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1.
Development ; 149(5)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35132991

RESUMO

A recent comparative transcriptomic study of Müller glia (MG) in vertebrate retinas revealed that fatty acid binding proteins (FABPs) are among the most highly expressed genes in chick ( Hoang et al., 2020). Here, we investigate how FABPs and fatty acid synthase (FASN) influence glial cells in the chick retina. During development, FABP7 is highly expressed by retinal progenitor cells and maturing MG, whereas FABP5 is upregulated in maturing MG. PMP2 (FABP8) is expressed by oligodendrocytes and FABP5 is expressed by non-astrocytic inner retinal glial cells, and both of these FABPs are upregulated by activated MG. In addition to suppressing the formation of Müller glia-derived progenitor cells (MGPCs), we find that FABP-inhibition suppresses the proliferation of microglia. FABP-inhibition induces distinct changes in single cell transcriptomic profiles, indicating transitions of MG from resting to reactive states and suppressed MGPC formation, with upregulation of gene modules for gliogenesis and decreases in neurogenesis. FASN-inhibition increases the proliferation of microglia and suppresses the formation of MGPCs. We conclude that fatty acid metabolism and cell signaling involving fatty acids are important in regulating the reactivity and dedifferentiation of MG, and the proliferation of microglia and MGPCs.


Assuntos
Galinhas/metabolismo , Células Ependimogliais/metabolismo , Ácido Graxo Sintases/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Retina/metabolismo , Células-Tronco/metabolismo , Animais , Proliferação de Células/fisiologia , Microglia/metabolismo , Neurogênese/fisiologia , Transdução de Sinais/fisiologia
2.
J Infect Dis ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38169323

RESUMO

BACKGROUND: Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections. METHODS: The expression of 3 genes (Dual specificity phosphatase 3- DUSP3, Guanylate-binding protein- GBP5, Krupple-like factor 2- KLF2) was analysed by RNA sequencing of archived whole blood from four cohorts of Vietnamese adults: 281 with TBM; 279 with pulmonary tuberculosis; 50 with other brain infections; and 30 healthy controls. 'TB scores' (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC). RESULTS: GBP5 was upregulated in TBM compared to other brain infections (p < 0.001), with no difference in DUSP3 and KLF2 expression. The diagnostic performance of GBP5 alone (AUC 0.74 (95% CI 0.67-0.81)) was slightly better than the 3-gene TB score (AUC 0.66, 95% CI 0.58-0.73) in TBM. Both GBP5 expression and TB score were higher in HIV-positive participants (P < 0.001), with good diagnostic performance of GBP5 alone (AUC 0.86, 95% CI 0.80-0.93). CONCLUSION: The 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in HIV-positive individuals. Validation in large prospective diagnostic study is now required.

3.
Cancer ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38922855

RESUMO

BACKGROUND: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers. METHODS: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or gas development. Survival analyses were conducted using Cox regression, adjusting for potential confounders. RESULTS: A total of 14.2% of cases lived within 1000 m of an oil or gas well or horizontal well. Living within 1000 m of an oil or gas well was associated with risk of mortality in cases with acute myeloid leukemia (AML) (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.01-1.84) and hepatoblastoma (aHR, 2.13; 95% CI, 1.03-4.39). An inverse association was observed with Ewing sarcoma (aHR, 0.35; 95% CI, 0.13-0.95). No associations were observed with horizontal well. There was evidence of a dose-response effect in children with AML or hepatoblastoma and residential proximity to oil or gas wells. In general, the magnitude of association increased with decreasing distance and with higher number of wells across the three distances. CONCLUSIONS: Residential proximity to oil or gas wells at diagnosis is associated with the risk of mortality in children with AML or hepatoblastoma.

4.
Phys Rev Lett ; 132(4): 043803, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335352

RESUMO

We introduce the concept of photonic flatband resonances and demonstrate it for an array of high-index dielectric particles. We employ the multiple Mie scattering theory and demonstrate that both short- and long-range interactions between the resonators are crucial for the emerging collective resonances and their associated photonic flatbands. By examining both near- and far-field characteristics, we uncover how the flatbands emerge due to a fine tuning of resonators' radiation fields, and predict that hybridization of a flatband resonance with an electric hot spot can lead to giant values of the Purcell factor for the electric dipolar emitters.

5.
Mol Psychiatry ; 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36899042

RESUMO

Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.

6.
Mol Psychiatry ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38052982

RESUMO

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

7.
AIDS Behav ; 28(6): 1858-1881, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38478323

RESUMO

Tobacco smoking is highly prevalent among people living with HIV (PLWH), yet there is a lack of data on smoking behaviours and effective treatments in this population. Understanding factors influencing tobacco smoking and cessation is crucial to guide the design of effective interventions. This systematic review and meta-analysis of studies conducted in both high-income (HICs) and low- and middle-income countries (LMICs) synthesised existing evidence on associated factors of smoking and cessation behaviour among PLWH. Male gender, substance use, and loneliness were positively associated with current smoking and negatively associated with smoking abstinence. The association of depression with current smoking and lower abstinence rates were observed only in HICs. The review did not identify randomised controlled trials conducted in LMICs. Findings indicate the need to integrate smoking cessation interventions with mental health and substance use services, provide greater social support, and address other comorbid conditions as part of a comprehensive approach to treating tobacco use in this population. Consistent support from health providers trained to provide advice and treatment options is also an important component of treatment for PLWH engaged in care, especially in LMICs.


Assuntos
Infecções por HIV , Abandono do Hábito de Fumar , Fumar Tabaco , Humanos , Infecções por HIV/psicologia , Infecções por HIV/complicações , Abandono do Hábito de Fumar/psicologia , Fumar Tabaco/epidemiologia , Masculino , Feminino , Países em Desenvolvimento , Prevalência , Depressão/epidemiologia , Depressão/psicologia , Apoio Social
8.
J Phys Chem A ; 128(8): 1543-1549, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38359462

RESUMO

Quantum chemical methods dealing with challenging systems while retaining low computational costs have attracted attention. In particular, many efforts have been devoted to developing new methods based on second-order perturbation that may be the simplest correlated method beyond Hartree-Fock. We have recently developed a self-consistent perturbation theory named one-body Møller-Plesset second-order perturbation theory (OBMP2) and shown that it can resolve issues caused by the noniterative nature of standard perturbation theory. In this work, we extend the method by introducing spin-opposite scaling to the double-excitation amplitudes, resulting in the O2BMP2 method. We assess the O2BMP2 performance on the triple-bond N2 dissociation, singlet-triplet gaps, and ionization potentials. O2BMP2 performs much better than standard MP2 and reaches the accuracy of coupled-cluster methods in all cases considered in this work.

10.
Environ Health ; 23(1): 28, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504322

RESUMO

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Assuntos
Hexaclorocicloexano , Hidrocarbonetos Clorados , Militares , Praguicidas , Neoplasias da Glândula Tireoide , Masculino , Humanos , Feminino , Câncer Papilífero da Tireoide/epidemiologia , Hexaclorobenzeno , Estudos de Casos e Controles , Neoplasias da Glândula Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/epidemiologia
11.
Pediatr Crit Care Med ; 25(4): e177-e185, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37966344

RESUMO

OBJECTIVES: Profound dengue shock syndrome (DSS) complicated by severe respiratory failure necessitating mechanical ventilation (MV) accounts for high case fatality rates among PICU-admitted patients. A major challenge to management is the assessment of intravascular volume, which can be hampered by severe plasma leakage and the use of MV. DESIGN: Retrospective cohort, from 2013 to 2021. PATIENTS: Sixty-seven children with profound DSS supported by MV, some of whom underwent bedside point-of-care ultrasound (POCUS) for assessment and monitoring of hemodynamics and fluid administration. SETTING: PICU of the tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data clinical and laboratory data during PICU stay. In particular, during use of MV (i.e., at times 0-, 6-, and 24-hr after commencement) and fluid resuscitation. The primary study outcome was 28-day in-hospital mortality, and the secondary outcomes were associations with changes in hemodynamics, blood lactate, and vasoactive-inotrope score (VIS). Patients had a median age of 7 years (interquartile range, 4-9). Use of POCUS during fluid management (39/67), as opposed to not using (28/67), was associated with lower mortality (6/39 [15%] vs. 18/28 [64%]; difference 49 % [95% CI, 28-70%], p < 0.001). Use of POCUS was associated with lower odds of death (adjusted odds ratio 0.17 [95% CI, 0.04-0.76], p = 0.02). The utilization of POCUS, versus not, was associated with greater use of resuscitation fluid, and reductions in VIS and pediatric logistic organ dysfunction (PELOD-2) score at 24 hours after MV and PICU discharge. CONCLUSIONS: In our experience of pediatric patients with profound DSS and undergoing MV (2013-2021), POCUS use was associated with lower odds of death, a higher volume of resuscitation fluid, and improvements in the blood lactate levels, VIS, and PELOD-2 score.


Assuntos
Respiração Artificial , Dengue Grave , Criança , Humanos , Lactente , Estudos Retrospectivos , Sistemas Automatizados de Assistência Junto ao Leito , Lactatos , Unidades de Terapia Intensiva Pediátrica
12.
Ophthalmic Plast Reconstr Surg ; 40(4): 453-459, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38319189

RESUMO

PURPOSES: Upper sunken eyelids, which are characterized by the hollowness of the upper eyelids, often cause a poor aesthetic appearance. Herein, we present a simplified technique using fascia-fat grafts for volume augmentation combined with blepharoplasty as a single-stage procedure. METHODS: From January 2021 to December 2021, 30 patients with sunken eyelids visiting our clinic for hollow eyelid treatment underwent a fascia-fat grafting derived from the inguinal crease combined with simultaneous eyelid reconstruction. A modified classification of sunken eyelids that was more suitable for the Asian population was proposed. RESULTS: Postoperatively, edema and ptosis were transient and addressed thanks to proper massage and compresses. Two cases had scar fibers leading to a slight tension of upper eyelids at 6-month follow-up. This event was addressed by triamcinolone acetonide injections at 4-6-week intervals with satisfactory results. The orbital volume of all patients was satisfying and stable up to 12 months after the surgery. The satisfaction rate was 100% and 88.8% in group 1 and group 2, respectively, at 12-month follow-up. CONCLUSIONS: Fascia-fat grafting combined with blepharoplasty as a single-stage procedure was a simplified method that did not require varied types of surgical tools but brought satisfactory results. This method facilitated the routine procedure and eased surgeons in the clinical practices.


Assuntos
Tecido Adiposo , Blefaroplastia , Pálpebras , Fáscia , Humanos , Blefaroplastia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Tecido Adiposo/transplante , Adulto , Pálpebras/cirurgia , Fáscia/transplante , Vietnã , Povo Asiático/etnologia , Idoso , Doenças Palpebrais/cirurgia , População do Sudeste Asiático
13.
J Neurosci ; 42(26): 5144-5158, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35672150

RESUMO

Photoreceptor degeneration leads to irreversible vision loss in humans with retinal dystrophies such as retinitis pigmentosa. Whereas photoreceptor loss is permanent in mammals, zebrafish possesses the ability to regenerate retinal neurons and restore visual function. Following acute damage, Müller glia (MG) re-enter the cell cycle and produce multipotent progenitors whose progeny differentiate into mature neurons. Both MG reprogramming and proliferation of retinal progenitor cells require reactive microglia and associated inflammatory signaling. Paradoxically, in zebrafish models of retinal degeneration, photoreceptor death does not induce the MG to reprogram and regenerate lost cells. Here, we used male and female zebrafish cep290 mutants to demonstrate that progressive cone degeneration generates an immune response but does not stimulate MG proliferation. Acute light damage triggered photoreceptor regeneration in cep290 mutants but cones were only restored to prelesion densities. Using irf8 mutant zebrafish, we found that the chronic absence of microglia reduced inflammation and rescued cone degeneration in cep290 mutants. Finally, single-cell RNA-sequencing revealed sustained expression of notch3 in MG of cep290 mutants and inhibition of Notch signaling induced MG to re-enter the cell cycle. Our findings provide new insights on the requirements for MG to proliferate and the potential for immunosuppression to prolong photoreceptor survival.SIGNIFICANCE STATEMENT Inherited retinal degenerations (IRDs) are genetic diseases that lead to the progressive loss of photoreceptors and the permanent loss of vision. Zebrafish can regenerate photoreceptors after acute injury by reprogramming Müller glia (MG) into stem-like cells that produce retinal progenitors, but this regenerative process fails to occur in zebrafish models of IRDs. Here, we show that Notch pathway inhibition can promote photoreceptor regeneration in models of progressive degeneration and that immunosuppression can prevent photoreceptor loss. These results offer insight into the pathways that promote MG-dependent regeneration and the role of inflammation in photoreceptor degeneration.


Assuntos
Degeneração Retiniana , Distrofias Retinianas , Animais , Animais Geneticamente Modificados , Proliferação de Células , Feminino , Terapia de Imunossupressão , Inflamação/metabolismo , Masculino , Mamíferos , Regeneração/fisiologia , Retina/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Degeneração Retiniana/patologia , Distrofias Retinianas/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
14.
Development ; 147(10)2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32291273

RESUMO

Retinal regeneration is robust in some cold-blooded vertebrates, but this process is ineffective in warm-blooded vertebrates. Understanding the mechanisms that suppress the reprogramming of Müller glia into neurogenic progenitors is key to harnessing the regenerative potential of the retina. Inflammation and reactive microglia are known to influence the formation of Müller glia-derived progenitor cells (MGPCs), but the mechanisms underlying this interaction are unknown. We used a chick in vivo model to investigate nuclear factor kappa B (NF-κB) signaling, a critical regulator of inflammation, during the reprogramming of Müller glia into proliferating progenitors. We find that components of the NF-κB pathway are dynamically regulated by Müller glia after neuronal damage or treatment with growth factors. Inhibition of NF-κB enhances, whereas activation suppresses, the formation of proliferating MGPCs. Following microglia ablation, the effects of NF-κB-agonists on MGPC-formation are reversed, suggesting that signals provided by reactive microglia influence how NF-κB impacts Müller glia reprogramming. We propose that NF-κB is an important signaling 'hub' that suppresses the reprogramming of Müller glia into proliferating MGPCs and this 'hub' coordinates signals provided by reactive microglia.


Assuntos
Proliferação de Células/genética , Galinhas/crescimento & desenvolvimento , Células Ependimogliais/metabolismo , NF-kappa B/metabolismo , Retina/metabolismo , Transdução de Sinais/genética , Células-Tronco/metabolismo , Animais , Reprogramação Celular/genética , Galinhas/genética , Inativação Gênica , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Microglia/metabolismo , NF-kappa B/agonistas , NF-kappa B/antagonistas & inibidores , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/genética , Neurogênese/efeitos dos fármacos , Neurogênese/genética , Retina/crescimento & desenvolvimento , Sulfassalazina/farmacologia
15.
Environ Res ; 226: 115675, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906268

RESUMO

Low-cost adsorbents derived from agricultural by-products incorporated magnetic nanoparticles (NPs) are promising for wastewater treatment. They are always preferred due to their great performance and easy separation. This study reports cobalt superparamagnetic (CoFe2O4) nanoparticles (NPs) incorporated with triethanolamine (TEA) based surfactants from cashew nut shell liquid, namely TEA-CoFe2O4, for the removal of chromium (VI) ions from aqueous solutions. To have detailed characteristics of the morphology and structural properties, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and vibrating sample magnetometry (VSM) were employed. The fabricated TEA-CoFe2O4 particles exhibit soft and superparamagnetic properties, which make the nanoparticles easily recycled by using a magnet. Chromate adsorption on the TEA-CoFe2O4 nanomaterials reached an optimal efficiency of 84.3% at pH = 3 with the initial adsorbent dose of 10 g/L and chromium (VI) concentration of 40 mg/L. The TEA-CoFe2O4 nanoparticles can maintain the effective adsorption of chromium (VI) ion (by 29% of efficiency loss) and retain the magnetic separation using a magnet up to three cycles of the regeneration, which promise a high potential of this low-cost adsorbent for long-term treatment of heavy metal ions from polluted waters.


Assuntos
Nanopartículas de Magnetita , Poluentes Químicos da Água , Cromatos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas de Magnetita/química , Adsorção , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Cinética
16.
Endocr Pract ; 29(5): 341-348, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37150580

RESUMO

OBJECTIVE: This 2023 updated protocol summarizes the American Association of Clinical Endocrinology's (AACE's) new framework for the development of clinical practice guidelines and other guidance documents that includes changes to methodology, processes, and policies. METHODS: AACE has critically reviewed its development processes for guidance documents over the last several years against the National Academy of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines and the Council of Medical Specialty Societies Principles for Development of Specialty Society Clinical Guidelines to determine areas for improvement. RESULTS: The new AACE framework for development of guidance documents incorporates many changes, including a revised conflicts of interest (COI) policy; strengthened commitment to collection of disclosures and management of relevant COI during development; open calls to membership for authors; new requirements for authors; new diversity, equity, and inclusion (DEI) policy; new empanelment process that incorporates consideration of DEI; and adoption of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to increase the quality of evidence assessment and standardize recommendation grades and statements, among other improvements. CONCLUSIONS: AACE has revised its policies and adopted a completely new methodology for guideline development in support of the mission to elevate the practice of clinical endocrinology to improve patient care. With the use of an evidence-based medicine framework and by continually assessing and improving its processes for development of guidance, AACE strives to deliver trustworthy, unbiased, and up-to-date information that ensures clinician and patient confidence in AACE content. Further, AACE hopes that these enhancements foster a more collaborative approach to development and increase engagement with the worldwide medical community to improve global health.


Assuntos
Endocrinologia , Estados Unidos , Humanos , Sociedades Médicas
17.
Bioessays ; 43(9): e2100030, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34106479

RESUMO

It is estimated that 300,000 children 0-14 years of age are diagnosed with cancer worldwide each year. While the absolute risk of cancer in children is low, it is the leading cause of death due to disease in children in high-income countries. In spite of this, the etiologies of pediatric cancer are largely unknown. Environmental exposures have long been thought to play an etiologic role. However, to date, there are few well-established environmental risk factors for pediatric malignancies, likely due to technical barriers in collecting biological samples prospectively in pediatric populations for direct measurements. In this review, we propose the use of novel or underutilized biospecimens (dried blood spots and teeth) and molecular approaches for exposure assessment (epigenetics, metabolomics, and somatic mutational profiles). Future epidemiologic studies of pediatric cancer should incorporate novel exposure assessment methodologies, data on molecular features of tumors, and a more complete assessment of gene-environment interactions.


Assuntos
Metabolômica , Neoplasias , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Neoplasias/epidemiologia , Neoplasias/etiologia , Dente Decíduo
18.
Am J Respir Crit Care Med ; 206(3): 321-336, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35536696

RESUMO

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate, <0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.


Assuntos
Metilação de DNA , Epigenoma , Ilhas de CpG , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Pulmão
19.
Mar Drugs ; 21(6)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37367683

RESUMO

Shell wastes pose environmental and financial burdens to the shellfish industry. Utilizing these undervalued shells for commercial chitin production could minimize their adverse impacts while maximizing economic value. Shell chitin conventionally produced through harsh chemical processes is environmentally unfriendly and infeasible for recovering compatible proteins and minerals for value-added products. However, we recently developed a microwave-intensified biorefinery that efficiently produced chitin, proteins/peptides, and minerals from lobster shells. Lobster minerals have a calcium-rich composition and biologically originated calcium is more biofunctional for use as a functional, dietary, or nutraceutical ingredient in many commercial products. This has suggested a further investigation of lobster minerals for commercial applications. In this study, the nutritional attributes, functional properties, nutraceutical effects, and cytotoxicity of lobster minerals were analyzed using in vitro simulated gastrointestinal digestion combined with growing bone (MG-63), skin (HaCaT), and macrophage (THP-1) cells. The calcium from the lobster minerals was found to be comparable to that of a commercial calcium supplement (CCS, 139 vs. 148 mg/g). In addition, beef incorporated with lobster minerals (2%, w/w) retained water better than that of casein and commercial calcium lactate (CCL, 21.1 vs. 15.1 and 13.3%), and the lobster mineral had a considerably higher oil binding capacity than its rivals (casein and CCL, 2.5 vs. 1.5 and 1.0 mL/g). Notably, the lobster mineral and its calcium were far more soluble than the CCS (98.4 vs. 18.6% for the products and 64.0 vs. 8.5% for their calcium) while the in vitro bioavailability of lobster calcium was 5.9-fold higher compared to that of the commercial product (11.95 vs. 1.99%). Furthermore, supplementing lobster minerals in media at ratios of 15%, 25%, and 35% (v/v) when growing cells did not induce any detectable changes in cell morphology and apoptosis. However, it had significant effects on cell growth and proliferation. The responses of cells after three days of culture supplemented with the lobster minerals, compared to the CCS supplementation, were significantly better with the bone cells (MG-63) and competitively quick with the skin cells (HaCaT). The cell growth reached 49.9-61.6% for the MG-63 and 42.9-53.4% for the HaCaT. Furthermore, the MG-63 and HaCaT cells proliferated considerably after seven days of incubation, reaching 100.3% for MG-63 and 115.9% for HaCaT with a lobster mineral supplementation of 15%. Macrophages (THP-1 cells) treated for 24 h with lobster minerals at concentrations of 1.24-2.89 mg/mL had no detectable changes in cell morphology while their viability was over 82.2%, far above the cytotoxicity threshold (<70%). All these results indicate that lobster minerals could be used as a source of functional or nutraceutical calcium for commercial products.


Assuntos
Cálcio , Nephropidae , Animais , Bovinos , Cálcio/metabolismo , Nephropidae/metabolismo , Caseínas/metabolismo , Disponibilidade Biológica , Solubilidade , Minerais , Quitina/metabolismo
20.
Lasers Med Sci ; 38(1): 258, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37934314

RESUMO

The purpose of this study is to determine the efficacy and safety of 595-nm pulsed dye laser (PDL) for port wine stains (PWS) treatment in Vietnamese patients. The study also analyzed the association between the response to treatment and the characteristics of patients and treatment regimens. Parallelly, the study contributed to further optimal treatment sessions for different subjects based on the data collected. One hundred twenty-five patients who underwent 595-nm PDL to treat PWS were included in the study, in which data from 124 patients was retrospectively analyzed. Data on demographic characteristics of patients, treatment regimens, and clinical improvement were collected. SPSS version 25 was used to analyze the relationship between associated factors and the response rate. The overall response rate of Vietnamese patients who had Fitzpatrick skin classification type III and IV was 73.4%. Age, gender, treatment sessions, and lesion positions were generally not associated with the response rate. The lesion grade was the sole element that affected the clinical improvement. The lesion grade 1 had the best response (100%) even after a short duration of treatment (six to ten treatments). Lesion grade 4 demanded over 16 treatments to reach > 60% of improvement. The lesion grades 1 and 2 could be blanched with regimen < 10 treatments while regimens exceeding 15 treatments should be carefully considered for lesions at grade 3 after evaluating associated conditions. Lesions at grade 4 demanded ≥ 16 treatments to reach acceptable outcomes. These results could help physicians establish a reasonable treatment strategy for patients.


Assuntos
Lasers de Corante , Mancha Vinho do Porto , Humanos , Estudos Retrospectivos , População do Sudeste Asiático
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