Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.193
Filtrar
1.
Carbohydr Polym ; 252: 117160, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33183611

RESUMO

Herein, an amidoxime-functionalized chitosan (CTS) AM/AO/AEBI-CTS containing imidazoline groups was facilely prepared through amidoximation of cyano groups in cross-linked CTS obtained by crosslinking of imidazoline-functionalized polyacrylamide and CTS. AM/AO/AEBI-CTS exhibited porous structure, good water wettability, and higher selectivity for Cu2+ than Ni2+. The adsorption process correlated well with Sips isotherm and pseudo-second-order kinetics models. The adsorption capacities for Cu2+ and Ni2+ onto AM/AO/AEBI-CTS were 190.7 and 128.9 mg/g, respectively. The adsorption thermodynamics demonstrated that the adsorption of Cu2+ and Ni2+ ions onto AM/AO/AEBI-CTS was a spontaneous endothermic process. The FTIR and XPS analyses revealed that nitrogen and oxygen atoms were involved in the chelation with metal ions. The presence of Na+, K+ and Ca2+ had weakly impact on the adsorption efficiency of AM/AO/AEBI-CTS. Furthermore, the adsorption efficiency of AM/AO/AEBI-CTS remained above 90 % after five adsorption-desorption successive cycles. Overall, this CTS material has a good application prospects for wastewater treatment.

2.
Int J Infect Dis ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33181330

RESUMO

OBJECTIVES: We aimed to estimate the time-varying transmission dynamics of COVID-19 in China, Wuhan City and Guangdong province, and compared them with that of severe acute respiratory syndrome (SARS). METHODS: Data on COVID-19 cases by March 20, 2020 in China was collected from epidemiological investigations or official websites. Data on SARS cases in Guangdong Province, Beijing and Hong Kong during 2002-2003 were also obtained. We estimated the doubling time, basic reproduction number (R0) and time-varying reproduction number (Rt) of COVID-19 and SARS. RESULTS: As of March 20, 2020, 80,739 COVID-19 indigenous cases were identified in mainland China. Most cases were reported between January 20 and February 29. The R0 of COVID-19 nationwide and in Wuhan were 5.0 and 4.8 respectively, which were greater than R0 of SARS in Guangdong (R0=2.3), Hong Kong (R0 = 2.3), and Beijing (R0 = 2.6). During the epidemic of COVID-19, the Rt nationwide first increased to a peak of 8.4 and declined quickly to below 1 in one month. In terms of SARS, the Rt curve saw a fluctuation change with more than one peak though the peak was lower than COVID-19. CONCLUSIONS: COVID-19 has much higher transmissibility than SARS, and a series of major actions for suppressing the outbreak are effective. However, persistent efforts are needed to prevent the rebound of the epidemic in the context of the global pandemic.

3.
ACS Appl Mater Interfaces ; 12(45): 50600-50609, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33131273

RESUMO

A combined photothermal simulation and experimental study leads to a novel internal reflection-assisted direct laser writing carbonization method (IR-DLWc), which enables in situ fabrication of carbon features/patterns that are self-sealed in the interior of a thin polyimide (PI) film in one step without additional packaging procedures. With this new method, carbon line patterns that are fully contained in a 50 µm PI film are fabricated, characterized, and evaluated for their electrical and piezoresistive performance. The self-sealing character of the carbon features created by IR-DLWc imparts them unprecedented mechanical stability/robustness as compared to those fabricated by the conventional DLWc method. Upon applying a double-writing scheme and strain-engineering treatment, the IR-DLWc-created carbon lines show significantly improved piezoresistive sensitivity with a gauge factor evaluated to be 428 in tension and 107 in compression. The high piezoresistive sensitivity, excellent dynamic response, reasonably good durability, self-sealing character, and compliant nature of the IR-DLWc generated carbon patterns make them suitable for a variety of wearable sensing applications. In this work, we demonstrated their use as a tactile sensor for sensing contact force; a functional bandage for monitoring physiological activities like swallowing, pulsing, and breathing; and a glove sensing system for finger gesture recognition.

4.
Brief Bioinform ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33142319

RESUMO

Alternative polyadenylation (APA) generates diverse mRNA isoforms, which contributes to transcriptome diversity and gene expression regulation by affecting mRNA stability, translation and localization in cells. The rapid development of 3' tag-based single-cell RNA-sequencing (scRNA-seq) technologies, such as CEL-seq and 10x Genomics, has led to the emergence of computational methods for identifying APA sites and profiling APA dynamics at single-cell resolution. However, existing methods fail to detect the precise location of poly(A) sites or sites with low read coverage. Moreover, they rely on priori genome annotation and can only detect poly(A) sites located within or near annotated genes. Here we proposed a tool called scAPAtrap for detecting poly(A) sites at the whole genome level in individual cells from 3' tag-based scRNA-seq data. scAPAtrap incorporates peak identification and poly(A) read anchoring, enabling the identification of the precise location of poly(A) sites, even for sites with low read coverage. Moreover, scAPAtrap can identify poly(A) sites without using priori genome annotation, which helps locate novel poly(A) sites in previously overlooked regions and improve genome annotation. We compared scAPAtrap with two latest methods, scAPA and Sierra, using scRNA-seq data from different experimental technologies and species. Results show that scAPAtrap identified poly(A) sites with higher accuracy and sensitivity than competing methods and could be used to explore APA dynamics among cell types or the heterogeneous APA isoform expression in individual cells. scAPAtrap is available at https://github.com/BMILAB/scAPAtrap.

5.
J Int Assoc Provid AIDS Care ; 19: 2325958220970827, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33143525

RESUMO

The need for HIV testing in US emergency departments (EDs) has not been assessed, particularly among Latino immigrants and Blacks. We surveyed Latino immigrant and Black 18 to 64-year-old patients at 4 EDs about demographic characteristics, HIV testing history, and health literacy. A subset of patients was further surveyed on HIV risk-taking behaviors. Of the 2,265 participants, 24% had never been tested for HIV. Latino immigrants were more likely than Blacks never to have been tested for HIV (28% vs. 16%). In multivariable logistic regression, for Latino immigrants, male gender and lower health literacy were associated with no previous HIV testing. Among the 1,141-participant subset providing HIV risk-taking behavior data, 23% reported at least one risk factor and of those with at least one risk factor, 23% had never been tested for HIV. There remains a need for HIV testing among adult Latino immigrant and Black patients in US EDs.

6.
Respiration ; : 1-9, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33147584

RESUMO

BACKGROUND: Effective auscultations are often hard to implement in isolation wards. To date, little is known about the characteristics of pulmonary auscultation in novel coronavirus (COVID-19) pneumonia. OBJECTIVES: The aim of this study was to explore the features and clinical significance of pulmonary auscultation in COVID-19 pneumonia using an electronic stethoscope in isolation wards. METHODS: This cross-sectional, observational study was conducted among patients with laboratory-confirmed COVID-19 at Wuhan Red-Cross Hospital during the period from January 27, 2020, to February 12, 2020. Standard auscultation with an electronic stethoscope was performed and electronic recordings of breath sounds were analyzed. RESULTS: Fifty-seven patients with average age of 60.6 years were enrolled. The most common symptoms were cough (73.7%) during auscultation. Most cases had bilateral lesions (96.4%) such as multiple ground-glass opacities (69.1%) and fibrous stripes (21.8%). High-quality auscultation recordings (98.8%) were obtained, and coarse breath sounds, wheezes, coarse crackles, fine crackles, and Velcro crackles were identified. Most cases had normal breath sounds in upper lungs, but the proportions of abnormal breath sounds increased in the basal fields where Velcro crackles were more commonly identified at the posterior chest. The presence of fine and coarse crackles detected 33/39 patients with ground-glass opacities (sensitivity 84.6% and specificity 12.5%) and 8/9 patients with consolidation (sensitivity 88.9% and specificity 15.2%), while the presence of Velcro crackles identified 16/39 patients with ground-glass opacities (sensitivity 41% and specificity 81.3%). CONCLUSIONS: The abnormal breath sounds in COVID-19 pneumonia had some consistent distributive characteristics and to some extent correlated with the radiologic features. Such evidence suggests that electronic auscultation is useful to aid diagnosis and timely management of the disease. Further studies are indicated to validate the accuracy and potential clinical benefit of auscultation in detecting pulmonary abnormalities in COVID-19 infection.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33136434

RESUMO

In this study, we prepared gelatin-coated mesoporous hollow silica nanospheres (GSN) as a drug carrier to improve the water solubility and regulate the release rate of glimepiride (GLM). GLM was loaded into GSN by an absorption method, and drug-loaded samples (GLM-GSN) were characterized by differential scanning calorimeter (DSC) and X-ray diffraction (XRD). Cellular uptake and in vivo intestinal uptake experiments were performed in rats. In addition, the studies of in-vitro drug dissolution, pharmacokinetics, and pharmacodynamic experiments also were performed. GLM-GSN showed excellent drug loading (39.7% ± 0.7%) and sustained GLM release. The state of GLM in GSN was amorphous according to DSC and XRD results. Cellular uptake and in vivo intestinal uptake experiments indicated that GSN could be effectively absorbed, and an MTT experiment demonstrated that GSN had good biocompatibility. Furthermore, the GLM-GSN had a higher bioavailability in pharmacokinetics experiments and a prominent hypoglycemic effect on type-2 diabetes model rats in pharmacodynamic experiments. This study clearly shows that GSN is a promising platform for delivering GLM for the treatment of type-2 diabetes.

8.
ACS Nano ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33137257

RESUMO

Specific cytotoxicity for catalytic nanomedicine triggered by the tumor microenvironment (TME) has attracted increasing interest. In this work, we prepared AgBiS2 hollow nanospheres with narrow bandgaps via rapid precipitation in a weakly polar solvent, which lowered the intrinsic energy gap for the active production of highly reactive hydroxyl radicals (•OH), especially in the TME. The as-prepared AgBiS2 hollow nanospheres exhibited enhanced optical absorption and high photothermal conversion efficiency (44.2%). In addition, the hollow structured AgBiS2 nanospheres were found to have a peroxidase-mimicking feature to induce cancer cell-specific cytotoxicity while exhibiting negligible cytotoxicity toward normal cells, which might be attributed to the efficient production of highly reactive •OH originating from the overexpression H2O2 in the TME caused by surface catalysis. In particular, the cancer cell-specific cytotoxicity of the nanospheres was greatly enhanced both in vitro and in vivo upon irradiation with a near-infrared (NIR) laser (808 nm). The above-mentioned features of the hollow structured AgBiS2 will make it a promising candidate for tumor therapy.

9.
J Nutr Sci Vitaminol (Tokyo) ; 66(5): 456-461, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132349

RESUMO

Selenium has been associated with many malignant tumors including esophagus cancer (EC). In current study, we examined the effects of three types of selenium, sodium selenite (SSE), methylseleninic acid (MSA) and methylselenocysteine (MSC) on EC cell line Eca109. Here, selenium attenuated cell viability and increased cell apoptosis, especially in MSC, when compared with control group (p<0.05). Meanwhile, MSC and MSA, but no SSE, arrested cell cycle in G0/G1 phase (p<0.05). Mechanistically, FAL1 and PTEN were found to participate in regulating cell cycle and cell apoptosis process by decreasing cyclinD1, CDK2, and promoting caspase-3, caspase-8. In addition, we found that cyclinD1, CDK2 were significantly downregulated by MSA and MSC, while caspase-3, caspase-8 were dramatically upregulated by SSE (p<0.05). Based on these results, we concluded that MSC and MSA inhibit the viability of Eca109 mainly through reducing cell proliferation, while SSE by promoting apoptosis.

10.
Environ Res ; : 110465, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33220247

RESUMO

BACKGROUND: Different interventions targeting live poultry markets (LPMs) are applied in China for controlling avian influenza A (H7N9), including LPM closure and "1110" policy (i.e., daily cleaning, weekly disinfection, monthly rest day, zero poultry stock overnight). However, the interventions' effectiveness has not been comprehensively assessed. METHODS: Based on the available data (including reported cases, domestic poultry volume, and climate) collected in Guangdong Province between October 2013 and June 2017, we developed a new compartmental model that enabled us to infer H7N9 transmission dynamics. The model incorporated the intrinsic interplay among humans and poultry as well as the impacts of absolute humidity and LPM intervention, in which intervention strategies were parameterized and estimated by Markov chain Monte Carlo method. RESULTS: There were 258 confirmed human H7N9 cases in Guangdong during the study period. If without interventions, the number would reach 646 (95%CI, 575-718) cases. Temporal, seasonal and permanent closures of LPMs can substantially reduce transmission risk, which might respectively reduce human infections by 67.2% (95%CI, 64.3%-70.1%), 75.6% (95%CI, 73.8%-77.5%), 86.6% (95%CI, 85.7-87.6%) in total four epidemic seasons, and 81.9% (95%CI, 78.7%-85.2%), 91.5% (95%CI, 89.9%-93.1%), 99.0% (95%CI, 98.7%-99.3%) in the last two epidemic seasons. Moreover, implementing the "1110" policy from 2014 to 2017 would reduce the cases by 34.1% (95%CI, 20.1%-48.0%), suggesting its limited role in preventing H7N9 transmission. CONCLUSIONS: Our study quantified the effects of different interventions and execution time toward LPMs for controlling H7N9 transmission. The results highlighted the importance of closing LPMs during epidemic period, and supported permanent closure as a long-term plan.

11.
J Vis Exp ; (165)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33226031

RESUMO

Protein analysis of small numbers of human cells is primarily achieved by targeted proteomics with antibody-based immunoassays, which have inherent limitations (e.g., low multiplex and unavailability of antibodies for new proteins). Mass spectrometry (MS)-based targeted proteomics has emerged as an alternative because it is antibody-free, high multiplex, and has high specificity and quantitation accuracy. Recent advances in MS instrumentation make MS-based targeted proteomics possible for multiplexed quantification of highly abundant proteins in single cells. However, there is a technical challenge for effective processing of single cells with minimal sample loss for MS analysis. To address this issue, we have recently developed a convenient protein carrier-assisted one-pot sample preparation coupled with liquid chromatography (LC) - selected reaction monitoring (SRM) termed cLC-SRM for targeted proteomics analysis of small numbers of human cells. This method capitalizes on using the combined excessive exogenous protein as a carrier and low-volume one-pot processing to greatly reduce surface adsorption losses as well as high-specificity LC-SRM to effectively address the increased dynamic concentration range due to the addition of exogeneous carrier protein. Its utility has been demonstrated by accurate quantification of most moderately abundant proteins in small numbers of cells (e.g., 10-100 cells) and highly abundant proteins in single cells. The easy-to-implement features and no need for specific devices make this method readily accessible to most proteomics laboratories. Herein we have provided a detailed protocol for cLC-SRM analysis of small numbers of human cells including cell sorting, cell lysis and digestion, LC-SRM analysis, and data analysis. Further improvements in detection sensitivity and sample throughput are needed towards targeted single-cell proteomics analysis. We anticipate that cLC-SRM will be broadly applied to biomedical research and systems biology with the potential of facilitating precision medicine.

12.
Aging (Albany NY) ; 122020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33203799

RESUMO

Transfer-RNA-derived small RNAs (tsRNAs) are a novel class of short non-coding RNAs, that possess regulatory functions. However, their biological roles in hemorrhagic stroke are not understood. In this study, by RNA sequencing, we investigated the tsRNA expression profiles of intracerebral hemorrhagic rat brains in the chronic phase. A total of 331 tsRNAs were identified (308 in sham and 309 in intracerebral hemorrhage). Among them, the validation revealed that 7 tsRNAs (1 up-regulated and 6 down-regulated) were significantly changed. Subsequently, we predicted the target mRNAs of the 7 tsRNAs. Through integrative analysis, the predicted targets were validated by mRNA microarray data. Moreover, we confirmed the functions of tsRNAs targeting mRNAs in vitro. Furthermore, using bioinformatics tools and databases, we developed a tsRNA-mRNA-pathway interaction network to visualize their potential functions. Bioinformatics analyses and confirmatory experiments indicated that the altered genes were mainly enriched in several signaling pathways. These pathways were interrelated with intracerebral hemorrhage, such as response to oxidative stress, endocytosis, and regulation of G protein-coupled receptor signaling pathway. In summary, this study systematically revealed the profiles of tsRNAs after an experimental intracerebral hemorrhage. These results may provide novel therapeutic targets following a hemorrhagic stroke in the chronic phase.

13.
Brain Behav ; : e01952, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205889

RESUMO

BACKGROUND: New evidence suggests that the centromedial amygdala (CMA) and the basolateral amygdala (BLA) play different roles in threat processing. Our study aimed to investigate the effects of trauma and post-traumatic stress disorder (PTSD) on the functional connectivity (FC) of the amygdala and its subregions. METHODS: Twenty-seven patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC) were scanned with a 3-Tesla magnetic resonance imaging scanner. The FCs of the BLA, the CMA, and the amygdala as a whole were examined using a seed-based approach, and then, the analysis of variance was used to compare the groups. RESULTS: We demonstrated that the BLA had a stronger connectivity with the prefrontal cortices (PFCs) and angular gyrus in the PTSD group than in the TEC group. Additionally, compared with the PTSD and the HC groups, the TEC group exhibited decreased and increased BLA FC with the ventromedial PFC and postcentral gyrus (PoCG), respectively. Furthermore, the PTSD group showed abnormal FC between the salience network and default-mode network, as well as the executive control network. Compared with the HC group, the TEC group and the PTSD group both showed decreased BLA FC with the superior temporal gyrus (STG). Finally, the FCs between the bilateral amygdala (as a whole) and the vmPFC, and between the BLA and the vmPFC have a negative correlation with the severity of PTSD. CONCLUSIONS: Decreased BLA-vmPFC FC and increased BLA-PoCG FC may reflect PTSD resilience factors. Trauma leads to decreased connectivity between the BLA and the STG, which could be further aggravated by PTSD.

14.
Cereb Cortex ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33152757

RESUMO

Literature studies have demonstrated the structural, connectional, and functional differences between cortical folding patterns in mammalian brains, such as convex and concave patterns. However, the molecular underpinning of such convex/concave differences remains largely unknown. Thanks to public access to a recently released set of marmoset whole-brain in situ hybridization data by RIKEN, Japan; this data's accessibility empowers us to improve our understanding of the organization, regulation, and function of genes and their relation to macroscale metrics of brains. In this work, magnetic resonance imaging and diffusion tensor imaging macroscale neuroimaging data in this dataset were used to delineate convex/concave patterns in marmoset and to examine their structural features. Machine learning and visualization tools were employed to investigate the possible transcriptome difference between cortical convex and concave patterns. Experimental results demonstrated that a collection of genes is differentially expressed in convex and concave patterns, and their expression profiles can robustly characterize and differentiate the two folding patterns. More importantly, neuroscientific interpretations of these differentially expressed genes, as well as axonal guidance pathway analysis and gene enrichment analysis, offer novel understanding of structural and functional differences between cortical folding patterns in different regions from a molecular perspective.

15.
Food Chem ; : 128455, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33129616

RESUMO

Mineral elements are important constituents in honey, which play vital roles in determining the quality and authenticity. The present work aims to systematically estimate the mineral profile of honeys, syrups, and adulterated honeys by syrup directly with chemometrics. Twelve mineral elements with higher contents were determined by ICP-OES in 67 honeys from 6 botanical origins, 17 syrups from 3 types, and 61 adulterations. Statistical analysis revealed honey was significantly different and higher than pale syrup in mineral profile except for barium. Five mono-floral models were established based on chemometrics analysis using the sPLS-DA method, and their discrimination accuracy were over 93% Although mineral contents in honeys from different botanical and geographical origins were quite different, the multi-floral model's classify accuracy was 87.7% as well as in blind test. The results revealed that mineral element chemometrics profiling can be a stable and robust tool to differentiate adulterated honey from pure honey.

16.
Virulence ; 11(1): 1569-1581, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33172355

RESUMO

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Área Sob a Curva , Betacoronavirus/genética , Biomarcadores , Sedimentação Sanguínea , Proteína C-Reativa/análise , China , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Laringe/virologia , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Valor Preditivo dos Testes , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Proteína Amiloide A Sérica/análise
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(11): 1044-1048, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33210600

RESUMO

The research and development of the coronavirus disease 2019 (COVID-19) vaccine is being carried out globally. Although vaccine research and development technology has made great progress, the possibility of obtaining a safe and effective vaccine that can control the global epidemic in a short period of time is still low due to the antibody-dependent enhancement effect (ADE) of the vaccine and the mutation of the virus. In the absence of specific treatment for COVID-19, finding other alternative protection schemes has become another treatment idea. Epidemiological studies have found that, in this COVID-19 epidemic, countries with long-term Bacillus Calmette-Guerin (BCG) vaccination policies have relatively less cases and lower mortality rates than countries without relevant policies. This phenomenon may be related to the "training immunity" effect of BCG. In order to further clarify the preventive and protective effects of BCG vaccine on SARS-CoV-2 infection, a number of clinical trials are underway.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , Ensaios Clínicos como Assunto , Humanos
18.
Nat Biomed Eng ; 4(11): 1063-1075, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33159193

RESUMO

The systemic biodistribution of endogenous extracellular vesicles is central to the maintenance of tissue homeostasis. Here, we show that angiogenesis and heart function in infarcted heart tissue can be ameliorated by the local accumulation of exosomes collected from circulation using magnetic nanoparticles. The nanoparticles consist of a Fe3O4 core and a silica shell that is decorated with poly (ethylene glycol) conjugated through hydrazone bonds to two types of antibody, which bind either to CD63 antigens on the surface of extracellular vesicles or to myosin-light-chain surface markers on injured cardiomyocytes. On application of a local magnetic field, accumulation of the nanoparticles and cleavage of the hydrazone bonds under the acidic pH of injured cardiac tissue lead to the local release of the captured exosomes. In rabbit and rat models of myocardial infarction, the magnetic-guided accumulation of captured CD63-expressing exosomes in infarcted tissue led to reductions in infarct size as well as improved left-ventricle ejection fraction and angiogenesis. The approach could be used to manipulate endogenous exosome biodistribution for the treatment of other diseases.

20.
Biochem Genet ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211221

RESUMO

Psoriasis is considered as a common chronic and relapsing inflammatory skin disease. MicroRNAs (miRNAs) were found to be related with psoriasis pathogenesis. Nevertheless, the function of miR-617 in psoriasis is still unclear. The miR-617 RNA level was detected using quantitative reverse transcription-PCR (qRT-PCR). Western blot analysis examined the protein level. Cell proliferation was analyzed via cell counting kit-8 (CCK-8) assay. Flow cytometry analysis detected cell cycle and apoptosis. The relationship between miR-617 and forkhead box protein O4 (FOXO4) was confirmed through dual luciferase assay. The miR-617 was up-regulated in psoriatic skin tissues and interleukin-22 (IL-22)-stimulated immortalized human keratinocyte HaCaT cells. Moreover, miR-617 mimics promoted proliferation, cell cycle, and suppressed apoptosis in IL-22-stimulated HaCaT cells. However, miR-617 inhibitor showed opposite effects. Additionally, FOXO4 was a target of miR-617. FOXO4 was down-regulated in psoriatic skin tissues and IL-22-stimulated HaCaT cells. Negative correlation between miR-617 and FOXO4 was identified. FOXO4 overexpression alleviated the effects of miR-617 proliferation, cell cycle and apoptosis in the IL-22-stimulated HaCaT cells. These results demonstrate that miR-617 increases the growth of IL-22-stimulated keratinocytes through targeting FOXO4, which provides a new therapeutic target for psoriasis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA