RESUMO
BACKGROUND: Oral cancer (OC) is a common malignancy in clinical practice. Saliva testing is a convenient and noninvasive early diagnostic technique for OC. Several salivary cytokines have been identified as potential biomarkers for OC, including IL-8, IL-6, TNF-α, IL-1ß, and IL-10. Nonetheless, the optimal cytokine for OC diagnosis remains inconclusive and highly contentious. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively retrieved to collect all case-control studies on OC. A meta-analysis was performed to compare the levels of salivary IL-8, IL-6, IL-10, TNF-α, and IL-1ß in OC patients and healthy controls. Network meta-analysis (NMA) was carried out to probe into the accuracy of these salivary cytokines in diagnosing OC. RESULTS: This analysis included 40 studies, encompassing 1280 individuals with OC and 1254 healthy controls. Significantly higher levels of salivary IL-8, IL-6, TNF-α, IL-1ß, and IL-10 were observed in patients with OC in comparison to healthy controls. The results of NMA showed that TNF-α had the highest diagnostic accuracy for OC, with a sensitivity of 79% and a specificity of 92%, followed by IL-6 (sensitivity: 75%, specificity: 86%) and IL-8 (sensitivity: 80%, specificity: 80%). CONCLUSION: This study suggests that IL-8, IL-6, IL-10, TNF-α, and IL-1ß may be potential diagnostic biomarkers for OC. Among them, TNF-α, IL-6, and IL-8 are highly accurate in the diagnosis of OC. Nevertheless, further studies that eliminate other confounding factors are warranted, and more standardized procedures and large-scale studies are needed to support the clinical use of saliva testing.
Assuntos
Biomarcadores Tumorais , Citocinas , Neoplasias Bucais , Saliva , Humanos , Neoplasias Bucais/diagnóstico , Saliva/química , Citocinas/análise , Citocinas/metabolismo , Biomarcadores Tumorais/análise , Metanálise em Rede , Interleucina-10/análise , Interleucina-6/análiseRESUMO
BACKGROUND: The biological mechanisms driving orthodontic tooth movement (OTM) remain incompletely understood. Gingival crevicular fluid (GCF) is an important indicator of the periodontal bioprocess, providing valuable cues for probing the molecular mechanisms of OTM. METHODS: A rigorous review of the clinical studies over the past decade was conducted after registering the protocol with PROSPERO and adhering to inclusion criteria comprising human subjects, specified force magnitudes and force application modes. The thorough screening investigated differentially expressed proteins (DEPs) in GCF associated with OTM. Protein-protein interaction (PPI) analysis was carried out using the STRING database, followed by further refinement through Cytoscape to isolate top hub proteins. RESULTS: A comprehensive summarization of the OTM-related GCF studies was conducted, followed by an in-depth exploration of biomarkers within the GCF. We identified 13 DEPs, including ALP, IL-1ß, IL-6, Leptin, MMP-1, MMP-3, MMP-8, MMP-9, PGE2, TGF-ß1, TNF-α, OPG, RANKL. Bioinformatic analysis spotlighted the top 10 hub proteins and their interactions involved in OTM. Based on these findings, we have proposed a hypothetic diagram for the time-course bioprocess in OTM, which involves three phases containing sequential cellular and molecular components and their interplay network. CONCLUSIONS: This work has further improved our understanding to the bioprocess of OTM, suggesting biomarkers as potential modulating targets to enhance OTM, mitigate adverse effects and support real-time monitoring and personalized orthodontic cycles.
Assuntos
Biomarcadores , Biologia Computacional , Líquido do Sulco Gengival , Técnicas de Movimentação Dentária , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/metabolismo , Técnicas de Movimentação Dentária/métodos , Humanos , Biologia Computacional/métodos , Biomarcadores/análise , Ligante RANK/metabolismo , Ligante RANK/análise , Mapas de Interação de Proteínas , Osteoprotegerina/metabolismo , Osteoprotegerina/análise , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/análise , Leptina/metabolismo , Leptina/análise , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/análise , Metaloproteinase 8 da Matriz/análise , Metaloproteinase 8 da Matriz/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/análise , Dinoprostona/metabolismo , Dinoprostona/análise , Metaloproteinase 1 da Matriz/metabolismoRESUMO
PURPOSE: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy. METHODS: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses. RESULTS: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn's multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3-4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1-5.3; P = 0.03). CONCLUSION: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy.
Assuntos
Antineoplásicos , Mediadores da Inflamação , Neoplasias , Saliva , Estomatite , Fator de Necrose Tumoral alfa , Humanos , Estomatite/induzido quimicamente , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Antineoplásicos/efeitos adversos , Idoso , Adulto , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-6/análise , Estudos de Coortes , Índice de Gravidade de DoençaRESUMO
PURPOSE: Lipopolysaccharides is well-known in the acute renal injury process. It causes widespread activation of inflammatory cascades. Tumor necrosis factor (TNF)-α and interleukin (Il)-6 are essential proinflammatory cytokines that can induce the production of other cytokines in host response. Adalimumab suppresses TNF-α, IL-1ß, and IL-6. We aimed to evaluate whether adalimumab would prevent the toxicity of lipopolysaccharide on the rat renal tissue. METHODS: Adult female Wistar rats were divided into four groups. To the control group, only intraperitoneal saline injection procedure was carried out. For adalimumab group, adalimumab was injected at a dose for two days. For lipopolysaccharide group, animals were injected with lipopolysaccharide (a dose). For lipopolysaccharide-adalimumab group, animals were given adalimumab treatment before the injection of lipopolysaccharide. Histopathological changes and immunohistochemical analysis for TNF-α and IL-6 were determined. RESULTS: The pathological changes and immunohistochemical staining for TNF-α or IL-6 were similar for control and adalimumab groups (p > 0.05). The lipopolysaccharide group had significantly higher distorted features in the renal tissues (p < 0.001), and also significantly prominent immunohistochemical staining for TNF-α or IL-6 (0.003), compared to the control group. No severe pathological feature was detected in the lipopolysaccharide-adalimumab group, but moderate necrosis was found in all cases (p = 0.003). TNF-α staining and IL-6 staining in the lipopolysaccharide group was found to significantly prominent compared to lipopolysaccharide-adalimumab group (p = 0.013). CONCLUSIONS: Because of its anti-inflammatory property, adalimumab pretreatment may have protective effects on experimental kidney injury. Adalimumab could be considered as a protective agent to acute effects of lipopolysaccharide induced renal injury.
Assuntos
Injúria Renal Aguda , Adalimumab , Interleucina-6 , Lipopolissacarídeos , Ratos Wistar , Fator de Necrose Tumoral alfa , Animais , Adalimumab/farmacologia , Adalimumab/uso terapêutico , Feminino , Fator de Necrose Tumoral alfa/análise , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/induzido quimicamente , Interleucina-6/análise , Rim/efeitos dos fármacos , Rim/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Imuno-Histoquímica , Ratos , Modelos Animais de Doenças , Reprodutibilidade dos TestesRESUMO
Insomnia is a major concern among stressed workers worldwide. Although stress generally has a detrimental effect on sleep quality, the impact of biological stress, especially the immunological stress response, on sleep quality is not yet fully understood. Stressed workers were recruited through a screening process using a Brief Job Stress Questionnaire. The participants were asked to complete various occupation-related questionnaires. Additionally, saliva samples were collected to assess interleukin-6 (IL-6) levels as an immunological stress response. Subsequently, they were asked to wear an Apple Watch to record their sleep pattern for one week. Their sleep architecture was estimated using a previously published and validated method. Finally, data from 73 participants were analyzed. Our multivariable analysis revealed that shorter durations of slow-wave sleep (non-rapid eye movement sleep stage 3) were significantly associated with elevated IL-6 levels (p = 0.005) and greater daytime sleepiness (p = 0.002) after controlling for total sleep time. Our finding that a higher immunological stress response is associated with poor sleep quality contributes to a better understanding of insomnia in stressed workers and emphasizes the importance of stress management in this population.
Assuntos
Interleucina-6 , Estresse Ocupacional , Saliva , Humanos , Saliva/metabolismo , Saliva/química , Masculino , Feminino , Interleucina-6/metabolismo , Interleucina-6/análise , Adulto , Japão , Estresse Ocupacional/metabolismo , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono/metabolismo , Inquéritos e Questionários , Qualidade do Sono , Estresse Psicológico/metabolismo , Sono/fisiologiaRESUMO
Background and Objectives: Surgical wound analgesia has been analyzed in many studies, but few have focused on its relationship with inflammatory markers. As such, we aimed to determine the influence of analgesic surgical wound infiltration in open colorectal surgery on the seric levels of pro- and anti-inflammatory markers and the associated efficacy in postoperative pain control. Materials and Methods: Forty patients who underwent open colorectal surgery were prospectively randomized: group 0, epidural analgesia; group 1, intravenous analgesia (control), group 2, preincision and prelaparoraphy infiltration; and, group 3, prelaparoraphy infiltration. Wound infiltration was performed with ropivacaine. We analyzed the levels of IL-6 and IL-10 cytokines before and 6 h after surgery and their correlation with pain scores. Results: The postoperative Il-6 levels were significantly lower in group 0 than in the control (p = 0.041). The postoperative Il-10 levels were significantly higher in group 3 (p = 0.029) than in the control. Six hours after the operation, the pain scores were significantly lower in all groups than in the control (p = 0.005, p = 0.022, and p = 0.017 for groups 0, 2, and 3, respectively). Pain scores were significantly correlated with Il-10 levels in group 2 (p = 0.047); in group 3, IL-10 levels directly correlated with those of Il-6 (p = 0.026). Conclusions: The analgetic effect of preincisional and prelaparoraphy analgetic infiltration was efficient. The analgetic infiltration of the surgical wound prior to closure stimulates both the inflammatory activator and regulator interleukins.
Assuntos
Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Projetos Piloto , Idoso , Interleucina-10/sangue , Interleucina-10/análise , Ropivacaina/uso terapêutico , Ropivacaina/administração & dosagem , Estudos Prospectivos , Citocinas/sangue , Interleucina-6/sangue , Interleucina-6/análise , Cirurgia Colorretal/métodos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Medição da Dor/métodos , Adulto , Ferida Cirúrgica/tratamento farmacológico , Ferida Cirúrgica/complicações , Analgésicos/uso terapêutico , Analgesia Epidural/métodosRESUMO
Interleukin-6 (IL-6) detection and monitoring are of great significance for evaluating the progression of many diseases and their therapeutic efficacy. Lateral flow immunoassay (LFIA) is one of the most promising point-of-care testing (POCT) methods, yet suffers from low sensitivity and poor quantitative ability, which greatly limits its application in IL-6 detection. Hence, in this work, we integrated Aushell nanoparticles (NPs) as new LFIA reporters and achieved the colorimetric and photothermal dual-mode detection of IL-6. Aushell NPs were conveniently prepared using a galvanic exchange process. By controlling the shell thickness, their localized surface plasmon resonance (LSPR) peak was easily tuned to near-infrared (NIR) range, which matched well with the NIR irradiation light. Thus, the Aushell NPs were endowed with good photothermal effect. Aushell NPs were then modified with IL-6 detection antibody to construct Aushell probes. In the LFIA detection, the Aushell probes were combined with IL-6, which were further captured by the capture IL-6 antibody on the test line of the strip, forming a colored band. By observation with naked eyes, the colorimetric qualitative detection of IL-6 was achieved with limit of 5 ng/mL. By measuring the temperature rise of the test line with a portable infrared thermal camera, the photothermal quantitative detection of IL-6 was performed from 1~1000 ng/mL. The photothermal detection limit reached 0.3 ng/mL, which was reduced by nearly 20 times compared with naked-eye detection. Therefore, this Aushell-based LFIA efficiently improved the sensitivity and quantitative ability of commercial colloidal gold LFIA. Furthermore, this method showed good specificity, and kept the advantages of convenience, speed, cost-effectiveness, and portability. Therefore, this Aushell-based LFIA exhibits practical application potential in IL-6 POCT detection.
Assuntos
Colorimetria , Ouro , Interleucina-6 , Interleucina-6/análise , Ouro/química , Imunoensaio/métodos , Colorimetria/métodos , Humanos , Nanoconchas/química , Ressonância de Plasmônio de Superfície/métodos , Nanopartículas Metálicas/química , Limite de Detecção , Técnicas Biossensoriais/métodosRESUMO
Eutectic gallium indium (EGaIn) nanoparticles can be modified with aniline derivatives to introduce versatile functional groups toward bioapplications beyond materials science. p-Aminobenzoic acid (PABA) modified EGaIn (EGaIn-PABA) demonstrated high wettability due to the presence of carboxyl groups, but the priority of binding of carboxyl and amino groups on the EGaIn surface remains unclear. To study the binding nature of PABA to EGaIn, the anti-mouse IgG antibody labeled with fluorescein isothiocyanate (FITC) (IgG-FITC) was covalently modified to EGaIn-PABA to verify the presence of terminal carboxyl groups on the EGaIn surface. The binding of gold nanoparticles (AuNPs) to EGaIn-PABA nanoparticles suggested the presence of terminal amino groups on the EGaIn surface. Then, taking advantage of the reductive nature of amino groups, the Almar blue fluorescence experiment was designed to determine the co-existence of carboxyl and amino groups on the EGaIn-PABA surface with an approximate ratio of 3 : 7, suggesting that carboxyl groups had a higher probability of binding with the EGaIn surface than that of amino groups. Then, an aptasensor was fabricated on the EGaIn-PABA surface with AuNPs for electrochemical detection of interleukin-6 with a sensitivity of 1 pg mL-1.
Assuntos
Técnicas Biossensoriais , Ouro , Índio , Nanopartículas Metálicas , Propriedades de Superfície , Técnicas Biossensoriais/métodos , Ouro/química , Nanopartículas Metálicas/química , Índio/química , Gálio/química , Interleucina-6/metabolismo , Interleucina-6/análise , Animais , Camundongos , Técnicas Eletroquímicas , Tamanho da Partícula , HumanosRESUMO
BACKGROUND: This study aimed to assess variations in the absolute counts of various leukocyte subsets in the peripheral blood of women with pregnancies affected by preterm prelabour rupture of membranes (PPROM), in relation to the presence of intra-amniotic inflammation (IAI). METHODS: The study included fifty-two women with singleton pregnancies experiencing PPROM. Absolute counts of different leukocyte subpopulations, such as granulocytes, monocytes, lymphocytes, T cells and their subsets, B cells and their subsets, and NK cells and their subsets, were measured in maternal peripheral blood samples using multicolour flow cytometry. IAI was identified by elevated concentrations of interleukin 6 (IL-6) in the amniotic fluid, which was collected through transabdominal amniocentesis. RESULTS: Women with IAI exhibited higher absolute counts of leukocytes (p = 0.003), granulocytes (p = 0.008), and monocytes (p = 0.009). However, the presence of IAI did not significantly affect the absolute counts of lymphocytes or their subpopulations. CONCLUSIONS: The study found that IAI is associated with changes in the absolute counts of leukocytes from the innate immunity compartment in the peripheral blood of women with pregnancies complicated by PPROM. Conversely, it does not significantly alter the counts of cells from the adaptive immune system. The changes observed may reflect the natural, temporal, and localised characteristics of IAI.
Preterm birth is the most serious complication in contemporary perinatal medicine. Preterm birth, which is defined as a labour before the completion of 37 weeks of pregnancy, is often accompanied by premature rupture of the amniotic membranes and drainage of amniotic fluid. Such a situation is often complicated by inflammation, which adversely affects the health of the foetus. A number of procedures and markers have been developed for the diagnosis of inflammation, but they are determined from hard-to-reach amniotic fluid. It is therefore appropriate to try to find reliable markers of inflammation in the much more accessible maternal peripheral blood. Such a marker can be increased numbers of leukocytes, which have been repeatedly investigated in this context. However, little attention is directed to other leukocyte populations and especially to various lymphocyte subpopulations. This study aimed to test changes in absolute counts of different types of leukocytes and lymphocyte subpopulations in women with premature rupture of membranes with respect to ongoing inflammation. The results of the study showed that inflammation is accompanied by increased numbers of leukocytes, granulocytes and monocytes, however, the results did not show significant changes in the number of lymphocytes and their subpopulations.
Assuntos
Corioamnionite , Ruptura Prematura de Membranas Fetais , Humanos , Feminino , Gravidez , Ruptura Prematura de Membranas Fetais/sangue , Adulto , Contagem de Leucócitos , Corioamnionite/sangue , Líquido Amniótico/citologia , Interleucina-6/sangue , Interleucina-6/análise , Citometria de Fluxo , Imunidade Inata , Leucócitos , AmniocenteseRESUMO
Implantable devices for brain-machine interfaces and managing neurological disorders have experienced rapid growth in recent years. Although functional implants offer significant benefits, issues related to transient trauma and long-term biocompatibility and safety are of significant concern. Acute inflammatory reaction in the brain tissue caused by microimplants is known to be an issue but remains poorly studied. This study presents the use of titanium oxynitride (TiNO) nanofilm with defined surface plasmon resonance (SPR) properties for point-of-care characterizing of acute inflammatory responses during robot-controlled micro-neuro-implantation. By leveraging surface-enriched oxynitride, TiNO nanofilms can be biomolecular-functionalized through silanization. This label-free TiNO-SPR biosensor exhibits a high sensitivity toward the inflammatory cytokine interleukin-6 with a detection limit down to 6.3 fg ml-1 and a short assay time of 25 min. Additionally, intraoperative monitoring of acute inflammatory responses during microelectrode implantation in the mice brain has been accomplished using the TiNO-SPR biosensors. Through intraoperative cerebrospinal fluid sampling and point-of-care plasmonic biosensing, the rhythm of acute inflammatory responses induced by the robot-controlled brain microelectrodes implantation has been successfully depicted, offering insights into intraoperative safety assessment of invasive brain-machine interfaces.
Assuntos
Ressonância de Plasmônio de Superfície , Titânio , Animais , Titânio/química , Camundongos , Técnicas Biossensoriais , Encefalite/etiologia , Microeletrodos , Interleucina-6/análise , Interleucina-6/líquido cefalorraquidiano , Encéfalo , Interfaces Cérebro-Computador , Desenho de Equipamento , Eletrodos Implantados/efeitos adversos , HumanosRESUMO
BACKGROUND: This study compared the concentrations of interleukin (IL)-6, IL-17, and IL-35 in the gingival crevicular fluid of periodontally healthy participants with individuals who had stage III and IV periodontitis. METHODS: In total, 60 participants with stage III grade B-C (n = 12)-stage IV grade C (n = 18) periodontitis and 30 healthy controls were included in this cross-sectional study. Full-mouth clinical periodontal measurements were performed. Concentrations of IL-6, IL-17, and IL-35 were determined using enzyme-linked immunosorbent assays. Parametric/nonparametric methods, Pearson's/Spearman's correlation, and logistic regression methods were used for data analyses. RESULTS: The periodontitis group exhibited significantly higher levels of IL-6, IL-17, and IL-35 compared with the healthy group (p < 0.001). IL-17 levels had a positive correlation with pocket depth (PD) (r = 0.395; p = 0.031) in the periodontitis group. IL-6, IL-17, and IL-35 levels were associated with periodontitis (odds ratio [OR] = 1.344, 95% confidence interval [CI] = 1.159-1.56; OR = 1.063, 95% CI = 1.025-1.102; OR = 1.261, 95% CI = 1.110-1.434, respectively) (p < 0.001, p = 0.001, p < 0.001, respectively). Full-mouth and sampling sites PD and clinical attachment loss (CAL) values were significantly higher in the periodontitis group than in the healthy group (p < 0.001). CONCLUSIONS: This study revealed upregulated levels of IL-6, IL-17, and IL-35 in periodontitis patients compared to healthy individuals. IL-17 shows a correlation with increased PD. These findings suggest a potential association between these cytokines and severe and advanced periodontitis. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov with this identifier NCT05306860 on 24/01/2022.
Assuntos
Líquido do Sulco Gengival , Interleucina-17 , Interleucina-6 , Interleucinas , Periodontite , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Líquido do Sulco Gengival/química , Interleucina-17/análise , Interleucina-17/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Interleucinas/análise , Interleucinas/metabolismo , Índice Periodontal , Periodontite/diagnóstico , Periodontite/metabolismo , Periodontite/patologia , Estudos Prospectivos , Adulto Jovem , IdosoRESUMO
The fabrication of ordered nanoarray electrode (NAE) using UV imprinting and their application as electrochemical (EC) immunosensor is described in this study. Especially, the influence of the array density factors on the performance of NAE was characterized electrochemically and compared with flat-electrode. Low-density (hole: 200 nm, hole space = 600 nm), medium-density (hole: 200 nm, hole space = 400 nm), and high-density NAE (hole: 200 nm, hole space = 200 nm) which have the same active area were fabricated and their redox cycling was compared with empirical results. We observed that the high-density is the optimum NAE exhibiting the lowest charge transfer resistance and the highest redox cycling performance among all NAEs. Finally, to observe the effect of their EC performance as biosensor, an EC immunoassay was performed using Interleukine-6 (IL-6), and high-density NAE has lowest a low limit of detection (LOD) of 0.45 pg/mL compared with other NAEs (medium-density: 3.91 pg/mL, low-density: 5.87 pg/mL).
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Eletrodos , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Técnicas Eletroquímicas/métodos , Transporte de Elétrons , Limite de Detecção , Interleucina-6/análise , HumanosRESUMO
Background and Objectives: Sepsis represents a global health challenge and requires advanced diagnostic and prognostic approaches due to its elevated rate of morbidity and fatality. Our study aimed to assess the value of a novel set of six biomarkers combined with severity scores in predicting 28 day mortality among patients presenting with sepsis in the Emergency Department (ED). Materials and Methods: This single-center, observational, prospective cohort included sixty-seven consecutive patients with septic shock and sepsis enrolled from November 2020 to December 2022, categorized into survival and non-survival groups based on outcomes. The following were assessed: procalcitonin (PCT), soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1), the soluble form of the urokinase plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and azurocidin 1 (AZU1), alongside clinical scores such as the Quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II and III (SAPS II/III), the National Early Warning Score (NEWS), Mortality in Emergency Department Sepsis (MEDS), the Charlson Comorbidity Index (CCI), and the Glasgow Coma Scale (GCS). The ability of each biomarker and clinical score and their combinations to predict 28 day mortality were evaluated. Results: The overall mortality was 49.25%. Mechanical ventilation was associated with a higher mortality rate. The levels of IL-6 were significantly higher in the non-survival group and had higher AUC values compared to the other biomarkers. The GCS, SOFA, APACHEII, and SAPS II/III showed superior predictive ability. Combining IL-6 with suPAR, AZU1, and clinical scores SOFA, APACHE II, and SAPS II enhanced prediction accuracy compared with individual biomarkers. Conclusion: In our study, IL-6 and SAPS II/III were the most accurate predictors of 28 day mortality for sepsis patients in the ED.
Assuntos
Biomarcadores , Serviço Hospitalar de Emergência , Sepse , Humanos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Masculino , Feminino , Estudos Prospectivos , Sepse/mortalidade , Sepse/sangue , Idoso , Biomarcadores/sangue , Biomarcadores/análise , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Pró-Calcitonina/análise , APACHE , Escores de Disfunção Orgânica , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Prognóstico , Estudos de Coortes , Valor Preditivo dos Testes , Interleucina-6/sangue , Interleucina-6/análise , Índice de Gravidade de DoençaRESUMO
AIM: The aim of the present study is to show how sodium nitrite alters the histology of submandibular salivary glands and livers of Albino rats, as well as how chlorogenic acid may have therapeutic benefits. METHODS: A sample size of thirty male Sprague Dawley Albino rats weighing between 100 and 150 g (5-6 weeks old) was randomly allocated into 3 equal groups. Group I: rats were used as controls and were given phosphate buffer solution, whereas Group II: rats were given an 80 mg/kg sodium nitrites (SN) daily dissolved in distilled water. The rats in Group III were given a daily dose of 80 mg/kg SN dissolved in distilled water and after 6 hours each rat received 50 mg/mL freshly prepared chlorogenic acid (CGA) every other day. For 12 weeks, all treatment modalities will be administered orally, every day. After the experiment, all rats were euthanized. Samples from salivary glands and livers were processed and stained with H&E and interleukin 6 (IL 6). Malondialdehyde (MDA) and superoxide dismutase (SOD) enzymes were detected using an ELISA assay. RESULTS: Groups III had nearly comparable findings to Group I regarding histological pattern with normal submandibular glands and livers features. Group III salivary gland treated with CGA exhibited higher SOD levels (20.60±4.81 U/g) in comparison to the SN group, and lower MDA levels (111.58±28.28 nmol/mg) in comparison to the SN treated samples. In comparison to the SN group, CGA treatment significantly reduced MDA levels in liver samples (167.56±21.17 nmol/mg) and raised SOD (30.85±6.77 U/g). CONCLUSIONS: Chlorogenic acid has a protective effect against salivary gland and liver toxicity induced by SN in rats. This was mediated via the anti-inflammatory and antioxidative properties of CGA and the restoration of oxidant/antioxidant balance in rat salivary gland and liver.
Assuntos
Ácido Clorogênico , Fígado , Malondialdeído , Ratos Sprague-Dawley , Nitrito de Sódio , Glândula Submandibular , Superóxido Dismutase , Animais , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Masculino , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/patologia , Glândula Submandibular/metabolismo , Ratos , Fígado/efeitos dos fármacos , Fígado/patologia , Nitrito de Sódio/farmacologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Malondialdeído/metabolismo , Distribuição Aleatória , Interleucina-6/análise , Interleucina-6/metabolismoRESUMO
BACKGROUND: Periodontal disease results in oral dysbiosis, increasing plaque virulence and oxidative stress. Stannous fluoride (SnF2) binds lipopolysaccharides to reduce plaque virulence. This study prospectively assessed SnF2 effects on oxidative stress in adults with gingivitis. METHODS: This was a 2-month, single-center, single-treatment clinical trial. Twenty "disease" (> 20 bleeding sites with ≥ 3 pockets 3 mm-4 mm deep) and 20 "healthy" (≤ 3 bleeding sites with pockets ≤ 2 mm deep) adults were enrolled. All participants were instructed to use SnF2 dentifrice twice daily for 2 months. An oral examination, Modified Gingival Index (MGI) examination and Gingival Bleeding Index (GBI) examination were conducted at baseline, 1 month and 2 months. Gingival crevicular fluid (GCF), saliva, oral lavage and supragingival plaque were collected at each visit to evaluate: Endotoxins, Protein Carbonyls, L-lactate dehydrogenase (LDH), Ferric reducing antioxidant power (FRAP), Oxidized low density lipoproteins (oxi-LDL), IL-6 and C-reactive protein (CRP). A subset-analysis examined participants considered at higher risk of cardiovascular disease. Change-from-baseline analyses within each group were of primary interest. RESULTS: The disease group showed statistically significant reductions in GBI at Month 1 (67%) and Month 2 (85%) and in MGI at Month 1 (36%) and Month 2 (51%) versus baseline (p < 0.001). At baseline, the disease group showed greater LDH in GCF and oxi-LDL levels in saliva versus the healthy group (p ≤ 0.01). Total antioxidant capacity (FRAP) in saliva increased versus baseline for the disease group at Months 1 and 2 (p < 0.05), and levels for the disease group were greater than the healthy group at both timepoints (p < 0.05). SnF2 treatment reduced endotoxins (lavage) for both disease and healthy groups at Month 2 (p ≤ 0.021) versus baseline. There was a reduction in oxidative stress markers, namely protein carbonyl in saliva, at Months 1 and 2 (p < 0.001) for both groups and a reduction in cytokine IL-6 (lavage) in the disease group at Month 2 (p = 0.005). A subset analysis of participants at higher coronary disease risk showed reductions in endotoxins in lavage, oxi-LDL, and CRP in saliva at Month 2 (p ≤ 0.04). CONCLUSION: SnF2 dentifrice use reversed gingival inflammation, suppressed endotoxins and reduced some harmful oxidant products in saliva and gingiva. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT05326373, registered on 13/04/2022.
Assuntos
Biomarcadores , Proteína C-Reativa , Dentifrícios , Líquido do Sulco Gengival , Gengivite , Interleucina-6 , Estresse Oxidativo , Índice Periodontal , Saliva , Fluoretos de Estanho , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Fluoretos de Estanho/uso terapêutico , Gengivite/prevenção & controle , Feminino , Masculino , Adulto , Saliva/química , Dentifrícios/uso terapêutico , Líquido do Sulco Gengival/química , Interleucina-6/análise , Interleucina-6/metabolismo , Proteína C-Reativa/análise , Biomarcadores/análise , Carbonilação Proteica/efeitos dos fármacos , Endotoxinas/análise , Antioxidantes/uso terapêutico , Pessoa de Meia-Idade , L-Lactato Desidrogenase/análise , Placa Dentária/prevenção & controle , Lipoproteínas LDL , Seguimentos , Adulto JovemRESUMO
(1) Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity and mortality both in the general population and heart failure patients. Inflammation may promote the initiation, maintenance and perpetuation of AF, but the impact of inflammatory molecular signaling on the association between AF and heart failure remains elusive. (2) Materials and Methods: In 111 patients with chronic stable heart failure, baseline values of conventional (IL-6 and hsCRP) and selected novel inflammatory biomarkers (IL-10, IL-6/IL-10 ratio, orosomucoid and endocan) were determined. Inflammatory biomarkers were compared with respect to the presenting cardiac rhythm. (3) Results: Patients aged below 75 years with AF had significantly higher values of IL-6 and IL-6/IL-10 ratio; IL-6 levels were a significant predictor of AF in both univariate (OR 1.175; 95%CI 1.013-1.363; p = 0.034) and multivariate logistic regression analysis when accounting for other inflammatory biomarkers (OR 1.327; 95% CI 1.068-1.650; p = 0.011). Conversely, there was no association between other novel inflammatory biomarkers and AF. (4) Conclusions: IL-6 levels and the IL-6/IL-10 ratio are associated with AF in patients with chronic stable heart failure under the age of 75 years, suggesting that inflammatory molecular signaling may play a role in the development of AF in the heart failure population.
Assuntos
Fibrilação Atrial , Biomarcadores , Insuficiência Cardíaca , Inflamação , Interleucina-6 , Humanos , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Biomarcadores/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Feminino , Masculino , Idoso , Interleucina-6/sangue , Interleucina-6/análise , Pessoa de Meia-Idade , Inflamação/sangue , Inflamação/complicações , Interleucina-10/sangue , Doença Crônica , Proteína C-Reativa/análise , Proteoglicanas/sangue , Orosomucoide/análise , Idoso de 80 Anos ou mais , Modelos Logísticos , Proteínas de NeoplasiasRESUMO
Background and Objectives: This study presents a retrospective analysis of 26 autopsy cases from a single centre, primarily focusing on forensic cases, with a majority of male individuals. Materials and Methods: We systematically analysed autopsy reports and cardiac tissue slides using haematoxylin-eosin stain and immunohistochemistry for CD3, CD163, and IL-6. The histological assessment evaluated key variables such as inflammation severity, necrosis, and background changes using a standardised grading system. Quantitative analysis of immunohistochemical markers was performed, calculating the percentage of positively stained cells within the inflammatory infiltrate. Results: The average age was 51.6 years, slightly skewed towards older males. The fatalities varied widely, with sudden death and drug abuse being the most common conditions linked to myocarditis findings on histological examination. A strong correlation was found between the severity of inflammation (measured by size within a myocardium section) and the scoring system based on the number of inflammatory foci per section (p ≤ 0.001). Most cases showed mild to minimal fibrosis, with some exhibiting moderate to severe fibrosis, arteriosclerosis, and myocyte hypertrophy. The presence of protein CD3 in the inflammatory infiltrate revealed a moderate inverse correlation between the CD3 values and the severity of inflammation and necrosis, and a strong inverse correlation with neutrophil levels. CD3 levels were higher in sudden death cases and lower in cases with numerous inflammatory foci, highlighting the discreet nature of lymphocytic myocarditis. Macrophage presence, assessed using CD163, showed a moderate inverse correlation with neutrophil levels and significant differences between sudden death and non-sudden death cases. Macrophage-rich inflammation was observed in cases with pneumonia/bronchopneumonia-associated lesions. IL-6 expression showed a moderate direct correlation with inflammation severity (p = 0.028), severity of necrosis (p = 0.005), and the number of inflammatory foci per section (p = 0.047). A moderate inverse correlation was found between CD3 and IL-6 expression (p = 0.005). Conclusions: These findings highlight the need for a unique immunohistochemical approach in forensic cases of myocarditis, differing from guidelines for endomyocardial biopsies due to diverse inflammatory cells. The study suggests exploring inflammatory chemokines within myocarditis foci for their significance in clinical scenarios. Specifically, IL-6, a crucial pro-inflammatory interleukin, correlated significantly with the severity of inflammation and necrosis (p < 0.05). This study provides novel and valuable insights into the histopathological and immunological markers of myocarditis in autopsy cases.
Assuntos
Autopsia , Imuno-Histoquímica , Miocardite , Humanos , Miocardite/patologia , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Imuno-Histoquímica/métodos , Adulto , Feminino , Idoso , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Complexo CD3/análise , Interleucina-6/análise , Miocárdio/patologia , Receptores de Superfície Celular/análiseRESUMO
Diabetes is a chronic disease with significant complications, necessitating regular treatment and checkups, which can be costly and time-consuming for patients. To address this, we developed the Sliding Microneedle (MN)-Lateral flow immunoassay strip (LFIAs) device that combines the advantages of MNs and LFIAs to detect IL-6, an independent biomarker for diabetes complications. This device offers rapid and highly sensitive detection of IL-6 by extracting interstitial fluid (ISF) through MNs and transferring it to LFIAs. The stainless MN, embedded in the 3D-printed Sliding MN-LFIAs device, was inserted into the skin at a 20° angle, minimizing blood contamination risk. With a filter paper attached to the MN surface, the device collected 4.65 ± 0.05 µL of ISF containing IL-6 within 90 s. The ISF was then transferred to the LFIAs using a running buffer. After a 15-min reaction, silver enhancement (SE) treatment was applied, allowing for the highly sensitive and specific detection of IL-6 at 102 pg/mL concentrations. The Sliding MN-LFIAs device successfully distinguished between normal and diabetic rat models, demonstrating its potential as an effective tool for detecting diabetes complications quickly and affordably.
Assuntos
Biomarcadores , Técnicas Biossensoriais , Líquido Extracelular , Interleucina-6 , Agulhas , Animais , Interleucina-6/análise , Líquido Extracelular/química , Imunoensaio/instrumentação , Imunoensaio/métodos , Técnicas Biossensoriais/instrumentação , Biomarcadores/análise , Ratos , Desenho de Equipamento , Diabetes Mellitus Experimental , Humanos , Ratos Sprague-DawleyRESUMO
Electrochemical detection methods hold many advantages over their optical counterparts, such as operation in complex sample matrices, low-cost and high volume manufacture and possible equipment miniaturisation. Despite these advantages, the use of electrochemical detection is currently limited in the clinical setting. There is a wide range of potential electrode materials, selected for optimal signal-to-noise ratios and reproducibility when detecting target analytes. The use of carbon paste electrodes (CPEs) for electrochemical detection can be limited by their analytical performance, however they remain very attractive due to their low cost and biocompatibility. This paper presents the fabrication of an easy-to-make and use graphite powder/paraffin wax paste combined with a substrate produced via additive manufacturing and confirms its functionality for both direct and indirect electrochemical measurements. The produced CPEs enable the direct voltammetric detection of hexaammineruthenium(III) chloride and dopamine at an experimental limit of detection (ELoD) of 62.5 µM. The key inflammatory biomarker Interleukin-6 through an enzyme-linked immunosorbant assay (ELISA) was also quantified, yielding a clinically-relevant ELoD of 150 pg ml-1 in 10% human serum. The performance of low-cost and easy-to-use CPEs obtained in 0.5 hours is showcased in this study, demonstrating the platform's potential uses for point-of-need electroanalytical applications.
Assuntos
Técnicas Eletroquímicas , Eletrodos , Grafite , Limite de Detecção , Grafite/química , Humanos , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Dopamina/sangue , Dopamina/análise , Carbono/química , Interleucina-6/sangue , Interleucina-6/análise , Ceras/química , Compostos de Rutênio/química , Ensaio de Imunoadsorção Enzimática/métodosRESUMO
SUMMARY: In this study we aimed to examine the effect of novel vasodilatory drug Riociguat co-administration along resveratrol to recover neurodegeneration in experimental stroke injury. For that purpose, thirty-five adult female rats were divided into five groups (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) of seven animals in each. Animals in Control group did not expose to any application during the experiment and sacrificed at the end of the study. Rats in the rest groups exposed to middle cerebral artery occlusion (MCAO) induced ischemic stroke. MCAO + R group received 30 mg/kg resveratrol, and MCAO + BAY group received 10 mg/kg Riociguat. The MCAO + C group received both drugs simultaneously. The drugs were administered just before the reperfusion, and the additional doses were administered 24h, and 48h hours of reperfusion. All animals in this study were sacrificed at the 72nd hour of experiment. Total brains were received for analysis. Results of this experiment indicated that MCAO led to severe injury in cerebral structure. Bax, IL-6 and IL-1ß tissue levels were up-regulated, but anti-apoptotic Bcl-2 immunoexpression was suppressed (p<0.05). In resveratrol and Riociguat treated animals, the neurodegenerations and apoptosis and inflammation associated protein expressions were improved compared to MCAO group, but the most success was obtained in combined treatment exposed animals in MCAO + C group. This study indicated that the novel soluble guanylate stimulator Riociguat is not only a potent neuroprotective drug in MCAO induced stroke, but also synergistic administration of Riociguat along with resveratrol have potential to increase the neuroprotective effect of resveratrol in experimental cerebral stroke exposed rats.
En este estudio, nuestro objetivo fue examinar el efecto de la coadministración del nuevo fármaco vasodilatador Riociguat junto con resveratrol para recuperar la neurodegeneración en lesiones por ataques cerebrovasculares experimentales. Para ello, se dividieron 35 ratas hembras adultas en cinco grupos (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) de siete animales en cada uno. Los animales del grupo control no fueron sometidos a ninguna aplicación durante el experimento y se sacrificaron al final del estudio. Las ratas de los grupos expuestas a la oclusión de la arteria cerebral media (MCAO) indujeron un ataque cerebrovascular isquémico. El grupo MCAO + R recibió 30 mg/kg de resveratrol y el grupo MCAO + BAY recibió 10 mg/kg de Riociguat. El grupo MCAO + C recibió ambos fármacos simultáneamente. Los fármacos se administraron antes de la reperfusión y las dosis adicionales se administraron a las 24 y 48 horas de la reperfusión. Todos los animales en este estudio fueron sacrificados a las 72 horas del experimento. Se recibieron cerebros totales para su análisis. Los resultados indicaron que la MCAO provocaba lesiones graves en la estructura cerebral. Los niveles tisulares de Bax, IL-6 e IL- 1ß estaban regulados positivamente, pero se suprimió la inmunoexpresión antiapoptótica de Bcl-2 (p <0,05). En los animales tratados con resveratrol y Riociguat, las neurodegeneraciones y las expresiones de proteínas asociadas a la apoptosis y la inflamación mejoraron en comparación con el grupo MCAO, sin embargo el mayor éxito se obtuvo en el tratamiento combinado de animales expuestos en el grupo MCAO + C. Este estudio indicó que el nuevo estimulador de guanilato ciclasa soluble Riociguat no solo es un fármaco neuroprotector potente en el ataque cerebrovascular inducido por MCAO, sino que también la administración sinérgica de Riociguat junto con resveratrol tiene el potencial para aumentar el efecto neuroprotector del resveratrol en ratas experimentales expuestas a un ataque cerebrovascular.