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1.
Artigo em Inglês | MEDLINE | ID: mdl-34826069

RESUMO

Carbon neutrality lays out a grand blueprint for carbon emission reduction and climate governance in China. How to reduce energy consumption is the key to achieving this goal. The economic development and energy consumption show a very large gap at the provincial level, and this paper divides China into six regions (North, Northeast, East, Mid-South, Southwest, and Northwest) and analyzes the dynamic changes and reveals the driving factors that have affected CO2 emission changes from 1997 to 2017. Then, the driving forces including energy intensity, energy structure, energy efficiency, economic activity, and population scale were discussed employing the logarithmic mean Divisia index (LMDI) based on provincial panel data. The results show that CO2 emissions from energy consumption show an upward trend, from 4145 Mt in 1997 to 13,250 Mt in 2017, with an annual average growth rate of 1.06%; coal consumption is the main source of CO2 emission. The regions with the highest proportion of CO2 emissions are the East and North, which account for 50% of total emissions. China's CO2 emissions from energy consumption, coal consumption, and output have shown significant spatial autocorrelation at the provincial scale. According to coal consumption, energy consumption CO2 emissions are divided into three stages: phase I (1997-2002), the increase in CO2 emissions in six regions was attributed to significant and positive impacts of energy intensity, economic activity, and population scale, the effects of which exceeded those of the energy structure and energy efficiency; phase II (2003-2012), the economic activity effect on CO2 emissions was highest in the East region, followed by the North and Mid-South regions; phase III (2013-2017), the East, Mid-South, and Southwest regions of China were dominated by the positive effects of energy intensity, economic activity, and population scale. The major driver of CO2 emissions is economic activity; the energy efficiency effect is an important inhibitory factor. Regional economic development and energy consumption in China are unbalanced; we conclude that differentiated emission reduction measures should be of particular concern for policymakers.

2.
Perfusion ; : 2676591211051860, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34689640

RESUMO

OBJECTIVE: Levosimendan has been demonstrated to reduce the incidence of cardiogenic shock and facilitate weaning from cardiopulmonary bypass. However, the beneficial effects of levosimendan treatment on hospital outcomes in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) are uncertain. We performed a systematic review and meta-analysis to evaluate the short-term effects of levosimendan use for patients undergoing VA-ECMO. METHODS: We searched PubMed, Embase, and the Cochrane Library for English articles published from inception to July 15, 2021. Observational studies comparing levosimendan versus non- levosimendan for VA-ECMO were considered eligible for the current study. RESULTS: Nine observational studies with 1058 patients were included. In-hospital mortality was 46.3% in the levosimendan group as compared with 50.7% in the control group. Levosimendan significantly reduced in-hospital mortality in patients undergoing VA-ECMO compared with the control group (RR, 0.80; 95% CI, 0.67-0.95; p = 0.013). The incidence of weaning from VA-ECMO was 79.3% in the levosimendan group as compared with 63.4% in the control group. Levosimendan significantly increase the incidence of weaning from VA-ECMO in patients as compared with the control group (RR, 1.20; 95% CI, 1.07-1.34; p = 0.002). In the one-way sensitivity analysis for estimating the effect of each study on mortality or weaning from VA-ECMO, omission of each study did not make a significant difference. CONCLUSIONS: Our study indicates that levosimendan use significantly reduced in-hospital mortality and increase the incidence of weaning in patients undergoing VA-ECMO.

3.
Acta Ophthalmol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477295

RESUMO

PURPOSE: To investigate the expression of CD146 and its role in proliferative diabetic retinopathy (PDR). METHODS: Enzyme linked immunosorbent assay was performed to analyse the expression and relationship of sCD146, vascular endothelial growth factor (VEGF), sVEGFR1 and sVEGFR2 in vitreous specimens from PDR and idiopathic epiretinal membranes (IERM) or idiopathic macular hole patients. The location of CD146 in ERMs was detected by immunofluorescence. The oxygen-induced retinopathy (OIR) mice model was established and the adeno-associated virus expressing a shRNA of CD146 (AAV1-shCD146-GFP) was administered via intravitreal injection. The effect of AAV1-shCD146-GFP was explored by immunofluorescence, Western blot and quantitative real-time PCR. RESULTS: The levels of sCD146 in vitreous specimens from PDR patients and CD146 in retinas from OIR mice were significantly increased. Immunofluorescence showed that CD146 was co-located with CD31, VEGF, VEGFR1 and VEGFR2, respectively. Intravitreal injection of AAV1-shCD146-GFP could dramatically reduce the formation of neovascularization and non-perfusion area by inhibiting VEGFR2 phosphorylation. CONCLUSION: Our results indicated that CD146 was involved in the development of retinal neovascularization via VEGFR2 pathway. Anti-CD146 may be an innovative or adjuvant therapy, which provides a new direction for the treatment of PDR and other ocular neovascular diseases.

4.
Sci Rep ; 11(1): 16956, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417523

RESUMO

Osteoarthritis (OA), a most common and highly prevalent joint disease, is closely associated with dysregulated expression and modification of RXRα. However, the role of RXRα in the pathophysiology of OA remains unknown. The present study aimed to investigate whether RXRα modulator, such as K-80003 can treat OA. Experimental OA was induced by intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats. Articular cartilage degeneration was assessed using Safranin-O and fast green staining. Synovial inflammation was measured using hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Expressions of MMP-13, ADAMTS-4 and ERα in joints were analyzed by immunofluorescence staining. Western blot, RT-PCR and co-Immunoprecipitation (co-IP) were used to assess the effects of K-80003 on RXRα-ERα interaction. Retinoid X receptor α (RXRα) modulator K-80003 prevented the degeneration of articular cartilage, reduced synovial inflammation, and alleviated osteoarthritic pain in rats. Furthermore, K-80003 markedly inhibited IL-1ß-induced p65 nuclear translocation and IκBα degradation, and down-regulate the expression of HIF-2α, proteinases (MMP9, MMP13, ADAMTS-4) and pro-inflammatory factors (IL-6 and TNFα) in primary chondrocytes. Additionally, knockdown of ERα with siRNA blocked these effects of K-80003 in chondrocytes. In conclusion, RXRα modulators K-80003 suppresses inflammatory and catabolic responses in OA, suggesting that targeting RXRα-ERα interaction by RXRα modulators might be a novel therapeutic approach for OA treatment.


Assuntos
Inflamação/complicações , Inflamação/metabolismo , Osteoartrite/complicações , Osteoartrite/metabolismo , Receptor X Retinoide alfa/metabolismo , Sulindaco/análogos & derivados , Animais , Cartilagem/diagnóstico por imagem , Cartilagem/patologia , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Modelos Animais de Doenças , Receptor alfa de Estrogênio/metabolismo , Células HEK293 , Humanos , Inflamação/diagnóstico por imagem , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , NF-kappa B/metabolismo , Osteoartrite/diagnóstico por imagem , Dor/complicações , Substâncias Protetoras/farmacologia , Ligação Proteica/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sulindaco/farmacologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Sinovite/complicações , Sinovite/patologia , Regulação para Cima
5.
Artigo em Inglês | MEDLINE | ID: mdl-34101605

RESUMO

Few-shot semantic segmentation remains an open problem for the lack of an effective method to handle the semantic misalignment between objects. In this article, we propose part-based semantic transform (PST) and target at aligning object semantics in support images with those in query images by semantic decomposition-and-match. The semantic decomposition process is implemented with prototype mixture models (PMMs), which use an expectation-maximization (EM) algorithm to decompose object semantics into multiple prototypes corresponding to object parts. The semantic match between prototypes is performed with a min-cost flow module, which encourages correct correspondence while depressing mismatches between object parts. With semantic decomposition-and-match, PST enforces the network's tolerance to objects' appearance and/or pose variation and facilities channelwise and spatial semantic activation of objects in query images. Extensive experiments on Pascal VOC and MS-COCO datasets show that PST significantly improves upon state-of-the-arts. In particular, on MS-COCO, it improves the performance of five-shot semantic segmentation by up to 7.79% with a moderate cost of inference speed and model size. Code for PST is released at https://github.com/Yang-Bob/PST.

6.
Graefes Arch Clin Exp Ophthalmol ; 259(9): 2795-2805, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34003361

RESUMO

PURPOSE: To quantitatively evaluate the lipid layer thickness (LLT) and blinking in children with or without allergic conjunctivitis (AC), and to compare those between the different types of AC. METHODS: For this case-control study, 81 children with symptomatic AC with an average age of 9.62 ± 2.67 years were enrolled and subdivided according to the subtypes of AC, including seasonal/perennial allergic conjunctivitis group and vernal keratoconjunctivitis (VKC)/atopic keratoconjunctivitis (AKC) group. Another 82 age-matched healthy children were enrolled as control group. All subjects underwent routine eye examination and measurements of LLT, the number of incomplete or total blinking, partial blinking rate by the LipiView interferometer over a 10-s period. Other ocular surface assessment included fluorescein tear breakup time (TBUT), lower tear meniscus height, meibomian gland loss (MGL), meibum expressibility and quality. RESULTS: Pediatric patients with AC had significant thinner LLT, shorter TBUT, decreased total blinking but increased partial blinking rate, especially in those with VKC/AKC (all P < 0.05). A significant deterioration of meibomian gland parameters was observed in AC group when compared with control subjects, demonstrated by severe upper and lower MGL, lid margin abnormalities, decreased meibum expressibility, and abnormal meibum quality, all of which were worse in the severe type of AC (all P < 0.05). Thinner LLT was significantly correlated with decreased TBUT (ß = 3.666, P < 0.001) and severity of upper MGL (ß = - 7.701, P = 0.002). CONCLUSION: Decreased LLT and blinking disorders in pediatric patients with AC may contribute to lipid layer deficiency in the long run, which should be considered and appropriately diagnosed for a more precise treatment.


Assuntos
Conjuntivite Alérgica , Síndromes do Olho Seco , Piscadela , Estudos de Casos e Controles , Criança , Conjuntivite Alérgica/diagnóstico , Humanos , Interferometria , Lipídeos , Glândulas Tarsais/diagnóstico por imagem , Lágrimas
7.
Biochim Biophys Acta Mol Basis Dis ; 1867(6): 166126, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33722744

RESUMO

Mitochondrial-derived peptide (MOTS-c) has gained increasing attention as a promising therapeutic or prevention strategy for obesity and diabetes mellitus. MOTS-c targets the folate cycle, leading to an accumulation of 5-aminomidazole-4-carboxamide ribonucleotide (AICAR) as well as AMPK activation. AMPK is a well-known upstream regulator of the proliferation-activated receptor co-activator 1 (PGC-1α), which can improve mitochondrial biogenesis via co-transcriptional modifications. We hypothesized that AMPK can induce the expression of MOTS-c through PGC-1α. Our study aimed to explore whether MOTS-c and/or exercise can regulate MOTS-c expression, attenuate insulin resistance and enhance glucose metabolism both in vitro and in vivo. It was found that C2C12 myotubes exposed to Compound C (an AMPK inhibitor) had deceases in the protein and mRNA expressions of PGC-1α and MOTS-c. PGC-1α knockdown downregulated the protein and mRNA expressions of MOTS-c in C2C12 myotubes, whereas both PGC-1α overexpression and recombinant MOTS-c supplementation upregulated the protein and mRNA expressions of MOTS-c in C2C12 myotubes. Furthermore, the skeletal muscle and plasma levels of MOTS-c were markedly reduced in high-fat diet-induced obese mice. Treadmill training remarkably upregulated the protein levels of MOTS-c, PGC-1α and GLUT4, along with the phosphorylation levels of AMPK and ACC. Altogether, these results indicate that AMPK/PGC-1α pathway can mediate the secretion and/or production of MOTS-c in skeletal muscle, implying the possible roles of exercise intervention and recombinant MOTS-c in treating obesity and diabetes mellitus.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Intolerância à Glucose/terapia , Glucose/metabolismo , Resistência à Insulina , Proteínas Mitocondriais/metabolismo , Fragmentos de Peptídeos/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal , Proteínas Quinases Ativadas por AMP/genética , Animais , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética
8.
Am J Physiol Heart Circ Physiol ; 320(4): H1634-H1645, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33635162

RESUMO

Wnt/ß-catenin signaling plays a key role in pathological cardiac remodeling in adults. The identification of a tissue-specific Wnt/ß-catenin interaction factor may provide a tissue-specific clinical targeting strategy. Drosophila Pygo encodes the core interaction factor of Wnt/ß-catenin. Two Pygo homologs (Pygo1 and Pygo2) have been identified in mammals. Different from the ubiquitous expression profile of Pygo2, Pygo1 is enriched in cardiac tissue. However, the role of Pygo1 in mammalian cardiac disease is yet to be elucidated. In this study, we found that Pygo1 was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios, and increased cell size. The canonical ß-catenin/T-cell transcription factor 4 (TCF4) complex was abundant in Pygo1-overexpressing transgenic (Pygo1-TG) cardiac tissue, and the downstream genes of Wnt signaling, that is, Axin2, Ephb3, and c-Myc, were upregulated. A tail vein injection of ß-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodeling in Pygo1-TG mice. Furthermore, in vivo downregulated pygo1 during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for tissue-specific clinical treatment via targeting this pathway.NEW & NOTEWORTHY In this study, we found that Pygo1 is associated with human pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy. Meanwhile, cardiac function was improved when expression of Pygo1 was interfered in hypertrophy-model mice. Our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Insuficiência Cardíaca/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Miocárdio/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Via de Sinalização Wnt , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteína Axina/genética , Proteína Axina/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/prevenção & controle , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/patologia , Isoproterenol , Masculino , Camundongos Transgênicos , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Receptor EphB3/genética , Receptor EphB3/metabolismo , Tiazolidinas/farmacologia , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores
9.
Environ Sci Pollut Res Int ; 28(11): 13649-13659, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33188521

RESUMO

In recent years, concern has been increasing regarding the carbon emissions generated by mining activities. China is an extremely large coal producer (3695 Mt/2015) and consumer (3698 Mt/2015), and Shanxi Province (i.e., a major coal-producing province in China) is a crucial element in China's energy conservation and emission reduction goals. In this study, the Pingshuo mining area (PMA) in Shanxi Province was chosen as a case to analyze the dynamic changes in carbon emissions based on the Intergovernmental Panel on Climate Change (IPCC) method, and the factors influencing carbon emissions were analyzed via the IPAT equation. Carbon emission sources in opencast mines mainly included fuel and explosive use, coal mine methane escape, coal and gangue spontaneous combustion, and electricity consumption. The carbon emission of the PMA increased from 4 × 104 Mg in 1986 to 1.05 × 106 Mg in 2015, with an average annual increase of 11.64%. In the PMA, 4.71 × 106 Mg of carbon emissions from fuel consumption accounted for 41.79% of carbon emissions, and 5.26 × 106 Mg of carbon emissions from methane emissions accounted for 46.66%. Carbon emissions from explosives and electricity use were 4.1 × 105 Mg and 8.8 × 105 Mg, respectively. In this mining area, the factors influencing carbon emissions included population, GDP, and coal output. The results of this study not only provide a reference for cleaner production in mining areas but also lay a foundation for the study of global opencast coal mining carbon emissions.


Assuntos
Carbono , Minas de Carvão , Carbono/análise , China , Carvão Mineral/análise , Combustão Espontânea
10.
BMC Genomics ; 21(1): 823, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228535

RESUMO

BACKGROUND: Current single cell analysis methods annotate cell types at cluster-level rather than ideally at single cell level. Multiple exchangeable clustering methods and many tunable parameters have a substantial impact on the clustering outcome, often leading to incorrect cluster-level annotation or multiple runs of subsequent clustering steps. To address these limitations, methods based on well-annotated reference atlas has been proposed. However, these methods are currently not robust enough to handle datasets with different noise levels or from different platforms. RESULTS: Here, we present gCAnno, a graph-based Cell type Annotation method. First, gCAnno constructs cell type-gene bipartite graph and adopts graph embedding to obtain cell type specific genes. Then, naïve Bayes (gCAnno-Bayes) and SVM (gCAnno-SVM) classifiers are built for annotation. We compared the performance of gCAnno to other state-of-art methods on multiple single cell datasets, either with various noise levels or from different platforms. The results showed that gCAnno outperforms other state-of-art methods with higher accuracy and robustness. CONCLUSIONS: gCAnno is a robust and accurate cell type annotation tool for single cell RNA analysis. The source code of gCAnno is publicly available at https://github.com/xjtu-omics/gCAnno .


Assuntos
Algoritmos , Análise de Célula Única , Teorema de Bayes , Análise por Conglomerados , Análise de Sequência de RNA
11.
Nanotechnology ; 31(47): 475501, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32886652

RESUMO

Carbonized polymer dots (CPDs), as a novel fluorescent material, have broad application prospects in the fields of bio-imaging, bio-sensors, disease diagnosis and photovoltaic devices due to their low cost, low toxicity, easy modification and little environmental impact. In this paper, folic acid (FA) modified CPDs (FA-CPDs) are synthesized from p-Phenylenediamine (p-PD) and FA molecules using a traditional one pot hydrothermal reaction in order to detect cancer cells containing a folate receptor (FR). The synthesized FA-CPDs were characterized by transmission electron microscopy, Fourier transfrom infrared spectroscopy, x-ray photoelectron spectroscopy, x-ray diffraction, UV-vis and fluorescence techniques. The red fluorescence emission is realized by doping phosphorus atoms into the carbonized polymer. Upon excitation at 513 nm, the maximum emission wavelength of FA-CPDs aqueous solution was obtained at 613 nm. Moreover, the as-prepared FA-CPDs exhibit excellent excitation-independent behavior and good stability with high quantum yield (QY) at about 30.6%. The binding of FA-CPDs with FRs on cancer cells produces target recognition and enters the cells through endocytosis. Additionally, it is worth noting that FA-CPDs have good biocompatibility and imaging in HeLa cells has been successfully achieved. Therefore, our FA-CPDs have potential applications as biocompatibility probes for cancer diagnosis and treatment.


Assuntos
Corantes Fluorescentes/química , Receptores de Folato com Âncoras de GPI/análise , Ácido Fólico/química , Neoplasias/diagnóstico por imagem , Polímeros/química , Pontos Quânticos/química , Carbono/química , Células HeLa , Humanos , Microscopia Confocal/métodos , Imagem Óptica/métodos
12.
J Pineal Res ; 69(1): e12660, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32323368

RESUMO

Choroidal neovascularization (CNV) is an important characteristic of advanced wet age-related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti-inflammation, and anti-angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser-induced mouse CNV model. Additionally, the results also show that the melatonin-treated retinal microglia in the laser-induced mice exhibited enhanced expression of M1-type markers, such as iNOS, CCL-3, CCL-5, and TNF-α, as well as decreased production of M2-type markers, such as Arg-1, Fizz-1, IL-10, YM-1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro-angiogenic M2 phenotype to anti-angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD.


Assuntos
Neovascularização de Coroide/metabolismo , Macrófagos/metabolismo , Melatonina/metabolismo , Microglia/metabolismo , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Neovascularização de Coroide/patologia , Macrófagos/patologia , Camundongos , Microglia/patologia
13.
JCI Insight ; 4(20)2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31619589

RESUMO

Efferocytosis, or phagocytic clearance of dead/dying cells by brain-resident microglia and/or infiltrating macrophages, is instrumental for inflammation resolution and restoration of brain homeostasis after stroke. Here, we identify the signal transducer and activator of transcription 6/arginase1 (STAT6/Arg1) signaling axis as a potentially novel mechanism that orchestrates microglia/macrophage responses in the ischemic brain. Activation of STAT6 was observed in microglia/macrophages in the ischemic territory in a mouse model of stroke and in stroke patients. STAT6 deficiency resulted in reduced clearance of dead/dying neurons, increased inflammatory gene signature in microglia/macrophages, and enlarged infarct volume early after experimental stroke. All of these pathological changes culminated in an increased brain tissue loss and exacerbated long-term functional deficits. Combined in vivo analyses using BM chimeras and in vitro experiments using microglia/macrophage-neuron cocultures confirmed that STAT6 activation in both microglia and macrophages was essential for neuroprotection. Adoptive transfer of WT macrophages into STAT6-KO mice reduced accumulation of dead neurons in the ischemic territory and ameliorated brain infarction. Furthermore, decreased expression of Arg1 in STAT6-/- microglia/macrophages was responsible for impairments in efferocytosis and loss of antiinflammatory modality. Our study suggests that efferocytosis via STAT6/Arg1 modulates microglia/macrophage phenotype, accelerates inflammation resolution, and improves stroke outcomes.


Assuntos
Arginase/metabolismo , Infarto Encefálico/imunologia , Macrófagos/imunologia , Microglia/imunologia , Fator de Transcrição STAT6/metabolismo , Idoso de 80 Anos ou mais , Animais , Encéfalo/patologia , Infarto Encefálico/patologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Macrófagos/metabolismo , Masculino , Camundongos , Microglia/metabolismo , Neurônios , Fagocitose , Cultura Primária de Células , Fator de Transcrição STAT6/genética , Transdução de Sinais/imunologia
14.
J Cell Mol Med ; 23(10): 6578-6594, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31449345

RESUMO

Quaking homolog (QKI) is a member of the RNA-binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'-untraslated region (3'-UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI-6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI-6 overexpression or knockdown. QKI-6 down-regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI-6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI-6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI-6 expression had opposite effects in vitro and in vivo. QKI-6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'-UTR, whereas E2F3 induced QKI-6 transcription by binding to the QKI-6 promoter in negative feedback mechanism. QKI-6 expression also suppressed activity and expression of nuclear factor-κB (NF-κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI-6. In conclusion, QKI-6 down-regulation contributes to bladder cancer development and progression.


Assuntos
Fator de Transcrição E2F3/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , NF-kappa B/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Fator de Transcrição E2F3/genética , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , NF-kappa B/antagonistas & inibidores , Estadiamento de Neoplasias , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas de Ligação a RNA/genética , Transdução de Sinais/genética , Transplante Heterólogo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
15.
Nanotechnology ; 30(47): 475701, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31430734

RESUMO

In this work, we first report Au nanoclusters/porous silica particles nanocomposites as fluorescence enhanced sensors for selective and sensitive detection of Cu (II). As red-emitting GSH-protected Au nanoclusters (Au NCs) were self-assemble into porous silica particles (PSPs) after ultrasonic treatment. As a result, the Au NCs can be immobilized in the nano-channels of PSPs, which leads to the observation of an immobilized induced emission enhancement phenomenon. The photoluminscence (PL) intensity of the nanocomposites can enhance dozens of times compared with Au NCs. As a result, we obtain a novel PL enhanced sensor of Au NCs/PSPs nanocomposites with excellent PL properties. The as-prepared Au NCs/PSPs nanocomposites show good water-solubility, high stability, low toxicity, and exhibit a high PL quenching for reliable, sensitive and selective detection of Cu2+. The limit of detection can reach as low as 1 ppb. What is more, the Au NCs/PSPs nanocomposites also show sensitive detection of Cu2+ in living cells. These properties provide the Au NCs/PSPs nanocomposites with promising PL sensors for Cu2+ detection in various environmental and biological systems.


Assuntos
Cobre/química , Ouro/química , Nanocompostos/química , Dióxido de Silício/química , Animais , Linhagem Celular , Sobrevivência Celular , Corantes Fluorescentes/química , Humanos , Nanocompostos/ultraestrutura , Espectroscopia Fotoeletrônica , Porosidade
16.
Curr Eye Res ; 44(10): 1104-1111, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31154859

RESUMO

Purpose: To investigate vasculature-function and structure-function relationship in healthy myopic eyes using optical coherence tomography angiography (OCT-A), optical coherence tomography (OCT) and microperimetry (MAIA). Methods: A total of 370 eyes from 190 participants were enrolled in this study. Subjects divided into three groups based on refractive status: low myopia (LM) (-3.00D ≤ spherical equivalent, SE ≤ -0.50D), moderate myopia (MM) (-6.00D ≤ SE < -3.00D) and high myopia (HM) (SE < -6.00D). The vessel density (VD), retinal thickness (RT) and light sensitivity (LS) were evaluated using OCT-A, OCT and MAIA. The global and regional vasculature-function and structure-function relationship were evaluated by the semi-partial correlation analysis according to ETDRS grid. The uni- and multivariate linear regression models were performed using LS as the dependent variable and covariates, included age, gender, intraocular pressure (IOP), axial length (AL), SE, ganglion cell complex thickness (GCCT), superficial (SVD) and deep vessel density (DVD) and RT as independent variables. Results: The LS negatively correlated with AL and positively correlated with SE, DVD, RT and GCCT (P < .05). The DVD was associated with the corresponding LS only in temporal and nasal sectors in HM (sr: 0.182-0.195, P < .05) but SVD not at all. The RT was associated with the corresponding LS in inferior and nasal sectors in MM (sr: 0.221-0.281, P < .005) and all sectors in HM (sr: 0.187-0.229, P < .05). Lower DVD and RT were independently associated with the declined LS in myopic eyes (P < .05). Conclusions: Reduced DVD and RT were independently associated with the declined LS in healthy myopic eyes, especially in HM.


Assuntos
Luz , Miopia/fisiopatologia , Retina/efeitos da radiação , Vasos Retinianos/fisiopatologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologia , Adolescente , Adulto , Comprimento Axial do Olho , Estudos Transversais , Feminino , Angiofluoresceinografia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Miopia/diagnóstico por imagem , Retina/diagnóstico por imagem , Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica , Testes de Campo Visual , Adulto Jovem
17.
Cell Prolif ; 52(3): e12590, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30883989

RESUMO

OBJECTIVES: 5α-reductase inhibitor (5-ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment. MATERIALS AND METHODS: Prostate specimens from patients were collected. Insulin-like growth factor 1 (IGF-1), Beclin-1, LC3 levels, was analysed by immunohistochemistry. The role IGF-1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated. RESULTS: We demonstrated that IGF-1 expression is down-regulated in prostate fibroblasts after long-term 5-ARI application. A decrease in IGF-1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF-1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long-term 5-ARI application reduces IGF-1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression. CONCLUSIONS: Focusing on the autophagy induced by low levels of IGF-1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Próstata/citologia , Próstata/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Receptores Androgênicos/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
18.
Acta Biomater ; 88: 392-405, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753941

RESUMO

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.


Assuntos
Cateteres , Materiais Revestidos Biocompatíveis/farmacologia , Macrófagos/patologia , Nanosferas/química , Transdução de Sinais , Dióxido de Silício/química , Uretra/patologia , Cicatrização/efeitos dos fármacos , Animais , Polaridade Celular , Cães , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , NF-kappa B/metabolismo , Nanosferas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Porosidade , Próstata/patologia , Próstata/cirurgia , Reepitelização/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Células THP-1 , Ressecção Transuretral da Próstata , Uretra/efeitos dos fármacos
19.
J Exp Clin Cancer Res ; 37(1): 221, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30200999

RESUMO

BACKGROUND: Prostate cancer is one of the most common malignancies. Increasing evidence suggested that endothelial cells may contribute to prostate cancer progression and metastasis. Most recently, autophagy has been proposed to plays a significant role in tumorigenesis and metastasis. Also, it is reported that downregulation of androgen receptor (AR) induces autophagy in prostate cancer cells. However, the underlying mechanisms remain unclear. Here, we aim to explore the role and mechanisms of endothelial cell in prostate cancer progression. METHODS: The coculture system was established to test the effect of endothelial cells on prostate cancer cells. We performed antibody array and ELISA were used to profile the cytokine expression pattern of endothelial cells in supernatant. Western blot and RT-PCR were used to determine the mechanism by endothelial cells to promote invasion ability of prostate cancer cells. Maraviroc and chloroquine were used to block the CCL5/CCR5 and autophagy pathway respectively. Orthotopic xenograft mouse models and drug treatment study were conducted to determine the role of endothelial cells in promoting metastatic potential in vivo. RESULTS: We use CPRC prostate cancer model and demonstrate that endothelial cells secrete large amount of CCL5 and induces autophagy by suppressing AR expression in prostate cancer cell lines. Consequently, elevated autophagy accelerates focal adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in vivo. CONCLUSIONS: Together, our data establish the function for endothelial cells in tumor metastasis and propose new drug target for mCRPC.


Assuntos
Autofagia/genética , Quimiocina CCL5/genética , Neoplasias da Próstata/genética , Receptores Androgênicos/genética , Receptores CCR5/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Técnicas de Cocultura , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Cell Death Dis ; 9(4): 431, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29568063

RESUMO

The activation of androgen receptor (AR) signaling plays an essential role in both prostate stromal cells and epithelial cells during the development of benign prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after 5α-reductase inhibitor (5-ARI) treatment induced autophagy in prostate stromal fibroblasts inhibiting cell apoptosis. In addition, we found that ATG9A expression was increased after androgen ablation, which facilitated autophagic flux development. Knockdown of ATG9A not only inhibited autophagy notably in prostate stromal fibroblasts, but also reduced the volumes of prostate stromal fibroblast and epithelial cell recombinant grafts in nude mice. In conclusion, our findings suggested that ATG9A upregulation after long-term 5-ARI treatment constitutes a possible mechanism of BPH progression. Thus, combined treatment with 5-ARI and autophagy inhibitory agents would reduce the risk of BPH progression.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Autofagia , Proteínas de Membrana/metabolismo , Hiperplasia Prostática/patologia , Transdução de Sinais , Proteínas de Transporte Vesicular/metabolismo , Inibidores de 5-alfa Redutase/farmacologia , Animais , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/antagonistas & inibidores , Proteínas Relacionadas à Autofagia/genética , Células Cultivadas , Progressão da Doença , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Próstata/citologia , Hiperplasia Prostática/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima , Proteínas de Transporte Vesicular/antagonistas & inibidores , Proteínas de Transporte Vesicular/genética
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