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1.
Chest ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39389342

RESUMO

BACKGROUND: It remains uncertain how long pure ground-glass nodules (pGGNs) detected on low dose computed tomography (LDCT) should be followed. Further studies with longer follow-up periods are needed to determine the optimal follow-up duration for pGGNs. RESEARCH QUESTION: What is the percentage of enlarging nodules among pGGNs that have remained stable for 10 years? STUDY DESIGN AND METHODS: This was a retrospective cohort study originating from subjects with pGGNs detected on LDCT scans between 1997 and 2006, whose natural courses were reported in 2013. We re-analyzed all the follow-up data until July 2022. The study subjects were followed by our institutional guidelines until they were no longer a candidate for definitive treatment. The growth of the pGGNs was defined as an increase in the diameter of the entire nodule by 2 mm or more or the appearance of new solid portions within the nodules. RESULTS: A total of 89 patients with 135 pGGNs were followed for a median of 193 months. Of 135 pGGNs, 23 (17.0%) increased in size, and the median time to the first detection of a size change was 71 months. Of the 23 growing pGGNs, 122 were detected on the first LDCT, and 13 were newly detected on the follow-up CT scan. An increase in size was observed within 5 years in 8 nodules (34.8%), between 5 and 10 years in 12 nodules (52.2%) and after 10 years in 3 nodules (13.0%). Fifteen nodules were histologically confirmed as adenocarcinoma by surgery. Among the 76 pGGNs stable for 10 years, 3 (3.9%) increased in size. INTERPRETATION: Among pGGNs that remained stable for 10 years, 3.9% eventually grew, indicating that some pGGNs can grow even after a long period of stability. We suggest that pGGNs may need to be followed for more than 10 years to confirm growth.

2.
Nat Commun ; 15(1): 5974, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358330

RESUMO

Commercial wearable biosignal sensing technologies encounter challenges associated with irritation or discomfort caused by unwanted objects in direct contact with the skin, which can discourage the widespread adoption of wearable devices. To address this issue, we propose a fabric-based lamina emergent MXene-based electrode, a lightweight and flexible shape-morphing wearable bioelectrode. This work offers an innovative approach to biosignal sensing by harnessing the high electrical conductivity and low skin-to-electrode contact impedance of MXene-based dry electrodes. Its design, inspired by Nesler's pneumatic interference actuator, ensures stable skin-to-electrode contact, enabling robust biosignal detection in diverse situations. Extensive research is conducted on key design parameters, such as the width and number of multiple semicircular legs, the radius of the anchoring frame, and pneumatic pressure, to accommodate a wide range of applications. Furthermore, a real-time wireless electrophysiological monitoring system has been developed, with a signal-to-noise ratio and accuracy comparable to those of commercial bioelectrodes. This work excels in recognizing various hand gestures through a convolutional neural network, ultimately introducing a shape-morphing electrode that provides reliable, high-performance biosignal sensing for dynamic users.


Assuntos
Eletrodos , Dispositivos Eletrônicos Vestíveis , Humanos , Têxteis , Condutividade Elétrica , Desenho de Equipamento , Fenômenos Eletrofisiológicos , Tecnologia sem Fio/instrumentação , Razão Sinal-Ruído , Impedância Elétrica
3.
Cancer Immunol Immunother ; 73(12): 260, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382668

RESUMO

Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07-0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48-17.34]; Group 3: PD-L1- and thyroid irAE- : 30.49 [6.60-140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor-Node-Metastasis staging. Our study suggests thyroid irAEs and PD-L1 expression are independent biomarkers that improve predicting PD-1 blockade efficacy in NSCLC. Thyroid irAEs would be helpful to identify NSCLC patients who benefit from PD-1 blockade in early course of treatment.


Assuntos
Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Feminino , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Glândula Tireoide/patologia , Glândula Tireoide/metabolismo , Estudos Longitudinais , Prognóstico , Adulto , Idoso de 80 Anos ou mais
4.
Nat Commun ; 15(1): 8628, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39366998

RESUMO

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39+CD9+ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39+CD9+ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39+CD9+ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39+CD9+ IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39+CD9+ IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.


Assuntos
Apirase , Asma , Armadilhas Extracelulares , Interleucina-23 , Neutrófilos , Tetraspanina 29 , Células Th17 , Asma/imunologia , Asma/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Interleucina-23/metabolismo , Interleucina-23/imunologia , Humanos , Animais , Apirase/metabolismo , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Tetraspanina 29/metabolismo , Tetraspanina 29/genética , Camundongos , Feminino , Masculino , Pulmão/imunologia , Pulmão/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Antígenos CD
5.
Imaging Sci Dent ; 54(3): 264-270, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39371303

RESUMO

Purpose: This study aimed to propose a methodological approach for reducing the radiation dose in pediatric conebeam computed tomography (CBCT), focusing exclusively on balancing image quality with dose optimization. Materials and Methods: The dose-area product (DAP) for exposure was reduced using copper-plate attenuation of an X-ray source. The thickness of copper (Cu) was increased from 0 to 2.2 mm, and 10 different DAP levels were used. The QUART DVT_AP phantom and pediatric radiologic dentiform were scanned under the respective DAP levels. The contrast-to-noise ratio (CNR), image homogeneity, and modulation transfer function (MTF) were analyzed using the QUART DVT_AP phantom. An expert evaluation (overall image grade, appropriateness of field of view, artifacts, noise, and resolution) was conducted using pediatric dentiform images. The critical DAP level was determined based on phantom and dentiform analysis results. Results: CNR and image homogeneity decreased as the DAP was reduced; however, there was an inflection point of image homogeneity at Cu 1.6 mm (DAP=138.00 mGy·cm2), where the value started increasing. The MTF showed constant values as the DAP decreased. The expert evaluation of overall image grades showed "no diagnostic value" for dentiform images with Cu 1.9-2.2 mm (DAP=78.00-103.33 mGy·cm2). The images with Cu 0-1.6 mm (DAP=138.00-1697.67 mGy·cm2) had a "good," "moderate," or "poor but interpretable" grade. Conclusion: Reducing DAP beyond a 1.6-mm Cu thickness degraded CBCT image quality. Image homogeneity and clinical image grades indicated crucial decision points for DAP reduction in pediatric CBCT scans.

6.
Sci Rep ; 14(1): 22233, 2024 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333200

RESUMO

Esophageal fibrosis can develop due to caustic or radiation injuries. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are known to mitigate fibrosis in various organs. However, the potential effects of UC-MSCs on human esophageal fibrosis remain underexplored. This study investigated the anti-fibrogenic properties and mechanisms of UC-MSC-derived conditioned media (UC-MSC-CM) on human esophageal fibroblasts (HEFs). HEFs were treated with TGF-ß1 and then cultured with UC-MSC-CM, and the expression levels of extracellular matrix (ECM) components, RhoA, myocardin related transcription factor A (MRTF-A), serum response factor (SRF), Yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) were measured. UC-MSC-CM suppressed TGF-ß1-induced fibrogenic activation in HEFs, as evidenced by the downregulation of ECM. UC-MSC-CM diminished the expression of RhoA, MRTF-A, and SRF triggered by TGF-ß1. In TGF-ß1-stimulated HEFs, UC-MSC-CM decreased the nuclear localization of MRTF-A and YAP. Additionally, UC-MSC-CM diminished the TGF-ß1-induced nuclear expressions of YAP and TAZ, while concurrently enhancing the cytoplasmic presence of phosphorylated YAP. Furthermore, UC-MSC-CM reduced TGF-ß1-induced phosphorylation of Smad2. These findings suggest that UC-MSC-CM may inhibit TGF-ß1-induced fibrogenic activation in HEFs by targeting the Rho-mediated MRTF/SRF and YAP/TAZ pathways, as well as the Smad2 pathway. This indicates its potential as a stem cell therapy for esophageal fibrosis.


Assuntos
Esôfago , Fibroblastos , Fibrose , Células-Tronco Mesenquimais , Transativadores , Fatores de Transcrição , Fator de Crescimento Transformador beta1 , Proteína rhoA de Ligação ao GTP , Humanos , Células-Tronco Mesenquimais/metabolismo , Meios de Cultivo Condicionados/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Esôfago/metabolismo , Esôfago/citologia , Fibroblastos/metabolismo , Transativadores/metabolismo , Transativadores/genética , Fatores de Transcrição/metabolismo , Cordão Umbilical/citologia , Proteínas de Sinalização YAP/metabolismo , Fator de Resposta Sérica/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transdução de Sinais , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Células Cultivadas , Matriz Extracelular/metabolismo , Proteína Smad2/metabolismo
7.
BMC Med Imaging ; 24(1): 256, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333936

RESUMO

BACKGROUND: Kidney biopsy is the standard of care for the diagnosis of various kidney diseases. In particular, chronic histopathologic lesions, such as interstitial fibrosis and tubular atrophy, can provide prognostic information regarding chronic kidney disease progression. In this study, we aimed to evaluate historadiological correlations between CT-based radiomic features and chronic histologic changes in native kidney biopsies and to construct and validate a radiomics-based prediction model for chronicity grade. METHODS: We included patients aged ≥ 18 years who underwent kidney biopsy and abdominal CT scan within a week before kidney biopsy. Left kidneys were three-dimensionally segmented using a deep learning model based on the 3D Swin UNEt Transformers architecture. We additionally defined isovolumic cortical regions of interest near the lower pole of the left kidneys. Shape, first-order, and high-order texture features were extracted after resampling and kernel normalization. Correlations and diagnostic metrics between extracted features and chronic histologic lesions were examined. A machine learning-based radiomic prediction model for moderate chronicity was developed and compared according to the segmented regions of interest (ROI). RESULTS: Overall, moderate correlations with statistical significance (P < 0.05) were found between chronic histopathologic grade and top-ranked radiomic features. Total parenchymal features were more strongly correlated than cortical ROI features, and texture features were more highly ranked. However, conventional imaging markers, including kidney length, were poorly correlated. Top-ranked individual radiomic features had areas under receiver operating characteristic curves (AUCs) of 0.65 to 0.74. Developed radiomics models for moderate-to-severe chronicity achieved AUCs of 0.89 (95% confidence interval [CI] 0.75-0.99) and 0.74 (95% CI 0.52-0.93) for total parenchymal and cortical ROI features, respectively. CONCLUSION: Significant historadiological correlations were identified between CT-based radiomic features and chronic histologic changes in native kidney biopsies. Our findings underscore the potential of CT-based radiomic features and their prediction model for the non-invasive assessment of kidney fibrosis.


Assuntos
Rim , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Feminino , Masculino , Rim/diagnóstico por imagem , Rim/patologia , Pessoa de Meia-Idade , Biópsia , Adulto , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/patologia , Idoso , Estudos Retrospectivos , Aprendizado Profundo , Radiômica
9.
Bioresour Technol ; 413: 131499, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299349

RESUMO

Predator-prey interactions play a crucial role in maintaining ecological balance and possibly provide inspiration for strategies to mitigate environmental changes such as harmful algal blooms (HABs). To this end, this study aims to develop a novel strategy to mitigate HABs based on predator-prey interaction, i.e., Daphnia magna and Microcystis aeruginosa interaction. Bio-compounds (urea and 9-octadecenamide) produced by D. magna when encounter M. aeruginosa, were identified, particularly with urea promoting the aggregation of M. aeruginosa. Then, a novel adsorbent against HABs was synthesized by integrating bio-compounds of urea, and its effectiveness in removing M. aeruginosa was demonstrated. Notably, the adsorbent displayed a high removal efficiency of 99.25 % within 6 h. Our eco-friendly strategy holds promise for controlling HABs, representing the successful application of biomimicry principles.

10.
Dev Cell ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39232563

RESUMO

Intestinal stem cells (ISCs) are highly vulnerable to damage, being in a constant state of proliferation. Reserve stem cells repair the intestinal epithelium following damage-induced ablation of ISCs. Here, we report that the epigenetic regulator plant homology domain (PHD) finger protein 16 (PHF16) restores homeostasis of the intestinal epithelium after initial damage-induced repair. In Phf16-/Y mice, revival stem cells (revSCs) showed defects in exiting the regenerative state, and intestinal crypt regeneration failed even though revSCs were still induced in response to tissue damage, as observed by single-cell RNA sequencing (scRNA-seq). Analysis of Phf16-/Y intestinal organoids by RNA sequencing (RNA-seq) and ATAC sequencing identified that PHF16 restores homeostasis of the intestinal epithelium by inducing retinoic acid receptor (RAR)/retinoic X receptor (RXR) target genes through HBO1-mediated histone H3K14 acetylation, while at the same time counteracting YAP/TAZ activity by ubiquitination of CDC73. Together, our findings demonstrate the importance of timely suppression of regenerative activity by PHF16 for the restoration of gut homeostasis after acute tissue injury.

11.
bioRxiv ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39257793

RESUMO

Weakening of synaptic transmission at the Drosophila larval neuromuscular junction triggers two forms of homeostatic compensation, one that increases the probability of glutamate release per action potential (Pr) and another that increases motoneuron (MN) activity. We investigated the molecular changes in MNs that underlie the increase in MN activity. RNA-seq analysis on MNs whose glutamate release is weakened by knockdown of components of the MN transmitter release machinery reveals a reduction in expression of a group of genes that encode potassium channels and their positive modulators. These results identify a mechanism of compensation for weakened synaptic transmission by MNs, which engages a transcriptional program in those cells to increase firing and, thereby, ensure sufficient locomotory drive.

12.
Angew Chem Int Ed Engl ; : e202415821, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39252675

RESUMO

Molecular crystals capable of colossal thermal expansion (TE) are fascinating owing to their substantial and continuous volume changes and reasonably linear responses to temperature. This makes them promising candidates for micromachine applications. Macroscopic motion is driven by subtle yet cooperative movements of molecules that respond to the thermal motions of dynamic functional units. The study of p-TIPS-DSB presented here offers a compelling case highlighting the relationship between the degree of dynamicity of functional units and TE behavior. In its α-phase, the p-TIPS-DSB crystal undergoes an irreversible martensitic transition to the ß-phase, accompanied by significant cooperative interlayer shear. This process substantially enhances the mobility of the side-chains driven by the increased free volume surrounding them. This nearly doubles the volumetric TE coefficient from 255.3 (10) to 444.9 (32) MK-1, particularly in the actuation direction from 175.0 (7) to 291.7 (20) MK-1, enabling about 4.5% elongation/contraction. As demonstrated here, p-TIPS-DSB exhibits a decent force density (> 1.4 × 107 N m-3) and precise motion control capabilities due to its hysteresis-free and non-abrupt TE nature. Furthermore, we demonstrated the limited operating distance of colossal TE materials can be amplified by utilizing levers, highlighting the high potential of these materials for use in micromachines.

13.
Biomed Pharmacother ; 179: 117313, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39167844

RESUMO

Mycobacteroides abscessus (Mabc) is a rapidly growing nontuberculous mycobacterium that poses a considerable challenge as a multidrug-resistant pathogen causing chronic human infection. Effective therapeutics that enhance protective immune responses to Mabc are urgently needed. This study introduces trans-3,5,4'-trimethoxystilbene (V46), a novel resveratrol analogue with autophagy-activating properties and antimicrobial activity against Mabc infection, including multidrug-resistant strains. Among the resveratrol analogues tested, V46 significantly inhibited the growth of both rough and smooth Mabc strains, including multidrug-resistant strains, in macrophages and in the lungs of mice infected with Mabc. Additionally, V46 substantially reduced Mabc-induced levels of pro-inflammatory cytokines and chemokines in both macrophages and during in vivo infection. Mechanistic analysis showed that V46 suppressed the activation of the protein kinase B/Akt-mammalian target of rapamycin signaling pathway and enhanced adenosine monophosphate-activated protein kinase signaling in Mabc-infected cells. Notably, V46 activated autophagy and the nuclear translocation of transcription factor EB, which is crucial for antimicrobial host defenses against Mabc. Furthermore, V46 upregulated genes associated with autophagy and lysosomal biogenesis in Mabc-infected bone marrow-derived macrophages. The combination of V46 and rifabutin exerted a synergistic antimicrobial effect. These findings identify V46 as a candidate host-directed therapeutic for Mabc infection that activates autophagy and lysosomal function via transcription factor EB.


Assuntos
Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Mycobacterium abscessus , Autofagia/efeitos dos fármacos , Animais , Mycobacterium abscessus/efeitos dos fármacos , Camundongos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Estilbenos/farmacologia , Humanos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Antibacterianos/farmacologia , Camundongos Endogâmicos C57BL , Feminino , Citocinas/metabolismo , Camundongos Endogâmicos BALB C
14.
Ecotoxicol Environ Saf ; 283: 116823, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39096687

RESUMO

BACKGROUND: This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants. RESULTS: A total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM2.5 (4.56 µg/m3) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath's clock), respectively. An IQR increase in PM2.5 (4.76 µg/m3) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath's clock) and 0.289 years of EAA (Wu's clock). PM10 (4.30 µg/m3) and O3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath's clock (0.280 years) and EAA in Horvath's skin and blood clock (0.163 years), respectively. CONCLUSION: We found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Epigênese Genética , Material Particulado , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Poluentes Atmosféricos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Material Particulado/toxicidade , Criança , Masculino , Epigênese Genética/efeitos dos fármacos , Poluição do Ar/efeitos adversos , Estudos de Coortes , Envelhecimento , Monóxido de Carbono/toxicidade , Exposição Ambiental/efeitos adversos , Ozônio/toxicidade , Dióxido de Nitrogênio/toxicidade , Metilação de DNA/efeitos dos fármacos , Exposição Materna/efeitos adversos , China
15.
Chemosphere ; 364: 143167, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39181460

RESUMO

Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005-2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend = 0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.


Assuntos
Ácidos Alcanossulfônicos , Caprilatos , Exposição Ambiental , Poluentes Ambientais , Fluorocarbonos , Degeneração Macular , Inquéritos Nutricionais , Humanos , Fluorocarbonos/sangue , Degeneração Macular/epidemiologia , Degeneração Macular/induzido quimicamente , Pessoa de Meia-Idade , Feminino , Idoso , Masculino , Ácidos Alcanossulfônicos/sangue , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Estados Unidos/epidemiologia , Caprilatos/sangue , Ácidos Sulfônicos/sangue , Adulto , Idoso de 80 Anos ou mais , Ácidos Graxos
16.
Cancer Metab ; 12(1): 25, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210390

RESUMO

BACKGROUND: Mitochondria are known to synthesize adenosine triphosphate (ATP) through oxidative phosphorylation. Understanding and accurately measuring mitochondrial ATP synthesis rate can provide insights into the functional status of mitochondria and how it contributes to overall cellular energy homeostasis. Traditional methods only estimate mitochondrial function by measuring ATP levels at a single point in time or through oxygen consumption rates. This study introduced the relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE), designed to detect real-time changes in ATP levels as the cells respond to substrates. METHODS: The sensitivity and specificity of the MitoRAISE assay were verified under various conditions, including the isolation of mitochondria, variations in cell numbers, cells exhibiting mitochondrial damage, and heterogeneous mixtures. Using peripheral blood mononuclear cells (PBMCs), we analyzed MitoRAISE data from 19 patients with breast cancer and 23 healthy women. RESULTS: The parameters observed in the MitoRAISE data increased depending on the quantity of isolated mitochondria and cell count, whereas it remained unmeasured in mitochondrial-damaged cell lines. Basal ATP, rotenone response, malonate response, and mitochondrial DNA copy numbers were lower in PBMCs from patients with breast cancer than in those from healthy women. CONCLUSIONS: The MitoRAISE assay has demonstrated its sensitivity and specificity by measuring relative ATP synthesis rates under various conditions. We propose MitoRAISE assay as a potential tool for monitoring changes in the mitochondrial metabolic status associated with various diseases.

17.
J Immunol ; 213(6): 886-897, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39101764

RESUMO

Intestinal microbiota and selected strains of commensal bacteria influence regulatory T (Treg) cell functionality in the colon. Nevertheless, whether and how microbiota changes the transcriptome profile and TCR specificities of colonic Tregs remain to be precisely defined. In this study, we have employed single-cell RNA sequencing and comparatively analyzed colonic Tregs from specific pathogen-free and germ-free (GF) mice. We found that microbiota shifts the activation trajectory of colonic Tregs toward a distinct phenotypic subset enriched in specific pathogen-free but not in GF mice. Moreover, microbiota induced the expansion of specific Treg clonotypes with shared transcriptional specificities. The microbiota-induced subset of colonic Tregs, identified as PD-1- CXCR3+ Tregs, displayed enhanced suppressive capabilities compared with colonic Tregs derived from GF mice, enhanced production of IL-10, and were the primary regulators of enteric inflammation in dextran sodium sulfate-induced colitis. These findings identify a hitherto unknown gut microbiota and immune cell interaction module that could contribute to the development of a therapeutic modality for intestinal inflammatory diseases.


Assuntos
Colite , Colo , Microbioma Gastrointestinal , Receptores de Antígenos de Linfócitos T , Linfócitos T Reguladores , Animais , Microbioma Gastrointestinal/imunologia , Camundongos , Linfócitos T Reguladores/imunologia , Colo/imunologia , Colo/microbiologia , Colite/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Camundongos Endogâmicos C57BL , Sulfato de Dextrana , Organismos Livres de Patógenos Específicos , Interleucina-10/imunologia
18.
Skin Res Technol ; 30(8): e13908, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39141418

RESUMO

BACKGROUND: Classifying diverse skin types is crucial for promoting skin health. However, efficiently identifying and analyzing relevant biomarkers from a vast array of available genetic data is challenging. Therefore, this study aimed to develop a precise and efficient platform for analyzing specific skin biomarkers using quantitative real-time PCR (qRT-PCR) with the minimal invasive skin sampling method (MISSM). MATERIALS AND METHODS: MISSM was used for RNA extraction from skin samples, followed by qRT-PCR analysis to quantify the expression of 20 biomarkers associated with skin characteristics (four biomarkers each for five skin characteristics). Noninvasive measurements from 299 Korean participants were utilized to correlate biomarker expression with skin parameters. Statistical analyses were conducted between biomarker expression levels and noninvasive skin measurements to select the relatively best-performing biomarker for each skin characteristic. RESULTS: Collagen type 1 alpha 1 (COL1A1) and moesin (MSN) were identified as skin aging biomarkers. Krüppel-like factor 4 (KLF4) and serine peptidase inhibitor Kazal type 5 (SPINK5) were identified as skin dryness biomarkers, whereas melan-A (MLANA) was selected as a biomarker for understanding pigmentation dynamics. Myelin protein zero like 3 (MPZL3) and high mobility group box 2 (HMGB2) were identified as markers of oily skin and skin sensitivity, respectively. Statistically significant correlations were found between the biomarker expression levels and noninvasive skin characteristic measurements. CONCLUSION: This study successfully developed a platform for the precise evaluation of individual skin characteristics using MISSM and qRT-PCR biomarker analysis. By selecting biomarkers that correlate with noninvasive measurements of skin characteristics, we demonstrated the platform's efficacy in assessing diverse skin conditions.


Assuntos
Biomarcadores , Fator 4 Semelhante a Kruppel , Reação em Cadeia da Polimerase em Tempo Real , Envelhecimento da Pele , Pele , Humanos , Biomarcadores/metabolismo , Biomarcadores/análise , Feminino , Masculino , Reação em Cadeia da Polimerase em Tempo Real/métodos , Pele/metabolismo , Adulto , Pessoa de Meia-Idade , Envelhecimento da Pele/genética , Envelhecimento da Pele/fisiologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Idoso , Adulto Jovem
19.
Sci Rep ; 14(1): 17776, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090167

RESUMO

Although previous studies have suggested that meteorological factors and air pollutants can cause dry eye disease (DED), few clinical cohort studies have determined the individual and combined effects of these factors on DED. We investigated the effects of meteorological factors (humidity and temperature) and air pollutants [particles with a diameter ≤ 2.5 µ m (PM2.5), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO)] on DED. A retrospective cohort study was conducted on 53 DED patients. DED was evaluated by Symptom Assessment in Dry Eye (SANDE), tear secretion, tear film break-up time (TBUT), ocular staining score (OSS), and tear osmolarity. To explore the individual, non-linear, and joint associations between meteorological factors, air pollutants, and DED parameters, we used generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR). After adjusting for all covariates, lower relative humidity or temperature was associated with a higher SANDE (p < 0.05). Higher PM2.5, O3, and NO2 levels were associated with higher SANDE and tear osmolarity (p < 0.05). Higher O3 levels were associated with lower tear secretion and TBUT, whereas higher NO2 levels were associated with higher OSS (p < 0.05). BKMR analyses indicated that a mixture of meteorological factors and air pollutants was significantly associated with increased SANDE, OSS, tear osmolarity, and decreased tear secretion.


Assuntos
Poluentes Atmosféricos , Síndromes do Olho Seco , Humanos , Estudos Retrospectivos , Masculino , Feminino , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/epidemiologia , Pessoa de Meia-Idade , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Idoso , Material Particulado/efeitos adversos , Material Particulado/análise , Adulto , Lágrimas/metabolismo , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/efeitos adversos , Umidade/efeitos adversos , Conceitos Meteorológicos , Ozônio/efeitos adversos , Ozônio/análise , Temperatura
20.
Int J Environ Health Res ; : 1-11, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39165084

RESUMO

We investigated the association between ambient air pollutant exposure and periodontal health using data from 17,271 adults in the Korea National Health and Nutrition Examination Survey (2012-2015). Participants' periodontal status was categorized based on their community periodontal index (CPI) scores. Using multiple logistic regression models, we examined the relationship between air pollutant levels and poor periodontal status at various lag periods. After adjusting for potential confounders, PM10 exposure was associated with a poor periodontal status (short-term: 0-1 and 0-2 lag days; medium-term: 0-1 and 0-2 lag months). SO2 exposure showed similar associations (short-term, 0-2 to 0-7 lag days; medium-term, 0-4 to 0-6 lag months). Only increased medium-term O3 exposure (0-2 to 0-6 lag months) was associated with a poor periodontal status. NO2 exposure was inversely associated with poor periodontal status for both short- and medium-term durations.

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