RESUMO
AIM: To investigate whether high-intensity interval training (HIIT) improves physical performance, systolic blood pressure, and markers of oxidative stress and inflammation in skeletal muscle of spontaneously hypertensive rats (SHR). METHODS: Nineteen male SHR rats were randomly assigned to two groups: sedentary (SHRC) and trained (SHR+T). The SHR+T group trained five times a week for eight weeks on a treadmill, while the SHR group remained without any exercise stimulus throughout the experimental period. Maximum physical performance and systolic blood pressure (SBP) were assessed before and after the training period. The following variables were measured in the tibialis anterior (TA) muscle: gene expression of the NADPH oxidase complex (NOX2, NOX4, p22phox, p47phox) and the NF-kB pathway (NF-kB and Ik-B), lipid peroxidation (malonaldehyde; MDA), protein carbonylation, hydrophilic antioxidant capacity (HAC) and pro-inflammatory cytokines (IL-6 and TNF-α). RESULTS: SHR+T rats showed higher physical performance and levels of IL-6, and lower SBP and protein carbonylation (p<0.05), compared with SHRC rats. No significant differences (p>0.05) were observed in the other variables. SIGNIFICANCE: Our results indicate that HIIT is an effective non-pharmacologic strategy to improve physical performance, reduce SBP, and modulate the skeletal muscle oxidative damage and inflammation in hypertensive rats.
Assuntos
Pressão Sanguínea , Treinamento Intervalado de Alta Intensidade , Músculo Esquelético , Estresse Oxidativo , Condicionamento Físico Animal , Ratos Endogâmicos SHR , Animais , Masculino , Músculo Esquelético/metabolismo , Treinamento Intervalado de Alta Intensidade/métodos , Ratos , Biomarcadores/metabolismo , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Inflamação/metabolismo , NF-kappa B/metabolismo , NADPH Oxidases/metabolismo , Interleucina-6/metabolismoRESUMO
Early diagnosis can be a beneficial factor for minimizing health risks related to multimorbidity. This study aims to assess the association of multimorbidity with interleukin 6 (IL-6), C-reactive protein (CRP), and adiponectin in 22-year-old participants of the Pelotas (Brazil) birth cohort. A total of 3,578 subjects had serum measurements of IL-6, CRP, and adiponectin at the 22-year-old visit. For multimorbidity evaluation, a list of 15 morbidities was used and divided into subgroups (cardiometabolic, pulmonary, allergic diseases, and mental disorders). The occurrence of ≥ 2 morbidities was higher in females (55.1%) than in males (45.2%). A negative association between multimorbidity and adiponectin was found in females, whereas positive associations between the number of diseases and IL-6 and CRP were observed in males. For both sexes, cardiometabolic problem was the morbidity most associated with the markers. The analysis for isolated diseases identified dyslipidemia was the only cardiometabolic condition associated with physiological markers. Our findings suggest an inverse association between multimorbidity and adiponectin in females, as well as a direct cumulative association between the number of diseases and IL-6 and CRP in males at a young age.
Assuntos
Adiponectina , Biomarcadores , Proteína C-Reativa , Interleucina-6 , Multimorbidade , Humanos , Masculino , Feminino , Brasil/epidemiologia , Adulto Jovem , Proteína C-Reativa/análise , Biomarcadores/sangue , Estudos Transversais , Interleucina-6/sangue , Adiponectina/sangue , Fatores Sexuais , Inflamação/sangue , Inflamação/epidemiologia , Fatores Socioeconômicos , Fatores de Risco , Estudos de Coortes , AdultoRESUMO
BACKGROUND: Vitamin D is beneficial for musculoskeletal health. Although low levels of vitamin D are linked to increased pain in knee osteoarthritis (OA), their association with functionality remains understudied. OBJECTIVE: This study aimed to investigate the association between vitamin D deficiency and functional status in elderly individuals with OA and explore the potential correlation between vitamin D deficiency and plasma levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). METHODS: The study included older adults (≥60 years) from an ageing study, encompassing 105 OA patients and 152 controls. OA diagnosis was confirmed radiographically, and the WOMAC questionnaire assessed functional impairment in these patients. Blood samples were collected to measure 25(OH) vitamin D levels by chemiluminescence and TNF-α and IL-6 levels by ELISA. RESULTS: Patients with vitamin D insufficiency/deficiency exhibited more severe cases of OA compared to those with normal vitamin D levels (p = 0.04). Vitamin D levels were inversely correlated with functional impairment in OA, according to the WOMAC Index (global: rS = -0.25, p = 0.01; pain: rS = -0.21, p = 0.03). Moreover, OA patients with vitamin D deficiency showed significantly higher levels of TNF-α and IL-6 (p < 0.05, Mann-Whitney test). CONCLUSIONS: Reduced levels of vitamin D are associated with more severe cases of hip and knee osteoarthritis, increased pain, greater functional impairment, and elevated serum levels of TNF-α and IL-6. Further research is required to elucidate the mechanisms underlying the influence of vitamin D on osteoarthritis and to evaluate the potential benefits of vitamin D supplementation for mitigating disease symptoms and progression.
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Interleucina-6 , Osteoartrite do Quadril , Osteoartrite do Joelho , Fator de Necrose Tumoral alfa , Deficiência de Vitamina D , Vitamina D , Humanos , Osteoartrite do Joelho/sangue , Feminino , Idoso , Masculino , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Vitamina D/análogos & derivados , Osteoartrite do Quadril/sangue , Osteoartrite do Quadril/complicações , Fator de Necrose Tumoral alfa/sangue , Interleucina-6/sangue , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Dor/sangue , Dor/etiologia , Estudos de Casos e Controles , Idoso de 80 Anos ou maisRESUMO
Erythema nodosum leprosum (ENL), an inflammatory reaction in leprosy, causes painful nodules, fever, and malaise due to immune system activation. Thalidomide is an effective treatment, although associated with important adverse effects. We aimed to evaluate the association of genetic variants in genes encoding tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) with the response to treatment of ENL with thalidomide. 148 patients from the South and Northeast regions of Brazil were included. Genomic DNA was isolated from blood and/or saliva samples using commercial kits, and genetic variants in TNF, IL6, IL1ß, and IFNγ genes were genotyped by TaqMan system. We identified an association between polymorphisms in TNF (rs1799964C, rs1800630A, rs1799724T and rs1800629A) IL1ß (rs4848306G, rs1143623G, rs16944A, and rs1143627A), IL6 (rs2069840C and rs2069845G) and IFNγ (rs2430561T) with thalidomide dose variation in a time-dependent manner. Associations of IL6 and TNF haplotypes with thalidomide dosage variation over the time of treatment were also observed. Polymorphisms in TNF, IL6, IL1ß, and IFNγ genes may modulate their expression levels, potentially impacting the required dosage of thalidomide in the treatment of ENL. Our findings should be confirmed in further studies to estimate the size effect of these polymorphisms on ENL treatment with thalidomide.
Assuntos
Eritema Nodoso , Interferon gama , Interleucina-1beta , Interleucina-6 , Hanseníase Virchowiana , Talidomida , Fator de Necrose Tumoral alfa , Humanos , Talidomida/uso terapêutico , Eritema Nodoso/tratamento farmacológico , Eritema Nodoso/genética , Brasil , Feminino , Masculino , Adulto , Interleucina-1beta/genética , Interferon gama/genética , Pessoa de Meia-Idade , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/genética , Fator de Necrose Tumoral alfa/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Genótipo , Hansenostáticos/uso terapêutico , AdolescenteRESUMO
BACKGROUND: The caterpillar of Premolis semirufa, known as Pararama, is found in the Brazilian Amazon, primarily on rubber trees of the genus Hevea. Pararamosis is an inflammatory disease resulting from accidental contact with the caterpillar's bristles, leading to acute and chronic symptoms. Chronic exposure can cause significant osteoarticular deformities, similar to those seen in osteoarthritis and rheumatoid arthritis, due to cartilage degradation and synovial inflammation. Currently, there are no specific treatments for Pararamosis, and research on the molecular mechanisms of the caterpillar's venom and its role in disease pathogenesis is limited. The chronic changes in Pararamosis are thought to be linked to chondrocyte activation and the NF-κB signaling pathway, influenced by the toxic components in the bristles. Understanding these interactions is crucial for developing preventive measures and therapeutic strategies, especially for rubber tappers at risk in the Amazon region. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated the effects of P. semirufa bristle extracts on human chondrocytes, focusing on the activation mechanism of the NF-κB transcription factor and the expression of osteoarthritis markers. Cell viability tests indicated that the extracts did not significantly affect chondrocyte survival. However, supernatant analysis revealed a time- and dose-dependent increase in IL-6 and IL-8 levels. Additionally, the expression of NF-κB and its inhibitor, IκB, was assessed, showing higher levels of phosphorylated IκB, which induces its proteosomal degradation, compared to the negative control, while native IκB expression was greater in the control group. Furthermore, the gene expression profile of treated chondrocytes demonstrated modulation in matrix metalloproteinases (MMPs), aggrecan (ACAN), collagen type II (COL2A1), interleukins (IL6 and IL8), and complement system molecules. CONCLUSIONS/SIGNIFICANCE: These findings highlight the significant impact of P. semirufa bristle extracts on human chondrocyte activation and the inflammatory processes associated with pararamosis.
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Condrócitos , NF-kappa B , Humanos , Condrócitos/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Inflamação , Venenos de Artrópodes/toxicidade , Venenos de Artrópodes/química , Interleucina-8/metabolismo , Interleucina-8/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Brasil , Osteoartrite/tratamento farmacológicoRESUMO
BACKGROUND: Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes-particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU). METHODS: We conducted a single-center, prospective study involving 56 unvaccinated COVID-19 patients admitted to the ICU. Plasma cytokine levels at admission were quantified using enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as median (IQR), and categorical variables as frequencies and percentages. Non-parametric tests assessed group differences. Logistic regression and receiver operating characteristic (ROC) curve analyses identified predictors of mortality, with bootstrapping (1000 re-samplings; 95 % BCa CI) applied for model validation. RESULTS: Deceased patients exhibited significantly higher levels of interleukin (IL)-1ß, IL-2, IL-6, transforming growth factor (TGF)-ß, and interferon (IFN)-γ compared to survivors. Conversely, IL-10 and IL-27 were associated with favorable outcomes. Logistic regression modeling identified elevated IL-2 and IFN-γ levels as significant predictors of mortality. Notably, individual ROC curve analyses demonstrated that IL-1ß and TGF-ß had excellent discriminatory ability for mortality, while IFN-γ, IL-2, and IL-27 showed very good to excellent discriminatory capacity. CONCLUSION: Our results indicate that distinct cytokine profiles differentiate survivors from non-survivors in critically ill, unvaccinated COVID-19 patients. These findings highlight the importance of cytokine dysregulation in severe COVID-19 cases and suggest potential targets for prognostic approaches. Further research is warranted to validate these results and translate them into effective clinical management strategies.
Assuntos
COVID-19 , Estado Terminal , Citocinas , Unidades de Terapia Intensiva , SARS-CoV-2 , Humanos , COVID-19/sangue , COVID-19/mortalidade , COVID-19/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Citocinas/sangue , Estudos Prospectivos , Idoso , Curva ROC , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-6/sangueRESUMO
Glioblastomas (GBM) are malignant tumours with poor prognosis. Treatment involves chemotherapy and/or radiotherapy; however, there is currently no standard treatment for recurrence, and prognosis remains unfavourable. Inflammatory mediators and microRNAs (miRNAs) influence the aggressiveness of GBM, being involved in the communication with the cells of the tumour parenchyma, including microglia/macrophages, and maintaining an immunosuppressive microenvironment. Hence, the modulation of miRNAs and inflammatory factors may improve GBM treatments. In this study, we investigated the effects of agathisflavone, a biflavonoid purified from Cenostigma pyramidale (Tul.), on the growth and migration of GBM cells, on the expression of inflammatory cytokines and microRNAs, as well on the response of microglia. Agathisflavone (5-30 µM) induced a dose- and time-dependent reduction in the viability of both human GL-15 and rat C6 cells, as determined by the MTT test, and reduced cell migration, as determined by cell scratch assay. RT-qPCR analysis revealed that agathisflavone (5 µM) down-regulated the expression of miR-125b and miR-155 in the secretome derived from GL-15 cells, which was associated with upregulation of the mRNA expression of IL-6 and arginase-1 immunoregulatory factors. Exposure of human microglia/macrophage to the secretome from GL-15 GMB cells modulated proliferation and morphology, effects that were modulated by agathisflavone treatment. These results demonstrate the effect of flavonoids on the growth of GBM cells, which impacts cells in the microenvironment and can be considered for preclinical studies for adjuvant treatments.
Assuntos
Arginase , Biflavonoides , Sobrevivência Celular , Glioblastoma , Interleucina-6 , MicroRNAs , Microglia , MicroRNAs/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Humanos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Arginase/genética , Arginase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ratos , Interleucina-6/metabolismo , Interleucina-6/genética , Biflavonoides/farmacologia , Linhagem Celular Tumoral , Animais , Ativação de Macrófagos/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proliferação de Células/efeitos dos fármacosRESUMO
Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, heightened chemosensory discharges of the carotid body (CB), which contributes to potentiate the ventilatory hypoxic response and elicits hypertension. We aimed to determine 1) whether the persistence of cardiorespiratory alterations found in long-term CIH depends on the inputs from the CB and 2) in what extension the activation of glial cells and neuroinflammation in the caudal region of the nucleus of the solitary tract (NTS) require functional CB chemosensory activity. To evaluate these hypotheses, we exposed male mice to CIH for 60 days. At 50 days of CIH, CBs were denervated and animals were kept in CIH for 10 additional days. At the end of the experiments, we measured arterial blood pressure, breathing regularity, and hypoxic ventilatory response (HVR) and assessed astrocyte and microglia cell activation. Compared to sham treatment, CIH induced hypertension [mean arterial blood pressure (MABP): 83.47 ± 1.39 vs. 95.00 ± 2.18 mmHg] and disordered breathing [irregularity score (IS): 7.77 ± 0.49 vs. 12.56 ± 1.66], increased the HVR [1.69 ± 0.17 vs. 4.31 ± 0.87 change in minute ventilation (ΔVÌe)/min], and produced an early transient activation of astrocytes followed by a late and persistent activation of microglia in the NTS. In addition, CIH increased IL-1ß, IL-6, and TNF-α levels in the NTS. Bilateral CB denervation after 50 days of CIH results in the restoration of normal glial cell activation in the NTS, lower levels of IL-6 and TNF-α, and reductions in arterial blood pressure (83.47 ± 1.38 mmHg) and HVR (1.63 ± 0.43 ΔVÌe/min). The present results suggest that CB inputs to the NTS during long-term CIH contribute to maintain the cardiorespiratory alterations and the formation of a neuroinflammatory niche at the NTS by modifying glial cell activity.NEW & NOTEWORTHY Chronic intermittent hypoxia (CIH), a feature of obstructive sleep apnea, causes cardiorespiratory alterations (i.e. hypertension) linked to oxidative stress, inflammation, and sympathoexcitation. In the present study, we highlight the role of enhanced carotid body (CB) chemosensory afferent discharges to the nucleus of the solitary tract (NTS) in long-term CIH-induced cardiorespiratory disorders. Indeed, we provide evidence that supports the notion that increased CB afferent activity contributes to persistent CIH-induced hypertension, likely triggering neuroinflammation in the NTS.
Assuntos
Corpo Carotídeo , Hipóxia , Neuroglia , Doenças Neuroinflamatórias , Núcleo Solitário , Animais , Corpo Carotídeo/metabolismo , Corpo Carotídeo/patologia , Corpo Carotídeo/fisiopatologia , Núcleo Solitário/metabolismo , Núcleo Solitário/patologia , Núcleo Solitário/fisiopatologia , Hipóxia/fisiopatologia , Hipóxia/metabolismo , Hipóxia/complicações , Masculino , Camundongos , Neuroglia/metabolismo , Neuroglia/patologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/fisiopatologia , Camundongos Endogâmicos C57BL , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/patologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertensão/patologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Microglia/metabolismo , Microglia/patologia , Pressão SanguíneaRESUMO
BACKGROUND: The therapeutic targeting of the intestinal microbiota has gained increasing attention as a promising avenue for addressing mood disorders. This study aimed to assess the potential effect of supplementing standard pharmacological treatment with the probiotic kefir in patients with Major Depressive Disorder (MDD). METHODS: Thirty-eight female participants diagnosed with moderate MDD by the Hamilton Rating Scale for Depression (HAM-D) were selected to receive the probiotic kefir in conjunction with antidepressant therapy for 12 weeks. The participants were evaluated at baseline (T0) and 90 days after probiotic kefir supplementation (T90). HAM-D scores and blood samples were collected at both time points. RESULTS: Probiotic supplementation significantly reduced MDD severity, as evidenced by lower HAM-D scores compared to baseline. Probiotic consumption for 90 days also significantly decreased interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels compared to baseline. However, probiotic kefir supplementation did not significantly affect serum serotonin levels. Additionally, after 90 days of probiotic consumption, insulin and morning cortisol levels were significantly reduced. In contrast, no significant changes were observed in serum levels of prolactin, vitamin D, and afternoon cortisol. CONCLUSION: This study provides valuable insights into the potential benefits of probiotics, specifically kefir, as adjunctive therapy for female patients with MDD. The findings highlight promising results in ameliorating depressive symptoms and modulating inflammatory and hormonal markers.
Assuntos
Antidepressivos , Transtorno Depressivo Maior , Probióticos , Humanos , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Feminino , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/tratamento farmacológico , Adulto , Antidepressivos/uso terapêutico , Pessoa de Meia-Idade , Kefir , Proteína C-Reativa/metabolismo , Resultado do Tratamento , Interleucina-6/sangue , Hidrocortisona/sangue , Serotonina/sangue , Serotonina/metabolismo , Escalas de Graduação PsiquiátricaRESUMO
INTRODUCTION: Persistent elevation of biomarkers associated with endothelial dysfunction in convalescent COVID-19 patients has been linked to an increased risk of long-term cardiovascular complications, including long COVID syndrome. Sulodexide, known for its vascular endothelial affinity, has demonstrated pleiotropic protective properties. This study aims to evaluate the impact of sulodexide on serum levels of endothelial dysfunction biomarkers in patients during the convalescent phase of COVID-19. METHODS: We conducted a double-blind, single-center, randomized, placebo-controlled trial in Mexico, comparing sulodexide (250 LRU orally, twice daily) with placebo over 8 weeks in adult patients during early COVID-19 convalescence. Differences in serum biomarkers between the groups were analyzed using repeated measures and post hoc tests, with Thrombomodulin (TM) as the primary endpoint. RESULTS: Among 206 analyzed patients (103 in each group), at week 8, the sulodexide group exhibited significantly lower mean levels of Thrombomodulin (TM) (25.2 ± 7.9â ng/mL vs 29.9 ± 14.7â ng/mL, P = .03), von Willebrand Factor (vWF) (232 ± 131 U/dL vs 266 ± 122 U/dL, P = .02) and Interleukin-6 (IL-6) (12.5 ± 13.2 pg/mL vs 16.2 ± 16.5 pg/mL, P = .03) compared to the placebo group. D-dimer and C reactive protein (CRP) in the sulodexide group were also lowered. No significant differences were observed for P-selectin, fibrinogen, VCAM-1, or ICAM-1 levels. CONCLUSIONS: Patients in the convalescent phase of COVID-19 who received sulodexide for eight weeks showed a reduction in TM, vWF, D-dimer, CRP, and IL-6 serum levels compared to placebo. These findings suggest a potential protective effect of sulodexide against thromboinflammation and endothelial damage.
Assuntos
Biomarcadores , Tratamento Farmacológico da COVID-19 , COVID-19 , Endotélio Vascular , Glicosaminoglicanos , Trombomodulina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Convalescença , COVID-19/sangue , COVID-19/complicações , Método Duplo-Cego , Regulação para Baixo , Endotélio Vascular/efeitos dos fármacos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Glicosaminoglicanos/uso terapêutico , Interleucina-6/sangue , México , Trombomodulina/sangueRESUMO
PURPOSE: Individuals in occupational environments are particularly susceptible to the impacts of pollutants; making it crucial to assess systemic inflammation markers. The study aimed to evaluate the immune response to inflammation through the assessment of a cytokine profile in individuals working in vulnerable conditions exposed to heavy metals. METHODS: A total of 137 adults participated in this study from three work environments: brickyards, waste scavenging and quarries. Levels of 12 metals were evaluated in urine using inductively coupled plasma mass spectrometry (ICP-MS), and serum levels of 6 cytokines were analyzed using Multi-Bead Cytokine Assay. RESULTS: In the brickyard scenario, a significant percentage of subjects presented concentrations above the reference levels of Hg, As, and Pb (83.7%, 62.8%, and 16.3%; respectively). The waste scavenging and quarry workers scenario exhibited percentages of 100% and 49% for Ni, respectively. Additionally, the brickyard and waste scavenging scenarios showed the highest levels of TNF-α and INF-γ and, lower levels of IL-4 and IL-10. In the quarry scenario, an increase of IL-6 and a decrease in INF-γ were observed. Furthermore, a clustering pattern based on the type of scenario was identified, indicating a higher exposure to As, Pb, and Hg in the brickyard scenario, along with TNF-α, IL-4, and IL-10 levels. CONCLUSIONS: The results suggest that exposure to heavy metals in workers with precarious work conditions, present elevated levels of inflammatory cytokines, which are related to the type of occupational environment.
Assuntos
Citocinas , Metais Pesados , Exposição Ocupacional , Humanos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Metais Pesados/urina , Metais Pesados/sangue , Adulto , Citocinas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Chumbo/sangue , Interleucina-10/sangue , Fator de Necrose Tumoral alfa/sangue , Inflamação/sangue , Inflamação/induzido quimicamente , Arsênio/urina , Arsênio/sangue , Interleucina-4/sangue , Interferon gama/sangue , Interleucina-6/sangue , Biomarcadores/sangue , Biomarcadores/urina , Mercúrio/urina , Mercúrio/sangue , Níquel/urina , Níquel/sangueRESUMO
OBJECTIVE: Submandibular salivary gland inflammation has been suggested as one of the mechanisms underlying impaired salivary secretion associated with sleep deprivation (SD). However, whether the salivary inflammatory response occurs to the same extent in paradoxical sleep deprivation with or without sleep recovery remains unknown. This study evaluated the extent to which inflammation influences salivary impairments associated with paradoxical sleep deprivation with or without sleep recovery. METHODOLOGY: Male Wistar rats were randomly assigned into three groups as control, partial SD (PSD) with sleep recovery for four hours a day and total SD (TSD). Paradoxical SD was carried out for seven days in the SD groups, after which saliva, blood, and submandibular gland samples were taken. Levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and nitrite were determined in saliva, serum, and the submandibular salivary gland. Leucocyte count and neutrophil-lymphocyte ratio were determined in all groups. One-way ANOVA and the Tukey's post hoc tests were used for data analysis. P-values < 0.05 were considered statistically significant. RESULTS: Levels of TNF-α, IL-6, and nitrite in the submandibular salivary glands were significantly higher in the TSD groups (p=0.04,p<0.001, p=0.03, respectively) than in the control. Saliva level of TNF-α was higher in the PSD and TSD groups (p=0.003 and p=0.01 respectively) than in the control. Neutrophil-lymphocyte ratio was significantly higher in both PSD and TSD groups than in the control (p<0.01 for both). CONCLUSION: While total SD produced higher inflammatory response in the submandibular salivary gland, four-hour sleep recovery ameliorated this impact. This finding suggests that sleep recovery is crucial to improve inflammatory salivary gland dysfunction induced by sleep deprivation.
Assuntos
Interleucina-6 , Distribuição Aleatória , Ratos Wistar , Saliva , Privação do Sono , Glândula Submandibular , Fator de Necrose Tumoral alfa , Animais , Masculino , Privação do Sono/fisiopatologia , Privação do Sono/complicações , Glândula Submandibular/fisiopatologia , Saliva/química , Interleucina-6/análise , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue , Fatores de Tempo , Nitritos/análise , Nitritos/sangue , Análise de Variância , Contagem de Leucócitos , Valores de Referência , Reprodutibilidade dos Testes , Sialadenite/fisiopatologia , Sialadenite/etiologia , RatosRESUMO
Intermittent hemodialysis (IH) is an important therapy in the context of kidney dysfunction in dogs. However, its impact on pro-inflammatory cytokines is unclear. This study assessed IL-1ß, IL-6, and TNF-α serum concentrations in dogs with chronic kidney disease (CKD) undergoing one session of IH without bypass (IH group, n = 4) and with bypass (IH + bypass group, n = 4). The control group (CG) included four healthy dogs. Cytokine levels were measured before, during, and after the first IH session. Comparative analyses of each cytokine within each group and time point were performed, along with a global comparison between groups. No significant changes were observed in cytokines across evaluation times in the IH groups. IL-1ß was significantly higher post-session in the IH and IH + bypass groups compared to CG. Globally, IL-1ß and TNF-α concentrations were significantly higher in the IH (11.41 pg/mL (10-16.17) and 2 pg/mL (2-88.54), respectively) and IH + bypass groups (10 pg/mL (10-10) and 2 pg/mL (2-215.5), respectively) compared to CG (0.96 pg/mL (0-3.56) and 0 pg/mL (0-0.003), respectively). The IH group also showed elevated IL-6 concentration (0.1 ng/mL (0.1-0.5)) compared to CG (0 ng/mL (0-0.1)). Higher IL-1ß and IL-6 concentrations were observed in the IH group (11.41 pg/mL (10-16.17) and 0.1 ng/mL (0.1-0.1), respectively) compared to the IH + bypass group (10 pg/mL (10-10) and 0.1 ng/mL (0.1-0.5), respectively). In conclusion, a single IH session, with or without bypass, did not increase pro-inflammatory cytokines in CKD dogs with uremic syndrome but maintained the inflammatory state. Dogs undergoing IH without bypass may receive a stronger stimulus for cytokine release.
Assuntos
Doenças do Cão , Interleucina-1beta , Interleucina-6 , Diálise Renal , Insuficiência Renal Crônica , Fator de Necrose Tumoral alfa , Uremia , Animais , Cães , Insuficiência Renal Crônica/veterinária , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Interleucina-1beta/sangue , Doenças do Cão/sangue , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Diálise Renal/veterinária , Masculino , Uremia/veterinária , Uremia/sangue , Uremia/terapia , FemininoRESUMO
Galectin-3 (Gal-3) is a ß-galactoside-binding lectin expressed in cells of the placental microenvironment. This lectin is involved in various biological processes, such as modulation of the immune system and control of parasitic illness. Toxoplasma gondii infection can lead to congenital transmission and cause miscarriages, prematurity and fetal anomalies. However, little is known about the role of Gal-3 in T. gondii infection in the placental microenvironment. This study aimed to unravel the underlying mechanisms of Gal-3 during T. gondii infection. For this purpose, we promoted the knockdown of Gal-3 expression by using RNA interference (RNAi) in BeWo cells or by using a synthetic inhibitor (GB1107) in human villous explants. We showed that the decreased Gal-3 expression in BeWo cells and human villous explants increases the invasion and proliferation of T. gondii probably by downregulating MIF and IL6 levels, highlighting thus the role of this lectin in modulating the immune response. Collectively, our study reveals Gal-3 as a promising target protein during congenital toxoplasmosis.
Assuntos
Galectina 3 , Interleucina-6 , Fatores Inibidores da Migração de Macrófagos , Toxoplasma , Trofoblastos , Humanos , Galectina 3/metabolismo , Galectina 3/genética , Trofoblastos/parasitologia , Trofoblastos/metabolismo , Feminino , Fatores Inibidores da Migração de Macrófagos/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Interleucina-6/metabolismo , Gravidez , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia , Galectinas/metabolismo , Galectinas/genética , Linhagem Celular , Placenta/parasitologia , Placenta/metabolismo , Interferência de RNA , Técnicas de Silenciamento de Genes , Proteínas Sanguíneas , Oxirredutases IntramolecularesRESUMO
Obstructive sleep apnea (OSA) causes intermittent hypoxia, increased production of reactive oxygen species, and inflammation, which may elevate morbidity and mortality from cardiovascular disease. The objective of the present study was to investigate the effect of the intraoral appliance (IOA) as a treatment for OSA when it comes to the modulation of inflammatory markers and oxidative damage in elderly individuals. This "before and after" clinical trial included 9 patients diagnosed with OSA recruited from a multicenter randomized clinical trial study that evaluated the treatment with IOA for 60 days. Demographic and anthropometric variables, apnea and hypopnea index (AHI), and oxygen desaturation index (ODI) were collected by type III polysomnography, Epworth Sleepiness Scale, and inflammatory and oxidative damage markers (interleukin 6 (1L-6); tumor necrosis factor α (TNF-α); interleukin 10 (IL-10); thiobarbituric acid reactive substances (TBARS); total thiols; advanced oxidation protein products (AOPP), and nitric oxide (NO)). Shapiro-Wilk test, paired t-test and Pearson's correlation tests were used to analyze the results, respectively (α=0.05). The sample had a mean age of 71.86 ± 4.63 years, the majority were women (55.55%), and had a significant reduction in AHI (p=0.003), ODI (p=0.038), IL-10 (p=0.0001), AOPP (p=0.038) and TBARS levels (p=0.0001). There was a significant correlation between IL-10 and NO (r=0.855) and between TBARS and IL-6 (r=0.669), both after treatment. This study demonstrated that treating elderly patients with OSA using an IOA for 60 days reduces oxidative damage through the modulation of AOPP and TBARS.
Assuntos
Biomarcadores , Estresse Oxidativo , Polissonografia , Apneia Obstrutiva do Sono , Substâncias Reativas com Ácido Tiobarbitúrico , Humanos , Feminino , Masculino , Idoso , Biomarcadores/análise , Apneia Obstrutiva do Sono/terapia , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Resultado do Tratamento , Valores de Referência , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue , Interleucina-6/análise , Interleucina-6/sangue , Interleucina-10/análise , Interleucina-10/sangue , Óxido Nítrico/análise , Produtos da Oxidação Avançada de Proteínas/sangue , Produtos da Oxidação Avançada de Proteínas/análise , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fatores de Tempo , Inflamação , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/sangueRESUMO
This study aimed to evaluate the pulp response to F18 and cobalt-doped F18 bioglass (F18Co) in comparison with calcium hydroxide (CH) after pulp capping. The maxillary first molars of 48 rats were divided into F18, F18Co, CH, and control (no intervention) groups. The pulp was exposed, the materials were placed, and the teeth were capped. After 7 and 15 days, the animals were euthanized for pulp evaluation and interleukin (IL) expression determination. Statistical analysis was carried out using the SigmaPlot® program (Systat Software Inc., for Windows, version 12.0). The data obtained in the analyses were subjected to the non-parametric Kruskal-Wallis test, followed by Dunn's test. For all tests, statistical significance was set at p < 0.05. The CH group exhibited mild to moderate inflammation, whereas the bioglass groups displayed moderate to severe inflammation, indicating a notable difference between the control and bioglass groups. At 7 days, both the CH and most of the bioglass specimens showed moderate disorganization. On day 15, CH displayed mildto-moderate disorganization, whereas F18 and F18Co exhibited significantly more moderate-to-severe disorganization. There were no significant differences in IL-6 and IL-10 expressions between groups at 7 days, but a noteworthy increase in IL-1ß was observed in both CH and F18. After 15 days, there was a greater expression of IL-6 and IL-1ß in the bioglass groups. No significant IL-10 expression was observed. Bioglass performed less effectively than CH when in direct contact with the pulp tissue.
Assuntos
Hidróxido de Cálcio , Cerâmica , Capeamento da Polpa Dentária , Polpa Dentária , Interleucina-10 , Interleucina-1beta , Interleucina-6 , Animais , Polpa Dentária/efeitos dos fármacos , Interleucina-1beta/análise , Hidróxido de Cálcio/farmacologia , Interleucina-10/análise , Interleucina-6/análise , Fatores de Tempo , Capeamento da Polpa Dentária/métodos , Masculino , Ratos Wistar , Reprodutibilidade dos Testes , Teste de Materiais , Estatísticas não Paramétricas , Resultado do Tratamento , Interleucinas/análise , Agentes de Capeamento da Polpa Dentária e Pulpectomia/farmacologia , Agentes de Capeamento da Polpa Dentária e Pulpectomia/uso terapêutico , Ratos , Valores de ReferênciaRESUMO
OBJECTIVE: In this study, the localization of tumor necrosis factor alpha (TNF-α) and interleukin (IL) -6 in the umbilical cord tissue of pregnant women with preeclampsia who smoke and in those who do not smoke was investigated using immunohistochemical methods. METHODS: The sample groups consisted of a control group, cigarette smokers, preeclampsia, and cigarette smokers with preeclampsia. Histological and immunohistochemical methods were applied to the tissue samples. RESULTS: It was determined that there were varying degrees of edemato s change in the layers of arteries and veins in the preeclampsia and the cigarette smokers with preeclampsia groups, with a statistically significant level of difference in thickness compared to the other groups. In addition, different levels of TNF α and IL-6 immunoreactivity were detected in the umbilical cord tissue across all the groups. In the preeclampsia group, TNF-α immunoreactivity was found to increase in the arterial muscle layer. Moreover, IL-6 immunoreactivity was found to decrease in the arterial endothelium and muscle layers in the cigarette smokers, preeclampsia, and cigarette smokers with preeclampsia groups and increase in the venous endothelium and muscle layers. In addition, immunoreactivity increased in the amniotic epithelium in the cigarette smokers with preeclampsia group. DISCUSSION: In conclusion, the differences in cytokine levels between the cigarette smokers, preeclampsia, and cigarette smokers with preeclampsia groups were thought to be caused by responses of the maternal immune system and histopathological changes in the umbilical cord tissue.
Assuntos
Interleucina-6 , Pré-Eclâmpsia , Fator de Necrose Tumoral alfa , Cordão Umbilical , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Adulto , Cordão Umbilical/patologia , Cordão Umbilical/metabolismo , Fumantes , Adulto Jovem , não Fumantes , Fumar/metabolismo , Imuno-HistoquímicaRESUMO
BACKGROUND: Plasmodium vivax infection, when it occurs during pregnancy, has often been associated with serious adverse pregnancy outcomes. However, immunological alterations in pregnancy and their consequences have been little explored. We characterized the humoral immune response in pregnant women exposed to malaria by P. vivax antigens and its association with the maternal inflammatory profile and poor pregnancy outcomes. METHODS: An observational cohort study in the Brazilian Amazon was conducted between 2013 and 2015. After applying exclusion criteria, 242 mother-child pairs were included in the analysis. Data on maternal infection, gestational outcomes, and inflammatory factors were evaluated in the maternal peripheral plasma. In samples from the first infection, the presence of total IgG and its subclasses in plasma against PvMSP119 protein were also quantified. RESULTS: Previous exposure to malaria, observed by anti-total IgG antibodies to the PvMSP119 antigen, increased the inflammatory response to infection when the pregnant woman had malaria during pregnancy. IL-6 and IL-10 levels were positively correlated with parasitemia and with total IgG levels; but they were negatively correlated with the gestational age at delivery from Pv-infected woman. In multivariate linear regression analyses, IgG 1, 2 and 4 was negatively and positively associated with cytokines IL-6 and IL-10, respectively, in P. vivax-infection. CONCLUSIONS: An association between the humoral immune response and the peripheral inflammatory cytokine profile with the adverse outcomes in malaria in pregnancy by P. vivax was observed. Previous exposure to the parasite can influence the IL-6 and IL-10 response, which is associated with increased parasitemia, reduced maternal weight gain and premature delivery.
Assuntos
Anticorpos Antiprotozoários , Imunidade Humoral , Imunoglobulina G , Malária Vivax , Plasmodium vivax , Humanos , Feminino , Gravidez , Malária Vivax/imunologia , Malária Vivax/parasitologia , Adulto , Plasmodium vivax/imunologia , Brasil/epidemiologia , Imunoglobulina G/sangue , Adulto Jovem , Anticorpos Antiprotozoários/sangue , Estudos de Coortes , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/parasitologia , Interleucina-10/sangue , Resultado da Gravidez , Inflamação/imunologia , Inflamação/sangue , Interleucina-6/sangue , Interleucina-6/imunologia , AdolescenteRESUMO
BACKGROUND: Aging is characterized by a decline in the cardiovascular hemodynamic response, which may be aggravated by undernutrition. However, no study has evaluated whether low caloric intake may affect cardiovascular hemodynamics and its possible relation with functional capacity and immune response in older adults. METHODS: Sixty-one older adults of both genders were enrolled in this study and were classified as normocaloric (n = 18) and hypocaloric (n = 43). All volunteers were evaluated for cardiovascular hemodynamics using impedance cardiography (PhysioFlow®); functional capacity by the 1' sit-to-stand test with SpO2 monitoring; whole-blood analysis using an automated hematocytometer (Sysmex®); and levels of IL-6, TNF-alpha, IL-10, and Klotho by ELISA. RESULTS: The hypocaloric group presented impaired functional capacity, measured by a reduced number of sit-to-stand repetitions (p < 0.0251) and impaired delta of SpO2 (p < 0.0307). In contrast, the hypocaloric group presented an improved stroke volume (p < 0.0352), systemic vascular resistance (p < 0.0075), and systemic vascular resistance index (p < 0.0184). In addition, no changes were observed in the whole-blood analysis (p > 0.05) or for IL-6 (p > 0.05), TNF-alpha (p < 0.05), IL-10 (p < 0.05), and Klotho (p > 0.05). CONCLUSIONS: A long-term hypocaloric diet in eutrophic older adults' resulted in an enhanced cardiovascular hemodynamic response but was associated with reduced functional capacity without changes in the immune response.
Assuntos
Hemodinâmica , Humanos , Masculino , Feminino , Idoso , Restrição Calórica , Comportamento Sedentário , Interleucina-10/sangue , Interleucina-6/sangue , Proteínas Klotho , Ingestão de Energia , Glucuronidase/sangue , Pessoa de Meia-Idade , Resistência Vascular , Doenças Cardiovasculares/prevenção & controle , Envelhecimento/fisiologia , Fator de Necrose Tumoral alfa/sangueRESUMO
CD155, also known as the poliovirus receptor (PVR), is a crucial molecule in the development and progression of cancer, as its overexpression favors immune evasion and resistance to immunotherapy. However, little is known about the mechanisms that regulate its overexpression. Proinflammatory factors produced by various cellular components of the tumor microenvironment (TME) have been associated with CD155 expression. We analyzed the effect of interleukin (IL)-6 on CD155 expression in lung adenocarcinoma. We found a positive relationship between mRNA and protein levels. This correlation was also observed in bioinformatics analysis and in biopsies and serum from patients with lung adenocarcinoma. Interestingly, lung adenocarcinoma cell lines expressing suppressor of cytokine signaling 1 (SOCS1) did not show increased CD155 levels upon IL-6 stimulation, and SOCS1 silencing reverted this effect. IL-6 and SOCS1 are critical regulators of CD155 expression in lung adenocarcinoma. Further basic and clinical studies are needed to define the role of these molecules during tumor development and to improve their clinical impact as biomarkers and targets for predicting the efficacy of immunotherapies. This study deepens the understanding of the intricate regulation of the immune checkpoints mediated by soluble factors and allows us to devise new ways to combine conventional treatments with the most innovative anticancer options.