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1.
Pest Manag Sci ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647195

RESUMO

BACKGROUND: Xylella fastidiosa is a multi-host bacterium that can be detected in hundreds of plant species including several crops. Diseases caused by X. fastidiosa are considered a threat to global food production. The primary method for managing diseases caused by X. fastidiosa involves using insecticides to control the vector. Hence, it is necessary to adopt new and sustainable disease management technologies to control not only the insect but also the bacteria and plant health. We demonstrated that N-acetylcysteine (NAC), a low-cost cysteine analogue, is a sustainable molecule that can be used in agriculture to decrease the damage caused by X. fastidiosa and improve plant health. RESULTS: Using 15N-NAC we proved that this analogue was absorbed by the roots and transported to different parts of the plant. Inside the plant, NAC reduced the bacterial population by 60-fold and the number of xylem vessels blocked by bacterial biofilms. This reflected in a recovery of 0.28-fold of the daily sap flow compared to health plants. In addition, NAC-treated citrus variegated chlorosis (CVC) plants decreased the oxidative stress by improving the activity of detoxifying enzymes. Moreover, the use of NAC in field conditions positively contributed to the increase in fruit yield of CVC-diseased plants. CONCLUSION: Our research not only advances the understanding of NAC absorption in plants, but also indicates its dual effect as an antimicrobial and antioxidant molecule. This, in turn, negatively affects bacterial survival while improving plant health by decreasing oxidative stress. Overall, the positive field-based evidence supports the viability of NAC as a sustainable agricultural application. © 2024 Society of Chemical Industry.

2.
Nutrients ; 16(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38674788

RESUMO

The Mediterranean diet (MD) is associated with improved longevity and the prevention and management of chronic inflammatory diseases (CIDs). Vitamin K, which is present in MD core components such as leafy green vegetables, is also known as a protective factor for CIDs. Estimates of vitamin K intake in Mediterranean settings are still scarce, and the association between MD and vitamin K intake is yet to be established. This study analyzed vitamin K intake and MD adherence in the Algarve region, in Portugal. We conducted a cross-sectional study in a nonrandom sample of adults using an online questionnaire which included a validated food-frequency questionnaire and a screener for MD adherence. A total of 238 participants were recruited (68% women and 32% men). Adherence to the MD was low (11%). Only 10% of the participants had vitamin K intake below the adequate intake. Adherence to the MD was positively correlated with vitamin K intake (r = 0.463; p < 0.001) and age (r = 0.223; p < 0.001). Our findings underscore the importance of promoting adherence to the MD for optimal vitamin K intake, and future research should focus on developing effective interventions to promote this dietary pattern, particularly among younger individuals and men.


Assuntos
Dieta Mediterrânea , Vitamina K , Humanos , Dieta Mediterrânea/estatística & dados numéricos , Feminino , Masculino , Estudos Transversais , Vitamina K/administração & dosagem , Pessoa de Meia-Idade , Adulto , Portugal , Idoso , Inquéritos sobre Dietas , Inquéritos e Questionários , Comportamento Alimentar
3.
Cardiovasc Res ; 120(5): 461-475, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38428029

RESUMO

Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis (AS). AS is known to increase the pressure load of the left ventricle, causing a compensative response of the cardiac muscle, which progressively will lead to dilation and heart failure. At a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes, known as cardiomyocyte hypertrophy, while their proliferation capacity is attenuated upon the first developmental stages. Cardiomyocytes, in order to cope with the increased workload (overload), suffer alterations in their morphology, nuclear content, energy metabolism, intracellular homeostatic mechanisms, contractile activity, and cell death mechanisms. Moreover, modifications in the cardiomyocyte niche, involving inflammation, immune infiltration, fibrosis, and angiogenesis, contribute to the subsequent events of a pathologic hypertrophic response. Considering the emerging need for a better understanding of the condition and treatment improvement, as the only available treatment option of AS consists of surgical interventions at a late stage of the disease, when the cardiac muscle state is irreversible, large animal models have been developed to mimic the human condition, to the greatest extend. Smaller animal models lack physiological, cellular and molecular mechanisms that sufficiently resemblance humans and in vitro techniques yet fail to provide adequate complexity. Animals, such as the ferret (Mustello purtorius furo), lapine (rabbit, Oryctolagus cunigulus), feline (cat, Felis catus), canine (dog, Canis lupus familiaris), ovine (sheep, Ovis aries), and porcine (pig, Sus scrofa), have contributed to research by elucidating implicated cellular and molecular mechanisms of the condition. Essential discoveries of each model are reported and discussed briefly in this review. Results of large animal experimentation could further be interpreted aiming at prevention of the disease progress or, alternatively, at regression of the implicated pathologic mechanisms to a physiologic state. This review summarizes the important aspects of the pathophysiology of LV hypertrophy and the applied surgical large animal models that currently better mimic the condition.


Assuntos
Estenose da Valva Aórtica , Modelos Animais de Doenças , Hipertrofia Ventricular Esquerda , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Humanos , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Pressão Ventricular , Especificidade da Espécie
4.
Am J Kidney Dis ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38423159

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease due to a dysregulation of the complement alternative pathway. Complement factor I (CFI) negatively regulates the alternative pathway and CFI gene rare variants have been associated to aHUS with a low disease penetrance. We report 10 unrelated cases of HUS associated to a rare CFI variant, p.Ile357Met (c.1071T>G). All patients with isolated p.Ile357Met CFI missense variant were retrospectively identified among patients included between January 2007 and January 2022 in the French HUS Registry. We identified 10 unrelated patients (70% women; median age at HUS diagnosis, 36.5 years) who carry the same rare variant p.Ile357Met in the CFI gene. Seven patients (cases 1-7) presented with aHUS in the native kidney associated with malignant hypertension in 5 patients. None received a C5 inhibitor. Two of these cases occurred in the peripartum period with complete recovery of kidney function, while 5 of these patients reached kidney failure requiring replacement therapy (KFRT). Four patients with KFRT subsequently underwent kidney transplantation. Three later developed C3 glomerulopathy in their kidney graft, but none had aHUS recurrence. Three other patients (cases 8-10) experienced de novo thrombotic microangiopathy after kidney transplantation, precipitated by various triggers. The rare CFI variant p.Ile357Met appears to be a facilitating genetic factor for HUS and for some forms of secondary HUS.

5.
Cureus ; 16(1): e52515, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38371058

RESUMO

Endocarditis is an uncommon infectious complication of congenital heart disease (CHD), typically presenting with fever as its primary symptom; however, its occurrence may not always be accompanied by fever. This paper elaborates on a case involving a patient with surgically corrected Berry syndrome and residual aortic coarctation. The clinical presentation of aortic endarteritis in this case manifested as seizures attributed to a hemorrhagic stroke. In this paper, we aim to raise awareness of this infrequent complication of aortic coarctation, as it may present itself with cerebral hemorrhage due to septic microemboli, even in the absence of fever at its initial presentation.

6.
Cureus ; 16(1): e52549, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38371087

RESUMO

Pulmonary arteriovenous malformations (AVMs) are abnormal connections between the pulmonary arteries and veins that can result in rapid-onset heart failure. We present a case of a fetus with pulmonary AVMs diagnosed at 22 weeks gestation. Fetal echocardiography showed cardiomegaly and dilated pulmonary arteries and veins reflecting the hemodynamic significance of the shunt. Inverted flow through the ductus arteriosus was also present. Fetal autopsy following medical termination of the pregnancy confirmed the morphological findings, including displacement of arteries and veins in proximity to the pleural surface. The genetic study was negative. This report highlights the cardiovascular impact of a rare disorder. Inverted flow through the ductus arteriosus may be another poor prognostic indicator, useful in parental counseling.

7.
FEMS Microbiol Lett ; 3712024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38244227

RESUMO

Xanthomonas is an important genus of plant-associated bacteria that causes significant yield losses of economically important crops worldwide. Different approaches have assessed genetic diversity and evolutionary interrelationships among the Xanthomonas species. However, information from clustered regularly interspaced short palindromic repeats (CRISPRs) has yet to be explored. In this work, we analyzed the architecture of CRISPR-Cas loci and presented a sequence similarity-based clustering of conserved Cas proteins in different species of Xanthomonas. Although absent in many investigated genomes, Xanthomonas harbors subtype I-C and I-F CRISPR-Cas systems. The most represented species, Xanthomonas citri, presents a great diversity of genome sequences with an uneven distribution of the CRISPR-Cas systems among the subspecies/pathovars. Only X. citri subsp. citri and X. citri pv. punicae have these systems, exclusively of subtype I-C system. Moreover, the most likely targets of the X. citri CRISPR spacers are viruses (phages). At the same time, few are plasmids, indicating that CRISPR/Cas system is possibly a mechanism to control the invasion of foreign DNA. We also showed in X. citri susbp. citri that the cas genes are regulated by the diffusible signal factor, the quorum sensing (QS) signal molecule, according to cell density increases, and under environmental stress like starvation. These results suggest that the regulation of CRISPR-Cas by QS occurs to activate the gene expression only during phage infection or due to environmental stresses, avoiding a possible reduction in fitness. Although more studies are needed, CRISPR-Cas systems may have been selected in the Xanthomonas genus throughout evolution, according to the cost-benefit of protecting against biological threats and fitness maintenance in challenging conditions.


Assuntos
Bacteriófagos , Xanthomonas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Percepção de Quorum/genética , Plasmídeos , Xanthomonas/genética , Xanthomonas/metabolismo , Bacteriófagos/genética
8.
Clin Chim Acta ; 554: 117750, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38176523

RESUMO

INTRODUCTION: The complement system is involved in numerous diseases, through diverse mechanisms and degree of activation. With the emergence of complement targeting therapeutic, simple and accessible tools to evaluate the extent of complement activation are strongly needed. METHODS: We evaluated two multiplex panels, measuring complement activation fragments (C4a, C3a, C5a, Bb, Ba, sC5b9) and intact components or regulators (C1q, C2, C3, C4, C5, FD, FP, FH, FI). The specificity of each measurement was assessed by using complement proteins depleted sera and plasma collected from patients with complement deficiencies. Normal values distribution was estimated using 124 plasma samples from healthy donors and complement activation profile was assessed in plasma collected from 31 patients with various complement-mediated disorders. RESULTS: We observed good inter-assay variation. All tested protein deficiencies were accurately detected. We established assay-specific reference values for each analyte. Except for C3, C4 and C4a, the majority of the measurements were in good agreement with references methods or published data. CONCLUSION: Our study substantiates the utility of the Complement Multiplex assay as a tool for measuring complement activation and deficiencies. Quantifying complement cleavage fragments in patients exhibiting classical or alternative pathway activation allowed evaluating the activation state of the whole cascade.


Assuntos
Ativação do Complemento , Proteínas do Sistema Complemento , Humanos , Biomarcadores , Plasma
9.
J Vis Exp ; (200)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37930007

RESUMO

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological similarities to humans. Efforts have been dedicated to creating a model of pressure-overload induced heart failure, and ascending aortic banding while still supra-coronary and not a perfect mimic of aortic stenosis in humans, closely resembling the human condition. The purpose of this study is to demonstrate a minimally invasive approach to induce left ventricular pressure overload by placing an aortic band, precisely calibrated with percutaneously introduced high-fidelity pressure sensors. This method represents a refinement of the surgical procedure (3Rs), resulting in homogenous trans-stenotic gradients and reduced intragroup variability. Additionally, it enables swift and uneventful animal recovery, leading to minimal mortality rates. Throughout the study, animals were followed for up to 2 months after surgery, employing transthoracic echocardiography and pressure-volume loop analysis. However, longer follow-up periods can be achieved if desired. This large animal model proves valuable for testing new drugs, particularly those targeting hypertrophy and the structural and functional alterations associated with left ventricular pressure overload.


Assuntos
Estenose da Valva Aórtica , Insuficiência Cardíaca , Humanos , Animais , Suínos , Coração , Insuficiência Cardíaca/etiologia , Estenose da Valva Aórtica/cirurgia , Ecocardiografia , Aorta/cirurgia , Hipertrofia Ventricular Esquerda , Modelos Animais de Doenças
10.
Clin J Am Soc Nephrol ; 18(11): 1435-1445, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37615951

RESUMO

BACKGROUND: C3 glomerulopathy and idiopathic immunoglobulin-mediated membranoproliferative GN (Ig-MPGN) are rare complement-mediated kidney diseases. Inherited forms of C3 glomerulopathy/Ig-MPGN are rarely described. METHODS: Three hundred ninety-eight patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102) from a national registry were screened for three complement genes: factor H ( CFH ), factor I ( CFI ), and C3 . Patients with rare variant (minor allele frequency <0.1%) were included. Epidemiologic, clinical, and immunologic data at diagnosis and kidney outcomes of patients were retrospectively collected. RESULTS: Fifty-three different rare variants, including 30 (57%), 13 (24%), and ten (19%) in CFH , CFI , and C3 variants, were identified in 66/398 (17%) patients. Thirty-eight (72%) variants were classified as pathogenic, including 20/30 (66%) and 11/13 (84%) variants in CFH and CFI , respectively, impairing synthesis of factor H or factor I regulators. Fifteen of 53 (27%) variants were of unknown significance. At diagnosis, 69% of patients were adult (median age of 31 years). With the exception of biologic stigma of thrombotic microangiopathy, which was more frequent in patients with CFI variants (5/14 [36%] versus 1/37 [3%] and 0% in the CFH group and C3 group, respectively, P < 0.001), the clinical and histologic features were similar among the three variants groups. The kidney outcome was poor regardless of the age at onset and treatment received. Sixty-five percent (43/66) of patients with rare variant reach kidney failure after a median delay of 41 (19-104) months, compared with 28% (55/195) after a median delay of 34 (12-143) months in the nonvariant group. Among 36 patients who received a kidney transplant, 2-year recurrence was frequent, occurring in 39% (12/31), without difference between variant groups, and led to graft failure in three cases. CONCLUSIONS: In our cohort, 17% of C3 glomerulopathy/Ig-MPGN cases were associated with rare variants in the CFH , CFI , or C3 genes. In most cases, a quantitative deficiency in factor H or factor I was identified. The presence of a rare variant was associated with poor kidney survival. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000252.mp3.


Assuntos
Glomerulonefrite Membranoproliferativa , Nefropatias , Adulto , Humanos , Glomerulonefrite Membranoproliferativa/genética , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Complemento C3/genética , Estudos Retrospectivos , Fator H do Complemento/genética , Imunoglobulinas , Nefropatias/genética , Fibrinogênio
11.
Environ Sci Technol ; 57(34): 12722-12731, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37585543

RESUMO

Methane is a powerful greenhouse gas that is produced in large quantities in marine sediments. Microbially mediated oxidation of methane in sediments, when in balance with methane production, prevents the release of methane to the overlying water. Here, we present a gene-based reactive transport model that includes both microbial and geochemical dynamics and use it to investigate whether the rate of growth of methane oxidizers in sediments impacts the efficiency of the microbial methane filter. We focus on iron- and methane-rich coastal sediments and, with the model, show that at our site, up to 10% of all methane removed is oxidized by iron and manganese oxides, with the remainder accounted for by oxygen and sulfate. We demonstrate that the slow growth rate of anaerobic methane-oxidizing microbes limits their ability to respond to transient perturbations, resulting in periodic benthic release of methane. Eutrophication and deoxygenation decrease the efficiency of the microbial methane filter further, thereby enhancing the role of coastal environments as a source of methane to the atmosphere.


Assuntos
Sedimentos Geológicos , Metano , Anaerobiose , Oxirredução , Ferro , Sulfatos
12.
Nutrients ; 15(13)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37447338

RESUMO

Vitamin K is a multifunctional micronutrient essential for human health, and deficiency has been linked to multiple pathological conditions. In this study, we aimed to develop and validate a new food frequency questionnaire (FFQ) to estimate total vitamin K intake, over the course of a 30-day interval, in a Portuguese, Mediterranean-based, population. We conducted a prospective study in a non-random sample of 38 healthy adult volunteers. The FFQ was designed based on a validated Portuguese FFQ used in nationally representative studies and on literature reviews, to include foods containing ≥5 µg of vitamin K/100 g and foods with a lower vitamin K content, yet commonly included in a Mediterranean diet. Vitamin K intake was estimated from 24 h recalls and six days of food records. The final FFQ included 54 food items which, according to regression analyses, explains 90% of vitamin K intake. Mean differences in vitamin K intake based on food records (80 ± 47.7 µg/day) and on FFQ (96.5 ± 64.3 µg/day) were statistically non-significant. Further, we found a strong correlation between both methods (r = 0.7; p = 0.003). Our results suggest that our new FFQ is a valid instrument to assess the last 30 days of vitamin K intake in the Portuguese Mediterranean population.


Assuntos
Dieta , Avaliação Nutricional , Adulto , Humanos , Estudos Prospectivos , Inquéritos e Questionários , Vitamina K , Micronutrientes , Reprodutibilidade dos Testes , Registros de Dieta , Ingestão de Energia
13.
FEMS Microbiol Lett ; 3702023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-37291701

RESUMO

The Oslofjord subsea road tunnel is a unique environment in which the typically anoxic marine deep subsurface is exposed to oxygen. Concrete biodeterioration and steel corrosion in the tunnel have been linked to the growth of iron- and manganese-oxidizing biofilms in areas of saline water seepage. Surprisingly, previous 16S rRNA gene surveys of biofilm samples revealed microbial communities dominated by sequences affiliated with nitrogen-cycling microorganisms. This study aimed to identify microbial genomes with metabolic potential for novel nitrogen- and metal-cycling reactions, representing biofilm microorganisms that could link these cycles and play a role in concrete biodeterioration. We reconstructed 33 abundant, novel metagenome-assembled genomes (MAGs) affiliated with the phylum Planctomycetota and the candidate phylum KSB1. We identified novel and unusual genes and gene clusters in these MAGs related to anaerobic ammonium oxidation, nitrite oxidation, and other nitrogen-cycling reactions. Additionally, 26 of 33 MAGs also had the potential for iron, manganese, and arsenite cycling, suggesting that bacteria represented by these genomes might couple these reactions. Our results expand the diversity of microorganisms putatively involved in nitrogen and metal cycling, and contribute to our understanding of potential biofilm impacts on built infrastructure.


Assuntos
Metagenoma , Planctomicetos , Nitrogênio , RNA Ribossômico 16S/genética , Manganês , Ferro , Oxirredução
14.
Environ Microbiol ; 25(11): 2277-2288, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37381163

RESUMO

The potential and drivers of microbial methane removal in the water column of seasonally stratified coastal ecosystems and the importance of the methanotrophic community composition for ecosystem functioning are not well explored. Here, we combined depth profiles of oxygen and methane with 16S rRNA gene amplicon sequencing, metagenomics and methane oxidation rates at discrete depths in a stratified coastal marine system (Lake Grevelingen, The Netherlands). Three amplicon sequence variants (ASVs) belonging to different genera of aerobic Methylomonadaceae and the corresponding three methanotrophic metagenome-assembled genomes (MOB-MAGs) were retrieved by 16S rRNA sequencing and metagenomic analysis, respectively. The abundances of the different methanotrophic ASVs and MOB-MAGs peaked at different depths along the methane oxygen counter-gradient and the MOB-MAGs show a quite diverse genomic potential regarding oxygen metabolism, partial denitrification and sulphur metabolism. Moreover, potential aerobic methane oxidation rates indicated high methanotrophic activity throughout the methane oxygen counter-gradient, even at depths with low in situ methane or oxygen concentration. This suggests that niche-partitioning with high genomic versatility of the present Methylomonadaceae might contribute to the functional resilience of the methanotrophic community and ultimately the efficiency of methane removal in the stratified water column of a marine basin.


Assuntos
Metano , Methylococcaceae , Metano/metabolismo , Ecossistema , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Oxirredução , Methylococcaceae/genética , Methylococcaceae/metabolismo , Água/metabolismo , Oxigênio/metabolismo , Filogenia
15.
Am J Kidney Dis ; 82(3): 279-289, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37061020

RESUMO

RATIONALE & OBJECTIVE: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with C3GN and concomitant TMA lesions on biopsy registered from 2009 to 2019 in the French National Registry of C3GN. FINDINGS: Among 278 registered patients with C3GN, 16 (6%) had biopsy-proven glomerular and/or vascular TMA lesions. Their median age at diagnosis was 39 years (range, 7-76), and 59% were female. Fourteen of the 16 patients (88%) had an estimated glomerular filtration rate of<30mL/min/1.73m2 and 3 of 16 (19%) required dialysis. Twelve of the 14 evaluated patients (86%) showed evidence of mechanical hemolysis. Fifty percent of the patients had low C3 levels. Six of the 14 evaluated patients had a rare variant in complement genes, and 4 of the 16 patients (25%) had monoclonal gammopathy. Among the 16 patients, 10 (63%) received eculizumab, 5 (31%) received immunosuppressive therapy, and 4 (25%) received clone-targeted chemotherapy. Median kidney survival was 49 months. LIMITATIONS: Small retrospective case series with a limited number of biopsies including electron microscopy. CONCLUSIONS: Concomitant C3GN and TMA is extremely rare and is associated with poor kidney outcomes. Genetic or acquired abnormalities of the alternative complement pathway are common as is the presence of monoclonal gammopathy, which may inform the selection of treatment approaches.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Paraproteinemias , Microangiopatias Trombóticas , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Retrospectivos , Rim , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Microangiopatias Trombóticas/terapia , Microangiopatias Trombóticas/complicações , Paraproteinemias/complicações
16.
Mol Ther ; 31(6): 1807-1828, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37073128

RESUMO

While it is experimentally supported that impaired myocardial vascularization contributes to a mismatch between myocardial oxygen demand and supply, a mechanistic basis for disruption of coordinated tissue growth and angiogenesis in heart failure remains poorly understood. Silencing strategies that impair microRNA biogenesis have firmly implicated microRNAs in the regulation of angiogenesis, and individual microRNAs prove to be crucial in developmental or tumor angiogenesis. A high-throughput functional screening for the analysis of a whole-genome microRNA silencing library with regard to their phenotypic effect on endothelial cell proliferation as a key parameter, revealed several anti- and pro-proliferative microRNAs. Among those was miR-216a, a pro-angiogenic microRNA which is enriched in cardiac microvascular endothelial cells and reduced in expression under cardiac stress conditions. miR-216a null mice display dramatic cardiac phenotypes related to impaired myocardial vascularization and unbalanced autophagy and inflammation, supporting a model where microRNA regulation of microvascularization impacts the cardiac response to stress.


Assuntos
Insuficiência Cardíaca , MicroRNAs , Animais , Camundongos , Células Endoteliais/metabolismo , Insuficiência Cardíaca/metabolismo , MicroRNAs/metabolismo , Miocárdio/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica/genética
18.
Blood ; 141(15): 1812-1816, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-36626252

RESUMO

Patients with paroxysmal nocturnal hemoglobinuria (PNH) are susceptible to complement-mediated intravascular hemolysis and thrombosis. Factor H (FH) is the main regulator of the complement alternative pathway, which protects cells from unwanted complement-mediated damage. Although FH is not a glycosylphosphatidylinositol-linked molecule, it may play a role in PNH. We sought to determine if rare germline variants in complement factor H (CFH) affect the PNH course, screening 84 patients with PNH treated with eculizumab for rare variants in CFH, CFI, and C3 genes. We compared the allelic frequencies with populational data and a geographically-matched control group, looking for an association between presence of the variants and treatment response (transfusion independence by 6 months). Sixteen patients presented rare variants, 9 in CFH (10.7%). Germline CFH variants were more frequent among patients with PNH than among controls (P = .02) or public data (P < .001) and were more likely to be transfusion-dependent at 6 months after eculizumab initiation (P = .015). With a median follow-up of 5.8 years, 8 of 9 patients with the CFH variant received transfusions, and 2 developed thromboses. None of the patients with the CFH variant had severe aplastic anemia from eculizumab initiation until 6 months. We demonstrated for the first time that rare CFH variants are over-represented among patients with PNH and that germline genetic background may affect the response to eculizumab.


Assuntos
Fator H do Complemento , Hemoglobinúria Paroxística , Trombose , Humanos , Anemia Aplástica , Fator H do Complemento/genética , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/genética , Hemólise
19.
Cardiovasc Res ; 119(2): 336-356, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35875883

RESUMO

Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multiorgan symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious perimyocarditis with consequent left or right ventricular failure, arterial wall inflammation, or microthrombosis in certain patient populations. Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, microthrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation, and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae.


Assuntos
COVID-19 , Cardiopatias , Humanos , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Coração , Miocárdio , Teste para COVID-19
20.
Psicol. (Univ. Brasília, Online) ; 39: e39409, 2023. tab
Artigo em Inglês | LILACS-Express | LILACS, Index Psicologia - Periódicos | ID: biblio-1448925

RESUMO

This research aimed to understand the structuring of psychological assessments in custody actions and, on the other hand, to identify the existence of homogeneity or heterogeneity in these practices. Twenty-nine Brazilian legal psychologists participated in this study and answered an online questionnaire built based on the literature. The analysis of the results was carried out through deductive and semantic Thematic Analysis, whose previous categories were created based on national and international guidelines. The most salient results indicate some divergences from the literature, but that its actions and dimensions are compatible with those found in the literature. Based on these results, a guide of systematized practices is proposed, aiming to promote greater uniformity in parental assessment.


Resumo Esta pesquisa teve como objetivos, por um lado, compreender a estruturação das avaliações psicológica em ações de guarda e, por outro, identificar a existência de homogeneidade ou heterogeneidade nessas práticas. Participaram neste estudo 29 psicólogos jurídicos brasileiros, que responderam a um questionário online construído com base na literatura. A análise dos resultados foi realizada através da Análise Temática dedutiva e semântica, cujas categorias prévias foram criadas com base em orientações nacionais e internacionais. Os resultados mais salientes indicam algumas divergências face à literatura, mas que as suas ações e dimensões são compatíveis com as encontradas na literatura. Com base nestes resultados, propõe-se um roteiro de práticas sistematizadas, visando promover uma maior uniformidade na avaliação parental.

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