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The chemical composition of spilt oils from events that took place on the north-eastern coast of Brazil in 2019 and 2022 was investigated to better understand their sources, and post-spill processes. Oils from both events originated from different sources, based on their fingerprints, hydrocarbons composition and specific biomarkers, such as the C23 tricyclic terpane and oleanane. Despite the differences, the source rocks share similarities in paleoenvironments and depositional conditions and both oils suffered little weathering, mainly due to evaporation and dissolution. Our findings for 2019 spilt oil reinforce that it is a mixed product, enriched both in lighter n-alkanes and 25-norhopanes. Differently, the 2022 samples exhibited characteristics of a non-processed crude oil that originated from a paraffinic deposit in storage tanks. The molecular composition and diagnostic ratios reported for samples from these spill events help to establish baselines for ongoing monitoring of oil spills in marine ecosystems.
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Understanding the sub-band gap luminescence in Ruddlesden-Popper 2D metal halide hybrid perovskites (2D HaPs) is essential for efficient charge injection and collection in optoelectronic devices. Still, its origins are still under debate with respect to the role of self-trapped excitons or radiative recombination via defect states. In this study, we characterized charge separation, recombination, and transport in single crystals, exfoliated layers, and polycrystalline thin films of butylammonium lead iodide (BA2PbI4), one of the most prominent 2D HaPs. We combined complementary defect- and exciton-sensitive methods such as photoluminescence (PL) spectroscopy, modulated and time-resolved surface photovoltage (SPV) spectroscopy, constant final state photoelectron yield spectroscopy (CFSYS), and constant light-induced magneto transport (CLIMAT), to demonstrate striking differences between charge separation induced by dissociation of excitons and by excitation of mobile charge carriers from defect states. Our results suggest that the broad sub-band gap emission in BA2PbI4 and other 2D HaPs is caused by radiative recombination via defect states (shallow as well as midgap states) rather than self-trapped excitons. Density functional theory (DFT) results show that common defects can readily occur and produce an energetic profile that agrees well with the experimental results. The DFT results suggest that the formation of iodine interstitials is the initial process leading to degradation, responsible for the emergence of midgap states, and that defect engineering will play a key role in enhancing the optoelectronic properties of 2D HaPs in the future.
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Background: Adrenal gland cysts are a rare entity, with a reported incidence in post-mortem series of 0.06-0.18%. However, the incidence seems to be increasing in recent years. The presentation of adrenal gland cysts is usually asymptomatic, but those cases in which symptoms are present are usually non-specific, which makes adrenal cysts generally recognized as incidentalomas. The finding is mainly made by computed tomography. The main objective of this article was to describe the clinical course of a patient with an adrenal gland pseudocyst, which is accompanied by symptoms of compression and persistent pain of long evolution in the left flank. Clinical case: A 65-year-old female patient attended the emergency room of a second-level hospital due to an increase in volume of the abdominal region with a sensation of fullness, heartburn, vomiting and pain. Computed tomography was performed, which reported a cystic mass and, later, exploratory laparotomy plus adrenalectomy were carried out. The pathology analysis reported a diagnosis of a 10 x 15 x 14 cm solid, cystic, and adherent tumor, coinciding with a pseudocyst of the adrenal gland. Conclusions: Adrenal gland cysts are rare. Computed tomography is recommended for its diagnosis and the standard of treatment is surgical intervention in the presence of symptoms.
Introducción: los quistes de glándula suprarrenal son una entidad rara, con un reporte en la incidencia de series post mortem de 0.06-0.18%. Sin embargo, la incidencia parece ir en aumento en los últimos años. La presentación de los quistes de glándula suprarrenal es habitualmente asintomática, pero en aquellos casos en que se presentan síntomas, estos suelen ser inespecíficos, lo cual hace que los quistes suprarrenales generalmente sean reconocidos como incidentalomas. El hallazgo se hace principalmente mediante tomografía computarizada. El objetivo principal de este artículo fue describir el curso clínico de una paciente con un pseudoquiste de glándula suprarrenal, que se acompaña de síntomas de compresión y dolor persistente de larga evolución en el flanco izquierdo. Caso clínico: mujer de 65 años que acudió a urgencias de un hospital de segundo nivel por aumento de volumen de región abdominal con sensación de plenitud, pirosis, vómito y dolor. Se realizó tomografía computarizada que reportó masa quística; posteriormente se realizó laparotomía exploradora y adrenalectomía. El análisis de patología reportó diagnóstico de tumor de 10 x 15 x 14 cm, sólido, quístico y adherido, coincidente con pseudoquiste de glándula suprarrenal. Conclusiones: los quistes de glándula suprarrenal son raros. Para su diagnóstico se recomienda realizar tomografía computarizada y el estándar de tratamiento es la intervención quirúrgica ante la presencia de sintomatología.
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Doenças das Glândulas Suprarrenais , Cistos , Humanos , Feminino , Idoso , Doenças das Glândulas Suprarrenais/diagnóstico , Doenças das Glândulas Suprarrenais/cirurgia , Cistos/diagnóstico , Cistos/cirurgiaRESUMO
BACKGROUND: Consensus is lacking on adequate deep histological margins in cutaneous squamous cell carcinoma (cSCC). Deep clearance for tumours located on the scalp is limited by anatomic constraints. OBJECTIVE: To determine whether clear but close deep histological margins (<1 mm) confer a higher risk of recurrence in cSCCs of the scalp treated by wide local excision, compared to deep histological margins ≥1 mm. METHODS: Multicentre retrospective observational cohort study and multivariate competing risk analysis to evaluate risk factors for recurrence. RESULTS: In total, 295 patients with 338 cSCCs were included. Close deep histological margins were not associated with an increased cumulative incidence of recurrence (subhazard ratio [SHR] 1.96 [95% CI 0.87-4.41]). However, an increased risk of recurrence was observed for those tumours that presented concurrent invasion of the galea aponeurotica and close deep margins, as opposed to patients without these factors (SHR 3.52 [1.24-10.01]). Tumours with clear but close peripheral margins (<1 mm) also had higher risk of recurrence (SHR 5.01 [1.68-14.97]). LIMITATIONS: Retrospective observational study based on pathology reports. CONCLUSION: Deep histological margins <1 mm do not confer a greater risk of recurrence as long as the tumour is completely excised and the galea aponeurotica is not involved. Surgical excision of cSCC on the scalp should include the galea to ensure proper assessment of deep margins.
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The aim of the present study was to evaluate skin temperature (Tsk) asymmetries, using infrared thermography, in professional padel players before (PRE), after (POST) and 10 min after training (POST10), and their relationship with perceptual variables and training characteristics. Thermal images were taken of 10 players before, after and 10 min after a standardized technical training. After training, Tsk of the dominant side was higher than before training in the anterior forearm (30.8 ± 0.4 °C vs. 29.1 ± 1.2 °C, p < 0.01; ES = 1.9), anterior shoulder (31.6 ± 0.6 °C vs. 30.9 ± 0.6 °C, p < 0.05; ES = 1.0) posterior arm (29.5 ± 1.0 °C vs. 28.3 ± 1.2 °C, p < 0.05; ES = 1.0), and posterior forearm (30.8 ± 0.9 °C vs. 29.3 ± 1.6 °C, p < 0.05; ES = 1.1). Likewise, these differences were significant POST10 in the anterior arm, anterior forearm, anterior shoulder, posterior arm and posterior forearm. Comparing the different moments of measurement (PRE, POST and POST10), the temperature was higher POST10 in all the regions analyzed except for the shoulder, abdominals, and lower back. Also, correlations were found between fatigue variation and temperature variation between limbs (Tsk dominance), and no correlation was found except between age and posterior thigh (|r| = 0.69; p < 0.05), and between the racket mass and anterior knee (|r| = 0.81; p < 0.01). In conclusion, infrared thermography allows monitoring of skin asymmetries between limbs in professional padel players, but these asymmetries were not related to overall fatigue variation, overall pain variation, years of experience and training hours.
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Temperatura Cutânea , Termografia , Humanos , Temperatura Cutânea/fisiologia , Termografia/métodos , Masculino , Adulto , Raios Infravermelhos , Adulto Jovem , Antebraço/fisiologia , AtletasAssuntos
Leucemia Linfocítica Granular Grande , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/patologia , Masculino , Anemia Hemolítica/etiologia , Anemia Hemolítica/patologia , Anemia Hemolítica/complicações , Idoso , Feminino , Pessoa de Meia-Idade , Anemia/etiologia , Anemia/complicaçõesRESUMO
Serine protease inhibitors (serpins) include thousands of structurally conserved proteins playing key roles in many organisms. Mutations affecting serpins may disturb their conformation, leading to inactive forms. Unfortunately, conformational consequences of serpin mutations are difficult to predict. In this study, we integrate experimental data of patients with mutations affecting one serpin with the predictions obtained by AlphaFold and molecular dynamics. Five SERPINC1 mutations causing antithrombin deficiency, the strongest congenital thrombophilia were selected from a cohort of 350 unrelated patients based on functional, biochemical, and crystallographic evidence supporting a folding defect. AlphaFold gave an accurate prediction for the wild-type structure. However, it also produced native structures for all variants, regardless of complexity or conformational consequences in vivo. Similarly, molecular dynamics of up to 1000 ns at temperatures causing conformational transitions did not show significant changes in the native structure of wild-type and variants. In conclusion, AlphaFold and molecular dynamics force predictions into the native conformation at conditions with experimental evidence supporting a conformational change to other structures. It is necessary to improve predictive strategies for serpins that consider the conformational sensitivity of these molecules.
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Simulação de Dinâmica Molecular , Mutação , Humanos , Conformação Proteica , Serpinas/genética , Serpinas/química , Serpinas/metabolismo , Dobramento de Proteína , Antitrombina III/genética , Antitrombina III/química , Antitrombina III/metabolismoRESUMO
One of the main factors that influences the fertility of cattle in grazing systems in hot tropical climates is heat stress. The objective of this study was to evaluate the effect of season, breed, hormonal and physiological condition on the quantity and quality of cumulus-oocyte complexes (COCs) and embryos produced in vitro, from Romosinuano (RM) and Tropical Milking (TM) donors. Three ovum pick-up and in vitro fertilization (OPU-IVF) were performed, one per season: hot dry (HD; 10, 10), hot humid (HH; 9, 9) and fresh dry (FD; 7, 10) in RM and LT donors. Serum levels of cortisol, insulin and glucose were measured, in addition to heart rate (HR), respiratory rate (RR) and rectal temperature (RT). Effect of season x genotype interaction (p ≤ 0.05) was observed in all COC variables and only in cleavage embryos (CLI) (p ≤ 0.05). Body weight (BW) affected all COC variables (p ≤ 0.01), except unviable (UNV) although affected degenerated embryos (DEG) (p ≤ 0.01) and total blastocysts (BLAST) (p ≤ 0.01). Cow age only affected viable COCs (VIAB) (p ≤ 0.05), code one blastocysts (BC1) and BLAST (p ≤ 0.01). Cortisol affected total COCs (COCsT), VIAB and total matured in vitro (TMIV) (p ≤ 0.01), as well as CLI, BC1 (p ≤ 0.01) and BLAST (p ≤ 0.05). Insulin affected COCsT (p ≤ 0.01), UNV (p ≤ 0.05), denuded oocytes (DE) (p ≤ 0.01), BC1 and code two blastocysts (BC2) (p ≤ 0.01). Glucose affected all COC variables (p ≤ 0.01), except UNV and all embryo variables except BC2. HR affected COCsT, DE, TMIV (p ≤ 0.01), CLI, BLAST and DEG (p ≤ 0.05). RR affected COCsT, UNV, VIAB, CLI (p ≤ 0.05), BC1, BLAST and DEG (p ≤ 0.01). RT only affected DE, VIAB (p ≤ 0.01) and BLAST (p ≤ 0.05). The seasonal climatic year variation of Veracruz and changes in physiological and hormonal variables have diverse effects on the cumulus-oocyte complexes and embryos produced by RM and TM donors.
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INTRODUCTION: Some epidemiological data suggest that there may be an inverse relationship between cholesterol levels and the risk of thyroid cancer in the overall population. The present study was aimed to evaluate the lipid profile specifically in subjects with Bethesda category IV thyroid nodules, and compare whether there were any differences between those with benign and malignant nodules. METHODS: Single-centre, retrospective study on 204 subjects treated by partial or total thyroidectomy for excision of a Bethesda category IV thyroid nodule, who had undergone a blood lipid profile test in the 12 months prior to surgery. In addition to lipid measures, other demographic, clinical, biochemical and ultrasound data were collected. RESULTS: Seventy-five subjects (36.8%) were diagnosed with thyroid carcinoma in the definitive histopathological examination. Patients with thyroid cancer had lower levels of total cholesterol, LDL-cholesterol and non-HDL-cholesterol than subjects with benign thyroid diseases. There were no differences in HDL-cholesterol, triglycerides or total cholesterol/HDL-cholesterol ratio. There were no differences either between groups in other clinical, biochemical and ultrasound variables, including the use of lipid-lowering drugs. In multivariate analysis, only LDL-cholesterol was independently associated with malignancy. Subjects with follicular carcinoma showed the lowest cholesterol levels, while those with papillary carcinoma had intermediate values between the group with follicular carcinoma and the group with benign thyroid diseases. CONCLUSIONS: In subjects with cytologically indeterminate Bethesda category IV thyroid nodules, levels of total cholesterol, non-HDL-cholesterol and, particularly, LDL-cholesterol are lower among those with malignant nodules.
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Colesterol , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/sangue , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Masculino , Estudos Retrospectivos , Feminino , Colesterol/sangue , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Carcinoma Papilar/sangue , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Adenocarcinoma Folicular/sangue , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/cirurgia , Tireoidectomia , IdosoRESUMO
Hematopoietic stem cell transplantation (HSCT) has improved outcomes for severe hematologic, malignant, and immune disorders, yet poses an increased risk of subsequent malignancies. This study aimed to examine the risk of skin cancer following HSCT and identify potential risk factors. The search was conducted in MEDLINE, EMBASE, and CINAHL databases until December 2023. Cohort studies reporting standardized incidence ratios (SIRs) for post-HSCT skin cancer or investigating risk factors were included. SIRs, or hazard ratios (HRs) with 95% confidence interval (CI), were calculated using random-effects inverse-variance models. Outcome endpoints were SIRs of skin cancer post-HSCT and risk factors, including gender, chronic graft-versus-host disease (cGVHD), voriconazole exposure, and total body irradiation (TBI). Twenty-six studies involving 164,944 HSCT recipients (allogeneic HSCT, n = 68,637; autologous HSCT, n = 95,435; mean age: 38.5 ± 13.8 years; 71,354 females [43.3%]) were analyzed. Overall, SIR for skin cancer post-HSCT was 7.21 (95% CI 3.98-13.08), with SIRs of 2.25 (95% CI: 1.37-3.68) for autologous HSCT, and 10.18 (95% CI 5.07-20.43) for allogeneic HSCT. Risk factors for skin cancer risk included cGVHD (HR = 2.86 [95% CI: 2.01-4.07]), specifically for basal cell and squamous cell carcinoma (SCC) (HR = 1.80 [95% CI: 1.31-2.46] and HR = 3.68 [95% CI: 2.39-5.68], respectively), male gender (HR = 1.56 [95% CI: 1.15-2.13]), especially for SCC (HR = 1.70 [95% CI: 1.03-2.80]), and voriconazole exposure (HR = 2.01 [95% CI: 1.12-3.61]). TBI showed no statistically significant association with subsequent skin cancer (HR = 1.12 [95% CI: 0.73-1.71]). These findings highlight the importance of rigorous skin cancer surveillance and preventive strategies in HSCT recipients, particularly in male individuals undergoing allogeneic transplants and those with identifiable risk factors, to enable early detection and intervention.
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Skin temperature responses have been advocated to indicate exercise-induced muscle soreness and recovery status. While the evidence is contradictory, we hypothesize that the presence of muscle damage and the time window of measurement are confounding factors in the skin temperature response. The objective was to determine whether skin temperature is influenced by different workloads and the time course of temperature measurements over the following 24 h. 24 trained male military were assigned to one of three groups: GC group (n = 8) serving as control not performing exercises, GE group (n = 8) performing a simulated military combat protocol in an exercise track with different obstacles but designed not to elicit muscle damage, and the GEMD group (n = 8) performing the simulated military combat protocol plus 5 sets of 20 drop jumps, with 10-sec between repetitions and with 2-min of rest between sets aiming to induce muscle damage. Skin temperature was measured using infrared thermography before exercise (Pre) and 4 (Post4h), 8 (Post8h) and 24h (Post24h) post-exercise. Perception of pain (DOMS) was evaluated Pre, Post24h, and Post48h, and countermovement jump height was evaluated at Pre and Post24h. DOMS did not differ between groups in the Pre and Post24h measures but GEMD presented higher DOMS than the other groups at Post48h (p < 0.001 and large effect size). Jump height did not differ for GEMD and GC, and GE presented higher jump height at Post24h than GC (p = 0.02 and large effect size). Skin temperature responses of GEMD and GG were similar in all measurement moments (p > 0.22), and GE presented higher skin temperature than the GC and the GEMD groups at Post24h (p < 0.01 and large effect sizes). In conclusion, although physical exercise elicits higher skin temperature that lasts up to 24 h following the efforts, muscle soreness depresses this response.
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Exercício Físico , Mialgia , Temperatura Cutânea , Humanos , Masculino , Adulto , Mialgia/fisiopatologia , Adulto Jovem , MilitaresRESUMO
The aim of this study was to evaluate the possible impact of the COVID-19 pandemic on prevalence rates and self-reported changes in patterns of alcohol use among first-year university students in Spain, considering the risk of problematic alcohol use. A serial cross-sectional study based on the uniHcos project was carried out. Data from 10 518 first-year university students (73.3% female, mean age 19 (SD = 1.6)) collected between 2012 and 2022 were analysed. The evolution of the pooled prevalence rates during the time series was analysed and the risk of problematic alcohol consumption was assessed using the AUDIT. Also, self-reported changes in alcohol use patterns during the pandemic were assessed. According to the results, during the COVID-19 pandemic, the prevalence of alcohol use in the past 30-days was reduced (76.3% in 2019 vs. 63.7% in COVID-19) increasing again in the New Normal period. Thus, a similar pattern in the practice of binge drinking was observed. Regarding the AUDIT score, 21.7% (95%CI 20.9, 22.6) of the students had harmful alcohol consumption, with a higher proportion among males. In the multivariable logistic models, a higher AUDIT score was significantly associated (p-value < 0.001) with being male and living with roommates. According to self-reported changes in consumption patterns during the COVID-19 pandemic, a higher proportion of participants with harmful use reported an increase in alcohol consumption compared to those at low-risk (43% vs 19%). Finally, despite the overall reduction in drinking prevalence during COVID-19, changes were not equal for all students and depended on their previous level of problematic drinking, highlighting that this should be considered in the development of strategies against alcohol use in this population.
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ABSTRACT: This scoping review aimed to explore the characteristics and performance factors of competitive Para-cyclists. A systematic search for studies on competitive Para-cycling on WOS, PubMed, SPORTDiscus and Scopus was performed until December 2023. Five methodological phases were followed: (i) identifying the research question, (ii) identifying relevant studies, (iii) study selection, (iv) charting the data, and (v) collating, summarizing, and reporting the results. A systematic search across multiple databases was performed until March 2024. Five methodological phases were employed: identifying the research question, relevant studies, study selection, charting data, and summarizing results. A total of 36 relevant studies were selected. Three main research themes emerged: Sport performance (n = 15), Biomechanics (n = 12), and Physical and mental health (n = 9). Despite progress, gaps were identified, particularly in physiological response to exercise, fitness, and training. Biomechanics studies focused on prosthetic use and aerodynamics, mostly involving lower-limb amputees and simulated tandem competition. Injury risk in Para-cycling appeared comparable to able-bodied cycling, but comprehensive studies considering confounding variables are needed. Overall, while research on Para-cycling is growing, more studies with larger and diverse samples across all sport classes are essential to advance scientific understanding in this field.
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The development of myeloid malignancies is a multi-step process starting from pre-malignant stages. Large-scale studies on clonal hematopoiesis of indeterminate potential (CHIP) identified this condition as a risk factor for developing hematologic malignancies, in particular myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In parallel, CHIP was found to confer an enhanced thrombotic risk, in particular for cardiovascular diseases. In a similar fashion, in recent years, alongside their life-threatening features, increasing attention has been drawn toward thrombotic complications in myeloid malignancies. The purpose of this review is to gather growing body of evidence on incidence, pathogenesis and clinical impact of thrombosis in myeloid malignancies at every step of malignant progression, from CHIP to AML.
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Nitrogen (N) and silicon (Si) are mineral elements that have shown a reduction in the damage caused by tan spot (Pyrenophora tritici-repentis (Ptr)) in wheat. However, the effects of these elements were studied separately, and the N and Si interaction effect on wheat resistance to tan spot remains elusive. Histocytological and biochemical defense responses against Ptr in wheat leaves treated with Si (+Si) at low (LN) and high N (HN) inputs were investigated. Soil amendment with Si reduced the tan spot severity in 18% due to the increase in the leaf Si concentration (around 30%), but it was affected by the N level used. The superoxide dismutase (SOD) activity was higher in +Si plants and inoculated with Ptr, leading to early and higher H2O2 and callose accumulation in wheat leaf. Interestedly, phenylalanine ammonia-lyase (PAL) activity was induced by the Si supplying, being negatively affected by the HN rate. Meanwhile, catalase (CAT), and peroxidase (POX) activities showed differential response patterns according to the Si and N rates used. Tan spot severity was reduced by both elements, but their interaction does not evidence synergic effects in this disease's control. Wheat plants from -Si and HN and +Si and LN treatments recorded lower tan spot severity.
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Enhancing the initial stages of plant growth by using polymeric gels for seed priming presents a significant challenge. This study aimed to investigate a microgel derived from polyetheramine-poly(propylene oxide) (PPO) and a bisepoxide (referred to as micro-PPO) as a promising alternative to optimize the seed germination process. The micro-PPO integrated with an iron micronutrient showed a positive impact on seed germination compared with control (Fe solutions) in which the root length yield improved up to 39%. Therefore, the element map by synchrotron-based X-ray fluorescence shows that the Fe intensities in the seed primers with the micro-PPO-Fe gel are about 3-fold higher than those in the control group, leading to a gradual distribution of Fe species through most internal embryo tissues. The use of micro-PPO for seed priming underscores their potential for industrial applications due to the nontoxicity results in zebrafish assays and environmentally friendly synthesis of the water-dispersible monomers employed.
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Aminas , Cucumis sativus , Germinação , Ferro , Microgéis , Sementes , Germinação/efeitos dos fármacos , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Cucumis sativus/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/química , Ferro/metabolismo , Ferro/química , Aminas/química , Aminas/metabolismo , Microgéis/química , Compostos de Epóxi/química , Compostos de Epóxi/metabolismo , Peixe-Zebra/metabolismo , AnimaisRESUMO
Endothelial dysfunction and blood-brain barrier (BBB) leakage have been suggested as a fundamental role in the development of cerebral small vessel disease (SVD) pathology. However, the molecular and cellular mechanisms that link cerebral hypoxic hypoperfusion and BBB disruption remain elusive. Sphingosine-1-phosphate (S1P) regulates the BBB integrity by binding to its receptor isoform 1 (S1PR1) on endothelial cells. This study tested the hypothesis that hypoxic hypoperfusion triggers capillary endothelial S1PR1 disruption, which compromises BBB integrity and leads to SVD-related neuropathological changes, using a chronic hypoxic hypoperfusion model with BBB dysfunction. Spontaneously hypertensive rat stroke-prone underwent unilateral carotid artery occlusion (UCAO) followed by a Japanese permissive diet (JPD) for up to 9 weeks. Selective S1PR1 agonist SEW2871 was used to activate S1PR1. Significant progressive reduction of S1PR1 was detected in rat brains from 4 to 9 weeks following UCAO/JPD onset, which was also detected in cerebral vasculature in human SVD. S1PR1 activation by SEW2871 significantly reduced lesions in both white and grey matter and ameliorated cerebral blood flow. SEW2871 reversed the loss of endothelial S1PR1 and tight junction proteins, and significantly attenuated UCAO/JPD induced accumulation of neuronal phosphorylated tau. This protective role of SEW2871 is associated with promotion of Akt phosphorylation and inhibition of S1PR2/Erk1/2 activation. Our data suggest S1PR1 signalling as a potential molecular mechanistic basis that links hypoxic hypoperfusion with BBB damage in the neuropathological cascades in SVD. The reversal of BBB disruption through pharmacological intervention of S1PR1 signalling likely reveals a novel therapeutic target for SVD.