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1.
Front Cell Dev Biol ; 9: 727822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790659

RESUMO

Anti-VEGF drugs are first-line treatments for retinal neovascular diseases, but these anti-angiogenic agents may also aggravate retinal damage by inducing hypoxia. Mitophagy can protect against hypoxia by maintaining mitochondrial quality, thereby sustaining metabolic homeostasis and reducing reactive oxygen species (ROS) generation. Here we report that the anti-VEGF agent bevacizumab upregulated the hypoxic cell marker HIF-1α in photoreceptors, Müller cells, and vascular endothelial cells of oxygen-induced retinopathy (OIR) model mice, as well as in hypoxic cultured 661W photoreceptors, MIO-MI Müller cells, and human vascular endothelial cells. Bevacizumab also increased expression of mitophagy-related proteins, and mitophagosome formation both in vivo and in vitro, but did not influence cellular ROS production or apoptosis rate. The HIF-1α inhibitor LW6 blocked mitophagy, augmented ROS production, and triggered apoptosis. Induction of HIF-1α and mitophagy were associated with upregulation of BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3) and FUN14 domain containing 1 (FUNDC1), and overexpression of these proteins in culture reversed the effects of HIF-1α inhibition. These findings suggest that bevacizumab does induce retinal hypoxia, but that concomitant activation of the HIF-1α-BNIP3/FUNDC1 signaling pathway also induces mitophagy, which can mitigate the deleterious effects by reducing oxidative stress secondary. Promoting HIF-1α-BNIP3/FUNDC1-mediated mitophagy may enhance the safety of anti-VEGF therapy for retinal neovascular diseases and indicate new explanation and possible new target of the anti-VEGF therapy with suboptimal effect.

2.
Front Med (Lausanne) ; 8: 719593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722564

RESUMO

Background: Vogt-Koyanagi-Harada (VKH) disease is a multisystem autoimmune disorder which could induce bilateral panuveitis involving the posterior pole and peripheral fundus. Optical coherence tomography angiography (OCTA) provides several advantages over traditional fluorescence angiography for revealing pathological abnormalities of the retinal vasculature. Until recently, however, the OCTA field of view (FOV) was limited to 6 × 6 mm2 scans. Purpose: This study examined retinal vasculature and choriocapillaris abnormalities across multiple regions of the retina (15 × 9 mm2 wide field, macular, peripapillary regions) among acute and convalescent VKH patients using a novel widefield swept-source OCTA (WSS-OCTA) device and assessed correlations between imaging features and best-corrected visual acuity (BCVA). Methods: Twenty eyes of 13 VHK disease patients in the acute phase, 30 eyes of 17 patients in the convalescent phase, and 30 eyes of 15 healthy controls (HCs) were included in this study. Vascular length density (VLD) in superficial and deep vascular plexuses (SVP, DVP), vascular perfusion density (VPD) in SVP, DVP, and choriocapillaris (CC), and flow voids (FV) in CC were measured across multiple retinal regions via WSS-OCTA (PLEX Elite 9000, Carl Zeiss Meditec Inc., USA) using the 15 × 9 mm2 scan pattern centered on the fovea and quantified by ImageJ. Results: Compared to HCs, acute phase VKH patients exhibited significantly reduced SVP-VLD, SVP-VPD, and CC-VPD across multiple retinal regions (all p < 0.01). Notably, the FV area was more extensive in VKH patients, especially those in the acute phase (p < 0.01). These changes were reversed in the convalescent phase. Stepwise multiple linear regression analysis demonstrated that macular DVP-VLD and macular CC-VPD were the best predictive factors for BCVA in the acute and convalescent VKH groups. Conclusion: The wider field of SS-OCAT provides more comprehensive and detailed images of the microvasculature abnormalities characterizing VKH disease. The quantifiable and layer-specific information from OCTA allows for the identification of sensitive and specific imaging markers for prognosis and treatment guidance, highlighting WSS-OCTA as a promising modality for the clinical management of VKH disease.

3.
Front Med (Lausanne) ; 8: 727151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604263

RESUMO

Purpose: To investigate the involvement of peripapillary zone vascular abnormalities in Behcet's uveitis (BU) and associated visual dysfunction. We evaluated the retinal and choroidal microvascular features in both macular and peripapillary areas of BU patients to identify vascular abnormalities contributing to reduced best-corrected visual acuity (BCVA) using optical coherence tomography angiography (OCTA). Methods: A prospective, observational study was conducted in 24 eyes of 13 patients with BU and 24 eyes of 15 healthy participants as controls. They received a standard eye examination and were recorded by OCTA measurements of macular and peripapillary areas. The vascular densities of superficial capillary plexus (SCP) and deep capillary plexus (DCP), choroidal flow area, radial peripapillary capillary network (RPCN) density, foveal avascular zone (FAZ) area and perimeter, full retinal thickness (FRT), and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured.Correlations among microvascular, structural, and functional changes were assessed. Results: Our findings uncovered that the vascular density was significantly reduced in the peripapillary zone of BU eyes compared to healthy eyes, especially in the inferior subfield of the RPCN. The vascular densities of SCP and DCP quadrants within the macular zone had no significant difference between BU and control groups except for DCP density of the nasal parafoveal quadrant. Both FAZ area and perimeter were greater but without statistical significance in the BU group. Compared to healthy eyes, the choriocapillaris flow area was smaller while the FRT and pRNFLT were greater in the BU group. Notably, there was a significant correlation between the reduction in RPCN vascular density and decreased BCVA in BU patients. Conclusion: Based on OCTA, vascular changes associated with BU are more prominent in the peripapillary zone than those in the macular zone. The vascular density of the RPCN could serve as a sensitive indicator to monitoring BU pathogenic progression and treatment response using a non-invasively method of OCTA.

4.
Eur Radiol ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34357448

RESUMO

OBJECTIVE: To assess the overall diagnostic accuracy of different MR imaging sequences in the detection of the dysplastic nodule (DN). METHODS: PubMed, Cochrane Library, and Web of Science were systematically searched. Study selection and data extraction were conducted by two authors independently. Quality assessment of diagnostic accuracy studies (QUADAS) 2 in RevMan software was used to score the included studies and assess their methodological quality. A random-effects model was used for statistical pooling by Meta-Disc. Subgroup analysis and sensitivity analysis were used to explore potential sources of heterogeneity. RESULTS: Fourteen studies (335 DN lesions in total) were included in our meta-analysis. The area under the curve (AUC) of summary receiver operating characteristic (SROC) of T2WI was 0.87. Pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of DWI were 0.81 (95%CI, 0.73-0.87), 0.90 (95%CI, 0.86-0.93), 7.04 (95%CI, 4.49-11.04), and 0.24 (95%CI, 0.17-0.33) respectively. In the arterial phase, pooled sensitivity, specificity, PLR, and NLR were 0.89 (0.84-0.93), 0.75 (0.72-0.79), 3.72 (2.51-5.51), and 0.17 (0.12-0.25), respectively. Pooled sensitivity, specificity, PLR, and NLR of the delayed phase were 0.78 (0.72-0.83), 0.60 (0.55-0.65), 2.19 (1.55-3.10), and 0.36 (0.23-0.55) separately. Pooled sensitivity, specificity, PLR, and NLR of the hepatobiliary phase were 0.77 (0.71-0.82), 0.92 (0.89-0.94), 8.74 (5.91-12.92), and 0.24 (0.14-0.41) respectively. Pooled sensitivity, specificity, and PLR were higher on DWI and hepatobiliary phase in diagnosing LGDN than HGDN. CONCLUSION: MR sequences, particularly DWI, arterial phase, and hepatobiliary phase imaging demonstrate high diagnostic accuracy for DN. KEY POINTS: • MRI has dramatically improved the detection and accurate diagnosis of DNs and their differentiation from hepatocellular carcinoma. • Overall diagnostic accuracy of different MRI sequences in the detection of DN has not been studied before. • Our meta-analysis demonstrates that MRI achieves a high diagnostic value for DN, especially when using DWI, arterial phase imaging, and hepatobiliary phase imaging.

5.
Sci Rep ; 11(1): 14663, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282250

RESUMO

Multiple small- to middle-scale cities, mostly located in northern China, became epidemic hotspots during the second wave of the spread of COVID-19 in early 2021. Despite qualitative discussions of potential social-economic causes, it remains unclear how this unordinary pattern could be substantiated with quantitative explanations. Through the development of an urban epidemic hazard index (EpiRank) for Chinese prefectural districts, we came up with a mathematical explanation for this phenomenon. The index is constructed via epidemic simulations on a multi-layer transportation network interconnecting local SEIR transmission dynamics, which characterizes intra- and inter-city population flow with a granular mathematical description. Essentially, we argue that these highlighted small towns possess greater epidemic hazards due to the combined effect of large local population and small inter-city transportation. The ratio of total population to population outflow could serve as an alternative city-specific indicator of such hazards, but its effectiveness is not as good as EpiRank, where contributions from other cities in determining a specific city's epidemic hazard are captured via the network approach. Population alone and city GDP are not valid signals for this indication. The proposed index is applicable to different epidemic settings and can be useful for the risk assessment and response planning of urban epidemic hazards in China. The model framework is modularized and the analysis can be extended to other nations.


Assuntos
COVID-19/epidemiologia , Epidemias , COVID-19/transmissão , China/epidemiologia , Cidades , Humanos , Modelos Teóricos , Transportes , População Urbana
6.
Front Cell Dev Biol ; 9: 669696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095138

RESUMO

Retinal ischemia is a common pathological event that can result in retinal ganglion cell (RGC) death and irreversible vision loss. The pathogenic mechanisms linking retinal ischemia to RGC loss and visual deficits are uncertain, which has greatly hampered the development of effective treatments. It is increasingly recognized that pyroptosis of microglia contributes to the indirect inflammatory death of RGCs. In this study, we report a regulatory NOD-like receptor, NOD-, LRR- and CARD-containing 5 (NLRC5), as a key regulator on microglial pyroptosis and the retinal ischemia process. Through an in-depth analysis of our recently published transcriptome data, we found that NLRC5 was significantly up-regulated in retina during ischemia-reperfusion injury, which were further confirmed by subsequent detection of mRNA and protein level. We further found that NLRC5 was upregulated in retinal microglia during ischemia, while NLRC5 knockdown significantly ameliorated retinal ischemic damage and RGC death. Mechanistically, we revealed that knockdown of NLRC5 markedly suppressed gasdermin D (GSDMD) cleavage and activation of interleukin-1ß (IL-1ß) and caspase-3, indicating that NLRC5 promotes both microglial pyroptosis and apoptosis. Notably, we found that NLRC5 directly bound to NLRP3 and NLRC4 in inflammasomes to cooperatively drive microglial pyroptosis and apoptosis mediating retinal ischemic damage. Overall, these findings reveal a previously unidentified key contribution of NLRC5 signaling to microglial pyroptosis under ischemia or hypoxia conditions. This NLRC5-dependent pathway may be a novel therapeutic target for treatment of ischemic retinopathy.

7.
Biomaterials ; 274: 120874, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34051629

RESUMO

To address the clinical need for readily available small diameter vascular grafts, biomimetic tubular scaffolds were developed for rapid in situ blood vessel regeneration. The tubular scaffolds were designed to have an inner layer that is porous, interconnected, and with a nanofibrous architecture, which provided an excellent microenvironment for host cell invasion and proliferation. Through the synthesis of poly(spirolactic-co-lactic acid) (PSLA), a highly functional polymer with a norbornene substituting a methyl group in poly(l-lactic acid) (PLLA), we were able to covalently attach biomolecules onto the polymer backbone via thiol-ene click chemistry to impart desirable functionalities to the tubular scaffolds. Specifically, heparin was conjugated on the scaffolds in order to prevent thrombosis when implanted in situ. By controlling the amount of covalently attached heparin we were able to modulate the physical properties of the tubular scaffold, resulting in tunable wettability and degradation rate while retaining the porous and nanofibrous morphology. The scaffolds were successfully tested as rat abdominal aortic replacements. Patency and viability were confirmed through dynamic ultrasound and histological analysis of the regenerated tissue. The harvested tissue showed excellent vascular cellular infiltration, proliferation, and migration with laminar cellular arrangement. Furthermore, we achieved both complete reendothelialization of the vessel lumen and native-like media extracellular matrix. No signs of aneurysm or hyperplasia were observed after 3 months of vessel replacement. Taken together, we have developed an effective vascular graft able to generate small diameter blood vessels that can function in a rat model.


Assuntos
Heparina , Nanofibras , Animais , Biomimética , Prótese Vascular , Poliésteres , Ratos , Regeneração , Engenharia Tecidual , Tecidos Suporte
8.
Ann Palliat Med ; 10(2): 1727-1738, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33302634

RESUMO

BACKGROUND: Chronic myelogenous leukemia (CML) is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells. CML is a relatively rare disease, mainly affecting elderly patients, but the prevalence of CML is expected to increase dramatically. The tyrosine kinase inhibitors (TKIs) have changed the CML patients' treatment patterns and improved its treatment effect, but drug resistance still remains a significant problem to be solved. Therefore, the identification of biomarkers of CML resistance involved therein is essential for treatment and prognosis prediction. METHODS: Bioinformatics was used to analyze and construct a lncRNA-miRNA-mRNA network of CML resistance to dasatinib and predict key lncRNAs. RESULTS: By screening differentially expressed genes in CML resistant to dasatinib and comprehensively analyzing their functions and signal pathways, the core genes in these differential genes were found, and by predictive analysis of the upstream targets of these core genes. Finally, a network diagram containing lncRNA, miRNA, and mRNA was constructed. CONCLUSIONS: MALAT1 as a lncRNA may be a tumor suppressor in patients with CML. According to our data, MALAT1 may have potential role as a molecular biomarker for the occurrence and development of CML resistance to dasatinib.


Assuntos
Dasatinibe , Resistencia a Medicamentos Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , MicroRNAs , RNA Longo não Codificante , Idoso , Dasatinibe/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
9.
Chemosphere ; 263: 128129, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297117

RESUMO

The catalysts' redox capacity and surface acidity was important during the catalytic combustion of chlorobenzene (CB). CeO2 showed great attractiveness due to its high oxygen storage capacity. Furthermore, the increase of acidity on the catalyst surface could improve the resistance to the chlorine poisoning. In this work, the silicotungstic (HSiW) modified CeO2 catalysts prepared by four cerium salts and exhibited the different morphologies and catalytic activity. The HSiW modified CeO2 catalyst prepared by Ce(CH3COO)3 (Cat-A) exhibited the best catalytic activity due to its abundant surface weak acid sites, more Ce3+ species and surface adsorption oxygen. The HSiW mainly located on the CeO2 (111) planes of the Cat-A, which was conducive to redox property of CeO2, thus promoting the deep oxidation of CB. Meanwhile the redox ability together with the weak acidity influenced the catalytic efficiency at low temperature. And the redox ability played a major role at high temperature. In addition, the Cat-A still possessed high stability and water resistance and maintained high activity after continuous catalytic oxidation of CB at 235 and 295 °C for 100h, exhibiting the possibility of industrial application.


Assuntos
Cério , Catálise , Clorobenzenos , Oxirredução , Silicatos , Compostos de Tungstênio
10.
Proc Natl Acad Sci U S A ; 117(41): 25712-25721, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32989127

RESUMO

Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11,259 human circulating monocytes and genetically defined their subpopulations. We constructed a precise atlas of human blood monocytes, identified six subpopulations-including S100A12, HLA, CD16, proinflammatory, megakaryocyte-like, and NK-like monocyte subsets-and uncovered two previously unidentified subsets: HLA and megakaryocyte-like monocyte subsets. Relative to healthy individuals, cellular composition, gene expression signatures, and activation states were markedly alternated in VKH patients utilizing cell type-specific programs, especially the CD16 and proinflammatory monocyte subpopulations. Notably, we discovered a disease-relevant subgroup, proinflammatory monocytes, which showed a discriminative gene expression signature indicative of inflammation, antiviral activity, and pathologic activation, and converted into a pathologic activation state implicating the active inflammation during VKH disease. Additionally, we found the cell type-specific transcriptional signature of proinflammatory monocytes, ISG15, whose production might reflect the treatment response. Taken together, in this study, we present discoveries on accurate classification, molecular markers, and signaling pathways for VKH disease-associated monocytes. Therapeutically targeting this proinflammatory monocyte subpopulation would provide an attractive approach for treating VKH, as well as other autoimmune diseases.


Assuntos
Monócitos/imunologia , Síndrome Uveomeningoencefálica/genética , Síndrome Uveomeningoencefálica/imunologia , Adulto , Autoimunidade , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de IgG/genética , Receptores de IgG/imunologia , Proteína S100A12/genética , Proteína S100A12/imunologia , Ubiquitinas/genética , Ubiquitinas/imunologia
11.
Mol Neurodegener ; 15(1): 26, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295623

RESUMO

BACKGROUND: Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. METHODS: A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. RESULTS: Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1ß (IL-1ß) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1ß in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. CONCLUSIONS: These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Glaucoma/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Células Ganglionares da Retina/patologia , Animais , Feminino , Glaucoma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Ganglionares da Retina/metabolismo , Transdução de Sinais/fisiologia
12.
Proc Math Phys Eng Sci ; 476(2233): 20190675, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32082068

RESUMO

A variational optimization approach is used to optimize kinematic dynamos in a unit sphere and locate the enstrophy-based critical magnetic Reynolds number for dynamo action. The magnetic boundary condition is chosen to be either pseudo-vacuum or perfectly conducting. Spectra of the optimal flows corresponding to these two magnetic boundary conditions are identical since theory shows that they are relatable by reversing the flow field (Favier & Proctor 2013 Phys. Rev. E 88, 031001 (doi:10.1103/physreve.88.031001)). A no-slip boundary for the flow field gives a critical magnetic Reynolds number of 62.06, while a free-slip boundary reduces this number to 57.07. Optimal solutions are found to possess certain rotation symmetries (or anti-symmetries) and optimal flows share certain common features. The flows localize in a small region near the sphere's centre and spiral upwards with very large velocity and vorticity, so that they are locally nearly Beltrami. We also derive a new lower bound on the magnetic Reynolds number for dynamo action, which, for the case of enstrophy normalization, is five times larger than the previous best bound.

13.
J Magn Reson Imaging ; 51(3): 812-823, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31245888

RESUMO

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced MRI (DCE-MRI) are sensitive imaging modalities for detecting liver lesions, but their value in evaluating cirrhosis-related nodules remains unclear. PURPOSE: To investigate whether IVIM-DWI and DCE-MRI can differentiate different types of cirrhosis-related nodules, and whether these modalities can monitor changes in cell density and angiogenesis during the malignant transformation of cirrhosis-related nodules in a rat model STUDY TYPE: Prospective. ANIMAL MODEL: Thirty-five male Sprague-Dawley rats with 106 cirrhosis-related nodules (19 regenerative nodules [RNs], 47 dysplastic nodules [DNs], and 40 hepatocellular carcinomas [HCCs]). FIELD STRENGTH/SEQUENCE: IVIM-DWI and DCE sequence at 3.0T MRI. ASSESSMENT: IVIM-DWI parameters (D, D*, f, and apparent diffusion coefficient [ADC]) and DCE-MRI parameters (Ktrans , Kep , and Ve ) were calculated by two radiologists using postprocessing software. The "cell density" and "unpaired arterial ratio" were analyzed with a microscope by two pathologists. STATISTICAL TESTS: MRI parameters were compared among the different types of nodules by one-way analysis of variance or the Kruskal-Wallis test. The Pearson correlation test was used to analyze the correlation of MRI parameters with the pathological types of nodules, cell density, and unpaired arterial ratio. RESULTS: The Ktrans , Kep , and Ve values of HCCs were significantly higher than those of DNs and RNs. D and ADC values were significantly lower in HCCs than in DNs and RNs. There were moderate positive correlations of Ktrans with the pathological types of nodules and the unpaired arterial ratio. Moderate negative correlations were observed among D, ADC, and the pathological types of nodules, between D and cell density, and between ADC and cell density. DATA CONCLUSION: IVIM-DWI and DCE-MRI are valuable in differentiating different types of cirrhotic-related nodules. D and ADC are correlated with changes in cell density during the malignant transformation of cirrhosis-related nodules, while Ktrans is correlated with increased angiogenesis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:812-823.


Assuntos
Meios de Contraste , Neoplasias Hepáticas , Animais , Contagem de Células , Imagem de Difusão por Ressonância Magnética , Cirrose Hepática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Movimento (Física) , Estudos Prospectivos , Ratos , Ratos Sprague-Dawley
14.
Pharmgenomics Pers Med ; 12: 319-327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802929

RESUMO

Background: Emery-Dreifuss muscular dystrophy, caused by mutations in genes such as emerin (EMD) or lamin A/C (LMNA), is a disorder affecting the joints, muscles, and heart, with a wide spectrum of patient phenotypes including muscle wasting and cardiac conduction defects. Methods and results: Here we report a multi-generation family from the Hunan Province of China. Affected family members displayed an uncommon clinical presentation of serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death along with mild skeletal muscular atrophy and joint contracture. Clinical analysis of affected members provided evidence of X-linked recessive inheritance. Consequently, using Sanger sequencing of X chromosome exomes, we identified a novel duplication mutation (c.405dup/p.Asp136X) in the EMD gene as the cause for the disease in this family. This variant is a novel mutation that has not been previously reported in Pubmed, Clinvar or other cases reported in the Human Gene Mutation Database. Conclusion: Our finding expands the mutation spectrum of Emery-Dreifuss muscular dystrophy and provides a rationale for EMD mutation testing in cases of X-linked inherited cardiac conduction disease and sudden cardiac death, even in those lacking pathognomonic neuromuscular features.

15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 666-669, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30440484

RESUMO

The detection of microorganisms is important in numerous applications such as water quality monitoring, blood analysis, and food testing. The conventional detection methods are tedious and labour-intensive. Establish methods involve culturing, counting and identification of the pathogen by an experienced technician which typically can take several days. The use of opto-fluidic technology to capture microorganism images offers 0 route to reduce the overall assay time. However, the detection still requires a trained technician. This paper proposes an image processing method that can be used to classify microorganism images captured by an opto-fluidic set up in an automatic manner. The proposed algorithm incorporates some of the features used in other microorganism image detection methods and proposes two new features-Entropy of Histogram of Oriented Gradients (HOG) and the filtered intensities. In addition, we propose to apply the minimal-Redundancy-Maximal-Relevance (mRMR) criterion to select and rank these features. The probability and joint probability distribution functions of the mRMR are estimated using a Gaussian model and the Kernel Density Estimation model. The performance of the proposed method was validated using SVM and data collected from an experimental setup. The results show that our proposed method outperforms existing methods and is capable of achieving a classification accuracy up to 95.8%.


Assuntos
Bactérias/classificação , Cryptosporidium/isolamento & purificação , Giardia/isolamento & purificação , Processamento de Imagem Assistida por Computador/métodos , Máquina de Vetores de Suporte , Algoritmos
16.
Proc Math Phys Eng Sci ; 474(2218): 20180412, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30839837

RESUMO

In his seminal work, Taylor (1963 Proc. R. Soc. Lond. A 274, 274-283. (doi:10.1098/rspa.1963.0130).) argued that the geophysically relevant limit for dynamo action within the outer core is one of negligibly small inertia and viscosity in the magnetohydrodynamic equations. Within this limit, he showed the existence of a necessary condition, now well known as Taylor's constraint, which requires that the cylindrically averaged Lorentz torque must everywhere vanish; magnetic fields that satisfy this condition are termed Taylor states. Taylor further showed that the requirement of this constraint being continuously satisfied through time prescribes the evolution of the geostrophic flow, the cylindrically averaged azimuthal flow. We show that Taylor's original prescription for the geostrophic flow, as satisfying a given second-order ordinary differential equation, is only valid for a small subset of Taylor states. An incomplete treatment of the boundary conditions renders his equation generally incorrect. Here, by taking proper account of the boundaries, we describe a generalization of Taylor's method that enables correct evaluation of the instantaneous geostrophic flow for any three-dimensional Taylor state. We present the first full-sphere examples of geostrophic flows driven by non-axisymmetric Taylor states. Although in axisymmetry the geostrophic flow admits a mild logarithmic singularity on the rotation axis, in the fully three-dimensional case we show that this is absent and indeed the geostrophic flow appears to be everywhere regular.

17.
J Plast Reconstr Aesthet Surg ; 70(9): 1292-1297, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28705589

RESUMO

BACKGROUND: The treatment of maxillonasal dysplasia in Binder's syndrome using autologous costal bone and cartilage is well established, but postoperative results may be compromised by scarring, unpredictable absorption of transferred autologous tissue, and donor site morbidity. Here, we propose a simple surgical technique to improve maxillonasal dysplasia using an expanded polytetrafluoroethylene (ePTFE) implant. MATERIALS AND METHODS: From February 1999 to May 2014, fifty-eight patients affected by maxillonasal dysplasia with different degrees of flattened nose and midfacial depression underwent surgical correction by augmentation of the nasal dorsum using an "L"-shaped ePTFE and subperiosteal implantation of an inverted "m"-shaped ePTFE at the base of the piriform aperture. The outcome was evaluated based on preoperative and postoperative patient pictures, 3D imaging technology for the assessment of nasolabial angle and facial convexity angle, and a postoperative patient satisfaction survey. RESULTS: Postoperative results showed improved facial aesthetics with a significantly increased nasolabial angle from initially 74.1° ± 8.9° to 93.7° ± 6.1° at 6 months postoperatively (p < 0.05). Temporary discomfort involving upper lip numbness, foreign body sensation, and stiff smiling expression were complained during the first 3 months postoperatively, but spontaneously resolved within 6 months. Complications included infection (2 cases), implant migration (2 cases), and implant exposure (1 case). The vast majority of patients (95.7%) rated their postoperative outcome as highly improved and improved. CONCLUSION: The present therapeutic strategy provides a simple and effective treatment for the correction of maxillonasal dysplasia with high patient acceptance in a single step approach. Further research is required to determine long-term outcomes.


Assuntos
Anormalidades Maxilofaciais/cirurgia , Politetrafluoretileno , Próteses e Implantes , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Med Sci Monit ; 23: 2143-2150, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28475566

RESUMO

BACKGROUND Sun's procedure is a surgical technique widely used in type A aortic dissection. The purpose of this study was to analyze clinical outcomes and morphologic changes in true and false lumen by computed tomography (CT) angiography after Sun's procedure. MATERIAL AND METHODS We retrospectively reviewed 51 patients who underwent Sun's procedure for acute Stanford type A aortic dissection extending down to iliac bifurcation between January 2013 and December 2014. The images of preoperative, one-month, three-month, and six-month follow-up were analyzed by CT angiography to measure the area and diameter of true and false lumen. RESULTS Four patients died before surgical intervention and postoperative deaths occurred in five patients (in-hospital mortality rate 10.6%). Only 42 patients (36 male, 6 female; mean age, 45.9±9.8 years; range, 24-65 years) with acute type A aortic dissection were involved in our study. Thirty-five patients (83.3%) suffered from chest or abdominal pain and only one patient (2.4%) was asymptomatic. Thirty-seven patients (88.1%) had hypertension as the most common comorbidity. In the ascending aorta, false lumen was eliminated and the change of true lumen was not significant (p>0.05). In the descending aorta, complete and partial thrombosis of false lumen were observed in eight patients (19.0%) and 33 patients (78.6%) by one-month follow-up CT scan, respectively. After the six-month follow-up, the rate of complete thrombosis increased to 36.1% and partial thrombosis decreased to 61.9%. The area and maximal diameter of true lumen were increased significantly (p<0.05), whereas significant decreases were found in the area and maximal diameter of false lumen (p<0.05). In the abdominal aorta, thrombosis was found in 52.4% patients at one-month follow-up CT. Furthermore, there were no significant changes in both true and false lumen within three months (p>0.05). Nevertheless, the false luminal area and maximal diameter decreased significantly (p<0.05) after six months, while these changes of true lumen were not significant (p>0.05). CONCLUSIONS After Sun's procedure, aortic remodeling was a continuous process and occurred in a predictable model, and the extent of aortic remodeling varied at different levels. Remodeling in descending thoracic aorta was earlier than it was in abdominal aorta.


Assuntos
Aneurisma Dissecante/cirurgia , Aorta/cirurgia , Remodelamento Atrial/fisiologia , Adulto , Idoso , Aorta Abdominal/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica , Implante de Prótese Vascular/métodos , Angiografia por Tomografia Computadorizada/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Trombose , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Amino Acids ; 47(12): 2475-82, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26142632

RESUMO

Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.


Assuntos
Valva Aórtica/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Osteoblastos/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Fosfatase Alcalina/metabolismo , Valva Aórtica/citologia , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/metabolismo , Apelina , Calcinose/metabolismo , Diferenciação Celular , Células Cultivadas , Cromonas/química , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Flavonoides/química , Humanos , Morfolinas/química , Músculo Liso Vascular/citologia , Transdução de Sinais
20.
Saudi Med J ; 32(1): 15-22, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21212910

RESUMO

OBJECTIVE: To study the synthesis of 131iodine (I) labeled histamine-indomethacin (His-IN), its in vivo distribution in Lewis-bearing mice, and its effects on suppression of Lewis lung cancer growth and induction of apoptosis. METHODS: The present study was carried out in the Experimental Research Center, Sheng Jing Hospital of China Medical University Hospital, Shenyang China between December 2008 and October 2009. Chemical synthesis of His-IN was carried out. Ninety-five C57 mice were allocated into 12 groups, and a series of experiments including the in vivo biological distribution of 131I-His-IN in C57 mice bearing Lewis lung cancer was explored, and the therapeutic effects of IN and 131I-His-IN in lung cancer-bearing mice were assessed through tumor suppression experiments, flow cytometry, and detection of tumor necrosis factor. RESULTS: The 131I-His-IN radionuclide count ratio of the tumor site and surrounding region significantly increased with time, namely, the retention time of 131I-His-IN radionuclide was longer in the tumor site. A 3.0 mg/kg and 3.5 mg/kg 131I-His-IN, as well as 3.0 mg/kg and 3.5 mg/kg IN all had tumor suppression and apoptosis induction effects on tumors, among which the 3.5 mg/kg 131I-His-IN group had significant differences compared with all other groups. CONCLUSION: The 131I-His-IN not only retains the tumor-affinity property of IN, the synergistic effect of these 2 also enhances the tumor suppression and pro-apoptotic function.


Assuntos
Carcinoma Pulmonar de Lewis/metabolismo , Radioisótopos do Iodo/farmacocinética , Neoplasias Pulmonares/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cromatografia em Camada Delgada , Sinergismo Farmacológico , Citometria de Fluxo , Histamina/farmacocinética , Masculino , Camundongos , Ratos , Ratos Endogâmicos Lew , Fator de Necrose Tumoral alfa/análise
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