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BACKGROUND: This study aimed to explore differences in vitreous humour metabolites and metabolic pathways between patients with and without diabetic retinopathy (DR) and identify potential metabolite biomarkers. METHODS: Clinical data and vitreous fluid samples were collected from 125 patients (40 without diabetes, 85 with DR). The metabolite profiles of the vitreous fluid samples were analysed using ultra-high performance liquid chromatography, Q-Exactive mass spectrometry, and multivariate statistical analysis. A machine learning model based on Least Absolute Shrinkage and Selection Operator Regularized logistic regression was used to build a risk scoring model based on selected metabolite levels. Candidate metabolites were regressed to glycated haemoglobin levels by a logistic regression model. RESULTS: Twenty differential metabolites were identified between the DR and control groups and were significantly enriched in five Kyoto Encyclopedia of Genes and Genomes pathways (arginine biosynthesis; tricarboxylic acid cycle; alanine, aspartate, and glutamate metabolism; tyrosine metabolism; and D-glutamate metabolism). Ferrous ascorbate significantly contributes to poorer glycaemic control outcomes, offering insights into potential new pathogenic pathways in DR. CONCLUSIONS: Disorders in the metabolic pathways of arginine biosynthesis, tricarboxylic acid cycle, alanine, aspartate, glutamate metabolism, tyrosine metabolism, and D-glutamate metabolism were associated with DR. Risk scores based on vitreous fluid metabolites can be used for the diagnosis and management of DR. Ferrous ascorbate can provide insights into potential new pathogenic pathways for DR.
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Ácido Ascórbico , Biomarcadores , Retinopatia Diabética , Metabolômica , Corpo Vítreo , Humanos , Retinopatia Diabética/metabolismo , Retinopatia Diabética/diagnóstico , Corpo Vítreo/metabolismo , Biomarcadores/metabolismo , Masculino , Metabolômica/métodos , Feminino , Pessoa de Meia-Idade , Ácido Ascórbico/metabolismo , Idoso , Cromatografia Líquida de Alta PressãoRESUMO
Background: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has been widely used for evaluating patients with soft tissue sarcoma (STS). However, uncertainties and overlap among individuals may be observed, and the relevance of these findings remains to be further explored. The present study was aimed at investigating the correlation between PET metabolic parameters and quantitative pathological characteristics in STS. Methods: We retrospectively collected 39 patients with STS who underwent 18F-FDG PET/computed tomography (CT) examination before treatment. Metabolic parameters including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and intratumoral FDG uptake heterogeneity (IFH) were measured. Histological grading was performed according to the French Federation of Cancer Centers grading system. Continuous staining of tissue sections and digital quantitative analysis methods were used, the characteristics of tumor nucleated cells were observed through hematoxylin-eosin staining, and the expression of CD163, CD68, CD8, and CD4 in tumor tissues was determined by immunohistochemistry (IHC), then the correlation between FDG metabolic parameters and the above quantitative pathological characteristics in patients with STS were evaluated. Results: The SUVmax of 18F-FDG PET/CT in STS was positively correlated with the total nuclear area (r=0.355, P=0.027). SUVmax was also positively correlated with the expression levels of CD163, CD68, CD8, and CD4 (r=0.582, 0.485, 0.343, and 0.324, with P<0.001, 0.002, 0.032, and 0.044, respectively), but was not significantly correlated with cell count and mean nuclear area (all P>0.05). However, MTV, TLG, and IFH were not significantly correlated with the above quantitative pathological characteristics. Further multivariate logistic regression analysis indicated that only CD163 expression and histological grade were independently correlated with SUVmax. Moreover, SUVmax remained positively correlated with CD163 expression in the low-grade STS (r=0.820, P=0.001) and high-grade STS groups (r=0.430, P=0.028). Conclusions: 18F-FDG uptake was positively correlated with the quantitative pathological features of soft tissue tumors. SUVmax may be a meaningful method reflecting the level of M2 macrophage infiltration and may provide additional valuable information for preclinical evaluation of STS.
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In this study, we have employed metabolomics technology in combination with network pharmacology to ascertain the key metabolites and hub genes. The objective was to explore the pathway of Qibai Pingfei Capsule (QBPF) in treating COPD through metabolomics. We identified 96 differential metabolites in the lung tissues of rats belonging to control and model groups, out of which 47 were observed to be critical (VIP >2, p < 0.05). Furthermore, 16 important differential metabolites were reversed after QBPF treatment. Using network pharmacology, we identified 176 core targets of 81 drug-active ingredients. Our comprehensive analysis of network pharmacology and metabolomics enabled us to identify a core target, prostaglandin-endoperoxide synthase 2 (PTGS2), and a core metabolic pathway for glutathione metabolism. Finally, the result of molecular docking showed that PTGS2 had strong binding activity to 18 compounds including Fumarine and Kaempferol, etc.. PTGS2 is a marker of ferroptosis, so we wanted to explore whether QBPF could inhibit ferroptosis in COPD. The results showed that ferroptosis was involved in the pathogenesis of COPD, and QBPF could inhibit the occurrence of ferroptosis. In conclusion, the mechanism of QBPF for treating COPD may be related to PTGS2 expression, glutathione metabolism and ferroptosis.
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Background: Alzheimer's disease is a common neurodegenerative disease, and patients with early-onset Alzheimer's disease (onset age < 65 years) often have atypical symptoms, which are easily misdiagnosed and missed. Multimodality neuroimaging has become an important diagnostic and follow-up method for AD with its non-invasive and quantitative advantages. Case presentation: We report a case of a 59-year-old female with a diagnosis of depression at the age of 50 after a 46-year-old onset and a 9-year follow-up observation, who developed cognitive dysfunction manifested by memory loss and disorientation at the age of 53, and eventually developed dementia. Combined with neuropsychological scales (MMSE and MOCA scores decreased year by year and finally reached the dementia criteria) and the application of multimodal imaging. MRI showed that the hippocampus atrophied year by year and the cerebral cortex was extensively atrophied. 18F-FDG PET image showed hypometabolism in right parietal lobes, bilateral frontal lobes, bilateral joint parieto-temporal areas, and bilateral posterior cingulate glucose metabolism. The 18F-AV45 PET image showed the diagnosis of early-onset Alzheimer's disease was confirmed by the presence of Aß deposits in the cerebral cortex. Conclusion: Early-onset Alzheimer's disease, which starts with depression, often has atypical symptoms and is prone to misdiagnosis. The combination of neuropsychological scales and neuroimaging examinations are good screening tools that can better assist in the early diagnosis of Alzheimer's disease. Graphical Abstract.
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Background: A potential link between asthma and frailty has been suggested in previous studies. However, the nature of the causal relationship between these two conditions warrants further investigation. Therefore, this study assessed the bidirectional causality between asthma and frailty risk using two-sample Mendelian randomization (MR). Methods: The study data were obtained from the genome-wide association study (GWAS) dataset, with 337,159 samples representing asthma data and 175,226 samples representing frailty. The causal relationship between the two disorders was assessed by selecting the single nucleotide polymorphisms (SNPs), significantly associated with both asthma and frailty. The inverse variance weighting (IVW) method was used as the main analytical method to estimate the possible influence of causality. Sensitivity analysis was also performed using Mr-Egger intercept, funnel plot, "leave-one-out," and Cochran Q test. In addition, potential mediators were investigated by risk factor analysis. Result: The IVW method showed an increased risk of frailty due to increased genetic susceptibility factors and the number of to asthma (OR = 2.325, 95%CI:1.958-2.761; p = 6.527498e-22), while no horizontal pleiotropy was observed for the Mr-Egger intercept (p = 0.609) and the funnel plot. The Cochran Q value was 72.858, p = 0.024, and there was heterogeneity in the Cochran Q-value. No single SNP was observed for "leave-one-out" that had a biasing effect on the instrumental variables. In addition, genetic susceptibility to frailty was associated with asthma (OR = 1.088, 95%CI:1.058-1.119; p = 4.815589e-09). In the causal relationship described above, several risk factors for frailty are complex, with asthma leading to a significant reduction in physical activity endurance. Conclusion: Our findings suggest a probable positive causal effect of asthma on the risk of developing frailty, potentially mediated by reduced physical activity endurance. At the same time, a causal relationship exists between frailty and asthma. Therefore, assessment strategies for frailty should include asthma and vice versa.
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Non-coding RNA is still one of the most popular fields in biology research. In recent years, people paid more attention to the roles of H19 in lung diseases, which expressed abnormally in various pathological process. Therefore, this review focus on the regulatory role of H19 in asthma, pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), lung injury, pneumonia, lung cancer, etc. And the potential therapeutic agents and molecular treatments of H19 are collected. The aim is to demonstrate its underlying mechanism in pulmonary diseases and to guide the basic research targeting H19 into clinical drug translation.
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Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a ß-amyloid-specific radiotracer, [18F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [18F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [18F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [18F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [18F]AV-45 uptake. Postoperative histopathological analysis confirmed the [18F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [18F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [18F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Glândula Tireoide , Fluordesoxiglucose F18 , Humanos , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
The aim of this study was to investigate the digestion and fermentation properties of fish protein fermented by Monascus. Semi-dried fish was fermented by applying Monascus purpureus Went M 3.439. Our results show that the Monascus fermentation of the fish protein enriched the free amino acids and achieved a relatively higher glutamate content than the control group. The Monascus treatment promoted the decomposition of the fish protein during in vitro digestion, reduced the ammonia and indole content and tended to increase the propionic acid content during in vitro fermentation. The Monascus treatment considerably changed the gut microbiota composition, and particularly increased the relative abundance of Parabacteroides in the in vitro fermentation model of human distal colon. Consumption of Monascus fermented fish protein could result in positive changes in fermentation metabolites and gut microbiota, which brings potential health benefits.
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Microbioma Gastrointestinal , Monascus , Animais , Digestão , Fermentação , Proteínas de Peixes/metabolismo , Humanos , Monascus/metabolismoRESUMO
Regulating the secretion and endothelial differentiation of human mesenchymal stem cells (hMSCs) plays an important role in the vascularization in tissue engineering and regenerative medicine. In this study, a recombinant cadherin fusion protein consisting of a human vascular endothelial-cadherin extracellular domain and immunoglobulin IgG Fc region (hVE-cad-Fc) was developed as a bioartificial matrix for modulating hMSCs. The hVE-cad-Fc matrix significantly enhanced the secretion of angiogenic factors, activated the VE-cadherin-VEGFR2/FAK-AKT/PI3K signaling pathway in hMSCs, and promoted the endothelial differentiation of hMSCs even without extra VEGF. Furthermore, the hVE-cad-Fc matrix was applied for the surface modification of a poly (lactic-co-glycolic acid) (PLGA) porous scaffold, which significantly improved the hemocompatibility and vascularization of the PLGA scaffold in vivo. These results revealed that the hVE-cad-Fc matrix should be a superior bioartificial ECM for remodeling the pro-vascularization extracellular microenvironment by regulating the secretion of hMSCs, and showed great potential for the vascularization in tissue engineering.
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Caderinas/metabolismo , Endotélio Vascular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica , Animais , Adesão Celular , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Endotélio Vascular/citologia , Humanos , Células-Tronco Mesenquimais/citologia , CamundongosRESUMO
BACKGROUND: Florbetapir (AV45) and fluorodeoxyglucose (FDG) PET imaging are valuable techniques to detect the amyloid-ß (Aß) load and brain glucose metabolism in patients with Alzheimer's disease (AD). OBJECTIVE: The purpose of this study is to access the characteristics of Aß load and FDG metabolism in brain for further investigating their relationships with cognitive impairment in AD patients. METHODS: Twenty-seven patients with AD (average 70.6 years old, Nâ=â13 male, Nâ=â14 female) were enrolled in this study. These AD patients underwent the standard clinical assessment and received detailed imaging examinations of the nervous system by using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), 18F-AV45, and 18F-FDG PET scans. RESULTS: Of 27 AD patients, 22 patients (81.5%) showed significantly increases in Aß load and 26 patients (96.3%) had significantly reductions in FDG metabolism. The moderate AD patients had more brain areas of reduced FDG metabolism and more severe reductions in some regions compared to mild AD patients, with no differences in Aß load observed. Moreover, the range and degree of reduced FDG metabolism in several regions were positively correlated with the total score of MMSE or MOCA, whereas the range of Aß load did not. No correlation was found between the range of Aß load and the range of reduced FDG metabolism in this study. CONCLUSION: The reduction in FDG metabolisms captured by 18F-FDG imaging can be used as a potential biomarker for AD diagnosis in the future. 18F-AV45 imaging did not present valuable evidence for evaluating AD patient in this study.
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Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Cognição , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Compostos de Anilina , Encéfalo/metabolismo , Encéfalo/patologia , Etilenoglicóis , Fluordesoxiglucose F18 , Humanos , Masculino , Testes de Estado Mental e Demência , Neuroimagem , Placa Amiloide/diagnóstico , Placa Amiloide/diagnóstico por imagem , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Tomografia por Emissão de Pósitrons , Índice de Gravidade de DoençaRESUMO
Conventional strategies of stem cell injection in treating myocardial infarction (MI) remain a challenge because of low retention rate and insufficient secretion of exogenous cytokines for efficiently improving the microenvironment in the infarcted myocardium, thus hampering the therapeutic effect. Herein, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human VE-cad-Fc fusion protein are fabricated and integrated with human mesenchymal stem cells (hMSCs) to construct functionalized MSC aggregates (FMAs). This fusion protein can effectively promote the paracrine activity of MSCs. The FMA is encapsulated with an injectable hyaluronic acid (HA)-based hydrogel, which is prepared by Schiff base reaction between oxidized HA (OHA) and hydrazided HA (HHA). The OHA@HHA hydrogel loading FMA is injected into the infarcted myocardium of rats, thereby efficiently improving the MI microenvironment in terms of decreased expressions of inflammatory cytokines and upregulated secretion of angiogenic factors compared to the plain hydrogel only and hydrogel encapsulating MSCs. The results of both echocardiography and histological analyses demonstrate the efficient reconstruction of cardiac function and structure and revascularization in the infarct myocardium. The delivery of functionalized stem cell aggregates with an injectable hydrogel offers a promising strategy for treating myocardial infarction and may be expanded to other tissue repair and reconstruction.
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Células-Tronco Mesenquimais , Infarto do Miocárdio , Animais , Humanos , Ácido Hialurônico , Hidrogéis , Infarto do Miocárdio/terapia , Miocárdio , RatosRESUMO
BACKGROUND: Accurate differentiation between malignant and benign changes in soft tissue and bone lesions is essential for the prevention of unnecessary biopsies and surgical resection. Nevertheless, it remains a challenge and a standard diagnosis modality is urgently needed. The objective of this study was to evaluate the usefulness of 18F-fluorodeoxyglucose (18F-FDG) PET/CT-derived parameters to differentiate soft tissue sarcoma (STS) and bone sarcoma (BS) from benign lesions. METHODS: Patients who had undergone pre-treatment 18F-FDG PET/CT imaging and subsequent pathological diagnoses to confirm malignant (STS and BS, n = 37) and benign (n = 33) soft tissue and bone lesions were retrospectively reviewed. The tumor size, PET and low-dose CT visual characteristics, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneous factor (HF) of each lesion were measured. Univariate and multivariate logistic regression analyses were conducted to determine the significant risk factors to distinguish sarcoma from benign lesions. To establish a regression model based on independent risk factors, and the receiver operating characteristic curves (ROCs) of individual parameters and their combination were plotted and compared. Conventional imaging scans were re-analyzed, and the diagnostic performance compared with the regression model. RESULTS: Univariate analysis results revealed that tumor size, SUVmax, MTV, TLG, and HF of 18F-FDG PET/CT imaging in the STS and BS group were all higher than in the benign lesions group (all P values were < 0.01). The differences in the visual characteristics between the two groups were also all statistically significant (P < 0.05). However, the multivariate regression model only included SUVmax and HF as independent risk factors, for which the odds ratios were 1.135 (95%CI: 1.026 ~ 1.256, P = 0.014) and 7.869 (95%CI: 2.119 ~ 29.230, P = 0.002), respectively. The regression model was constructed using the following expression: Logit (P) = - 2.461 + 0.127SUVmax + 2.063HF. The area under the ROC was 0.860, which was higher than SUVmax (0.744) and HF (0.790). The diagnostic performance of the regression model was superior to those of individual parameters and conventional imaging. CONCLUSION: The regression model including SUVmax and HF based on 18F-FDG PET/CT imaging may be useful for differentiating STS and BS from benign lesions.
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Neoplasias Ósseas/diagnóstico por imagem , Fluordesoxiglucose F18/administração & dosagem , Osteossarcoma/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Sarcoma/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Adulto , Idoso , Neoplasias Ósseas/patologia , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteossarcoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Curva ROC , Estudos Retrospectivos , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Carga TumoralRESUMO
Multidrug resistance (MDR) is a common phenomenon in clinical oncology and is a major obstacle to cancer chemotherapy. Many nanoparticle (NP)-based drug delivery systems have been developed to overcome MDR depending on increasing intracellular drug concentrations via increased cellular uptake and rapid drug release. The objective of this work was to investigate the performance and possible mechanisms of enzyme-sensitive mPEGylated dendron-GFLG-DOX conjugate based nanoparticles for blockading the MDR phenotype of MCF-7/ADR. In vitro, mPEGylated dendron-GFLG-DOX conjugate based nanoparticles could significantly promote cellular uptake and accumulation, potent cytotoxicity and apoptosis compared to free DOX in resistant cells. mPEGylated dendron-GFLG-DOX conjugate based nanoparticles were found to translocate across the membranes of resistant cells via active endocytic pathways leading to more DOX accumulating in the nuclei of MCF-7/ADR cells. Importantly, we found that mPEGylated dendron-GFLG-DOX conjugate based nanoparticles could induce cathepsin B in the cytoplasm and enhance lysosomal-mediated cell death compared to free DOX. Furthermore, mPEGylated dendron-GFLG-DOX conjugate based nanoparticles enhanced the drug's penetration, toxicity, and growth inhibition compared to free DOX in the three-dimensional multicellular tumor spheroid model. In vivo, mPEGylated dendron-GFLG-DOX conjugate based nanoparticles significantly improved the therapeutic efficacy against MDR xenograft tumors, and showed better biocompatibility than free DOX. These results indicated that mPEGylated dendron-GFLG-DOX conjugate based nanoparticles could be used as an alternative drug delivery system for MDR tumor treatment through initiating the lysosomal apoptosis pathway.
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Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Dendrímeros/química , Doxorrubicina/farmacologia , Peptídeos/química , Polímeros/química , Antibióticos Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Lisossomos/metabolismo , Nanopartículas/química , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
OBJECTIVES: Pancreatic islet amyloid deposition occurs before ß-cell damage in type 2 diabetes mellitus patients. The islet and Alzheimer's disease ß-amyloid shares similar secondary structures. The Alzheimer's disease ß-amyloid targeting tracer [F]FDDNP could be used to image pancreatic islet amyloid with PET. PATIENTS AND METHODS: Consecutive pancreatic tissue sections from a 69-year-old male type 2 diabetes mellitus patient were stained by hematoxylin and eosin, anti-amylin antibody, Congo Red, periodic acid-Schiff, and [F]FDDNP reference compound, respectively. The pancreatic tissue sections were also incubated with [F]FDDNP with and without its reference compound for autoradiography. Subsequently, we performed control [F]FDDNP pancreatic PET/CT imaging in four healthy individuals. The mean standardized uptake values of [F]FDDNP uptake in the pancreatic head, neck, body, and tail, blood pool, liver, and vertebral bone from 5 to 120 min after injection were determined. RESULTS: Islet amyloid was observed in all four standard staining methods in the pancreas tissue. Similar islet amyloid distribution and phenotypes were observed clearly in the [F]FDDNP reference compound-stained pancreas tissue. [F]FDDNP was intensively accumulated in the same pancreatic tissue in autoradiography, which was largely blocked by its reference compound. In the PET/CT scans of control human participants, the mean standardized uptake values in pancreas decreased to the blood pool level in 30 min and all parts of the pancreas had similar [F]FDDNP uptake. The pancreas could be distinguished clearly from the liver at all-time points. CONCLUSION: These results suggested that [F]FDDNP is a potential tracer for pancreatic islet amyloid PET imaging.
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Amiloide/metabolismo , Ilhotas Pancreáticas/diagnóstico por imagem , Ilhotas Pancreáticas/metabolismo , Nitrilas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Projetos PilotoRESUMO
To accelerate the vascularization of engineered tissue, an endothelial-specific fusion protein (VEGF-Fc), which consists of a human vascular endothelial growth factor (VEGF) and an immunoglobulin G Fc region, was fabricated and used to construct a bioactive interface in a porous scaffold. In this study, VEGF-Fc was immobilized on polycarprolactone (PCL) porous scaffolds by steeping, which is mediated by the hydrophobic binding of the Fc domain. The VEGF-Fc proteins were distributed stably and uniformly throughout the PCL porous scaffolds without affecting their surface morphology and mechanical properties. The immobilized VEGF-Fc activated the phosphorylation of VEGF2 receptor continuously, and further promoted the expressions of PI3K and MAPK, which effectively enhanced the adhesion and proliferation of human vascular endothelial cells (HUVECs). Furthermore, the immobilized VEGF-Fc promoted the migration of HUVECs into the scaffolds, and also enhanced the cellularization and ECM deposition in the subcutaneous implanted scaffolds in rats, which synergistically supported the vascularization of the scaffold in vivo. In view of the advantages of easy use, stability and efficiency, the VEGF-Fc fusion protein appeared to be a promising candidate for surface modification of porous scaffolds for tissue engineering.
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Hormone suppression has been the primary modality of treatment for prostate cancer. However long-term androgen deprivation may induce androgen-independent (AI) recurrence. Intermittent androgen suppression (IAS) is a potential way to delay or avoid the AI relapse. Mathematical models of tumor growth and treatment are simple while they are capable of capturing the essence of complicated interactions. Game theory models have analyzed that tumor cells can enhance their fitness by adopting genetically determined survival strategies. In this paper, we consider the survival strategies as the competitive advantage of tumor cells and propose a new model to mimic the prostate tumor growth in IAS therapy. Then we investigate the competition effect in tumor development by numerical simulations. The results indicate that successfully IAS-controlled states can be achieved even though the net growth rate of AI cells is positive for any androgen level. There is crucial difference between the previous models and the new one in the phase diagram of successful and unsuccessful tumor control by IAS administration, which means that the suggestions from the models for medication can be different. Furthermore we introduce quadratic logistic terms to the competition model to simulate the tumor growth in the environment with a finite carrying capacity considering the nutrients or inhibitors. The simulations show that the tumor growth can reach an equilibrium state or an oscillatory state with the net growth rate of AI cells being androgen independent. Our results suggest that the competition and the restraint of a limited environment can enhance the possibility of relapse prevention.
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Antagonistas de Androgênios/uso terapêutico , Modelos Biológicos , Dinâmica não Linear , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/farmacologia , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Fatores de TempoRESUMO
Stem cell therapy is an emerging therapeutic modality in the treatment of stroke. We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells (NSPCs) and mesenchymal stromal cells (MSCs) in patients with ischemic stroke. Eight patients were enrolled in this study. All patients had a hemisphere with infarct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging (MRI). The patients received one of the following two types of treatment: the first treatment involved four intravenous injections of MSCs at 0.5 × 10(6)/kg body weight; the second treatment involved one intravenous injection of MSCs at 0.5 × 10(6)/kg weight followed by three injections of MSCs at 5 × 10(6)/patient and NSPCs at 6 × 10(6)/patient through the cerebellomedullary cistern. The patients' clinical statuses were evaluated with the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel index (BI). Six patients were given four cell transplantations. The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2-4 days after each therapy. One patient exhibited minor dizziness. All side effects appeared within the first 2-24 h of cell transplantation, and they resolved without special treatment. There was no evidence of neurological deterioration or neurological infection. Most importantly, no tumorigenesis was found at a 2-year follow-up. The neurological functions, disability levels, and daily living abilities of the patients in this study were improved. While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function, further studies that include larger samples, longer follow-ups, and control groups are still needed. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
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Isquemia Encefálica/terapia , Células-Tronco Mesenquimais/citologia , Células-Tronco Neurais/transplante , Transplante de Células-Tronco , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neurais/citologia , Acidente Vascular Cerebral/complicaçõesRESUMO
A deep ultraviolet plasmonic structure is designed and a surface plasmon interference lithography method using the structure is proposed to generate large-area periodic nanopatterns. By exciting the anti-symmetric coupled surface plasmon polaritons in the structure, ultrahigh resolution periodic patterns can be formed in a photoresist. The resolution of the generated patterns can be tuned by changing the refractive index and thickness of the photoresist. We demonstrate numerically that one-dimensional and two-dimensional patterns with a half-pitch resolution of 14.6 nm can be generated in a 25 nm-thick photoresist by using the structure under 193 nm illumination. Furthermore, the half-pitch resolution of the generated patterns can be down to 13 nm if high refractive index photoresists are used. Our findings open up an avenue to push the half-pitch resolution of photolithography towards 10 nm.
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Hypertrophic pachymeningitis is a rare chronic inflammatory disorder characterized by marked fibrous thickening of the cerebral and/or spinal dura mater. Clinical, laboratory, neuroradiologic and therapeutic data from 12 patients with idiopathic hypertrophic pachymeningitis (IHP) from our department were retrospectively studied. There were four men and eight women with a mean age of 49±15.3 years, and more than half of the patients (58%) were aged 40-60 years. Headache was the most common symptom, occurring in 92% of patients. Headache improved markedly and rapidly after glucocorticoid treatment. Optic nerve involvement was noted in seven patients (58%). C-reactive protein levels increased in 80% and the erythrocyte sedimentation rate increased in 71% of patients. Three patients were positive for autoantibodies, including antinuclear antibodies (ANA), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), anti-cardiolipin antibodies (ACA) and rheumatoid factor (RF). Cerebrospinal fluid showed inflammatory changes, and protein levels were low to moderately elevated. MRI revealed a thickened dura in all patients, and five patients (42%) were diagnosed with sinus stenosis/occlusion. IHP is a chronic inflammatory disorder of the dura with three groups of symptoms, namely headache, cranial nerve palsy and symptoms due to sinus stenosis/occlusion. However, IHP has different features in China in that it predominantly affects women and the age of onset is younger. Sinus stenosis/occlusion is relatively common in IHP patients in China.
Assuntos
Hipertrofia , Meningite , Adulto , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Anticorpos Antinucleares , Autoanticorpos/sangue , Proteína C-Reativa/metabolismo , Cardiolipinas , China , Constrição Patológica/etiologia , Feminino , Glucocorticoides/uso terapêutico , Cefaleia/tratamento farmacológico , Cefaleia/etiologia , Humanos , Hipertrofia/complicações , Hipertrofia/diagnóstico , Hipertrofia/tratamento farmacológico , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Meningite/complicações , Meningite/diagnóstico , Meningite/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
We propose a novel method to correct the chromatic dispersion in a planar waveguide with volume holograms fabricated by the three-step exposure technique. The 532 nm green laser is used to illuminate the holographic plate in three groups of different angles for achieving the desired holograms. When it is used in the planar waveguide, the chromatic dispersion of the original display can be corrected and an image with the real color can be obtained. The experiments are performed, and the results are in good agreement with the theory. It is believed that this technique is a good way to correct the chromatic problems in the display systems in the future.