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The domestication process of the common bean gave rise to six different races which come from the two ancestral genetic pools, the Mesoamerican (Durango, Jalisco, and Mesoamerica races) and the Andean (New Granada, Peru, and Chile races). In this study, a collection of 281 common bean landraces from Chile was analyzed using a 12K-SNP microarray. Additionally, 401 accessions representing the rest of the five common bean races were analyzed. A total of 2543 SNPs allowed us to differentiate a genetic group of 165 accessions that corresponds to the race Chile, 90 of which were classified as pure accessions, such as the bean types 'Tórtola', 'Sapito', 'Coscorrón', and 'Frutilla'. Our genetic analysis indicates that the race Chile has a close relationship with accessions from Argentina, suggesting that nomadic ancestral peoples introduced the bean seed to Chile. Previous archaeological and genetic studies support this hypothesis. Additionally, the low genetic diversity (π = 0.053; uHe = 0.53) and the negative value of Tajima' D (D = -1.371) indicate that the race Chile suffered a bottleneck and a selective sweep after its introduction, supporting the hypothesis that a small group of Argentine bean genotypes led to the race Chile. A total of 235 genes were identified within haplotype blocks detected exclusively in the race Chile, most of them involved in signal transduction, supporting the hypothesis that intracellular signaling pathways play a fundamental role in the adaptation of organisms to changes in the environment. To date, our findings are the most complete investigation associated with the origin of the race Chile of common bean.
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Phaseolus , Phaseolus/genética , Chile , Argentina , Domesticação , Pool GênicoRESUMO
Common bean (Phaseolus vulgaris L.) is the primary grain legume cultivated worldwide for direct human consumption due to the high nutritional value of its seeds and pods. The high protein content of common beans highlights it as the most promising source of plant-based protein for the food industry. Additionally, landraces of common bean have great variability in nutritional traits, which is necessary to increase the nutritional quality of elite varieties. Therefore, the main objective of this study was to nutritionally characterize 23 Chilean landraces and 5 commercial varieties of common bean to identify genotypes with high nutritional value that are promising for the food industry and for genetic improvement programs. The landrace Phv23 ('Palo') was the most outstanding with high concentrations of minerals such as P (7.53 g/kg), K (19.8 g/kg), Mg (2.43 g/kg), Zn (52.67 mg/kg), and Cu (13.67 mg/kg); essential amino acids (364.8 mg/g protein); and total proteins (30.35 g/100 g seed). Additionally, the landraces Phv9 ('Cimarrón'), Phv17 ('Juanita'), Phv3 ('Araucano'), Phv8 ('Cabrita/Señorita'), and Phv4 ('Arroz') had a high protein content. The landrace Phv24 ('Peumo') stood out for its phenolic compounds (TPC = 218.1 mg GA/100 g seed) and antioxidant activity (ORAC = 22,167.9 µmol eq trolox/100 g extract), but it has moderate to low mineral and protein concentrations. In general, the concentration of nutritional compounds in some Chilean landraces was significantly different from the commercial varieties, highlighting their high nutritional value and their potential use for the food industry and for genetic improvement purposes.
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BACKGROUND AND OBJECTIVE: There is no clear understanding of molecular events occurring in the periodontal microenvironment during clinical disease progression. Our aim was to explore qualitative and quantitative differences in gingival crevicular fluid (GCF) protein profiles from patients diagnosed with periodontitis between non-progressive and progressive periodontal sites. METHODS: Five systemically healthy patients diagnosed with periodontitis were monitored weekly in their progression of the disease and GCF samples from 10 candidate sites were obtained. Two groups of five sites, matched from an equal number of teeth, were selected from the five patients: Progression (PG) and Non-Progression (NP). Global protein identification was performed with high-throughput proteomic approaches and label-free analysis determined their relative abundances. Proteins were identified by Proteome Discoverer v2.4 and searched against human SwissProt protein databases. Enrichment bioinformatic analyses were performed in STRING-DB and ShinyGO environment. RESULTS: 1504 and 1500 proteins were identified in NP and PG respectively. Forty-eight proteins were exclusively identified in PG, while 52 were identified in NP. Moreover, 35 proteins were more abundant in PG and 29 proteins in NP (twofold change, p < .05). The NP group was mainly represented by proteins from "response to biotic stimuli and other organisms," "processes of cell death regulation," "peptidase regulation," "protein ubiquitination," and "ribosomal activity" GO categories. The most represented GO categories of the PG group were "assembly of multiprotein complexes," "catabolic processes," "lipid metabolism," and "binding to hemoglobin and haptoglobin." CONCLUSIONS: There are quantitative and qualitative differences in the proteome of GCF from periodontal sites according to the status of clinical progression of periodontitis. Progressive periodontitis sites are characterized by a protein profile associated with catabolic processes, immune response, and response to cellular stress, while stable periodontitis sites show a protein profile mainly related to wound repair and healing processes, cell death regulation, and chaperone-mediated autophagy. Understanding the etiopathogenic role of these profiles in progressive periodontitis may help to develop new diagnostic and therapeutic approaches.
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Periodontite , Proteoma , Humanos , Líquido do Sulco Gengival/química , Proteômica , Periodontite/metabolismo , Progressão da DoençaRESUMO
In cancer, activation of the IRE1/XBP1s axis of the unfolded protein response (UPR) promotes immunosuppression and tumor growth, by acting in cancer cells and tumor infiltrating immune cells. However, the role of IRE1/XBP1s in dendritic cells (DCs) in tumors, particularly in conventional type 1 DCs (cDC1s) which are cellular targets in immunotherapy, has not been fully elucidated. Here, we studied the role of IRE1/XBP1s in subcutaneous B16/B78 melanoma and MC38 tumors by generating loss-of-function models of IRE1 and/or XBP1s in DCs or in cDC1s. Data show that concomitant deletion of the RNase domain of IRE1 and XBP1s in DCs and cDC1s does not influence the kinetics of B16/B78 and MC38 tumor growth or the effector profile of tumor infiltrating T cells. A modest effect is observed in mice bearing single deletion of XBP1s in DCs, which showed slight acceleration of melanoma tumor growth and dysfunctional T cell responses, however, this effect was not recapitulated in animals lacking XBP1 only in cDC1s. Thus, evidence presented here argues against a general pro-tumorigenic role of the IRE1/XBP1s pathway in tumor associated DC subsets.
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Melanoma Experimental , Ribonucleases , Camundongos , Animais , Ribonucleases/metabolismo , Endorribonucleases/genética , Endorribonucleases/metabolismo , Imunidade Adaptativa , Ribonuclease Pancreático/metabolismo , Melanoma Experimental/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Células DendríticasRESUMO
This article describes and analyzes various aspects related to the neurobiology of disorganized attachment (DA), which is associated with personality, eating, affective, dissociative, and addictive disorders. We included primary studies in humans, published in PubMed from 2000 to 2022. Eight genetic and one epigenetic study were considered. Three molecular studies describe possible roles of oxytocin and cortisol, seven neurophysiological studies investigated functional correlates, and five morphological studies describe anatomical changes. Findings in candidate genes involved in dopaminergic, serotonergic, and oxytonergic systems have not been able to be replicated in large-scale human studies. Alterations in the functioning of cortisol and oxytocin are preliminary. Neurophysiological studies show changes in subcortical structures (mainly in the hippocampus) and occipital, temporal, parietal, and insular cortices. Since there is a lack of robust evidence on the neurobiology of DA in humans, the possible inferences of these studies are preliminary, which restricts their translation to clinical parameters.
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Los riesgos teratogénicos ocasionados por la exposición intrauterina a fármacos antiepilépticos (FAE) son conocidos, por lo que su prescripción se mantiene bajo estricto control. Describir los efectos adversos fetales de la exposición a FAE durante la gestación, reportados en la literatura durante el período 2016-2022. Revisión sistematizada de estudios que reportaron los efectos adversos fetales inducidos por la exposición a FAE en mujeres embarazadas en tratamiento por diagnósticos neurológicos, principalmente de epilepsia. La búsqueda se realizó en PubMed, Cochrane, Web of Science, SCOPUS, Biblioteca Virtual en Salud, Lilacs y SciELO. Se identificaron 37 artículos distribuidos en 13 países de Asia, Europa, América del Norte y Oceanía. Se observaron resultados perinatales adversos, tanto físicos como cognitivos, en la mayoría de los estudios. Los fármacos identificados como los más utilizados en los últimos años fueron valproato, topiramato, carbamazepina, lamotrigina y levetiracetam. Los FAE tienen potencial teratogénico en distintos grados de riesgo, provocando anomalías congénitas o efectos adversos en múltiples sistemas del cuerpo humano, siendo los sistemas nervioso, circulatorio y osteomuscular los más afectados.
The teratogenic risks caused by intrauterine exposure to antiepileptic drugs (AED) are known, so their prescription is kept under strict control. To describe the fetal adverse effects AED exposure during gestation, reported in the literature during the period 2016-2022. Systematized review of studies that reported fetal adverse effects induced for the exposure to AED in pregnant women in treatment for neurological diagnoses, mainly epilepsy. The search was carried out in PubMed, Cochrane, Web of Science, SCOPUS, Virtual Health Library, Lilacs and SciELO. 37 articles distributed in thirteen countries in Asia, Europe, North America and Oceania were identified. Adverse perinatal outcomes, both physical and cognitive, were observed in most studies. The most common drugs identified were valproate, topiramate, carbamazepine, lamotrigine and levetiracetam. AED have teratogenic potential in different degrees of risk, causing congenital anomalies or adverse effects in multiple systems of the human body, being the nervous, circulatory and musculoskeletal systems the most affected.
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Humanos , Feminino , Gravidez , Complicações na Gravidez/induzido quimicamente , Epilepsia/induzido quimicamente , Doenças Fetais/induzido quimicamente , Anticonvulsivantes/efeitos adversos , Teratogênicos , Anormalidades Induzidas por Medicamentos , Recém-Nascido , Doenças do Recém-NascidoRESUMO
Food contamination with microorganisms is responsible for food spoilage, deterioration and change of organoleptic properties of foods. Besides, the growth of pathogenic microorganisms can provoke serious health problems if food is consumed. Innovative packaging, such as active packaging, is increasing rapidly in the food industry, especially in applying antimicrobials into delivery systems, such as sachets. Chile is a relevant hotspot for biodiversity conservation and a source of unique bio-resources with antimicrobial potential. In this review, fifteen native plants with antimicrobial properties are described. Their antimicrobial effects include an effect against human pathogens. Considering the emergence of antimicrobial resistance, searching for new antimicrobials to design new strategies for food pathogen control is necessary. Chilean flora is a promising source of antimicrobials to be used in active packaging. However, further studies are required to advance from laboratory tests of their antimicrobial effects to their possible effects and uses in active films.
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The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.
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COVID-19/imunologia , Eosinófilos/imunologia , Plasmócitos/imunologia , SARS-CoV-2/fisiologia , Células Th1/imunologia , Idoso , Anticorpos Antivirais/sangue , Convalescença , Progressão da Doença , Feminino , Humanos , Imunidade Celular , Imunoglobulina G/sangue , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Resumen Introducción Este texto presenta la experiencia acumulada durante 10 años en las Jornadas de Terapia Ocupacional del Bio Bio en Chile, actividad de extensión académica y recreativa en la cual se tratan temas relevantes para la formación de terapeutas ocupacionales. Objetivo Analizar los principales aprendizajes y contribuciones a la formación profesional de las metodologías de enseñanza que se exponen en estas Jornadas, a través de la opinión de los estudiantes que han participado como asistentes. Método se desarrolla una sistematización, ya que esta metodología permite la reflexión crítica a partir de la experiencia vivida. La información se produce a través de entrevistas a 12 estudiantes. Se realiza análisis del contenido de temas predefinidos, que corresponden a pensamiento crítico, herramientas para la intervención y valores compartidos. Resultados El grupo de estudiantes valoran las metodologías de carácter práctico, participativas y dialogantes que permitan compartir opiniones y experiencias. Las herramientas que se adquieren corresponden a habilidades relacionales que facilitan el trato y manejo terapéutico. Los valores compartidos que los estudiantes identifican se encuentran presentes en las Jornadas incluyen la solidaridad, el respeto a la diversidad y la empatía. Conclusiones Las actividades de extensión académica enriquecen la formación profesional porque acerca a los estudiantes con la realidad social, fortalecen la identidad disciplinar y promoverían su formación ciudadana. Los desafíos de las actividades de extensión son generar transformaciones en las vidas cotidianas de los/as sujetos/as de intervención, y que éstos/as puedan participar activamente en los ajustes curriculares de los planes de estudios.
Resumo Introdução Este texto apresenta a experiência acumulada ao longo de 10 anos na Conferência de Bio Bio Terapia Ocupacional no Chile, uma atividade de extensão acadêmica e recreativa na qual são discutidos temas relevantes para a formação de terapeutas ocupacionais. Objetivo Analisar as principais aprendizagens e contribuições das metodologias de ensino expostas nestes Congressos para a formação profissional, através da opinião dos alunos que participaram como assistentes. Método desenvolveu-se uma sistematização, uma vez que esta metodologia permite a reflexão crítica a partir da experiência vivida. As informações foram produzidas por meio de entrevistas com 12 alunos e efetuada análise de conteúdo de temas predefinidos, que corresponderam ao pensamento crítico, ferramentas de intervenção e valores partilhados. Resultados O grupo de alunos valoriza as metodologias de carácter prático, participativo e dialógico que lhes permitem partilhar opiniões e experiências. As ferramentas adquiridas correspondem a habilidades relacionais que facilitam o tratamento e o manejo terapêutico. Os valores partilhados que os alunos identificaram presentes na Conferência incluem solidariedade, respeito pela diversidade e empatia. Conclusões As atividades de extensão acadêmica enriquecem a formação profissional, pois aproxima os alunos da realidade social, fortalece a identidade disciplinar e promove sua formação cidadã. Os desafios das atividades de extensão são gerar transformações no cotidiano dos sujeitos da intervenção e que eles possam participar ativamente das adequações curriculares dos planos de estudos.
Abstract Introduction This text shows the experience accumulated over 10 years in the Bio Bio Occupational Therapy Conference in Chile, an academic extension and recreational activity in which relevant topics for the training of occupational therapists are discussed. Objective To analyze the main learning and contributions to the professional training of the teaching methodologies that are exposed in this conference, through the opinion of the students who have participated as assistants. Method systematization is developed since this methodology allows critical reflection from the lived experience. The information is produced through interviews with 12 students. Analysis of the content of predefined topics is carried out, which correspond to critical thinking, tools for intervention, and shared values. Results The group of students values the methodologies of a practical, participatory, and dialogue nature that allow them to share opinions and experiences. The tools that are acquired correspond to relational skills that facilitate treatment and therapeutic management. The shared values that the students identify are present in the conference, including solidarity, respect for diversity, and empathy. Conclusions The academic extension activities enrich professional training because it brings students closer to social reality, strengthens disciplinary identity and promotes their citizenship training. The challenges of extension activities are to generate transformations in the daily lives of the intervention subjects, and that they can actively participate in the curricular adjustments of the study plans.
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BACKGROUND: Immune checkpoint blocker (ICB) therapy has shown survival benefits for some patients with cancer. Nevertheless, many individuals remain refractory or acquire resistance to treatment, motivating the exploration of complementary immunotherapies. Accordingly, cancer vaccines offer an attractive alternative. Optimal delivery of multiple tumor-associated antigens combined with potent adjuvants seems to be crucial for vaccine effectiveness. METHODS: Here, a prototype for a generic melanoma vaccine, named TRIMELVax, was tested using B16F10 mouse melanoma model. This vaccine is made of heat shock-treated tumor cell lysates combined with the Concholepas concholepas hemocyanin as adjuvant. RESULTS: While B16F10 lysate provides appropriate melanoma-associated antigens, both a generic human melanoma cell lysate and hemocyanin adjuvant contributes with danger signals promoting conventional dendritic type 1 cells (cDC1), activation, phagocytosis and effective antigen cross-presentation. TRIMELVax inhibited tumor growth and increased mice survival, inducing cellular and humoral immune responses. Furthermore, this vaccine generated an increased frequency of intratumor cDC1s but not conventional type 2 dendritic cells (cDC2s). Augmented infiltration of CD3+, CD4+ and CD8+ T cells was also observed, compared with anti-programmed cell death protein 1 (PD-1) monotherapy, while TRIMELVax/anti-PD-1 combination generated higher tumor infiltration of CD4+ T cells. Moreover, TRIMELVax promoted an augmented proportion of PD-1lo CD8+ T cells in tumors, a phenotype associated with prototypic effector cells required for tumor growth control, preventing dysfunctional T-cell accumulation. CONCLUSIONS: The therapeutic vaccine TRIMELVax efficiently controls the weakly immunogenic and aggressive B16F10 melanoma tumor growth, prolonging tumor-bearing mice survival even in the absence of ICB. The strong immunogenicity shown by TRIMELVax encourages clinical studies in patients with melanoma.
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Vacinas Anticâncer/imunologia , Imunoterapia/métodos , Melanoma Experimental/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NODRESUMO
We report the mitochondrial genome sequences of two migratory shorebirds, the Hudsonian godwit (Limosa haemastica) and the Red knot (Calidris canutus) obtained through shotgun sequencing. The mitogenome is of 16.445 bp for the godwit and 15.609 bp for the knot containing thirteen protein-coding genes, two rRNAs, twenty-two tRNAs, and a control region. The ATP8 and tRNA-Glu were not found in the knot. Bayesian phylogenetic analysis supported the position of both species in the clade of the Scolopacidae Family.
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Ovarian epithelial carcinoma (OEC) is the most frequent ovarian tumor, characterized by a high mortality in advanced stages where conventional therapies are not effective. Based on the role of the immune system in the progression of this disease, immunotherapy using checkpoint blockade has been considered as a therapeutic alternative. Nevertheless, its results do not match up to the positive results in entities like melanoma and other malignancies, suggesting the need to find other therapies to be used alone or in combination. Dendritic cell- (DC-) based vaccines have shown promising results in several types of cancer, such as melanoma, prostate, and lung cancers, due to the essential role played by DCs in the activation of specific T cells, thus using other ways of activating the immune response than immune checkpoint blockade. During the last decade, we have used DC-based vaccines loaded with an allogeneic heat shock-conditioned melanoma cell lysate in the treatment of advanced stage patients in a series of clinical trials. In these studies, 60% of treated patients showed immunological responses which correlated positively with improved survival. Considering the relevance of ovarian cancer and the promising results of our DC-based vaccine, we show here that heat shock-conditioned cell lysates derived from ovarian epithelial carcinoma cell lines have the potential to induce the phenotypic and functional maturation of human DC, which in turn, is able to induce an efficient CD4+ and CD8+ T cell-mediated immune responses against ovarian cancer cell lines in vitro. In summary, OEC heat shock-conditioned cell lysate-loaded DCs may be considered for future combined immunotherapy approaches against ovarian tumors.
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Carcinoma Epitelial do Ovário/imunologia , Células Dendríticas/imunologia , Resposta ao Choque Térmico , Neoplasias Ovarianas/imunologia , Linfócitos T/imunologia , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Feminino , Resposta ao Choque Térmico/genética , Resposta ao Choque Térmico/imunologia , Humanos , Imunoterapia , Interferon gama/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia , Linfócitos T/metabolismoRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by increased autoantibody production that leads to multiple tissue injuries. Dendritic cells (DCs) are important orchestrators of immune responses and key components in fine-tuning the balance between tolerance and immunity. However, their role in autoimmune disorders such as SLE remains uncertain. We analyzed the contribution of DCs in triggering SLE by adoptively transferring splenic DCs from aged autoimmune [NZB×NZW]F1 (BWF1) mice to young healthy BWF1 mice. We observed that the transfer of DCs from autoimmune mice to pre-autoimmune mice induced high autoantibody titers in the serum of recipient mice. Moreover, autoimmune DCs from aged BWF1 mice were crucial for the expansion and differentiation of plasmablasts and CD5+ B cells or B1-like cells in the peripheral blood, and spleen of recipient BWF1 mice, a phenomenon that is observed in autoimmune BWF1 mice. On the other hand, DCs from aged BWF1 mice participated in the expansion and differentiation of DCs and IFN-γ-producing T cells. These results reveal that DCs from autoimmune BWF1 mice exhibit functional and phenotypic characteristics that allow them to trigger B cell hyperactivation, as well as DC and T cell expansion and differentiation, thereby promoting an exacerbated humoral response in lupus-prone mice.
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Envelhecimento/fisiologia , Linfócitos B/imunologia , Células Dendríticas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Baço/patologia , Linfócitos T/imunologia , Transferência Adotiva , Animais , Autoanticorpos/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Células Dendríticas/transplante , Humanos , Imunidade Humoral , Interferon gama/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos NZBRESUMO
The ability of dendritic cells (DCs) to trigger tolerance or immunity is dictated by the context in which an antigen is encountered. A large body of evidence indicates that antigen presentation by steady-state DCs induces peripheral tolerance through mechanisms such as the secretion of soluble factors, the clonal deletion of autoreactive T cells, and feedback control of regulatory T cells. Moreover, recent understandings on the function of DC lineages and the advent of murine models of DC depletion have highlighted the contribution of DCs to lymphocyte tolerance. Importantly, these findings are now being applied to human research in the contexts of autoimmune diseases, allergies, and transplant rejection. Indeed, DC-based immunotherapy research has made important progress in the area of human health, particularly in regards to cancer. A better understanding of several DC-related aspects including the features of DC lineages, milieu composition, specific expression of surface molecules, the control of signaling responses, and the identification of competent stimuli able to trigger and sustain a tolerogenic outcome will contribute to the success of DC-based immunotherapy in the area of lymphocyte tolerance. This review will discuss the latest advances in the biology of DC subtypes related to the induction of regulatory T cells, in addition to presenting current ex vivo protocols for tolerogenic DC production. Particular attention will be given to the molecules and signals relevant for achieving an adequate tolerogenic response for the treatment of human pathologies.
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CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-ß. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-ß, RA, and IL-2 resulted in a striking enrichment of Foxp3(+) T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive capacity. Finally, RA-iTreg cells showed alloantigen-specific immunosuppressive capacity in a skin allograft model in immunodeficient mice. Altogether, these data indicate that functional and stable allogeneic-specific Treg cells may be generated using TGF-ß, RA, and IL-2. Thus, RA-iTreg cells may have a potential use in the development of more effective cellular therapies in clinical transplantation.
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Rejeição de Enxerto/prevenção & controle , Transplante de Pele , Pele/imunologia , Linfócitos T Reguladores/imunologia , Tretinoína/farmacologia , Transferência Adotiva , Aloenxertos , Animais , Técnicas de Cocultura , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Expressão Gênica , Sobrevivência de Enxerto , Interleucina-2/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/administração & dosagem , Pele/citologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/transplante , Fator de Crescimento Transformador beta/farmacologiaRESUMO
El objetivo fue describir las diferentes presiones intraorales que se presentan en los espacios interoclusal vestibular (EIO) y subpalatino (ESP) bajo distintas condiciones biofuncionales en pacientes adultos desdentados totales maxilares. Fueron seleccionados 15 pacientes en la Clínica Odontológica Docente Asistencial, Universidad de la Frontera (Temuco, Chile). La medición de presiones intraorales se realizó con un dispositivo digital GMH 3156, mediante los métodos de cánulas (control) y escudo oral. Se realizó una medición de calibración por 15 minutos y luego cuatro mediciones funcionales: B1 (condición abierta; 025 s); B2 (condición semiabierta; 3585 s); B3 (condición cerrada; 95145 s) y B4 (presión bajo deglución; 150165 s). Con el escudo oral, la Fase B1 mostró en el EIO una presión constante entre 04 mBar y el ESP entre 1 y 3 mBar. En la Fase B2, el EIO llegó a 10 mBar y el ESP entre 0 y 1 mBar. La Fase B3 mostró en el EIO oscilaciones entre 0 y 20 mBar, y en el ESP un aumento hasta 20 mBar. En la Fase B4, el EIO presentó un peak de 40 mBar, mientras que el ESP un peak desde 20 hasta 140 mBar. La formación de dos compartimientos cerrados con presión intraoral negativa también ocurre en pacientes edéntulos, donde el ESP muestra cambios de presión negativa mayores al EIO. Patrones regulares de presión intraoral en espacios biofuncionales se observan en más del 50% de los casos.
The aim was to describe the different intraoral pressures that occur in the vestibular interocclusal space (IOS) and subpalatal space (SPS) under different oral functions in adult patients with maxillary edentulism. A descriptive and cross-sectional study was conducted. We selected 15 patients at the Dental Clinic of the Dentistry Faculty (CODA), Universidad de la Frontera (Temuco, Chile). Intraoral pressure measurement was performed using a digital manometer GMH 3156, by methods of cannulas (control) and oral shield. A calibration measurement was made for 15 minutes; then four functional measurements were performed: B1 (open-mouth condition, 0-25 s), B2 (semi-open compartment condition, 35-85 s), B3 (closed compartments condition; 95-145 s) and B4 (swallowing, 150-165 s). With the oral shield, the B1 phase in the IOS showed a constant pressure between 0-4 mBar and SPS between 1 and 3 mBar. In B2 phase, the IOS reached 10 mBar and SPS between 0 and 1 mBar . Phase B3 OIS oscillations showed between 0 and 20 mBar, and the SPS increased to 20 mbar. In B4 phase, the IOS showed a peak of 40 mbar, while the SPS showed a peak from 20 to 140 mbar. The formation of two closed compartments with negative intra-oral pressure also occurs in edentulous patients, where the SPS shows greater negative pressure changes than IOS. Regular patterns of intra-oral pressure in biofunctional compartments were observed in over 50% of cases.