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Although Down syndrome (DS) is considered a risk factor for hemodynamic instabilities (mainly pulmonary hypertension-PH) following surgery for congenital cardiac communications, many DS patients do surprising well postoperatively. We prospectively analyzed perioperative factors for a possible correlation with post-cardiopulmonary bypass (CPB) inflammatory reaction and postoperative PH in pediatric subjects. Sixty patients were enrolled (age 3 to 35 months), 39 of them with DS. Clinical and echocardiographic parameters (anatomical and hemodynamic) were computed preoperatively. Pulmonary and systemic mean arterial pressures (PAP and SAP) were assessed invasively intra and postoperatively. Immediate postoperative PAP/SAP ratio (PAP/SAPIPO) and the behavior of pressure curves were selected as primary outcome. Serum levels of 36 inflammatory proteins were measured by chemiluminescence preoperatively and 4 h post CPB. Of all factors analyzed, peripheral oxygen saturation (O2Sat, bedside assessment) was the only preoperative predictor of PAP/SAPIPO at multivariate analysis (p = 0.007). Respective values in non-DS, DS/O2Sat ≥ 95% and DS/O2Sat < 95% subgroups were 0.34 (0.017), 0.40 (0.027) and 0.45 (0.026), mean (SE), p = 0.004. The difference between non-DS and DS groups regarding postoperative PAP curves (upward shift in DS patients, p = 0.015) became nonsignificant (p = 0.114) after adjustment for preoperative O2Sat. Post-CPB levels of at least 5 cytokines were higher in patients with O2Sat < 95% versus those at or above this level, even within the DS group (p < 0.05). Thus, a baseline O2Sat < 95% representing pathophysiological phenomena in the airways and the distal lung, rather than DS in a broad sense, seems to be associated with post-CPB inflammation and postoperative PH in these patients.
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Síndrome de Down , Cardiopatias Congênitas , Hemodinâmica , Humanos , Feminino , Masculino , Lactente , Síndrome de Down/fisiopatologia , Pré-Escolar , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/fisiopatologia , Período Pós-Operatório , Estudos Prospectivos , Ponte Cardiopulmonar/efeitos adversos , Complicações Pós-Operatórias/etiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Fatores de RiscoRESUMO
Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T. cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti-inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding.
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Anti-Inflamatórios não Esteroides , Doença de Chagas , Modelos Animais de Doenças , Trypanosoma cruzi , Animais , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Camundongos , Trypanosoma cruzi/efeitos dos fármacos , HumanosRESUMO
INTRODUCTION: Carbon monoxide (CO) has been shown to exert protective effects in multiple organs following ischemic injury, including the lung. The purpose of this study was to examine the effects of CO administration during ex vivo lung perfusion (EVLP) on lung grafts exposed to prolonged cold ischemia. METHODS: Ten porcine lungs were subjected to 18 h of cold ischemia followed by 6 h of EVLP. Lungs were randomized to EVLP alone (control, n = 5) or delivery of 500 ppm of CO during the 1st hour of EVLP (treatment, n = 5). Following EVLP, the left lungs were transplanted and reperfused for 4 h. RESULTS: At the end of EVLP, pulmonary vascular resistance (P = 0.007) and wet to dry lung weight ratios (P = 0.027) were significantly reduced in CO treated lungs. Posttransplant, lung graft PaO2/FiO2 (P = 0.032) and compliance (P = 0.024) were significantly higher and peak airway pressure (P = 0.032) and wet to dry ratios (P = 0.003) were significantly lower in CO treated lungs. Interleukin-6 was significantly reduced in plasma during reperfusion in the CO treated group (P = 0.040). CONCLUSIONS: In this preclinical porcine model, CO application during EVLP resulted in better graft performance and outcomes after reperfusion.
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Monóxido de Carbono , Isquemia Fria , Transplante de Pulmão , Pulmão , Perfusão , Animais , Transplante de Pulmão/métodos , Perfusão/métodos , Pulmão/irrigação sanguínea , Suínos , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/etiologia , Interleucina-6/sangue , Interleucina-6/metabolismoRESUMO
A positive relationship has been reported between advanced periodontitis and carotid intima-media thickness (cIMT) measurement. The aim of this study was to investigate this relationship with parameters for periodontitis, such as PISA and systemic inflammation biomarkers. An observational descriptive cross-sectional study was conducted. A blood sample was collected from 75 subjects to analyze glucose, total cholesterol, HDL, LDL, and cytokine values. Increased cIMT was found in 32% of the patients with fewer teeth. Patients with periodontitis had a larger periodontal inflamed surface area (PISA) (p = 0.000) and had a 1.42-times-higher risk of having increased cIMT values compared to periodontally healthy individuals, though without a statistically significant association. Higher values in the left cIMT, IL-8, and TNF-α were found in men than in women with significant differences. In the multivariate analysis involving cytokines, age continues to be linked to increased cIMT values. INF-γ showed a trend towards a protective effect; as the IMT-M decreases, there is an increase in the expression of INF-γ, and a higher proportion of subjects with elevated INF-γ concentrations demonstrated normal IMT-C. This study did not find a statistically significant association between cIMT and periodontal disease, but the risk of having increased cIMT is 1.42-times higher for individuals with periodontitis.
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High scores of lymphocyte-to-high-density lipoprotein cholesterol ratio (lymphocyte-to-HDL-c) may be a new indicator of inflammation and metabolic syndrome. Here, we investigated the associations of the lymphocyte-to-HDL-c with traditional and non-traditional cardiometabolic risk markers in subjects at high cardiovascular risk. This study is a cross-sectional analysis with subjects assisted in a Secondary Health Care (n = 581, age = 63.06 ± 13.86 years; 52.3% women). Lymphocyte-to-HDL-c ratio were assessed by routine laboratory tests. Anthropometric and/or biochemical variables were used to calculate traditional (body mass index - BMI, and waist-to-height ratio - WHtR) and non-traditional (lipid accumulation product index-LAP, visceral adiposity index-VAI, deep-abdominal-adipose-tissue index-DAAT, atherogenic index of plasma-AIP, and waist-hypertriglyceridemic phenotype-HTGW) cardiometabolic risk markers. Furthermore, anthropometric measurement waist circumference (WC), blood pressure, metabolic syndrome (MS), and biochemical markers (lipid and glycemic profile) were considered traditional markers of cardiometabolic risk. Pearson's chi-square test, Poisson regression with robust variance, or multinomial logistic regression were performed (α = 0.05). Individuals with a high lymphocyte-HDL-c ratio (> 0.84, 3rd tertile) were associated with the HTGW phenotype, high VAI, high LAP, hypertriglyceridemia, high AIP, high very low-density lipoprotein-cholesterol (VLDL-c), pre-diabetes, and 3 and 4 MS components compared with individuals in the first tertile, independent of confounders. Our findings supported the lymphocyte-to-HDL-c ratio as a potential biomarker during the screening of subjects at high cardiovascular risk.
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Background: Uncaria tomentosa (Willd. ex Schult.) DC. (Rubiaceae) is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. To date, there are no systematic reviews and meta-analyses on the use of U. tomentosa for inflammation control in animals supporting the traditional knowledge about this species. This study was conducted to evaluate the effect of U. tomentosa extracts in modulating inflammatory mediators and to determine which types of inflammatory diseases can be treated by this species. Methods: We conducted a systematic review and meta-analysis of preclinical studies published before 26 July 2023, identified in PubMed, Embase, and Scopus. Four independent reviewers extracted the data and assessed the risks of bias. The effects of U. tomentosa on inflammatory diseases and the inflammatory mediators involved were extracted from the studies. Standardized mean differences (SMD) and 95% confidence intervals (95%CI) of the outcomes were estimated. The meta-analyses were conducted using RevMan 5.4 (Cochrane Collaboration). This protocol was registered in PROSPERO (CRD42023450869). Results: Twenty-four of 523 studies were included. U. tomentosa extracts decreased the cytokines interleukin (IL)-6 (SMD: -0.72, 95%CI: -1.15, -0.29, p = 0.001) and transcription factor nuclear factor kappa-B (NF-κB) (SMD: -1.19, 95%CI: -1.89, -0.48, p = 0.001). However, the extracts did not significantly alter IL-1 (SMD: -0.16, 95%CI: -0.87, +0.56, p = 0.67), IL-10 (SMD: -0.05, 95%CI:-0.35, 0.45, p = 0.80), or tumor necrosis factor-alpha (TNF-α) levels (SMD: 0.18, 95%CI: -0.25, 0.62, p = 0.41). Conclusion: Many extracts of stem bark, roots, and leaves of U. tomentosa, mostly aqueous and hydroethanolic, exhibited anti-inflammatory and/or immunomodulatory activities and low toxicity. The extracts decreased NF-κB and IL-6. These findings suggest that this species has the potential to treat inflammatory diseases in which these markers are increased, according to the ethnopharmacological use. These activities are not related to a specific class of compounds.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450869, Identifier CRD42023450869.
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Colombia hosts the largest number of refugees and migrants fleeing the humanitarian emergency in Venezuela, many of whom experience high levels of displacement-related trauma and adversity. Yet, Colombian mental health services do not meet the needs of this population. Scalable, task-sharing interventions, such as Group Problem Management Plus (Group PM+), have the potential to bridge this gap by utilizing lay workers to provide the intervention. However, the current literature lacks a comprehensive understanding of how and for whom Group PM+ is most effective. This mixed methods study utilized data from a randomized effectiveness-implementation trial to examine the mediators and moderators of Group PM+ on mental health outcomes. One hundred twenty-eight migrant and refugee women in northern Colombia participated in Group PM+ delivered by trained community members. Patterns in moderation effects showed that participants in more stable, less marginalized positions improved the most. Results from linear regression models showed that Group PM+-related skill acquisition was not a significant mediator of the association between session attendance and mental health outcomes. Participants and facilitators reported additional possible mediators and community-level moderators that warrant future research. Further studies are needed to examine mediators and moderators contributing to the effectiveness of task-shared, scalable, psychological interventions in diverse contexts.
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Saúde Mental , Refugiados , Migrantes , Humanos , Colômbia , Refugiados/psicologia , Feminino , Venezuela , Adulto , Migrantes/psicologia , Migrantes/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: The aim of the present study was to assess the cytocompatibility of epoxy resin-based AH Plus Jet (Dentsply De Trey, Konstanz, Germany), Sealer Plus (MK Life, Porto Alegre, Brazil), calcium silicate-based Bio-C Sealer (Angelus, Londrina, PR, Brazil), Sealer Plus BC (MK Life) and AH Plus BC (Dentsply) through a tridimensional (3D) culture model of human osteoblast-like cells. METHODS: Spheroids of MG-63 cells were produced and exposed to fresh root canal sealers extracts by 24 h, and the cytotoxicity was assessed by the Lactate Dehydrogenase assay (LDH). The distribution of dead cells within the microtissue was assessed by fluorescence microscopy, and morphological effects were investigated by histological analysis. The secreted inflammatory mediators were detected in cell supernatants through flow luminometry (XMap Luminex). RESULTS: Cells incubated with AH Plus Jet, AH Plus BC, Sealer Plus BC and Bio-C Sealer extracts showed high rates of cell viability, while the Sealer Plus induced a significant reduction of cell viability, causing reduction on the spheroid structure. Sealer Plus and Seaker Plus BC caused alterations on 3D microtissue morphology. The AH Plus BC extract was associated with the downregulation of secretion of pro-inflammatory cytokines IL-5, IL-7, IP-10 and RANTES. CONCLUSIONS: The new AH Plus BC calcium silicate-based endodontic sealer did not reduce cell viability in vitro, while led to the downregulation of pro-inflammatory cytokines. CLINICAL SIGNIFICANCE: Choosing the appropriate endodontic sealer is a crucial step. AH Plus BC demonstrated high cell viability and downregulation of pro-inflammatory cytokines, appearing reliable for clinical use, while Sealer Plus presented lower cytocompatibility.
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Compostos de Cálcio , Sobrevivência Celular , Resinas Epóxi , Teste de Materiais , Materiais Restauradores do Canal Radicular , Silicatos , Materiais Restauradores do Canal Radicular/farmacologia , Humanos , Compostos de Cálcio/farmacologia , Silicatos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cultura de Células em Três Dimensões/métodos , Mediadores da Inflamação/metabolismo , Microscopia de Fluorescência , Osteoblastos/efeitos dos fármacosRESUMO
Emotional and behavioral regulations are crucial for the development of perceptive, responsive, and flexible parenting. Moreover, maternal emotional dysregulation constitutes a risk for maltreatment behaviors. The present study aimed to conduct a systematic review of empirical studies on the associations between mothers' emotional and behavioral regulations and parenting practices with their children or adolescents. A systematic review was conducted, including papers that addressed these variables, analyzing the direct effects, and moderation or mediation effects of maternal emotional and behavioral regulation on parenting practices, targeting child and adolescent samples. We identified 35 studies for analysis. Most of the studies (86%) showed significant associations between maternal emotional and behavioral regulation and parenting practices. Mothers' emotional dysregulation was related to a high risk of maltreatment and negative parenting, such as unsupportive reactions and harsh discipline. High maternal emotional dysregulation and negative parenting, in turn, were associated with children's aggressive behaviors. Conversely, when mothers exhibited high emotional regulation, they engaged in more positive and supportive parenting. Additionally, maternal behavioral regulation with inhibitory control and effortful control led to supportive and warm parenting. Individual and contextual factors, such as maternal victimization history and symptoms of inattention and hyperactivity, had effects on maternal emotional dysregulation, which, in turn, impacted their parenting practices. Consequently, emotional and behavioral regulation played a crucial role in mothers' parenting practices with their children and adolescents. The findings of the current review could contribute to planning parenting interventions, including maternal emotional and behavioral regulation skills, aimed at preventing maltreatment of their children.
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Protectin DX (PDX), a specialized pro-resolving lipid mediator, presents potential therapeutic applications across various medical conditions due to its anti-inflammatory and antioxidant properties. Since type-1 diabetes mellitus (T1DM) is a disease with an inflammatory and oxidative profile, exploring the use of PDX in addressing T1DM and its associated comorbidities, including diabetic neuropathic pain, depression, and anxiety becomes urgent. Thus, in the current study, after 2 weeks of T1DM induction with streptozotocin (60 mg/kg) in Wistar rats, PDX (1, 3, and 10 ng/animal; i.p. injection of 200 µl/animal) was administered specifically on days 14, 15, 18, 21, 24, and 27 after T1DM induction. We investigated the PDX's effectiveness in alleviating neuropathic pain (mechanical allodynia; experiment 1), anxiety-like and depressive-like behaviors (experiment 2). Also, we studied whether the PDX treatment would induce antioxidant effects in the blood plasma, hippocampus, and prefrontal cortex (experiment 3), brain areas involved in the modulation of emotions. For evaluating mechanical allodynia, animals were repeatedly submitted to the Von Frey test; while for studying anxiety-like responses, animals were submitted to the elevated plus maze (day 26) and open field (day 28) tests. To analyze depressive-like behaviors, the animals were tested in the modified forced swimming test (day 28) immediately after the open field test. Our data demonstrated that PDX consistently increased the mechanical threshold throughout the study at the two highest doses, indicative of antinociceptive effect. Concerning depressive-like and anxiety-like behavior, all PDX doses effectively prevented these behaviors when compared to vehicle-treated T1DM rats. The PDX treatment significantly protected against the increased oxidative stress parameters in blood plasma and in hippocampus and prefrontal cortex. Interestingly, treated animals presented improvement on diabetes-related parameters by promoting weight gain and reducing hyperglycemia in T1DM rats. These findings suggest that PDX improved diabetic neuropathic pain, and induced antidepressant-like and anxiolytic-like effects, in addition to improving parameters related to the diabetic condition. It is worth noting that PDX also presented a protective action demonstrated by its antioxidant effects. To conclude, our findings suggest PDX treatment may be a promising candidate for improving the diabetic condition per se along with highly disabling comorbidities such as diabetic neuropathic pain and emotional disturbances associated with T1DM.
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Ansiedade , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Ácidos Docosa-Hexaenoicos , Ratos Wistar , Animais , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/psicologia , Ratos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Depressão/tratamento farmacológico , Depressão/etiologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Hiperalgesia/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Neuropatias Diabéticas/tratamento farmacológicoRESUMO
School-based interventions are needed due to the low levels of physical activity (PA) in adolescents. The aim is to examine the mediation effects of psychosocial factors (attitude, self-efficacy, social support from parents, friends, general teachers, and PE teachers, and environment school perception) and moderation by sex, school grade, and socioeconomic level of a school-based PA intervention on the PA practice among adolescents. The Movimente Programme is a randomised controlled trial at schools in southern Brazil (n = 921 adolescents). Strategies included teacher training, educational actions, and environmental changes. Adolescents self-reported their weekly PA. Potential psychosocial mediators and moderators were investigated through validated questionnaires in a Brazilian sample. The product of the coefficients with percentile bootstrapping 95% confidence interval was performed. The Movimente Programme was related to positive changes in adolescents' perception of the school environment and social support from general and physical education teachers. Most psychosocial variables (attitude, self-efficacy, social support from friends, and social support from teachers) were associated with PA, but none mediated the impact of the Movimente Programme on PA. Results varied according to sex and school grade. The Movimente Programme increased the adolescents' perception of the school environment and social support from teachers, but no mediators were confirmed.
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Exercício Físico , Promoção da Saúde , Humanos , Adolescente , Brasil , Promoção da Saúde/métodos , Instituições Acadêmicas , Apoio SocialRESUMO
Complex inflammatory crosstalk between muscular and adipose organs during ageing is controlled by adipokines and myokines. The Adiponectin/Leptin ratio (A/L ratio) has proven to be a promising biomarker for identifying insulin sensitivity, cardiovascular risk and adipose tissue inflammation. Although the A/L ratio has been related to inflammatory conditions, its ability to associate with or indicate the behavior of other inflammatory mediators remains unknown. The present study aimed to verify the association between the A/L ratio and a panel of inflammatory biomarkers in community-dwelling older women. The plasmatic concentrations of adiponectin, leptin, resistin, brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukins 2, 4, 5, 6, 8 and 10, tumour necrosis factor (TNF) and its soluble receptors (sTNF-r) 1 and 2 were evaluated in 71 community-dwelling older women with 75 (±7) years. The A/L ratio was negative and inverse correlated with BNDF (r = -0.29; p = 0.01), IL-8 (r = -0.37; p = 0.001) and sTNFr- 1 (r = -0.98; p < 0.001) levels. A strong and inverse association, with proportional effect, between A/L ratio and sTNFr-1 concentrations was found (Adjusted R2 = 0.22; ß = -0.48; p > 0.001). It suggests that the presence of sTNFr-1 causes an inflammatory effect that affect cross-talk between muscle and adipose tissue, contributing to pro-inflammatory imbalance, which may have molecular and functional consequences. In addition, we provide insights into diagnostic biomarkers for inflammation, especially related to muscle wasting and intrinsic capacity in older people.
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Adiponectina , Leptina , Humanos , Feminino , Idoso , Resistina , Biomarcadores , Inflamação , Fator de Necrose Tumoral alfaRESUMO
Innate immunity is present in all animals. In this review, we explore the main conserved mechanisms of recognition and innate immune responses among animals. In this sense, we discuss the receptors, critical for binding to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs); the downstream signaling proteins; and transcription factors that govern immune responses. We also highlight conserved inflammatory mediators that are induced after the recognition of DAMPs and PAMPs. At last, we discuss the mechanisms that are involved in the regulation and/or generation of reactive oxygen species (ROS), influencing immune responses, like heme-oxygenases (HOs).
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Imunidade Inata , Moléculas com Motivos Associados a Patógenos , Animais , Imunidade Inata/genética , Alérgenos , Fatores de Transcrição , Proteínas de TransporteRESUMO
SUMMARY OBJECTIVE: In this study, we aimed to investigate the role of erythrocyte sedimentation rate, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio, red blood cell distribution width, mean platelet volume, monocyte/HDL ratio, and C-reactive protein/albumin ratio in the diagnosis and treatment follow-up of active and remission Takayasu arteritis patients compared with healthy control group. METHODS: This is a retrospective case-control study in which 56 Takayasu arteritis patients and 40 age- and sex-matched healthy control were included. The blood values of Takayasu arteritis patients were analyzed during their active period and post-treatment remission periods, after comparing them with the healthy control. Furthermore, all parameters were evaluated by receiver operating characteristic analysis. RESULTS: Erythrocyte sedimentation rate, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio, monocyte/HDL ratio, and C-reactive protein/albumin ratio values were significantly higher in active Takayasu arteritis patients compared with healthy control and remission Takayasu arteritis groups. In the receiver operating characteristic analysis performed in active Takayasu arteritis and Takayasu arteritis patients in remission, C-reactive protein had the highest power to indicate disease activity, followed by C-reactive protein/albumin ratio, erythrocyte sedimentation rate, and monocyte/HDL ratio. When Takayasu arteritis in remission was compared with the healthy control, a significant difference was found between erythrocyte sedimentation rate, C-reactive protein, red blood cell distribution width, and C-reactive protein/albumin ratio, while no significant difference was found between monocyte/HDL ratio values. CONCLUSION: C-reactive protein/albumin ratio and red blood cell distribution width can be used in the diagnosis of Takayasu arteritis, and C-reactive protein/albumin ratio, red blood cell distribution width, and monocyte/HDL ratio measurements can be used in the follow-up. As C-reactive protein/albumin ratio is more powerful than C-reactive protein in differentiating the Takayasu arteritis group from the healthy control group, evaluation of C-reactive protein/albumin ratio together with albumin instead of evaluation of C-reactive protein alone when diagnosing the disease may help us to obtain more accurate results in daily practice.
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OBJECTIVES: The present study aimed to identify optimal inflammatory biomarkers involved in cardiorenal risk in response to major lifestyle factors. METHODS: One hundred and twenty-nine adults aged 35-77 years participated voluntarily from 2017 to 2019 (Córdoba, Argentina) in a cross-sectional study to collect sociodemographic, clinical, and lifestyle data. Blood biomarkers (different cytokines, monocyte chemoattractant protein-1 [MCP-1], and high-sensitivity C-reactive protein [hs-CRP]) were measured using standard methods and then evaluated by principal component analysis and structural equation modeling (SEM) according to Mediterranean diet adherence, physical activity level, and waist circumference, while cardiorenal risk involved blood diastolic pressure, HDL-cholesterol, triacylglycerols, creatinine, and glycosylated hemoglobin. RESULTS: A principal component included TNF-α (tumor necrosis factor-alpha), IL-8 (interleukin-8), IL-6 (interleukin-6), hs-CRP, and MCP-1, with absolute rotated factor loadings >0.10. SEM showed that IL-6 (ß=0.38, 95â¯% IC=0.08-0.68), hs-CRP (ß=0.33, 95â¯% IC=0.17-0.48), and TNF-α (ß=0.22, 95â¯% IC=0.11-0.32) were the mediators that better explained an inflammatory profile positively related to waist circumference (ß=0.77, 95â¯% IC=0.61-0.94). Moreover, this profile was associated with an increased cardiorenal risk (ß=0.78, 95â¯% IC=0.61-0.94), which was well-defined by the variable used. CONCLUSIONS: Immune mediators are key elements in profiling the cardiorenal risk associated with lifestyle factors, for which the combination of hs-CRP, IL-6, and TNF-α has emerged as a robust indicator. This work reaffirms the need for biomarker optimization for early diagnosis and risk assessment.
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Proteína C-Reativa , Interleucina-6 , Adulto , Humanos , Biomarcadores , Proteína C-Reativa/análise , Estudos Transversais , Fator de Necrose Tumoral alfa , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the biotechnological potential to develop novel drugs. AIMS: Therefore, the aim of this study was to perform a systematic review to provide an overview of the anti-inflammatory substances isolated from marine sponges with therapeutic potential. METHODS: This systematic review was performed on the Embase, PubMed, Scopus and Web of Science electronic databases. In total, 613 were found, but 340 duplicate studies were excluded, only 100 manuscripts were eligible, and 83 were included. RESULTS: The results were based on in vivo and in vitro assays, and the anti-inflammatory effects of 251 bioactive compounds extracted from marine sponges were investigated. Their anti-inflammatory activities include inhibition of pro-inflammatory mediators, such as tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), nitrite or nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), prostaglandin E2 (PGE2), phospholipase A2 (PLA2), nuclear transcription factor-kappa B (NF-κB), leukotriene B4 (LTB4), cyclooxygenase- 1 (COX-1), and superoxide radicals. CONCLUSION: In conclusion, data suggest (approximately 98% of articles) that substances obtained from marine sponges may be promising for the development of novel anti-inflammatory drugs for the treatment of different pathological conditions.
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NF-kappa B , Poríferos , Animais , NF-kappa B/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Poríferos/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo , Óxido Nítrico/metabolismoRESUMO
Resumen Las estatinas son ampliamente utilizadas para el control de los niveles de colesterol en pacientes con hipercolesterolemia, lo cual permite prevenir enfermedades cardiovasculares. Además de controlar la síntesis endógena de colesterol, las estatinas tienen efectos pleiotrópicos diversos, como son las propiedades antiinflamatoria, antioxidante y de inmunomodulación. La enfermedad causada por el virus SARS-CoV-2 (COVID-19) provoca una tormenta de citocinas que contribuye a la generación del síndrome respiratorio agudo, que puede llevar a cuadros graves de esta enfermedad e incluso a la muerte del paciente. Diversos estudios realizados en enfermos con COVID-19 que recibieron estatinas, antes o durante el curso de la enfermedad, registraron cuadros menos graves, estancias hospitalarias más cortas y menor mortalidad. El beneficio de las estatinas en la COVID-19 debe ser explorado más ampliamente, ya que potencialmente pueden contribuir al control de esta pandemia que ha postrado a la humanidad.
Abstract Statins are widely used to control cholesterol levels in patients with hypercholesterolemia, which helps prevent cardiovascular diseases. In addition to controlling endogenous cholesterol synthesis, statins have diverse pleiotropic effects, such as anti-inflammatory, antioxidant, and immunomodulatory properties. The disease caused by the SARS-CoV-2 virus (COVID-19) causes a cytokine storm that contributes to the generation of acute respiratory syndrome, which can lead to severe symptoms of this disease and even the death of the patient. Various studies carried out on patients with COVID-19 who received statins, before or during the disease, registered less severe symptoms, shorter hospital stays and lower mortality. The benefit of statins in COVID-19 should be explored more widely, as they can potentially contribute to the control of this pandemic that has devastated humanity.
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The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.
Assuntos
Ácidos Graxos Ômega-3 , Hepatopatias , Humanos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Anti-Inflamatórios/uso terapêutico , Hepatopatias/metabolismo , Fenótipo , Mediadores da Inflamação/metabolismoRESUMO
COVID-19's severity has been associated with a possible imbalance in the cross-regulation of cytokines and vascular mediators. Since the beginning of the pandemic, kidney transplant recipients (KTRs) have been identified as patients of high vulnerability to more severe diseases. Thus, aiming to describe the patterns of cytokines and vascular mediators and to trace patients' differences according to their KTR status, this prospective study enrolled 67 COVID-19 patients (20 KTRs) and 29 non-COVID-19 controls before vaccination. A panel comprising 17 circulating cytokines and vascular mediators was run on samples collected at different time points. The cytokine and mediator patterns were investigated via principal component analysis (PCA) and correlation-based network (CBN). In both groups, compared to their respective controls, COVID-19 was associated with higher levels of cytokines and vascular mediators. Differentiating between the KTRs and non-KTRs, the number of correlations was much higher in the non-KTRs (44 vs. 14), and the node analysis showed the highest interactions of NGAL and sVCAM-1 in the non-KTRs and KTRs (9 vs. 4), respectively. In the PCA, while the non-KTRs with COVID-19 were differentiated from their controls in their IL-10, IFN-α, and TNF-α, this pattern was marked in the NGAL, sVCAM-1, and IL-8 of the KTRs.
Assuntos
COVID-19 , Transplante de Rim , Humanos , Citocinas , Estudos Prospectivos , Lipocalina-2 , TransplantadosRESUMO
Objective: Correlate inflammatory mediators and biochemical parameters in patients with active pulmonary tuberculosis (TB) treated at a public hospital in São Luís, MA. Methods: This is a case-control study of patients with a positive diagnosis of active pulmonary TB. Serum samples from patients and the control group were collected for the clinical trials, and epidemiological data were collected through medical records and interviews. The control group consisted of healthy volunteers with no previous contact with TB cases, matched by age and sex to the clinical group. To measure inflammatory cytokines, we used the Human IL-6 ELISA Set and Human IFN-γ ELISA Set kits. Oxidative stress was measured by quantification of thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO). In biochemistry, the levels of uric acid, antistreptolysin "O" (AEO), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), calcium, total cholesterol, gamma-glutamyl transferase (Gamma GT), glucose, alkaline phosphatase, high-density lipoprotein (HDL), C-reactive protein (CRP) and triglycerides were measured. Results: The clinical group consisted of 53 patients. There was a substantial decrease in IFN-γ (p<0.0001) and a significant increase in IL-6 (p<0.0001). TBARS production increased significantly (p= 0.0414). There was no significant difference in NO production (p= 0.3194). In biochemistry, there was a significant increase in ALT (p= 0.0072), AST (p= 0.0016), Gamma GT (p= 0.0011), alkaline phosphatase (p<0.0001), CRP (p<0. .0001) and triglycerides (p= 0.0343), and a significant decrease in calcium (p<0.0001). A significant positive correlation was found between IL-6 and IFN-γ (p= 0.0448), as well as AST and ALT (p<0.0001); CRP and gamma GT (p<0.0001); Gamma GT and ALT (p= 0.0016); Gamma GT and AST (p=0.0004); triglycerides and cholesterol (p= 0.0002); alkaline phosphatase and gamma GT (p<0.0001); CRP and alkaline phosphatase (p<0.0001); triglycerides and calcium (p= 0.0121); cholesterol and calcium (p= 0.0261); glucose and cholesterol (p= 0.0373); and triglycerides and glucose (p= 0.0127) in biochemistry, with a significant negative correlation between glucose and uric acid (p= 0.0092); and CRP and HDL (p=0.0037). The correlation between inflammatory mediators and biochemical markers was positive between IL-6 and gamma GT (p= 0.0011); IL-6 and CRP (p<0.0001); IL-6 and alkaline phosphatase (p=0.0076); and NO and triglycerides (p= 0.0016), and significant negative correlation between IFN-γ and cholesterol (p= 0.0171) and TBARS and cholesterol (p= 0.0138). Conclusion: Immunosuppression of IFN-γ activity was observed. A correlation was found between IL-6 and inflammatory biochemical markers, indicating damage and injury caused by M. tuberculosis (AU).
Objetivo: Correlacionar mediadores inflamatórios e parâmetros bioquímicos em pacientes com tuberculose (TB) pulmonar ativa atendidos em um hospital público, em São Luís, MA. Métodos: Trata-se um caso-controle de pacientes com diagnóstico positivo para TB pulmonar ativa. Amostras de soro dos pacientes e grupo controle foram coletadas para os experimentos clínicos e os dados epidemiológicos foram coletados por meio de prontuários e entrevistas. O grupo controle foi formado por voluntários saudáveis sem contato prévio com casos de TB, pareados com idade e sexo ao grupo clínico. Para dosar citocinas inflamatórias, utilizaram-se os kits Human IL-6 ELISA Set e Human IFN-γ ELISA Set. Mediu-se o estresse oxidativo pela quantificação das espécies reativas do ácido tiobarbitúrico (TBARS) e óxido nítrico (ON). Na bioquímica, mediram-se os níveis de ácido úrico, anti-estreptolisina-O (AEO), alanina aminotransferase (ALT), amilase, aspartato aminotransferase (AST), cálcio, colesterol total, gama glutamil transferase (Gama GT), glicose, fosfatase alcalina, lipoproteína de alta densidade (HDL), proteína C reativa (PCR) e triglicerídeos. A análise estatística foi realizada pelo software Graph Pad Prism 8, com p<0,05 significativo. Re -sultados: O grupo clínico foi formado por 53 pacientes. Houve uma diminuição significativa de IFN-γ (p<0,0001), e aumento significativo de IL-6 (p<0,0001). A produção de TBARS aumentou significativamente (p= 0,0414). Não houve diferença significativa na produção de ON (p= 0,3194). Na bioquímica, houve aumento significativo em ALT (p= 0,0072), AST (p= 0,0016), gama GT (p= 0,0011), fosfatase alcalina (p<0,0001), PCR (p<0,0001) e triglice-rídeos (p= 0,0343), e diminuição significativa de cálcio (p<0,0001). Encontrou-se correlação positiva significativa entre IL-6 e IFN-γ (p= 0,0448), assim como AST e ALT (p<0,0001); PCR e gama GT (p<0,0001); gama GT e ALT (p= 0,0016); gama GT e AST (p= 0,0004); triglicerídeos e colesterol (p= 0,0002); fosfatase alcalina e gama GT (p<0,0001); PCR e fosfatase alcalina (p<0,0001); triglicerídeos e cálcio (p= 0,0121); colesterol e cálcio (p= 0,0261); glicose e colesterol (p= 0,0373); e triglicerídeos e glicose (p= 0,0127) na bioquímica, sendo negativa significativa entre glicose e ácido úrico (p= 0,0092); e PCR e HDL (p= 0,0037). A correlação entre marcadores infla-matório e bioquímicos foi positiva entre IL-6 e gama GT (p= 0,0011); IL-6 e PCR (p<0,0001); IL-6 e fosfatase alcalina (p= 0,0076); e ON e triglicerídeos (p= 0,0016), e negativa significativa entre IFN-γ e colesterol (p= 0,0171) e TBARS e colesterol (p= 0,0138). Conclusões: Observou-se imunossupressão da atividade de IFN-γ. Encontrou-se correlação entre IL-6 e marcadores bioquímicos inflamatórios, indicando dano e lesão causados por M. tuberculosis (AU).