Fraxetin inhibits IKKβ, blocks NF-κB pathway and NLRP3 inflammasome activation, and alleviates spleen injury in sepsis

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111406 - 111406

Published: Feb. 1, 2025

Language: Английский

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Association between D-dimer to lymphocyte ratio and in hospital all-cause mortality in elderly patients with sepsis: a cohort of 1123 patients

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 14, 2025

Background The D-dimer to lymphocyte ratio (DLR), a novel inflammatory biomarker, had been shown be related adverse outcomes in patients with various diseases. However, there was limited research on the relationship between DLR and infectious diseases, particularly those sepsis. Therefore, this study aimed explore association hospital all-cause mortality elderly Methods A total of 1123 admitted intensive care unit (ICU) were included study. categorized into quartiles (Q1-Q4) based their values. primary ICU mortality. Kaplan-Meier analysis conducted compare among four groups. sepsis further elucidated using receiver operating characteristic (ROC) curve Cox proportional hazards regression analysis. Results participants median age 75 (65-84) years, 707 (63.0%) being male. rates 33.7% 31.9%, respectively. highlighted significantly increased risk elevated values (log-rank p < 0.001). ROC analyses revealed that stronger ability predict than or Lym. Multivariable as an independent predictor death [per 1 SD increase DLR: HR (95% CI): 1.098 (1.020-1.181); = 0.013] 1.095 (1.017-1.180); 0.017] during stay. Conclusions higher value associated This finding demonstrated could convenient useful prognostic marker for prognosis.

Language: Английский

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Editorial: Understanding molecular mechanisms to facilitate the development of biomarkers for therapeutic intervention in gastrointestinal diseases and sepsis

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: March 11, 2025

Gastrointestinal (GI) disorders include a range of pathological conditions with varying severities and outcomes that impact the integrity function GI tract. These indigestion, inflammatory bowel diseases (IBDs) ulcerative colitis (UC) Crohn's disease (CD), malignant tumors. The resulting dysfunction intestinal barrier, leading to impaired permeability, allows for translocation luminal contents, including intact microbes microbial products. This situation can cause severe sepsis potentially fatal if timely intervention is not provided. Advancements in omics technology have facilitated identification evaluation molecular biomarkers diagnosis. encompass genomic (e.g., single nucleotide polymorphisms), transcriptomic (including non-coding RNAs), epigenetic DNA methylation), proteomic, metabolomic, microbiome (Dalal et al., 2020;Sahoo 2022bSahoo , 2024a) ) (Figure 1). hold significant clinical potential improving diagnosis, prognosis, treatment strategies patients sepsis. For diagnosing sepsis, addition lactate as widely utilized biomarker, other surrogate markers, such C-reactive protein (CRP) procalcitonin, which are produced response infection inflammation, may assist identifying at risk developing before organ occurs (Faix, 2013). As oxidative stress (OS) plays key role progression septic shock multiple failure (Sahoo 2024b;Wong 2025), OS markers associated specifically, superoxide dismutase, soluble endoglin, asymmetric dimethylarginine, neopterin, merit further investigation (Helan 2022). Several emerging microRNA-486-5p, circular RNAs (circRNAs), HOXA distal transcript antisense RNA (a lncRNA located on chromosome 7q15.2), C vitamin K-dependent glycoprotein), prokineticin 2, triiodothyronine also enhancing early detection prognostic assessment high sensitivity specificity (He 2024).Mendelian randomization (MR) examines causal effects modifiable exposures, factors, health by utilizing genetic variants linked those specific exposures (Richmond, MR analysis Zhang al. showed CMPF (3-carboxy-4-methyl-5propyl-2-furanpropanoate) has an association 28-day all-cause mortality cases metabolic pathway alpha-linolenic acid linoleic was identified crucial factor development study Ye demonstrated levels suppression tumorigenicity 2 (sST2) blood diagnostic implications Moreover, sST2 comparable predictive capability SOFA (Sequential Organ Failure Assessment) APACHE II (Acute Physiology Chronic Health Evaluation II) scores had greater than lactic assessing prognosis Jin used single-cell sequencing (scRNA-seq) several PIM1 (proviral integration site Moloney murine leukemia virus kinase 1), HIST1H1C (Histone Cluster 1 H1 Family Member C), IGSF6 (Immunoglobulin Superfamily 6). involvement modulating immune-inflammatory during verified through experimental validation, indicating promising novel therapeutic target.The endoscopic suspected IBD collection mucosal biopsies histopathological confirmation continues be gold standard establishing efficacy, post-operative recurrence; however, it costs invasiveness. Biomarkers enable non-invasive evaluation, fecal calprotectin being most frequently current practice. T>C substitution SNPs affect functionality DLG5 (discs large homolog 5) protein, along lack CARD15/NOD2 (caspase recruitment domain family number 15/nucleotide-binding oligomerization domain-containing 2) CD pathogenesis, could serve (Dudzińska 2018). (microbial markers) been reported. example, Faecalibacterium prausnitzii its phylogroups elevated Escherichia coli counts Akkermansia muciniphila pediatric Additionally, reductions Firmicutes (Clostridiales) correlate severity, while increased abundance Lactobacilllaceae Enterococcaceae families, well genera Lactobacillus, Enterococcus, Eggerthella, noted UC (Wang 2024). In dogs CIE, there notable dysbiotic profile both bacteria, marked reduction Clostridium Bacteroides increase Enterobacteriaceae 2022a).The regulation gene expression mediated microRNA (miRNA) essential appropriate functioning intestine (Shanahan 2021). Numerous studies effectively unique miRNA profiles indicate upregulation or downregulation one more miRNAs biopsy samples from (James, 2020) affected chronic enteropathy (CIE) 2024a). colonic mucosa active shown overexpress miRNAs, miR-21, miR-150, miR-155, like miR-143 miR-145 when compared healthy controls (Alghoul Comparing controls, miR-196 miR-7 differential saliva, blood, colon tissue analyzed (Schaefer 2015). research highlighted (specifically, miR-31, miR-142-3p, miR-142-5p) exhibiting changes across all three sample types comparing non-IBD Recent methylation genes contributes pathogenesis IBD, implying their utility (Cooke 2012;Nimmo 2012). A comprehensive patterns genome, performed rectal biopsies, revealed signatures, Fanconi anemia complementation group (FANCC), thyroid hormone receptor-associated (THRAP2), globoside alpha-1,3-Nacetylgalactosaminyltransferase (GBGT1), tumor necrosis ligand superfamily member 4 (TNFSF4), 12 (TNFSF12), docking (DOK2), fucosyltransferase 7 (FUT7). exhibited differences specimens individuals Response infliximab resulted decreases macrophage-derived cluster differentiation 14 (CD14) CD86 levels, chemokine CCL2 (Magnusson 2015), highlighting monitor treatment.The Song employing suggests interleukin-13 (IL-13) pathophysiology (CD UC). Whereas macrophage migration inhibitory appears specifically related CD, stem cell likely play Another Qian gastric cancer exhibit decreased tryptophan, nonadecanoate (19:0), erythritol. Zhu employed GPBAR1 (G protein-coupled bile receptor IL1RL1 (Interleukin receptor-like PRKCB (Protein Kinase Beta), PNMT (Phenylethanolamine N-Methyltransferase) IBD. protective effect against GPX1 (Glutathione peroxidase GPBAR1, implicated UC. scRNA-seq Keever-Keigher common were observed disorders, extensive MTRNR2L8 (MT-RNR2 Like 8) various types. XIST (X Inactive Specific Transcript) different Th2 (T helper 2)-associated eosinophilic noteworthy.Colorectal (CRC) neoplasia. To facilitate CRC, minimally invasive reproducible technique known liquid (LB) established. method isolates cancer-derived components patients' peripheral and/or body fluids, circulating cells (CTC), miRNA, long (lncRNAs), (ctDNA) (Zhang 2023). Heat-shock 27 (Hsp27) expressed explicitly well-differentiated CRC biomarkers, epidermal growth (EGFR), B (AKT), human (ERBB2) (Gan 2014). Glutathione S-transferase pi1 (GSTP1) KTR8 overexpressed poorly differentiated CRCs. contrast, triosephosphate isomerase (TPI), tubulin beta chain (TUBB), fatty acid-binding (FABP1) upregulated exclusively welldifferentiated Human leukocyte antigen (HLA-A) Circular (circRNAs) hsa_circ_001978, hsa_circ_103627, hsa_circ_105039, circ_0124554 indicators diagnosis CRC. Levels serum miR-29a, miR-125b differentiate colorectal neoplasia ones (Yamada Serum miR-92a, miR-182S, miR-223, miR-17-5p, miR-18a-5p, miR-18b-5p, miR-103a-3p, miR-127-3p, miR-151a-5p, miR-181a-5p screening CircRNAs synergize proteins RNAs, circ_0000523 methyltransferase-like 3 (METTL3), enhance accuracy 2022).Carcinoembryonic (CEA) carbohydrate 19-9 (CA19-9) currently primary conducted Dai indicates overall survival rate disease-free progressively decline increasing positive after surgical intervention. Nomograms pre-and postoperative CEA CA19-9 demonstrate predicting recurrence stage I-III following radical surgery, significantly outperforming American Joint Committee Cancer (AJCC) 8th Tumor-Node-Metastasis (TNM) stage. Rad highlights machine learning algorithms recurrence, examining least serial measurements necessary accurate prediction recurrence. Pan involved retrospective data 36,708 who underwent gastroscopy colonoscopy between 2005 2022. Conventional adenomas (CAs), serrated polyps (SPs), non-adenomatous (NAPs), Helicobacter pylori older age. presence moderate metaplasia NAP CAs. found low-grade intraepithelial neoplasia, whereas high-grade correlation advanced pathology CRC.In individual without signs, biomarker panels resource identify recognize precancerous conditions. symptomatic patients, these help cancerous benign states. Furthermore, undergoing procedures, radiation therapy, chemotherapy, valuable tools evaluating success elimination (complete resection remission) Identifying validating optimal step, offers considerable personalized medicine outcomes. However, into they

Language: Английский

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miRNAs and Hematological Markers in Non-Alcoholic Fatty Liver Disease—A New Diagnostic Path?

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 230 - 230

Published: Jan. 18, 2025

Background: Asymptomatic liver steatosis constitutes an emerging issue worldwide. Therefore, we decided to explore relationships between selected types of microRNAs (miRNAs), serological markers fibrosis and hematological parameters in the course non-alcoholic fatty disease (NAFLD). Methods: Two hundred seven persons were included survey: 97 with NAFLD 110 healthy controls. Serological concentrations miR-126-3p, miR-197-3p, miR-1-3p measured all participants. Direct indices [procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming factor-α (TGF-α) laminin] together indirect (AAR, APRI, FIB-4 GPR) also evaluated. The assessment concerned: mean platelet volume (MPV), distribution width (PDW), plateletcrit (PCT), red blood cell (RDW), MPV (PLT) ratio (MPR), RDW PLT (RPR), neutrophil lymphocyte (LYM) (NLR), LYM (PLR) (RLR). Additionally, score BARD applied. Results: concentration miR-126-3p was higher, miR-197-3p lower group (p < 0.0001). correlated notably indices: negatively PDW 0.05) positively PLR 0.05). Conclusions: Significant correlations miRNA molecules indicate inflammation as a potential background create new possibilities for diagnostic approach.

Language: Английский

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The Efficacy of a Novel Medical Artificial Intelligence Large Model(MedGo)-Guided Identification and Personalized Treatment of Sepsis: Study Protocol for a Single- centered Randomized Controlled Trial

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Background Sepsis, a life-threatening organ dysfunction resulting from dysregulated host response to infection, remains major global health challenge with high morbility and mortality. Current diagnostic management frameworks still lack the satisfied sensitivity specificity for early detection personalized treatment. In this study, we aim evaluate efficacy of MedGo-Sepsis, novel large language model developed by our collaborating team us that integrates clinical immunological data, guide identification treatment sepsis in emergency department. Methods This single-center, randomized controlled trial will enroll adult patients presenting department suspected sepsis. Participants be 1:1 at physician level either intervention group receiving standard care augmented MedGo-Sepsis guidance or control alone. provides real-time risk assessments, detailed immune parameter profiling, stratification based on phenotypes, recommendations. The primary outcome is 28-day all-cause Secondary outcomes include changes Sequential Organ Failure Assessment (SOFA) score, accuracy, time appropriate antibiotic administration, resource utilization, patient-reported outcomes, workload. Discussion assess whether through integration individualized data technology, improves compared care. combination enhanced diagnostics tailored therapeutic strategies has potential advance precision critical setting. Trial registration been prospectively registered Chinese Clinical Trial Registry (ChiCTR2400094116) December 17, 2024.

Language: Английский

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Prokineticin-2 and Procalcitonin\'s Diagnostic Accuracy for Sepsis in Critically Ill Patients: A Prospective Observational Study

Indian Journal of Critical Care Medicine, Journal Year: 2025, Volume and Issue: 29(3), P. 268 - 272

Published: Feb. 28, 2025

Sepsis stands as a significant contributor to mortality in ICU settings worldwide. Early diagnosis and appropriate treatment are therefore essential reduce mortality. We planned this study investigate the diagnostic significance of prokineticin-2 (PK-2) patients with sepsis. Adult sepsis who were admitted our intensive care unit (ICU) included prospective observational study. On day admission 7th stay, levels procalcitonin (PCT) PK-2 assessed. Patients' was observed for 28 days. This research involved 83 meeting inclusion criteria. Prokineticin-2 showed sensitivity 70.6% sepsis, outperforming PCT 64.7%. In predicting mortality, displayed 95.5%, whereas demonstrated an even higher at 98.4%. Prokinectin-2 can be used screening adult ICU. Bhat K, Kothari N, Sharma A, Goyal S, Meshram T, Paliwal B, et al. Procalcitonin's Diagnostic Accuracy Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2025;29(3):268-272.

Language: Английский

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Comprehensive integration of diagnostic biomarker analysis and immune cell infiltration features in sepsis via machine learning and bioinformatics techniques

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Introduction Sepsis, a critical medical condition resulting from an irregular immune response to infection, leads life-threatening organ dysfunction. Despite advancements, the need for research into dependable diagnostic markers and precise therapeutic targets. Methods We screened out five gene expression datasets (GSE69063, GSE236713, GSE28750, GSE65682 GSE137340) Gene Expression Omnibus. First, we merged first two datasets. then identified differentially expressed genes (DEGs), which were subjected KEGG GO enrichment analyses. Following this, integrated DEGs with key modules as determined by Weighted Co-expression Network Analysis (WGCNA), identifying 262 overlapping genes. 12 core subsequently selected using three machine-learning algorithms: random forest (RF), Least Absolute Shrinkage Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVW-RFE). The utilization of receiver operating characteristic curve in conjunction nomogram model served authenticate discriminatory strength efficacy CIBERSORT was utilized evaluate inflammatory immunological sepsis. Astragalus, Salvia, Safflower are primary elements Xuebijing, commonly used clinical treatment Using Traditional Chinese Medicine Systems Pharmacology Database Platform (TCMSP), chemical constituents these herbs their target Results found that CD40LG is not only one identified, but also common active components quercetin, luteolin, apigenin herbs. extracted structure ingredients -flavonoids. Through docking analysis, further validated interaction between flavonoids CD40LG. Lastly, blood samples collected healthy individuals sepsis patients, without administration extraction peripheral mononuclear cells (PBMCs). By qPCR WB analysis. observed significant differences across groups. In this study, pinpointed candidate hub constructed its diagnosis. Discussion This provides potential evidence diagnosis offers insights pathogenesis disease progression

Language: Английский

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LINC02363: a potential biomarker for early diagnosis and treatment of sepsis

BMC Immunology, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 15, 2025

Sepsis remains a leading cause of global morbidity and mortality, yet early diagnosis is hindered by the limited specificity sensitivity current biomarkers. The aim this study was to identify lncRNAs that play key role in sepsis provide potential biomarkers for treatment sepsis. Transcriptomic data from patients were retrieved Chinese National Genebank (CNGBdb). Differential expression analysis identified 2,348 LncRNAs 5,125 mRNAs (|FC|≥2, FDR < 0.05). Weighted gene co-expression network (WGCNA) meta-analysis applied screen core genes. Gene set enrichment (GSEA) explored functional pathways, while single-cell sequencing qPCR validated cellular localization patterns. WGCNA three genes: LINC02363 (LncRNA), DYNLT1, FCGR1B. Survival meta-analyses revealed strong correlations between these genes outcomes. GSEA highlighted LINC02363's involvement "herpes simplex virus type 1 infection," "tuberculosis," ribosome pathways. Single-cell showed FCGR1B's broad distribution across immune cells, DYNLT1 localized predominantly macrophages. confirmed significant upregulation (p 0.01), FCGR1B 0.05), 0.05) compared controls. may serve as new biomarker

Language: Английский

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Prof. Dr. Giovanni De Toni—Editorial for the Commemoration of a Pediatric Luminary

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3198 - 3198

Published: March 30, 2025

Living in Liguria, acknowledging that the sea may be a metaphor for human condition is not difficult [...]

Language: Английский

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Sepsis and post-sepsis syndrome: a multisystem challenge requiring comprehensive care and management—a review

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 8, 2025

Sepsis, a medical emergency with high mortality rates, demands comprehensive care spanning from early identification to patient rehabilitation. The sepsis survival chain encompasses recognition, severity assessment, activation of services, initial antimicrobial therapy, hemodynamic stabilization, and integrated These interconnected steps are critical reducing morbidity mortality. Despite advancements in international guidelines, adherence remains limited, contributing significant disease burden. Beyond its acute phase, post-sepsis syndrome (PSS) is characterized by long-term immune dysregulation, chronic inflammation, metabolic dysfunction, predisposing survivors recurrent infections, cardiovascular disease, neurocognitive decline. Mitochondrial dysfunction epigenetic modifications play central role prolonged immunosuppression, impairing adaptive innate responses. Sepsis-induced organ impacts multiple systems, including the brain, heart, kidneys. In it associated neuroinflammation, blood-brain barrier accumulation neurotoxic proteins, leading cognitive impairment. Myocardial involves inflammatory mediators such as TNF-α IL-6, while sepsis-associated kidney injury (SA-AKI) arises hypoperfusion heightening risk progression disease. Additionally, alterations neutrophil continuous platelet activation, suppressed antitumoral responses contribute increased infection complications. Timely targeted interventions, cytokine modulation, restoration, support, structured rehabilitation strategies, pivotal for improving outcomes. However, financial infrastructural limitations low-resource settings pose barriers effective management. Precision medicine, AI-driven warning optimized referral networks can enhance detection personalized treatments. Promoting public professional awareness sepsis, strengthening multidisciplinary care, integrating follow-up programs imperative priorities quality life survivors.

Language: Английский

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