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To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.
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Diabetes Mellitus Tipo 2 , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios de Casos y Controles , Insecticidas , Glucemia/análisis , Malatión/análogos & derivados , Compuestos Organotiofosforados , China , Adulto , InflamaciónRESUMEN
Background: Cell energy metabolism controls the activation and function of dendritic cells (DCs). Inflammatory dendritic epidermal cells (IDECs) in skin lesions of atopic dermatitis (AD) express high-affinity IgE receptor (FcϵRI) and toll-like receptor 2 (TLR2), which mediate the generation and maintenance of inflammation. However, cellular energy metabolism and effector function of IDECs mediated by FcϵRI and TLR2 have not been fully elucidated. Methods: IDECs in vitro were treated with TLR2 agonist Pam3CSK4 and anti-IgE alone or in combination for 24 h. Further, we analyzed the expression of cell surface activation markers, production of inflammatory factors, and cellular energy metabolism profiles of IDECs by using flow cytometry, multiplex assay, RNA sequencing, targeted energy metabolism, and seahorse assays. Results: Compared to the unstimulated or anti-IgE groups, Pam3CSK4 alone or combined with anti-IgE groups significantly increased the expression of CD80, CD83, and CD86 on IDECs, but did not affect the expression of the above markers in the anti-IgE group. The release of inflammatory cytokines increased in the Pam3CSK4 alone or combined with anti-IgE groups, while there was a weak increasing trend in the anti-IgE group. The glycolysis/gluconeogenesis pathway of carbon metabolism was affected in all treatment groups. Furthermore, compared to the control group, we found a decrease in pyruvic acid, upregulation of PFKM, downregulation of FBP1, and increase in extracellular lactate, glycolysis rate, and glycolysis capacity after all treatments, while there was no difference between each treatment group. However, there was no difference in glycolytic reserve and mitochondrial basic and maximum respiration among all groups. Conclusion: Our results indicate that glycolysis of IDECs may be activated through FcϵRI and TLR2 to upregulate inflammatory factors, suggesting that danger signals from bacteria or allergens might evoke an inflammatory response from AD through the glycolysis pathway.
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Células Dendríticas , Glucosa , Lipopéptidos , Monocitos , Receptor Toll-Like 2 , Humanos , Lipopéptidos/farmacología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/efectos de los fármacos , Glucosa/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/agonistas , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Metabolismo Energético/efectos de los fármacos , Inflamación/inmunología , Inflamación/metabolismo , Células Cultivadas , Receptores de IgE/metabolismo , Citocinas/metabolismo , Inmunoglobulina E/inmunología , Glucólisis , Diferenciación CelularRESUMEN
The treatment of wound inflammation is intricately linked to the concentration of reactive oxygen species (ROS) in the wound microenvironment. Among these ROS, H2O2 serves as a critical signaling molecule and second messenger, necessitating the urgent need for its rapid real-time quantitative detection, as well as effective clearance, in the pursuit of effective wound inflammation treatment. Here, we exploited a sophisticated 3D Cu2- x Se/GO nanostructure-based nanonzymatic H2O2 electrochemical sensor, which is further decorated with evenly distributed Pt nanoparticles (Pt NPs) through electrodeposition. The obtained Cu2- x Se/GO@Pt/SPCE sensing electrode possesses a remarkable increase in specific surface derived from the three-dimensional surface constructed by GO nanosheets. Moreover, the localized surface plasma effect of the Cu2- x Se nanospheres enhances the separation of photogenerated electron-hole pairs between the interface of the Cu2- x Se NPs and the Pt NPs. This innovation enables near-infrared light-enhanced catalysis, significantly reducing the detection limit of the Cu2- x Se/GO@Pt/SPCE sensing electrode for H2O2 (from 1.45 µM to 0.53µM) under NIR light. Furthermore, this biosensor electrode enables in-situ real-time monitoring of H2O2 released by cells. The NIR-enhanced Cu2- x Se/GO@Pt/SPCE sensing electrode provide a simple-yet-effective method to achieve a detection of ROS (H2O2ã-OH) with high sensitivity and efficiency. This innovation promises to revolutionize the field of wound inflammation treatment by providing clinicians with a powerful tool for accurate and rapid assessment of ROS levels, ultimately leading to improved patient outcomes.
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Cobre , Peróxido de Hidrógeno , Inflamación , Nanopartículas del Metal , Platino (Metal) , Peróxido de Hidrógeno/metabolismo , Platino (Metal)/química , Cobre/química , Nanopartículas del Metal/química , Inflamación/metabolismo , Animales , Ratones , Nanoestructuras/química , Técnicas Biosensibles/métodos , Selenio/química , Humanos , Rayos Infrarrojos , Especies Reactivas de Oxígeno/metabolismo , Células RAW 264.7RESUMEN
Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1ß to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17ß-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.
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Acné Vulgar , Aromatasa , Furanos , Lignanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Animales , Furanos/química , Furanos/farmacología , Ratones , Lignanos/farmacología , Lignanos/química , Lignanos/uso terapéutico , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Aromatasa/metabolismo , Aromatasa/química , Transducción de Señal/efectos de los fármacos , Piel/patología , Piel/efectos de los fármacos , Piel/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Inflamasomas/metabolismo , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Propionibacterium acnes/efectos de los fármacos , Interleucina-1beta/metabolismo , Modelos Animales de EnfermedadRESUMEN
Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Asma , Inflamación , Animales , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Ratones , Asma/metabolismo , Asma/genética , Inflamación/metabolismo , Humanos , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Células Epiteliales/metabolismo , Ratones Endogámicos BALB C , Femenino , Hipersensibilidad/metabolismo , Hipersensibilidad/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Some systemic inflammatory indices have been reported to be associated with intracerebral hemorrhage in adults. However, the relationship between systemic inflammatory indices and intraventricular hemorrhage (IVH) in premature neonates is still not completely understood. OBJECTIVE: To evaluate the relationship between systemic inflammatory indices obtained on the first day of life in premature infants and the development of severe IVH. PATIENTS AND METHOD: Premature newborns < 32 weeks of gestational age were included. Eligible patients were divided into 2 groups: Group 1: without IVH or grade I and II hemorrhage, and Group 2: grade III and IV HIV. Demographic characteristics, clinical outcomes, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), pan-immune inflammation value (PIV), and Systemic inflammation response index (SIRI) were compared between groups. RESULTS: A total of 1176 newborns were included in the study, 1074 in Group 1 and 102 premature babies in Group 2. There was no difference between the groups in terms of the count of leukocytes, neutrophils, monocytes, lymphocytes and platelets (p > 0.05). The values of NLR, MLR, PLR, PIV, SII and SIRI were similar in both groups (p > 0.05). CONCLUSION: While the relationship between inflammation, hemodynamics and IVH is still under discussion, our results show that systemic inflammatory indices have no predictive value for IVH.
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Recien Nacido Prematuro , Inflamación , Humanos , Recién Nacido , Femenino , Masculino , Inflamación/sangre , Enfermedades del Prematuro/sangre , Enfermedades del Prematuro/diagnóstico , Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico , Neutrófilos , Hemorragia Cerebral Intraventricular/sangre , Recuento de Plaquetas , Índice de Severidad de la Enfermedad , Monocitos/inmunología , Valor Predictivo de las Pruebas , Edad Gestacional , Biomarcadores/sangreRESUMEN
This study aims to further elucidate the efficacy targets of celastrol(CEL) intervention in central inflammation in mice with obesity-depression comorbiditiy, based on the differential mRNA expression in the amygdala(AMY) and dorsal raphe nucleus(DRN) after CEL intervention. C57BL/6J mice were randomly divided into a normal diet group(Chow), a obesity-depression comorbidity(COM) group, and low-, medium-, and high-dose CEL groups(CEL-L, CEL-M, CEL-H, 0.5, 1.0, 2.0 mg·kg~(-1)). The Chow group received a normal diet, while the COM group and CEL-L, CEL-M, CEL-H groups received a high-fat diet combined with chronic stress from wet bedding. After 10 weeks of feeding, the mice were orally administered CEL for three weeks. Subsequently, the AMY and DRN of mice in the Chow, COM, and CEL-H groups were subjected to transcriptome analysis, and the intersection of target differentially expressed genes in both nuclei was visualized using a Venn diagram. The intersected genes were then imported into STRING for protein-protein interaction(PPI) analysis, and Gene Ontology(GO) analysis was performed using DAVID to identify the core targets regulated by CEL in the AMY and DRN. Independent samples were subjected to quantitative real-time PCR(qPCR) to validate the intersection genes. The results revealed that the common genes regulated by CEL in the AMY and DRN included chemokine family genes Ccl2, Ccl5, Ccl7, Cxcl10, Cxcr6, and Hsp70 family genes Hspa1a, Hspa1b, as well as Myd88, Il2ra, Irf7, Slc17a8, Drd2, Parp9, and Nampt. GO analysis showed that the top 5 nodes Ccl2, Cxcl10, Myd88, Ccl5, and Irf7 were all involved in immune-inflammation regulation(P<0.01). The qPCR results from independent samples showed that in the AMY, compared with the results in the Chow group, chemokine family genes, Hsp70, Myd88, Il2ra, Irf7, Slc17a8, Parp9, and Nampt were significantly up-regulated in the COM group, with Drd2 showing a decreasing trend; these pathological changes were significantly improved in the CEL-H group compared to the COM group. In the DRN, compared with the results in the Chow group, chemokine family genes, Hsp70, Myd88, Il2ra, Irf7, Parp9, and Nampt were significantly down-regulated, while Slc17a8 was significantly up-regulated in the COM group; compared with those in the COM group, Cxcr6, Irf7, and Drd2 were significantly up-regulated, while Slc17a8 was significantly down-regulated in the CEL-H group. In both the AMY and DRN, the expression of Irf7 by CEL showed both inhibition and activation in a dose-dependent manner(R~2 were 0.709 8 and 0.917 2, respectively). These findings suggest that CEL can effectively improve neuroinflammation by regulating bidirectional expression of the same target proteins, thereby intervening in the immune activation of the AMY and immune suppression of the DRN in COM mice.
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Amígdala del Cerebelo , Depresión , Núcleo Dorsal del Rafe , Ratones Endogámicos C57BL , Obesidad , Triterpenos Pentacíclicos , Triterpenos , Animales , Ratones , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Masculino , Depresión/tratamiento farmacológico , Depresión/genética , Depresión/metabolismo , Obesidad/genética , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Triterpenos/farmacología , Núcleo Dorsal del Rafe/metabolismo , Núcleo Dorsal del Rafe/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/genética , HumanosRESUMEN
Garlic (Allium sativum) is recognized as functional food, rich in bioactive compounds that can combat diseases associated with oxidative stress. This study aims to investigate the protective potential of aqueous garlic extract against hemolysis and oxidation. Despite being caused by membrane fragility, hemolysis can lead to inflammation through the oxidation of its products, and in some cases, even exacerbate it in certain pathological contexts. Supplementation with antioxidant molecules can improves oxidative status, in this study, we selected garlic, an excellent functional food, and targeted its effects using aqueous extract and pure molecules. The aqueous garlic extract was prepared under safe conditions and subjected to toxicity on human neutrophils and red blood cells before experimentation. The results indicate that aqueous garlic extract significantly reduces hemolysis with a maximum protection of 98. 74 ± 1. 08 % at a concentration of 5µg/ml. Additionally, experiments were conducted with pure compounds found in garlic such as quercetin, gallic acid, and caffeic acid. The outcomes show that quercetin reduces hemolysis of RBC with a maximum protection of 88. 8 ± 2. 89 % at 20 µM followed by caffeic acid and gallic acid. The action mechanism of the extract was tested on human neutrophil cells, the extract significantly reduced luminol-amplified chemiluminescence of PMA-stimulated neutrophils up to 50 % at 10 µg/ml in addition to its ability to directly scavenge hydrogen peroxide. Our results suggest that aqueous garlic extract exerts promising anti-inflammatory activity in vitro. Through its dual protection against hemolysis and Ros production, garlic may indirectly prevent inflammation reducing the oxidation of hemolysis products. These abilities make garlic aqueous extract promising candidate for improving cardiovascular health, reducing oxidative stress and modulating immunity.
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Antioxidantes , Eritrocitos , Ajo , Hemólisis , Inflamación , Neutrófilos , Oxidación-Reducción , Extractos Vegetales , Ajo/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hemólisis/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Inflamación/prevención & control , Inflamación/tratamiento farmacológico , Oxidación-Reducción/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Agua/químicaRESUMEN
Programmed death-ligand 1 interacts with fungal ribosomal Rpl20b in phagosomes and induces interleukin-10 secretion.
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Antígeno B7-H1 , Inflamación , Micosis , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Inflamación/inmunología , Humanos , Micosis/inmunología , Micosis/microbiología , Animales , Ratones , Proteínas Ribosómicas/inmunologíaRESUMEN
Virus and T cell inflammation persist in the tissues of patients with Long Covid.
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COVID-19 , Inflamación , SARS-CoV-2 , Linfocitos T , COVID-19/inmunología , Humanos , SARS-CoV-2/inmunología , Inflamación/inmunología , Linfocitos T/inmunologíaRESUMEN
The etiology of perinatal brain injury is multifactorial, but exposure to perinatal hypoxiaischemia (HI) is a major underlying factor. This review discusses the role of exposure to infection/inflammation in the evolution of HI brain injury, changes in immune responsiveness to subsequent inflammatory challenges after HI and modulation of neural outcomes with interaction between perinatal HI and inflammatory insults. The authors critically assess the clinical and preclinical evidence for the neuroprotective efficacy of therapeutic hypothermia and other anti-inflammatory treatments for inflammation-sensitized HI injury.
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Asfixia Neonatal , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Inflamación , Humanos , Recién Nacido , Asfixia Neonatal/inmunología , Asfixia Neonatal/terapia , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/inmunología , Hipotermia Inducida/métodos , Inflamación/inmunología , Animales , Antiinflamatorios/uso terapéuticoRESUMEN
This article summarizes the current evidence regarding inflammatory biomarkers (placental and postnatal) and provides a comprehensive understanding of their roles: (1) diagnostic accuracy to predict the severity of hypoxic-ischemia encephalopathy (HIE), (2) value in assessing treatment responses, and (3) prediction of both short- and long-term neurodevelopmental outcomes. In the early critical stages of perinatal asphyxia, inflammatory biomarkers may guide clinical decision-making. Additional research is required to increase our understanding of the optimal utility of biomarkers to predict the severity, evolution, and developmental outcomes after exposure to HIE.
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Asfixia Neonatal , Biomarcadores , Hipoxia-Isquemia Encefálica , Humanos , Asfixia Neonatal/metabolismo , Biomarcadores/metabolismo , Recién Nacido , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/diagnóstico , Femenino , Embarazo , Inflamación/metabolismo , Placenta/metabolismoRESUMEN
Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.
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Acrilamida , Daño del ADN , Inflamación , Estrés Oxidativo , Rutina , Animales , Rutina/farmacología , Femenino , Estrés Oxidativo/efectos de los fármacos , Acrilamida/toxicidad , Daño del ADN/efectos de los fármacos , Ratas , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Ratas Wistar , Simulación por Computador , Antioxidantes/farmacología , Antioxidantes/metabolismoRESUMEN
Necrosis is an overarching term that describes cell death modalities caused by (extreme) adverse conditions in which cells lose structural integrity. A guaranteed consequence of necrosis is the production of necrotic cell remnants, or debris. Necrotic cell debris is a strong trigger of inflammation, and although inflammatory responses are required for tissue healing, necrotic debris may lead to uncontrolled immune responses and collateral damage. Besides local phagocytosis by recruited leukocytes, there is accumulating evidence that extracellular mechanisms are also involved in necrotic debris clearance. In this review, we focused on systemic clearance mechanisms present in the bloodstream and vasculature that often cooperate to drive the clearance of cell debris. We reviewed the contribution and cooperation of extracellular DNases, the actin-scavenger system, the fibrinolytic system and reticuloendothelial cells in performing clearance of necrotic debris. Moreover, associations of the (mis)functioning of these clearance systems with a variety of diseases were provided, illustrating the importance of the mechanisms of clearance of dead cells in the organism.
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Necrosis , Fagocitosis , Humanos , Animales , Inflamación/patología , Inflamación/metabolismoRESUMEN
BACKGROUND: Current evidence linking sedentary behavior (SB), physical activity (PA), and inflammation raises questions about their causal relationships, prompting concerns about potential residual confounding or reverse causation. METHODS: A bidirectional Mendelian randomization (MR) analysis was conducted. SB data (n = 408,815) from "computer use," "television watching," and "driving" were included. The PA data encompassed nine types of PA (n = 460,376) over the last four weeks and included data on the frequency of vigorous PA (n = 440,512) and moderate PA (n = 440,266) for over 10 min. Additionally, three genome-wide association study datasets (n = 64,949) on light, moderate, and vigorous exercise were included to minimize potential bias from changes in exercise intensity. Inflammation data included levels of C-reactive protein (CRP) (n = 575,531), glycoprotein acetyl (GlycA) (n = 115,082), interleukin (IL)-8, IL-6, IL-6 receptor (IL-6R), and soluble IL-6R (sIL-6R) (n = 35,278). All datasets represented participants of European ancestry. RESULTS: Television watching as an SB showed significant positive causal effects on GlycA and CRP (inverse variance weighted (IVW), odds ratios (OR): 1.34, 95% confidence intervals (CI): 1.25-1.44, p = 3.570 × 10-17; IVW, OR: 1.21, 95% CI: 1.16-1.26, p = 1.500 × 10-19, respectively), with more robust evidence for GlycA. In the direction from inflammation to PA, a negative causal relationship between CRP and"number of days/week of moderate PA 10+ minutes"was observed (IVW, OR: 0.92, 95% CI: 0.89-0.96, p = 3.260 × 10-5). Sensitivity analyses were used to verify the robustness and reliability of the results. However, other initially observed associations ceased to be significant after controlling for obesity-related confounders. CONCLUSION: Our MR analysis suggested a potential causal relationship between television watching and chronic low-grade inflammation, with more substantial evidence for GlycA. Additionally, different types of SB may have varying effects on inflammation. Obesity-related traits could partly or entirely influence the relationship between SB, PA, and inflammatory markers. Furthermore, Our findings indicate that SB is an independent risk factor for inflammation, separate from PA, and highlight the different mechanisms by which SB and PA affect disease.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Conducta Sedentaria , Televisión , Humanos , Inflamación/genética , Inflamación/metabolismo , Ejercicio Físico , Proteína C-Reactiva/metabolismo , Masculino , FemeninoRESUMEN
OBJECTIVES: This study examined whether a higher dietary inflammatory index (DII®) is associated with the risk of sarcopenic obesity (SO) and frailty among Korean older adults. METHODS: A total of 950 participants aged 70-84 years, who completed the baseline nutrition survey of the Korean Frailty and Aging Cohort Study, were included in the analysis. The DII, quantifying the dietary inflammatory potential, was calculated using 23 foods and nutrients as assessed by a 24-h dietary recall. SO was defined as the coexistence of sarcopenia (dual-energy X-ray absorptiometry-measured appendicular skeletal muscle mass index of < 7.0 for males; <5.4 for females) and abdominal obesity (waist circumference of ≥ 90 cm for males; ≥85 cm for females). Frailty status was assessed using the Fried frailty index (range, 0-5), a simple tool for defining frailty that consists of three or more of five frailty items. Multinomial logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for confounders. RESULTS: The prevalence of SO and frailty was 9.8% and 10.8%, respectively. The DII was significantly higher in the frail group (2.7) compared to the robust and SO groups (2.0 vs. 1.8) (P < 0.001). Among nutrients and foods included in the DII, the frail group exhibited lower vitamin E, niacin, vitamin B6, energy, and protein intakes than the robust and SO groups. Multivariable-adjusted OR (95% CI) for frailty versus robust (comparing DII tertile 3 to tertile 1) was 2.3 (1.1-4.8; P-trend = 0.02). However, no significant association was observed between the DII and SO (OR, 1.1; 95% CI, 0.5-2.1; P-trend = 0.6). CONCLUSIONS: A higher DII score was associated with increased odds of frailty but not with SO in Korean older adults, suggesting that proinflammatory diets have a greater impact on frailty than that on SO in the older population.
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Dieta , Fragilidad , Inflamación , Sarcopenia , Humanos , Anciano , Masculino , Femenino , Anciano de 80 o más Años , Sarcopenia/epidemiología , Sarcopenia/diagnóstico , Fragilidad/epidemiología , Fragilidad/diagnóstico , Inflamación/epidemiología , Dieta/métodos , Dieta/efectos adversos , República de Corea/epidemiología , Obesidad/epidemiología , Obesidad/diagnóstico , Anciano Frágil , Estudios de Cohortes , Evaluación Geriátrica/métodosRESUMEN
BACKGROUND: Differentiating between degenerative disc disease (DDD), diffuse idiopathic skeletal hyperostosis (DISH), and axial spondyloarthritis (axSpA) represents a diagnostic challenge in patients with low back pain (LBP). We aimed to evaluate the distribution of inflammatory and degenerative imaging features in a real-life cohort of LBP patients referred to a tertiary university rheumatology center. METHODS: In a retrospective cross-sectional analysis of patients referred for LBP, demographics, symptom information, and available imaging were collected. SpA-like changes were considered in the spine in the presence of one of the following lesions typically related to SpA: erosions, sclerosis, squaring, and syndesmophytes on conventional radiographs (CR) and bone marrow oedema (BMO), erosions, sclerosis, and fat lesions (FL) on MRI. SIJ CR were graded per New York criteria; on MRIs, SIJs were evaluated by quadrant for BMO, erosions, FL, sclerosis and ankylosis, similar to the approach used by the Berlin SIJ MRI scoring system. The final diagnosis made by the rheumatologist was the gold standard. Data were presented descriptively, by patient and by quadrant, and compared among the three diagnosis groups. RESULTS: Among 136 referred patients, 71 had DDD, 38 DISH, and 27 axSpA; median age 62 years [IQR55-73], 63% males. On CR, SpA-like changes were significantly higher in axSpA in the lumbar (50%, vs. DDD 23%, DISH 22%), in DISH in the thoracic (28%, vs. DDD 8%, axSpA 12%), and in DDD in the cervical spine (67% vs. DISH 0%, axSpA 33%). On MRI, BMO was significantly higher in DISH in the thoracic (37%, vs. DDD 22%, axSpA 5%) and equally distributed in the lumbar spine (35-42%). FL were significantly more frequently identified in DISH and axSpA in the thoracic (56% and 52%) and DDD and axSpA in the lumbar spine (65% and 74%, respectively). Degenerative changes were frequent in the three groups. Sacroiliitis (NY criteria) was identified in 49% (axSpA 76%, DDD 48%, DISH 29%). CONCLUSION: A significant overlap was found among DDD, DISH, and axSpA for inflammatory and degenerative imaging features. Particularly, SpA-like spine CR features were found in one-fourth of patients with DISH, and MRI BMO was found in one-third of those patients.
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Espondiloartritis Axial , Hiperostosis Esquelética Difusa Idiopática , Degeneración del Disco Intervertebral , Imagen por Resonancia Magnética , Humanos , Masculino , Hiperostosis Esquelética Difusa Idiopática/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Degeneración del Disco Intervertebral/diagnóstico por imagen , Espondiloartritis Axial/diagnóstico por imagen , Estudios de Cohortes , Adulto , Anciano , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/etiología , Radiografía/métodos , Inflamación/diagnóstico por imagen , Diagnóstico Diferencial , Espondiloartritis/diagnóstico por imagenRESUMEN
Purpose: Lignin is the most abundant source of aromatic biopolymers and has gained interest in industrial and biomedical applications due to the reported biocompatibility and defense provided against bacterial and fungal pathogens, besides antioxidant and UV-blocking properties. Especially in the form of nanoparticles (NPs), lignin may display also antioxidant and anti-inflammatory activities. Methods: To evaluate these characteristics, sonochemically nano-formulated pristine lignin (LigNPs) and enzymatically-phenolated one (PheLigNPs) were used to expose zebrafish embryos, without chorion, at different concentrations. Furthermore, two different zebrafish inflammation models were generated, by injecting Pseudomonas aeruginosa lipopolysaccharide (LPS) and by provoking a wound injury in the embryo caudal fin. The inflammatory process was investigated in both models by qPCR, analyzing the level of genes as il8, il6, il1ß, tnfα, nfkbiaa, nfk2, and ccl34a.4, and by the evaluation of neutrophils recruitment, taking advantage of the Sudan Black staining, in the presence or not of LigNPs and PheLigNPs. Finally, the Wnt/ß-catenin pathway, related to tissue regeneration, was investigated at the molecular level in embryos wounded and exposed to NPs. Results: The data obtained demonstrated that the lignin-based NPs showed the capacity to induce a positive response during an inflammatory event, increasing the recruitment of cytokines to accelerate their chemotactic function. Moreover, the LigNPs and PheLigNPs have a role in the resolution of wounds, favoring the regeneration process. Conclusion: In this paper, we used zebrafish embryos within 5 days post fertilization (hpf). Despite being an early-stage exemplary, the zebrafish embryos have proven their potential as predicting models. Further long-term experiments in adults will be needed to explore completely the biomedical capabilities of lignin NPs. The results underlined the safety of both NPs tested paved the way for further evaluations to exploit the anti-inflammatory and pro-healing properties of the lignin nanoparticles examined.
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Inflamación , Lignina , Nanopartículas , Pez Cebra , Animales , Lignina/química , Lignina/farmacología , Nanopartículas/química , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Modelos Animales de Enfermedad , Citocinas/metabolismo , Citocinas/genética , Embrión no Mamífero/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Background: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery. Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II-III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups. Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels. Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.
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Benzodiazepinas , Relación Dosis-Respuesta a Droga , Hemodinámica , Inflamación , Laparoscopía , Propofol , Humanos , Hemodinámica/efectos de los fármacos , Masculino , Femenino , Propofol/administración & dosificación , Propofol/farmacología , Adulto , Persona de Mediana Edad , Inflamación/tratamiento farmacológico , Benzodiazepinas/administración & dosificación , Benzodiazepinas/farmacología , Remifentanilo/administración & dosificación , Remifentanilo/farmacología , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/farmacología , Adulto JovenRESUMEN
Introduction: Genetic mutations in critical nodes of pulmonary epithelial function are linked to the pathogenesis of pulmonary fibrosis (PF) and other interstitial lung diseases. The slow progression of these pathologies is often intermitted and accelerated by acute exacerbations, complex non-resolving cycles of inflammation and parenchymal damage, resulting in lung function decline and death. Excess monocyte mobilization during the initial phase of an acute exacerbation, and their long-term persistence in the lung, is linked to poor disease outcome. Methods: The present work leverages a clinical idiopathic PF dataset and a murine model of acute inflammatory exacerbations triggered by mutation in the alveolar type-2 cell-restricted Surfactant Protein-C [SP-C] gene to spatially and phenotypically define monocyte/macrophage changes in the fibrosing lung. Results: SP-C mutation triggered heterogeneous CD68+ macrophage activation, with highly active peri-injured cells relative to those sampled from fully remodeled and healthy regions. Ingenuity pathway analysis of sorted CD11b-SigF+CD11c+ alveolar macrophages defined asynchronous activation of extracellular matrix re-organization, cellular mobilization, and Apolipoprotein E (Apoe) signaling in the fibrosing lung. Cell-cell communication analysis of single cell sequencing datasets predicted pro-fibrogenic signaling (fibronectin/Fn1, osteopontin/Spp1, and Tgfb1) emanating from Trem2/TREM2 + interstitial macrophages. These cells also produced a distinct lipid signature from alveolar macrophages and monocytes, characterized by Apoe expression. Mono- and di-allelic genetic deletion of ApoE in SP-C mutant mice had limited impact on inflammation and mortality up to 42 day after injury. Discussion: Together, these results provide a detailed spatio-temporal picture of resident, interstitial, and monocyte-derived macrophages during SP-C induced inflammatory exacerbations and end-stage clinical PF, and propose ApoE as a biomarker to identify activated macrophages involved in tissue remodeling.