Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.
- MeSH
- biologický transport MeSH
- extracelulární vezikuly * metabolismus MeSH
- myši MeSH
- NF-kappa B * metabolismus MeSH
- signální transdukce MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients. BACKGROUND: Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective. METHODS: In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation. RESULTS: By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis. CONCLUSIONS: Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.
Hypervirulentní kmeny Klebsiella pneumoniae (hvKP) mohou způsobovat atypické multilokulární infekce u jinak zdravých pacientů. Diagnostika infekce vyvolané hvKP je založena především na klinickém nálezu a laboratorních výsledcích včetně detekce genů virulence. Typicky se projevuje jako jaterní absces s metastatickým šířením. Léčba je založena na chirurgickém řešení v kombinaci s cílenou antimikrobiální terapií. Výskyt infekce hvKP je relativně častý v Asii. V Evropě je sice stále vzácný, ale incidence onemocnění se zvyšuje. Cílem článku je poskytnout stručný přehled problematiky a upozornit na možný výskyt infekcí hvKP.
Hypervirulent strains of Klebsiella pneumoniae (hvKP) can cause atypical multilocular infections in otherwise healthy patients. Diagnosis of infection caused by hvKP is based mainly on clinical findings and laboratory results, including detection of virulence genes. It typically manifests as hepatic abscess with metastatic spread. Treatment is based on surgical intervention in combination with targeted antimicrobial therapy. The occurrence of hvKP infection is relatively common in Asia, and while still rare in Europe, incidence is increasing. The article aims to provide a short overview of the issue and increase awareness of the possible occurrence of hvKP infections.
- MeSH
- amputace MeSH
- antibakteriální látky terapeutické užití MeSH
- dospělí MeSH
- faktory virulence MeSH
- infekce bakteriemi rodu Klebsiella * diagnóza epidemiologie terapie MeSH
- infekce měkkých tkání chirurgie diagnóza etiologie farmakoterapie MeSH
- Klebsiella pneumoniae MeSH
- lidé MeSH
- sepse MeSH
- virulence MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The aim of this study was to evaluate the serum levels of calprotectin and calgranulin C and routine biomarkers in patients with bacterial sepsis (BS). The initial serum concentrations of calprotectin and calgranulin C were significantly higher in patients with BS (n = 66) than in those with viral infections (n = 24) and the healthy controls (n = 26); the level of calprotectin was found to be the best predictor of BS, followed by the neutrophil-lymphocyte count ratio (NLCR) and the level of procalcitonin (PCT). The white blood cell (WBC) count and the NLCR rapidly returned to normal levels, whereas PCT levels normalized later and the increased levels of calprotectin, calgranulin C, and C-reactive protein persisted until the end of follow-up. Our results suggest that the serum levels of calprotectin are a reliable biomarker of BS and that the WBC count and the NLCR are rapid predictors of the efficacy of antimicrobial therapy.
- MeSH
- bakteriální infekce krev diagnóza MeSH
- biologické markery krev MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- kinetika MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutrofily cytologie MeSH
- počet leukocytů MeSH
- počet lymfocytů MeSH
- protein S100A12 krev MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- sepse krev diagnóza MeSH
- virové nemoci krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Pancreatic tumors and their surgical resection are associated with significant morbidity and mortality, and the biomarkers currently used for these conditions have limited sensitivity and specificity. Because calprotectin and calgranulin C serum levels have been demonstrated to be potential biomarkers of certain cancers and complications of major surgery, the levels of both proteins were tested in the current study in patients with benign and malignant pancreatic tumors that were surgically removed. The baseline serum levels and kinetics of calprotectin and calgranulin C during the 7-day postoperative period were evaluated with immunoassays in 98 adult patients who underwent pancreatic surgery. The baseline serum levels of calprotectin and calgranulin C in patients with malignant (n = 84) and benign tumors (n = 14) were significantly higher (p < 0.01) when compared to those in the healthy controls (n = 26). The serum levels of both proteins were also significantly (p < 0.05) higher in patients with benign tumors than in those with malignant tumors. After surgery, the serum levels of calprotectin and calgranulin C were significantly (p < 0.01) higher than their baseline values, and this elevation persisted throughout the seven days of the follow-up period. Interestingly, starting on day 1 of the postoperative period, the serum levels of both proteins were significantly (p < 0.05) higher in the 37 patients who developed postoperative pancreatic fistulas (POPFs) than in the patients who had uneventful recoveries (n = 61). Moreover, the serum levels of calprotectin and calgranulin C demonstrated a significant predictive value for the development of POPF; the predictive values of these two proteins were better than those of the serum level of C-reactive protein and the white blood cell count. Taken together, the results of this study suggest that calprotectin and calgranulin C serum levels are potential biomarkers for pancreatic tumors, surgical injury to the pancreatic tissue and the development of POPFs.
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé MeSH
- nádory slinivky břišní chirurgie MeSH
- pooperační období MeSH
- prospektivní studie MeSH
- protein S100A12 krev MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl studie: Sledování kinetiky calprotectinu a calgranulinu C v krvi u polytraumatizovaných pacientů, posouzení sérových koncentrací obou proteinů jako prediktorů nozokomiální infekce a srovnání sérových koncentrací calprotectinu a calgranulinu C s rutinními prozánětovými faktory a skórovacími systémy. Typ pracoviště: Pracoviště intenzivní medicíny fakultní nemocnice. Typ studie: Monocentrická prospektivní studie. Materiál a metoda: Do studie bylo zařazeno 25 pacientů s polytraumatem a 20 zdravých dobrovolníků. Pacientům byla odebrána krev při příjmu (1. den) a 3., 5. a 7. den hospitalizace a byla stanovena sérová koncentrace calprotectinu a calgranulinu C enzymoimunoanalyticky. Pacienti byli skórováni dle Injury Severity Score, Acute Physiology And Chronic Health Evaluation II a Sequential Organ Failure Assessment Score (SOFA). Z rutinních laboratorních parametrů byl stanoven počet leukocytů, C-reaktivní protein (CRP), prokalcitonin (PCT), glykemie, laktát. Dále byl sledován případný rozvoj nozokomiální infekce. Výsledky: U polytraumatizovaných pacientů byly zjištěny signifikantní elevace sérové koncentrace calprotectinu a calgranulinu C oproti zdravým kontrolám po celou dobu sledování. Dále byla zjištěna pozitivní korelace mezi oběma proteiny a SOFA skóre 1. a 3. den hospitalizace. Calprotectin a calgranulin C pozitivně korelovaly 3. den s CRP a PCT a calprotectin koreloval s CRP i 5. den studie. Patrný byl trend nižší koncentrace calprotectinu a calgranulinu C u 10 pacientů s nozokomiální infekcí a u těchto nemocných byla pozorována 1., 3. a 5. den signifikantně vyšší glykemie oproti pacientům bez infekční komplikace (n = 8). Závěr: Výsledky naznačují využití sérových koncentrací calprotectinu a calgranulinu C jako potencionálních biomarkerů polytraumatu.
Objective: To study the kinetics of calprotectin and calgranulin C in the serum of patients with polytrauma, to evaluate the serum levels of both the proteins as predictors of nosocomial infection (NI), and to compare calprotectin and calgranulin C with routine biomarkers and scoring systems. Design: Monocentric, prospective, clinical study Setting: University Hospital ICU Materials and methods: The study included 25 polytrauma patients and 20 healthy volunteers. The blood specimens were collected on admission (day 1) and then on days 3, 5 and 7 of hospitalization. Concentrations of calprotectin and calgranulin C were determined by enzyme immunometric assay. Patients were scored with Injury Severity Score, Acute Physiology And Chronic Health Evaluation II a Sequential Organ Failure Assessment Score (SOFA). The white blood cell count and the serum concentrations of the C-reactive protein (CRP), procalcitonin (PCT), glucose and lactate were the measured routine biomarkers. Other parameters included length of ICU stay, duration of mechanical ventilation, antibiotic therapy and development of nosocomial infection. Results: Significant elevations of the calprotectin and calgranulin C serum levels in trauma patients in comparison to healthy subjects were observed during the whole study period. Concentrations of both the proteins correlated positively with the SOFA score on days 1 and 3, CRP and PCT on day 3; and calprotectin also correlated with CRP on day 5. A trend of low serum levels of calprotectin a calgranulin C was observed in patients with nosocomial infection (n=10). In addition, these patients had significantly higher glycaemia on days 1, 3 and 5 in comparison to patients without infectious complication (n=8). Conclusions: The results suggest calprotectin and calgranulin C serum levels as suitable biomarkers of severe injury.
- MeSH
- C-reaktivní protein analýza MeSH
- infekce spojené se zdravotní péčí diagnóza etiologie MeSH
- interpretace statistických dat MeSH
- kalcitonin krev MeSH
- leukocytární L1-antigenní komplex * analýza farmakologie MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- polytrauma * diagnóza komplikace patologie MeSH
- prospektivní studie MeSH
- protein S100A12 * farmakologie krev MeSH
- vyhodnocení orgánové dysfunkce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The microbial etiology and source of sepsis influence the inflammatory response. Therefore, the plasma levels of cytokines (IL-6, IL-8, and IL-10), chemokines (CCL2/MCP-1, MIP-1β), heparin-binding protein (HBP), soluble CD14 (sCD14), and cortisol were analyzed in blood from septic patients obtained during the first 96 hours of intensive care unit hospitalization. The etiology was established in 56 out of a total of 62 patients enrolled in the study. Plasma concentrations of MCP-1, sCD14, IL-6, and IL-10 were significantly higher in patients with community-acquired pneumonia (CAP; n = 10) and infective endocarditis (IE; n = 11) compared to those with bacterial meningitis (BM; n = 18). Next, cortisol levels were higher in IE patients than in those with BM and CAP, and at one time point, cortisol was also higher in patients with gram-negative sepsis when compared to those with gram-positive infections. Furthermore, cortisol and MCP-1 levels correlated positively with the daily measured SOFA score. In addition, HBP levels were significantly higher in patients with IE than in those with BM. Our findings suggest that MCP-1, sCD14, IL-6, IL-10, cortisol, and HBP are modulated by the source of sepsis and that elevated MCP-1 and cortisol plasma levels are associated with sepsis-induced organ dysfunction.
- MeSH
- biologické markery metabolismus MeSH
- chemokin CCL2 metabolismus MeSH
- chemokin CCL4 metabolismus MeSH
- hydrokortison metabolismus MeSH
- interleukin-10 metabolismus MeSH
- interleukin-6 metabolismus MeSH
- interleukin-8 metabolismus MeSH
- kationické antimikrobiální peptidy metabolismus MeSH
- krevní proteiny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipopolysacharidové receptory metabolismus MeSH
- péče o pacienty v kritickém stavu MeSH
- senioři MeSH
- sepse metabolismus MeSH
- transportní proteiny metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
