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1.
Cureus ; 16(3): e55999, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38476508

RESUMO

Introduction Our department conducted a retrospective cohort study to compare the efficacy of continuous glucose monitoring devices versus capillary blood glucose in the glycemic control of inpatient type 2 diabetes on intensive insulin therapy in a Portuguese hospital. The use of continuous glucose monitoring devices was associated with improved glycemic control, including an increased number of glucose readings within target range and reduced hyperglycemic events, being safe concerning hypoglycemias. This is the cost-effectiveness analysis associated with these results. Aim The primary objective was to compare the cost-effectiveness of achieving glycemic control, defined as the number of patients within glycemic goals, between groups. Secondary endpoints included cost-effectiveness analyses of each time in range goal, and each percentual increment in time in range. Methods We defined each glycemic goal as: "readings within range (70-180 mg/dL) >70%", "readings below range (below 70 mg/dL) <4%", "severe hypoglycemia (below 54 mg/dL) <1%", "readings above range (above 180 mg/dL) <25%", "very high glycemic readings (above 250 mg/dL) <5%". Results Continuous glucose monitoring showed lower median cost per effect for the primary outcome (€11.1 vs. €34.9/patient), with lower cost for readings in range (€7.8 vs. €11.6/patient) and for both readings above range goals ("above 180mg/dL": €7.4 vs. €9.9/patient, and "above 250mg/dL": €6.9 vs. €17.4/patient). Conclusions There are no published data regarding the cost-effectiveness of continuous glucose monitoring devices in inpatient settings. Our results show that continuous glucose monitoring devices were associated with an improved glycemic control, at a lower cost, and endorse the feasibility of incorporating these devices into hospital settings, presenting a favorable cost-effective option compared to capillary blood glucose.

2.
Front Immunol ; 15: 1350101, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550576

RESUMO

Glycosylation is a critical post-translational modification that plays a pivotal role in several biological processes, such as the immune response. Alterations in glycosylation can modulate the course of various pathologies, such as the case of congenital disorders of glycosylation (CDG), a group of more than 160 rare and complex genetic diseases. Although the link between glycosylation and immune dysfunction has already been recognized, the immune involvement in most CDG remains largely unexplored and poorly understood. In this study, we provide an update on the immune dysfunction and clinical manifestations of the 12 CDG with major immune involvement, organized into 6 categories of inborn errors of immunity according to the International Union of Immunological Societies (IUIS). The immune involvement in phosphomannomutase 2 (PMM2)-CDG - the most frequent CDG - was comprehensively reviewed, highlighting a higher prevalence of immune issues during infancy and childhood and in R141H-bearing genotypes. Finally, using PMM2-CDG as a model, we point to links between abnormal glycosylation patterns in host cells and possibly favored interactions with microorganisms that may explain the higher susceptibility to infection. Further characterizing immunopathology and unusual host-pathogen adhesion in CDG can not only improve immunological standards of care but also pave the way for innovative preventive measures and targeted glycan-based therapies that may improve quality of life for people living with CDG.


Assuntos
Defeitos Congênitos da Glicosilação , Humanos , Criança , Glicosilação , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/tratamento farmacológico , Defeitos Congênitos da Glicosilação/patologia , Qualidade de Vida , Genótipo , Processamento de Proteína Pós-Traducional
3.
JCI Insight ; 9(7)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441970

RESUMO

Compromised vascular integrity facilitates extravasation of cancer cells and promotes metastatic dissemination. CD93 has emerged as a target for antiangiogenic therapy, but its importance for vascular integrity in metastatic cancers has not been evaluated. Here, we demonstrate that CD93 participates in maintaining the endothelial barrier and reducing metastatic dissemination. Primary melanoma growth was hampered in CD93-/- mice, but metastatic dissemination was increased and associated with disruption of adherens and tight junctions in tumor endothelial cells and elevated expression of matrix metalloprotease 9 at the metastatic site. CD93 directly interacted with vascular endothelial growth factor receptor 2 (VEGFR2) and its absence led to VEGF-induced hyperphosphorylation of VEGFR2 in endothelial cells. Antagonistic anti-VEGFR2 antibody therapy rescued endothelial barrier function and reduced the metastatic burden in CD93-/- mice to wild-type levels. These findings reveal a key role of CD93 in maintaining vascular integrity, which has implications for pathological angiogenesis and endothelial barrier function in metastatic cancer.


Assuntos
Células Endoteliais , Neoplasias , Animais , Camundongos , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Neoplasias/patologia , Neovascularização Patológica/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Am J Physiol Renal Physiol ; 326(4): F644-F660, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38420674

RESUMO

Patients with hypertension or obesity can develop glomerular dysfunction characterized by injury and depletion of podocytes. To better understand the molecular processes involved, young mice were treated with either deoxycorticosterone acetate (DOCA) or fed a high-fat diet (HFD) to induce hypertension or obesity, respectively. The transcriptional changes associated with these phenotypes were measured by unbiased bulk mRNA sequencing of isolated podocytes from experimental models and their respective controls. Key findings were validated by immunostaining. In addition to a decrease in canonical proteins and reduced podocyte number, podocytes from both hypertensive and obese mice exhibited a sterile inflammatory phenotype characterized by increases in NLR family pyrin domain containing 3 (NLRP3) inflammasome, protein cell death-1, and Toll-like receptor pathways. Finally, although the mice were young, podocytes in both models exhibited increased expression of senescence and aging genes, including genes consistent with a senescence-associated secretory phenotype. However, there were differences between the hypertension- and obesity-associated senescence phenotypes. Both show stress-induced podocyte senescence characterized by increased p21 and p53. Moreover, in hypertensive mice, this is superimposed upon age-associated podocyte senescence characterized by increased p16 and p19. These results suggest that senescence, aging, and inflammation are critical aspects of the podocyte phenotype in experimental hypertension and obesity in mice.NEW & NOTEWORTHY Hypertension and obesity can lead to glomerular dysfunction in patients, causing podocyte injury and depletion. Here, young mice given deoxycorticosterone acetate or a high-fat diet to induce hypertension or obesity, respectively. mRNA sequencing of isolated podocytes showed transcriptional changes consistent with senescence, a senescent-associated secretory phenotype, and aging, which was confirmed by immunostaining. Ongoing studies are determining the mechanistic roles of the accelerated aging podocyte phenotype in experimental hypertension and obesity.


Assuntos
Hipertensão , Nefropatias , Podócitos , Humanos , Camundongos , Animais , Idoso , Podócitos/metabolismo , Camundongos Obesos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Fenótipo , Nefropatias/metabolismo , Obesidade/metabolismo , Hipertensão/genética , Hipertensão/metabolismo , Desoxicorticosterona , Acetatos/metabolismo , RNA Mensageiro/metabolismo
5.
Microorganisms ; 12(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38399756

RESUMO

INTRODUCTION: This study standardized a semi-quantitative dot blotting assay (DB) and a quantitative real-time polymerase chain reaction (qPCR) to detect specific antibodies for Paracoccidioides brasiliensis and its DNA in PCM patients. METHODOLOGY: We evaluated 42 confirmed PCM patients upon admission using a serological double agar gel immunodiffusion test (DID), DB, and molecular tests (qPCR in total blood). The control groups included 42 healthy individuals and 37 patients with other infectious diseases. The serological progress during treatment was evaluated in eight patients, and there was a relapse diagnosis in ten patients using the Pb B.339 strain antigen. The cut-off points for the serological tests were determined by a receiver operator characteristic curve. RESULTS: The DB and DID tests showed similar accuracy, but the DB identified lower antibody concentrations. Cross-reactions were absent in the DB assay. In the relapse diagnoses, DB exhibited much higher sensitivity (90%) than DID (30%). CONCLUSIONS: A DB assay is easier and faster than a DID test to be performed; DB and DID tests show the same accuracy, while blood qPCR is not recommended in the diagnosis at the time of admission; cross-reactions were not observed with other systemic diseases; DB and DID tests are useful for treatment monitoring PCM patients; and a DB assay is the choice for diagnosing relapse. These findings support the introduction of semi-quantitative DB assays in clinical laboratories.

6.
J Fungi (Basel) ; 10(2)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38392819

RESUMO

Paracoccidioidomycosis (PCM) is a systemic mycosis that is diagnosed by visualizing the fungus in clinical samples or by other methods, like serological techniques. However, all PCM diagnostic methods have limitations. The aim of this study was to develop a diagnostic tool for PCM based on Fourier transform infrared (FTIR) spectroscopy. A total of 224 serum samples were included: 132 from PCM patients and 92 constituting the control group (50 from healthy blood donors and 42 from patients with other systemic mycoses). Samples were analyzed by attenuated total reflection (ATR) and a t-test was performed to find differences in the spectra of the two groups. The wavenumbers that had p < 0.05 had their diagnostic potential evaluated using receiver operating characteristic (ROC) curves. The spectral region with the lowest p value was used for variable selection through principal component analysis (PCA). The selected variables were used in a linear discriminant analysis (LDA). In univariate analysis, the ROC curves with the best performance were obtained in the region 1551-1095 cm-1. The wavenumber that had the highest AUC value was 1264 cm-1, achieving a sensitivity of 97.73%, specificity of 76.01%, and accuracy of 94.22%. The total separation of groups was obtained in the PCA performed with a spectral range of 1551-1095 cm-1. LDA performed with the eight wavenumbers with the greatest weight from the group discrimination in the PCA obtained 100% accuracy. The methodology proposed here is simple, fast, and highly accurate, proving its potential to be applied in the diagnosis of PCM. The proposed method is more accurate than the currently known diagnostic methods, which is particularly relevant for a neglected tropical mycosis such as paracoccidioidomycosis.

7.
Ageing Res Rev ; 95: 102204, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272265

RESUMO

The pursuit for the fountain of youth has long been a fascination amongst scientists and humanity. Ageing is broadly characterized by a cellular decline with increased susceptibility to age-related diseases, being intimately associated with epigenetic modifications. Recently, reprogramming-induced rejuvenation strategies have begun to greatly alter longevity research not only to tackle age-related defects but also to possibly reverse the cellular ageing process. Hence, in this review, we highlight the major epigenetic changes during ageing and the state-of-art of the current emerging epigenetic reprogramming strategies leveraging on transcription factors. Notably, partial reprogramming enables the resetting of the ageing clock without erasing cellular identity. Promising chemical-based rejuvenation strategies harnessing small molecules, including DNA methyltransferase and histone deacetylase inhibitors are also discussed. Moreover, in parallel to longevity interventions, the foundations of epigenetic clocks for accurate ageing assessment and evaluation of reprogramming approaches are briefly presented. Going further, with such scientific breakthroughs, we are witnessing a rise in the longevity biotech industry aiming to extend the health span and ideally achieve human rejuvenation one day. In this context, we overview the main scenarios proposed for the future of the socio-economic and ethical challenges associated with such an emerging field. Ultimately, this review aims to inspire future research on interventions that promote healthy ageing for all.


Assuntos
Metilação de DNA , Longevidade , Humanos , Adolescente , Longevidade/genética , Envelhecimento/genética , Senescência Celular/genética , Epigênese Genética , Reprogramação Celular/genética
8.
Am J Physiol Renal Physiol ; 326(1): F120-F134, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37855038

RESUMO

As life expectancy continues to rise, age-related diseases are becoming more prevalent. For example, proteinuric glomerular diseases typified by podocyte injury have worse outcomes in the elderly compared with young patients. However, the reasons are not well understood. We hypothesized that injury to nonaged podocytes induces senescence, which in turn augments their aging processes. In primary cultured human podocytes, injury induced by a cytopathic antipodocyte antibody, adriamycin, or puromycin aminonucleoside increased the senescence-related genes CDKN2A (p16INK4a/p14ARF), CDKN2D (p19INK4d), and CDKN1A (p21). Podocyte injury in human kidney organoids was accompanied by increased expression of CDKN2A, CDKN2D, and CDKN1A. In young mice, experimental focal segmental glomerulosclerosis (FSGS) induced by adriamycin and antipodocyte antibody increased the glomerular expression of p16, p21, and senescence-associated ß-galactosidase (SA-ß-gal). To assess the long-term effects of early podocyte injury-induced senescence, we temporally followed young mice with experimental FSGS through adulthood (12 m of age) and middle age (18 m of age). p16 and Sudan black staining were higher at middle age in mice with earlier FSGS compared with age-matched mice that did not get FSGS when young. This was accompanied by lower podocyte density, reduced canonical podocyte protein expression, and increased glomerular scarring. These results are consistent with injury-induced senescence in young podocytes, leading to increased senescence of podocytes by middle age accompanied by lower podocyte lifespan and health span.NEW & NOTEWORTHY Glomerular function is decreased by aging. However, little is known about the molecular mechanisms involved in age-related glomerular changes and which factors could contribute to a worse glomerular aging process. Here, we reported that podocyte injury in young mice and culture podocytes induced senescence, a marker of aging, and accelerates glomerular aging when compared with healthy aging mice.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefropatias , Podócitos , Pessoa de Meia-Idade , Humanos , Camundongos , Animais , Idoso , Podócitos/metabolismo , Glomerulosclerose Segmentar e Focal/metabolismo , Glomérulos Renais/metabolismo , Nefropatias/metabolismo , Envelhecimento , Doxorrubicina/toxicidade , Doxorrubicina/metabolismo
10.
Rev Bras Enferm ; 76(5): e20220707, 2023.
Artigo em Inglês, Português | MEDLINE | ID: mdl-38018617

RESUMO

OBJECTIVES: to synthesize scientific evidence on vaccine hesitancy in children under five years of age and its associated factors. METHODS: a scoping review, conducted according to the methodological structure proposed by the JBI. Searches were carried out in the Latin American and Caribbean Center on Health Sciences Information, Scientific Electronic Library Online and PubMed databases, including gray literature. Studies in English, Spanish and Portuguese were included, without temporal delimitation. Editorials, studies that did not address vaccine hesitancy in children under five years of age and were not aligned with the objective and research question were excluded. The sample consisted of 18 articles. RESULTS: misinformation, concern about adverse effects, distrust about efficacy, affliction regarding administration simultaneously, and insecurity in relation to the laboratories were the reported reasons. CONCLUSIONS: strategies are needed to combat the lack of information about immunobiological agents, as misinformation was the main factor in parents' vaccine hesitation.


Assuntos
Pais , Vacinação , Criança , Humanos , Pré-Escolar , Comunicação
12.
Rev. baiana saúde pública ; 47(2): 199-229, 20230808.
Artigo em Português | LILACS | ID: biblio-1451842

RESUMO

Este estudo objetivou compreender as concepções que guiam a produção do cuidado em saúde mental na atenção básica (AB) por meio de uma metassíntese da literatura. Por meio das bases de dados e bibliotecas virtuais Scopus, LILACS, BDENF, SciELO, BVS e PubMed e utilizando os Descritores em Ciências da Saúde (DeCS), buscaram-se textos qualitativos em português, inglês e espanhol, publicados no Brasil entre 2010 e 2020, que abordassem como a produção do cuidado em saúde mental está sendo desenvolvida na AB do país; cujos objetivos se referissem a atos e saberes desenvolvidos em saúde mental na AB; que abordassem o conceito de integralidade do cuidado em saúde mental desenvolvido na AB do Brasil; e que tratassem do entendimento quanto à mudança da prática profissional a partir dessas iniciativas. Foram selecionados 66 trabalhos, a partir dos quais se identificou que a saúde mental ainda sofre com as consequências herdadas do modelo hospitalocêntrico e asilar de produção do cuidado. Além disso, evidenciaram-se impactos das questões e experiências pessoais na saúde mental dos sujeitos, negligência e visão restrita do cuidado psicossocial, predomínio de práticas biomédicas, centralização nas ações intramuros e psiquiatrização das práticas de saúde mental na AB, os quais constituem barreiras ao processo de desinstitucionalização e integralidade do cuidado em saúde mental. Assim, é importante reconhecer a legitimidade dos saberes e repensar práticas menos cristalizadas, a fim de enfrentar e problematizar modelos hegemônicos, para que se avance na produção do cuidado em saúde mental na AB.


This study aimed to understand the concepts that guide the production of mental health care developed in Primary Care (PC), with a meta-synthesis of the literature. From the databases and virtual libraries Scopus, LILACS, BDENF, SciELO, VHL, and PubMed and using Descriptors in Health Sciences (DeCS), qualitative texts in Portuguese, English, and Spanish, published in Brazil between 2010 and 2020 were sought., which addressed how the production of mental health care is being developed in PC in the country; works whose objectives refer to acts and knowledge developed in mental health in PC; works that address the concept of comprehensive mental health care developed in PC in Brazil; and works on understanding the change in professional practice based on these initiatives. A total of 66 papers were selected, from which it was identified that mental health still suffers from the consequences inherited from the hospital-centered and asylum model of care production. In addition, the impacts of personal issues and experiences on the subjects' mental health, negligence and restricted view of psychosocial care, predominance of biomedical practices, centralization in intramural actions, and psychiatrization of mental health practices in PC were evidenced, which constitute barriers to process of deinstitutionalization and integrality of mental health care. Thus, it is important to recognize the legitimacy of knowledge and rethink less crystallized practices, to face and problematize hegemonic models, so that the production of mental health care in PC can advance.


Este estudio tuvo como objetivo comprender los conceptos que orientan la producción del cuidado en salud mental en la atención primaria (AP), mediante una metasíntesis de la literatura. Desde las bases de datos y bibliotecas virtuales Scopus, LILACS, BDENF, SciELO, BVS y PubMed, y utilizando los Descriptores en Ciencias de la Salud (DeCS), se buscaron textos cualitativos en portugués, inglés y español, publicados en Brasil entre 2010 y 2020, que abordaron cómo la producción de atención a la salud mental se desarrolla en AP en el país; trabajos cuyos objetivos se refieran a actos y saberes desarrollados en salud mental en AP; los que abordaron el concepto de atención integral a la salud mental desarrollado en AP en Brasil; y aquellos que trataron de la comprensión del cambio en la práctica profesional a partir de estas iniciativas. Se seleccionaron 66 artículos, y se identificó que la salud mental aún sufre las consecuencias heredadas del modelo hospitalario y el aislamiento de la producción del cuidado. Además, los impactos de los problemas y experiencias personales en la salud mental de los sujetos, la negligencia y la visión restringida de la atención psicosocial, el predominio de las prácticas biomédicas, la centralización en las acciones intramuros y la psiquiatrización de las prácticas de salud mental en AP constituyen barreras para el proceso de desinstitucionalización e integralidad de la atención en salud mental. Así, es importante reconocer la legitimidad de los saberes y repensar las prácticas menos cristalizadas para enfrentar modelos hegemónicos y problematizarlos para que la producción de cuidados en salud mental en AP pueda avanzar.

13.
J Endod ; 49(9): 1207-1215, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37468061

RESUMO

The loss of periodontal tissue support and vertical buccal bone loss in apico-marginal defects can often be mistaken for features indicative of vertical root fractures and this study reports thirteen cases with persistent symptomatic apical periodontitis, apico-marginal defects, and large periapical lesions that were managed with endodontic microsurgery in conjunction with bone grafts and barrier placements with a follow-up period of up to 9 years. At the recall sessions, all cases were asymptomatic with radiographical success with only 2 cases exhibiting residual apical radiolucency, but with evident reduction in the lesion size, indicative of healing. This study highlights the potential of utilizing endodontic microsurgery combined with guided tissue regeneration that proved effective in stimulating the regeneration of periodontal tissue in cases of apico-marginal defects that can lead to favourable long-term outcomes.


Assuntos
Microcirurgia , Periodontite Periapical , Humanos , Regeneração Tecidual Guiada Periodontal , Periodontite Periapical/diagnóstico por imagem , Periodontite Periapical/cirurgia , Cicatrização , Periodonto
14.
Front Cell Neurosci ; 17: 1195843, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37416507

RESUMO

Organophosphates (OP) are highly toxic chemical nerve agents that have been used in chemical warfare. Currently, there are no effective medical countermeasures (MCMs) that mitigate the chronic effects of OP exposure. Oxidative stress is a key mechanism underlying OP-induced cell death and inflammation in the peripheral and central nervous systems and is not mitigated by the available MCMs. NADPH oxidase (NOX) is one of the leading producers of reactive oxygen species (ROS) following status epilepticus (SE). In this study, we tested the efficacy of the mitochondrial-targeted NOX inhibitor, mitoapocynin (MPO) (10 mg/kg, oral), in a rat diisopropylfluorophosphate (DFP) model of OP toxicity. In DFP-exposed animals, MPO decreased oxidative stress markers nitrite, ROS, and GSSG in the serum. Additionally, MPO significantly reduced proinflammatory cytokines IL-1ß, IL-6, and TNF-α post-DFP exposure. There was a significant increase in GP91phox, a NOX2 subunit, in the brains of DFP-exposed animals 1-week post-challenge. However, MPO treatment did not affect NOX2 expression in the brain. Neurodegeneration (NeuN and FJB) and gliosis [microglia (IBA1 and CD68), and astroglia (GFAP and C3)] quantification revealed a significant increase in neurodegeneration and gliosis after DFP-exposure. A marginal reduction in microglial cells and C3 colocalization with GFAP in DFP + MPO was observed. The MPO dosing regimen used in this study at 10 mg/kg did not affect microglial CD68 expression, astroglial count, or neurodegeneration. MPO reduced DFP-induced oxidative stress and inflammation markers in the serum but only marginally mitigated the effects in the brain. Dose optimization studies are required to determine the effective dose of MPO to mitigate DFP-induced changes in the brain.

15.
iScience ; 26(7): 107172, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37404372

RESUMO

Idiopathic inflammatory myopathies (IIM) are a group of chronic autoimmune diseases mainly affecting proximal muscles. Absence of meaningful prognostic factors in IIM has hindered new therapies development. Glycans are essential molecules that regulate immunological tolerance and consequently the onset of autoreactive immune response. We showed that muscle biopsies from patients with IIM revealed a deficiency in the glycosylation pathway resulting in loss of branched N-glycans. At diagnosis, this glycosignature predicted disease relapse and treatment refractoriness. Peripheral CD4+ T cells from active-disease patients shown a deficiency in branched N-glycans, linked to increased IL-6 production. Glycan supplementation, restoring homeostatic glycosylation profile, led to a decrease in IL-6 levels. This study highlights the biological and clinical importance of glycosylation in IIM immunopathogenesis, providing a potential mechanism for IL-6 production. This pinpoints muscle glycome as promising biomarker for personalized follow-up and a potential target for new therapies in a patients' subgroup with an ominous evolution.

16.
Aging (Albany NY) ; 15(14): 6658-6689, 2023 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-37487005

RESUMO

The decrease in the podocyte's lifespan and health-span that typify healthy kidney aging cause a decrease in their normal structure, physiology and function. The ability to halt and even reverse these changes becomes clinically relevant when disease is superimposed on an aged kidney. RNA-sequencing of podocytes from middle-aged mice showed an inflammatory phenotype with increases in the NLRP3 inflammasome, signaling for IL2/Stat5, IL6 and TNF, interferon gamma response, allograft rejection and complement, consistent with inflammaging. Furthermore, injury-induced NLRP3 signaling in podocytes was further augmented in aged mice compared to young ones. The NLRP3 inflammasome (NLRP3, Caspase-1, IL1ß IL-18) was also increased in podocytes of middle-aged humans. Higher transcript expression for NLRP3 in human glomeruli was accompanied by reduced podocyte density and increased global glomerulosclerosis and glomerular volume. Pharmacological inhibition of NLRP3 with MCC950, or gene deletion, reduced podocyte senescence and the genes typifying aging in middle-aged mice, which was accompanied by an improved podocyte lifespan and health-span. Moreover, modeling the injury-dependent increase in NLRP3 signaling in human kidney organoids confirmed the anti-senescence effect of MC9950. Finally, NLRP3 also impacted liver aging. Together, these results suggest a critical role for the NLRP3 inflammasome in podocyte and liver aging.


Assuntos
Podócitos , Humanos , Animais , Camundongos , Pessoa de Meia-Idade , Podócitos/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Glomérulos Renais/metabolismo , Envelhecimento
17.
Cell Mol Immunol ; 20(8): 955-968, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37344746

RESUMO

T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens. Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the N-glycosylation profile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showed remarkable defects in key developmental checkpoints, including ß-selection, regulatory T-cell generation and γδT-cell development, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstrated that a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. In conclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.


Assuntos
Timócitos , Timo , Camundongos , Animais , Humanos , Glicosilação , Receptores de Antígenos de Linfócitos T/metabolismo , Proteínas de Homeodomínio/genética , Polissacarídeos
18.
Environ Sci Pollut Res Int ; 30(26): 68987-68997, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37131003

RESUMO

Marine biofouling pollution is a process that impacts ecosystems and the global economy. On the other hand, traditional antifouling (AF) marine coatings release persistent and toxic biocides that accumulate in sediments and aquatic organisms. To understand the putative impact on marine ecosystems of recently described and patented AF xanthones (xanthones 1 and 2), able to inhibit mussel settlement without acting as biocides, several in silico environmental fate predictions (bioaccumulation, biodegradation, and soil absorption) were calculated in this work. Subsequently, a degradation assay using treated seawater at different temperatures and light exposures was conducted for a period of 2 months to calculate their half-life (DT50). Xanthone 2 was found to be non-persistent (DT50 < 60 days) at 50 µM, contrary to xanthone 1 (DT50 > 60 days). To evaluate the efficacy of both xanthones as AF agents, they were blended into four polymeric-based coating systems: polyurethane- and polydimethylsiloxane (PDMS)-based marine paints, as well as room-temperature-vulcanizing PDMS- and acrylic-based coatings. Despite their low water solubility, xanthones 1 and 2 demonstrated suitable leaching behaviors after 45 days. Overall, the generated xanthone-based coatings were able to decrease the attachment of the Mytilus galloprovincialis larvae after 40 h. This proof-of-concept and environmental impact evaluation will contribute to the search for truly environmental-friendly AF alternatives.


Assuntos
Incrustação Biológica , Desinfetantes , Incrustação Biológica/prevenção & controle , Ecossistema , Solubilidade , Água do Mar , Desinfetantes/toxicidade
19.
Mar Environ Res ; 188: 106017, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37178663

RESUMO

Invasive alien species have been rising exponentially in the last decades impacting biodiversity and ecosystem functioning. The soniferous weakfish, Cynoscion regalis, is a recent invasive sciaenid species in the Iberian Peninsula and was first reported in the Tagus estuary in 2015. There is concern about its possible impacts on native species, namely the confamiliar meagre, Argyrosomus regius, as there is overlap in their feeding regime, habitat use, and breeding behaviour. Here, we characterised the sciaenid-like sounds recently recorded in the Tagus estuary and showed that they are made by weakfish as they have similar numbers of pulses and pulse periods to the sounds made by captive breeding weakfish. We further demonstrate that breeding grunts from weakfish and the native sciaenid, recorded either in captivity or Tagus estuary, differ markedly in sound duration, number of pulses and pulse period in the two species, but overlap in their spectral features. Importantly, these differences are easily detected through visual and aural inspections of the recordings, making acoustic recognition easy even for the non-trained person. We propose that passive acoustic monitoring can be a cost-effective tool for in situ mapping of weakfish outside its natural distribution and an invaluable tool for early detection and to monitor its expansion.


Assuntos
Espécies Introduzidas , Perciformes , Animais , Ecossistema , Peixes , Acústica
20.
J Pediatr Endocrinol Metab ; 36(6): 584-591, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37071811

RESUMO

OBJECTIVES: Regular physical activity and adequate food are part of a healthy lifestyle for the maintenance of physical and metabolic health. To verify the moderating role of physical activity (PA) in the relationship between dietary patterns and body adiposity in adolescents, according to somatic maturation. METHODS: Study with cross-sectional design, sample of 336 adolescents of both sexes, aged between 11 and 17 years. Body mass, height, and waist circumference (WC) were evaluated. Body mass index (BMI), BMI z-score (BMI-z), waist-to-height ratio (WHtR), and somatic maturation by peak height velocity (PHV) were calculated. The level of PA was measured by the International Physical Activity Questionnaire and dietary pattern by the Food Frequency Questionnaire ELSA - Brazil (short version). Moderation analyzes were tested using multiple linear regression models, by PROCESS macro for SPSS. RESULTS: An inverse interaction of PA was observed in the relationship between food consumption factor 5 (ultra-processed foods category) and WC in boys categorized as pre-pubertal and pubertal PHV (ß=-5.344; CI95 % -10.108 -0.580; p=0.028). For girls, no interaction was observed in any of the models analyzed. CONCLUSIONS: It was observed that the level of PA can influence food choices in prepubertal and pubertal boys, since the active boys showed better dietary pattern and lower central adiposity. Therefore, the findings reinforce the need to encourage the regular practice of physical activities from an early age, mainly aimed at preventing obesity in children and adolescents.


Assuntos
Adiposidade , Obesidade Pediátrica , Masculino , Criança , Feminino , Humanos , Adolescente , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/prevenção & controle , Estudos Transversais , Índice de Massa Corporal , Exercício Físico , Circunferência da Cintura
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