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1.
J Cell Physiol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951022

RESUMO

Traumatic osteonecrosis of femoral head (TONFH) is a common orthopedic disease caused by physical injury in hip. However, the unclear pathogenesis mechanism of TONFH and lacking of simple noninvasive early diagnosis method cause the necessity of hip replacement for most patients with TONFH. In this study, we aimed to identify circulating microRNAs (miRNAs) by integrated bioinformatics analyses as potential biomarker of TONFH. mRNA expression profiles were downloaded from the Gene Expression Omnibus database. Then we combined two miRNA screen methods: Weighted gene co-expression network analysis and fold change based differentially expressed miRNAs analysis. As a result, we identified 14 key miRNAs as potential biomarkers for TONFH. Besides, 302 target genes of these miRNAs were obtained and the miRNA-mRNA interaction network was constructed. Furthermore, the results of Kyoto Encyclopedia of Gene and Genome pathway analysis, Gene Ontology function analysis, protein-protein interaction (PPI) network analysis and PPI network module analysis showed close correlation between these 14 key miRNAs and TONFH. Then we established receiver operating characteristic curves and identified 6-miRNA signature with highly diagnosis value including miR-93-5p (area under the curve [AUC] = 0.93), miR-1324 (AUC = 0.92), miR-4666a-3p (AUC = 0.92), miR-5011-3p (AUC = 0.92), and miR-320a (AUC = 0.89), miR-185-5p (AUC = 0.89). Finally, the results of quantitative real-time polymerase chain reaction confirmed the significantly higher expression of miR-93-5p and miR-320a in the serum of patients with ONFH. These circulating miRNAs could serve as candidate early diagnosis markers and potential treatment targets of TONFH.

2.
Mod Rheumatol ; 30(2): 269-275, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30880555

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic inflammatory arthropathy characterized by excessive synovial hyperplasia and progressive joint destruction. Pro-inflammatory cytokines play major roles in the regulation of synovial inflammation. The contribution of interleukin-34 (IL-34) in RA pathogenesis has been strongly suggested in clinical studies.Aim: To investigate the correlation between plasma IL-34 and disease parameters in RA patients including disease activity score (DAS28), receptor activator of NF-[Formula: see text]B ligand (RANKL) concentration, synovitis and bone erosions under ultrasound.Methods: 60 RA patients and 20 healthy controls were from Huashan Hospital, patient's medical history, physical examination, laboratory examination and ultrasound data were collected and recorded, respectively. Blood samples of all participants were collected and the levels of IL-34 and RANKL were tested. The levels of IL-34 and RANKL in RA patients were compared with those of healthy controls. Furthermore, the correlation between IL-34, RANKL and disease parameters in RA patients was analyzed.Results: Both plasma levels of IL-34 and RANKL in RA patients were significantly higher than the healthy controls (p < .05). IL-34 was significantly related to disease activity scores (r = 0.43, p = .001); RANKL (r = 0.46, p = .0003) and bone erosions by ultrasound (r = 0.38, p = .002).Conclusions: The plasma IL-34 concentration in RA was significantly higher than the healthy controls and was significantly correlated with RANKL, as well as disease activity score and bone erosions by ultrasound. The IL-34 may be a new biological marker for disease activity and predictor for bone erosions in RA. Targeting IL-34 holds promise in the management of RA and, potentially, other osteoclasts driven diseases (erosive osteoarthritis and psoriatic arthritis for example).

3.
Antiviral Res ; 173: 104652, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31751590

RESUMO

Both classical swine fever (CSF) and pseudorabies are highly contagious, economically significant diseases of swine in China. Although vaccination with the C-strain against classical swine fever virus (CSFV) is widely carried out and severe outbreaks of CSF seldom occur in China, CSF is sporadic in many pig herds and novel sub-subgenotypes of CSFV endlessly emerge. Thus, new measures are needed to eradicate CSFV from Chinese farms. The emergence of a pseudorabies virus (PRV) variant also posed a new challenge for the control of swine pseudorabies. Here, the recombinant PRV strain JS-2012-ΔgE/gI-E2 expressing E2 protein of CSFV was developed by inserting the E2 expression cassette into the intergenic region between the gG and gD genes of the gE/gI-deletion PRV variant strain JS-2012-ΔgE/gI. The recombinant virus was stable when passaged in vitro. A single vaccination of JS-2012-ΔgE/gI-E2 via intramuscular injection fully protected against lethal challenges of PRV and CSFV. Vaccination of piglets with the recombinant JS-2012-ΔgE/gI-E2 in the presence of high levels of maternally derived antibodies (Abs) to PRV can provide partial protection against lethal challenge of CSFV. Vaccination of the recombinant PRV JS-2012-ΔgE/gI-E2 strain did not induce the production of Abs to the gE protein of PRV or to the CSFV proteins other than E2. Thus, JS-2012-ΔgE/gI-E2 appears to be a promising recombinant marker vaccine candidate against PRV and CSFV for the control and eradication of the PRV variant and CSFV.

4.
Autophagy ; : 1-16, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31868081

RESUMO

Interferon-induced BST2 (bone marrow stromal cell antigen 2) inhibits viral replication by tethering enveloped virions to the cell surface to restrict viral release and by inducing the NFKB-dependent antiviral immune response. However, the mechanism by which BST2 uses the selective autophagy pathway to inhibit viral replication is poorly understood. In this study, we showed that BST2 expression was significantly increased during porcine epidemic diarrhea virus (PEDV) infection of Vero cells by IRF1 targeting its promoter. We also showed that BST2 suppressed PEDV replication by binding and degrading the PEDV-encoded nucleocapsid (N) protein. The downregulation of N protein was blocked by macroautophagy/autophagy inhibitors but not a proteasome inhibitor, implying that the N protein was degraded via the selective autophagy pathway. Both the BST2 and N protein interacted with the E3 ubiquitin ligase MARCHF8/MARCH8 and the cargo receptor CALCOCO2/NDP52, and the ubiquitination of N protein was necessary for the degradation of N mediated by the BST2-MARCHF8 axis. The knockdown of MARCHF8 or ATG5 with small interfering RNAs blocked the selective autophagy pathway, rescued the protein abundance of PEDV N in 293T cells, and prevented the inhibition of PEDV replication by BST2 in Vero cells. Together, our data demonstrate the novel mechanism of BST2-mediated virus restriction, in which BST2 recruits MARCHF8 to catalyze the ubiquitination of the PEDV N protein. The ubiquitinated N protein is then recognized by CALCOCO2/NDP52, which delivers it to autolysosome for degradation through the selective autophagy pathway.Abbreviations: 3MA: 3-methyladenine; ATG: autophagy-related; Baf A1: bafilomycin A1; BST2: bone marrow stromal cell antigen 2; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CC: coiled-coil; ChIP: chromatin immunoprecipitation; Co-IP: co-immunoprecipitation; CQ: chloroquine; CT: cytoplasmic tail; DAPI: 4',6-diamidino-2-phenylindole; GPI: glycosyl-phosphatidylinositol; hpi: hours post infection; IRF1: interferon regulatory factor 1; ISG: IFN-stimulated gene; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF8/MARCH8: membrane-associated ring-CH-type finger 8; MOI: multiplicity of infection; N protein: nucleocapsid protein; PED: porcine epidemic diarrhea; PEDV: porcine epidemic diarrhea virus; RT: room temperature; siRNA: small interfering RNA; STAT: signal transducer and activator of transcription; TCID50: 50% tissue culture infectious doses; TM: transmembrane.

5.
J Cell Biochem ; 120(12): 19891-19901, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31338874

RESUMO

By differentiating into and the balance being regulated between M1 (pro-inflammatory) and M2 (anti-inflammatory) heterogeneous populations, macrophages play critical roles during the host immune response in various physiological contexts in both health and diseases. Besides regulating innate and adaptive immune capacity, macrophages are also decisively involved in tissue homeostasis. However, how resident macrophages are regulated after tissue damages is still far from elucidation. In the present study, we found that adipose-derived stem cells (ADSCs) apparently promote bone defect rehabilitation in vivo via skewing differentiation of bone marrow-derived macrophage (BMDMs) towards anti-inflammatory M2 macrophages. In vitro data demonstrated that although ADSCs have the potential to differentiate to osteoblasts and adipose cells by using standard tissue culture-differentiating conditions, these mesenchymal progenitors are mainly regulated to differentiate into osteoblasts with overexpressed runt-related transcription factor 2, osteoprotegerin, osterix, and downregulated receptor activator of nuclear factor κB ligand in the presence of BMDMs-conditioned medium. Whereas BMDMs are polarized toward M2 macrophages with higher levels of arginase 1 and mannose receptor, but lower levels of inducible nitric oxide synthase and tumor necrosis factor-α when cocultured with ADSCs. In short, all these findings collectively demonstrated that ADSCs and resident host cells can synergistically contribute to the bony repair through mutual regulation of their differentiation and cytokine secretion.

6.
Dev Comp Immunol ; 98: 157-165, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31028761

RESUMO

Most of the bivalve C1q domain containing proteins (C1qDCs) are either only composed of the globular head domain, or contain an N-terminal coiled-coil domain, presumed to cover a role in oligomerization. On the other hand, collagen regions, widespread in vertebrate C1qDCs, are very uncommon in bivalves. In the present study, a C1qDC with a collagen-like domain (designated CgC1qDC-6) was identified from the Pacific oyster Crassostrea gigas and its possible involvement in immune responses was also characterized. The coding sequence of CgC1qDC-6 was of 756 bp, encoding a peptide of 251 amino acids with an N-terminal signal peptide, a central collagen-like domain, and a C-terminal ghC1q domain. CgC1qDC-6 was clustered with the C1qDCs from several mollusks in the phylogenetic tree. CgC1qDC-6 was detected at both mRNA and protein levels in all tested tissues including hepatopancreas, gonad, gill, mantle, adductor muscle, and hemocytes. The recombinant CgC1qDC-6 protein (rCgC1qDC-6) exhibited binding activity to various pathogen-associated molecular patterns (PAMPs) including LPS, PGN, mannose and Poly I:C, and microorganisms including Gram-negative bacteria (Escherichia coli and Vibrio splendidus), Gram-positive bacteria (Micrococcus luteus and Staphylococcus aureus), and fungus (Pichia pastoris). The phagocytic rates of oyster hemocytes towards V. splendidus pre-incubation with rCgC1qDC-6 were significantly enhanced (p < 0.05). In the chemotaxis assay, rCgC1qDC-6 could mediate the migration of oyster hemocytes in a dose-dependent manner, which exhibited a positive chemotactic effect at low concentration (<10 nM). These results collectively indicated that CgC1qDC-6 could serve as a pattern recognition receptor and mediate the hemocyte phagocytosis and migration to eliminate the invading pathogens.


Assuntos
Movimento Celular/genética , Complemento C1q/genética , Crassostrea/genética , Hemócitos/metabolismo , Proteínas Opsonizantes/genética , Fagocitose/genética , Sequência de Aminoácidos , Animais , Bactérias/imunologia , Bactérias/metabolismo , Sequência de Bases , Movimento Celular/imunologia , Complemento C1q/imunologia , Complemento C1q/metabolismo , Crassostrea/imunologia , Crassostrea/metabolismo , Hemócitos/citologia , Hemócitos/imunologia , Proteínas Opsonizantes/imunologia , Proteínas Opsonizantes/metabolismo , Padrões Moleculares Associados a Patógenos/metabolismo , Fagocitose/imunologia , Receptores de Reconhecimento de Padrão/genética , Receptores de Reconhecimento de Padrão/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Homologia de Sequência de Aminoácidos , Vibrio/imunologia , Vibrio/metabolismo , Vibrio/fisiologia
7.
Fish Shellfish Immunol ; 89: 207-216, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30936045

RESUMO

Beclin-1, the mammalian ortholog of yeast Atg6, plays essential roles in the regulation of various processes, including autophagy, apoptosis, embryonic development and immune responses in vertebrates. However, the information about Beclin-1 in invertebrates especially in crustaceans is still very limited. In the present study, a novel Beclin-1 (designated as EsBeclin-1) was identified from Chinese mitten crab Eriocheir sinensis. The open reading frame of EsBeclin-1 cDNA was of 1,275 bp, encoding a typical APG6 domain. The deduced amino acid sequence of EsBeclin-1 shared high similarity ranging from 42.9% to 63.6% with the previously identified Beclins. In the phylogenetic tree, EsBeclin-1 was firstly clustered with Drosophila melanogaster Atg6 and then assigned into the branch of invertebrate Beclin-1. The mRNA transcripts of EsBeclin-1 were highly expressed in hepatopancreas, hemocytes and gill. After lipopolysaccharide (LPS) and Aeromonas hydrophila stimulations, the relative mRNA expression of EsBeclin-1 in hemocytes was significantly increased from 3 to 24 h with the peak level of 4.70-fold (p < 0.01) and 2.91-fold (p < 0.01) at 6 h, respectively. EsBeclin-1 protein was diffusely distributed in the cytoplasm of crab hemocytes under normal conditions, whereas it displayed predominantly punctuate distribution after LPS stimulation. After EsBeclin-1 was interfered with specific EsBeclin-1-dsRNA, the mRNA transcripts of some antimicrobial peptides, including EsALF2, EsLYZ, EsCrus and EsCrus2 in crab hemocytes were significantly decreased at 6 h post LPS stimulation. These results implicated that EsBeclin-1 played a role in regulating the antimicrobial peptides expressions in the immune responses of E. sinensis.


Assuntos
Proteína Beclina-1/genética , Proteína Beclina-1/imunologia , Braquiúros/genética , Braquiúros/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Proteína Beclina-1/química , Perfilação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Filogenia , Alinhamento de Sequência
8.
Arch Virol ; 164(2): 653-656, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569277

RESUMO

The complete genome of a bear picornavirus 1 (BePV-1) in the viscera of an Asian black bear (Ursus thibetanus) from China was characterized using viral metagenomics and RT-PCR/Sanger sequencing. The genome of BePV1 is 6703 nt long, contains a type-IV IRES 5'UTR with the '8-like' motif, encodes a 2053-aa-long polyprotein showing a 3-4-4 organization pattern and two 2A genes. BePV-1 showed the highest overall genome nucleotide sequence identity of 71.7% to a picornavirus genome from an Arctic ringed seal (Phoca hispida) from Canada, classified as a member of the species Aquamavirus A, currently the only one in the genus Aquamavirus. Phylogenetic and genetic distance analyses of P1 and 3D indicated that Asian bear picornavirus (aquamavirus B) represents the second sequenced member of the genus Aquamavirus.


Assuntos
Infecções por Picornaviridae/veterinária , Picornaviridae/classificação , Picornaviridae/isolamento & purificação , Focas Verdadeiras/virologia , Ursidae/virologia , Regiões 5' não Traduzidas , Animais , Sequência de Bases , China , Genoma Viral , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Picornaviridae/genética , Infecções por Picornaviridae/virologia , RNA Viral/genética , Proteínas Virais/genética
9.
Chem Commun (Camb) ; 54(68): 9525-9528, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30091760

RESUMO

We report a novel lanthanide-doped core-shell nanostructure NaYF4:Yb,Er@NaGdF4:Nd@SiO2-RB with a unique design feature that integrates luminescence imaging in biological window II, magnetic resonance imaging, and NIR-excited photodynamic antimicrobial chemotherapy, in a single nanoscale entity.

10.
Monoclon Antib Immunodiagn Immunother ; 37(2): 73-77, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29708867

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important viral pathogens that has caused tremendous economic losses to the swine industry worldwide. Although extensive research has been focused on PRRSV, little is known about the structure and biological functions of individual nonstructural viral proteins, especially the nonstructural protein 12 (Nsp12). In this study, we generated and identified the monoclonal antibody (mAb) against PRRSV Nsp12. Six strains of hybridoma cells named 2B10, 2B12, 5E1, 5G6, 5E7, and 8B2 secreting anti-Nsp12 mAbs were obtained by the hybridoma technique. All the mAbs were specifically reacted with PRRSV by indirect immunofluorescence assay and four of them (2B12, 5E1, 5G6, and 5E7) were specifically reacted by Western blot. Furthermore, the 5E7 specifically recognized multiple type 2 PRRSV strains, including highly pathogenic and classical PRRSV strains, but not type 1 PRRSV strain. Taken together, the mAbs against Nsp12 provide a valuable tool to specifically recognize type 2 PRRSV as a diagnostic reagent and study the biological function of Nsp12 in the future.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Antivirais/biossíntese , Especificidade de Anticorpos , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Proteínas não Estruturais Virais/administração & dosagem , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/química , Anticorpos Antivirais/isolamento & purificação , Fusão Celular , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Hibridomas/química , Hibridomas/imunologia , Imunização Secundária , Camundongos , Camundongos Endogâmicos BALB C , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Baço/citologia , Baço/imunologia , Suínos , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/imunologia
11.
Monoclon Antib Immunodiagn Immunother ; 37(2): 69-72, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29630477

RESUMO

The purified whole-virus proteins derived from A/swine/Shanghai/1/2014 (H1N1) (SH1) were chosen to immunize BALB/c mice to prepare the monoclonal antibody (MAb) against hemagglutinin (HA) protein of an European avian-like (EA) H1N1 swine influenza virus (SIV). After cloning three times by limiting dilution, one strain of hybridoma cells named 3C7 secreting anti-HA protein MAb was obtained by hybridoma technique. The results of indirect immunofluorescence assay and western blot analyses showed that the MAb 3C7 specifically reacted with the HA protein of EA H1N1 SIV. This work indicated that the MAb 3C7 would be a valuable tool as a specific diagnostic reagent for SIV epidemiological surveys and identification of HA protein epitopes of the EA H1N1 SIVs in the future.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Antivirais/biossíntese , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Vírus da Influenza A Subtipo H1N1/imunologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/imunologia , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/química , Anticorpos Antivirais/isolamento & purificação , Fusão Celular , China/epidemiologia , Cães , Europa (Continente)/epidemiologia , Feminino , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Hibridomas/química , Hibridomas/imunologia , Imunização Secundária , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Baço/citologia , Baço/imunologia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia
12.
Dalton Trans ; 47(14): 4827-4832, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29541703

RESUMO

We utilise the dual synthesis strategy in terms of bimetallic inorganic building blocks and sulfur containing organic ligand. A novel sulfur-containing bimetallic metal organic framework (Fe2Co-TPDC) with two types of 4-fold meso-helical structures has been successfully synthesized. Benefitting from the uniform distribution of active sulfur sites and the structural stability of the mixed-metallic method, Fe2Co-TPDC can efficiently prevent a shuttle behavior of sulfur and endow a commendable specific capacity. As far as we know, this is the first time that a sulfur-containing bimetallic crystalline MOF with helical structure and prominent specific capacity and remarkable cycling stability has served as an electrode material for LIBs.

13.
Arthritis Res Ther ; 20(1): 9, 2018 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-29370826

RESUMO

BACKGROUND: Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs. METHODS: The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined. Next, the antigen-presenting function and autoantibody production in B cells were evaluated by co-culture with effector T cells and iTregs, respectively, both in vitro and in vivo. Then, the mechanisms underlying these interactions were studied by adding neutralizing antibodies or transwell inserts and by adoptive transfer to B-cell-depleted CIA mice. RESULTS: The BANK1 level decreased in the peripheral blood, spleen and lymph nodes of CIA mice, particularly during the acute stage of arthritis, and exhibited negative correlation with disease severity and autoantibody production. B cell responses were enhanced by this decrease. B cells from CIA mice (CIA-B cells) promoted iTreg differentiation, proliferation and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression. Meanwhile, BANK1 expression in CIA-B cells increased after co-culture with iTregs, limiting B cell responses. All these interactions depended on cell contact with CTLA-4-overexpressing iTregs but were independent of CTLA-4 cytokine. CONCLUSION: Decreased BANK1 expression promotes B cell responses, resulting in an increased antigen presentation ability and autoantibody production that subsequently influences the communication between B cells and iTregs through a cell-contact-dependent and CTLA-4- cytokine-independent mechanism in CIA mice.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Artrite Experimental/imunologia , Linfócitos B/imunologia , Linfócitos T Reguladores/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apresentação do Antígeno/imunologia , Artrite Experimental/genética , Artrite Experimental/metabolismo , Linfócitos B/citologia , Linfócitos B/metabolismo , Comunicação Celular/genética , Comunicação Celular/imunologia , Diferenciação Celular/imunologia , Técnicas de Cocultura , Citocinas/imunologia , Citocinas/metabolismo , Expressão Gênica/imunologia , Granzimas/imunologia , Granzimas/metabolismo , Masculino , Camundongos Endogâmicos DBA , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo
14.
Oncotarget ; 8(34): 57379-57385, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915678

RESUMO

BACKGROUND: To conduct a systematic review and meta-analysis to assess the overall incidence and risk of interstitial lung disease (ILD) and QTc prolongation associated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) in non-small-cell lung cancer (NSCLC) patients. RESULTS: A total of 1,770 patients from 8 clinical trials were included. The incidences of high-grade ILD and QTc prolongation was 2.5% (95% CI 1.7-3.6%), and 2.8% (95% CI 1.8-4.3%), respectively. Meta-analysis demonstrated that the use of ALK-TKIs in NSCLC patients significantly increased the risk of developing high-grade ILD (Peto OR, 3.27, 95%CI: 1.18-9.08, p = 0.023) and QTc prolongation (Peto OR 7.51, 95% CI, 2.16-26.15; p = 0.002) in comparison with chemotherapy alone. MATERIALS AND METHODS: A systematic literature search was performed to identify related citations up to January 31, 2017. Data were extracted, and summary incidence rates, Peto odds ratios (Peto ORs), and 95% confidence intervals (CIs) were calculated. CONCLUSIONS: The use of ALK-TKIs significantly increases the risk of developing high-grade ILD and QTc prolongation in lung cancer patients. Clinicians should pay attention to the risks of severe ILD and QTc prolongation with the administration of these drugs.

15.
J Immunol Res ; 2017: 7573154, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28702462

RESUMO

OBJECTIVE: Tolerogenic dendritic cells (tDCs) can expand TGF-ß-induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTregmtDC) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model. METHODS: After induction by TGF-ß and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTregmtDC were assessed by flow cytometry. The ability of iTregs and iTregmtDC to inhibit CD4+ T cell proliferation and suppress Th17 cell differentiation was compared. Following adoptive transfer of iTregs and iTregmtDC to mice with CIA, the clinical and histopathologic scores, serum levels of IFN-γ, TNF-α, IL-17, IL-6, IL-10, TGF-ß and anti-CII antibodies, and the distribution of the CD4+ Th subset were assessed. RESULTS: Compared with iTregs, iTregmtDC expressed higher levels of Foxp3 and suppressed CD4+ T cell proliferation and Th17 cell differentiation to a greater extent. In vivo, iTregmtDC reduced the severity and progression of CIA more significantly than iTregs, which was associated with a modulated inflammatory cytokine profile, reduced anti-CII IgG levels, and polarized Treg/Th17 balance. CONCLUSION: This study highlights the potential therapeutic utility of iTregmtDC in autoimmune arthritis and should facilitate the future design of iTreg immunotherapeutic strategies.


Assuntos
Artrite Experimental/terapia , Doenças Autoimunes/terapia , Células Dendríticas/imunologia , Tolerância Imunológica , Imunoterapia Adotiva , Linfócitos T Reguladores/imunologia , Animais , Artrite Experimental/imunologia , Doenças Autoimunes/imunologia , Diferenciação Celular , Proliferação de Células , Citocinas/sangue , Células Dendríticas/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Interleucina-17/sangue , Interleucina-6/sangue , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos DBA , Linfócitos T Reguladores/fisiologia , Células Th17/imunologia , Células Th17/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/sangue
16.
Dermatology ; 233(1): 37-46, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28490011

RESUMO

OBJECTIVES: New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA). METHODS: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs) were recruited. Blood samples were obtained for detecting the levels of ILs, IL-12/23p40, and tumor necrosis factor α (TNF-α). The severity of skin lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and receptor activator of nuclear factor-κB ligand) and numbers of osteoclast precursors were evaluated. Radiographic features of affected joints in these patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Correlations among levels of these ILs, Ps, and PsA disease activities and bone erosions were studied. RESULTS: Ps and PsA patients had higher serum levels of TNF-α, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had higher serum levels of IL-36α and IL-38 than patients with Ps vulgaris or HCs. Increased serum levels of IL-36α were positively correlated with PASI. CONCLUSION: Certain ILs were elevated in the circulation of patients with Ps and PsA, which might contribute to the pathogenesis of skin lesions and arthritis.

17.
Springerplus ; 5(1): 2047, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27995024

RESUMO

Canine kobuvirus (CaKVs) was a newly described virus detected in dogs in the US and Italy. To learn more about CaKVs, 5 of 106 fecal samples from diarrhea dogs were positive with CaKVs in China, and the full genome of CaKVs strain CH-1 isolated from dog with diarrhea was sequenced. The genome consists of 8186 nucleotides, excluding the 3' poly (A) tail, and an open reading frame that maps between nucleotide positions 601 and 7943 which encodes a 2446 amino acid polyprotein. Based on the complete amino acid sequence of polyprotein, phylogenetic analysis showed that CH-1 was grouped along with other canine kobuvirus strains detected in the USA (US-PC0082, AN211D).

18.
PLoS One ; 11(8): e0161508, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27560518

RESUMO

Porcine epidemic diarrhea virus (PEDV) has recently caused high mortality in suckling piglets with subsequent large economic losses to the swine industry. Many intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, are activated by viral infection. The PI3K/Akt pathway is an important cellular pathway that has been shown to be required for virus replication. In the present study, we found that the PEDV JS-2013 strain activated Akt in Vero cells at early (5-15 min) and late stages (8-10 h) of infection. Inhibiting PI3K, an upstream activator of Akt, enhanced PEDV replication. Inhibiting GSK-3α/ß, one of the downstream effectors of PI3K/Akt pathway and regulated by Akt during PEDV infected Vero cells, also enhanced PEDV replication. Collectively, our data suggest that PI3K/Akt/GSK-3α/ß signaling pathway is activated by PEDV and functions in inhibiting PEDV replication.


Assuntos
Infecções por Coronavirus/virologia , Quinase 3 da Glicogênio Sintase/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Vírus da Diarreia Epidêmica Suína/patogenicidade , Transdução de Sinais , Animais , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/veterinária , Fosforilação , Vírus da Diarreia Epidêmica Suína/fisiologia , Suínos , Doenças dos Suínos/metabolismo , Doenças dos Suínos/virologia , Células Vero , Replicação Viral
19.
J Ophthalmol ; 2016: 4952340, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27340562

RESUMO

Purpose. The study aimed to evaluate the effect of all-trans retinoic acid-loaded nanostructured lipid carriers (ATRA-NLCs) on the zymosan-induced expression of the cytokines IL-4, IL-10, and IFN-γ and the matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) and TLR2 in rabbit corneal fibroblasts (RCFs). Methods. ATRA-NLCs were prepared by emulsification. RCFs were isolated and harvested after four to seven passages in monolayer culture. Cytokine release (IL-4, IL-10, and IFN-γ) induced by zymosan was analyzed by cytokine release assay, reverse transcription, and real-time polymerase chain reaction (RT-PCR) analysis detection. MMP-1, MMP-3, and MMP-13, TIMP-1 and TIMP-2, and TLR2 expression were analyzed by immunoblotting. Results. ATRA-NLCs were resistant to light and physically stable, and the average size of the ATRA-NLCs was 200 nm. ATRA-NLCs increased the zymosan-induced release of IL-4 and IL-10 and decreased the release of IFN-γ by RCFs. ATRA-NLCs decreased the levels of TLR2 and MMPs/TIMPs above. Conclusions. ATRA may be a potent anti-inflammatory agent for the therapy of fungal keratitis (FK).

20.
Monoclon Antib Immunodiagn Immunother ; 35(3): 172-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27148642

RESUMO

The bone marrow stromal cell antigen 2 (BST-2) protein was identified as a novel virus restriction factor that potently restricts the replication and egress of enveloped viruses. In this study, we generated monoclonal antibodies (MAbs) against porcine BST-2 encoding 34-112 aa of porcine BST-2, which was cloned and inserted into the prokaryotic expression vector pCold-I to construct a recombinant plasmid pCold-pBST-2. The recombinant porcine BST-2 protein (rpBST-2 protein) was induced by isopropyl-ß-D-thiogalactoside in Escherichia coli BL21 (DE3). Then, BALB/c mice were immunized with the purified rpBST-2 protein to prepare MAbs of BST-2. After subcloning, one strain of hybridoma cells named 1B2 secreting porcine BST-2 protein monoclonal antibody (MAb) was obtained. Indirect immunofluorescence assay and western blot analysis showed that the MAb was specifically reacted with the overexpressed porcine BST-2 protein in Vero cells. The specific MAb of porcine BST-2 provides a valuable tool for further studies of BST-2 to restrict virus infection.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD/imunologia , Infecções por Coronavirus/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Especificidade de Anticorpos/imunologia , Infecções por Coronavirus/virologia , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Diarreia Epidêmica Suína/imunologia , Vírus da Diarreia Epidêmica Suína/patogenicidade , Proteínas Recombinantes , Suínos/imunologia , Células Vero
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