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AIM: To determine whether tumour vascular and cellular heterogeneity of high-grade glioma (HGG) is predictive of isocitrate dehydrogenase (IDH) mutation status and overall survival (OS) by using tumour habitat-based analysis constructed by perfusion and/or diffusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventy-eight HGG patients that met the 2021 World Health Organization WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), were enrolled to predict IDH mutation status, of which 32 grade 4 patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter were enrolled for prognostic analysis. The deep-learning-based model nnU-Net and K-means clustering algorithm were applied to construct the Traditional Habitat, Vascular Habitat (VH), Cellular Density Habitat (DH), and their Combined Habitat (CH). Quantitative parameters were extracted and compared between IDH-mutant and IDH-wild-type patients, respectively, and the prediction potential was evaluated by receiver operating characteristic (ROC) curve analysis. OS was analysed using Kaplan-Meier survival analysis and the log-rank test. RESULTS: Compared with IDH-mutants, median relative cerebral blood volume (rCBVmedian) values in the whole enhancing tumour (WET), VH1, VH3, CH1-4 habitats were significantly increased in IDH-wild-type HGGs (all p<0.05). Additionally, the accuracy of rCBVmedian values in CH1 outperformed other habitats in identifying IDH mutation status (p<0.001) at a cut-off value of 4.83 with AUC of 0.815. Kaplan-Meier survival analysis highlighted significant differences in OS between the populations dichotomised by the median of rCBVmedian in WET, VH1, CH1-3 habitats (all p<0.05). CONCLUSIONS: The habitat imaging technique may improve the accuracy of predicting IDH mutation status and prognosis, and even provide a new direction for subsequent personalised precision treatment.
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Neoplasias Encefálicas , Glioma , Humanos , Isocitrato Deshidrogenasa/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Glioma/diagnóstico por imagen , Glioma/genética , Imagen de Difusión por Resonancia Magnética , Pronóstico , Mutación/genética , Perfusión , Imagen por Resonancia Magnética/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Data regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited. METHODS: In a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis. RESULTS: A total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (IGHV) mutation, ibrutinib-rituximab resulted in better progression-free survival than chemoimmunotherapy (90.7% vs. 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50). The 3-year progression-free survival among patients with IGHV mutation was 87.7% in the ibrutinib-rituximab group and 88.0% in the chemoimmunotherapy group (hazard ratio for progression or death, 0.44; 95% CI, 0.14 to 1.36). The incidence of adverse events of grade 3 or higher (regardless of attribution) was similar in the two groups (in 282 of 352 patients [80.1%] who received ibrutinib-rituximab and in 126 of 158 [79.7%] who received chemoimmunotherapy), whereas infectious complications of grade 3 or higher were less common with ibrutinib-rituximab than with chemoimmunotherapy (in 37 patients [10.5%] vs. 32 [20.3%], P<0.001). CONCLUSIONS: The ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Rituximab/administración & dosificación , Adenina/análogos & derivados , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Femenino , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Piperidinas , Supervivencia sin Progresión , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Rituximab/efectos adversos , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
Objective: To evaluate the perfusion features of the anterior segment in patients with different types of strabismus. Methods: A cross-sectional study. Sixteen strabismus patients (16 eyes) who received the examination of iris indocyanine green angiography (ICGA) in Tianjin Eye Hospital from November 2016 to December 2021 were enrolled and divided into two groups according to whether they had a history of extraocular muscle injury/rectus muscle surgery. All patients underwent routine ophthalmic examinations. Angiographic images were obtained by the anterior segment camera, and indicators such as arm to iris circulation time, whole iris filling time, regression onset time, and complete regression time were recorded. The independent sample t test or Mann-Whitney U test was used to compare iris perfusion aspects of the two groups, and the Pearson/Spearman correlation tests was used to analyze the correlation of arm to iris circulation time and whole iris filling time with age and course of strabismus. Results: Among the 16 patients, there were 10 males and 6 females. The mean age was (49.2±13.2) years, and the course of strabismus ranged from 2 to 31 months. There were 7 patients in the group of without extraocualr muscle injury and 9 patients in the extraocular muscle injury/surgery group. There was no significant difference in age and course of strabismus between the two groups (both P>0.05). The arm to iris circulation time [M (Q1, Q3)] of the group without extraocular muscle injury and the group with extraocular muscle injury/surgery were 18 (18, 21) and 22 (20, 24) s, respectively. The average whole iris filling time was (13.86±1.95) and (12.22±3.60) s, respectively. There was no statistical significance between the two groups (both P>0.05). Correlation analysis showed that arm to iris circulation time was not correlated with age and course of strabismus (r=-0.033, -0.079; both P>0.05). And the whole iris filling time was not correlated with age and course of disease (r=0.057, -0.119; both P>0.05). The matrix scatter plots showed that in the group of extraocular muscle injury/surgery, there were three patients who were older than the average (49.2 years) and above the median of arm to iris circulation time (20 s) (two cases with the vertical muscle involved), meanwhile, there were three patients (all with the vertical muscle involved) whose course of strabismus was longer than 6 months and above the median of arm to iris circulation time, which were more than those in the group of without extraocular muscle injury (1 case, respectively). Conclusions: ICGA in patients with strabismus show that a history of injury to the extraocular muscle or surgical treatment beyond 2 months had no effect on iris perfusion. Age and course have no correlation with iris reperfusion. The vertical muscle involvement has more effects on the blood supply to the anterior segment.
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Verde de Indocianina , Estrabismo , Segmento Anterior del Ojo , Preescolar , Estudios Transversales , Femenino , Angiografía con Fluoresceína/métodos , Humanos , Lactante , Iris/diagnóstico por imagen , Isquemia , Masculino , Estrabismo/cirugíaRESUMEN
Objective: To explore the role of lysophosphatidic acid, vascular endothelial growth facor and endothelin in the pathogenesis of pulmonary fibrosis in coal workers'pneumoconiosis patients, the relationship of lysophosphatidic acid, VEGF and ET in serum was studied. Methods: Sixty two pneumoconiosis patients were selected as cases group, which included 23 cases of stage â , 25 cases of stageâ ¡and 14 cases of stageâ ¢. Twenty workers were selected as dust exposure group who exposed to coal dust for more than 2 years and had not been diagnosed as pneumoconiosis. Ten healthy people who had no occupational dust exposure were simultaneously selected as the control group. The serum levels of LPA, VEGF and ET were measured by ELISA. Results: The serum levels of VEGF and ET in coal dust exposed group and pneumoconiosis group were much higher than in the control group. The differences were statistically significant among the three groups (P<0.01) . The serum levels of LPA increased in the dust exposed group, stage â and stage â ¡group. The serum levels of LPA correlated positively with the levels of VEGF and ET (P<0.05) . Conclusions: The serum levels of LPA, VEGF and ET had evident correlation with the pulmonary fibrosis caused by coal dust, which indicate that LPA, VEGF and ET may play a pivotal role in the process of pulmonary fibrosis. The study will throw light on both pathogenesis and early intervention for pneumoconiosis.
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Minas de Carbón , Polvo , Endotelinas/sangre , Lisofosfolípidos/sangre , Exposición Profesional , Neumoconiosis/sangre , Fibrosis Pulmonar/patología , Factor A de Crecimiento Endotelial Vascular/sangre , Antracosis , Ensayo de Inmunoadsorción Enzimática , Humanos , Enfermedades Profesionales/patología , Neumoconiosis/patologíaRESUMEN
Objective: To observe the clinical and pathological features of uveal metastatic carcinoma. Methods: It was a retrospective case series study. The clinical manifestation, growth pattern, tumor types and relative pathological features of 13 patients visiting from January 1980 to December 2014 with uveal metastatic carcinoma in Tianjin Eye Hospital were analyzed retrospectively. Results: There were 13 cases, 6 cases of male and 7 of female. Age was from 37.0 to 66.0 years old. The mean age was 52.1 years old. all cases were monocular. There were 5 cases with right eye and 8 cases with left eye. Among 13 cases, 10 tumors were in posterior choroid, one tumor was in anterior choroid and ciliary body, 2 tumors were in the iris. There were 5 patients with lung cancer, 4 patients with breast cancer, 1 patient with prostate cancer, 1 patient with thyroid cancer and 1 patient with esophageal cancer. The primary tumor wasn't found in 1 patient. The rapid decrease of visual acuity showed in 10 patients with posterior choroidal metastatic carcinoma, 8 of them accompanied with extensive retinal detachment and 6 of them had secondary glaucoma. The multiple gray-white nodule or pink cauliflower mass on the papillary margin of iris were showed respectively in 2 patients with iris metastatic carcinoma. The pathological examination found that posterior choroidal metastatic carcinoma mainly located in temporal or nasal side choroids in 10 cases, among them, local or diffuse flat choroidal masses showed in 6cases, extensive mass involving choroid and ciliary body showed in 1 case, large nodular or globular choroidal mass showed in 2 cases, choroidal mass surrounded the optic disc in 1 case, optic nerve invasion showed in 3 cases and extraocular or orbital invasion showed in 3 cases. The scleral and subconjunctival invasion showed in 1 case of anterior choroid and ciliary body metastatic carcinoma. Conclusions: Uveal metastatic carcinoma manifested various growth pattern, the rapid decrease of visual acuity, flat or nodular choroidal solid mass, secondary retinal detachment and glaucoma were common clinical features. Some cases might invade extraocular or orbital tissue. (Chin J Ophthalmol, 2016, 52: 769-774).
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Cuerpo Ciliar/patología , Melanoma/secundario , Neoplasias de la Úvea/secundario , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Coroides/secundario , Neoplasias Esofágicas/patología , Femenino , Humanos , Neoplasias del Iris/secundario , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Desprendimiento de Retina/diagnóstico , Estudios Retrospectivos , Enfermedades de la Esclerótica/patología , Neoplasias de la Tiroides/patología , Agudeza VisualRESUMEN
The article "METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2, by Q.-Z. Meng, C.-H. Cong, X.-J. Li, F. Zhu, X. Zhao, F.-W. Chen, published in Eur Rev Med Pharmacol Sci 2020; 24 (8): 4328-4336-DOI: 10.26355/eurrev_202004_21014-PMID: 32373970" has been retracted by the authors. After publication, several issues were raised on PubPeer about the reliability of the published results. The same authors stated that the study was not performed in accordance with the standard procedures required. In particular, Figure 1 also presents some concerns as it does not reflect the experimental data reported in the study. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21014.
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Motor learning can improve both the accuracy and precision of motor performance. We analyzed changes in the average trajectory and the variability of smooth eye movements during motor learning in rhesus monkeys. Training with a compound visual-vestibular stimulus could reduce the variability of the eye movement responses without altering the average responses. This improvement of eye movement precision was achieved by shifting the reliance of the movements from a more variable, visual signaling pathway to a less variable, vestibular signaling pathway. Thus, cerebellum-dependent motor learning can improve the precision of movements by reweighting sensory inputs with different variability.
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Movimientos Oculares/fisiología , Aprendizaje/fisiología , Estimulación Luminosa/métodos , Desempeño Psicomotor/fisiología , Vías Visuales/fisiología , Animales , Macaca mulatta , Masculino , Inhibición Neural/fisiologíaRESUMEN
In line with its rapidly transforming economy, thousands of development proposals undergo Environmental Impact Assessment (EIA) in Vietnam each year. Since its inception in 1993, Vietnam's EIA system has undergone numerous amendments via a suite of legislative reforms to the Law on Environmental Protection (LEP) and its associated Circulars and Decrees, a testament to the Government's will to improve environmental performance. Here we evaluate the effectiveness of Vietnam's EIA system through a unique empirical study focusing on those engaged in the EIA system undertaken in Hanoi in 2016 comprising 20 semi-structured interviews with respondents from government, NGOs, academia, and industry. By evaluating the effectiveness of the EIA system in Vietnam from the stakeholder perspective, this paper aims to identify where, how, and why the EIA system is effective or otherwise. Stakeholders vary in their perceptions of the system. Those external to it identified several inhibiting characteristics. Results suggest that like other developing countries and jurisdictions, Vietnam's EIA procedural performance falls short of EIA goals. Criticisms of discordant dual planning law and environmental management laws, fragmented decision making, conflicts of interest in appraisal committee appointments, and information deprivation that impedes public participation suggest that like other developing countries and jurisdictions, Vietnam's EIA performance, in practice, faces several challenges that potentially undermine its role in environmental protection.
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Mitochondrial DNA (mtDNA) damage is a very important molecular event, which has significant effects on living organisms. Therefore, a particularly important challenge for biomaterials research is to develop functionalized nanoparticles that can activate and monitor mtDNA damage and instigate cancer cell apoptosis, and as such eliminate the negative effects on living organisms. Toward that goal, with this research, we have developed a hydroxyapatite ultrathin nanosheet (HAP-PDCns)-a high Ca2+ content biomaterial. HAP-PDCns undergoes proton-triggered decomposition after entering cancer cells via clathrin-mediated endocytosis, and then, it selectively concentrates in the charged mitochondrial membrane. This kind of proton-triggered decomposition phenomenon facilitates mtDNA damage by causing instantaneous local calcium overload in the mitochondria of cancer cells, and inhibits tumor growth. Importantly, at the same time, a real-time green-red-green fluorescence change occurs that correlates with the degree of mtDNA deterioration because of the changes in the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gaps during this process. Significantly, the decomposition and the fluorescence changes cannot be triggered in normal cells. Thus, HAP-PDCns can selectively induce apoptosis and the death of a cancer cell by facilitating mtDNA damage, but does not affect normal cells. In addition, HAP-PDCns can simultaneously monitor the degree of mtDNA damage. We anticipate that this design strategy can be generalized to develop other functionalized biomaterials that can be used to instigate the positive effects of mtDNA damage on living organisms while eliminating any negative effects.
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Daño del ADN , ADN Mitocondrial/genética , Durapatita/química , Nanoestructuras/química , Técnicas Biosensibles/métodos , Calcio/química , Línea Celular , Daño del ADN/efectos de los fármacos , Durapatita/farmacología , Células Hep G2 , Humanos , ProtonesRESUMEN
OBJECTIVE: The aim of this study was to investigate whether METTL3 promoted the progression of nasopharyngeal carcinoma (NPC) by silencing CDKN1C through EZH2. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression level of METTL3 in 48 pairs of NPC tissues and adjacent normal tissues. METTL3 expression in patients with different tumor lymph node metastasis (TNM) stages was detected by qRT-PCR as well. The Kaplan-Meier method was used to analyze the interplay between METTL3 expression and the prognosis of patients with NPC. At the same time, METTL3 expression in normal epithelial cell line (BEAS-2B) and NPC cell lines (SUNE-1 and C666-1) was examined using qRT-PCR. After METTL3 was knocked down in SUNE-1 cells, cell viability and migration abilities were analyzed by cell counting kit-8 (CCK-8) test and wound healing assay, respectively. The mRNA and protein expressions of EZH2 were detected by qRT-PCR and Western blot, respectively. RNA immunoprecipitation (RIP) assay was applied to detect the binding of METTL3 to EZH2 mRNA and the m6A modification on EZH2 mRNA. After knockdown of EZH2 in SUNE-1 cells, qRT-PCR was used to detect the mRNA expression of CDKN1C. Meanwhile, chromatin immunoprecipitation (ChIP) assay was conducted to analyze the binding of EZH2 to the CDKN1C promoter region. After down-regulation of METTL3 in SUNE-1 cells, the protein expressions of EZH2 and CDKN1C were detected using Western blot. After simultaneous knockdown of METTL3 and CDKN1C in SUNE-1 cells, CCK8 assay and wound healing assay were applied to examine cell viability and migration abilities. RESULTS: METTL3 expression in NPC tissues was remarkably higher than that of adjacent normal tissues. Meanwhile, METTL3 expression in T3 and T4 tumors was significantly higher than that of T1 and T2 tumors. In patients with lymph node metastasis, the expression of METTL3 was remarkably higher than those without metastasis. Survival analysis demonstrated that patients with higher expression of METTL3 exhibited significantly longer overall survival time than those with lower METTL3 expression. QRT-PCR revealed that METTL3 was highly expressed in NPC cell lines, including SUNE-1 and C666-1. After knock-down of METTL3 in SUNE-1 cells, cell viability and migration abilities were both markedly weakened. Meanwhile, the protein expression of EZH2 was remarkably reduced. However, no significant changes were observed in EZH2 mRNA level. RIP assay revealed that METTL3 could bind to EZH2 mRNA, and a m6A modification was verified on EZH2 mRNA. After knockdown of EZH2, the mRNA level of CDKN1C in SUNE-1 cells was significantly up-regulated. CHIP assay indicated that EZH2 could bind to CDKN1C. Western blot showed that, after interfering with METTL3 in SUNE-1 cells, the protein expression of EZH2 decreased significantly, while CDKN1C was up-regulated. In addition, simultaneous downregulation of METTL3 and CDKN1C in SUNE-1 cells reversed the influence of METTL3 on cell viability and migration abilities. CONCLUSIONS: METTL3 was highly expressed in NPC tissues, which might inhibit EZH2 expression by mediating M6A modification of EZH2 mRNA. Furthermore, CDKN1C could increase the malignancy of NPC cells and promote the progression of NPC.
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Adenosina/análogos & derivados , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Metiltransferasas/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Adenosina/metabolismo , Células Cultivadas , Proteína Potenciadora del Homólogo Zeste 2/genética , Humanos , Metiltransferasas/genética , Carcinoma Nasofaríngeo/diagnóstico , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to clarify the role of microRNA-433-5p (miRNA-433-5p) in influencing pathological lesions following acute spinal cord injury (SCI) by targeting mitogen-activated protein kinase 1 (MAPK1). PATIENTS AND METHODS: SCI model was successfully established in mice by performing hitting injury procedures. Serum levels of miRNA-433-5p and MAPK1 in SCI patients and mice were determined. Grip strengths of both forelimbs in SCI mice and controls were determined. Dual-Luciferase reporter gene assay was applied to verify the binding relation between miRNA-433-5p and MAPK1. After overexpression of miRNA-433-5p and MAPK1 in vivo, the grip strength changes in SCI mice were assessed. Furthermore, the protein level of inflammatory factor iNOS in 293T cells influenced by miRNA-433-5p and MAPK1 was detected by Western blot. RESULTS: MiRNA-433-5p was significantly downregulated in the serum of SCI patients and mice, whereas MAPK1 was up-regulated. Grip strengths of SCI mice were significantly lower than those of controls at different postoperative time points. However, this could be markedly reversed by the in vivo overexpression of miRNA-433-5p. Western blot indicated that the protein level of iNOS was remarkably downregulated in 293T cells overexpressing miRNA-433-5p. MAPK1 was confirmed as the target of miRNA-433-5p, whose expression level was negatively regulated by miRNA-433-5p. Importantly, MAPK1 partially reversed the protective role of miRNA-433-5p in grip strength of SCI mice and inflammatory response at post-SCI. CONCLUSIONS: Overexpression of miRNA-433-5p protects SCI-induced motor dysfunction and inflammatory response by targeting MAPK1.
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MicroARNs/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , MicroARNs/genética , Traumatismos de la Médula Espinal/patologíaRESUMEN
Hypoxia and reoxygenation (H/R)-induced damage often happens soon after islets are transplantation. The process of islet isolation and purification causes the rapid onset of hypoxia. We sought to develop a functional scaffold to sustain the structure and function of islets as well as to recover some of the surface molecules damaged during isolation, seeking to improve islet transplantation outcomes. Self-assembling peptide nanofiber (SAPNF), a new type of substrate has been shown to be an excellent biological material for neuronal cell culture and tissue engineering in animals. In this study, we investigated the protective effect of SAPNF on damage to rat islets. Freshly prepared rat islets from male Sprague-Dawley rats were seeded in plates coated with (SAPNF-treated group) or without (control group) SAPNF. The islets were then divided into two groups culture under normoxia for 7 days versus exposure to hypoxia (< 1% O2) for 6 hours followed by reoxygenation for 24 hours. The results showed that SAPNF exhibited improving effects on viability and function of cultured islets, protecting the one from H/R-induced damage. In both groups, the stimulation index of SAPNF-treated groups were about two times the controls. SAPNF treatment decreased apoptotic rates of islet cells. These results suggested the usefulness of SAPNF to maintain the viability and function of rat pancreatic islets. SAPNF may be a potential scaffold for clinical islet transplantation.
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Diabetes Mellitus Experimental/cirugía , Trasplante de Islotes Pancreáticos/métodos , Péptidos , Animales , Apoptosis , Técnicas de Cultivo de Célula/métodos , Hipoxia de la Célula , Supervivencia Celular , Glucosa/farmacología , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/citología , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , Andamios del TejidoRESUMEN
OBJECTIVES: A pig-to-monkey transplant model was initiated to investigate the outcome of pig-to-human xenotransplantation. Though monkey is close to human in biology and physiology, the genetic differences between the two species remains unclear. This study sought to compare the gene expressions of three tissues from humans and rhesus monkey. METHODS: RNA samples extracted from liver, spleen, and peripheral blood cells were hybridized onto Illumina gene expression microarray. Genes with detected signals greater than 1000 and diff-scores higher than 100 were selected as significant results. The data were analyzed with Illumina software. mRNA expression levels were confirmed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis. RESULTS: Of the 47,293 transcripts tested on every gene chip, more than 6000 genes were expressed in three tissues. Total numbers of genes detected and the similarity ratios followed the same rule as liver < PBC < spleen. The 136 IRI-related genes, 192 immunological-related genes, and 131 cell cycle-related genes selected and analyzed showed gene expression concordance rates of 82.35%, 72.92%, and 77.10%, respectively. RT-PCR tests indicated similar mRNA expression levels of RTN4, interleukin (IL)-1beta, NF-kappaB1, IL-8, and G0S2 to the results on chips. CONCLUSIONS: The detected mRNA expressions in human and monkey tissues showed an average consistency in 85.78%, indicating that a human microarray might provide a part of the information for monkey sample testing. Therefore, in pig-to-monkey transplant models, monkey microarray may be used to determine recipient gene expressions. The genetic difference between human and monkey must be taken into account in interpreting the experimental results.
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Perfilación de la Expresión Génica , Macaca mulatta/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Trasplante Heterólogo , Animales , Amplificación de Genes , Humanos , Masculino , ARN/genética , ARN/aislamiento & purificación , Valores de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Porcinos , Transcripción GenéticaRESUMEN
The aim of the present experiment was to determine whether a single 30 s of exposure to -2 Gz (foot-to-head inertial forces) as orthostatic stress results in altered brain oxygenation control in response to active standing. Cerebral oxygenation (oxy-Hb), cerebral blood volume (CBV), and mean arterial blood pressure at brain level (MAPbrain) were recorded in 12 subjects in supine and then in standing position (10 min), before and after -2 Gz centrifugation. The decrease in oxy-Hb (-5 +/- 9 vs. -9 +/- 10 microM, P < 0.001) and in CBV (-2 +/- 11 vs. -4 +/- 12 microM, P < 0.05) upon standing was more important after -2 Gz centrifugation, with unchanged MAPbrain (-6 +/- 7 vs. -6 +/- 9 mmHg). These findings suggest a downward shift in the static cerebral autoregulation curve.
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Encéfalo/metabolismo , Gravedad Alterada , Hipotensión Ortostática , Oxígeno/metabolismo , Postura , Adulto , Presión Sanguínea , Volumen Sanguíneo , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: miRNA-21 (miRNA-21) has recently been recognized to tumor suppressive in various types of cancers. However, the role of miRNA-21 in gastrointestinal stromal tumors (GISTs) is still ambiguous. In this study, we investigated the regulation by miRNA-21 on the sensitivity of gastrointestinal stromal tumors (GISTs) cells to Imatinib. MATERIALS AND METHODS: We examined the expression of miRNA-21 and B-cell lymphoma 2 (Bcl-2) in GIST specimens by the real-time quantitative PCR assay (RT-qPCR). Then we explored the regulation by miRNA-21 on the Bcl-2 expression by the RT-qPCR assay, Western blotting assay and the luciferase assay in GIST-T1 cells. In addition, we examined the influence of miRNA-21 on the sensitivity to Imatinib of GIST-T1 cells with colony forming assay and apoptotic assay. RESULTS: Results indicated that miRNA-21 expression was suppressed in GIST tissues. And we identified putative miRNA-21 binding sites within the 3'-untranslated region (3'-UTR) of the human Bcl-2 gene. Transient transfection of miRNA-21 mimics into human GIST GIST-T1 cell line significantly downregulated the Bcl-2 expression in both mRNA and protein levels. Moreover, the miRNA-21 mimics transfection markedly aggravated the Imatinib-mediated growth inhibition and apoptosis induction in GIST-T1 cells. CONCLUSIONS: Our results demonstrated that miRNA-21 suppressed Bcl-2 expression in GIST cells and could function as a potent tumor suppressor in GIST. And the miRNA-21 promotion could sensitize GIST cells to Imatinib. It implies a potential role in the GIST treatment.
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Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/genética , Mesilato de Imatinib/uso terapéutico , MicroARNs , Benzamidas , Línea Celular Tumoral , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Linfoma de Células B , MicroARNs/genética , Piperazinas/uso terapéutico , Pirimidinas/uso terapéuticoRESUMEN
Magnetic interactions in solids are normally mediated by short-range exchange or weak dipole fields. Here we report a magnetic interaction that can propagate over long distances (â¼10 nm) across a polar insulating oxide spacer. Evidence includes oscillations of magnetization, coercivity and field-cooled loop shift with the thickness of LaAlO3 in La0.67Sr0.33MnO3/LaAlO3/SrTiO3 heterostructures. Similar modifications of the hysteresis loop appear when two coupled films of La0.67Sr0.33MnO3 are separated by LaAlO3, or another polar insulator, but they are absent when the oxide spacer layer is nonpolar. The loop shift is attributed to strong spin-orbit coupling and Dzyaloshinskii-Moriya interaction at the interfaces. There is evidence from inelastic light scattering that the polar spacer mediates long-range transmission of orbital magnetization. This coupling mechanism is expected to apply for any conducting ferromagnetic oxide with mixed valence; in view of electron hopping frequency involved, it raises the prospect of terahertz tunability of magnetic coupling.
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The climbing fiber input to the cerebellum from the inferior olive is thought to act as a teacher whose activity controls the induction of motor learning. We designed training conditions that did not elicit instructive signals in the climbing fibers, but nevertheless induced robust and consistent motor learning in the vestibulo-ocular reflex of rhesus monkeys. Our results indicate that instructive signals in the climbing fibers are not necessary for cerebellum-dependent learning. Instead, instructive signals carried by either the climbing fibers or Purkinje cell simple spikes may be sufficient to induce motor learning, with additive effects occurring when both instructive signals are present during training.