expression levels of circ-ABCB10 and FABP5 in glioma tissues and cells were significantly higher than those in their normal counterparts. Moreover, the expression of miR-620 was lower in glioma tissues. Silencing of circ-ABCB10 in glioma cells significantly inhibited the proliferation, migration and invasion of glioma cells. Moreover, downregulation of circ-ABCB10 induced cell cycle arrest and apoptosis in glioma cells. Furthermore, inhibition of miR-620 showed the opposite effects to silencing circ-ABCB10 on glioma cells. Dual-Luciferase reporter assays demonstrated that circ-ABCB10 could bind to miR-620 and that FABP5 was a direct target of miR-620. Western blot results showed that circ-ABCB10 could stabilize the expression of FABP5, while miR-620 decreased the expression of FABP5. Furthermore, overexpression of FABP5 abrogated the silencing effects of circ-ABCB10 in glioma cells. CONCLUSIONS: These data suggest that circ-ABCB10 affects glioma progression by regulating the miR-620/FABP5 axis, and circ-ABCB10 might be used as a potential target for the treatment of glioma.
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Neoplasias do Sistema Nervoso Central/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Glioma/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Apoptose , Ciclo Celular , Movimento Celular , Proliferação de Células , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Proteínas de Ligação a Ácido Graxo/genética , Glioma/metabolismo , Glioma/patologia , Humanos , MicroRNAs/genética , RNA Circular/genética , Células Tumorais CultivadasRESUMO
OBJECTIVE: Increasing studies reported that the serum- and glucocorticoid-inducible kinases (SGKs) contributed to the tumorigenesis of various cancer. In this article, we are aiming to explore the function of SGK2 in renal cell cancer (RCC). PATIENTS AND METHODS: In this study, the SGK2 expression was quantified by Western blot (WB) in multiple RCC cell lines. And in vitro SGK2 knockdown and overexpression experiments were also performed. In addition, molecular function analysis was performed using FunRich software V3. The Cancer Genome Atlas (TCGA) database was retrieved to verify the association between the SGK2 expression and the prognosis of RCC patients. RESULTS: We found that SGK2 was up-regulated in RCC tissues compared with adjacent normal tissues, and the SGK2 expression also increased in various RCC cell lines compared to that in the normal epithelial cell line HK-2. Meanwhile, the SGK2 expression was significantly associated with the survival rate of RCC patients. Functional experiments showed that silencing SGK2 expression inhibited RCC cells proliferation, migration, colony formation and invasion abilities in vitro, whereas opposite results were uncovered after overexpressing SGK2 in RCC cells. Furthermore, functional analyses showed that SGK2 related genes were associated with protein serine/threonine kinase activity, guanosine triphosphatase (GTPase) activity, guanyl-nucleotide exchange factor activity, and motor activity. Protein interaction analysis identified that growth factor receptor-bound protein 2 (GRB2), one of the most important upstream components in the growth factor signaling pathway, was significantly enriched in SGK2 related genes. In addition, the WB assay validated that SGK2 could promote the phosphorylation of ERK 1/2 and AKT. CONCLUSIONS: Our results suggested that SGK2 promoted RCC progression by mediating the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and Protein kinase B (AKT/PKB), indicating that SGK2 might serve as a potential prognostic marker and therapeutic target for renal cancer patients.
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Carcinoma de Células Renais/metabolismo , Proteínas Imediatamente Precoces/metabolismo , Neoplasias Renais/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Regulação para Cima , Linhagem Celular Tumoral/metabolismo , Progressão da Doença , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Guanosina Trifosfato/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Objective: To explore the relationship between different dimensions of infectious disease-specific health literacy scale in China. Methods: Structural equation model (SEM) was employed to assess the psychometric properties of the infectious disease-specific health literacy scale. Based on the database from a randomly selected sample of 4 499 adult residents in three provinces in China, from March to May 2015. AMOS 21.0 software was used to build the SEM for data analyses. Results: SEM analyses showed a good model fit of data, with the following satisfied parameters: goodness-of-fit index was 0.969, adjusted goodness-of-fit index was 0.962, root mean square residual was 0.038, root mean square error of approximation was 0.038, standardized root mean square residual was 0.032, Tacker-Lewis index/non-normed fit index was 0.926, comparative fit index was 0.934, normed fit index was 0.925, relative fit index was 0.915, incremental fit index was 0.934, parsimony goodness-of-fit index was 0.782, parsimony-adjusted normed fit index was 0.817, parsimony-adjusted comparative fit index was 0.825 and critical N was 702. The established SEM showed that the total influence path coefficient of "infectious disease-related knowledge and values" on the "infectious disease prevention" , "management or treatment of infectious diseases" and "identification of infection sources" were 0.771, 0.744 and 0.843, respectively. The total influence path coefficients of "identification of infection sources" , "infectious disease prevention" on "management or treatment of infectious diseases" were 0.164 and 0.535, respectively. The effect of "infectious disease-related knowledge and values" on "management or treatment of infectious diseases" appeared the greatest (55.4%), followed by "infectious disease prevention" (28.6%) and "identification of infection sources" (2.7%). Conclusion: This SEM could be optimistically used for planning and evaluation of health education and promotion programs on infectious diseases prevention.
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Letramento em Saúde , Modelos Teóricos , Adulto , China , Humanos , Psicometria , Inquéritos e QuestionáriosRESUMO
We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (â¼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (â¼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.
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We aimed to summarize the results of genetic association studies for obesity and provide a comprehensive annotation of all susceptibility single nucleotide polymorphisms (SNPs). A total of 72 studies were summarized, resulting in 90,361 susceptibility SNPs (738 index SNPs and 89,623 linkage disequilibrium SNPs). Over 90% of the susceptibility SNPs are located in non-coding regions, and it is challenging to understand their functional significance. Therefore, we annotated these SNPs by using various functional databases. We identified 24,623 functional SNPs, including 4 nonsense SNPs, 479 missense SNPs, 399 untranslated region SNPs which might affect microRNA binding, 262 promoter and 5,492 enhancer SNPs which might affect transcription factor binding, 7 splicing sites, 76 SNPs which might affect gene methylation levels, 1,839 SNPs under natural selection and 17,351 SNPs which might modify histone binding. Expression quantitative trait loci analyses for functional SNPs identified 98 target genes, including 69 protein coding genes, 27 long non-coding RNAs and 3 processed transcripts. The percentage of protein coding genes that could be correlated with obesity-related pathways directly or through gene-gene interaction is 75.36 (52/69). Our results may serve as an encyclopaedia of obesity susceptibility SNPs and offer guide for functional experiments.
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Predisposição Genética para Doença/genética , Obesidade/genética , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Locos de Características QuantitativasRESUMO
OBJECTIVE: To study the inflammatory factors in donor livers and its effect on recipient myocardial injury after liver transplantation recipients. PATIENTS AND METHODS: Eighteen patients who underwent orthotopic liver transplantations between January 2014 and December 2015 in our hospital were selected. A portion of the hepatic venous blood of donor's livers was preserved in heparinized tubes after partial resection. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and the activity of lactate dehydrogenase (LDH) in serum were measured. The concentrations of TNF-α, IL-6, cTnI, and CK-MB, and the activity of LDH in serum from the central venous blood of recipients were measured at several time points. RESULTS: Persistent myocardial injuries were found in five patients, six experienced a transient increase of cardiac markers after surgery and returned to normal levels 24 h after surgery, and the others were normal. The comparison of the levels of inflammatory factors in serum between the five donors and recipients at different stages showed that the levels of myocardial markers of the donor livers which were supplied to the five cardiac injured patients were all significantly higher than those of other donor's livers, while the levels of serum inflammatory factors in recipients showed no changes during the T0-T2 stage but increased significantly during T3-T5 (p < 0.05). The cardiac function after surgery was significantly different from that before surgery and that of the recipients without myocardial injury (p < 0.05). CONCLUSIONS: Blood pressure changes before surgery may affect the levels of inflammatory factors in donor's liver and cause postoperative myocardial injury in recipients. Proper hypotensive therapy for donors before partial liver resection can prevent postoperative myocardial injury in recipients.
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Transplante de Fígado/métodos , Fígado/metabolismo , Miocárdio/metabolismo , Doadores de Tecidos , Biomarcadores/sangue , Creatina Quinase/sangue , Creatina Quinase Forma MB/sangue , Humanos , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Período Pós-Operatório , Troponina I/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: To investigate whether the genetic variants of TGFB1, TLE4, MUC22 and IKZF3 are associated with the development of asthma in Chinese children. METHODS: 572 adolescent asthma patients and 590 age-matched healthy controls were included in this study. A total of four SNPs were genotyped, including rs2241715 of TGFB1, rs2378383 of TLE4, rs2523924 of MUC22, and rs907092 of IKZF3. Allele frequencies of the patients and the control group were compared by the Chi-square test. The Student t test was used to analyse the relationship between genotypes and clinical feature of the patients. RESULTS: Patients were found to have significantly different frequencies of allele A of rs2241715, allele G of rs2378383 and allele A of rs2523924 as compared with the controls (40.4% vs. 45.9%, p=0.01 for rs2241715; 17.2% vs. 13.4%, p=0.01 for rs2378383; 15.3% vs. 11.9%, p=0.02 for rs2523924). For patients with severe asthma, those with genotype AA/AG of rs2241715 had remarkably higher FEV1% as compared with those with genotype GG (59.1±4.3% vs. 55.4±3.7%, p<0.001). Moreover, those with genotype GG/GA of rs2378383 had remarkably lower FEV1% as compared with those with genotype AA (54.6±2.9% vs. 58.6±4.1%, p<0.001). CONCLUSIONS: Genes TGFB1, TLE4 and MUC22 are associated with the risk of childhood asthma in Chinese population. Our results associating TGFB1 and TLE4 with clinical features of asthma suggest potential application of these parameters in the management of asthma children.
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Asma/genética , Mucinas/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Fator de Crescimento Transformador beta1/genética , Adolescente , Estudos de Casos e Controles , Criança , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: IgE-expressing (IgE+ ) plasma cells (PCs) provide a continuous source of allergen-specific IgE that is central to allergic responses. The extreme sparsity of IgE+ cells in vivo has confined their study almost entirely to mouse models. OBJECTIVE: To characterize the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs. METHODS: To generate human IgE+ cells, we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR, we examined the phenotype of generated IgE+ cells, the capacity of tonsil B-cell subsets to generate IgE+ PCs and the class switching pathways involved. RESULTS: We have identified three phenotypic stages of IgE+ PC development pathway, namely (i) IgE+ germinal centre (GC)-like B cells, (ii) IgE+ PC-like 'plasmablasts' and (iii) IgE+ PCs. The same phenotypic stages were also observed for IgG1+ cells. Total tonsil B cells give rise to IgE+ PCs by direct and sequential switching, whereas the isolated GC B-cell fraction, the main source of IgE+ PCs, generates IgE+ PCs by sequential switching. PC differentiation of IgE+ cells is accompanied by the down-regulation of surface expression of the short form of membrane IgE (mIgES ), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgEL ), which is associated with an enhanced B-cell survival and expressed in humans, but not in mice. CONCLUSION: Generation of IgE+ PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL /mIgES ratio may be implicated in survival of IgE+ B cells during PC differentiation and allergic disease.
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Linfócitos B/metabolismo , Expressão Gênica , Imunoglobulina E/genética , Plasmócitos/metabolismo , Linfócitos B/citologia , Linfócitos B/imunologia , Biomarcadores , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Células Cultivadas , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Humanos , Switching de Imunoglobulina/genética , Switching de Imunoglobulina/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Imunofenotipagem , Fenótipo , Plasmócitos/citologia , Plasmócitos/imunologiaRESUMO
Melon (Cucumis melo L.) is an important vegetable crop that ranks second in salt tolerance among the Cucurbitaceae. Previous studies on the two muskmelon cultivars 'Bing XueCui' (BXC) and 'Yu Lu' (YL) revealed that they had different characteristics under salt stress, but the molecular basis underlying their different physiological responses is unclear. Here, we combined a physiological study with a genome-wide transcriptome analysis to understand the molecular basis of genetic variation that responds to salt stress in the melon. BXC performed better under salt stress than YL in terms of biomass and photosynthetic characteristics, because it exhibited less reduction in transpiration rate, net photosynthesis rate, and stomatal conductance under 150-mM NaCl stress than YL. A transcriptome comparison of the leaves of the cultivars revealed that 1171 genes responded to salt stress in BXC while 1487 genes were identified as salt-stress-responsive in YL. A real-time polymerase chain reaction analysis of 12 of the responsive genes revealed that there was a strong, positive correlation with RNA sequencing data. The genes were involved in several pathways, including photosynthesis, the biosynthesis of secondary metabolites, metabolism, and plant hormone signal transduction, and their expression levels differed between the two cultivars in response to salt stress. This study provides a molecular perspective of two melon cultivars in response to salt stress, and its results could be used to investigate the complex molecular mechanisms underlying salt tolerance in the melon.
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Cucumis melo/fisiologia , Plantas Tolerantes a Sal/fisiologia , Cucumis melo/genética , Expressão Gênica , Perfilação da Expressão Gênica , Salinidade , Tolerância ao Sal/genética , Plantas Tolerantes a Sal/genética , Estresse Fisiológico/genética , TranscriptomaRESUMO
We analyzed the association between polymorphisms in three glutathione S-transferase genes (GSTP1, GSTM1, and GSTT1) and the treatment outcome for advanced non-small cell lung cancer (NSCLC). We recruited 284 NSCLC patients at advanced stage from Department of Radiotherapy in Peace Hospital Attached to Changzhi Medical College between May 2009 and May 2011, who had received cisplatin-based chemotherapy. The GSTP1, GSTM1, and GSTT1 genotyping for was determined using DNA pyrosequencing on an ABI Prism 3100 DNA analyzer. In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes of GSTP1 were associated with lower risk of disease progression compared with the IIe/IIe genotype, and the HRs (95%CIs) were 0.37 (0.18-0.74) and 0.15 (0.06-0.35), respectively. The IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with NSCLC, and the HRs (95%CIs) were 0.52 (0.29-0.92) and 0.37 (0.17- 0.79), respectively No significant association was observed between GSTM1 and GSTT1 polymorphisms and progression-free survival and overall survival in the NSCLC patients. In summary, we suggest that GSTP1 polymorphisms might influence the treatment outcome of advanced NSCLC patients, and our results could help improve individualized therapy.
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Carcinoma Pulmonar de Células não Pequenas/genética , Glutationa S-Transferase pi/genética , Adulto , Idoso , Povo Asiático , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/terapia , China , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Feminino , Estudos de Associação Genética , Glutationa Transferase/genética , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Investigation of the relationship between mitochondrial DNA (mtDNA) variants and Parkinson disease (PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking. METHODS: The index mtDNA variants and their defining mitochondrial haplogroup were determined in 725 PD patients and 744 non-PD controls. Full-length mtDNA sequences were also conducted in 110 cases harboring various haplogroups. Cybrid cellular models, composed by fusion of mitochondria-depleted rho-zero cells and donor mitochondria, were used for a rotenone-induced PD simulation study. RESULTS: Multivariate logistic regression analysis revealed that subjects harboring the mitochondrial haplogroup B5 have resistance against PD (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002). Furthermore, a composite mtDNA variant group consisting of A10398G and G8584A at the coding region was found to have resistance against PD (odds ratio 0.50, 95% confidence interval 0.33-0.78; P = 0.001). In cellular studies, B4 and B5 cybrids were selected according to their higher resistance to rotenone, in comparison with cybrids harboring other haplogroups. The B5 cybrid, containing G8584A/A10398G variants, showed more resistance to rotenone than the B4 cybrid not harboring these variants. This is supported by findings of low reactive oxygen species generation and a low apoptosis rate in the B5 cybrid, whereas a higher expression of autophagy was observed in the B4 cybrid particularly under medium dosage and longer treatment time with rotenone. CONCLUSIONS: Our studies, offering positive results from clinical investigations and cybrid experiments, provide data supporting the role of variant mtDNA in the risk of PD.
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DNA Mitocondrial/genética , Variação Genética , Doença de Parkinson/genética , Idoso , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: The paracrine effects of mesenchymal stem cells (MSCs) were weakened during aging. This study explored whether resveratrol can attenuate senescence of adipose-derived MSCs (ADMSCs) and whether Pim-1 is involved in resveratrol's effect on paracrine of ADMSCs and insulin secretion of INS-1 cells. MATERIALS AND METHODS: CCK-8 assay and SA-b-gal assay were performed to test the protective effect of resveratrol on senescent models. QRT-PCR and western blot analysis were performed to analyze of senescence- and ß-cell associated genes. QRT-PCR and ELISA analysis was performed to test telomere length and activity. Immunofluorescence and ELISA assay were performed to assess the paracrine effects on promoting insulin secretion of INS-1 cells. RESULTS: Resveratrol could protect ADMSCs from H2O2 and D-glucose-induced senescence and also attenuate senescence in long-term cultured ADMSCs in vitro. In addition, resveratrol attenuated H2O2 induced higher expression of senescence-associated genes, including P53, P21, Cyclin D1, IL-6 and MMP1, but increased the expression of Sirt1, a well-known anti-senescence gene. Resveratrol significantly enhanced Pim-1 expression in aging ADMSCs through PI3K/AKT signal pathway. The conditioned medium (CM) of ADMSCs enhanced insulin secretion and expression of the key genes for ß-cell function including TFAM, PDX1, GLUT2 and HNF-1α via Pim-1. INS-1 cells with Pim-1 knockdown had decreased insulin secretion. CONCLUSIONS: This study firstly reported that resveratrol has a protective effect on senescence of ADMSCs and can preserve the paracrine effect of the ADMSCs on promoting insulin secretion of INS-1 cells via Pim-1. Therefore, it might be a promising adjuvant agent for future MSCs based therapy.
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Insulina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Estilbenos/farmacologia , Envelhecimento , Animais , Glucose/farmacologia , Ratos , Resveratrol , TransfecçãoRESUMO
Intervertebral disc degeneration is the main cause of lumbago disease, in which the extracellular matrix structure and moisture in the nucleus pulposus is lost continuously. In this study, we aimed to detect differential expression of silence mating type information regulation 2 homolog 1 (SIRT1) and matrix metalloproteinase-1 (MMP-1) in human intervertebral disc nucleus pulposus cells and to explore the effects of SIRT1 and MMP-1 on the development of the intervertebral disc degeneration. Intervertebral disc nucleus pulposus specimens from 41 patients who underwent lumbar protrusion resection at HuiZhou Municipal Central Hospital, during the period from October 2011 to December 2013, were studied in comparison with 23 control cases from patients who underwent fractured lumbar resection. In degenerated human intervertebral disc nucleus pulposus cells, the expression of SIRT1 is decreased and MMP-1 is increased compared with that of the control cells. Resveratrol could reverse these effects, thereby increasing the expression of SIRT1 (0.87 ± 0.07 vs 0.54 ± 0.04), Coll2α1 (0.90 ± 0.08 vs 0.38 ± 0.01), and aggrecan (0.69 ± 0.07 vs 0.42 ± 0.05) and decreasing the expression of MMP-1 (0.61 ± 0.03 vs 0.93 ± 0.08). These results suggest that resveratrol could possibly reverse the process of intervertebral disc degeneration and thus could be applied as a potential drug for the disease.
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Regulação da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 1 da Matriz/genética , Sirtuína 1/genética , Estilbenos/farmacologia , Adulto , Idoso , Agrecanas/metabolismo , Células Cultivadas , Colágeno Tipo II/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Resveratrol , Sirtuína 1/metabolismo , Adulto JovemRESUMO
BACKGROUND: Antigen-specific human IgEs are important reagents in immunoassays to quantify antigen-specific IgEs in allergic patients, but they are not easy to prepare. METHODS: We constructed a knockin homozygous mouse strain, referred to as HεκKI strain, whose gene segment encoding γ1 constant region has been replaced by that encoding human ε constant region and gene segment encoding κ constant region replaced by that encoding human κ constant region. The mice were tested for their ability to produce antigen-specific chimeric human IgE (with mouse variable regions) upon the immunization with ovalbumin and papain. Subsequently, the spleen cells from the immunized mice were used as the source of B cells for the preparation of hybridomas, which secreted monoclonal human IgE antibodies specific for the antigens. RESULTS: The HεκKI mice expressed human IgE (ε, κ) in serum at levels 10- to 30-fold higher than those of mouse IgE. Upon immunization with an antigen, the mice yielded splenic B cells for preparing hybridomas that secrete chimeric human IgE specific for the antigen. Purified IgEs from those hybridomas could activate a basophilic cell line to undergo degranulation upon the stimulation with their respective antigens. CONCLUSIONS: We have developed a human ε gene and κ gene knockin mouse strain, which is useful for producing various antigen-specific chimeric human IgEs for potential use as standards in immunoassays.
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Alérgenos/imunologia , Imunoensaio , Imunoglobulina E/imunologia , Cadeias épsilon de Imunoglobulina/genética , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Especificidade de Anticorpos , Antígenos/imunologia , Basófilos/imunologia , Degranulação Celular/imunologia , Ensaio de Imunoadsorção Enzimática , Ordem dos Genes , Marcação de Genes , Loci Gênicos , Humanos , Hibridomas , Hipersensibilidade/diagnóstico , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Imunização , Imunoglobulina E/sangue , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Leves de Imunoglobulina/genética , Imunoglobulinas/sangue , Imunoglobulinas/imunologia , Camundongos , Camundongos TransgênicosRESUMO
CN17 is a functional stay-green wheat variety that exhibits delayed leaf senescence and enhanced photosynthetic competence. To better understand these valuable traits, levels of chlorophyll a and b, soluble proteins, unsaturated fatty acids, and other components of CN17 were assayed. In addition, chloroplast ultrastructure, chloroplast number, and differences in gene expression between CN17 and a control variety, MY11, were examined. By 21 d post-anthesis (DPA), CN17 leaves exhibited a significantly higher maximal photochemical efficiency for photosystem II (PSII) (F(v) /F(m) ) and a significantly higher efficiency of excitation capture by open PSII reaction centres (F(v) '/F(m) '). In addition, chlorophyll degradation in CN17 was delayed by approximately 14 d, and was not blocked as observed in cosmetic stay-green phenotypes. The soluble protein content (Ps) of CN17 was higher than MY11 at all timepoints assayed, and the ratio of unsaturated to saturated fatty acids was significantly higher. CN17 also exhibited isolated granal lamellae associated with vesicles and diminished peroxidation, and between 35 and 42 DPA, a sharp decrease in chloroplast number was detected. Taken together, these results strongly support the hypothesis that chloroplast ultrastructure regeneration is responsible for the functional stay-green trait of CN17, and gene expression data provide insight into the mechanistic details.
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Clorofila/metabolismo , Cloroplastos/ultraestrutura , Complexo de Proteína do Fotossistema II/metabolismo , Triticum/fisiologia , Clorofila A , Cloroplastos/fisiologia , Etiquetas de Sequências Expressas , Ácidos Graxos Insaturados/metabolismo , Biblioteca Gênica , Fotossíntese , Folhas de Planta/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Triticum/ultraestruturaRESUMO
Embryonal cancer can arise from postnatally persistent embryonal remnant or rest cells, which are uniquely characterized by the absence of p53 mutations. Perinatal overexpression of the MycN oncoprotein in embryonal cancer precursor cells causes postnatal rests, and later tumor formation through unknown mechanisms. However, overexpression of Myc in adult tissues normally activates apoptosis and/or senescence signals as an organismal defense mechanism against cancer. Here, we show that perinatal neuroblastoma precursor cells exhibited a transiently diminished p53 response to MycN oncoprotein stress and resistance to trophic factor withdrawal, compared with their adult counterpart cells from the TH-MYCN(+/+) transgenic mouse model of neuroblastoma. The adult stem cell maintenance factor and Polycomb group protein, Bmi1 (B-cell-specific Moloney murine leukemia virus integration site), had a critical role at neuroblastoma initiation in the model, by repressing p53 responses in precursor cells. We further show in neuroblastoma tumor cells that Bmi1 could directly bind p53 in a complex with other Polycomb complex proteins, Ring1A or Ring1B, leading to increased p53 ubiquitination and degradation. Repressed p53 signal responses were also seen in precursor cells for other embryonal cancer types, medulloblastoma and acute lymphoblastic leukemia. Collectively, these date indicate a general mechanism for p53 inactivation in some embryonal cell types and consequent susceptibility to MycN oncogenesis at the point of embryonal tumor initiation.
Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Células-Tronco Neoplásicas/patologia , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Estresse Fisiológico , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Humanos , Leucemia/metabolismo , Leucemia/patologia , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Camundongos , Proteína Proto-Oncogênica N-Myc , Neoplasias Embrionárias de Células Germinativas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Poliubiquitina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Estabilidade Proteica , Proteólise , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais , UbiquitinaçãoRESUMO
BACKGROUND: Patients with vascular Ehlers-Danlos syndrome (EDS) can develop internal carotid artery (ICA) aneurysms. Any surgical procedure is hazardous and often unrewarding because of fragile blood vessels. Endovascular treatment may be an alternative approach to the treatment of ICA aneurysms in patients with vascular EDS. CASE: A 23-year-old woman with vascular EDS developed a cervical right ICA aneurysm and a left petrous ICA aneurysm, which were successfully treated with endovascular interventions without major complications. CONCLUSION: This case report suggests that endovascular treatment of ICA aneurysms is feasible and can be achieved in patients with vascular EDS.
Assuntos
Doenças das Artérias Carótidas/cirurgia , Síndrome de Ehlers-Danlos/complicações , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Angiografia Digital , Implante de Prótese Vascular , Doenças das Artérias Carótidas/etiologia , Artéria Carótida Interna/cirurgia , Humanos , Aneurisma Intracraniano/etiologia , Masculino , Stents , Resultado do Tratamento , Adulto JovemRESUMO
Benign prostatic hyperplasia (BPH) is a kind of common noncancerous prostate gland enlargement with growing tendency in recent years. 5α-reductase is the key enzyme responsible for dihydrotestosterone biosynthesis and has been considered as an important target for designing inhibitors as potent therapeutic agents for BPH. Finasteride, the first steroidal 5α-reductase inhibitor, has been marketed worldwide as a drug for BPH. During these years, many other novel types of 5α-reductase inhibitors are being studied. This review summarizes recent advancement in steroidal 5α-reductase inhibitors.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/química , Inibidores de 5-alfa Redutase/química , Hiperplasia Prostática/tratamento farmacológico , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Inibidores de 5-alfa Redutase/uso terapêutico , Azasteroides/química , Azasteroides/uso terapêutico , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Humanos , Masculino , Pregnanos/química , Pregnanos/uso terapêutico , Hiperplasia Prostática/enzimologiaRESUMO
It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DC) helps to reduce acute allograft rejection. However, this method cannot effectively prevent grafts from infiltration of inflammatory cells and fibrosis, and thus has minimal effect on chronic allograft rejection. In this study, we used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor (Balb/c)-derived MMC-DC could induce hyporesponsiveness of recipient (C57BL/6) T cells in vitro, potentially by inducing T-cell apoptosis, decreasing IL-2 and IL-12 secretion, and increasing regulatory T-cell numbers and IL-10 secretion. Furthermore, anti-CD154 monoclonal antibody (mAb) treatment combined with donor-derived MMC-DC prolonged the survival of the allografts in vivo. The mechanisms were similar to those in vitro. Impressively, both acute and chronic rejection were prevented when donor and F1 generation (Balb/c × C57BL/6) derived MMC-DC were injected together with anti-CD154 mAb into recipients before heart allotransplantation. In summary, we showed that donor and F1-derived tolerogenic DC have a synergistic effect on induction and maintenance of T-cell regulation and the secretion of immunosuppressive cytokines. Moreover, adoptive transfer of these two types of DC could inhibit both acute and chronic transplant rejection in mice.