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SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process.
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BACKGROUND: Congenital heart disease (CHD) are the most common malformations from birth. The severity of the different forms of CHD varies extensively from superficial mild lesions with follow-up for decades without any treatment to complex cyanotic malformations requiring urgent surgical intervention. microRNAs have been found to be crucial in cardiac development, giving rise to possible phenotypes in CHD. OBJECTIVES: We aimed to evaluate the expression of miRNAs in 86 children with CHD and divided into cyanotic and non-cyanotic heart defects and 110 controls. METHODS: The miRNAs expression of miR-21-5p, miR-155-5p, miR-221-3p, miR-26a-5p, and miR-144-3p were analyzed by RT-qPCR. In addition, the expressions of the miRNAs studied were correlated with the clinical characteristics of both the children and the mothers. RESULTS: The expression levels of miR-21-5-5p, miR-15-5p5, miR-221-3p, and miR-26-5p significantly differed between CHD and control subjects. Moreover, miR-21-5p levels were higher in patients with cyanotic versus non-cyanotic CHD patients. CONCLUSION: The expression levels of miRNAs of pediatric patients with CHD could participating in the development of cardiac malformations. Additionally, the high expression of miR-21-5p in cyanotic CHD children may be related to greater severity of illness relative to non-cyanotic CHD. IMPACT: This study adds to knowledge of the association between microRNAs and congenital heart disease in children. The expression levels of miR-21-5-5p, miR-15-5p5, miR-221-3p, and miR-26-5p of pediatric patients with CHD could be involved in the development and phenotype present in pediatric patients. miR-21-5p may help to discriminate between cyanotic and non-cyanotic CHD. In the future, the miRNAs studied could have applications as clinical biomarkers.
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INTRODUCTION: iWHELD is a digital person-centered care program for people with dementia in nursing homes adapted for remote delivery during the COVID-19 pandemic. METHODS: A 16-week two-arm cluster-randomized controlled trial in 149 UK nursing homes compared iWHELD with treatment as usual (TAU). Primary outcome was the overall quality of life with secondary outcomes of agitation and psychotropic use. RESULTS: iWHELD conferred benefit to quality of life on the primary (F = 4.3, p = 0.04) and secondary measures of quality of life (F = 6.45, p = 0.01) and reduced psychotropic medication use (χ2 = 4.08, p = 0.04) with no worsening of agitation. Benefit was seen in participants who contracted COVID-19, those with agitation at baseline, and those taking psychotropic medications. DISCUSSION: iWHELD confers benefits to quality of life and key measures of well-being, can be delivered during the challenging conditions of a pandemic, and should be considered for use alongside any emerging pharmacological treatment for neuropsychiatric symptoms. HIGHLIGHTS: iWHELD is the only remote, digital delivery nursing home training programme for dementia care iWHELD improved quality of life in people with dementia and reduced antipsychotic use without worsening of agitation Residents who contracted Covid-19 during the study also experienced benefits from iWHELD iWHELD offers a valuable, pandemic-safe tool for improving dementia care.
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COVID-19 , Demência , Humanos , Idoso , Pandemias , Instituição de Longa Permanência para Idosos , Qualidade de Vida , Demência/diagnóstico , COVID-19/complicações , Casas de Saúde , Assistência Centrada no Paciente , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/diagnósticoRESUMO
Type 2 diabetes mellitus (T2DM) is associated with various complications, including diabetic foot, which can lead to significant morbidity and mortality. Non-healing foot ulcers in diabetic patients are a major risk factor for infections and amputations. Despite conventional treatments, which have limited efficacy, there is a need for more effective therapies. MicroRNAs (miRs) are small non-coding RNAs that play a role in gene expression and have been implicated in diabetic wound healing. miR expression was analyzed through RT-qPCR in 41 diabetic foot Mexican patients and 50 controls. Diabetic foot patients showed significant increases in plasma levels of miR-17-5p (p = 0.001), miR-191-5p (p = 0.001), let-7e-5p (p = 0.001), and miR-33a-5p (p = 0.005) when compared to controls. Elevated levels of miR-17, miR-191, and miR-121 correlated with higher glucose levels in patients with diabetic foot ulcers (r = 0.30, p = 0.004; r = 0.25, p = 0.01; and r = 0.21, p = 0.05, respectively). Levels of miR-17 showed the highest diagnostic potential (AUC 0.903, p = 0.0001). These findings underscore the possible role of these miRs in developing diabetes complications. Our study suggests that high miR-17, miR-191, and miR-121 expression is strongly associated with higher glucose levels and the development of diabetic foot ulcers.
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MicroRNA Circulante , Diabetes Mellitus Tipo 2 , Pé Diabético , Humanos , Pé Diabético/sangue , Pé Diabético/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Masculino , Feminino , Pessoa de Meia-Idade , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Idoso , MicroRNAs/sangue , MicroRNAs/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Perfilação da Expressão GênicaRESUMO
Type II pneumocytes are the target of the SARS-CoV-2 virus, which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. In this study, we evaluated whether treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), lipid peroxidation (LPO), and thiol groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There were significant increases in LPO and carbonyl quantities (p ≤ 0.03) and decreases in TAC and the quantities of NO2-, thiols, and GSH (p < 0.001) in COVID-19 patients. The activities of the antioxidant enzymes such as ecSOD, TrxR, GPx, GST, GR, and peroxidases were decreased (p ≤ 0.04) after the MT treatment. The treatment with MT favored the activity of the antioxidant enzymes that contributed to an increase in TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis, functioning as a glycolytic agent, and inhibited the Warburg effect. Thus, MT restores the redox homeostasis that is altered in COVID-19 patients and can be used as adjuvant therapy in SARS-CoV-2 infection.
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Antioxidantes , Tratamento Farmacológico da COVID-19 , COVID-19 , Homeostase , Melatonina , Oxirredução , Estresse Oxidativo , SARS-CoV-2 , Melatonina/uso terapêutico , Melatonina/farmacologia , Humanos , Oxirredução/efeitos dos fármacos , COVID-19/metabolismo , COVID-19/virologia , COVID-19/sangue , Homeostase/efeitos dos fármacos , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Idoso , Adulto , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo , Glutationa/sangueRESUMO
BACKGROUND: Extrusion cooking of cereal-legume flour mixture is an innovative strategy to introduce nutrient-enriched ready-to-eat snacks to the market. However, this thermal process triggers the formation of compounds that could impact safety aspects of these products. Maillard reaction markers and the end products known as melanoidins were evaluated to assess the toxicological and bioactive profiles of extruded snacks from corn-plus-common-bean-flour combinations. Different molecular weight fractions were isolated and purified to analyze their antioxidant activity and to investigate the role of melanoidins. RESULTS: The snack formulated with an 84:16 ratio of corn:common bean flours exhibited an enhanced toxicological profile. It displayed the lowest levels of acrylamide and furanic compounds, along with reduced blockage of lysine residues in the protein. Extrusion increased the antioxidant activity of uncooked flours (30 to 64%) and total phenolic compounds (26 to 50%), and decreased the available lysine (-72.7 to -79.5%). During the fractionation process, it was established that compounds within the range of 3-10 kDa made the greatest contribution to antioxidant activity. The fraction greater than 10 kDa, which included melanoidins, displayed 7 to 33% lower antioxidant activity. The purification of the fraction greater than 10 kDa revealed that pure melanoidins represented approximately one-third of the antioxidant activity in that fraction. Non-covalent adducts linked to the melanoidin core therefore had a relevant role in the antioxidant action of formulated snacks. CONCLUSION: This investigation illustrates the importance of considering both potential risks and associated benefits of compounds formed during the Maillard reaction while developing new extruded snacks. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Lysosomal accumulation of the glycosphingolipid globotriaosylceramide Gb3 is linked to the deficient activity of the α-galactosidase A in the Anderson-Fabry disease and an elevated level of deacylated Gb3 is a hallmark of this condition. Localization of Gb3 in the plasma membrane is critical for studying how the membrane organization and its dynamics are affected in this genetic disorder. Gb3 analogs containing a terminal 6-azido-functionalized galactose in its head group globotriose (αGal1, 4ßGal1, and 4Glc) are attractive chemical reporters for bioimaging, as the azido-group may act as a chemical tag for bio-orthogonal click chemistry. We report here the production of azido-Gb3 analogs employing mutants of galactokinase, UTP-glucose-1-phosphate uridylyltransferase, and α-1,4-galactosyltransferase LgtC, which participate in the synthesis of the sugar motif globotriose. Variants of enzymes galactokinase/UTP-glucose-1-phosphate uridylyltransferase generate UDP-6-azido-6-deoxy-d-galactose, which is the galactosyl-donor used by LgtC for transferring the terminal galactose moiety to lactosyl-acceptors. Residues at the galactose-binding site of the 3 enzymes were modified to facilitate the accommodation of azido-functionalized substrates and variants outperforming the wild-type enzymes were characterized. Synthesis of 6-azido-6-deoxy-d-galactose-1-phosphate, UDP-6-azido-6-deoxy-d-galactose, and azido-Gb3 analogs by variants GalK-E37S, GalU-D133V, and LgtC-Q187S, respectively, is 3-6-fold that of their wild-type counterparts. Coupled reactions with these variants permit the production of the pricy, unnatural galactosyl-donor UDP-6-azido-6-deoxy-d-galactose with ~90% conversion yields, and products azido-globotriose and lyso-AzGb3 with substrate conversion of up to 70%. AzGb3 analogs could serve as precursors for the synthesis of other tagged glycosphingolipids of the globo-series.
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Galactoquinase , Galactose , Galactose/metabolismo , Galactoquinase/genética , Galactoquinase/metabolismo , UTP-Glucose-1-Fosfato Uridililtransferase/metabolismo , Sítios de Ligação , Mutação , Difosfato de UridinaRESUMO
Cobalamin availability can influence primary productivity and ecological interactions in marine microbial communities. The characterization of cobalamin sources and sinks is a first step in investigating cobalamin dynamics and its impact on productivity. Here, we identify potential cobalamin sources and sinks on the Scotian Shelf and Slope in the Northwest Atlantic Ocean. Functional and taxonomic annotation of bulk metagenomic reads, combined with analysis of genome bins, were used to identify potential cobalamin sources and sinks. Cobalamin synthesis potential was mainly attributed to Rhodobacteraceae, Thaumarchaeota, and cyanobacteria (Synechococcus and Prochlorococcus). Cobalamin remodelling potential was mainly attributed to Alteromonadales, Pseudomonadales, Rhizobiales, Oceanospirilalles, Rhodobacteraceae, and Verrucomicrobia, while potential cobalamin consumers include Flavobacteriaceae, Actinobacteria, Porticoccaceae, Methylophiliaceae, and Thermoplasmatota. These complementary approaches identified taxa with the potential to be involved in cobalamin cycling on the Scotian Shelf and revealed genomic information required for further characterization. The Cob operon of Rhodobacterales bacterium HTCC2255, a strain with known importance in cobalamin cycling, was similar to a major cobalamin producer bin, suggesting that a related strain may represent a critical cobalamin source in this region. These results enable future inquiries that will enhance our understanding of how cobalamin shapes microbial interdependencies and productivity in this region.
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Alphaproteobacteria , Flavobacteriaceae , Gammaproteobacteria , Synechococcus , Vitamina B 12 , Archaea/genética , Oceano AtlânticoRESUMO
Plant pathogenic fungi pose a significant and ongoing threat to agriculture and food security, causing economic losses and significantly reducing crop yields. Effectively managing these fungal diseases is crucial for sustaining agricultural productivity, and in this context, mycoviruses have emerged as a promising biocontrol option. These viruses alter the physiology of their fungal hosts and their interactions with the host plants. This review encompasses the extensive diversity of reported mycoviruses, including their taxonomic classification and range of fungal hosts. We highlight representative examples of mycoviruses that affect economically significant plant-pathogenic fungi and their distinctive characteristics, with a particular emphasis on mycoviruses impacting Sclerotinia sclerotiorum. These mycoviruses exhibit significant potential for biocontrol, supported by their specificity, efficacy, and environmental safety. This positions mycoviruses as valuable tools in crop protection against diseases caused by this pathogen, maintaining their study and application as promising research areas in agricultural biotechnology. The remarkable diversity of mycoviruses, coupled with their ability to infect a broad range of plant-pathogenic fungi, inspires optimism, and suggests that these viruses have the potential to serve as an effective management strategy against major fungi-causing plant diseases worldwide.
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Ascomicetos , Micovírus , Micoses , Vírus , Fungos , Micoses/microbiologia , Plantas , Micovírus/fisiologia , Doenças das Plantas/microbiologiaRESUMO
PURPOSE: NUTRI-ONCOCARE algorithm has been developed to identify and treat patients with solid tumors who are at risk of malnutrition. The present study is aimed at analyzing users' opinion about this new tool and at assessing whether it is perceived as useful to achieve the behavioral change required for a successful integration of nutritional assessment into routine cancer care. METHODS: Design thinking Double Diamond process was applied. A multidisciplinary team composed of ten potential end-users (four oncologists, three endocrinologists, one nutritionist, and two hospital pharmacists) participated in three different workshops aiming to analyze the different tasks included within the NUTRI-ONCOCARE algorithm. RESULTS: Users agreed on the need to perform nutritional assessment around cancer diagnosis and through the course of the disease using standardized tools included in hospital nutritional protocols and involving healthcare professionals with nutrition expertise. Nutritional evaluation and intervention should be individual and comprehensive, considering not only nutritional parameters but also patients' functional status. According to participants' opinion, the implementation of nutritional screening in routine clinical practice is limited by the lack of time and staff to conduct nutritional assessments, the low level of nutrition expert participation, and the poor support provided by hospital managers, which are often unaware of nutrition's impact in cancer care. CONCLUSIONS: Experts recognized the importance of considering nutritional status in cancer patients and identified the opportunity provided by the NUTRI-ONCOCARE algorithm for this purpose, as it meets main requirements for being used routinely in clinical practice.
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Desnutrição , Neoplasias , Humanos , Estado Nutricional , Espanha , Avaliação Nutricional , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/prevenção & controle , Neoplasias/complicações , Neoplasias/terapia , AlgoritmosRESUMO
BACKGROUND: Despite efforts to increase cervical cancer screening access in rural Bolivia, uptake remains low. Bolivia has one of the highest cervical cancer mortality rates in the Americas. As it redoubles efforts to deliver Universal Health Care, the Bolivian government needs information on the factors constraining cervical cancer screening access and utilization, especially in rural areas. METHODS: Our qualitative study explored cervical cancer screening barriers and described community and provider perceptions and experiences of care. Bolivian and US researchers analyzed data collected from eight focus groups with male and female community members (n = 80) and interviews with healthcare providers (n = 6) in four purposively selected rural communities in Hernando Siles, Bolivia. Deductive and inductive codes were used to thematically analyze data using MaxQDA software. RESULTS: Four themes emerged from the data: lack of knowledge/misconceptions, health system inadequacy, lack of confidence in providers, and opportunities for improvement. Both men and women displayed misconceptions about the causes of cervical cancer, its consequences, the recommended screening frequency, and the means of accessing care. Providers noted community members' lack of knowledge and low risk-perception as utilization barriers but also highlighted poor health service quality and inconsistent health education as factors. Poor healthcare quality was a significant barrier; this included poor patient-provider communication, lack of transportation to screening facilities, and severe delays in receiving test results. Providers also noted problems with provider training and physical space for screening. Community members reported low confidence in nurses to perform screening, preferring doctors and specialists. They also expressed discomfort in having male healthcare providers conduct screening. Suggestions for improvements included more intensive cervical cancer outreach to rural areas and having specialists train lower-level providers to perform screening. CONCLUSIONS: Our findings suggest that poor healthcare quality has affected screening uptake in addition to physical barriers to care. They indicate a need for initiatives to reduce reporting time for Pap test results, the incorporation of community-based HPV self-sampling into screening protocols, and the implementation of programs to improve community confidence in providers' ability to perform screening.
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Neoplasias do Colo do Útero , Feminino , Masculino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Bolívia , Detecção Precoce de Câncer/métodos , População Rural , Pesquisa Qualitativa , Programas de Rastreamento/métodosRESUMO
Frailty is a global health problem that impacts clinical practice. It is complex, having a physical and a cognitive component, and it is the result of many contributing factors. Frail patients have oxidative stress and elevated proinflammatory cytokines. Frailty impairs many systems and results in a reduced physiological reserve and increased vulnerability to stress. It is related to aging and to cardiovascular diseases (CVD). There are few studies on the genetic factors of frailty, but epigenetic clocks determine age and frailty. In contrast, there is genetic overlap of frailty with cardiovascular disease and its risk factors. Frailty is not yet considered a risk factor for CVD. It is accompanied by a loss and/or poor functioning of muscle mass, which depends on fiber protein content, resulting from the balance between protein breakdown and synthesis. Bone fragility is also implied, and there is a crosstalk between adipocytes, myocytes, and bone. The identification and assessment of frailty is difficult, without there being a standard instrument to identify or treat it. Measures to prevent its progression include exercises, as well as supplementing the diet with vitamin D and K, calcium, and testosterone. In conclusion, more research is needed to better understand frailty and to avoid complications in CVD.
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Doenças Cardiovasculares , Fragilidade , Humanos , Idoso , Fragilidade/complicações , Doenças Cardiovasculares/complicações , Idoso Fragilizado , Músculo Esquelético , Tecido AdiposoRESUMO
The renal system is engaged in metabolic syndrome (MS) and metabolites of arachidonic acid (AA) participate in renal homeostasis and disruption of functionality. Hibiscus sabdariffa L (HSL) is used as a diuretic and could improve renal function. The aim of this study was to assess if treatment with HSL at 2% improves renal function in MS through the metabolites of AA. A total of 24 male Wistar rats were divided into four groups: Group 1, control (C); Group 2, MS with 30% sucrose in drinking water, Group 3, MS plus HSL infusion at 2% (MS+HSL); and Group 4, C+HSL. We evaluated the perfusion pressure changes (∆-PP), the activities of cyclooxygenases (COXs), the percentage of AA, the expressions of PLA2, COX2, COX1, 5-LOX, TAXS and CYP450, and the concentrations of prostaglandins in the kidney from rats with MS. There was a decrease in the ∆-PP, in the activities of COXs, and the expressions of COX2 and CYP450 (p ≤ 0.03, respectively)as well asPGE2, TxB2, and LKB4 (p ≤ 0.01, respectively). However, the percentage of AA and expressions of PLA2 and PGE1 (p = 0.01, respectively) were increased in C and MS+HSL. The HSL treatment improved the function and anatomical structure of the kidneys in the MS rats, through antioxidant molecules, and inhibited the pathways that metabolize the AA including that of PLA2, COX2, 5-LOX, TAXS, and CYP450 while favoring the COX1 pathway. This improves the vascular resistance of renal arterioles.
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Hibiscus , Síndrome Metabólica , Masculino , Ratos , Animais , Ácido Araquidônico , Ratos Wistar , Ciclo-Oxigenase 2 , Síndrome Metabólica/tratamento farmacológico , Rim/fisiologia , Fosfolipases A2RESUMO
Marfan syndrome (MFS) is an autosomal dominant disorder caused by a heterozygous mutation of the FBN1 gene. MFS patients present oxidative stress that disturbs redox homeostasis. Redox homeostasis depends in part on the enzymatic antioxidant system, which includes thioredoxin reductase (TrxR) and glutathione peroxidases (GPx), both of which require an adequate concentration of selenium (Se). Therefore, the aim of this study was to determine if Se levels are decreased in the TAA of patients with MFS since this could contribute to the formation of an aneurysm in these patients. The results show that interleukins IL-1ß, IL-6 TGF-ß1, and TNF-α (p ≤ 0.03), and carbonylation (p ≤ 0.03) were increased in the TAA of patients with MFS in comparison with control subjects, while Se, thiols (p = 0.02), TrxR, and GPx (p ≤ 0.001) were decreased. TLR4 and NOX1 (p ≤ 0.03), MMP9 and MMP2 (p = 0.04) and NOS2 (p < 0.001) were also increased. Therefore, Se concentrations are decreased in the TAA of MFS, which can contribute to a decrease in the activities of TrxR and GPx, and thiol groups. A decrease in the activities of these enzymes can lead to the loss of redox homeostasis, which can, in turn, lead to an increase in the pro-inflammatory interleukins associated with the overexpression of MMP9 and MMP2.
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Aneurisma , Síndrome de Marfan , Selênio , Humanos , Aorta Torácica , Tiorredoxina Dissulfeto Redutase , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Aneurisma/complicações , Glutationa PeroxidaseRESUMO
MicroRNAs (miRs) regulate gene expression at the post-transcriptional level and are found to be present in monocytes. This study aimed to investigate miR-221-5p, miR-21-5p, and miR-155-5p, their expression in monocytes, and their role in coronary arterial disease (CAD). The study population comprised 110 subjects, and RT-qPCR was used to examine the miR-221-5p, miR-21-5p, and miR-155-5p expressions in monocytes. Results: the miR-21-5p (p = 0.001) and miR-221-5p (p < 0.001) expression levels were significantly higher in the CAD group, and the miR-155-5p (p = 0.021) expression levels were significantly lower in the CAD group; only miR-21-5p and miR-221-5p upregulation was found to be associated with an increased CAD risk. The results show significant increases in miR-21-5p in the unmedicated CAD group with the metformin patients vs. the healthy control group (p = 0.001) and vs. the medicated CAD group with metformin (p = 0.022). The same was true for miR-221-5p in the CAD patients unmedicated with metformin vs. the healthy control group (p < 0.001). Our results from Mexican CAD patients show that the overexpression in monocytes of miR-21-5p and miR-221-5p increases the risk of the development of CAD. In addition, in the CAD group, the metformin downregulated the expression of miR-21-5p and miR-221-5p. Also, the expression of endothelial nitric oxide synthase (NOS3) decreased significantly in our patients with CAD, regardless of whether they were medicated. Therefore, our findings allow for the proposal of new therapeutic strategies for the diagnosis and prognosis of CAD and the evaluation of treatment efficacy.
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Doença da Artéria Coronariana , MicroRNAs , Humanos , Doença da Artéria Coronariana/metabolismo , Monócitos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação para Cima/genéticaRESUMO
Bacterial surface motility is a complex microbial trait that contributes to host colonization. However, the knowledge about regulatory mechanisms that control surface translocation in rhizobia and their role in the establishment of symbiosis with legumes is still limited. Recently, 2-tridecanone (2-TDC) was identified as an infochemical in bacteria that hampers microbial colonization of plants. In the alfalfa symbiont Sinorhizobium meliloti, 2-TDC promotes a mode of surface motility that is mostly independent of flagella. To understand the mechanism of action of 2-TDC in S. meliloti and unveil genes putatively involved in plant colonization, Tn5 transposants derived from a flagellaless strain that were impaired in 2-TDC-induced surface spreading were isolated and genetically characterized. In one of the mutants, the gene coding for the chaperone DnaJ was inactivated. Characterization of this transposant and newly obtained flagella-minus and flagella-plus dnaJ deletion mutants revealed that DnaJ is essential for surface translocation, while it plays a minor role in swimming motility. DnaJ loss-of-function reduces salt and oxidative stress tolerance in S. meliloti and hinders the establishment of efficient symbiosis by affecting nodule formation efficiency, cellular infection, and nitrogen fixation. Intriguingly, the lack of DnaJ causes more severe defects in a flagellaless background. This work highlights the role of DnaJ in the free-living and symbiotic lifestyles of S. meliloti.
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Fixação de Nitrogênio , Sinorhizobium meliloti , Fixação de Nitrogênio/genética , Sinorhizobium meliloti/genética , Simbiose/genética , Medicago sativa/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1ß, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFß), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.
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Melatonina , Choque Séptico , Humanos , Antioxidantes/uso terapêutico , Interleucina-6 , Síndrome da Liberação de Citocina/tratamento farmacológico , Interleucina-10 , Choque Séptico/tratamento farmacológico , Reprodutibilidade dos Testes , Estresse Oxidativo , Ácido Ascórbico/uso terapêutico , Vitamina E/uso terapêutico , Acetilcisteína/uso terapêutico , Melatonina/uso terapêutico , Adjuvantes Imunológicos/uso terapêuticoRESUMO
BACKGROUND: The left ventricle (LV) journey in their transition from hypertrophy to heart failure is marked by many subcellular events partially understood yet. The moment in which the structural abnormalities reach the umbral to induce myocardial dysfunction remains elusive. AIMS: To evaluate the anatomic-functional relationship between LV wall thickness and longitudinal systolic dysfunction. MATERIAL AND METHODS: We prospectively performed clinical assessment and transthoracic echocardiogram on healthy individuals and hypertensive patients with left ventricle ejection fraction (LVEF) ≥50% and absence of heart failure symptoms. RESULTS: A total of 226 patients and 101 healthy individuals were recruited. The distribution for sex was similar between groups. The mean age was 67±13 years old in the patients, and 44% had concentric LV hypertrophy. LVEF was identical in both groups (63±6%); in contrast, global longitudinal strain (GLS) (-18.8±2.5% vs -20.4±2%) and mitral annulus plane systolic excursion (MAPSE) (13.8±2.8 vs 15.5±2 mm) were lower. ROC curve optimally classified decreased GLS with LV septum thickness ≥13 mm and decreased MAPSE with thickness ≥14 mm. Multivariable logistic regression found that LV septum thickness is the only variable associated with longitudinal systolic dysfunction (OR = 1.1, CI95% = 1.05 - 1.15, P = 0.001, R squared = .38). DISCUSSION: A progressive increase in LV wall thickness due to myocyte hypertrophy and interstitial expansion is associated with LV systolic longitudinal dysfunction. CONCLUSIONS: Patients with moderate or severe ventricular hypertrophy (septum ≥13 mm) had longitudinal systolic dysfunction, GLS decreases with minor structural change than MAPSE, and LVEF is insensitive in detecting longitudinal myocardial dysfunction in patients with hypertension.
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Cardiomiopatias , Hipertensão , Disfunção Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico por imagem , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Pessoa de Meia-Idade , Volume Sistólico , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular EsquerdaRESUMO
BACKGROUND: The overburdening of the healthcare system during the coronavirus disease 19 (COVID-19) pandemic is driving the need to create new tools to improve the management of inter-hospital transport for patients with a severe COVID-19 infection. OBJECTIVE: The aim of this study was to analyse the usefulness of the application of a prioritization score (IHTCOVID-19) for inter-hospital transfer of patients with COVID-19 infection. METHODS: The study has a quasi-experimental design and was conducted on the Medical Emergency System, the pre-hospital emergency department of the public company belonging to the Autonomous Government of Catalonia that manages urgent healthcare in the region. Patients with a severe COVID-19 infection requiring inter-hospital transport were consecutively included. The pre-intervention period was from 1 to 31 March 2020, and the intervention period with the IHTCOVID-19 score was from 1 to 30 April 2020 (from 8 am to 8 pm). The prioritization score comprises four priority categories, with Priority 0 being the highest and Priority 3 being the lowest. Inter-hospital transfer (IHT) management times (alert-assignment time, resource management time and total central management time) and their variability were evaluated according to whether or not the IHTCOVID-19 score was applied. RESULTS: A total of 344 IHTs were included: 189 (54.9%) in the pre-intervention period and 155 (45.1%) in the post-intervention period. The majority of patients were male and the most frequent age range was between 50 and 70 years. According to the IHTCOVID-19 score, 12 (3.5%) transfers were classified as Priority 0, 66 (19.4%) as Priority 1, 247 (71.8%) as Priority 2 and 19 (5.6%) as Priority 3. Overall, with the application of the IHTCOVID-19 score, there was a significant reduction in total central management time [from 112.4 (inter-quartile range (IQR) 281.3) to 89.8 min (IQR 154.9); P = 0.012]. This significant reduction was observed in Priority 0 patients [286.2 (IQR 218.5) to 42.0 min (IQR 58); P = 0.018] and Priority 1 patients [130.3 (IQR 297.3) to 75.4 min (IQR 91.1); P = 0.034]. After applying the IHTCOVID-19 score, the average time of the process decreased by 22.6 min, and variability was reduced from 618.1 to 324.0 min. CONCLUSION: The application of the IHTCOVID-19 score in patients with a severe COVID-19 infection reduces IHT management times and variability.
Assuntos
COVID-19 , Idoso , COVID-19/epidemiologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Gerenciamento do TempoRESUMO
Bacteria can spread on surfaces to colonize new environments and access more resources. Rhizobia, a group of α- and ß-Proteobacteria, establish nitrogen-fixing symbioses with legumes that rely on a complex signal interchange between the partners. Flavonoids exuded by plant roots and the bacterial transcriptional activator NodD control the transcription of different rhizobial genes (the so-called nod regulon) and, together with additional bacterial regulatory proteins (such as TtsI, MucR or NolR), influence the production of different rhizobial molecular signals. In Sinorhizobium fredii HH103, flavonoids and NodD have a negative effect on exopolysaccharide production and biofilm production. Since biofilm formation and motility are often inversely regulated, we have analysed whether flavonoids may influence the translocation of S. fredii HH103 on surfaces. We show that the presence of nod gene-inducing flavonoids does not affect swimming but promotes a mode of surface translocation, which involves both flagella-dependent and -independent mechanisms. This surface motility is regulated in a flavonoid-NodD1-TtsI-dependent manner, relies on the assembly of the symbiotic type 3 secretion system (T3SS), and involves the participation of additional modulators of the nod regulon (NolR and MucR1). To our knowledge, this is the first evidence indicating the participation of T3SS in surface motility in a plant-interacting bacterium. Interestingly, flavonoids acting as nod-gene inducers also participate in the inverse regulation of surface motility and biofilm formation, which could contribute to a more efficient plant colonisation.