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1.
Nat Immunol ; 25(2): 316-329, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182669

RESUMO

Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16+ natural killer cells and interleukin-17-producing helper T cells and a decreased frequency of type 1 helper T cells. Men displayed this phenotype more robustly and mounted weaker PCV13 responses than women. Baseline expression levels of a distinct gene set predicted PPSV23 responses. This pneumococcal precision vaccinology study in older adults uncovered distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.


Assuntos
Anticorpos Antibacterianos , Streptococcus pneumoniae , Masculino , Humanos , Feminino , Idoso , Vacinas Conjugadas , Método Duplo-Cego , Vacinação , Vacinas Pneumocócicas , Polissacarídeos
2.
Eur J Neurosci ; 59(5): 982-995, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38378276

RESUMO

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and, in turn, modulate reward-seeking behaviours: here, we have investigated such a possibility following a brief EE exposure. Adult male Sprague-Dawley rats were exposed to EE for 22 h and the expression of critical elements of the glutamate synapse was measured 2 h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT-1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes in glutamatergic mPFC, NAc and Hipp. Such changes are area-specific and involve postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins, thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to dynamically modulate the glutamatergic synapses in mPFC-NAc-Hipp circuits, which may modulate rewarding and memory processes.


Assuntos
Ácido Glutâmico , Receptores de AMPA , Ratos , Animais , Masculino , Ácido Glutâmico/metabolismo , Ratos Sprague-Dawley , Receptores de AMPA/metabolismo , N-Metilaspartato/farmacologia , Sinapses/fisiologia , Núcleo Accumbens , Receptores de N-Metil-D-Aspartato/metabolismo
3.
Cell Mol Neurobiol ; 44(1): 21, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349562

RESUMO

It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1ß. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in https://github.com/dadriba05/SystematicReview.git ). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted.


Assuntos
Citocinas , Viroses , Humanos , Microglia , Fator de Necrose Tumoral alfa , Anti-Inflamatórios
4.
Nanotechnology ; 35(28)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522104

RESUMO

Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique that has found application in the trace detection of a wide range of contaminants. In this paper, we report on the fabrication of 2D silver nanodendrites, on silicon chips, synthesized by electrochemical reduction of AgNO3at microelectrodes. The formation of nanodendrites is tentatively explained in terms of electromigration and diffusion of silver ions. Electrochemical characterization suggests that the nanodendrites do not stay electrically connected to the microelectrode. The substrates show SERS activity with an enhancement factor on the order of 106. Density functional theory simulations were carried out to investigate the suitability of the fabricated substrate for pesticide monitoring. These substrates can be functionalized with cyclodextrin macro molecules to help with the detection of molecules with low affinity with silver surfaces. A proof of concept is demonstrated with the detection of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA).

5.
PLoS Genet ; 17(1): e1009277, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411704

RESUMO

The nuclear protein CCCTC-binding factor (CTCF) has diverse roles in chromatin architecture and gene regulation. Functionally, CTCF associates with thousands of genomic sites and interacts with proteins, such as cohesin, or non-coding RNAs to facilitate specific transcriptional programming. In this study, we examined CTCF during the cellular stress response in human primary cells using immune-blotting, quantitative real time-PCR, chromatin immunoprecipitation-sequence (ChIP-seq) analysis, mass spectrometry, RNA immunoprecipitation-sequence analysis (RIP-seq), and Airyscan confocal microscopy. Unexpectedly, we found that CTCF is exquisitely sensitive to diverse forms of stress in normal patient-derived human mammary epithelial cells (HMECs). In HMECs, a subset of CTCF protein forms complexes that localize to Serine/arginine-rich splicing factor (SC-35)-containing nuclear speckles. Upon stress, this species of CTCF protein is rapidly downregulated by changes in protein stability, resulting in loss of CTCF from SC-35 nuclear speckles and changes in CTCF-RNA interactions. Our ChIP-seq analysis indicated that CTCF binding to genomic DNA is largely unchanged. Restoration of the stress-sensitive pool of CTCF protein abundance and re-localization to nuclear speckles can be achieved by inhibition of proteasome-mediated degradation. Surprisingly, we observed the same characteristics of the stress response during neuronal differentiation of human pluripotent stem cells (hPSCs). CTCF forms stress-sensitive complexes that localize to SC-35 nuclear speckles during a specific stage of neuronal commitment/development but not in differentiated neurons. We speculate that these particular CTCF complexes serve a role in RNA processing that may be intimately linked with specific genes in the vicinity of nuclear speckles, potentially to maintain cells in a certain differentiation state, that is dynamically regulated by environmental signals. The stress-regulated activity of CTCF is uncoupled in persistently stressed, epigenetically re-programmed "variant" HMECs and certain cancer cell lines. These results reveal new insights into CTCF function in cell differentiation and the stress-response with implications for oxidative damage-induced cancer initiation and neuro-degenerative diseases.


Assuntos
Fator de Ligação a CCCTC/genética , Proteínas de Ligação a DNA/genética , Neoplasias/genética , Doenças Neurodegenerativas/genética , Fatores de Processamento de Serina-Arginina/genética , Sítios de Ligação , Diferenciação Celular , Linhagem Celular Tumoral , Cromatina , Cromossomos , Epigênese Genética/genética , Regulação da Expressão Gênica , Genômica , Humanos , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/metabolismo , Neoplasias/patologia , Doenças Neurodegenerativas/patologia , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/genética , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/patologia , Ligação Proteica , Processamento Pós-Transcricional do RNA/genética , Estresse Fisiológico/genética
6.
Sensors (Basel) ; 24(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38931591

RESUMO

In recent years, there has been a growing interest in developing portable and personal devices for measuring air quality and surrounding pollutants, partly due to the need for ventilation in the aftermath of COVID-19 situation. Moreover, the monitoring of hazardous chemical agents is a focus for ensuring compliance with safety standards and is an indispensable component in safeguarding human welfare. Air quality measurement is conducted by public institutions with high precision but costly equipment, which requires constant calibration and maintenance by highly qualified personnel for its proper operation. Such devices, used as reference stations, have a low spatial resolution since, due to their high cost, they are usually located in a few fixed places in the city or region to be studied. However, they also have a low temporal resolution, providing few samples per hour. To overcome these drawbacks and to provide people with personalized and up-to-date air quality information, a personal device (smartwatch) based on MEMS gas sensors has been developed. The methodology followed to validate the performance of the prototype was as follows: firstly, the detection capability was tested by measuring carbon dioxide and methane at different concentrations, resulting in low detection limits; secondly, several experiments were performed to test the discrimination capability against gases such as toluene, xylene, and ethylbenzene. principal component analysis of the data showed good separation and discrimination between the gases measured.


Assuntos
COVID-19 , Dióxido de Carbono , Monitoramento Ambiental , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Humanos , Dióxido de Carbono/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Gases/análise , SARS-CoV-2/isolamento & purificação , Metano/análise
7.
J Therm Biol ; 123: 103893, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38924931

RESUMO

Species are expected to migrate to higher latitudes as warming intensifies due to anthropogenic climate change since physiological mechanisms have been adapted to maximize fitness under specific temperatures. However, literature suggests that upwellings could act as thermal refugia under climate warming protecting marine ecosystem diversity. This research aimed to predict the effects of climate warming on commercial and non-commercial fish species reported in official Mexican documents (>200 species) based on their thermal niche to observe if upwellings can act as potential thermal refugia. Present (2000-2014) and Representative Concentration Pathway (6.0 and 8.5) scenarios (2040-2050 and 2090-2100) have been considered for this work. Current and future suitability patterns, species distribution, richness, and turnover were calculated using the minimum volume ellipsoids as algorithm. The results in this study highlight that beyond migration to higher latitudes, upwelling regions could protect marine fishes, although the mechanism differed between the innate characteristics of upwellings. Most modeled species (primarily tropical fishes) found refuge in the tropical upwelling in Northern Yucatan. However, the highest warming scenario overwhelmed this region. In contrast, the Baja California region lies within the Eastern Boundary Upwelling Systems. While the area experiences an increase in suitability, the northern regions have a higher upwelling intensity acting as environmental barriers for many tropical species. Conversely, in the southern regions where upwelling is weaker, species tend to congregate and persist even during elevated warming, according to the turnover analysis. These findings suggest that tropicalization in higher latitudes may not be as straightforward as previously assumed. Nevertheless, climate change affects numerous ecosystem features, such as trophic relationships, phenology, and other environmental variables not considered here. In addition, uncertainty still exists about the assumption of increasing intensity of upwelling systems.

8.
Mol Ecol ; 32(1): 95-109, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36261873

RESUMO

Distinguishing among the mechanisms underlying the spatial distribution of genetic variation resulting from the environmental or physical barriers from those arising due to simple geographic distance is challenging in complex landscapes. The Andean uplift represents one of the most heterogeneous habitats where multiple mechanisms may interact, confounding their relative roles. We explore this broad question in the leaf-cutting ant Atta cephalotes, a species that is distributed across the Andes mountains, using nuclear microsatellite markers and mtCOI gene sequences. We investigate spatial genetic divergence across the western range of the northern Andes in Colombia by testing the relative role of alternative scenarios of population divergence, including isolation by geographic distance (IBD), climatic conditions (IBE), and the physical barriers presented by the Andes mountains (IBB). Our results reveal substantial genetic differentiation among A. cephalotes populations for both types of markers, but only nuclear divergence followed a hierarchical pattern with multiple models of genetic divergence imposed by the western range. Model selection showed that the IBD, IBE (temperature and precipitation), and IBB (Andes mountains) models, often proposed as individual drivers of genetic divergence, interact, and explain up to 33% of the genetic divergence in A. cephalotes. The IBE model remained significant after accounting for IBD, suggesting that environmental factors play a more prominent role than IBB. These factors, in combination with the idiosyncratic dispersal patterns of ants, appear to determine the hierarchical patterns of gene flow. This study enriches our understanding of the forces shaping population divergence in complex habitat landscapes.


Assuntos
Formigas , Animais , Formigas/genética , Variação Genética/genética , Deriva Genética , Ecossistema , Temperatura , Genética Populacional
9.
J Anat ; 243(5): 886-891, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37350256

RESUMO

Little is known about gender differences in stiffness of forearm muscles during voluntary actions. This study aimed to investigate the effect of forearm rotation on flexor carpi ulnaris (FCU) stiffness in men and women during submaximal handgrip contractions. During a single session, measurements were made on 20 young participants (9 females). Two positions of the forearm were compared in random order with the elbow flexed 90 degrees: (i) neutral position and (ii) maximal supination. In each position, participants performed two submaximal handgrip contractions at 25% and 50% of maximal voluntary contraction, while compressive stiffness was collected using a hand myometer (MyotonPRO). A mixed repeated measurement ANOVA was applied to assess the interaction between gender, forearm position, and contraction intensity. The FCU stiffness is affected by handgrip contraction intensity (p < 0.001), gender (p < 0.001), BMI (p = 0.009), and forearm rotation (p = 0.007). Only the gender factor was found to have significant interaction with forearm rotation (p = 0.037). Men's FCU was stiffer than women's in both positions and contraction intensities (p < 0.05). Only in men a significant increase in FCU stiffness was observed when comparing contraction intensities at both forearm positions (p < 0.05), as well as when the forearm was rotated from neutral to supine at both intensities (p < 0.05). In conclusion, FCU stiffness during handgrip contraction differed significantly between men and women. Women have fewer stiffness changes in FCU when performing different levels of handgrip contraction. We also observed that only men increased FCU stiffness by changing the forearm position from neutral to supine position for both handgrip intensities.


Assuntos
Cotovelo , Antebraço , Masculino , Humanos , Feminino , Antebraço/fisiologia , Força da Mão/fisiologia , Fatores Sexuais , Músculo Esquelético/fisiologia
10.
Cereb Cortex ; 32(10): 2197-2215, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-34613369

RESUMO

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer's disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aß42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Idoso , Ritmo alfa/fisiologia , Doença de Alzheimer/psicologia , Córtex Cerebral , Disfunção Cognitiva/psicologia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Descanso/fisiologia , Estudos Retrospectivos
11.
Global Health ; 19(1): 78, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891675

RESUMO

BACKGROUND: The US-Mexico border is the busiest in the world, with millions of people crossing it daily. However, little is known about cross-border utilization of cancer care, or about the reasons driving it. We designed a cross sectional online survey to understand the type of care patients with cancer who live in the US and Mexico seek outside their home country, the reasons why patients traveled across the border to receive care, and the barriers faced when seeking cross-border care. RESULTS: The online survey was sent to the 248 cancer care providers working in the six Mexican border states who were registered members of the Mexican Society of Oncology. Responses were collected between September-November 2022. Sixty-six providers (response rate 26%) completed the survey. Fifty-nine (89%) reported interacting with US-based patients traveling to Mexico to receive various treatment modalities, with curative surgery (n = 38) and adjuvant chemotherapy (n = 31) being the most common. Forty-nine (74%) reported interacting with Mexico-based patients traveling to the US to receive various treatment modalities, with immunotherapy (n = 29) and curative surgery (n = 27) being the most common. The most frequently reported reason US-based patients sought care in Mexico was inadequate health insurance (n = 45). The most frequently reported reason Mexico-based patients sought care in the US was patients' perception of superior healthcare (n = 38). CONCLUSIONS: Most Mexican oncologists working along the Mexico-US border have interacted with patients seeking or receiving binational cancer care. The type of care sought, as well as the reasons for seeking it, differ between US and Mexico-based patients. These patterns of cross-border healthcare utilization highlight unmet needs for patients with cancer in both countries and call for policy changes to improve outcomes in border regions.


Assuntos
Acessibilidade aos Serviços de Saúde , Neoplasias , Humanos , Estados Unidos , México , Estudos Transversais , Aceitação pelo Paciente de Cuidados de Saúde , Inquéritos e Questionários , Neoplasias/terapia
12.
J Therm Biol ; 114: 103495, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37276747

RESUMO

Ocean warming is expected to occur due to anthropogenic climate change bringing a spatial shift of marine communities. Experimental data that characterize the aerobic power budget via an aerobic scope, thermal metabolic scope, or thermal preferences have been proposed as tools that can describe species distribution since they characterize species fitness or performance under different temperatures. This study tested the potential relationship between observed occurrences and different physiological studies in the Americas for 11 commercially important species in Mexico. Projections were also developed for Mexico's exclusive economic zone under different climate warming scenarios. The physiological data were fitted from optimum up to pejus temperatures and projected to sea surface temperatures for present (2003-2014) and Representative Concentration Pathway (RCP) scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5) for the period 2040-2050 and 2090-2100. For species with wide distributions in the Americas, the number of occurrences reported decreases at higher latitudes related to the decrease in species performance calculated from laboratory experiments. In addition, higher species occurrences are usually reported around optimum temperatures. Overall, the results suggest that pejus temperatures likely restrict latitudinal distribution, at least for widely distributed taxons. Regarding Mexican projections, the results varied widely by species. For example, in the Atlantic Ocean, Octopus maya and Panulirus argus are vulnerable to warming scenarios, while Centropomus undecimalis is not. Interestingly, northern Campeche Bank, the Gulf of California, and Western Baja California may act as thermal refugia for marine species indicating they could be assigned as protected areas to support fisheries throughout the Mexican exclusive economic zone. This research adds to the increasing evidence of the relationship between thermal niche and wild population distribution.


Assuntos
Mudança Climática , Meio Ambiente , México , Temperatura , Refúgio de Vida Selvagem , Ecossistema
13.
Arch Orthop Trauma Surg ; 143(4): 1915-1922, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35275283

RESUMO

INTRODUCTION: Hallux valgus (HV) deformity affects the orientation of the metatarsophalangeal (MTP) joint in three planes. Displacement in the coronal plane results in axial rotation of the first metatarsal, with progressive subluxation of the first MTP joint. Multiple techniques have been described to correct the malrotation itself. However, none of them have checked intraoperatively the final position of the first metatarsal head and sesamoids previous to the fixation of the Lapidus procedure or first metatarsal bone osteotomies. The aim of this article is to describe a novel technique to check the first ray rotation and sesamoids position through sonographic assistance. MATERIALS AND METHODS: Before fixation of the Lapidus procedure, with the ankle in maximal dorsiflexion, the surgeon takes the linear ultrasound probe and places it on the sole to visualize the sesamoids, which should be viewed at the same level, with the flexor hallucis longus (FHL) centered between both. Once the ideal position of the head of the first ray has been achieved, temporary fixation with K-wires is performed over the first TMT joint and M1-M2 joint for further sonographic verification of the sesamoids beneath the first metatarsal head. The height of the sesamoids relative to the second metatarsal head should be checked by sonographic control too. RESULTS: Four patients were included. Three females and one male. Their mean age was 76.4 years (R 61-72). Their mean BMI was 29 (R 27.5-32.24). The mean IMA (intermetatarsal angle) was 18.2 (R 17.2-19) degrees and the mean MPA (metatarsophalangeal angle) was 50 (R 36-63) degrees. CONCLUSIONS: Sonographic assistance, is a widely available, inexpensive, and comparative imaging technique that can guide the first ray rotation and sesamoids position in HV surgery, theoretically improving radiological outcomes.


Assuntos
Hallux Valgus , Ossos do Metatarso , Feminino , Humanos , Masculino , Idoso , Rotação , Estudos Retrospectivos , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Radiografia
14.
J Infect Dis ; 225(3): 392-395, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850028

RESUMO

There is a paucity of reports on the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in infants, because most studies have grouped infants with older children. We analyzed the viral loads of 45318 SARS-CoV-2-positive nasopharyngeal swab samples obtained in Buenos Aires, Argentina. Infants younger than 6 months presented higher viral loads than any other age group. Children older than 6 months showed significantly lower viral loads, similar to those founds in adults. This observation raises new questions regarding the role of infants in the spreading of SARS-CoV-2 infection.


Assuntos
COVID-19 , Sistema Respiratório/virologia , SARS-CoV-2 , Carga Viral , Argentina/epidemiologia , COVID-19/diagnóstico , Humanos , Lactente , SARS-CoV-2/isolamento & purificação
15.
J Infect Dis ; 226(10): 1717-1720, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-35723970

RESUMO

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is usually asymptomatic or mild and appears to be poorly immunogenic at least in unvaccinated individuals. Here, we found that health care workers vaccinated with 2 doses of Sputnik V and a booster dose of ChAdOx1 mount a vigorous neutralizing-antibody response after Omicron breakthrough infection.


Assuntos
Formação de Anticorpos , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinação , Anticorpos Neutralizantes , Anticorpos Antivirais
16.
J Cell Biochem ; 123(7): 1197-1206, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35538691

RESUMO

A reduction in extracellular pH (pHe) is a characteristic of most malignant tumors. The aryl hydrocarbon receptor (AhR) is a transcription factor localized in a cytosolic complex with c-Src, which allows it to trigger nongenomic effects through c-Src. Considering that the slightly acidic tumor microenvironment promotes breast cancer progression in a similar way to the AhR/c-Src axis, our aim was to evaluate whether this pathway could be activated by low pHe. We examined the effect of pHe 6.5 on AhR/c-Src axis using two breast cancer cell lines (MDA-MB-231 and LM3) and mammary epithelial cells (NMuMG) and found that acidosis increased c-Src phosphorylation only in tumor cells. Moreover, the presence of AhR inhibitors prevented c-Src activation. Low pHe reduced intracellular pH (pHi), while amiloride treatment, which is known to reduce pHi, induced c-Src phosphorylation through AhR. Analyses were conducted on cell migration and metalloproteases (MMP)-2 and -9 activities, with results showing an acidosis-induced increase in MDA-MB-231 and LM3 cell migration and MMP-9 activity, but no changes in NMuMG cells. Moreover, all these effects were blocked by AhR and c-Src inhibitors. In conclusion, acidosis stimulates the AhR/c-Src axis only in breast cancer cells, increasing cell migration and MMP-9 activity. Although the AhR activation mechanism still remains elusive, a reduction in pHi may be thought to be involved. These findings suggest a critical role for the AhR/c-Src axis in breast tumor progression stimulated by an acidic microenvironment.


Assuntos
Acidose , Neoplasias da Mama , Neoplasias da Mama/metabolismo , Proteína Tirosina Quinase CSK , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Microambiente Tumoral
17.
Br J Haematol ; 197(3): 283-292, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35076084

RESUMO

Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4+ T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T-cell dysfunction in COVID-19. We observed a high frequency of CD4+ T cell-platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID-19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)-α production by CD4+ T cells. In addition, interferon (IFN)-γ production was increased by platelets from HD but not from COVID-19 inpatients. A high expression of PD-L1 was found in platelets from COVID-19 patients to be inversely correlated with IFN-γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD-L1-blocking antibody significantly restored platelets' ability to stimulate IFN-γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID-19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.


Assuntos
Antígeno B7-H1 , COVID-19 , Antígeno B7-H1/metabolismo , Plaquetas/metabolismo , Linfócitos T CD4-Positivos , Humanos , Interferon gama
18.
Plasmid ; 119-120: 102620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35134433

RESUMO

For the production of recombinant protein therapeutics in mammalian cells, a high rate of gene expression is desired and hence strong viral-derived promoters are commonly used. However, they usually induce cellular stress and can be susceptible to epigenetic silencing. Endogenous promoters, which coordinates their activity with cellular and bioprocess dynamics while at the same time they maintain high expression levels, may help to avoid such drawbacks. In this work, new endogenous promoters were discovered based on high expression levels in RNA-seq data of CHO-K1 cells cultured in high density. The promoters of Actb, Ctsz, Hmox1, Hspa5, Vim and Rps18 genes were selected for generating new expression vectors for the production of recombinant proteins in mammalian cells. The in silico-derived promoter regions were experimentally verified and the majority showed transcriptional activity comparable or higher than CMV. Also, stable expression following a reduction of culture temperature was investigated. The characterized endogenous promoters (excluding Rps18) constitute a promising alternative to CMV promoter due to their high strength, long-term expression stability and integration into the regulatory network of the host cell. These promoters may also comprise an initial panel for designing cell engineering strategies and synthetic promoters, as well as for industrial cell line development.


Assuntos
Técnicas de Cultura de Células , Infecções por Citomegalovirus , Animais , Células CHO , Cricetinae , Mamíferos , Plasmídeos , Regiões Promotoras Genéticas , Proteínas Recombinantes/genética
19.
J Ultrasound Med ; 41(11): 2897-2905, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35170800

RESUMO

To properly diagnose and treat injuries to the ankle or foot, the physician must have good anatomical knowledge of the ligaments involved. The bundles can be distinguished and identified by ultrasound examination of the medial aspect, but this may be a challenging task. In the present illustrated study, we discuss how a detailed ultrasound examination can be made of the different ligaments within the medial aspect of the ankle and foot.


Assuntos
Tornozelo , Ligamentos Articulares , Humanos , Tornozelo/diagnóstico por imagem , Ligamentos Articulares/diagnóstico por imagem , Ligamentos Articulares/lesões , Articulação do Tornozelo/diagnóstico por imagem , Ultrassonografia , Extremidade Inferior
20.
J Infect Dis ; 224(4): 575-585, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398243

RESUMO

Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.


Assuntos
Anticorpos Antivirais/imunologia , Complexo Antígeno-Anticorpo/imunologia , COVID-19/imunologia , Imunoglobulina G/imunologia , Ativação de Neutrófilo/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Complexo Antígeno-Anticorpo/sangue , Antígenos CD/imunologia , Antígeno CD11b/imunologia , Moléculas de Adesão Celular/imunologia , Feminino , Proteínas Ligadas por GPI/imunologia , Humanos , Imunoglobulina G/sangue , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Receptores de IgG/imunologia , SARS-CoV-2/imunologia , Adulto Jovem
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