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1.
Anticancer Res ; 39(10): 5653-5662, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570463

RESUMO

BACKGROUND/AIM: Factors influencing fulvestrant efficacy may be useful in selecting the optimal treatment regimen for postmenopausal Japanese women with metastatic/recurrent HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated progression-free and overall survival (PFS and OS) in 100 fulvestrant-treated patients according to metastatic site. RESULTS: Median PFS was significantly better in patients with non-visceral (bone and regional metastases; 22.8 months) vs. visceral metastasis (lung, liver, and other organs; 8.2 months; p=0.024), although median OS did not differ (p=0.922). Median PFS in patients with lung metastasis (20.8 months) and non-visceral metastasis (22.8 months) were comparable; patients with liver metastasis (6.1 months) and other organ metastases (3.7 months) had worse prognoses. CONCLUSION: Patients with non-visceral metastases had a better prognosis than those with visceral metastases. Fulvestrant induced a longer PFS in patients with non-visceral metastasis, and also in those with lung metastasis without liver or other organ involvement.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Fulvestranto/uso terapêutico , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/genética , Receptores de Superfície Celular/genética , Estudos Retrospectivos
2.
Arch Virol ; 164(11): 2793-2797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31440811

RESUMO

The DC-SIGN glycoprotein is responsible for the initial adhesion of dengue virus (DENV) to immune cells by the carbohydrate recognition domain (CRD). There are thirteen soluble and membrane-bound DC-SIGN isoforms, but the role of soluble isoforms in the DENV internalization process is not known. Five isoforms with an altered or absent CRD were identified, and three different soluble isoforms were used to confirm the interactions with mannose residues. The results show the loss of binding ability of one soluble isoform and binding ability of two of them. All of them will be used to verify their role in the DENV internalization process.


Assuntos
Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Vírus da Dengue/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Manose/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Ligação Viral , Internalização do Vírus , Sequência de Aminoácidos , Sequência de Bases , Dengue/virologia , Vírus da Dengue/genética , Ligantes , Ligação Proteica/genética , Isoformas de Proteínas/genética
3.
Artigo em Chinês | MEDLINE | ID: mdl-31327199

RESUMO

Objective:The aim of this study is to investigate the relationship between the level of (pro) renin(P)RR in obstructive sleep apnea syndrome (OSA) patients, and the gender and disease severity of the disease.b>Method:From March 2010 to March 2018, eighty OSA patients who were treated and diagnosed in our hospital were selected as subjects. Another 20 healthy subjects were selected as the control group.Plasma soluble (pro) renin receptor ï¼»s(P)RRï¼½ levels and clinical parameters were measured in healthy subjects and OSA patients with different sex and disease severity. Result:The plasma s(P)RR concentrations were significantly higher in OSA patients than that in control group. In all patients, plasma s(P)RR concentrations increased with increasing disease levels and showed the same trend between men and women. In addition,in all patients, plasma s(P)RR concentrations were significantly positively correlated with waist-to-hip ratio, HbA1c, AHI, and oxygen desaturation index. There was a significant negative correlation between saturation (MSpO2) and minimum oxygen saturation (minSpO2) (P<0.05).In female subjects,plasma s(P)RR concentrations were significantly positively correlated with waist-to-hip ratio and AHI,but significantly negatively correlated with eGFR (P<0.05).In male subjects,plasma s(P)RR concentration was significantly positively correlated with waist-to-hip ratio,HbA1c,renin level,AHI and oxygen desaturation index, but negatively correlated with eGFR, MSpO2 and minSpO2 (P<0.05). Plasma s(P)RR concentrations were significantly reduced after treatment with nasal continuous positive airway pressure ventilator. In addition, ESS,AHI,MSpO2,minSpO2,and oxygen desaturation index were all significantly improved (P<0.05).Conclusion: Plasma s(P)RR levels in OSA patients are significantly positively correlated with the severity of the disease and can directly reflect the severity of the disease. In addition, the patient with higher waist-to-hip ratio and HbA1c, and lower eGFR can effect plasma s(P)RR levels, and may lead to OSA aggravation.


Assuntos
Receptores de Superfície Celular/sangue , Fatores Sexuais , Apneia Obstrutiva do Sono/fisiopatologia , ATPases Vacuolares Próton-Translocadoras/sangue , Estudos de Casos e Controles , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Masculino , Oxigênio , Polissonografia , Receptores de Superfície Celular/genética , Apneia Obstrutiva do Sono/genética , ATPases Vacuolares Próton-Translocadoras/genética
4.
Vet Microbiol ; 235: 101-109, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282367

RESUMO

Highly virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains have increasingly overwhelmed Asia and Europe in recent years. This study aims to compare the clinical signs, gross and microscopic findings as well as the expression of CD163 within live pulmonary alveolar macrophages (PAMs) from bronchoalveolar lavage fluid (BALF) of pigs experimentally infected with two PRRSV strains of different virulence. Pigs were infected with either a subtype 1 PRRSV-1 3249 strain or a subtype 3 PRRSV-1 Lena strain and consecutively euthanized at 1, 3, 6, 8 and 13 days post-inoculation. Clinical signs were reported daily and BALF and lung tissue samples were collected at the different time-points and accordingly processed for their analysis. Pigs infected with Lena strain exhibited greater clinical signs as well as gross and microscopic lung scores compared to 3249-infected pigs. A decreased frequency of PAMs from BALF was observed early in pigs infected with Lena strain. Moreover, the frequency and median fluorescence intensity (MFI) of CD163 within PAMs were much lower in Lena-infected pigs than in 3249-infected pigs. This downregulation in CD163 was also observed in lung sections after the assessment of macrophages expressing CD163 by means of immunohistochemistry. This outcome may result from the effect of PRRSV replication, PRRSV-induced inflammation, the influx of immature macrophages to restore lung homeostasis and/or the evidence of CD163low cells after CD163+ cells decrease in BALF.


Assuntos
Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Broncopneumonia/veterinária , Macrófagos Alveolares/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Receptores de Superfície Celular/genética , Animais , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Broncopneumonia/virologia , Regulação para Baixo , Feminino , Pulmão/citologia , Pulmão/virologia , Macrófagos Alveolares/virologia , Masculino , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Receptores de Superfície Celular/imunologia , Suínos , Virulência
5.
Medicine (Baltimore) ; 98(29): e16457, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335702

RESUMO

The impact of genetic polymorphisms on the occurrence of recurrent ischemic stroke (RIS) is not fully understood. This study was aimed to examine the relationships among the 106PEAR1 and 168PTGS1 polymorphisms and RIS.This was a single-center, retrospective, case-control study of patients seen in consultation between March 2016 and December 2016 at the Shandong Provincial Hospital. The 106PEAR1 (G>A) and 168PTGS1 (-842A>G) polymorphisms were determined by fluorescence in situ hybridization.There were 56 patients with RIS and 137 with initial stroke. Compared with the initial group, the RIS group showed lower LDL-C levels (P = .04). 168PTGS1 (-842A>G) did not meet the Hardy-Weinberg equilibrium. The AA genotype of the 106PEAR1 (G>A) polymorphism was more frequent in the RIS group (17.9% vs 5.8%, P = .009). The A allele also showed a higher frequency than the G allele in the RIS group (P = .02). The multivariable logistic regression analysis showed that 106PEAR1 (G>A) (OR = 3.24, 95%CI: 1.04-10.14, P = .04) and lipid-lowering agents (OR = 9.18, 95%CI: 4.48-18.84, P < .001) were independently associated with RIS.The polymorphism at 106PEAR1 (G>A) was independently associated with RIS in Chinese patients. The assessment of genetic polymorphisms in the prediction of RIS warrants further investigation in order to improve patient management and prognosis after a first ischemic stroke.


Assuntos
Isquemia Encefálica , Ciclo-Oxigenase 1/genética , Receptores de Superfície Celular/genética , Acidente Vascular Cerebral , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética
6.
Nat Commun ; 10(1): 2402, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160588

RESUMO

Platelet-leukocyte interactions amplify inflammatory reactions, but the underlying mechanism is still unclear. CLEC5A and CLEC2 are spleen tyrosine kinase (Syk)-coupled C-type lectin receptors, abundantly expressed by leukocytes and platelets, respectively. Whereas CLEC5A is a pattern recognition receptor (PRR) to flaviviruses and bacteria, CLEC2 is the receptor for platelet-activating snake venom aggretin. Here we show that dengue virus (DV) activates platelets via CLEC2 to release extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles (MVs). DV-induced EXOs (DV-EXOs) and MVs (DV-MVs) further activate CLEC5A and TLR2 on neutrophils and macrophages, thereby induce neutrophil extracellular trap (NET) formation and proinflammatory cytokine release. Compared to  stat1-/- mice, simultaneous blockade of CLEC5A and TLR2 effectively attenuates DV-induced inflammatory response and increases survival rate from 30 to 90%. The identification of critical roles of CLEC2 and CLEC5A/TLR2 in platelet-leukocyte interactions will support the development of novel strategies to treat acute viral infection in the future.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/imunologia , Dengue/imunologia , Vesículas Extracelulares/imunologia , Lectinas Tipo C/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Receptores de Superfície Celular/imunologia , Receptor 2 Toll-Like/imunologia , Animais , Micropartículas Derivadas de Células/imunologia , Micropartículas Derivadas de Células/metabolismo , Citocinas/imunologia , Dengue/virologia , Exossomos/imunologia , Exossomos/metabolismo , Armadilhas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Humanos , Inflamação , Lectinas Tipo C/genética , Camundongos , Camundongos Knockout , Ativação Plaquetária , Receptores de Superfície Celular/genética , Fator de Transcrição STAT1/genética , Taxa de Sobrevida
7.
Parasit Vectors ; 12(1): 317, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234897

RESUMO

Glycophorins are heavily glycosylated sialoglycoproteins of human and animal erythrocytes. In humans, there are four glycophorins: A, B, C and D. Glycophorins play an important role in the invasion of red blood cells (RBCs) by malaria parasites, which involves several ligands binding to RBC receptors. Four Plasmodium falciparum merozoite EBL ligands have been identified: erythrocyte-binding antigen-175 (EBA-175), erythrocyte-binding antigen-181 (EBA-181), erythrocyte-binding ligand-1 (EBL-1) and erythrocyte-binding antigen-140 (EBA-140). It is generally accepted that glycophorin A (GPA) is the receptor for P. falciparum EBA-175 ligand. It has been shown that α(2,3) sialic acid residues of GPA O-glycans form conformation-dependent clusters on GPA polypeptide chain which facilitate binding. P. falciparum can also invade erythrocytes using glycophorin B (GPB), which is structurally similar to GPA. It has been shown that P. falciparum EBL-1 ligand binds to GPB. Interestingly, a hybrid GPB-GPA molecule called Dantu is associated with a reduced risk of severe malaria and ameliorates malaria-related morbidity. Glycophorin C (GPC) is a receptor for P. falciparum EBA-140 ligand. Likewise, successful binding of EBA-140 depends on sialic acid residues of N- and O-linked oligosaccharides of GPC, which form a cluster or a conformational structure depending on the presence of peptide fragment encompassing amino acids (aa) 36-63. Evaluation of the homologous P. reichenowi EBA-140 unexpectedly revealed that the chimpanzee homolog of human glycophorin D (GPD) is probably the receptor for this ligand. In this review, we concentrate on the role of glycophorins as erythrocyte receptors for Plasmodium parasites. The presented data support the long-lasting idea of high evolutionary pressure exerted by Plasmodium on the human glycophorins, which emerge as important receptors for these parasites.


Assuntos
Proteínas de Transporte/metabolismo , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Glicoforina/metabolismo , Plasmodium falciparum/fisiologia , Proteínas de Protozoários/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Proteínas de Transporte/genética , Glicoforina/genética , Humanos , Ligantes , Merozoítos , Pan troglodytes , Ligação Proteica , Proteínas de Protozoários/genética , Receptores de Superfície Celular/genética
8.
Vet Microbiol ; 234: 25-33, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31213269

RESUMO

Porcine productive and respiratory syndrome virus (PRRSV) and classical swine fever virus (CSFV) both are major pathogens of swine that pose a great threat to the Chinese pig industry. It has been found that PRRSV infection can lead to vaccination failure of CSFV C strain-derived modified live vaccine (CSFV-C) by interfering with the immune responses to the latter. To investigate whether PRRSV can suppress CSFV-C replication, we created a 3D4/21-based cell line PAM39 that is susceptible to both viruses by expressing PRRSV receptors CD163 and CD169, and then investigated their interplay under the condition of either sequential or simultaneous co-infection. The most significant suppressive effect came from the sequential infection when the cells were first infected by PRRSV and then followed by CSFV-C at an interval of 6 h. In addition, this effect was independent of PRRSV strains. Mechanistically, PRRSV induced an elevated level of a subset of pro-inflammatory cytokines, especially tumor necrosis factor (TNF-α), through the nuclear factor κB (NF-κB) signaling pathway to inhibit the replication of CSFV-C in vitro. Thus, our studies provide an alternative explanation on PRRSV-induced CSFV vaccination failure, and this has an important implication in CSF vaccination and control.


Assuntos
Vírus da Febre Suína Clássica/fisiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína , Fator de Necrose Tumoral alfa/imunologia , Replicação Viral , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Linhagem Celular , Imunofluorescência , NF-kappa B/metabolismo , RNA Interferente Pequeno , Receptores de Superfície Celular/genética , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Transdução de Sinais , Suínos , Fator de Necrose Tumoral alfa/genética
9.
Plant Physiol Biochem ; 139: 660-671, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31048123

RESUMO

In Arabidopsis, the serine/threonine protein kinase Constitutive Triple Response 1 (CTR1) and Ethylene Insensitive 2 polypeptide (EIN2) functions are key negative and positive components, respectively, in the ethylene signalling route. Here, we report on an in silico study of members of the CTR1-like and EIN2-like polypeptide families from poplars. The expression of CTR1-like and EIN2-like genes such as Ptre-CTR1, Ptre-CTR3 and Ptre-EIN2a was studied in Populus tremula buds and leaves in response to dehydration, various light conditions and under senescence. In buds under dehydration, the maximal fold-change of the Ptre-CTR1, Ptre-CTR3 and Ptre-EIN2a expression level recorded almost identical values. This suggests that maintenance of a constant ratio between the transcript levels of genes encoding positive and negative ethylene signalling components is required under stress. The expression of the studied genes was 1.4-to 3-fold higher in response to darkness, but 4.5- to 51.2-fold and 21.6- to 51.2-fold higher under the early and moderate leaf senescence, respectively. It is worth noting that the senescence-related Ptre-EIN2a and Ptre-CTR3a expression profiles were very similar. Using in vitro assays, we demonstrated the ability of the catalytic domain of Ptre-CTR1 to phosphorylate the Ptre-EIN2a-like polypeptide, which is similar to that in Arabidopsis. The target substrate, the Ptre-CEND2a polypeptide (C-terminal part of Ptre-EIN2a), was only phosphorylated by the protein kinase Ptre-CTR1 and not by Ptre-CTR3. Moreover, the addition of Ptre-CTR3 polypeptides (-CTR3a or -CTR3b forms) to the reaction mixture had an inhibitory effect on Ptre-CTR1 auto- and trans-phosphorylation. In contrast to Ptre-CTR1, Ptre-CTR3 may act as a positive regulator in ethylene signalling in poplar; however, this hypothesis requires in vivo confirmation. Thus, the ethylene signalling route in poplar seems to be under the control of certain additional mechanisms which have not been reported in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Populus/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Etilenos/metabolismo , Fosforilação , Folhas de Planta/metabolismo , Populus/genética , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo
10.
Parasit Vectors ; 12(1): 205, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060579

RESUMO

BACKGROUND: Vitellogenin (Vg), a key molecule for oocyte development synthesized in the fat body during blood-feeding, is released into the hemolymph and then taken into the oocytes via Vg receptor (VgR) in ticks. Previously, we showed that VgR mRNA is expressed in the ovary at the adult stage of parthenogenetic Haemaphysalis longicornis ticks and its expression increases after blood-feeding. However, intracellular localization of VgR mRNA and protein at each developmental stage of oocytes during oogenesis remains largely unclear. METHODS: mRNA and protein expression profiles of H. longicornis VgR (HlVgR) in the oocytes from the unfed to oviposition periods were analyzed by real-time PCR, in situ hybridization, and immunostaining. To elucidate the timing of the onset of Vg uptake, RNA interference (RNAi)-mediated gene silencing of HlVgR was performed. RESULTS: In situ hybridization revealed that HlVgR mRNA was detected in the cytoplasm of stage I-III oocytes, and weaker positive signals for HlVgR mRNA were found in the cell periphery of stage IV and V oocytes. Likewise, HlVgR protein was detected by immunostaining in the cytoplasm of stage I-III oocytes and in the cell periphery of stage IV and V oocytes. Each developmental stage of the oocytes showed distinct patterns of mRNA and protein expression of HlVgR. Moreover, RNAi of HlVgR caused delayed or arrested development in the oocytes. The ovaries of control ticks showed all developmental stages of oocytes, whereas stage I-III oocytes were found in the ovaries of HlVgR-RNAi ticks at 5 days after engorgement. CONCLUSIONS: These results suggest that active uptake of Vg is required for development from stage III to stage IV during oogenesis. Our data clearly revealed an apparent shift in the intracellular localization of VgR for both mRNA and protein level in oocytes during oogenesis.


Assuntos
Proteínas do Ovo/metabolismo , Ixodidae/metabolismo , Oogênese/fisiologia , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/metabolismo , Vitelogeninas/metabolismo , Animais , Proteínas do Ovo/genética , Feminino , Ixodidae/genética , Ixodidae/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos BALB C , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Oogênese/genética , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/genética , Transcriptoma
11.
Anticancer Res ; 39(5): 2341-2350, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092426

RESUMO

BACKGROUND/AIM: Chitinase 3 like 1 (CHI3L1) is a secretion glycoprotein. Elevated levels of this protein are observed in cancer diseases. The biological role of CHI3L1 is not yet fully known, but the connection between CHI3L1 and angiogenesis has been shown. Recent reports also describe the association of Nogo isoforms and Nogo-B receptor (NgBR) with a proliferative potential, cancer cell invasiveness, and angiogenesis. The aim of this study was to evaluate the levels of CHI3L1, Nogo-A, Nogo-A/B, and NgBR and correlate them with clinical-pathological data, to study their role in angiogenesis in invasive ductal breast carcinoma (IDC). MATERIALS AND METHODS: A total of 77 IDC cases were used in the study. Immunohistochemistry was used to determine the level of expression of CHI3L1, Nogo-A, Nogo-A/B, NgBR and vascular endothelial growth factors (VEGFA, VEGFC and VEGFD). The obtained results were subjected to statistical analysis including clinicalpathological data. RESULTS: A statistically significant positive correlation of CHI3L1 and Nogo-A expression (r=0.474, p>0.0001) and a positive correlation of Nogo-A and VEGFC expression (r=0.280, p=0.013) were found. CONCLUSION: CHI3L1 and Nogo-A are important in angiogenesis in IDC.


Assuntos
Carcinoma Ductal de Mama/genética , Proteína 1 Semelhante à Quitinase-3/genética , Neovascularização Patológica/genética , Proteínas Nogo/genética , Fator C de Crescimento do Endotélio Vascular/genética , Idoso , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Receptores de Superfície Celular/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator D de Crescimento do Endotélio Vascular/genética
12.
mSphere ; 4(3)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092602

RESUMO

The Plasmodium vivax Duffy binding protein region II (DBPII) is a vital ligand for the parasite's invasion of reticulocytes, thereby making this molecule an attractive vaccine candidate against vivax malaria. However, strain-specific immunity due to DBPII allelic variation in Bc epitopes may complicate vaccine efficacy, suggesting that an effective DBPII vaccine needs to target conserved epitopes that are potential targets of strain-transcending neutralizing immunity. The minimal epitopes reactive with functionally inhibitory anti-DBPII monoclonal antibody (MAb) 3C9 and noninhibitory anti-DBPII MAb 3D10 were mapped using phage display expression libraries, since previous attempts to deduce the 3C9 epitope by cocrystallographic methods failed. Inhibitory MAb 3C9 binds to a conserved conformation-dependent epitope in subdomain 3, while noninhibitory MAb 3D10 binds to a linear epitope in subdomain 1 of DBPII, consistent with previous studies. Immunogenicity studies using synthetic linear peptides of the minimal epitopes determined that the 3C9 epitope, but not the 3D10 epitope, could induce functionally inhibitory anti-DBPII antibodies. Therefore, the highly conserved binding-inhibitory 3C9 epitope offers the potential as a component in a broadly inhibitory, strain-transcending DBP subunit vaccine.IMPORTANCE Vivax malaria is the second leading cause of malaria worldwide and the major cause of non-African malaria. Unfortunately, efforts to develop antimalarial vaccines specifically targeting Plasmodium vivax have been largely neglected, and few candidates have progressed into clinical trials. The Duffy binding protein is considered a leading blood-stage vaccine candidate because this ligand's recognition of the Duffy blood group reticulocyte surface receptor is considered essential for infection. This study identifies a new target epitope on the ligand's surface that may serve as the target of vaccine-induced binding-inhibitory antibody (BIAb). Understanding the potential targets of vaccine protection will be important for development of an effective vaccine.


Assuntos
Antígenos de Protozoários/imunologia , Epitopos/imunologia , Plasmodium vivax/imunologia , Proteínas de Protozoários/imunologia , Receptores de Superfície Celular/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/genética , Ensaio de Imunoadsorção Enzimática , Epitopos/genética , Ligantes , Vacinas Antimaláricas , Malária Vivax/imunologia , Malária Vivax/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Biblioteca de Peptídeos , Plasmodium vivax/química , Proteínas de Protozoários/genética , Receptores de Superfície Celular/genética
13.
Parasit Vectors ; 12(1): 248, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109364

RESUMO

BACKGROUND: Mice are susceptible to infections with the rodent filarial nematode Litomosoides sigmodontis and develop immune responses that resemble those of human filarial infections. Thus, the L. sigmodontis model is used to study filarial immunomodulation, protective immune responses against filariae and to screen drug candidates for human filarial diseases. While previous studies showed that type 2 immune responses are protective against L. sigmodontis, the present study directly compared the impact of eosinophils, IL-5, and the IL-4R on the outcome of L. sigmodontis infection. METHODS: Susceptible wildtype (WT) BALB/c mice, BALB/c mice lacking eosinophils (dblGATA mice), IL-5-/- mice, IL-4R-/- mice and IL-4R-/-/IL-5-/- mice were infected with L. sigmodontis. Analyses were performed during the peak of microfilaremia in WT animals (71 dpi) as well as after IL-4R-/-/IL-5-/- mice showed a decline in microfilaremia (119 dpi) and included adult worm counts, peripheral blood microfilariae levels, cytokine production from thoracic cavity lavage, the site of adult worm residence, and quantification of major immune cell types within the thoracic cavity and spleen. RESULTS: Our study reveals that thoracic cavity eosinophil numbers correlated negatively with the adult worm burden, whereas correlations of alternatively activated macrophage (AAM) numbers with the adult worm burden (positive correlation) were likely attributed to the accompanied changes in eosinophil numbers. IL-4R-/-/IL-5-/- mice exhibited an enhanced embryogenesis achieving the highest microfilaremia with all animals becoming microfilariae positive and had an increased adult worm burden combined with a prolonged adult worm survival. CONCLUSIONS: These data indicate that mice deficient for IL-4R-/-/IL-5-/- have the highest susceptibility for L. sigmodontis infection, which resulted in an earlier onset of microfilaremia, development of microfilaremia in all animals with highest microfilariae loads, and an extended adult worm survival.


Assuntos
Suscetibilidade a Doenças/imunologia , Eosinófilos/imunologia , Filariose/imunologia , Interleucina-5/genética , Receptores de Superfície Celular/genética , Animais , Modelos Animais de Doenças , Filariose/sangue , Filarioidea/fisiologia , Técnicas de Inativação de Genes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Microfilárias/imunologia , Ácaros/parasitologia , Transdução de Sinais , Baço/imunologia
14.
Vet Res Commun ; 43(3): 187-195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31104196

RESUMO

The emergence of virulent strains of porcine reproductive and respiratory syndrome virus (PRRSV), causing atypical and severe outbreaks, has been notified worldwide. This study assesses the expression, distribution and kinetics of PRRSV N-protein, CD163 and CD107a in the lung and tonsil from experimentally-infected piglets with three different PRRSV-1 strains: a virulent PRRSV-1 subtype 3 strain (SU1-bel) and two low-virulent subtype 1 strains, Lelystad virus (LV) and 215-06. SU1-bel replicated more efficiently in the lungs and tonsils. The number of CD163+ cells decreased in both tissues from all infected groups at 7 dpi, followed by an increase at the end of the study, highlighting a negative correlation with the number of N-protein+-infected cells. A significant increase in CD107a was observed in all infected groups at 35 dpi but no differences were observed among them. Whereas the initial decrease of CD163+ cells appears to be associated to virus replication and cell death, the later recovery of the CD163+ population may be due to either the induction of CD163 in immature cells, the recruitment of CD163+ cells in the area of infection, or both. These results highlight the ability of macrophage subpopulations in infected animals to recover and restore their potential biological functions at one-month post-infection, with the greatest improvement observed in SU1-bel-infected animals.


Assuntos
Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Regulação da Expressão Gênica/imunologia , Pulmão/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/genética , Tonsila Palatina/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Receptores de Superfície Celular/genética , Animais , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/imunologia , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Receptores de Superfície Celular/imunologia , Suínos , Virulência/imunologia
15.
Genome Biol Evol ; 11(5): 1451-1462, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31087101

RESUMO

Signaling through ligand/receptor interactions is a widespread mechanism across all living taxa. During evolution, however, there has been a diversification in multigene families and changes in their interaction patterns. Among the events that led to the creation of new genes is the whole-genome duplication, which made possible some major innovations. Teleost fishes descended from a common ancestor which underwent one such whole-genome duplication. In our study, we investigated the effect of complete genome duplication on the evolution of ligand-receptor pairs in teleosts. We selected ten teleost species and used bioinformatics programs and phylogenetic tools in order to study the evolution of the human ligands and receptors that have orthologous genes in fishes, as well as the rest of the fish genomes. We established that since the complete duplication of the fish genomes, the conservation in duplicate copy of ligand and receptor genes is higher than expected. However, the ligand/receptor pair partners did not necessarily evolve in the same way, and a lot of situations occurred in which one of the partners returned in singleton copy when the other one was maintained in duplicate. This suggests that changes in interaction partners may have taken place during the evolution of teleosts. Moreover, the fate of the ligands and receptor coding genes is partly congruent with the phylogeny of teleosts. However, some incongruences can be observed. We suggest that these incongruences are correlated to the environment.


Assuntos
Evolução Molecular , Peixes/genética , Receptores de Superfície Celular/genética , Animais , Duplicação Gênica , Genoma , Humanos , Ligantes
16.
Planta ; 250(1): 381-390, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31062160

RESUMO

MAIN CONCLUSION: Ethylene receptor is crucial for PCD and aerenchyma formation in Typha angustifolia leaves. Not only does it receive and deliver the ethylene signal, but it probably can determine the cell fate during aerenchyma morphogenesis, which is due to the receptor expression quantity. Aquatic plant oxygen delivery relies on aerenchyma, which is formed by a programmed cell death (PCD) procedure. However, cells in the outer edge of the aerenchyma (palisade cells and septum cells) remain intact, and the mechanism is unclear. Here, we offer a hypothesis: cells that have a higher content of ethylene receptors do not undergo PCD. In this study, we investigated the leaf aerenchyma of the aquatic plant Typha angustifolia. Ethephon and pyrazinamide (PZA, an inhibitor of ACC oxidase) were used to confirm that ethylene is an essential hormone for PCD of leaf aerenchyma cells in T. angustifolia. That the ethylene receptor was an indispensable factor in this PCD was confirmed by 1-MCP (an inhibitor of the ethylene receptor) treatment. Although PCD can be avoided by blocking the ethylene receptor, excessive ethylene receptors also protect cells from PCD. TaETR1, TaETR2 and TaEIN4 in the T. angustifolia leaf were detected by immunofluorescence (IF) using polyclonal antibodies. The result showed that the content of ethylene receptors in PCD-unsusceptible cells was 4-14 times higher than that one in PCD-susceptible cells, suggesting that PCD-susceptible cells undergo the PCD programme, while PCD-unsusceptible cells do not due to the content difference in the ethylene receptor in different cells. A higher level of ethylene receptor content makes the cells insensitive to ethylene, thereby avoiding cell death and degradation.


Assuntos
Reguladores de Crescimento de Planta/farmacologia , Proteínas de Plantas/metabolismo , Receptores de Superfície Celular/metabolismo , Typhaceae/fisiologia , Aminoácido Oxirredutases/antagonistas & inibidores , Apoptose/genética , Diferenciação Celular/genética , Ciclopropanos/farmacologia , Etilenos/metabolismo , Compostos Organofosforados/farmacologia , Reguladores de Crescimento de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/enzimologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Pirazinamida/farmacologia , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/genética , Typhaceae/efeitos dos fármacos , Typhaceae/enzimologia , Typhaceae/crescimento & desenvolvimento
17.
Mem Inst Oswaldo Cruz ; 114: e190004, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141020

RESUMO

BACKGROUND: Dengue is an arthropod-borne viral disease with a majority of asymptomatic individuals and clinical manifestations varying from mild fever to severe and potentially lethal forms. An increasing number of genetic studies have outlined the association between host genetic variations and dengue severity. Genes associated to viral recognition and entry, as well as those encoding mediators of the immune response against infection are strong candidates for association studies. OBJECTIVES: The aim of this study was to investigate the association between MBL2, CLEC5A, ITGB3 and CCR5 genes and dengue severity in children. METHODS: A matched case-control study was conducted and 19 single nucleotide polymorphisms (SNPs) were investigated. FINDINGS: No associations were observed in single SNP analysis. However, when MBL2 SNPs were combined in haplotypes, the allele rs7095891G/rs1800450C/ rs1800451C/rs4935047A/rs930509G/rs2120131G/rs2099902C was significantly associated to risk of severe dengue under α = 0.05 (aOR = 4.02; p = 0.02). A second haplotype carrying rs4935047G and rs7095891G alleles was also associated to risk (aOR = 1.91; p = 0.04). MAIN CONCLUSIONS: This is the first study to demonstrate the association between MBL2 haplotypes and dengue severity in Brazilians including adjustment for genetic ancestry. These results reinforce the role of mannose binding lectin in immune response to DENV.


Assuntos
Dengue/genética , Integrina beta3/genética , Lectinas Tipo C/genética , Lectina de Ligação a Manose/genética , Receptores CCR5/genética , Receptores de Superfície Celular/genética , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença
18.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075901

RESUMO

The alveolar epithelial cells represent an important part of the alveolar barrier, which is maintained by tight junction proteins, particularly JAM-A, occludin, and claudin-18, which regulate paracellular permeability. In this study, we report on a strong increase in epithelial JAM-A expression in P2X7 receptor knockout mice when compared to the wildtype. Precision-cut lung slices of wildtype and knockout lungs and immortal epithelial lung E10 cells were treated with bleomycin, the P2X7 receptor inhibitor oxATP, and the agonist BzATP, respectively, to evaluate early changes in JAM-A expression. Biochemical and immunohistochemical data showed evidence for P2X7 receptor-dependent JAM-A expression in vitro. Inhibition of the P2X7 receptor using oxATP increased JAM-A, whereas activation of the receptor decreased the JAM-A protein level. In order to examine the role of GSK-3ß in the expression of JAM-A in alveolar epithelial cells, we used lithium chloride for GSK-3ß inhibiting experiments, which showed a modulating effect on bleomycin-induced alterations in JAM-A levels. Our data suggest that an increased constitutive JAM-A protein level in P2X7 receptor knockout mice may have a protective effect against bleomycin-induced lung injury. Bleomycin-treated precision-cut lung slices from P2X7 receptor knockout mice responded with a lower increase in mRNA expression of JAM-A than bleomycin-treated precision-cut lung slices from wildtype mice.


Assuntos
Moléculas de Adesão Celular/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Células Epiteliais Alveolares/metabolismo , Animais , Bleomicina , Moléculas de Adesão Celular/genética , Camundongos , Agonistas do Receptor Purinérgico P2X/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/genética , Receptores Purinérgicos P2X7/deficiência
19.
BMC Genomics ; 20(1): 428, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138111

RESUMO

BACKGROUND: Deciphering the molecular mechanisms mediating the chemical senses, taste, and smell has been of vital importance for understanding the nature of how insects interact with their chemical environment. Several gene families are implicated in the uptake, recognition, and termination of chemical signaling, including binding proteins, chemosensory receptors and degrading enzymes. The cotton leafworm, Spodoptera littoralis, is a phytophagous pest and current focal species for insect chemical ecology and neuroethology. RESULTS: We produced male and female Illumina-based transcriptomes from chemosensory and non-chemosensory tissues of S. littoralis, including the antennae, proboscis, brain and body carcass. We have annotated 306 gene transcripts from eight gene families with known chemosensory function, including 114 novel candidate genes. Odorant receptors responsive to floral compounds are expressed in the proboscis and may play a role in guiding proboscis probing behavior. In both males and females, expression of gene transcripts with known chemosensory function, including odorant receptors and pheromone-binding proteins, has been observed in brain tissue, suggesting internal, non-sensory function for these genes. CONCLUSIONS: A well-curated set of annotated gene transcripts with putative chemosensory function is provided. This will serve as a resource for future chemosensory and transcriptomic studies in S. littoralis and closely related species. Collectively, our results expand current understanding of the expression patterns of genes with putative chemosensory function in insect sensory and non-sensory tissues. When coupled with functional data, such as the deorphanization of odorant receptors, the gene expression data can facilitate hypothesis generation, serving as a substrate for future studies.


Assuntos
Proteínas de Insetos/genética , Spodoptera/genética , Animais , Antenas de Artrópodes/metabolismo , Encéfalo/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Esterases/genética , Esterases/metabolismo , Feminino , Perfilação da Expressão Gênica , Genes de Insetos , Proteínas de Insetos/metabolismo , Masculino , Família Multigênica , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Spodoptera/enzimologia , Spodoptera/metabolismo , Spodoptera/fisiologia , Percepção Gustatória
20.
Vet Microbiol ; 232: 137-145, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31030838

RESUMO

The emergence of "highly pathogenic" isolates of porcine reproductive and respiratory syndrome virus (HP-PRRSV) has raised new concerns about PRRS control. Cells from the porcine monocyte-macrophage lineage represent the target for this virus, which replicates mainly in the lung, and especially in HP-PRRSV strains, also in lymphoid organs, such as the thymus. This study aimed at evaluating the impact of two PRRSV strains of different virulence on thymic macrophages as well as after heterologous vaccination. After experimental infection with PR11 and PR40 PRRSV1 subtype 1 strains (low and high virulent, respectively) samples from thymus were analysed by histopathology and immunohistochemistry for PRRSV N protein, TUNEL, CD172a, CD163, CD107a and BA4D5 expression. Mortality was similar in both infected groups, but lung lesions and thymus atrophy were more intense in PR40 group. Animals died at 10-14 dpi after PR11 or PR40 infection showed the most severe histopathological lesions, with a strong inflammatory response of the stroma and extensive cell death phenomena in the cortex. These animals presented an increase in the number of N protein, CD172a, CD163 and BA4D5 positive cells in the stroma and the cortex together with a decrease in the number of CD107a positive cells. Our results highlight the recruitment of macrophages in the thymus, the increase in the expression of CD163 and the regulation of the host cytotoxic activity by macrophages. However, no marked differences were observed between PR11- and PR40-infected animals. Heterologous vaccination restrained virus spread and lesions extent in the thymus of PR40-infected animals.


Assuntos
Macrófagos/virologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Timo/virologia , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Pulmão/patologia , Macrófagos/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Receptores de Superfície Celular/genética , Suínos , Timo/imunologia , Carga Viral , Vacinas Virais/uso terapêutico , Virulência
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