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1.
Nat Commun ; 15(1): 5016, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38876998

RESUMEN

Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.


Asunto(s)
Comunicación Celular , Queratinocitos , Periodontitis , Análisis de la Célula Individual , Humanos , Queratinocitos/metabolismo , Queratinocitos/inmunología , Periodontitis/microbiología , Periodontitis/metabolismo , Periodontitis/inmunología , Periodontitis/patología , Citocinas/metabolismo , Periodoncio/microbiología , Periodoncio/metabolismo , Periodoncio/patología , Inmunidad Innata , Hibridación Fluorescente in Situ , Masculino , Metagenómica/métodos , Bacterias/metabolismo , Bacterias/genética , Femenino , Adulto , Inmunidad Adaptativa
2.
Nat Commun ; 14(1): 5382, 2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37666819

RESUMEN

Regulatory T cells (Treg) are CD4+ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4+ T cells, Treg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1+ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1- subpopulation. Lrig1-deficiency impairs the suppressive function of Treg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4+Lrig1+ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.


Asunto(s)
Autoinmunidad , Colitis , Animales , Ratones , Linfocitos T CD4-Positivos , Linfocitos T Reguladores , Traslado Adoptivo , Factores de Transcripción , Factores de Transcripción Forkhead/genética
3.
Plast Reconstr Surg ; 151(3): 420e-431e, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36730531

RESUMEN

SUMMARY: Over the past 30 years, there has been a dramatic increase in the use of autologous fat grafting for soft-tissue augmentation and to improve facial skin quality. Several studies have highlighted the impact of aging on adipose tissue, leading to a decrease of adipose tissue volume and preadipocyte proliferation and increase of fibrosis. Recently, there has been a rising interest in adipose tissue components, including adipose-derived stem/stromal cells (ASCs) because of their regenerative potential, including inflammation, fibrosis, and vascularization modulation. Because of their differentiation potential and paracrine function, ASCs have been largely used for fat grafting procedures, as they are described to be a key component in fat graft survival. However, many parameters as surgical procedures or adipose tissue biology could change clinical outcomes. Variation on fat grafting methods have led to numerous inconsistent clinical outcomes. Donor-to-donor variation could also be imputed to ASCs, tissue inflammatory state, or tissue origin. In this review, the authors aim to analyze (1) the parameters involved in graft survival, and (2) the effect of aging on adipose tissue components, especially ASCs, that could lead to a decrease of skin regeneration and fat graft retention. CLINICAL RELEVANCE STATEMENT: This review aims to enlighten surgeons about known parameters that could play a role in fat graft survival. ASCs and their potential mechanism of action in regenerative medicine are more specifically described.


Asunto(s)
Adipocitos , Tejido Adiposo , Humanos , Tejido Adiposo/trasplante , Adipocitos/trasplante , Envejecimiento , Células Madre , Fibrosis , Supervivencia de Injerto
4.
Vet Sci ; 9(10)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36288171

RESUMEN

Feline oral squamous cell carcinoma (FOSCC) is the most common oral neoplasia in cats. This malignant tumor is locally invasive, has a high mortality rate, and its etiology is not yet known. In humans, head and neck squamous cell carcinoma is associated with tobacco smoke, alcohol consumption, and human papillomavirus infection. Herein, a critical review about the potential etiologic factors of FOSCC was performed, considering publications between 2000 and 2022, aiming to synthesize all available scientific evidence regarding this issue. Recommendations of the PRISMA statement and the Cochrane Collaboration were followed and the PubMed database searched by using the MeSH terms MeSH terms "oral", "mouth", "lingual", "labial", "gingiva", "carcinoma", "squamous", and "feline". The selection process for eligible studies was based on specific inclusion and exclusion criteria and the quality of the studies assessed. The initial search resulted in 553 publications, with only 26 of these being included in the review. Sixteen studies were related to viral etiology and nine related to environmental factors such as exposure to tobacco smoke, ectoparasitic products, and the presence of oral comorbidities. When evaluated, feline papillomavirus was detected in 16.2% of samples of FOSCC. In the three studies focused on exposure to tobacco smoke, 35.2% (30/85) of cats with FOSCC had a history of this exposure. The consumption of canned food and the use of deworming collars were associated, in only one publication, with a risk of neoplasia increased by 4.7 and 5.3 times, respectively. Among 485 cats with FOSCC, 6.4% had dental and oral pathology (i.e., periodontal disease or feline chronic gingivostomatitis). The present study demonstrates that the available evidence on the etiology of FOSCC is still limited, however, there has been an increasing interest on this topic. To better understand the role of the possible etiological factors of this aggressive disease, and model for its human counterpart, large, prospective multi-institutional studies are needed.

5.
Life (Basel) ; 12(3)2022 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-35330154

RESUMEN

Solar elastosis is associated with a diffuse yellow hue of the skin. Photoaging is related to lipid peroxidation leading to the formation of carbonyl groups. Protein carbonylation can occur by addition of reactive aldehydes, such as malondialdehyde (MDA), 4-hydroxy-nonenal (4-HNE), and acrolein. All the proteins concerned with this modification, and the biological consequences of adduct formation, are not completely identified. The link between yellowish skin and dermal carbonylated proteins induced by aldehyde adducts was investigated. The study was carried out on ex vivo skin samples from sun-exposed or sun-protected areas and on in vitro dermal equivalent models incubated with 5 mM MDA, 4-HNE, or acrolein. The yellow color and the level of MDA, 4-HNE, and acrolein adducts were evaluated. Yellowish color differences were detected in the dermis of sun-exposed skin compared to sun-protected skin and in in vitro models following addition of MDA, 4-HNE, or acrolein. The yellowing was correlated with the carbonyl adducts increasing in the dermis and in in vitro models incubated with aldehydes. The stronger yellowing seemed to be mediated more by MDA than 4-HNE and acrolein. These observations suggest that dermal carbonylation especially induced by MDA result in the yellow hue of dermis and is involved, in part, in the yellowing observed during skin photoaging.

6.
Anal Bioanal Chem ; 413(30): 7363-7383, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34799750

RESUMEN

The early detection of head and neck cancer is a prolonged challenging task. It requires a precise and accurate identification of tissue alterations as well as a distinct discrimination of cancerous from healthy tissue areas. A novel approach for this purpose uses microspectroscopic techniques with special focus on hyperspectral imaging (HSI) methods. Our proof-of-principle study presents the implementation and application of darkfield elastic light scattering spectroscopy (DF ELSS) as a non-destructive, high-resolution, and fast imaging modality to distinguish lingual healthy from altered tissue regions in a mouse model. The main aspect of our study deals with the comparison of two varying HSI detection principles, which are a point-by-point and line scanning imaging, and whether one might be more appropriate in differentiating several tissue types. Statistical models are formed by deploying a principal component analysis (PCA) with the Bayesian discriminant analysis (DA) on the elastic light scattering (ELS) spectra. Overall accuracy, sensitivity, and precision values of 98% are achieved for both models whereas the overall specificity results in 99%. An additional classification of model-unknown ELS spectra is performed. The predictions are verified with histopathological evaluations of identical HE-stained tissue areas to prove the model's capability of tissue distinction. In the context of our proof-of-principle study, we assess the Pushbroom PCA-DA model to be more suitable for tissue type differentiations and thus tissue classification. In addition to the HE-examination in head and neck cancer diagnosis, the usage of HSI-based statistical models might be conceivable in a daily clinical routine.


Asunto(s)
Luz , Dispersión de Radiación , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de la Lengua/diagnóstico por imagen , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Análisis de Componente Principal , Reproducibilidad de los Resultados
7.
Front Cell Dev Biol ; 9: 682143, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34381771

RESUMEN

Epithelial tissues are the most rapidly dividing tissues in the body, holding a natural ability for renewal and regeneration. This ability is crucial for survival as epithelia are essential to provide the ultimate barrier against the external environment, protecting the underlying tissues. Tissue stem and progenitor cells are responsible for self-renewal and repair during homeostasis and following injury. Upon wounding, epithelial tissues undergo different phases of haemostasis, inflammation, proliferation and remodelling, often resulting in fibrosis and scarring. In this review, we explore the phenotypic differences between the skin, the oesophagus and the oral mucosa. We discuss the plasticity of these epithelial stem cells and contribution of different fibroblast subpopulations for tissue regeneration and wound healing. While these epithelial tissues share global mechanisms of stem cell behaviour for tissue renewal and regeneration, the oral mucosa is known for its outstanding healing potential with minimal scarring. We aim to provide an updated review of recent studies that combined cell therapy with bioengineering exporting the unique scarless properties of the oral mucosa to improve skin and oesophageal wound healing and to reduce fibrotic tissue formation. These advances open new avenues toward the ultimate goal of achieving scarless wound healing.

8.
Sci Total Environ ; 783: 147065, 2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34088143

RESUMEN

Many methods have been used to isolate and identify microplastics from biological matrices. In biological samples, Nile Red can stain undigested residues, such as fats, soaps, and gels formed during organic matter removal, hindering the identification of fluorescent microplastics (≥2 µm). Thus, adjustments on sample preparation (e.g., fat removal) are required for the accurate identification of Nile Red stained microplastics. Multiples tests allowed to identify that digestion with 10% KOH at 60 °C for 24 h, followed by treatments with boiling water, acetone, and staining, produced good results in fourteen biological samples, including vertebrates and invertebrates. Digestion efficiencies were 94-100%, except for feces, which were 87%. Recovery rates of spiked microplastics were 97-100%, and few effects were observed in the infrared spectra and carbonyl index of seven polymers, with only the occasional yellowing suggesting surface changes. Filtration rates were improved by reducing the amount of sample. Small fluorescent microplastics could be identified in all samples under the microscope. Overall, the proposed method was efficient in removing natural organic matter from biological samples for Nile Red staining, requiring minimal sample handling, improving sample throughput, and allowing quantification of fluorescent microplastics in biological samples.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Animales , Monitoreo del Ambiente , Oxazinas , Plásticos , Contaminantes Químicos del Agua/análisis
9.
Mar Pollut Bull ; 160: 111681, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33181954

RESUMEN

Widespread contamination of microplastics may lead to internalization in fish. This literature review from March 2019 to March 2020 details that a median of 60% of fish, belonging to 198 species captured in 24 countries, contain microplastics in their organs. Carnivores species ingested more microplastics than omnivores. Only 14% of fish were from aquaculture. Most studies focused on digestive systems, with presence in other organs currently being insufficiently assessed. Based on this assessment, knowledge gaps that should be addressed in future studies were identified.


Asunto(s)
Plásticos , Contaminantes Químicos del Agua , Animales , Monitoreo del Ambiente , Peces , Microplásticos , Contaminantes Químicos del Agua/análisis
10.
Nat Commun ; 11(1): 5671, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33168804

RESUMEN

To establish whether 4-nitroquinoline N-oxide-induced carcinogenesis mirrors the heterogeneity of human oral squamous cell carcinoma (OSCC), we have performed genomic analysis of mouse tongue lesions. The mutational signatures of human and mouse OSCC overlap extensively. Mutational burden is higher in moderate dysplasias and invasive SCCs than in hyperplasias and mild dysplasias, although mutations in p53, Notch1 and Fat1 occur in early lesions. Laminin-α3 mutations are associated with tumour invasiveness and Notch1 mutant tumours have an increased immune infiltrate. Computational modelling of clonal dynamics indicates that high genetic heterogeneity may be a feature of those mild dysplasias that are likely to progress to more aggressive tumours. These studies provide a foundation for exploring OSCC evolution, heterogeneity and progression.


Asunto(s)
Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Genómica , Neoplasias de la Boca/genética , 4-Nitroquinolina-1-Óxido/efectos adversos , Animales , Cadherinas/genética , Carcinogénesis/inducido químicamente , Carcinoma de Células Escamosas/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Exoma/genética , Genes Relacionados con las Neoplasias , Genes p53/genética , Ratones , Ratones Endogámicos C57BL , Neoplasias de la Boca/patología , Mutación , Invasividad Neoplásica , Receptor Notch1/genética
11.
Cell Stem Cell ; 26(3): 441-457.e7, 2020 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-32109378

RESUMEN

Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment, and differentiation. Here, we use single-cell RNA sequencing and single-molecule RNA FISH to provide a systematic molecular atlas of full-thickness skin, determining gene expression profiles and spatial locations that define 56 cell types and states during hair growth and rest. These findings reveal how the outer root sheath (ORS) and inner hair follicle layers coordinate hair production. We found that the ORS is composed of two intermingling but transcriptionally distinct cell types with differing capacities for interactions with stromal cell types. Inner layer cells branch from transcriptionally uncommitted progenitors, and each lineage differentiation passes through an intermediate state. We also provide an online tool to explore this comprehensive skin cell atlas, including epithelial and stromal cells such as fibroblasts, vascular, and immune cells, to spur further discoveries in skin biology.


Asunto(s)
Folículo Piloso , Cabello , Animales , Diferenciación Celular , Ratones , Piel
12.
Cell Stem Cell ; 25(6): 814-829.e6, 2019 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-31809739

RESUMEN

Stem cells in stratified epithelia are generally believed to adhere to a non-hierarchical single-progenitor model. Using lineage tracing and genetic label-retention assays, we show that the hard palatal epithelium of the oral cavity is unique in displaying marked proliferative heterogeneity. We identify a previously uncharacterized, infrequently-dividing stem cell population that resides within a candidate niche, the junctional zone (JZ). JZ stem cells tend to self-renew by planar symmetric divisions, respond to masticatory stresses, and promote wound healing, whereas frequently-dividing cells reside outside the JZ, preferentially renew through perpendicular asymmetric divisions, and are less responsive to injury. LRIG1 is enriched in the infrequently-dividing population in homeostasis, dynamically changes expression in response to tissue stresses, and promotes quiescence, whereas Igfbp5 preferentially labels a rapidly-growing, differentiation-prone population. These studies establish the oral mucosa as an important model system to study epithelial stem cell populations and how they respond to tissue stresses.


Asunto(s)
Mucosa Bucal/citología , Mucosa Bucal/metabolismo , Células Madre/citología , Células Madre/metabolismo , Animales , División Celular/fisiología , Linaje de la Célula/fisiología , Células Cultivadas , Femenino , Citometría de Flujo , Fluorescencia , Inmunohistoquímica , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Cicatrización de Heridas/fisiología
13.
Cell Stress ; 3(4): 136-138, 2019 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-31225508

RESUMEN

Keratins are intermediate filament proteins expressed by epithelial cells and provide mechanical support for diverse epithelia. In our recent study (Sequeira et al., Nat Comm 9(1):3437), we analysed the role of keratin 76 (Krt76) in inflammation and cancer. Krt76 is expressed throughout embryonic development in the differentiated epithelial layers of a subset of stratified epithelia including tongue, palate and stomach. It is significantly downregulated in human oral squamous cell carcinoma (OSCC), correlating strongly with poor prognosis. We have shown that Krt76-/- mice exhibit systemic inflammation with increased levels of circulating B cells, regulatory T cells and effector T cells. When mice are given a chemical carcinogen in the drinking water, tongue and gastric cancer formation is accelerated in Krt76-/- mutant mice. Our data suggest that the increased tumour susceptibility of Krt76-/- mice is in part due to the enhanced accumulation of regulatory T cells in the tumour microenvironment. Our results support the notion that keratins, in addition to their function as cytoskeletal components, regulate immunity and affect tumour susceptibility of epithelial cells.

14.
Exp Dermatol ; 28(4): 391-394, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-29509981

RESUMEN

Myosins are molecular motors that are well known for their role in cell movement and contractile functions. Although extensively studied in muscle physiology, little is known about the function of myosins in mammalian skin. As part of the Sanger Institute Mouse Genetics Project, we have identified a role for Myo10 in pigmentation, with a phenotype unlike those of Myo5a or Myo7a. Adult mice homozygous for a disrupted Myo10 allele on a C57BL/6N background displayed a high degree of penetrance for white patches on their abdomen and dorsal surface. Forepaw syndactyly and hind paw syndactyly were also observed in these mice. Tail epidermal wholemounts showed a complete lack of melanocytes in the hair follicles and interfollicular epidermis. Myo10 has previously been implicated in human pigmentation. Our current study reveals involvement of Myo10 in murine skin pigmentation.


Asunto(s)
Folículo Piloso/patología , Miosinas/genética , Trastornos de la Pigmentación/genética , Pigmentación de la Piel/genética , Alelos , Animales , Femenino , Expresión Génica , Color del Cabello/genética , Masculino , Melanocitos/metabolismo , Melanocitos/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Penetrancia , Trastornos de la Pigmentación/patología , Sindactilia/genética
15.
Nat Commun ; 9(1): 3437, 2018 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-30143634

RESUMEN

Keratin 76 (Krt76) is expressed in the differentiated epithelial layers of skin, oral cavity and squamous stomach. Krt76 downregulation in human oral squamous cell carcinomas (OSCC) correlates with poor prognosis. We show that genetic ablation of Krt76 in mice leads to spleen and lymph node enlargement, an increase in regulatory T cells (Tregs) and high levels of pro-inflammatory cytokines. Krt76-/- Tregs have increased suppressive ability correlated with increased CD39 and CD73 expression, while their effector T cells are less proliferative than controls. Loss of Krt76 increases carcinogen-induced tumours in tongue and squamous stomach. Carcinogenesis is further increased when Treg levels are elevated experimentally. The carcinogenesis response includes upregulation of pro-inflammatory cytokines and enhanced accumulation of Tregs in the tumour microenvironment. Tregs also accumulate in human OSCC exhibiting Krt76 loss. Our study highlights the role of epithelial cells in modulating carcinogenesis via communication with cells of the immune system.


Asunto(s)
Queratinas/inmunología , Neoplasias de la Boca/inmunología , Neoplasias Gástricas/inmunología , 5'-Nucleotidasa/metabolismo , Animales , Antígenos CD/metabolismo , Apirasa/metabolismo , Línea Celular Tumoral , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Hibridación Fluorescente in Situ , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Mutantes , Linfocitos T Reguladores/metabolismo
16.
Nature ; 556(7701): 376-380, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29643507

RESUMEN

Ribosome-associated mRNA quality control mechanisms ensure the fidelity of protein translation1,2. Although these mechanisms have been extensively studied in yeast, little is known about their role in mammalian tissues, despite emerging evidence that stem cell fate is controlled by translational mechanisms3,4. One evolutionarily conserved component of the quality control machinery, Dom34 (in higher eukaryotes known as Pelota (Pelo)), rescues stalled ribosomes 5 . Here we show that Pelo is required for mammalian epidermal homeostasis. Conditional deletion of Pelo in mouse epidermal stem cells that express Lrig1 results in hyperproliferation and abnormal differentiation of these cells. By contrast, deletion of Pelo in Lgr5-expressing stem cells has no effect and deletion in Lgr6-expressing stem cells induces only a mild phenotype. Loss of Pelo results in accumulation of short ribosome footprints and global upregulation of translation, rather than affecting the expression of specific genes. Translational inhibition by rapamycin-mediated downregulation of mTOR (mechanistic target of rapamycin kinase) rescues the epidermal phenotype. Our study reveals that the ribosome-rescue machinery is important for mammalian tissue homeostasis and that it has specific effects on different stem cell populations.


Asunto(s)
Evolución Biológica , Epidermis/metabolismo , Homeostasis , Ribosomas/metabolismo , Células Madre/metabolismo , Animales , Proteínas de Ciclo Celular/deficiencia , Proteínas de Ciclo Celular/genética , Diferenciación Celular , Proliferación Celular , Progresión de la Enfermedad , Endonucleasas , Células Epidérmicas , Epidermis/patología , Femenino , Homeostasis/genética , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Proteínas de Microfilamentos/deficiencia , Proteínas de Microfilamentos/genética , Mutación , Proteínas del Tejido Nervioso/metabolismo , Fenotipo , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células Madre/citología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo
17.
Viral Immunol ; 30(9): 675-677, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28972455

RESUMEN

Rubella is an acute viral disease that usually does not generate sequels; however, in pregnant women the infection can cause serious abnormalities to fetuses, which are collectively called congenital rubella syndrome. In Brazil, population immunization was started in 1992, but few epidemiological studies have been conducted to assess vaccination coverage and seroconversion since then. The aim of this work is to evaluate the seropositivity of pregnant women to rubella virus after vaccination campaign was carried out in 2008. Serological tests for rubella diagnosis were performed in 87 pregnant women who attended the University of Brasilia Hospital, Federal District, Brazil. Antirubella IgG antibodies were detected in 83 out of 87 pregnant women (95.4%), with an age-independent seroprevalence. Only one woman was positive in IgM serological tests. Our data suggest high levels of vaccination coverage and antirubella immunization in the Brazil Federal District population.


Asunto(s)
Anticuerpos Antivirales/sangre , Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología , Complicaciones Infecciosas del Embarazo/epidemiología , Virus de la Rubéola/inmunología , Rubéola (Sarampión Alemán) , Adolescente , Adulto , Brasil/epidemiología , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Vacunación Masiva , Persona de Mediana Edad , Programas Nacionales de Salud , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/virología , Rubéola (Sarampión Alemán)/diagnóstico , Rubéola (Sarampión Alemán)/epidemiología , Rubéola (Sarampión Alemán)/prevención & control , Estudios Seroepidemiológicos , Vacunación , Adulto Joven
18.
Arch. endocrinol. metab. (Online) ; 61(5): 476-483, Sept.-Oct. 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-887593

RESUMEN

ABSTRACT Objective The purpose of this study was to verify the presence of endothelial dysfunction and initial structural atherosclerotic changes in children with Type 1 diabetes mellitus (T1DM). Subjects and methods The study population comprised 31 diabetic children aged 6 to 12 years, divided into two subgroups according to the duration of the T1DM diagnosis: subgroup 1, with less than 5 years elapsed since diagnosis, and subgroup 2, with more than 5 years elapsed since diagnosis. The control group comprised 58 age-matched healthy children. Ultrasonographic techniques were used to measure the flow-mediated dilatation (FMD) of the brachial artery and the intima-media thickness (IMT) of the carotid arteries. Results Children with T1DM with longer disease duration showed significantly decreased mean values of FMD compared with those in the control group. No significant differences between the groups were found in relation to IMT. The FMD percentage presented a moderate negative correlation with glycated hemoglobin (HbA1c) and fasting glucose levels. Conclusion Our findings suggest that endothelial dysfunction may be already present in children with 5 years or more elapsed since diagnosis, even in the absence of atherosclerotic structural changes. The decreased vasodilation response correlated with hyperglycemia.


Asunto(s)
Humanos , Masculino , Femenino , Niño , Endotelio Vascular/fisiopatología , Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Estudios de Casos y Controles , Aterosclerosis/fisiopatología
19.
J Invest Dermatol ; 137(11): 2270-2281, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28668474

RESUMEN

B-lymphocyte-induced maturation protein 1 (Blimp1) is a transcriptional repressor that regulates cell growth and differentiation in multiple tissues, including skin. Although in the epidermis Blimp1 is important for keratinocyte and sebocyte differentiation, its role in dermal fibroblasts is unclear. Here we show that Blimp1 is dynamically regulated in dermal papilla cells during hair follicle (HF) morphogenesis and the postnatal hair cycle, preceding dermal Wnt/ß-catenin activation. Blimp1 ablation in E12.5 mouse dermal fibroblasts delayed HF morphogenesis and growth and prevented new HF formation after wounding. By combining targeted quantitative PCR screens with bioinformatic analysis and experimental validation we demonstrated that Blimp1 is both a target and a mediator of key dermal papilla inductive signaling pathways including transforming growth factor-ß and Wnt/ß-catenin. Epidermal overexpression of stabilized ß-catenin was able to override the HF defects in Blimp1 mutant mice, underlining the close reciprocal relationship between the dermal papilla and adjacent HF epithelial cells. Overall, our study reveals the functional role of Blimp1 in promoting the dermal papilla inductive signaling cascade that initiates HF growth.


Asunto(s)
Regulación de la Expresión Génica , Folículo Piloso/crecimiento & desarrollo , Factores de Transcripción/genética , Factor de Crecimiento Transformador beta/genética , Vía de Señalización Wnt/genética , Animales , Biopsia con Aguja , Comunicación Celular/genética , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo , Células Epidérmicas , Epidermis/metabolismo , Femenino , Folículo Piloso/fisiología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Factor 1 de Unión al Dominio 1 de Regulación Positiva , ARN Mensajero/análisis , Distribución Aleatoria , Reacción en Cadena en Tiempo Real de la Polimerasa , Regeneración/genética , beta Catenina/metabolismo
20.
Arch Endocrinol Metab ; 61(5): 476-483, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28658349

RESUMEN

OBJECTIVE: The purpose of this study was to verify the presence of endothelial dysfunction and initial structural atherosclerotic changes in children with Type 1 diabetes mellitus (T1DM). SUBJECTS AND METHODS: The study population comprised 31 diabetic children aged 6 to 12 years, divided into two subgroups according to the duration of the T1DM diagnosis: subgroup 1, with less than 5 years elapsed since diagnosis, and subgroup 2, with more than 5 years elapsed since diagnosis. The control group comprised 58 age-matched healthy children. Ultrasonographic techniques were used to measure the flow-mediated dilatation (FMD) of the brachial artery and the intima-media thickness (IMT) of the carotid arteries. RESULTS: Children with T1DM with longer disease duration showed significantly decreased mean values of FMD compared with those in the control group. No significant differences between the groups were found in relation to IMT. The FMD percentage presented a moderate negative correlation with glycated hemoglobin (HbA1c) and fasting glucose levels. CONCLUSION: Our findings suggest that endothelial dysfunction may be already present in children with 5 years or more elapsed since diagnosis, even in the absence of atherosclerotic structural changes. The decreased vasodilation response correlated with hyperglycemia.


Asunto(s)
Aterosclerosis/fisiopatología , Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Endotelio Vascular/fisiopatología , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino
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