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1.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892248

RESUMO

Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity. The primary goal is to investigate if adding such realistic constraints could produce firing patterns similar to those measured in real neurons. Biological characteristics included in the work are excitability, connectivity, and synaptic signaling of neuron types defined primarily by their axonal and dendritic morphologies. We investigate the spiking dynamics in specific neuron types and the synaptic activities between groups of neurons. Modeling the rodent hippocampal formation keeps the simulations to a computationally reasonable scale while also anchoring the parameters and results to experimental measurements. Our model generates grid cell activity that well matches the spacing, size, and firing rates of grid fields recorded in live behaving animals from both published datasets and new experiments performed for this study. Our simulations also recreate different scales of those properties, e.g., small and large, as found along the dorsoventral axis of the medial entorhinal cortex. Computational exploration of neuronal and synaptic model parameters reveals that a broad range of neural properties produce grid fields in the simulation. These results demonstrate that the continuous attractor network model of grid cells is compatible with a spiking neural network implementation sourcing data-driven biophysical and anatomical parameters from Hippocampome.org. The software (version 1.0) is released as open source to enable broad community reuse and encourage novel applications.


Assuntos
Potenciais de Ação , Córtex Entorrinal , Células de Grade , Modelos Neurológicos , Sinapses , Animais , Células de Grade/fisiologia , Sinapses/fisiologia , Córtex Entorrinal/fisiologia , Córtex Entorrinal/citologia , Potenciais de Ação/fisiologia , Simulação por Computador , Neurônios/fisiologia , Neurônios/citologia , Hipocampo/fisiologia , Hipocampo/citologia , Rede Nervosa/fisiologia , Rede Nervosa/citologia , Redes Neurais de Computação
2.
Chem Biol Interact ; 398: 111111, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38878851

RESUMO

The aldo-keto reductase (AKR) superfamily is a large family of proteins found across the kingdoms of life. Shared features of the family include 1) structural similarities such as an (α/ß)8-barrel structure, disordered loop structure, cofactor binding site, and a catalytic tetrad, and 2) the ability to catalyze the nicotinamide adenine dinucleotide (phosphate) reduced (NAD(P)H)-dependent reduction of a carbonyl group. A criteria of family membership is that the protein must have a measured function, and thus, genomic sequences suggesting the transcription of potential AKR proteins are considered pseudo-members until evidence of a functionally expressed protein is available. Currently, over 200 confirmed AKR superfamily members are reported to exist. A systematic nomenclature for the AKR superfamily exists to facilitate family and subfamily designations of the member to be communicated easily. Specifically, protein names include the root "AKR", followed by the family represented by an Arabic number, the subfamily-if one exists-represented by a letter, and finally, the individual member represented by an Arabic number. The AKR superfamily database has been dedicated to tracking and reporting the current knowledge of the AKRs since 1997, and the website was last updated in 2003. Here, we present an updated version of the website and database that were released in 2023. The database contains genetic, functional, and structural data drawn from various sources, while the website provides alignment information and family tree structure derived from bioinformatics analyses.


Assuntos
Aldo-Ceto Redutases , Bases de Dados de Proteínas , Aldo-Ceto Redutases/metabolismo , Aldo-Ceto Redutases/genética , Aldo-Ceto Redutases/química , Humanos , Internet , Aldeído Redutase/metabolismo , Aldeído Redutase/química , Aldeído Redutase/genética , Animais
3.
AMIA Jt Summits Transl Sci Proc ; 2024: 499-508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827081

RESUMO

Varying case definitions of COPD have heterogenous genetic risk profiles, potentially reflective of disease subtypes or classification bias (e.g., smokers more likely to be diagnosed with COPD). To better understand differences in genetic loci associated with ICD-defined versus spirometry-defined COPD we contrasted their GWAS results with those for heavy smoking among 337,138 UK Biobank participants. Overlapping risk loci were found in/near the genes ZEB2, FAM136B, CHRNA3, and CHRNA4, with the CHRNA3 locus shared across all three traits. Mediation analysis to estimate the effects of lead genotyped variants mediated by smoking found significant indirect effects for the FAM136B, CHRNA3, and CHRNA4 loci for both COPD definitions. Adjustment for mediator-outcome confounders modestly attenuated indirect effects, though in the CHRNA4 locus for spirometry-defined COPD the proportion mediated increased an additional 8.47%. Our results suggest that differences between ICD-defined and spirometry-defined COPD associated genetic loci are not a result of smoking biasing classification.

4.
Epidemiol Infect ; 152: e83, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38705586

RESUMO

The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.


Assuntos
Quirópteros , Histoplasma , Histoplasmose , Animais , Quirópteros/microbiologia , Brasil/epidemiologia , Histoplasma/genética , Histoplasma/isolamento & purificação , Histoplasmose/epidemiologia , Histoplasmose/veterinária , Histoplasmose/microbiologia , Reação em Cadeia da Polimerase/veterinária
5.
Adv Rheumatol ; 64(1): 29, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627861

RESUMO

Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.


Assuntos
Doenças Ósseas , Policondrite Recidivante , Humanos , Policondrite Recidivante/diagnóstico , Policondrite Recidivante/tratamento farmacológico , Policondrite Recidivante/genética , Inflamação/complicações , Doenças Ósseas/complicações
6.
PeerJ ; 12: e16797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529306

RESUMO

The topographical, geological, climatic and biodiversity complexity of Mesoamerica has made it a primary research focus. The Mesoamerican highlands is a region with particularly high species richness and within-species variation. The Cinnamon-bellied Flowerpiercer, Diglossa baritula (Wagler, 1832), is a species endemic to the Mesoamerican highlands, with three allopatric subspecies currently recognized. To characterize divergence within this species, we integrated genomics, morphology, coloration and ecological niche modeling approaches, obtained from sampling individuals across the entire geographic distribution of the species. Our results revealed a clear genomic divergence between the populations to the east versus the west of the Isthmus of Tehuantepec. In contrast to the genomic results, morphology and coloration analyses showed intermediate levels of differentiation, indicating that population groups within D. baritula have probably been under similar selective pressures. Our morphology results indicated that the only sexually dimorphic morphological variable is the wing chord, with males having a longer wing chord than females. Finally, ecological data indicated that there are differences in ecological niche within D. baritula. Our data suggest that D. baritula could contain two or more incipient species at the intermediate phase of the speciation continuum. These results highlight the importance of the geographical barrier of the Isthmus of Tehuantepec and Pleistocene climatic events in driving isolation and population divergence in D. baritula. The present investigation illustrates the speciation potential of the D. baritula complex and the capacity of Mesoamerican highlands to create cryptic biodiversity and endemism.


Assuntos
Aves , Ecossistema , Animais , Feminino , Masculino , Biodiversidade , Geografia , Filogenia
7.
medRxiv ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38352545

RESUMO

BACKGROUND: Aeroallergen testing can improve precision care for persistent asthma and is recommended by the U.S. clinical guidelines. How testing benefits diverse populations of adults with asthma, and the importance of the testing modality used, are not fully understood. OBJECTIVE: We sought to evaluate whether receipt of aeroallergen testing was associated with a reduction in oral corticosteroid (OCS) bursts. METHODS: We used electronic health record data to conduct a retrospective, observational cohort study of adults with asthma who were prescribed an inhaled corticosteroid and had an Allergy/Immunology visit in a large health system between 1/1/2017-6/30/2022. Negative binomial regression models were used to evaluate whether OCS bursts in the 12-month period after an initial visit were reduced for patients who received aeroallergen testing. We also measured differences in benefit after excluding patients with chronic obstructive pulmonary disease (COPD) and smoking histories, and whether testing receipt was via skin prick or serum. RESULTS: 668/1,383 (48.3%) patients received testing. Receipt of testing was not associated with fewer bursts in all patients (incidence rate ratio (IRR)=0.83 versus no testing, p=0.059), but it was among never smokers without COPD (417/844 tested, IRR=0.68, p=0.004). The receipt of skin testing was associated with fewer bursts in all patients (418/1,383 tested, IRR=0.77, p=0.02) and among never smokers without COPD (283/844 tested, IRR=0.59 versus no testing, p=0.001). CONCLUSION: Guideline-concordant aeroallergen testing in the context of Allergy/Immunology care was associated with clinical benefit in a real-life, diverse cohort of adults with asthma. This benefit varied according to patient comorbidities and the testing modality.

8.
Nutrients ; 16(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38337625

RESUMO

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.


Assuntos
Asma , MicroRNAs , Humanos , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , MicroRNAs/genética , Remodelação das Vias Aéreas , Asma/tratamento farmacológico , Asma/genética , Asma/complicações , Pulmão , Inflamação/complicações , Suplementos Nutricionais
9.
J Allergy Clin Immunol ; 153(4): 954-968, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38295882

RESUMO

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.


Assuntos
Asma , Hipersensibilidade , Estados Unidos , Humanos , National Institute of Allergy and Infectious Diseases (U.S.) , Hipersensibilidade/genética , Asma/etiologia , Genômica , Proteômica , Metabolômica
10.
Am J Infect Control ; 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38185380

RESUMO

BACKGROUND: Reporting on the International Nosocomial Infection Control Consortium study results from 2015 to 2020, conducted in 630 intensive care units across 123 cities in 45 countries spanning Africa, Asia, Eastern Europe, Latin America, and the Middle East. METHODS: Prospective intensive care unit patient data collected via International Nosocomial Infection Control Consortium Surveillance Online System. Centers for Disease Control and Prevention/National Health Care Safety Network definitions applied for device-associated health care-associated infections (DA-HAI). RESULTS: We gathered data from 204,770 patients, 1,480,620 patient days, 936,976 central line (CL)-days, 637,850 mechanical ventilators (MV)-days, and 1,005,589 urinary catheter (UC)-days. Our results showed 4,270 CL-associated bloodstream infections, 7,635 ventilator-associated pneumonia, and 3,005 UC-associated urinary tract infections. The combined rates of DA-HAIs were 7.28%, and 10.07 DA-HAIs per 1,000 patient days. CL-associated bloodstream infections occurred at 4.55 per 1,000 CL-days, ventilator-associated pneumonias at 11.96 per 1,000 MV-days, and UC-associated urinary tract infections at 2.91 per 1,000 UC days. In terms of resistance, Pseudomonas aeruginosa showed 50.73% resistance to imipenem, 44.99% to ceftazidime, 37.95% to ciprofloxacin, and 34.05% to amikacin. Meanwhile, Klebsiella spp had resistance rates of 48.29% to imipenem, 72.03% to ceftazidime, 61.78% to ciprofloxacin, and 40.32% to amikacin. Coagulase-negative Staphylococci and Staphylococcus aureus displayed oxacillin resistance in 81.33% and 53.83% of cases, respectively. CONCLUSIONS: The high rates of DA-HAI and bacterial resistance emphasize the ongoing need for continued efforts to control them.

11.
Zookeys ; 1188: 169-195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38230381

RESUMO

Factors such as the Andean uplift, Isthmus of Panama, and climate changes have influenced bird diversity in the Neotropical region. Studying bird species that are widespread in Neotropical highlands and lowlands can help us understand the impact of these factors on taxa diversification. Our main objectives were to determine the biogeographic factors that contributed to the diversification of Euphoniinae and re-evaluate their phylogenetic relationships. The nextRAD and mitochondrial data were utilized to construct phylogenies. The ancestral distribution range was then estimated using a time-calibrated phylogeny, current species ranges, and neotropical regionalization. The phylogenies revealed two main Euphoniinae clades, Chlorophonia and Euphonia, similar to previous findings. Furthermore, each genus has distinctive subclades corresponding to morphology and geography. The biogeographic results suggest that the Andean uplift and the establishment of the western Amazon drove the vicariance of Chlorophonia and Euphonia during the Miocene. The Chlorophonia lineage originated in the Andes mountains and spread to Central America and the Mesoamerican highlands after the formation of the Isthmus of Panama. Meanwhile, the ancestral area of Euphonia was the Amazonas, from which it spread to trans-Andean areas during the Pliocene and Pleistocene due to the separation of the west lowlands from Amazonas due to the Northern Andean uplift. Chlorophonia and Euphonia species migrated to the Atlantic Forest during the Pleistocene through corridors from the East Andean Humid Forest and Amazonas. These two genera had Caribbean invasions with distinct geographic origins and ages. Finally, we suggested taxonomic changes in the genus Euphonia based on the study's phylogenetic, morphological, and biogeographic findings.

12.
Food Chem Toxicol ; 183: 114306, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38052406

RESUMO

This study aims to analyse the risk to consumers given the presence of heavy metals and bromine in honey from different countries. A probabilistic approach was applied to assess carcinogenic risk. Concerning exposure, Al in Spain (3.3E-04 mg/kgBw/day), B in Dominican Republic and Mexico (2E-04 mg/kgBw/day in both cases) and Fe in Mexico and Mozambique had the highest values (5E-05 and 4.8E-05 mg/kgBw/day). In risk characterisation, the values were less than 1 for hazard index (HI), meaning that the consumption of honey represents a low level of concern for non-genotoxic effects. A combination of margin of exposure and probability of exceedance results that exposure to Pb pose no threat. The probability of suffering cancer for Br, Cd, Ni and Pb was lower than 1.0E-06 and, therefore, considered safe. However, the risk at the 95th percentile of Br in Dominican Republic was 1.18E-04 in adults and 2.45E-04 in children, exceeding 1.0E-04, and therefore, considered intolerable. Finally, the sensitivity analysis indicated that the most influential factor in the HI was the consumption in adults and the concentration of Ni in children, whereas for cancer risk, were the concentrations of Ni, Cd, Br and Pb, in both cases.


Assuntos
Mel , Metais Pesados , Neoplasias , Poluentes do Solo , Criança , Adulto , Humanos , Bromo/análise , Mel/análise , República Dominicana , México , Moçambique , Espanha , Cádmio/análise , Chumbo/análise , Medição de Risco , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Metais Pesados/análise , Poluentes do Solo/análise , China
13.
J Hazard Mater ; 463: 132906, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-37939567

RESUMO

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood. Here, we identified F2RL2, TRIM16L, and PANX2 as novel targets of Nuclear factor erythroid 2-related factor 2 (NRF2)-the master transcriptional factor for the oxidative stress response-that are commonly upregulated with both Pb and As in human neural progenitor cells (NPCs). Using a ChIP (Chromatin immunoprecipitation)-qPCR assay, we showed that NRF2 directly binds to the promoter region of F2RL2, TRIM16L, and PANX2 to regulate expression of these genes. We demonstrated that F2RL2, PANX2, and TRIM16L have differential effects on cell death, proliferation, and differentiation of NPCs in both the presence and absence of metal exposures, highlighting their roles in regulating NPC function. Furthermore, the analyses of the transcriptomic data on NPCs derived from autism spectrum disorder (ASD) patients revealed that dysregulation of F2RL2, TRIM16L, and PANX2 was associated with ASD genetic backgrounds and ASD risk genes. Our findings revealed that Pb and As induce a shared NRF2-dependent transcriptional response in NPCs and identified novel genes regulating NPC function. While further in vivo studies are warranted, this study provides a novel mechanism linking metal exposures to NPC function and identifies potential genes of interest in the context of neurodevelopment.


Assuntos
Intoxicação por Arsênico , Arsênio , Transtorno do Espectro Autista , Células-Tronco Neurais , Criança , Humanos , Arsênio/toxicidade , Arsênio/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Chumbo/toxicidade , Chumbo/metabolismo , Transtorno do Espectro Autista/metabolismo , Células-Tronco Neurais/metabolismo , Conexinas/metabolismo
14.
Am J Infect Control ; 52(5): 580-587, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38154739

RESUMO

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSIs) occurring in the intensive care unit (ICU) are common and associated with a high burden. METHODS: We implemented a multidimensional approach, incorporating an 11-element bundle, education, surveillance of CLABSI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CLABSI rates and clinical outcomes, and performance feedback in 316 ICUs across 30 low- and middle-income countries. Our dependent variables were CLABSI per 1,000-CL-days and in-ICU all-cause mortality rates. These variables were measured at baseline and during the intervention, specifically during the second month, third month, 4 to 16 months, and 17 to 29 months. Comparisons were conducted using a two-sample t test. To explore the exposure-outcome relationship, we used a generalized linear mixed model with a Poisson distribution to model the number of CLABSIs. RESULTS: During 1,837,750 patient-days, 283,087 patients, used 1,218,882 CL-days. CLABSI per 1,000 CL-days rates decreased from 15.34 at the baseline period to 7.97 in the 2nd month (relative risk (RR) = 0.52; 95% confidence interval [CI] = 0.48-0.56; P < .001), 5.34 in the 3rd month (RR = 0.35; 95% CI = 0.32-0.38; P < .001), and 2.23 in the 17 to 29 months (RR = 0.15; 95% CI = 0.13-0.17; P < .001). In-ICU all-cause mortality rate decreased from 16.17% at baseline to 13.68% (RR = 0.84; P = .0013) at 17 to 29 months. CONCLUSIONS: The implemented approach was effective, and a similar intervention could be applied in other ICUs of low- and middle-income countries to reduce CLABSI and in-ICU all-cause mortality rates.

15.
JHEP Rep ; 6(1): 100902, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38074507

RESUMO

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of lipid droplets (LDs) within hepatocytes. Perilipin 2 (PLIN2) is the most abundant protein in hepatic LDs and its expression correlates with intracellular lipid accumulation. A recently discovered PLIN2 coding variant, Ser251Pro (rs35568725), was found to promote the accumulation of small LDs in embryonic kidney cells. In this study, we investigate the role of PLIN2-Ser251Pro (PLIN2-Pro251) on hepatic LD metabolism in vivo and research the metabolic phenotypes associated with this variant in humans. Methods: For our animal model, we used Plin2 knockout mice in which we expressed either human PLIN2-Pro251 (Pro251 mice) or wild-type human PLIN2-Ser251 (Ser251 mice) in a hepatocyte-specific manner. We fed both cohorts a lipogenic high-fat, high-cholesterol, high-fructose diet for 12 weeks. Results: Pro251 mice were associated with reduced liver triglycerides (TGs) and had lower mRNA expression of fatty acid synthase and diacylglycerol O-acyltransferase-2 compared with Ser251 mice. Moreover, Pro251 mice had a reduction of polyunsaturated fatty acids-TGs and reduced expression of epoxygenase genes. For our human study, we analysed the Penn Medicine BioBank, the Million Veteran Program, and UK Biobank. Across these databases, the minor allele frequency of PLIN2-Pro251 was approximately 5%. There was no association with the clinical diagnosis of NAFLD, however, there was a trend toward reduced liver fat in PLIN2-Pro251 carriers by MRI-spectroscopy in UK Biobank subjects. Conclusions: In mice lacking endogenous Plin2, expression of human PLIN2-Pro251 attenuated high-fat, high-fructose, high-cholesterol, diet-induced hepatic steatosis compared with human wild-type PLIN2-Ser251. Moreover, Pro251 mice had lower polyunsaturated fatty acids-TGs and epoxygenase genes expression, suggesting less liver oxidative stress. In humans, PLIN2-Pro251 is not associated with NAFLD. Impact and Implications: Lipid droplet accumulation in hepatocytes is the distinctive characteristic of non-alcoholic fatty liver disease. Perilipin 2 (PLIN2) is the most abundant protein in hepatic lipid droplets; however, little is known on the role of a specific polymorphism PLIN2-Pro251 on hepatic lipid droplet metabolism. PLIN2-Pro251 attenuates liver triglycerides accumulation after a high-fat-high-glucose-diet. PLIN2-Pro251 may be a novel lipid droplet protein target for the treatment of liver steatosis.

16.
Adv Rheumatol ; 64: 29, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1556790

RESUMO

Abstract Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.

17.
J Clin Med ; 12(23)2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38068322

RESUMO

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (ß2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population.

18.
Nutrients ; 15(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38004098

RESUMO

Postmenopausal women are at an increased risk of developing metabolic syndrome (MetS) due to hormonal changes and lifestyle factors. Gut microbiota (GM) have been linked to the development of MetS, and they are influenced by dietary habits. However, the interactions between dietary patterns (DP) and the GM of postmenopausal women, as well as their influence on MetS, still need to be understood. The present study evaluated the DP and microbiota composition of postmenopausal Mexican women with MetS and those in a control group. Diet was assessed using a food frequency questionnaire, and the GM were profiled using 16S rRNA gene sequencing. Greater adherence to a "healthy" DP was significantly associated with lower values of MetS risk factors. GM diversity was diminished in women with MetS, and it was negatively influenced by an "unhealthy" DP. Moreover, a higher intake of fats and proteins, as well as lower amounts of carbohydrates, showed a reduction in some of the short-chain fatty acid-producing genera in women with MetS, as well as increases in some harmful bacteria. Furthermore, Roseburia abundance was positively associated with dietary fat and waist circumference, which may explain 7.5% of the relationship between this macronutrient and MetS risk factors. These findings suggest that GM and diet interactions are important in the development of MetS in postmenopausal Mexican women.


Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Humanos , Feminino , Síndrome Metabólica/metabolismo , Pós-Menopausa , RNA Ribossômico 16S/genética , Dieta
19.
J Allergy Clin Immunol Glob ; 2(4): 100167, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37841071

RESUMO

Background: Aeroallergen testing informs precision care for adults with asthma, yet the epidemiology of testing in this population remains poorly understood. Objective: We sought to identify factors associated with receiving aeroallergen testing, the results of these tests, and subsequent reductions in exacerbation measures among adults with asthma. Methods: We used electronic health record data to conduct a retrospective, observational cohort study of 30,775 adults with asthma who had an office visit with a primary care provider or an asthma specialist from January 1, 2017, to August 26, 2022. We used regression models to identify (1) factors associated with receiving any aeroallergen test and tests to 9 allergen categories after the index visit, (2) factors associated with positive test results, and (3) reductions in asthma exacerbation measures in the year after testing compared with before testing. Results: Testing was received by 2201 patients (7.2%). According to multivariable models, receiving testing was associated with having any office visit with an allergy/immunology specialist during the study period (odds ratio [OR] = 91.3 vs primary care only [P < .001]) and having an asthma emergency department visit (OR = 1.62 [P = .004]) or hospitalization (OR = 1.62 [P = .03]) in the year before the index visit. Age 65 years or older conferred decreased odds of testing (OR = 0.74 vs age 18-34 years [P = .008]) and negative test results to 6 categories (P ≤ .04 for all comparisons). Black race conferred increased odds of testing (OR =1.22 vs White race [P = .01]) and positive test results to 8 categories (P < .04 for all comparisons). Exacerbation measures decreased after testing. Conclusion: Aeroallergen testing was performed infrequently among adults with asthma and was associated with reductions in asthma exacerbation measures.

20.
J Clin Med ; 12(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37685567

RESUMO

Several studies have reported that viral infection is closely associated with the onset, progression, and exacerbation of asthma. The purpose of this review is to summarize the role that viral infections have in the pathogenesis of asthma onset and exacerbations, as well as discuss interrelated protective and risk factors of asthma and current treatment options. Furthermore, we present current knowledge of the innate immunological pathways driving host defense, including changes in the epithelial barrier. In addition, we highlight the importance of the genetics and epigenetics of asthma and virus susceptibility. Moreover, the involvement of virus etiology from bronchiolitis and childhood wheezing to asthma is described. The characterization and mechanisms of action of the respiratory viruses most frequently related to asthma are mentioned.

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