Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

Biomedicines, Год журнала: 2024, Номер 12(1), С. 175 - 175

Опубликована: Янв. 13, 2024

Severe infection can lead to sepsis. In sepsis, the host mounts an inappropriately large inflammatory response in attempt clear invading pathogen. This sustained high level of inflammation may cause tissue injury and organ failure. Later a paradoxical immunosuppression occurs, where is unable preexisting susceptible secondary infections. A major issue with sepsis treatment that it difficult for physicians ascertain which stage patient in. Sepsis will depend on patient’s immune status across spectrum disease, these statuses are nearly polar opposites early late stages Furthermore, there no approved resolve without contributing within host. Here, we review mechanisms sepsis-induced biomarkers immunosuppressive phase We focused reviewing three main These lymphocyte apoptosis, monocyte/macrophage exhaustion, increased migration myeloid-derived suppressor cells (MDSCs). The septic discuss include MDSC production/migration IL-10 levels, decreased counts HLA-DR expression, GPR18 expression. also literature use specialized pro-resolving mediators (SPMs) different models and/or as compounds have been reported being immunosuppressive. To obtain necessary information, searched PubMed database using keywords macrophage MDSCs, biomarkers, SPMs.

Язык: Английский

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Emerging Implications of Serum Resolvin D2 as a Biochemical Marker for Severity Assessment and Prognosis Prediction Following Moderate-Severe Traumatic Brain Injury: A Prospective Cohort Study

Neuropsychiatric Disease and Treatment, Год журнала: 2025, Номер Volume 21, С. 53 - 65

Опубликована: Янв. 1, 2025

Background: Resolvin D2 (RvD2), which exhibits anti-inflammatory properties, is neuroprotective. This study aimed to ascertain the potential of serum RvD2 level as a prognostic predictor moderate-to-severe traumatic brain injury (msTBI). Methods: In this prospective cohort study, levels were measured in 136 patients with msTBI and 100 healthy controls. The severity scoring systems encompassed Rotterdam computed tomography classification Glasgow Coma Scale (GCS). Post-trauma six-month outcome scale (GOS) was deemed an indicator, GOS scores below 4 indicating poor prognosis. Sequential univariate multivariate analyses used determine correlative factors changeable predictors adverse Results: Patients displayed marked decline compared controls (median, 95.2 versus 252.8 pg/mL; P< 0.001). Serum independently correlated GCS (beta, 8.989; 95% confidence interval (CI), 3.678– 14.280; P=0.001) − 14.676; CI, 25.885--3.468; P=0.011), associated continuous 0.004; 0.002– 0.007; P=0.003), ordinal (odds ratio, 1.008; 1.002– 1.015; P=0.015), prognosis 0.991; 0.983– 0.999; P=0.037) at mark. A linear correlation observed between likelihood (P for nonlinear = 0.090). exhibited strong discrimination efficiency probability (P< 0.001), similar ability (P=0.337) (P=0.300). integrative model encompassing RvD2, performed well using series statistical methods. Conclusion: significant decrease after may accurately indicate trauma efficiently distinguish possibility neurological outcomes msTBI, signifying that be clinical significance prediction TBI. Keywords: resolvin 2, injury, prognosis, severity, biomarkers

Язык: Английский

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Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Язык: Английский

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Xuanfei Baidu Decoction Alleviated Sepsis-Induced ALI by Modulating Gut Microbial Homeostasis and Promoting Inflammation Resolution: Bioinformatics and Experimental Study

ACS Omega, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

The Xuanfei Baidu Decoction (XFBD) has shown effective therapeutic potential for acute lung injury (ALI) induced by lipopolysaccharide and immunoglobin G immune complexes. Herein, the protective effects mechanisms of XFBD were investigated in a sepsis-induced ALI mouse model along with its on gut microbiota. Notably, bioinformatics molecular docking analyses revealed that components exhibited strong binding affinity to G-protein-coupled receptor 18 (GPR18). In murine model-induced cecal ligation puncture (CLP)-XFBD markedly improved histopathology, reduced M1 macrophage polarization, decreased pro-inflammatory cytokine levels both tissues MH-S macrophages. Furthermore, downregulated key inflammatory pathways, including nuclear factor (NF)-κB, phosphorylated-NF-κB, CCAAT/enhancer protein-δ, nucleotide-binding oligomerization domain-like pyrin domain-containing 3/Caspase-1/gasdermin D axis. Additionally, restored CLP-induced disruption microbiota balance, increasing abundance Prevotellaceae Ruminococcaceae_UCG_014. Altogether, findings this study suggest alleviates modulating microbial homeostasis inhibiting associated particularly via GPR18 activation, presenting promising treating ALI.

Язык: Английский

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RvD2 mitigates TNFɑ-Induced mitochondrial reactive oxygen species through NRF2 signaling in placental trophoblasts

Frontiers in Physiology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

Hypertensive disorders of pregnancy (HDP) are marked by elevated levels TNFα, which increases reactive oxygen species (ROS) and disrupts metabolism trophoblasts. Resolvin D2 (RvD2), an omega-3 fatty acid-derived lipid mediator, is known to resolve inflammation, but its role in protecting trophoblasts promoting antioxidant responses alleviate ROS remains unclear. Nuclear translocation nuclear factor erythroid 2-related 2 (NRF2) controls cellular defense mechanisms against oxidative stress helps with the maintenance redox homeostasis. Upon nucleus, NRF2 activates response element (ARE), inducing expression genes that can mitigate ROS. Hence, we hypothesized RvD2 prevents TNFα-induced mitochondrial dysfunction We investigated RvD2's potential protective pretreating JEG cells 100 nM RvD2, followed exposure 50 or ng/mL TNFα. also observed placental TNFα were elevated, while protein reduced human HDP tissues compared normotensive placentas. demonstrate alone enhances translocation, glutathione function, reduces In contrast, decreases levels, consumption rates, impairs migration. Notably, pretreatment before protects ROS, restores rates These findings functions as a positive regulator endogenous properties enhancing mitigating

Язык: Английский

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Leucine‐Rich Repeat‐Containing G Protein‐Coupled Receptor 6 Ameliorates Pressure Overload‐Induced Cardiac Hypertrophy by Regulating Cardiomyocyte Metabolic Reprogramming

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Abstract Metabolic reprogramming is a pivotal mechanism in the pathogenesis of pathological cardiac hypertrophy. Leucine‐rich repeat‐containing G protein‐coupled receptor 6 (Lgr6) has emerged as significant player cardiovascular diseases. In this study, potential Lgr6 to counteract pressure overload (PO)‐induced hypertrophy investigated, and underlying mechanisms involved are elucidated. Transverse aortic constriction (TAC) induced establish an vivo model. Adeno‐associated virus 9 adenovirus vectors utilized knock down overexpress cardiomyocytes, respectively. The effects its downstream molecules subsequently determined using RNA sequencing chromatin immunoprecipitation. Significant downregulation expression observed heart after TAC cardiomyocytes treated with phenylephrine. deficiency accelerated overexpression inhibits dysfunction TAC. Mechanistically, vitro experiments suggest that regulates ubiquitin specific protease 4 (USP4) peroxisome proliferator‐activated alpha (PPARα) by activating cGMP/PKG/CREB1 signalling pathway, thereby regulating cardiomyocyte metabolic PO. Targeting can be therapeutic strategy treat

Язык: Английский

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Resolvin D2 activates anti-inflammatory microglia via restoring autophagy flux and alleviate neuropathic pain following spinal cord injury in rats

Experimental Neurology, Год журнала: 2023, Номер 370, С. 114573 - 114573

Опубликована: Окт. 18, 2023

Язык: Английский

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Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116564 - 116564

Опубликована: Апрель 11, 2024

During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation SPMs pathways in pathological vascular remodeling and resolvin D2 (RvD2) prevent contractile endothelial dysfunction model obesity hypertension. In aortic samples patients with or without abdominal aneurysms (AAA), we evaluated gene expression enzymes involved synthesis (ALOXs), receptors pro-inflammatory genes. an experimental dilation induced by high fat diet (HFD, 60%, eighteen weeks) angiotensin II (AngII) infusion (four weeks), studied the effect RvD2 administration aorta small mesenteric arteries structure function markers inflammation. human macrophages effects AngII profile. patients, found positive correlations between AAA obesity, ALOX15, receptor GPR18, There was inverse correlation ALOX15 growth rate. mice model, partially prevented HFD plus AngII-induced adipose hypertension, remodeling, hypercontratility dysfunction, proinflammatory cell apoptosis. macrophages, impaired efferocytosis switched represent novel protective strategy preventing damage associated hypertension likely through immune cells.

Язык: Английский

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Gpr18 agonist dampens inflammation, enhances myogenesis, and restores muscle function in models of Duchenne muscular dystrophy

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Авг. 14, 2023

Introduction: Muscle wasting in Duchenne Muscular Dystrophy is caused by myofiber fragility and poor regeneration that lead to chronic inflammation muscle replacement fibrofatty tissue. Our recent findings demonstrated Resolvin-D2, a bioactive lipid derived from omega-3 fatty acids, has the capacity dampen stimulate alleviate disease progression. This therapeutic avenue many advantages compared glucocorticoids, current gold-standard treatment for Dystrophy. However, use of lipids as drugs also faces technical challenges such their instability oral bioavailability. Methods: Here, we explored potential PSB-KD107, synthetic agonist resolvin-D2 receptor Gpr18, alternative Results discussion: We showed PSB-KD107 can myogenic patient iPSC-derived myoblasts vitro . RNAseq analysis revealed an enrichment biological processes related acid metabolism, biosynthesis, small molecule steroid-related PSB-KD107-treated mdx myoblasts, well signaling pathways Peroxisome proliferator-activated receptors, AMP-activated protein kinase, mammalian target rapamycin, sphingolipid pathways. In vivo , dystrophic mice with resulted reduced inflammation, enhanced myogenesis, improved function. The positive impact on function similar one Resolvin-D2. Overall, our provide proof-of concept analogs receptors hold

Язык: Английский

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Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

Biomedicines, Год журнала: 2023, Номер 11(12), С. 3109 - 3109

Опубликована: Ноя. 21, 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the IPF related genes, so as investigate potential molecular provide guidance for clinical treatment. Next-generation sequencing dataset GSE213001 obtained from Gene Expression Omnibus (GEO), differentially expressed (DEGs) were identified between normal control group. The DEGs group screened DESeq2 package R language. Ontology (GO) REACTOME pathway enrichment analyses performed. Using g:Profiler, function Then, protein-protein interaction (PPI) network constructed via Integrated Interactions Database (IID) database. Cytoscape Network Analyzer identify hub genes. miRNet NetworkAnalyst databaseswereused construct targeted microRNAs (miRNAs), transcription factors (TFs), small drug molecules. Finally, receiver operating characteristic (ROC) curve analysis validate A total 958 out in study, including 479 up regulated down Most significantly enriched response stimulus, GPCR ligand binding, microtubule-based process, defective GALNT3 causes HFTC. combination results PPI network, miRNA-hub gene regulatory TF-hub LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8, EFHC2 selected. Cyclothiazide rotigotinethe predicted molecules Our findings will contribute identification biomarkers novel strategies treatment IPF, strategy therapy.

Язык: Английский

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