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1.
PLoS Genet ; 19(2): e1010652, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36827454

RESUMO

Adaptive immunity's success relies on the extraordinary diversity of protein receptors on B and T cell membranes. Despite this diversity, the existence of public receptors shared by many individuals gives hope for developing population-wide vaccines and therapeutics. Using probabilistic modeling, we show many of these public receptors are shared by chance in healthy individuals. This predictable overlap is driven not only by biases in the random generation process of receptors, as previously reported, but also by their common functional selection. However, the model underestimates sharing between repertoires of individuals infected with SARS-CoV-2, suggesting strong specific antigen-driven convergent selection. We exploit this discrepancy to identify COVID-associated receptors, which we validate against datasets of receptors with known viral specificity. We study their properties in terms of sequence features and network organization, and use them to design an accurate diagnostic tool for predicting SARS-CoV-2 status from repertoire data.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Linfócitos T , Antígenos , Receptores de Antígenos de Linfócitos T
2.
PLoS Genet ; 19(3): e1010636, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36857386

RESUMO

Plants can regenerate new organs from damaged or detached tissues. In the process of de novo root regeneration (DNRR), adventitious roots are frequently formed from the wound site on a detached leaf. Salicylic acid (SA) is a key phytohormone regulating plant defenses and stress responses. The role of SA and its acting mechanisms during de novo organogenesis is still unclear. Here, we found that endogenous SA inhibited the adventitious root formation after cutting. Free SA rapidly accumulated at the wound site, which was accompanied by an activation of SA response. SA receptors NPR3 and NPR4, but not NPR1, were required for DNRR. Wounding-elevated SA compromised the expression of AUX1, and subsequent transport of auxin to the wound site. A mutation in AUX1 abolished the enhanced DNRR in low SA mutants. Our work elucidates a role of SA in regulating DNRR and suggests a potential link between biotic stress and tissue regeneration.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácido Salicílico/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
3.
Am J Med Genet C Semin Med Genet ; 196(1): e32078, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38041246

RESUMO

We report the case of an 18-year-old woman with Down syndrome (DS) who developed Takotsubo cardiomyopathy (TSC) immediately after the administration of electroconvulsive therapy (ECT), a treatment prescribed for Down syndrome regression disorder resistant to oral psychotropic drugs. TSC is a nonischemic cardiomyopathy related to psychological or physical stress, which has been described as a rare complication of ECT (Kinoshita et al., 2023, Journal of Electroconvulsive Therapy, 39, 185-192). The clinical description of the case is accompanied by a discussion of the peculiarities of the autonomic nervous system in DS.


Assuntos
Síndrome de Down , Eletroconvulsoterapia , Cardiomiopatia de Takotsubo , Feminino , Adulto Jovem , Humanos , Adolescente , Eletroconvulsoterapia/efeitos adversos , Síndrome de Down/complicações , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/terapia
4.
J Clin Immunol ; 44(6): 143, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847936

RESUMO

Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.


Assuntos
Biomarcadores , Imunodeficiência de Variável Comum , Humanos , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/imunologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Modelos Logísticos , Adulto Jovem , Adolescente , Idoso , Cadeias kappa de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/genética , Sensibilidade e Especificidade , Linfócitos B/imunologia , Cadeias lambda de Imunoglobulina , Células B de Memória/imunologia
5.
Histochem Cell Biol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954026

RESUMO

Skin represents the main barrier against the external environment, but also plays a role in human relations, as one of the prime determinants of beauty, resulting in a high consumer demand for skincare-related pharmaceutical products. Given the importance of skin aging in both medical and social spheres, the present research aims to characterize microscopic changes in human skin composition due to intrinsic aging (as opposed to aging influenced by external factors) via histological analysis of a photoprotected body region. Samples from 25 autopsies were taken from the periumbilical area and classified into four age groups: group 1 (0-12 years), group 2 (13-25 years), group 3 (26-54 years), and group 4 (≥ 55 years). Different traditional histological (hematoxylin-eosin, Masson's trichrome, orcein, toluidine, Alcian blue, and Feulgen reaction) and immunohistochemical (CK20, CD1a, Ki67, and CD31) stains were performed. A total of 1879 images photographed with a Leica DM3000 optical microscope were morphometrically analyzed using Image ProPlus 7.0 for further statistical analysis with GraphPad 9.0. Our results showed a reduction in epidermis thickness, interdigitation and mitotic indexes, while melanocyte count was raised. Papillary but not reticular dermis showed increased thickness with aging. Specifically, in the papillary layer mast cells and glycosaminoglycans were expanded, whereas the reticular dermis displayed a diminution in glycosaminoglycans and elastic fibers. Moreover, total cellularity and vascularization of both dermises were diminished with aging. This morphometric analysis of photoprotected areas reveals that intrinsic aging significantly influences human skin composition. This study paves the way for further research into the molecular basis underpinning these alterations, and into potential antiaging strategies.

6.
Br J Dermatol ; 190(5): 740-750, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38214572

RESUMO

BACKGROUND: Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge. OBJECTIVES: To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management. METHODS: In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM. RESULTS: We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample. CONCLUSIONS: These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.


Melanoma is a type of skin cancer that can be deadly if it is not detected at an early stage. Unfortunately, the early detection of melanoma is challenging. Our team has developed a model that could be used to predict whether a person has stage I malignant melanoma based on blood serum analysis. The model was trained on data from a group of people with melanoma and it was found to be accurate in predicting melanoma at an early stage. This means that the model could be used to identify people who have skin cancer before it progresses and becomes more complicated to treat. Although the researchers recommend that further studies are conducted to validate the model in a larger population of people, this research could help with the early diagnosis of melanoma and work toward improving survival rates.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Projetos Piloto , Detecção Precoce de Câncer , Metabolômica , Biomarcadores , Espectrometria de Massa com Cromatografia Líquida
7.
Ann Hematol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38763941

RESUMO

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years. An observational, descriptive, multicentre and ambispective study of adult and paediatric patients with haemoglobinopathies and rare anaemias registered in REHem was performed. The data are from a cross-sectional analysis performed on 1 June, 2023. The study population comprised 1,756 patients, of whom 1,317 had SCD, 214 had thalassaemia and 224 were diagnosed with another condition. Slightly more than one third of SCD patients (37%) were diagnosed based on neonatal bloodspot screening, and the mean age at diagnosis was 2.5 years; 71% of thalassaemia patients were diagnosed based on the presence of anaemia. Vaso-occlusive crisis and acute chest syndrome continue to be the most frequent complications in SCD. HSCT was performed in 83 patients with SCD and in 50 patients with thalassaemia. Since the previous publication, REHem-AR has grown in size by more than 500 cases. SCD and TM are less frequent in Spain than in other European countries, although the data show that rare anaemias are frequent within rare diseases. REHem-AR constitutes an important structure for following the natural history of rare anaemias and enables us to calculate investment needs for current and future treatments.

8.
Bioorg Med Chem ; 99: 117596, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38232459

RESUMO

Codification of DNA Encoded Libraries (DELs) is critical for successful ligand identification of molecules that bind a protein of interest (POI). There are different encoding strategies that permit, for instance, the customization of a DEL for testing single or dual pharmacophores (single strand DNA) or for producing and screening large diversity libraries of small molecules (double strand DNA). Both approaches challenges, either from the synthetic and encoding point of view, or from the selection methodology to be utilized for the screening. The Head-Piece contains the DNA sequence that is attached to a chemical compound, allowing the encoding of each molecule with a unique DNA tag. Designing the Head-Piece for a DNA-encoded library involves careful consideration of several key aspects including DNA barcode identity, sequence length and attachment chemistry. Here we describe a double stranded DNA versatile Head-Piece that can be used for the generation of single or dual pharmacophore libraries, but also shows other advanced DEL functionalities, stability and enlarged encoding capacity.


Assuntos
Descoberta de Drogas , Bibliotecas de Moléculas Pequenas , Descoberta de Drogas/métodos , Bibliotecas de Moléculas Pequenas/química , DNA/química , Biblioteca Gênica , DNA de Cadeia Simples
9.
Artigo em Inglês | MEDLINE | ID: mdl-38411353

RESUMO

BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.

10.
Contact Dermatitis ; 90(4): 402-410, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38010086

RESUMO

BACKGROUND: There is speculation that some environmental factors may be impacting the increasing incidence of frontal fibrosing alopecia (FFA). In a recent publication, sensitisation to benzyl salicylate was shown to be prevalent among 36 patients with FFA. Ethylhexyl salicylate (EHS), a light stabiliser, ultraviolet (UV) B absorber and UV filter, frequently found in photoprotectors/cosmetics and, rarely reported as a sensitiser, was not patch tested in said research. METHODS: From January 2021 to February 2022, 33 patients with FFA were patch-tested with the European Photopatch Series, including EHS 10% pet. in two hospitals. In addition, we conducted a literature review and a market survey. RESULTS: Patch test reactions to EHS were identified in 9 of 33 (27.3%). Four of nine also reacted to their personal sunscreens (containing EHS). All involved women with a mean age of 54 (30-65). Five patients had been diagnosed with FFA before the patch tests; and, four were diagnosed with FFA during the patch test investigations. CONCLUSION: Sensitisation to EHS was frequently found in a selected population of patients with FFA. We propose to expand the spectrum of contact allergens described in patients with FFA to include EHS and discuss the possible need for optimization of the patch test preparation.


Assuntos
Cosméticos , Dermatite Alérgica de Contato , Humanos , Feminino , Pessoa de Meia-Idade , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/epidemiologia , Protetores Solares/efeitos adversos , Alopecia/complicações , Testes do Emplastro/efeitos adversos , Salicilatos/efeitos adversos
11.
Contact Dermatitis ; 90(3): 245-252, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37987093

RESUMO

BACKGROUND: Monitoring of adverse events induced by cosmetics performed by health authorities, known as cosmetovigilance, has been relied on the collection of case notifications. OBJECTIVES: We aimed to show how a contact dermatitis registry can contribute to the cosmetovigilance of emerging allergens. We used the example of phenylethyl resorcinol, an infrequent allergen with only 6 previous cases reported in Europe and Japan since 2013. METHODS: A systematic search in the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC) database was performed to identify patients with positive patch test to phenylethyl resorcinol or cosmetics that contains it between June 2018 and January 2023. We collected the main clinical features of these patients and compared them with those of patients recorded in the registry with similar epidemiological features. RESULTS: Thirteen patients with positive patch test to phenylethyl resorcinol were identified. All the patients were women with a mean age of 42 years (range 32-59) and their lesions were mainly in the face. CONCLUSION: Assessing the importance of infrequent allergens based solely on a case series is difficult. Multicentre registries facilitate the collection of cases and provide appropriate background information for new allergens.


Assuntos
Compostos Benzidrílicos , Cosméticos , Dermatite Alérgica de Contato , Resorcinóis , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Espanha/epidemiologia , Estudos Retrospectivos , Cosméticos/efeitos adversos , Testes do Emplastro/efeitos adversos , Sistema de Registros
12.
Contact Dermatitis ; 90(5): 486-494, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38348533

RESUMO

BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.


Assuntos
Dermatite Alérgica de Contato , Humanos , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Espanha/epidemiologia , Têxteis/efeitos adversos , Testes do Emplastro , Corantes/efeitos adversos
13.
Contact Dermatitis ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965446

RESUMO

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.

14.
Contact Dermatitis ; 90(5): 507-513, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38351475

RESUMO

BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.


Assuntos
Dermatite Alérgica de Contato , Dermatite Ocupacional , Humanos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Espanha/epidemiologia , Metacrilatos/efeitos adversos , Acrilatos , Testes do Emplastro
15.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38928330

RESUMO

Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.


Assuntos
Cicatriz , Fibrose , Infarto do Miocárdio , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/genética , Animais , Camundongos , Humanos , Cicatriz/metabolismo , Cicatriz/patologia , Cicatriz/genética , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Colágenos Fibrilares/metabolismo , Colágenos Fibrilares/genética , Feminino , Modelos Animais de Doenças , Colágeno/metabolismo , Pessoa de Meia-Idade , Camundongos Endogâmicos C57BL
17.
Cytokine ; 170: 156334, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37598478

RESUMO

The tumor microenvironment (TME) is a heterogeneous mixture of resident and tumor cells that maintain close communication through their secretion products. The composition of the TME is dynamic and complex among the different types of cancer, where the immune cells play a relevant role in the elimination of tumor cells, however, under certain circumstances they contribute to tumor development. In cervical cancer (CC) the human papilloma virus (HPV) shapes the microenvironment in order to mediate persistent infections that favors transformation and tumor development. Interleukin-2 (IL-2) is an important TME cytokine that induces CD8+ effector T cells and NKs to eliminate tumor cells, however, IL-2 can also suppress the immune response through Treg cells. Recent studies have shown that CC cells express the IL-2 receptor (IL-2R), that are induced to proliferate at low concentrations of exogenous IL-2 through alterations in the JAK/STAT pathway. This review provides an overview of the main immune cells that make up the TME in CC, as well as the participation of IL-2 in the tumor promotion. Finally, it is proposed that the low density of IL-2 produced by immunocompetent cells is used by tumor cells through its IL-2R as a mechanism to proliferate simultaneously depleting this molecule in order to evade immune response.


Assuntos
Interleucina-2 , Neoplasias do Colo do Útero , Feminino , Humanos , Transformação Celular Neoplásica , Janus Quinases , Receptores de Interleucina-2 , Transdução de Sinais , Fatores de Transcrição STAT , Microambiente Tumoral
18.
Acta Neuropathol ; 146(2): 263-282, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37243699

RESUMO

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Células Supressoras Mieloides , Animais , Camundongos , Esclerose Múltipla/patologia , Células Supressoras Mieloides/patologia , Estudos Retrospectivos , Encefalomielite Autoimune Experimental/patologia , Progressão da Doença , Camundongos Endogâmicos C57BL
19.
Cereb Cortex ; 32(9): 1894-1910, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-34519346

RESUMO

The remedy of memory deficits has been inadequate, as all potential candidates studied thus far have shown limited to no effects and a search for an effective strategy is ongoing. Here, we show that an expression of RGS14414 in rat perirhinal cortex (PRh) produced long-lasting object recognition memory (ORM) enhancement and that this effect was mediated through the upregulation of 14-3-3ζ, which caused a boost in BDNF protein levels and increase in pyramidal neuron dendritic arborization and dendritic spine number. A knockdown of the 14-3-3ζ gene in rat or the deletion of the BDNF gene in mice caused complete loss in ORM enhancement and increase in BDNF protein levels and neuronal plasticity, indicating that 14-3-3ζ-BDNF pathway-mediated structural plasticity is an essential step in RGS14414-induced memory enhancement. We further observed that RGS14414 treatment was able to prevent deficits in recognition, spatial, and temporal memory, which are types of memory that are particularly affected in patients with memory dysfunctions, in rodent models of aging and Alzheimer's disease. These results suggest that 14-3-3ζ-BDNF pathway might play an important role in the maintenance of the synaptic structures in PRh that support memory functions and that RGS14414-mediated activation of this pathway could serve as a remedy to treat memory deficits.


Assuntos
Córtex Perirrinal , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Humanos , Transtornos da Memória/metabolismo , Transtornos da Memória/prevenção & controle , Camundongos , Plasticidade Neuronal/fisiologia , Ratos , Roedores/metabolismo
20.
Contact Dermatitis ; 89(6): 471-479, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37667591

RESUMO

BACKGROUND: Allergic contact dermatitis from (meth)acrylic monomers (ACDMA) in manicure products is increasing. OBJECTIVE: To evaluate the prognosis, work performance impairment and sequelae of a cohort of beauticians and manicure consumers with ACDMA sensitized from the exposure to manicure products. METHODS: We conducted a telephone survey with patients diagnosed with ACDMA. RESULTS: One hundred and six patients were evaluated, including 75 (70.8%) beauticians and 31 (29.2%) consumers. All were women with a mean age of 39 (19-62). Thirty-seven of 75 beauticians (49.3%) continued to work. Twenty-seven of 106 (25.5%) patients continued to use manicure products with (meth)acrylates regularly. Seventeen of 51 (33.3%) patients who discontinued the exposure described ongoing nail/periungual changes. Nine of 58 (15.5%) patients who required dental restoration, orthodontic or occlusal splint materials recalled reactions from them; and, 25 of 96 (26%) who used sanitary napkins recalled intolerance to them starting after the diagnosis of ACDMA. Fifteen of 25 (60%) discontinued the use of sanitary napkins. CONCLUSION: 49.3% beauticians continued to work; most patients stopped wearing acrylic manicure materials; reactions from dental materials were not uncommon, however, removal of dental materials was never required; and, reactions to sanitary napkins developing after the diagnosis of ACDMA were common most leading to discontinuation of use.


Assuntos
Dermatite Alérgica de Contato , Dermatite Ocupacional , Humanos , Feminino , Adulto , Masculino , Dermatite Alérgica de Contato/diagnóstico , Acrilatos/efeitos adversos , Testes do Emplastro , Prognóstico , Materiais Dentários , Metacrilatos/efeitos adversos
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