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1.
Physiol Plant ; 176(5): e14521, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39252413

RESUMO

Knowledge is scarce to what extent environmental drivers and native symbiotic fungi in soil induce abrupt (short-term), systemic (multiple traits), or specific (a subset of traits) shifts in C3 plants' ecophysiological/mycorrhizal responses. We cultivated an emblematic native C3 species (Capsicum annuum var. glabriusculum, "Chiltepín") to look at how the extreme heat of the Sonoran desert, sunlight regimes (low = 2, intermediate = 15, high = 46 mol m2 d-1) and density of native arbuscular mycorrhizal fungi in soil (low AMF = 1% v/v, high AMF = 100% v/v), drive shifts on mycorrhizal responses through multiple functional traits (106 traits). The warming thresholds were relentlessly harsh even under intensive shade (e.g. superheat maximum thresholds reached ranged between 47-63°C), and several pivotal traits were synergistically driven by AMF (e.g. photosynthetic capacity, biomass gain/allometry, and mycorrhizal colonization traits); whereas concurrently, sunlight regimes promoted most (76%) alterations in functional acclimation traits in the short-term and opposite directions (e.g. survival, phenology, photosynthetic, carbon/nitrogen economy). Multidimensional reduction analysis suggests that the AMF promotes a synergistic impact on plants' phenotypic integration and functional plasticity in response to sunlight regimes; however, complex relationships among traits suggest that phenotypic variation determines the robustness degree of ecophysiological/mycorrhizal phenotypes between/within environments. Photosynthetic canopy surface expansion, Rubisco activity, photosynthetic nitrogen allocation, carbon gain, and differential colonization traits could be central to plants' overall ecophysiological/mycorrhizal fitness strengthening. In conclusion, we found evidence that a strong combined effect among environmental factors in which AMF are key effectors could drive important trade-offs on plants' ecophysiological/mycorrhizal fitness in the short term.


Assuntos
Clima Desértico , Micorrizas , Fenótipo , Micorrizas/fisiologia , Capsicum/microbiologia , Capsicum/fisiologia , Capsicum/efeitos da radiação , Fotossíntese/fisiologia , Simbiose/fisiologia , Luz Solar , Biomassa
2.
Basic Res Cardiol ; 118(1): 28, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452166

RESUMO

Endothelial dysfunction is an early event in coronary microvascular disease. Integrin-linked kinase (ILK) prevents endothelial nitric oxide synthase (eNOS) uncoupling and, thus, endothelial dysfunction. However, the specific role of endothelial ILK in cardiac function remains to be fully elucidated. We hypothesised that endothelial ILK plays a crucial role in maintaining coronary microvascular function and contractile performance in the heart. We generated an endothelial cell-specific ILK conditional knock-out mouse (ecILK cKO) and investigated cardiovascular function. Coronary endothelial ILK deletion significantly impaired cardiac function: ejection fraction, fractional shortening and cardiac output decreased, whilst left ventricle diastolic internal diameter decreased and E/A and E/E' ratios increased, indicating not only systolic but also diastolic dysfunction. The functional data correlated with extensive extracellular matrix remodelling and perivascular fibrosis, indicative of adverse cardiac remodelling. Mice with endothelial ILK deletion suffered early ischaemic-like events with ST elevation and transient increases in cardiac troponins, which correlated with fibrotic remodelling. In addition, ecILK cKO mice exhibited many features of coronary microvascular disease: reduced cardiac perfusion, impaired coronary flow reserve and arterial remodelling with patent epicardial coronary arteries. Moreover, endothelial ILK deletion induced a moderate increase in blood pressure, but the antihypertensive drug Losartan did not affect microvascular remodelling whilst only partially ameliorated fibrotic remodelling. The plasma miRNA profile reveals endothelial-to-mesenchymal transition (endMT) as an upregulated pathway in endothelial ILK conditional KO mice. Our results show that endothelial cells in the microvasculature in endothelial ILK conditional KO mice underwent endMT. Moreover, endothelial cells isolated from these mice and ILK-silenced human microvascular endothelial cells underwent endMT, indicating that decreased endothelial ILK contributes directly to this endothelial phenotype shift. Our results identify ILK as a crucial regulator of microvascular endothelial homeostasis. Endothelial ILK prevents microvascular dysfunction and cardiac remodelling, contributing to the maintenance of the endothelial cell phenotype.


Assuntos
Células Endoteliais , Isquemia Miocárdica , Humanos , Animais , Camundongos , Células Endoteliais/patologia , Transdução de Sinais , Remodelação Ventricular , Isquemia Miocárdica/patologia , Vasos Coronários , Fibrose
3.
Phys Chem Chem Phys ; 25(48): 33193-33197, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38047619

RESUMO

In this comment we discuss some aspects of Phys. Chem. Chem. Phys., 2022, 24, 15851, by Allison et al., an article intensely motivated by our study of grazing incidence fast atom diffraction (GIFAD) for He-KCl(001) [G. A. Bocan, H. Breiss, S. Szilasi, A. Momeni, M. E. Staicu Casagrande, M. S. Gravielle, E. A. Sánchez and H. Khemliche, Phys. Rev. Lett., 2020, 125, 096101; G. A. Bocan, H. Breiss, S. Szilasi, A. Momeni, M. E. Staicu Casagrande, E. A. Sánchez, M. S. Gravielle and H. Khemliche, Phys. Rev. B, 2021, 104, 235401]. In particular, (a) we show that, contrary to first order perturbation prediction, the surface corrugation is not proportional to the tangent of the rainbow angle and, (b) we analyze whether a Morse-like formula, like the one Allison et al. use, is able to reproduce the atom-surface potential derived from density functional theory (DFT) calculations. In addition, we give some clarifications regarding specific remarks the authors made about our articles.

4.
Int J Mol Sci ; 24(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37569562

RESUMO

Plastic production, disposal, and recycling systems represent one of the higher challenges for the planet's health. Its direct consequence is the release of endocrine disruptors, such as bisphenol A (BPA), and its emerging substitute molecules, bisphenol F and S (BPF and BPS), into the environment. Consequently, bisphenols are usually present in human biological fluids. Since BPA, BPS, and BPF have structural analogies and similar hormonal activity, their combined study is urgently needed. The present manuscript studied the effect of the mixture of bisphenols (BPmix) in one of the world's largest human cohorts (NHANES cohort). Descriptive and comparative statistics, binomial and multinomial logistic regression, weighted quantile sum regression, quantile g-computation, and Bayesian kernel machine regression analysis determined a positive association between BPmix and heart disease, including confounders age, gender, BMI, ethnicity, Poverty/Income Ratio, and serum cotinine. Endothelial dysfunction is a hallmark of cardiovascular disease; thus, the average ratio of bisphenols found in humans was used to conduct murine aortic endothelial cell studies. The first results showed that BPmix had a higher effect on cell viability than BPA, enhancing its deleterious biological action. However, the flow cytometry, Western blot, and immunofluorescence assays demonstrated that BPmix induces a differential effect on cell death. While BPA exposure induces necroptosis, its combination with the proportion determined in the NHANES cohort induces apoptosis. In conclusion, the evidence suggests the need to reassess research methodologies to study endocrine disruptors more realistically.


Assuntos
Disruptores Endócrinos , Cardiopatias , Humanos , Animais , Camundongos , Disruptores Endócrinos/toxicidade , Endotélio Vascular/metabolismo , Teorema de Bayes , Inquéritos Nutricionais , Compostos Benzidrílicos/farmacologia
5.
New Phytol ; 235(6): 2406-2423, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35704043

RESUMO

The analysis of plant elemental composition and the underlying factors affecting its variation are a current hot topic in ecology. Ecological adaptation to atypical soils may shift plant elemental composition. However, no previous studies have evaluated its relevance against other factors such as phylogeny, climate or individual soil conditions. We evaluated the effect of the phylogeny, environment (climate, soil), and affinity to gypsum soils on the elemental composition of 83 taxa typical of Iberian gypsum ecosystems. We used a new statistical procedure (multiple phylogenetic variance decomposition, MPVD) to decompose total explained variance by different factors across all nodes in the phylogenetic tree of target species (covering 120 million years of Angiosperm evolution). Our results highlight the relevance of phylogeny on the elemental composition of plants both at early (with the development of key preadaptive traits) and recent divergence times (diversification of the Iberian gypsum flora concurrent with Iberian gypsum deposit accumulation). Despite the predominant phylogenetic effect, plant adaptation to gypsum soils had a strong impact on the elemental composition of plants, particularly on sulphur concentrations, while climate and soil effects were smaller. Accordingly, we detected a convergent evolution of gypsum specialists from different lineages on increased sulphur and magnesium foliar concentrations.


Assuntos
Sulfato de Cálcio , Ecossistema , Filogenia , Plantas/genética , Solo , Enxofre
6.
J Cell Physiol ; 235(11): 8210-8223, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31970782

RESUMO

The underlying mechanism of normal lung organogenesis is not well understood. An increasing number of studies are demonstrating that extracellular vesicles (EVs) play critical roles in organ development by delivering microRNAs (miRNA) to neighboring and distant cells. miRNAs are important for fetal lung growth; however, the role of miRNA-EVs (miRNAs packaged inside the EVs) during fetal lung development is unexplored. The aim of this study was to examine the expression of miRNA-EVs in MLE-12, a murine lung epithelial cell line subjected to mechanical stretch in vitro with the long-term goal to investigate their potential role in the fetal lung development. Both cyclic and continuous mechanical stretch regulate miRNA differentially in EVs released from MLE-12 and intracellularly, demonstrating that mechanical signals regulate the expression of miRNA-EVs in lung epithelial cells. These results provide a proof-of-concept for the potential role that miRNA-EVs could play in the development of fetal lung.


Assuntos
Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Pulmão/embriologia , MicroRNAs/metabolismo , Animais , Linhagem Celular , Camundongos , Estresse Mecânico
7.
J Food Sci Technol ; 55(9): 3564-3574, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150815

RESUMO

Onion is one of the oldest and most consumed crops in the world. Its quality deteriorates gradually during prolonged storage. In the present study, white onions of the variety "Sierra Blanca" were stored in a controlled atmosphere (CA) for 7 months. The color, total pungency, microbiological load and total carbohydrates were evaluated. Three treatments were applied: control treatment (CT), regular atmosphere at 2.5 °C without controlled relative humidity (RH); (T1)1% O2 + 1% CO2 at 2.5 °C and 60-75% RH and (T2)3% O2 + 5% CO2 at 2.5 °C and 60-75% RH. The statistical analysis showed a significant effect of the treatments and storage time in most of the variables analyzed. The CA managed to preserve the quality of the onion during the storage period while the control bulbs exhibited greater deterioration. These increased 2.9 times their level of pungency, had a higher microbial load and showed a very noticeable color change at the end of storage with respect to freshly harvested onions and those stored in a CA. They had a more yellow-green coloration. Both CA treatments were effective in preserving onion quality, but a more positive effect for T1 than T2 was observed on most of the parameters evaluated.

8.
Neuropediatrics ; 48(1): 45-48, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27434885

RESUMO

Febrile infection-related epilepsy syndrome (FIRES) is a rare condition which evolves into refractory status epilepticus (SE), with poor outcome in most cases. Conventional antiepileptic drugs fail to control SE in FIRES patients. We report the case of a previously healthy 4-year-old boy who was diagnosed with FIRES. One week after pharyngitis and high fever he started seizures, followed by refractory SE. Benzodiazepines, phenytoin, high-dose barbiturates that induce burst suppression, high doses of corticosteroids, plasmapheresis, immunoglobulins, propofol, lidocaine, ketamine, inhaled desflurane, ketogenic diet, lacosamide, and therapeutic hypothermia were tried at different times in a period of 8 weeks, but all of them were ineffective. Electroconvulsive therapy (ECT) has been used in refractory SE in children. We report a case in which ECT was successfully used for treatment of refractory SE in a pediatric patient with FIRES syndrome.


Assuntos
Encefalopatia Aguda Febril/complicações , Eletroconvulsoterapia/métodos , Estado Epiléptico/etiologia , Estado Epiléptico/terapia , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Eletroencefalografia , Humanos , Masculino , Estado Epiléptico/líquido cefalorraquidiano
9.
Phys Chem Chem Phys ; 19(28): 18580-18586, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28686267

RESUMO

We studied the growth of Ge layers on Au(111) under ultra-high vacuum conditions from the submonolayer regime up to a few layers with Scanning Tunneling Microscopy (STM), Direct Recoiling Spectroscopy (DRS) and Low Energy Electron Diffraction (LEED). Most STM images for the thicker layers are consistent with a commensurate 5 × 8 arrangement. The high surface sensitivity of TOF-DRS allows us to confirm the coexistence of Au and Ge atoms in the top layer for all stages of growth. An estimation of the Au to Ge ratio at the surface of the thick layer gives about 1 Au atom per 2 Ge ones. When the growth is carried out at sample temperatures higher than about 420 K, a fraction of the deposited Ge atoms migrate into the bulk of Au. This incorporation of Ge into the bulk reduces the growth rate of the Ge films, making it more difficult to obtain films thicker than a few layers. After sputtering the Ge/Au surface, the segregation of bulk Ge atoms to the surface occurs for temperatures ≥600 K. The surface obtained after segregation of Ge reaches a stable condition (saturation) with an n × n symmetry with n on the order of 14.

10.
Molecules ; 22(8)2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28817105

RESUMO

As Mexico is located within Mesoamerica, it is considered the site where the bean plant originated and where it was domesticated. Beans have been an integral part of the Mexican diet for thousands of years. Within the country, there are a number of genotypes possessing highly diverse physical and chemical properties. This review describes the major bioactive compounds contained on the Mexican varieties of the common bean. A brief analysis is carried out regarding the benefits they have on health. The effect of seed coat color on the nutraceutical compounds content is distinguished, where black bean stands out because it is high content of anthocyanins, polyphenols and flavonoids such as quercetin. This confers black bean with an elevated antioxidant capacity. The most prominent genotypes within this group are the "Negro San Luis", "Negro 8025" and "Negro Jamapa" varieties. Conversely, the analyzed evidence shows that more studies are needed in order to expand our knowledge on the nutraceutical quality of the Mexican bean genotypes, either grown or wild-type, as well as their impact on health in order to be used in genetic improvement programs or as a strategy to encourage their consumption. The latter is based on the high potential it has for health preservation and disease prevention.


Assuntos
Antioxidantes/uso terapêutico , Phaseolus/química , Sementes/química , Antocianinas/química , Antocianinas/uso terapêutico , Antioxidantes/química , Flavonoides/química , Flavonoides/uso terapêutico , Genótipo , Humanos , México , Phaseolus/genética , Polifenóis/química , Polifenóis/uso terapêutico , Sementes/genética
11.
BMC Genomics ; 16: 1059, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26666532

RESUMO

BACKGROUND: The initiation of translation via cellular internal ribosome entry sites plays an important role in the stress response and certain physiological conditions in which canonical cap-dependent translation initiation is compromised. Currently, only a limited number of these regulatory elements have been experimentally identified. Notably, cellular internal ribosome entry sites lack conservation of both the primary sequence and mRNA secondary structure, rendering their identification difficult. Despite their biological importance, the currently available computational strategies to predict them have had limited success. We developed a bioinformatic method based on a support vector machine for the prediction of internal ribosome entry sites in fungi using the 5'-UTR sequences of 20 non-redundant fungal organisms. Additionally, we performed a comparative analysis and characterization of the functional relationships among the gene products predicted to be translated by this cap-independent mechanism. RESULTS: Using our method, we predicted 6,532 internal ribosome entry sites in 20 non-redundant fungal organisms. Some orthologous groups were enriched with our positive predictions. This is the case of the HSP70 chaperone family, which remarkably has two verified internal ribosome entry sites, one in humans and the other in flies. A second example is the orthologous group of the eIF4G repression protein Sbp1p, which has two homologous genes known to be translated by this cap-independent mechanism, one in mice and the other in yeast. These examples emphasize the wide conservation of these regulatory elements as a result of selective pressure. In addition, we performed a protein-protein interaction network characterization of the gene products of our positive predictions using Saccharomyces cerevisiae as a model, which revealed a highly connected and modular topology, suggesting a functional association. A remarkable example of this functional association is our prediction of internal ribosome entry sites elements in three components of the RNA polymerase II mediator complex. CONCLUSIONS: We developed a method for the prediction of cellular internal ribosome entry sites that may guide experimental and bioinformatic analyses to increase our understanding of protein translation regulation. Our analysis suggests that fungi show evolutionary conservation and functional association of proteins translated by this cap-independent mechanism.


Assuntos
Biologia Computacional/métodos , Proteínas Fúngicas/genética , Fungos/genética , Sítios Internos de Entrada Ribossomal , Regiões 5' não Traduzidas , Fungos/classificação , Filogenia , Mapas de Interação de Proteínas , RNA Fúngico/análise , Máquina de Vetores de Suporte
12.
Respir Res ; 16: 60, 2015 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-26006045

RESUMO

BACKGROUND: Mechanical ventilation plays a central role in the injury of premature lungs. However, the mechanisms by which mechanical signals trigger an inflammatory cascade to promote lung injury are not well-characterized. Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable mechanoreceptor channel has been shown to be a major determinant of ventilator-induced acute lung injury in adult models. However, the role of these channels as modulators of inflammation in immature lungs is unknown. In this study, we tested the hypothesis that TRPV4 channels are important mechanotransducers in fetal lung injury. METHODS: Expression of TRPV4 in the mouse fetal lung was investigated by immunohistochemistry, Western blot and qRT-PCR. Isolated fetal epithelial cells were exposed to mechanical stimulation using the Flexcell Strain Unit and inflammation and differentiation were analyzed by ELISA and SP-C mRNA, respectively. RESULTS: TRPV4 is developmentally regulated in the fetal mouse lung; it is expressed in the lung epithelium and increases with advanced gestation. In contrast, in isolated epithelial cells, TRPV4 expression is maximal at E17-E18 of gestation. Mechanical stretch increases TRPV4 in isolated fetal epithelial cells only during the canalicular stage of lung development. Using the TRPV4 agonist GSK1016790A, the antagonist HC-067047, and the cytokine IL-6 as a marker of inflammation, we observed that TRPV4 regulates release of IL-6 via p38 and ERK pathways. Interestingly, stretch-induced differentiation of fetal epithelial cells was also modulated by TRPV4. CONCLUSION: These studies demonstrate that TRPV4 may play an important role in the transduction of mechanical signals in the fetal lung epithelium by modulating not only inflammation but also the differentiation of fetal epithelial cells.


Assuntos
Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Mecanotransdução Celular/fisiologia , Canais de Cátion TRPV/biossíntese , Animais , Células Cultivadas , Células Epiteliais/patologia , Feminino , Feto , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Mucosa Respiratória/embriologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia
13.
Surg Innov ; 22(1): 54-60, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24902692

RESUMO

BACKGROUND: The suture dehiscence has traditionally represented a major surgical problem that has not fully resolved. Surgeons should perform sutures in nonoptimal conditions using different methods of sealing and/or reinforcement of suture. The aim is to assess the effectiveness of TachoSil in an experimental model of colon perforations in a simulated precarious situation. METHODS: Forty Wistar rats of both genders (14-24 weeks old) were equally divided in 2 groups; study group was submitted to extended starvation and segmental ischemia. The surgical complications analyzed were animal death, colonic leaks, or intra-abdominal infection, either as local abscesses or diffuse peritonitis. The burst pressure was measured in millimeters of mercury. The histological analysis was performed according to Ehrlich and Hunt numerical scale modified by Phillips. RESULTS: Only 1 animal belonging to the study group died as a consequence of the colonic ischemia. The eventual colonic leak or diffuse peritonitis was reported. Three local abscesses were observed in the study group and one in the control group, and numerous microscopic abscesses in histological analysis (12 vs. 11) were detected. The average burst pressure in the study group was 209.47 ± 50.274 versus 203 ± 51.514 mm Hg in the control group. No differences were observed in any of the variables analyzed in the histological activity. CONCLUSION: TachoSil has proven useful as a sealant of colonic perforations in our experimental study. We therefore conclude that its use in situations of insecurity may be adequate, even in optimal conditions in which reinforcement of previous suture is not strictly required.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Fibrinogênio/uso terapêutico , Perfuração Intestinal/cirurgia , Trombina/uso terapêutico , Animais , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Infecções Intra-Abdominais , Masculino , Complicações Pós-Operatórias , Pressão , Ratos , Ratos Wistar
14.
J Biol Chem ; 288(35): 25646-25657, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23888051

RESUMO

Mechanical forces are critical for normal fetal lung development. However, the mechanisms regulating this process are not well-characterized. We hypothesized that strain-induced release of HB-EGF and TGF-α is mediated via integrin-ADAM17/TACE interactions. Employing an in vitro system to simulate mechanical forces in fetal lung development, we showed that mechanical strain of fetal epithelial cells actives TACE, releases HB-EGF and TGF-α, and promotes differentiation. In contrast, in samples incubated with the TACE inhibitor IC-3 or in cells isolated from TACE knock-out mice, mechanical strain did not release ligands or promote cell differentiation, which were both rescued after transfection of ADAM17. Cell adhesion assay and co-immunoprecipitation experiments in wild-type and TACE knock-out cells using several TACE constructs demonstrated not only that integrins α6 and ß1 bind to TACE via the disintegrin domain but also that mechanical strain enhances these interactions. Furthermore, force applied to these integrin receptors by magnetic beads activated TACE and shed HB-EGF and TGF-α. The contribution of integrins α6 and ß1 to differentiation of fetal epithelial cells by strain was demonstrated by blocking their binding site with specific antibodies and by culturing the cells on membranes coated with anti-integrin α6 and ß1 antibodies. In conclusion, mechanical strain releases HB-EGF and TGF-α and promotes fetal type II cell differentiation via α6ß1 integrin-ADAM17/TACE signaling pathway. These investigations provide novel mechanistic information on how mechanical forces promote fetal lung development and specifically differentiation of epithelial cells. This information could be also relevant to other tissues exposed to mechanical forces.


Assuntos
Proteínas ADAM/metabolismo , Diferenciação Celular/fisiologia , Células Epiteliais/metabolismo , Integrina alfa6beta1/metabolismo , Pulmão/embriologia , Mucosa Respiratória/embriologia , Transdução de Sinais/fisiologia , Proteínas ADAM/genética , Proteína ADAM17 , Animais , Células Epiteliais/citologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Integrina alfa6beta1/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pulmão/citologia , Camundongos , Camundongos Knockout , Ligação Proteica , Mucosa Respiratória/citologia , Estresse Fisiológico/fisiologia , Fator de Crescimento Transformador alfa/genética , Fator de Crescimento Transformador alfa/metabolismo
15.
J Recept Signal Transduct Res ; 34(1): 58-63, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24283698

RESUMO

CONTEXT: Epidermal growth factor receptor (EGFR) is critical for normal fetal lung development. However, the role of this receptor in lung injury induced by mechanical ventilation is controversial. OBJECTIVE: To investigate in vitro whether EGFR plays a protective role or contributes to stretch-induced lung injury. METHODS: Fetal lung fibroblasts were isolated from wild-type and EGFR knockout mice and exposed to physiologic stretch (2.5% elongation) or injurious stretch (20% distention). Cells were evaluated for necrosis, apoptosis, proliferation and inflammation. RESULTS: Injurious stretch increased lactate dehydrogenase (LDH) release to similar degree in wild-type and knockout cells. In contrast, 20% stretch increased cleaved caspase-3 and decreased proliferating cell nuclear antigen (PCNA) only in wild-type cells. Furthermore, 20% stretch increased macrophage inflammatory protein-2 (MIP-2) and monocyte chemotactic protein-1 (MCP-1) by 3-5 fold in wild-type cells. In contrast, in knockout cells MIP-2 decreased by 50% and MCP-1 only increased by 60% when compared to physiologic stretch. CONCLUSION: Our data show a decrease of apoptosis and inflammation and absence of decreased proliferation after injurious stretch of fetal fibroblasts lacking EGFR. These data suggest that EGFR contributes to lung injury mediated by stretch. We speculate that EGFR may contribute to the arrest of lung development observed after mechanical ventilation by decreasing the population of lung fibroblasts.


Assuntos
Receptores ErbB/genética , Lesão Pulmonar/genética , Pulmão/crescimento & desenvolvimento , Estresse Mecânico , Animais , Apoptose/genética , Receptores ErbB/biossíntese , Desenvolvimento Fetal , Fibroblastos/patologia , Camundongos , Camundongos Knockout , Fosforilação , Transdução de Sinais
18.
Heliyon ; 10(1): e23404, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38169926

RESUMO

Demand charges are widely used for commercial and industrial consumers. These costs are often not well known, let alone the effects that PV can have on them. This work proposes a methodology to assess the effect of PV on reducing these charges and to optimise the power to be contracted, using techniques taken from exploratory data analysis. This methodology is applied to five case studies of industrial consumers from different sectors in Spain, finding savings between 5 % and 11 % of demand charges in industries with continuous operation and up to 28 % in cases of discontinuous operation. These savings can be even greater if the maximum power that can be contracted is lower than the optimum. The demand charges in Spain consist of a fixed part proportional to the contracted power and a variable part depending on the power peaks exceeding it. Since for the variable part the coincident and non-coincident models coexist, a comparison is made between the two models, finding that in the general case PV users can achieve higher savings with the coincident model.

19.
AJP Rep ; 14(3): e239-e243, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39386163

RESUMO

The rapid identification and management of air leak syndrome in the neonatal intensive care unit is critical to prevent and/or minimize short- and long-term complications. Traditionally, chest X-ray is used to diagnose pneumothorax or pneumomediastinum. However, point-of-care ultrasound is increasingly being used for procedural and diagnostic purposes. Current ultrasound guidelines recommend specific criteria to diagnose pneumothorax in newborns including sharp A-lines, absence of B-lines, lack of shimmering of the pleural line, and the presence of a lung point. Pneumomediastinum may have similar ultrasound characteristics. In this case report, we present two cases of pneumomediastinum in newborns, describe the associated ultrasound findings, and review some of the criteria to differentiate from pneumothorax, including the presence of a still lung point. A high index of suspicion for pneumomediastinum should be maintained when using ultrasound to diagnose air leak given the overlapping sonographic features with pneumothorax. This distinction is of particular importance if evacuation of air by needle thoracentesis or the placement of a chest tube is under consideration.

20.
Cells ; 13(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38534325

RESUMO

Calcific Aortic Valve Disease (CAVD) is a significant concern for cardiovascular health and is closely associated with chronic kidney disease (CKD). Aortic valve endothelial cells (VECs) play a significant role in the onset and progression of CAVD. Previous research has suggested that uremic toxins, particularly indoxyl sulfate (IS), induce vascular calcification and endothelial dysfunction, but the effect of IS on valve endothelial cells (VECs) and its contribution to CAVD is unclear. Our results show that IS reduced human VEC viability and increased pro-calcific markers RUNX2 and alkaline phosphatase (ALP) expression. Additionally, IS-exposed VECs cultured in pro-osteogenic media showed increased calcification. Mechanistically, IS induced endothelial-to-mesenchymal transition (EndMT), evidenced by the loss of endothelial markers and increased expression of mesenchymal markers. IS triggered VEC inflammation, as revealed by NF-kB activation, and decreased integrin-linked kinase (ILK) expression. ILK overexpression reversed the loss of endothelial phenotype and RUNX2, emphasizing its relevance in the pathogenesis of CAVD in CKD. Conversely, a lower dose of IS intensified some of the effects in EndMT caused by silencing ILK. These findings imply that IS affects valve endothelium directly, contributing to CAVD by inducing EndMT and calcification, with ILK acting as a crucial modulator.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Proteínas Serina-Treonina Quinases , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Indicã , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Células Endoteliais/metabolismo , Células Cultivadas , Calcificação Vascular/metabolismo , Insuficiência Renal Crônica/patologia
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