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1.
Nat Immunol ; 23(5): 679-691, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35484408

RESUMO

Here we report the identification of human CD66b-CD64dimCD115- neutrophil-committed progenitor cells (NCPs) within the SSCloCD45dimCD34+ and CD34dim/- subsets in the bone marrow. NCPs were either CD45RA+ or CD45RA-, and in vitro experiments showed that CD45RA acquisition was not mandatory for their maturation process. NCPs exclusively generated human CD66b+ neutrophils in both in vitro differentiation and in vivo adoptive transfer experiments. Single-cell RNA-sequencing analysis indicated NCPs fell into four clusters, characterized by different maturation stages and distributed along two differentiation routes. One of the clusters was characterized by an interferon-stimulated gene signature, consistent with the reported expansion of peripheral mature neutrophil subsets that express interferon-stimulated genes in diseased individuals. Finally, comparison of transcriptomic and phenotypic profiles indicated NCPs represented earlier neutrophil precursors than the previously described early neutrophil progenitors (eNePs), proNeus and COVID-19 proNeus. Altogether, our data shed light on the very early phases of neutrophil ontogeny.


Assuntos
Antígenos CD , Medula Óssea , Moléculas de Adesão Celular , Diferenciação Celular , Neutrófilos , Receptor de Fator Estimulador de Colônias de Macrófagos , Receptores de IgG , Células da Medula Óssea , COVID-19 , Proteínas Ligadas por GPI , Humanos , Interferons , Neutrófilos/citologia
2.
Pediatr Blood Cancer ; 70(12): e30671, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37712719

RESUMO

We report a novel case of SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2) mutation successfully treated with hematopoietic stem cell transplantation. The female patient presented delayed cord separation, chronic diarrhea, skin abscesses, skeletal dysmorphisms, and neutropenia with specific granule deficiency. Analysis of the transcriptomic profile of peripheral blood sorted mature and immature SMARCD2 neutrophils showed defective maturation process that associated with altered expression of genes related to specific, azurophilic, and gelatinase granules, such as LTF, CRISP3, PTX3, and CHI3L1. These abnormalities account for the prevalence of immature neutrophils in the peripheral blood, impaired function, and deregulated inflammatory responses.

3.
J Prosthet Dent ; 130(3): 369-375, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34879988

RESUMO

STATEMENT OF PROBLEM: Complete arch implant-supported zirconia prostheses appear to have less plaque accumulation than titanium prostheses, but a comparison of the materials and the possible influence on the adjacent soft tissue is lacking. PURPOSE: The purpose of this clinical study was to compare the plaque accumulation and soft-tissue inflammation of complete arch implant-supported fixed maxillary prostheses fabricated with either a titanium framework or monolithic zirconia. MATERIAL AND METHODS: Twenty participants with a complete arch implant-supported fixed maxillary prosthesis were enrolled in the study. The participants were divided into 2 groups according to the prosthesis material, titanium (Ti) or zirconia (Zir). The prosthesis had to have been in function for at least 6 months, and participants were examined during at least 3 maintenance appointments at 3-month intervals. Clinical information collected in each appointment included standardized photographs to record the Plaque Area Index (PAI) of the intaglio surface of the prosthesis; clinical parameters including modified Plaque Index (mPI), modified Bleeding Index (mBI), implant mobility (MOB), probing depths ≥5 mm (PD), suppuration (SUP), keratinized tissue band ≥2 mm (KT), and an intraoral photograph of the maxillary arch without the prosthesis to evaluate the redness of the soft tissues. RESULTS: MOB was not present at any implant at any time point. SUP could not be analyzed because it was an infrequent finding. Both groups exhibited significant increases in mBI over time. No significant differences were observed for PD between the groups at any time point. Implants in the Ti group had significantly higher KT values than those in the Zir group; levels remained constant over time for both groups. Zirconia prostheses had slightly lower PAI levels than Ti prostheses. The PAI in the Zir group significantly decreased over time (P=.035); in the Ti group, they remained constant (P=.45). Higher PAI levels were correlated with increased levels of erythema; both groups had a significant decrease in erythema values over time (P=.04). CONCLUSIONS: Zirconia complete arch implant-supported fixed maxillary prostheses displayed a significant decrease in plaque accumulation in individuals who had received periodic maintenance and oral hygiene instructions. Ti prostheses had significantly higher plaque levels than zirconia prostheses at all time points, which was not reduced by maintenance and oral hygiene measures. The present study suggests that patients receiving zirconia prostheses respond well to plaque control measures, while plaque control for those with titanium prostheses may be more challenging.


Assuntos
Implantes Dentários , Prótese Maxilofacial , Humanos , Titânio , Zircônio , Prótese Dentária Fixada por Implante
4.
FASEB J ; 34(7): 9269-9284, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32413173

RESUMO

Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan+ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan+ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan+ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan+ -cells, conventional CD1c+ DCs (cDC2) and CD11b+ CD14+ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan+ -monocytes. Data demonstrate that the main trajectory of human slan+ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b+ CD14+ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan+ -monocytes, which is relevant for inflammatory diseases and lymphomas.


Assuntos
Amino Açúcares/metabolismo , Células Dendríticas/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Tonsila Palatina/metabolismo , Tonsilite/genética , Estudos de Casos e Controles , Células Cultivadas , Células Dendríticas/citologia , Perfilação da Expressão Gênica , Humanos , Macrófagos/citologia , Monócitos/citologia , Tonsila Palatina/citologia , Tonsilite/metabolismo , Tonsilite/patologia
5.
Clin Rehabil ; 34(2): 242-251, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31847574

RESUMO

OBJECTIVE: To investigate the effects of adding stretching to a moderate-intensity aerobic exercise programme in women with fibromyalgia. DESIGN: Randomized controlled trial. SUBJECTS: Sixty-four female patients who were diagnosed with fibromyalgia syndrome based on the American College of Rheumatology criteria were recruited (mean age: 54.27 ± 6.94 years). INTERVENTIONS: The control group (n = 32) underwent supervised moderate-intensity cycling (50%-70% of the age-predicted maximum heart rate) three times per week for 12 weeks. The experimental group (n = 32) underwent the same exercise programme plus a stretching programme once per week for 12 weeks. MAIN MEASURES: The main measures of this study were sleep quality assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, the impact of fibromyalgia on quality of life assessed by the Fibromyalgia Impact Questionnaire, and pain perception assessed by the visual analogue scale at baseline, after 4 weeks, and after 12 weeks. RESULTS: The experimental group experienced significant improvements at 4-week measure compared with control group: Pittsburgh Sleep Quality Index (P < 0.001); Epworth Sleepiness Scale (P = 0.002); Fibromyalgia Impact Questionnaire (0.93 ± 7.39, P < 0.001); and visual analogue scale (0.52 ± 0.05, P < 0.001). Also at 12-week measure, experimental group experienced significant improvements compared with control group: Pittsburgh Sleep Quality Index (P < 0.001), Epworth Sleepiness Scale (P < 0.001); Fibromyalgia Impact Questionnaire (1.15 ± 9.11, P < 0.001); and visual analogue scale (0.81 ± 0.62, P < 0.001). CONCLUSION: Adding stretching to a moderate-intensity aerobic exercise programme increased sleep quality, decreased the impact of fibromyalgia on the quality of life, and reduced pain compared with just a moderate-intensity aerobic exercise programme in our sample of women with fibromyalgia.


Assuntos
Exercício Físico , Fibromialgia/reabilitação , Exercícios de Alongamento Muscular , Medição da Dor , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Escala Visual Analógica
6.
Eur J Clin Invest ; 48 Suppl 2: e12952, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29772063

RESUMO

Polymorphonuclear neutrophils are the most numerous leucocytes present in human blood, and function as crucial players in innate immune responses. Neutrophils are indispensable for the defence towards microbes, as they effectively counter them by releasing toxic enzymes, by synthetizing reactive oxygen species and by producing inflammatory mediators. Interestingly, recent findings have highlighted an important role of neutrophils also as promoters of the resolution of inflammation process, indicating that their biological functions go well beyond simple pathogen killing. Consistently, data from the last decades have highlighted that neutrophils may even contribute to the development of adaptive immunity by performing previously unanticipated functions, including the capacity to extend their survival, directly interact with other leucocytes or cell types, and produce and release a variety of cytokines. In this article, we will summarize the main features of, as well as emphasize some important concepts on, the production of cytokines by human neutrophils.


Assuntos
Citocinas/biossíntese , Neutrófilos/metabolismo , Sobrevivência Celular , Humanos , Interleucina-17/metabolismo , Neutrófilos/fisiologia , Biossíntese de Proteínas/fisiologia
7.
Sensors (Basel) ; 17(1)2017 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-28075364

RESUMO

Autonomous mobile nodes in mobile wireless sensor networks (MWSN) allow self-deployment and self-healing. In both cases, the goals are: (i) to achieve adequate coverage; and (ii) to extend network life. In dynamic environments, nodes may use reactive algorithms so that each node locally decides when and where to move. This paper presents a behavior-based deployment and self-healing algorithm based on the social potential fields algorithm. In the proposed algorithm, nodes are attached to low cost robots to autonomously navigate in the coverage area. The proposed algorithm has been tested in environments with and without obstacles. Our study also analyzes the differences between non-hierarchical and hierarchical routing configurations in terms of network life and coverage.

8.
Parasitol Res ; 115(3): 1339-44, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26691858

RESUMO

Phlebotomine sand flies (Diptera, Psychodidae) are vectors of multiple Leishmania species, among which Leishmania infantum stands out as a being frequently pathogenic to humans and dogs in Mediterranean countries. In this study, Sergentomyia minuta sand flies were collected using CDC miniature light traps in different 431 biotopes from Southwest Spain. A total of 114 females were tested for the presence of Leishmania DNA by targeting ITS-1 and cyt-B sequences by PCR. Leishmania DNA was detected in one S. minuta. Characterization of the obtained DNA sequences by phylogenetic analyses revealed close relatedness with Leishmania tarentolae Wenyon, 1921 as well as with both human and canine pathogenic strains of Asian origin (China), previously described as Leishmania sp. To our knowledge, this is the first report of phlebotomine sand flies naturally infected with L. tarentolae-like in Spain. The possible infection of sand flies with novel Leishmania species should be taken into consideration in epidemiological studies of vector species in areas where leishmaniosis is endemic.


Assuntos
DNA de Protozoário/genética , Leishmania/genética , Leishmaniose/parasitologia , Psychodidae/parasitologia , Animais , DNA de Protozoário/isolamento & purificação , Feminino , Humanos , Leishmania/classificação , Leishmania/isolamento & purificação , Leishmaniose/epidemiologia , Filogenia , Reação em Cadeia da Polimerase , Espanha/epidemiologia
9.
Knee Surg Sports Traumatol Arthrosc ; 24(9): 2845-2853, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25649731

RESUMO

PURPOSE: To translate the patellofemoral disorder questionnaire "Kujala Score" into Spanish and to adapt it for Spanish culture . METHODS: International recommendations were followed to translate the "Kujala Score" into Spanish together with a cultural adaptation and validation. We analysed the following parameters: internal consistency, agreement construct validity, test-retest reliability, ceiling and floor effects, and responsiveness. The reproducibility and responsiveness were tested in 72 patients with patellofemoral pain syndrome in a test-retest design with follow-up testing at 7 days. The "Kujala Score" and the VISA-P were administered to 98 patients and 30 patients, respectively, who completed the "Kujala Score" and VISA-P after physiotherapy treatment, which consisted of rest, ice, proprioceptive exercise and manual therapy. RESULTS: The Spanish "Kujala Score" had high internal consistency (Cronbach α = 0.8; if an item was deleted, Cronbach α = 0.77-0.80), excellent reliability and agreement (interclass correlation coefficient = 0.99), and good construct validity that was significantly correlated with the outcome of the Spanish VISA-P (Spearman rho = 0.7; P < 0.001). No ceiling or floor effects was detected for the Spanish "Kujala Score" or the responsiveness of the participants based on 40 patients receiving physical therapy, rest, ice and proprioceptive exercises for 1 month, demonstrating that it is a good determinant of changes in the symptomatology of patients with knee pain. CONCLUSIONS: The Spanish adaptation of the patellofemoral disorder questionnaire "Kujala Score" proved to be valid and sensitive to clinical changes and to be a reliable instrument to assess the severity of pain and disability in patients with patellofemoral disorders. This questionnaire will be useful in clinical practice and research as an appropriate tool to evaluate and record the symptomatology of patients with patellofemoral pain syndrome among Spanish population. LEVEL OF EVIDENCE: Diagnostic study, Level I.


Assuntos
Assistência à Saúde Culturalmente Competente , Síndrome da Dor Patelofemoral/diagnóstico , Índice de Gravidade de Doença , Traduções , Adulto , Avaliação da Deficiência , Feminino , Humanos , Masculino , Medição da Dor , Psicometria , Reprodutibilidade dos Testes , Espanha , Tradução
10.
Biomed Environ Sci ; 29(11): 834-839, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27998391

RESUMO

This study analyze the relation between body composition, physical activity (PA), and sex in Chilean children from rural and urban public educational institutions. The prevalence of obesity (according to BMI) was 30.88% in urban children and 28.93% in rural children. Central obesity presented mainly in the rural girls. Approximately 90% of the participants reported <7 h of PA/week, regardless of residential area. In addition, central fat was strongly associated with rural residence; the children reported lower PA levels, and they presented a higher prevalence of central fat. The results reflect the need to implement programs to improve PA conditions in the child urban-rural population.


Assuntos
Distribuição da Gordura Corporal/estatística & dados numéricos , Exercício Físico , Obesidade/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Criança , Chile/epidemiologia , Feminino , Humanos , Masculino
11.
Sensors (Basel) ; 16(7)2016 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-27399709

RESUMO

In mobile wireless sensor networks (MWSN), nodes are allowed to move autonomously for deployment. This process is meant: (i) to achieve good coverage; and (ii) to distribute the communication load as homogeneously as possible. Rather than optimizing deployment, reactive algorithms are based on a set of rules or behaviors, so nodes can determine when to move. This paper presents an experimental evaluation of both reactive deployment approaches: rule-based and behavior-based ones. Specifically, we compare a backbone dispersion algorithm with a social potential fields algorithm. Most tests are done under simulation for a large number of nodes in environments with and without obstacles. Results are validated using a small robot network in the real world. Our results show that behavior-based deployment tends to provide better coverage and communication balance, especially for a large number of nodes in areas with obstacles.

12.
Artigo em Inglês | MEDLINE | ID: mdl-24370900

RESUMO

The accident with the oil tanker Prestige in November 2002 resulted in a major spill of about 63,000 tons of heavy fuel oil. More than 300,000 people participated in the clean-up activities, which lasted for up to 10 months. Previous studies reported increases in genotoxicity endpoints in individuals exposed to Prestige oil, both at the moment of exposure [DNA breakage, micronuclei (MN), sister chromatid exchange] and two years later (chromosomal aberrations). In this work we carried out for the first time the follow-up of genotoxic effects in subjects exposed to an oil spill seven years after the exposure. The main objective was to determine the possible persistence of genotoxic damage in individuals exposed to Prestige oil seven years after the accident. The exposed group was composed of 54 residents of Galician villages in Spain that were heavily affected by the spill. This group was involved in clean-up labor for at least two months in the period November 2002-September 2003. They were compared with 50 matched controls. Primary DNA damage was evaluated by the comet assay, mutagenicity by the T-cell receptor (TCR) mutation assay, and MN frequency was determined both by the cytokinesis-block test and by flow cytometry. The results obtained showed no significant differences between the exposed and the controls in the comet assay, the TCR mutation assay and the cytokinesis-block MN test. An unexpected and significant decrease was observed in the exposed group for the results of the MN test evaluated by flow cytometry, probably influenced by modifying factors - other than age, sex and smoking - not considered in this study. Our results show no evidence of the persistence of genotoxic damage in individuals exposed to Prestige oil seven years later. Nevertheless, the need to plan biomonitoring studies on people participating in clean-up activities in case a new oil spill occurs should be established.


Assuntos
Acidentes/estatística & dados numéricos , Dano ao DNA , Poluentes Ambientais/intoxicação , Óleos Combustíveis/intoxicação , Exposição Ocupacional/análise , Poluição por Petróleo/estatística & dados numéricos , Adulto , Idoso , Ensaio Cometa , Monitoramento Ambiental , Feminino , Seguimentos , Geografia , Humanos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Troca de Cromátide Irmã/efeitos dos fármacos , Espanha , Fatores de Tempo
14.
J Leukoc Biol ; 115(4): 695-705, 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38114064

RESUMO

The advent of recent cutting-edge technologies has allowed the discovery and characterization of novel progenitors of human neutrophils, including SSCloCD66b+CD15+CD11b-CD49dhiproNeu1s, SSChiCD66b+CD15+CD11b-CD49dintproNeus2s, CD66b+CD15+CD11b+CD49d+CD101-preNeus, and Lin-CD66b+CD117+CD71+eNePs. In this research field, we recently identified CD66b-CD38+CD64dimCD115-, CD34+, and CD34dim/- cells exclusively committed to the neutrophil lineage (which we renamed as CD34+ and CD34dim/- neutrophil-committed progenitors), representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify 4 populations of neutrophil-committed progenitors: CD34+CD45RA-/NCP1s, CD34+CD45RA+/NCP2s, CD34dim/-CD45RA+/NCP3s, and CD34dim/-CD45RA-/NCP4s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors, termed either neutrophil progenitors or "early neutrophil-committed progenitors," would generate immunosuppressive neutrophil-like CXCR1+CD14+CD16- monocytes. Hence, presuming that neutrophil progenitors/"early neutrophil-committed progenitors" correspond to neutrophil-committed progenitors, the selective neutrophil commitment that we attributed to neutrophil-committed progenitors is contradicted by Ikeda and coworkers' article. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by neutrophil-committed progenitors 2 and 4 (selected as representatives of neutrophil-committed progenitors), we categorically exclude that neutrophil-committed progenitors generate neutrophil-like CXCR1+CD14+CD16- monocytes. Rather, we provide substantial evidence indicating that the cells generated by neutrophil progenitors/"early neutrophil-committed progenitors" are neutrophilic cells at a different stage of maturation, displaying moderate levels of CD14, instead of neutrophil-like CXCR1+CD14+CD16- monocytes, as pointed by Ikeda and coworkers. Hence, the conclusion that neutrophil progenitors/"early neutrophil-committed progenitors" aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation.


Assuntos
Monócitos , Neutrófilos , Humanos , Neutrófilos/metabolismo , Monócitos/metabolismo , Antígenos CD34/metabolismo , Citometria de Fluxo
15.
Cell Rep Med ; 5(2): 101380, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38242120

RESUMO

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.


Assuntos
Células Supressoras Mieloides , Neoplasias , Humanos , Neutrófilos , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/metabolismo , Neoplasias/patologia , Antígeno CD52/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo
16.
Front Immunol ; 14: 1287656, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965335

RESUMO

Introduction: Peripheral monocytes in humans are conventionally divided into classical (CL, CD14++CD16-), intermediate (INT, CD14++CD16+) and non-classical (NC, CD14dim/-CD16++) cells, based on their expression levels of CD14 and CD16. A major fraction of the NC-monocytes has been shown to express the 6-sulfo LacNAc (slan) antigen, but whether these slan+/NC-monocytes represent the prototypical non-classical monocytes or whether they are simply a sub-fraction with identical features as the remainder of NC monocytes is still unclear. Methods: We analyzed transcriptome (by bulk and single cell RNA-seq), proteome, cell surface markers and production of discrete cytokines by peripheral slan+/NC- and slan-/NC-monocytes, in comparison to total NC-, CL- and INT- monocytes. Results: By bulk RNA-seq and proteomic analysis, we found that slan+/NC-monocytes express higher levels of genes and proteins specific of NC-monocytes than slan-/NC-monocytes do. Unsupervised clustering of scRNA-seq data generated one cluster of NC- and one of INT-monocytes, where all slan+/NC-monocytes were allocated to the NC-monocyte cluster, while slan-/NC-monocytes were found, in part (13.4%), within the INT-monocyte cluster. In addition, total NC- and slan-/NC-monocytes, but not slan+/NC-monocytes, were found by both bulk RNA-seq and scRNA-seq to contain a small percentage of natural killer cells. Conclusion: In addition to comparatively characterize total NC-, slan-/NC- and slan+/NC-monocyte transcriptomes and proteomes, our data prove that slan+/NC-, but not slan-/NC-, monocytes are more representative of prototypical NC-monocytes.


Assuntos
Monócitos , Proteômica , Humanos , Leucócitos Mononucleares
17.
Cancer Immunol Res ; 11(9): 1280-1295, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37343073

RESUMO

Patterns of receptors for chemotactic factors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represents a selective pathway for the homing of natural killer (NK) cells to the lung. C-C motif chemokine receptor-like 2 (CCRL2) is a nonsignaling seven-transmembrane domain receptor able to control lung tumor growth. CCRL2 constitutive or conditional endothelial cell targeted ablation, or deletion of its ligand chemerin, were found to promote tumor progression in a Kras/p53Flox lung cancer cell model. This phenotype was dependent on the reduced recruitment of CD27- CD11b+ mature NK cells. Other chemotactic receptors identified in lung-infiltrating NK cells by single-cell RNA sequencing (scRNA-seq), such as Cxcr3, Cx3cr1, and S1pr5, were found to be dispensable in the regulation of NK-cell infiltration of the lung and lung tumor growth. scRNA-seq identified CCRL2 as the hallmark of general alveolar lung capillary endothelial cells. CCRL2 expression was epigenetically regulated in lung endothelium and it was upregulated by the demethylating agent 5-aza-2'-deoxycytidine (5-Aza). In vivo administration of low doses of 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells, and reduced lung tumor growth. These results identify CCRL2 as an NK-cell lung homing molecule that has the potential to be exploited to promote NK cell-mediated lung immune surveillance.


Assuntos
Neoplasias Pulmonares , Receptores CCR , Humanos , Receptores CCR/genética , Células Endoteliais , Pulmão , Células Matadoras Naturais/metabolismo
18.
Neurobiol Dis ; 47(1): 135-43, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22504536

RESUMO

The identification of mutations in genes encoding proteins of the synaptic neurexin-neuroligin pathway in different neurodevelopmental disorders, including autism and mental retardation, has suggested the presence of a shared underlying mechanism. A few mutations have been described so far and for most of them the biological consequences are unknown. To further explore the role of the NRXN1ß gene in neurodevelopmental disorders, we have sequenced the coding exons of the gene in 86 cases with autism and mental retardation and 200 controls and performed expression analysis of DNA variants identified in patients. We report the identification of four novel independent mutations that affect nearby positions in two regions of the gene/protein: i) sequences important for protein translation initiation, c.-3G>T within the Kozak sequence, and c.3G>T (p.Met1), at the initiation codon; and ii) the juxtamembrane region of the extracellular domain, p.Arg375Gln and p.Gly378Ser. These mutations cosegregate with different psychiatric disorders other than autism and mental retardation, such as psychosis and attention-deficit/hyperactivity disorder. We provide experimental evidence for the use of an alternative translation initiation codon for c.-3G>T and p.Met1 mutations and reduced synaptic levels of neurexin-1ß protein resulting from p.Met1 and p.Arg375Gln. The data reported here support a role for synaptic defects of neurexin-1ß in neurodevelopmental disorders.


Assuntos
Transtorno Autístico/genética , Deficiência Intelectual/genética , Transtornos Mentais/genética , Mutação , Proteínas do Tecido Nervoso/genética , Sinapses/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo
19.
J Adv Nurs ; 68(4): 758-66, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22077914

RESUMO

AIM: The aim of this study was to assess the efficacy of continuous low-pressure suction drainage compared with closed high-pressure suction following total knee arthroplasty. BACKGROUND: Closed wound drainage systems are used in surgical interventions to reduce the incidence of haematomas, promote wound healing and reduce infections. However, evidence shows that using a closed wound drainage system can increase transfusion requirements. DATA SOURCES: A randomized, double-blind and parallel controlled trial was performed. Adult knee replacement patients recruited between May 2006 and March 2007 were assigned to receive low-pressure suction of 50 mmHg (experimental drainage) or high-pressure suction of 700 mmHg (comparator drainage). METHODS: The primary outcome was total blood loss after surgery. Secondary outcomes were incidence of transfusion, complications and mortality. Statistical analysis was based on an intention-to-treat approach. Linear regression was performed to account for factors that could influence blood loss. RESULTS: A total of 169 patients were included. Mean age was 73 (±6) years, 128 women and 41 men. A total of 84 patients were randomized to the experimental drainage and 85 to the comparator drainage. Analysis showed a total postoperative blood loss of 541·8 mL in the experimental group and 524·4 mL in the comparator group (P = 0·734). The only factor that showed an association with blood loss was the length of surgery. Linear regression did not show differences between the groups. CONCLUSION: Continuous low-pressure suction of 50 mmHg is not more effective than the higher aspiration pressure system to diminish the blood loss in total knee arthroplasty. The results do not support any change in current nursing practice relating to the use of this drain system.


Assuntos
Artroplastia do Joelho/métodos , Hematoma/prevenção & controle , Hemorragia Pós-Operatória/prevenção & controle , Sucção/métodos , Idoso , Artroplastia do Joelho/reabilitação , Transfusão de Sangue/estatística & dados numéricos , Método Duplo-Cego , Drenagem , Feminino , Hematoma/epidemiologia , Humanos , Análise de Intenção de Tratamento , Modelos Lineares , Masculino , Enfermagem Ortopédica/métodos , Cuidados Pós-Operatórios , Pressão , Resultado do Tratamento , Cicatrização
20.
Invest Ophthalmol Vis Sci ; 63(12): 26, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36394846

RESUMO

Purpose: The stereoscopic anisotropy is one of the most intriguing phenomena of stereoscopic vision. It shows that the disparity thresholds to detect three-dimensional sinusoidal horizontal corrugations are much lower than for vertical corrugations for spatial frequencies lower than 1 cycles/deg. A recent study has shown that the anisotropy increases during childhood and that visual experience probably plays an important role in its development (Serrano-Pedraza et al., 2016). Here we want to determine the impact that the visual experience has throughout life in the stereoscopic anisotropy. Methods: We performed two experiments testing two age groups of 35 participants each: the young group aged 18 to 45 years and the old group aged 62 to 90 years. We measured disparity thresholds for three-dimensional sinusoidal corrugations of 0.1 cyc/deg, with either vertical or horizontal orientation. Detection thresholds were obtained using Bayesian adaptive staircases. For each participant we computed the anisotropy index by subtracting the thresholds in logarithmic units of the vertical minus the horizontal corrugation. Results: The analyses show that stereo thresholds for vertical corrugations are similar for both groups, however, for horizontal corrugations the thresholds are much lower for the young group. Therefore, the anisotropy was much stronger in the young group (mean, 0.67 ± 0.46) than for the old group (mean, 0.24 ± 0.3). Pearson correlation between the anisotropy index and age shows a negative and significant correlation (r = -0.49; P = 1.83 × 10-5; N = 70), that is, as age advances, the anisotropy decreases. Conclusions: Thus, visual experience plays an important role in the development of stereo vision. Although disparity thresholds for horizontal corrugations in the older group are higher, surprisingly, disparity thresholds for vertical corrugations remain stable and do not change. Therefore, the stereoscopic anisotropy decreases with aging.


Assuntos
Percepção de Profundidade , Disparidade Visual , Humanos , Idoso , Anisotropia , Teorema de Bayes , Limiar Sensorial
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