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1.
Curr Med Sci ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652629

RESUMO

The purpose of this review is to provide a comprehensive update on recent advances in heart transplantation in China. Despite advances in pharmacologic and device treatment of chronic heart failure, long-term morbidity and mortality remain high, and many patients progress to endstage heart failure. Heart transplantation has become standard treatment for selected patients with end-stage heart failure, though challenges still exist. However, multiple advances over the past few years will improve the survival and quality-of-life of heart transplant recipients. This article elaborates on the specific characteristics of heart transplantation in China, the current issues, development trends, and related experiences with heart transplantation in Wuhan Union Hospital.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34506290

RESUMO

Phylogenetic trees are unable to represent the evolutionary process for a collection of species if reticulation events happened, and a generalized model named phylogenetic network was introduced consequently. However, the representation of the evolutionary process for one gene is actually a phylogenetic tree that is '`contained'' in the phylogenetic network for the considered species containing the gene. Thus a fundamental computational problem named Tree Containment problem arises, which asks whether a phylogenetic tree is contained in a phylogenetic network. The previous research on the problem mainly focused on its rooted version of which the considered tree and network are rooted, and several algorithms were proposed when the considered network is binary or structure-restricted. There is almost no algorithm for its unrooted version except the recent fixed-parameter algorithm with runtime O(4kn2), where k and n are the reticulation number and size of the considered unrooted binary phylogenetic network N, respectively. As the runtime is a little expensive when considering big values of k, we aim to improve it and successfully propose a fixed-parameter algorithm with runtime O(2.594kn2) in the paper. Additionally, we experimentally show its effectiveness on biological data and simulated data.

4.
Bioengineered ; 12(1): 6332-6342, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34488537

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that are closely associated with cancer progression and drug resistance, however, up until now, the involvement of miR-556-5p in regulating cisplatin-sensitivity in non-small cell lung cancer (NSCLC) has not been studied. In the present study, we found that miR-556-5p was significantly upregulated in the cisplatin-resistant NSCLC (CR-NSCLC) patients' tissues and cells, instead of the corresponding cisplatin-sensitive NSCLC (CS-NSCLC) tissues and cells. Further experiments validated that knock-down of miR-556-5p suppressed cell viability and tumorigenesis, and induced cell apoptosis in the cisplatin-treated CR-NSCLC cells, and conversely, upregulation of miR-556-5p increased cisplatin-resistance in CS-NSCLC cells. Interestingly, miR-556-5p ablation triggered pyroptotic cell death in cisplatin-treated CR-NSCLC cells via upregulating NLRP3, and the promoting effects of miR-556-5p silence on cisplatin-sensitivity in CR-NSCLC cells were abrogated by both cell pyroptosis inhibitor NSA and NLRP3 downregulation. Taken together, this study firstly evidenced that induction of NLRP3-mediated cell pyroptosis by miR-556-5p downregulation was effective to increase cisplatin-sensitivity in NSCLC, which provided new therapy strategies to overcome chemo-resistance for NSCLC patients in clinic.

5.
J Control Release ; 338: 705-718, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481023

RESUMO

Albumin nanoparticles represent an approved anti-tumor drug delivery system. However, there is only one albumin nanoparticle product (paclitaxel-albumin nanoparticle) on the market. The application of albumin carriers is limited by the lack of universal preparation technology and insufficient targeting effect. Herein, we developed multifunctional albumin sub-microspheres prepared by coaxial-electrospray technology to co-delivery bufalin and nintedanib for tumor-targeted combination therapy. The biguanide and ursodeoxycholic acid dual-modified multifunctional albumin was synthesized to enhance the anti-tumor effect and tumor target efficiency. Coaxial-electrospray technology was utilized in preparing albumin sub-microspheres with a core-shell structure that enables payload efficiency and stability. More importantly, the in vitro and in vivo experiments demonstrated that the multifunctional albumin sub-microspheres possessed superior tumor target efficiency. Furthermore, nintedanib and bufalin combined therapy relieved the tumor microenvironment and exerted a synergistic therapeutic effect. Therefore, this work provides a novel method for fabricating an albumin-based drug delivery system and a potential efficient combination therapeutic strategy for tumor treatment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34574444

RESUMO

Resource and environmental issues related to urban building systems have recently become a hot research topic in the field of urban environmental management research. Taking Jinan city as an example, this paper establishes a system dynamic model for an urban residential building stock system. The simulated results show that the urban residential building stock will be 1.99 × 108 m2 in 2050; and the annual total demolition buildings will be at 3.36 × 106 m2 in 2082. Policy measures were developed based on four important action fields such as per capita floor area (PCFA), the building structure proportion of new construction, lifetime of the residential building, and the recycling of the C&D waste. Among these approaches, the set of policy measures focusing on the recycling of C&D waste appears to be more effective in reducing environmental and resource impacts than the other three fields. It is also found that the recycling of brick and concrete waste plays a considerable role in reducing environment and resource impacts due to the development of urban residential building stock with the lapse of time.

7.
Fitoterapia ; 154: 105027, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34492330

RESUMO

Two novel kojic acid derivatives, kojicones A and B (1 and 2), along with the precursors kojic acid (3) and (2R,4R)-4-hydroxy-5-methoxy-2,4-dimethyl-2- [(2R)-2-methylbutyryloxy]-5-cyclohexen-1,3-dione (4), were isolated from a fungal strain Aspergillus versicolor. Their structures and absolute configurations were accurately confirmed by HRESIMS data, NMR analysis, and electronic circular dichroism (ECD) calculations. Kojicones A and B were the first examples of kojic acid adducts with cyclohexen-1,3-dione possessing unprecedented tricycle skeletons. Compounds 1-3 were found to have inhibition on the NO production of murine RAW 264.7 cells. They can also reduce the mRNA expression of four cytokines (IL-6, IL-1ß, TNF-α, and iNOS) and promote the expression of IL-4 at 20 µM. Moreover, kojic acid (3) could treat the DSS (dextran sulfate sodium)-induced colitis on mice with the effectiveness similar to that of the positive control. The results suggested that kojic acid and its derivatives could be a promising anti-inflammatory source for the medicinal and cosmetic industry.


Assuntos
Anti-Inflamatórios/farmacologia , Aspergillus/química , Colite/tratamento farmacológico , Pironas/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , China , Colite/induzido quimicamente , Citocinas/metabolismo , Heterópteros/microbiologia , Camundongos , Estrutura Molecular , Óxido Nítrico , Pironas/isolamento & purificação , Células RAW 264.7
8.
Artigo em Inglês | MEDLINE | ID: mdl-34453221

RESUMO

PURPOSE: The aim of this retrospective study was to compare the clinical outcomes of pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) versus lenvatinib-TACE sequential therapy in selected populations of Chinese patients with initially unresectable hepatocellular carcinoma (uHCC) harbouring programmed cell death ligand-1 (PD-L1) expression. METHODS: Consecutive patients with initial PD-L1-positive uHCC who received pembrolizumab-lenvatinib-TACE or lenvatinib-TACE sequential therapy were retrospectively identified from three medical institutions during 2016-2020. The primary endpoints included the rate of conversion therapy, defined as converting initially uHCC to hepatectomy, overall survival (OS), and progression-free survival (PFS); secondary endpoint was the frequency of key adverse events (AEs). RESULTS: In total, 220 consecutively recruited patients were retrospectively reviewed, 78 of whom were ineligible according to the current criteria, leaving 142 patients [pembrolizumab-lenvatinib-TACE: n = 70, median age 58 years (range 36-69) and lenvatinib-TACE: n = 72, 57 years (35-68)] who were eligible for the study. The median duration of follow-up was 27 months [95% confidence interval (CI), 26.3-28.7 months]. At the last follow-up, the rate of conversion therapy was 25.7% in the pembrolizumab-lenvatinib-TACE group and 11.1% in the lenvatinib-TACE group (p = 0.025). The median OS was 18.1 months (95% CI 16.5-20.7) in the pembrolizumab-lenvatinib-TACE group versus 14.1 months (95% CI 12.2-16.9) in the lenvatinib-TACE group [hazard ratio (HR) 0.56, 95% CI 0.38-0.83; p = 0.004]. A distinct difference in the median PFS interval between the groups was detected [9.2 months (95% CI 7.1-10.4) in the pembrolizumab-lenvatinib-TACE group vs. 5.5 months (95% CI 3.9-6.6) in the lenvatinib-TACE group (HR 0.60; 95% CI 0.39-0.91; p = 0.006)]. The rates of the key AEs assessed, which were hypertension, nausea, and rash, were higher in the pembrolizumab-lenvatinib-TACE group than in the lenvatinib-TACE group (all p < 0.05). CONCLUSION: Among the selected populations of patients with initial PD-L1-positive uHCC, pembrolizumab-lenvatinib-TACE sequential therapy may have promising antitumour activity, with an acceptable conversion rate and a well-characterized safety profile.

9.
Neuroradiology ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34368897

RESUMO

PURPOSE: EphA2 is a key factor underlying invasive propensity of gliomas, and is associated with poor prognosis of tumors. We aimed to develop a radiomics-based imaging index for predicting EphA2 expression in diffuse gliomas, and further estimating its value for grading of tumors. METHODS: A total of 182 patients with diffuse gliomas were included. All subjects underwent pre-operative MRI and post-operative pathological diagnosis. EphA2 expression of tumors was scored on pathological sections with immunohistochemical staining using monoclonal EphA2 antibody. MRI radiomics features were extracted from three-dimensional contrast-enhanced T1-weighted imaging and diffusion kurtosis imaging. Predictive models were constructed using machine learning-based radiomics features selection and three classifiers for predicting EphA2 expression and tumor grade. Features of best EphA2 expression model were subsequently used to construct another model of tumor grading. For each model, 146 cases (80%) were randomly picked as training and the rest 36 (20%) were testing cohorts. EphA2 expression was further correlated to the radiomics features in both grade models using Spearman's correlation. RESULTS: Logistic regression model presented highest performance for predicting EphA2 expression (AUC: 0.836/0.724 in training/validation set). Tumor gradings model guided by features from EphA2 expression model demonstrated comparable performance (AUC: 0.930/0.983) to that constructed directly using imaging radiomics features (AUC: 0.960/0.977). Two radiomics features which included in both LR-grade models showed strong correlation (P < 0.05) with EphA2 expression. CONCLUSION: The expression of EphA2 in gliomas could be predicted by radiomics features extracted from diffusion kurtosis MRI, which could also be used to assist tumor grading.

10.
Comput Math Methods Med ; 2021: 6438861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422095

RESUMO

Background: It is often tricky to differentiate cystic pituitary adenoma from Rathke cleft cyst with visual inspection because of similar MRI presentations between them. We aimed to design an MR-based radiomics model for improving differential diagnosis between them. Methods: Conventional diagnostic MRI data (T1-,T2-, and postcontrast T1-weighted MR images) were obtained from 215 pathologically confirmed patients (105 cases with cystic pituitary adenoma and the other 110 cases with Rathke cleft cyst) and were divided into training (n = 172) and test sets (n = 43). MRI radiomics features were extracted from the imaging data, and semantic imaging features (n = 15) were visually estimated by two radiologists. Four classifiers were used to construct radiomics models through 5-fold crossvalidation after feature selection with least absolute shrinkage and selection operator. An integrated model by combining radiomics and semantic features was further constructed. The diagnostic performance was validated in the test set. Receiver operating characteristic curve was used to evaluate and compare the performance of the models at the background of diagnostic performance by radiologist. Results: In test set, the combined radiomics and semantic model using ANN classifier obtained the best classification performance with an AUC of 0.848 (95% CI: 0.750-0.946), accuracy of 76.7% (95% CI: 64.1-89.4%), sensitivity of 73.9% (95% CI: 56.0-91.9%), and specificity of 80.0% (95% CI: 62.5-97.5%) and performed better than multiparametric model (AUC = 0.792, 95% CI: 0.674-0.910) or semantic model (AUC = 0.823, 95% CI: 0.705-0.941). The two radiologists had an accuracy of 69.8% and 74.4%, respectively, sensitivity of 69.6% and 73.9%, and specificity of 70.0% and 75.0%. Conclusions: The MR-based radiomics model had technical feasibility and good diagnostic performance in the differential diagnosis between cystic pituitary adenoma and Rathke cleft cyst.

11.
Analyst ; 146(17): 5362-5368, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34337622

RESUMO

To prevent the transmission of brucellosis, rapid vertical flow technology (RVFT) was developed to detect brucellosis antibodies. To improve the sensitivity of the technique, lipopolysaccharides (LPS) were purified and used to detect brucellosis antibodies. To improve the sensitivity of serum antibody detection, a single multifunctional buffer was established in whole blood and other biological samples, and the advantages of the lateral flow immunoassay were retained. Flower-like gold nanoparticles were applied to RVFT for the first time. In this study, silver ions were catalyzed by flower-like gold nanoparticles into metal silver deposited on the surface of gold nanoparticles for the first time, which not only increased the particle size of gold nanoparticles, but also showed a more distinguishable black color on the test zone, further improving the sensitivity of RVFT. Standard Brucella-positive serum (containing Brucella antibody at 4000 IU mL-1) could be detected in this system even for a dilution factor of 2 × 10-3. The detection limit was 2 IU mL-1. RVFT can effectively avoid the false negative phenomenon in lateral flow immunoassay. RVFT is simple to operate, with a short reaction time, 2-3 minutes visible to the naked eye, without any equipment. Because it is very important to control the brucellosis epidemic, this approach has great application prospects in basic medical units and for veterinarians.


Assuntos
Brucella , Nanopartículas Metálicas , Ouro , Imunoensaio , Sensibilidade e Especificidade , Prata , Tecnologia
12.
Oxid Med Cell Longev ; 2021: 4158495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426759

RESUMO

Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.

13.
Eur J Radiol ; 142: 109890, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34375811

RESUMO

BACKGROUND AND AIM: Hepatic arterial infusion chemotherapy (HAIC) has shown encouraging efficacy in the treatment of hepatocellular carcinoma (HCC). This study aims to establish and validate a novel nomogram to predict individualized survival outcomes for patients with unresectable HCC after HAIC. METHODS: Between January 2016 and December 2018, 463 patients diagnosed with HCC who initially received HAIC were included in this study (training cohort: n = 308; validation cohort: n = 153). The prognostic nomogram was constructed based on the training cohort using the independent predictors assessed by the multivariate Cox proportional hazards model. The predictive accuracy and discriminative ability of the model were evaluated by the concordance index (C-index), calibration curve and area under the time-dependent receiver operating characteristic (tdAUC) curve. RESULTS: After a median follow-up of 35.4 months, 358 patients had died. Six factors, including C-reactive protein, albumin-bilirubin grade, alpha fetoprotein, extrahepatic metastasis, portal vein invasion and tumor size, were selected to establish the nomogram. In the training cohort, the C-index of the nomogram was 0.710, which was significantly better than that of six conventional staging systems (P < 0.001), and the nomogram had a higher tdAUC over time. The calibration curve showed good agreement between the predicted probability and actual outcome. According to specified values, the nomogram stratified patients into three or four risk groups (P < 0.001). Similar findings could be observed in the validation cohort. CONCLUSION: The nomogram in this study accurately predicted the OS of patients with unresectable HCC after HAIC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Nomogramas , Prognóstico , Modelos de Riscos Proporcionais
14.
IEEE Trans Med Imaging ; PP2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383647

RESUMO

Early and accurate severity assessment of Coronavirus disease 2019 (COVID-19) based on computed tomography (CT) images offers a great help to the estimation of intensive care unit event and the clinical decision of treatment planning. To augment the labeled data and improve the generalization ability of the classification model, it is necessary to aggregate data from multiple sites. This task faces several challenges including class imbalance between mild and severe infections, domain distribution discrepancy between sites, and presence of heterogeneous features. In this paper, we propose a novel domain adaptation (DA) method with two components to address these problems. The first component is a stochastic class-balanced boosting sampling strategy that overcomes the imbalanced learning problem and improves the classification performance on poorly-predicted classes. The second component is a representation learning that guarantees three properties: 1) domain-transferability by prototype triplet loss, 2) discriminant by conditional maximum mean discrepancy loss, and 3) completeness by multi-view reconstruction loss. Particularly, we propose a domain translator and align the heterogeneous data to the estimated class prototypes (i.e., class centers) in a hyper-sphere manifold. Experiments on cross-site severity assessment of COVID-19 from CT images show that the proposed method can effectively tackle the imbalanced learning problem and outperform recent DA approaches.

15.
Medicine (Baltimore) ; 100(29): e26587, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398013

RESUMO

ABSTRACT: Poor availability and a lack of affordability of bypassing agents (recombinant activated factor VII and activated prothrombin complex concentrate) in west China prompted us to investigate an alternative cost-effective combination therapy. We aimed to explore the feasibility of therapeutic plasma exchange (TPE)-based combination therapy in the treatment of acquired hemophilia A (AHA).We retrospectively investigated the clinical features of AHA in 6 patients who were treated with a combination of TPE, corticosteroids, and rituximab in our department for 9 years between January, 2011 and December, 2019.We examined 1 male and 5 female patients. The median age at diagnosis of AHA was 51 years (18-66 years). In all patients, FVIII activity levels were low (median: 1.5%; 1-3%), FVIII inhibitor titers were high (median: 24.5 BU/mL; 13.2-48.6 BU/mL), and activated partial thromboplastin time was markedly prolonged (median: 99.4 s; 60.9-110.1 s). They underwent 2 to 8 cycles of plasma exchange and were given varying combinations of dexamethasone, methylprednisolone, prednisone, and rituximab. After TPE bleeding gradually stopped, and activated partial thromboplastin time decreased. After 3 months of treatment, FVIII inhibitors completely disappeared.TPE when combined with corticosteroids and rituximab, as adjunctive immunosuppressive agents, may be an effective and reliable treatment for AHA. When there is no alternative, intensive first-line treatment including TPE may be lifesaving.


Assuntos
Hemofilia A/terapia , Troca Plasmática/normas , Adulto , China , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Troca Plasmática/métodos , Troca Plasmática/estatística & dados numéricos , Estudos Retrospectivos
17.
Pharmacol Res ; 172: 105846, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34438063

RESUMO

Early onset and progression of liver diseases can be driven by aberrant transcriptional regulation. Different transcriptional regulation processes, such as RNA/DNA methylation, histone modification, and ncRNA-mediated targeting, can regulate biological processes in healthy cells, as well also under various pathological conditions, especially liver disease. Numerous studies over the past decades have demonstrated that liver disease has a strong epigenetic component. Therefore, the epigenetic basis of liver disease has challenged our knowledge of epigenetics, and epigenetics field has undergone an important transformation: from a biological phenomenon to an emerging focus of disease research. Furthermore, inhibitors of different epigenetic regulators, such as m6A-related factors, are being explored as potential candidates for preventing and treating liver diseases. In the present review, we summarize and discuss the current knowledge of five distinct but interconnected and interdependent epigenetic processes in the context of hepatic diseases: RNA methylation, DNA methylation, histone methylation, miRNAs, and lncRNAs. Finally, we discuss the potential therapeutic implications and future challenges and ongoing research in the field. Our review also provides a perspective for identifying therapeutic targets and new hepatic biomarkers of liver disease, bringing precision research and disease therapy to the modern era of epigenetics.

18.
Chemistry ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34423878

RESUMO

The shift from fossil carbon sources to renewable ones is vital for developing sustainable chemical processes to produce valuable chemicals. In this work, value-added formamides were synthesized in good yields by the reaction of amines with C2 and C3 biomass-based platform molecules such as glycolic acid, 1,3-dihydroxyacetone and glyceraldehyde. These feedstocks were selectively converted by catalysts based on Cu-containing zeolite 5A through the in situ formation of carbonyl-containing intermediates. To the best of our knowledge, this is the first example in which all the carbon atoms in biomass-based feedstocks could be amidated to produce formamide. Combined catalyst characterization results revealed preferably single CuII sites on the surface of Cu/5A, some of which form small clusters, but without direct linking via oxygen bridges. By combining the results of electron paramagnetic resonance (EPR) spin-trapping, operando attenuated total reflection (ATR) IR spectroscopy and control experiments, it was found that the formation of formamides might involve a HCOOH-like intermediate and . NHPh radicals, in which the selective formation of . OOH radicals might play a key role.

19.
Environ Toxicol Pharmacol ; 87: 103725, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34416396

RESUMO

The objective of this study was to evaluate the toxic effects of Cr6+ on bioaccumulation, digestion, immunity, oxidative stress, apoptosis and inflammation-related genes in Channa asiatica. The fish was exposed to waterborne Cr6+ concentrations (0, 0.5, 1.0 and 2.0 mg/L) for 28 and 56 days. Our results demonstrated that the accumulation of Cr6+ in tissues increased in a concentration-dependent manner, and the content in tissue was liver > gill > gut > muscle. Meanwhile, Cr6+ exposure led to a remarkable suppression of digestion, immunity and antioxidant capacity in C. asiatica. Inversely, MDA and PC content were positively correlated with Cr6+ exposure concentration. Furthermore, the expression of genes went up with the increase of waterborne Cr6+ concentration. Among them, HSP90, NF-κB and TNF-α have a sharp increase. These results elucidate that waterborne Cr6+ exposure may induce bioaccumulation, inhibit digestion and immunity, promote oxidative stress and up-regulate the expression of apoptosis and inflammation-related genes in C. asiatica.


Assuntos
Cromo/toxicidade , Poluentes Químicos da Água/toxicidade , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Bioacumulação , Citocinas/sangue , Citocinas/genética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Peixes/genética , Peixes/imunologia , Peixes/metabolismo , Expressão Gênica/efeitos dos fármacos , Brânquias/metabolismo , Imunoglobulina M/sangue , Mucosa Intestinal/metabolismo , L-Lactato Desidrogenase/sangue , Fígado/metabolismo , Muramidase/sangue , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estômago/efeitos dos fármacos , Estômago/enzimologia
20.
Front Immunol ; 12: 676337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421892

RESUMO

Dendritic cells (DCs) are key mediators of transplant rejection. Numerous factors have been identified that regulate transplant immunopathology by modulating the function of DCs. Among these, microRNAs (miRNAs), small non-coding RNA molecules, have received much attention. The miRNA miR-223 is very highly expressed and tightly regulated in hematopoietic cells. It plays an important role in modulating the immune response by regulating neutrophils and macrophages, and its dysregulation contributes to multiple types of immune diseases. However, the role of miR-223 in immune rejection is unclear. Here, we observed expression of miR-223 in patients and mice who had undergone heart transplantation and found that it increased in the serum of both, and also in DCs from the spleens of recipient mice, although it was unchanged in splenic T cells. We also found that miR-223 expression decreased in lipopolysaccharide-stimulated DCs. Increasing the level of miR-223 in DCs promoted polarization of DCs toward a tolerogenic phenotype, which indicates that miR-223 can attenuate activation and maturation of DCs. MiR-223 effectively induced regulatory T cells (Tregs) by inhibiting the function of antigen-presenting DCs. In addition, we identified Irak1 as a miR-223 target gene and an essential regulator of DC maturation. In mouse allogeneic heterotopic heart transplantation models, grafts survived longer and suffered less immune cell infiltration in mice with miR-223-overexpressing immature (im)DCs. In the miR-223-overexpressing imDC recipients, T cells from spleen differentiated into Tregs, and the level of IL-10 in heart grafts was markedly higher than that in the control group. In conclusion, miR-223 regulates the function of DCs via Irak1, differentiation of T cells into Tregs, and secretion of IL-10, thereby suppressing allogeneic heart graft rejection.

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