Search Results (5,277)

Klebsiella pneumoniae (K. pneumoniae), a kind of zoonotic bacteria, is among the most common antibiotic-resistant pathogens, and it causes nosocomial infections that pose a threat to public health. In this study, the roles of synthetic bovine neutrophil β-defensin-5 (B5) in regulating inflammatory response and metabolic response against multidrug-resistant K. pneumoniae infection in a mouse model were investigated. Mice were administrated intranasally with 20 μg of B5 twice and challenged with K. pneumoniae three days after B5 pretreatment. Results showed that B5 failed to directly kill K. pneumoniae in vitro, but it provided effective protection against multidrug-resistant K. pneumoniae via decreasing the bacterial load in the lungs and spleen, and by alleviating K. pneumoniae-induced histopathological damage in the lungs. Furthermore, B5 significantly enhanced the mRNA expression of TNF-α, IL-1β, Cxcl1, Cxcl5, Ccl17, and Ccl22 and obviously enhanced the rapid recruitment of macrophages and dendritic cells in the lungs in the early infection phase, but significantly down-regulated the levels of TNF-α, IL-1β, and IL-17 in the lungs in the later infection phase. Moreover, RNA-seq results showed that K. pneumoniae infection activated signaling pathways related to natural killer cell-mediated cytotoxicity, IL-17 signaling pathway, inflammatory response, apoptosis, and necroptosis in the lungs, while B5 inhibited these signaling pathways. Additionally, K. pneumoniae challenge led to the suppression of glycerophospholipid metabolism, the phosphotransferase system, the activation of microbial metabolism in diverse environments, and metabolic pathways in the lungs. However, B5 significantly reversed these metabolic responses. Collectively, B5 can effectively regulate the inflammatory response caused by K. pneumoniae and offer protection against K. pneumoniae. B5 may be applied as an adjuvant to the existing antimicrobial therapy to control multidrug-resistant K. pneumoniae infection. Our study highlights the potential of B5 in enhancing pulmonary bacterial clearance and alleviating K. pneumoniae-caused inflammatory damage. Full article

Background/Objectives: Odontogenic abscesses are a common cause of emergency visits to oral and maxillofacial surgery departments and can lead to life-threatening complications if they are not recognized and treated promptly. The aim of this study was to evaluate the prognostic value of the Aggregate Index of Systemic Inflammation (AISI) in comparison to other systemic inflammatory indices, including the Systemic Immune Inflammation Index (SII), the Neutrophil-to-Lymphocyte Ratio (NLR), the Platelet-to-Lymphocyte Ratio (PLR), and the Lymphocyte-to-Monocyte Ratio (LMR), in predicting the severity of odontogenic abscesses. Methods: This retrospective study included 221 patients hospitalized for odontogenic abscesses at Dubrava University Hospital between January 2019 and December 2023. Clinical and laboratory data, including AISI, SII, NLR, PLR, and LMR, were collected. The severity of the abscesses was assessed using the Symptom Severity (SS) Score and patients were categorized into less severe and severe groups based on their scores. An ROC curve analysis was used to assess the predictive accuracy of each inflammatory index. Results: The AISI was identified as the most effective predictor of abscess severity and had the highest sensitivity (SE = 82.93) and specificity (SP = 81.63) among the indices analyzed. It outperformed C-reactive protein (CRP) in predicting severe abscesses with an AUC of 0.90 compared to 0.74 for CRP. In addition, AISI showed significant correlations with length of hospital stay and the occurrence of systemic inflammatory response syndrome (SIRS). Conclusions: The AISI index is a better predictor of odontogenic abscess severity compared to other systemic inflammatory markers and CRP. Its integration into clinical practice could improve the early detection of high-risk patients, leading to better treatment outcomes and lower risks of complications. Full article

Objectives: The purpose of this study was to compare and contrast Kawasaki disease (KD) with multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: A retrospective analysis of the medical records of patients diagnosed with KD and MIS-C at a single institution from July 2020 to November 2021 was performed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. The MIS-C patients were older (p < 0.001) and had prolonged hospitalizations (p = 0.023), elevated neutrophil counts (p < 0.001), C-reactive protein (p < 0.001), procalcitonin (p < 0.001), interleukin-6 (p < 0.014), ferritin (p < 0.001), fibrinogen (p < 0.001), troponin I (p = 0.001), NT-proBNP (p < 0.001), and D-dimer levels (p < 0.001). There were more cases of hypotension (p = 0.024), decreased left ventricular function (p = 0.023), and a greater need for corticosteroids (p < 0.001), enoxaparin (p = 0.045), and therapeutic plasma exchange (p < 0.001). Kawasaki disease patients had a greater incidence of rash (p < 0.001), changes in oral mucosa (p < 0.001), conjunctival injection (p < 0.001), extremity changes (p < 0.001), and cervical lymphadenopathy (p < 0.001). They had a longer duration of fever (p < 0.001), elevated white blood cell count (p < 0.001), platelet count (p < 0.001), and alanine aminotransferase level (p < 0.001). The two groups were similar regarding the hemoglobin levels, erythrocyte sedimentation rates, albumin levels, and the frequency of coronary aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Advanced patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas prolonged fever and classical clinical features of KD favor KD. Full article

Background: Previous studies of the hydroethanolic extract of Virola elongata inner stem bark (HEVe) have demonstrated its antioxidant, gastroprotective, and antiulcer properties, but have not evaluated its anti-inflammatory potential. Methods: HEVe was obtained by maceration and phytochemically analyzed. Its systemic anti-inflammatory activity was assessed by its effect on lipopolysaccharide (LPS)-induced peritonitis in mice. HEVe gel (HEgVe) was employed to evaluate topical anti-inflammatory activity by measuring the ear edema resulting from croton-oil-induced dermatitis in mice. A cell viability assay was conducted to determine the non-cytotoxic concentrations of the HEVe. RAW 264.7 cells were stimulated by LPS to determinate cytokine and nitric oxide production. Results: A phytochemical analysis of the HEVe revealed the presence of phenolic acids, neolignans, flavonoids, and monomeric catechins. The oral treatment of acute peritonitis with HEVe reduced the total leukocytes, neutrophils, TNF-α, and IL-1β and elevated IL-10 levels. The application of the HEgVe reduced local edema. The HEVe on the RAW 264.7 cells exhibited no cytotoxicity, and the cells with HEVe displayed reduced TNF-α, IL-1β, and NO levels and increased IL-13 levels. Conclusions: HEVe demonstrated systemic and topical multitarget anti-inflammatory activity, likely due to the combined effects of secondary metabolites. HEVe emerges as a promising herbal remedy for inflammation with minimal cytotoxicity, emphasizing its potential therapeutic significance. Full article

The innate immune system (IIS) is an ancient and essential defense mechanism that protects animals against a wide range of pathogens and diseases. Although extensively studied in mammals, our understanding of the IIS in other taxa remains limited. The zebrafish (Danio rerio) serves as a promising model organism for investigating IIS-related processes, yet the immunogenetics of fish are not fully elucidated. To address this gap, we conducted a meta-analysis of single-cell RNA sequencing (scRNA-seq) datasets from zebrafish kidney marrow, encompassing approximately 250,000 immune cells. Our analysis confirms the presence of key genetic pathways in zebrafish innate immune cells that are similar to those identified in mammals. Zebrafish macrophages specifically express genes encoding cathepsins, major histocompatibility complex class II proteins, integral membrane proteins, and the V-ATPase complex and demonstrate the enrichment of oxidative phosphorylation ferroptosis processes. Neutrophils are characterized by the significant expression of genes encoding actins, cytoskeleton organizing proteins, the Arp2/3 complex, and glycolysis enzymes and have demonstrated their involvement in GnRH and CLR signaling pathways, adherents, and tight junctions. Both macrophages and neutrophils highly express genes of NOD-like receptors, phagosomes, and lysosome pathways and genes involved in apoptosis. Our findings reinforce the idea about the existence of a wide spectrum of immune cell phenotypes in fish since we found only a small number of cells with clear pro- or anti-inflammatory signatures. Full article

Background/Objectives: Coronavirus Disease 2019 (COVID-19) can cause liver injury and a deterioration of hepatic function. The Model for End-Stage Liver Disease (MELD) score is a good predictor for poor prognosis of hospitalized COVID-19 patients in the United States, Egypt and Turkey. Nevertheless, the best cut-off value for the MELD score to predict mortality in the Mexican population has yet to be established. Methods: A total of 234 patients with COVID-19 were studied in a tertiary-level hospital. Patients were stratified into survivors (n = 139) and non-survivors (n = 95). Receiver operating characteristic curves, Cox proportional hazard models, Kaplan–Meier method, and Bonferroni corrections were performed to identify the predictors of COVID-19 mortality. Results: MELD score had an area under the curve of 0.62 (95% CI: 0.56–0.68; p = 0.0009), sensitivity = 53.68%, and specificity = 73.38%. Univariate Cox proportional hazard regression analysis suggested that the leukocytes > 10.6, neutrophils > 8.42, neutrophil-to-lymphocyte ratio (NLR) > 8.69, systemic immune-inflammation index (SII) > 1809.21, MELD score > 9, and leukocyte glucose index (LGI) > 2.41 were predictors for mortality. However, the multivariate Cox proportional hazard model revealed that only the MELD score >9 (Hazard Ratio [HR] = 1.83; 95% confidence interval [CI]: 1.2–2.8; P_corrected = 0.03) was an independent predictor for mortality of COVID-19. Conclusions: Although the MELD score is used for liver transplantation, we suggest that a MELD score >9 could be an accurate predictor for COVID-19 mortality at admission to ICU requiring mechanical ventilation. Full article

Background: This real-life study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after autologous stem cell transplantation (auto-SCT). Methods: Sixty consecutive NDMM patients received four cycles of induction therapy with D-VTd. The conditioning regimen consisted of melphalan 200 mg/m². These patients were compared with a historical control group of 80 patients who received four cycles of VTd as induction therapy. Results: The median days to reach neutrophil and platelet engraftment significantly differed between patients treated with D-VTd (11 and 13 days, respectively) and VTd (10 and 12 days). Univariate Cox analyses show that patients treated with D-VTd had a hazard ratio of neutrophil engraftment that was 42% significantly lower than those in the VTd arm (HR: 0.58, p = 0.002), and a multivariate model confirmed this result. Patients treated with D-VTd developed FN more frequently. Univariate and multivariate logistic regressions revealed an association between D-VTd and FN. Delayed engraftment did not correlate with more extended hospitalization. No patients died in the first six months after transplantation. Conclusions: Our real-life study showed that a four-drug induction therapy containing DARA does not impact transplant safety outcomes. Full article

Staphylococcus aureus (S. aureus) is the leading cause of surgical site infections (SSIs) and is capable of biofilm growth on implanted foreign devices. The use of surgical irrigation solutions has become a common strategy to combat bacterial contamination events that occur during surgery. Despite their antimicrobial activity, SSI rates remain consistent, suggesting that low-level contamination persists. In these cases, circulating neutrophils must traffic from the blood to contamination sites to aid in bacterial clearance. The influence of irrigation solutions on neutrophils’ ability to engage with bacteria has not been explored. The effects of three commonly used irrigation solutions: Xperience (sodium lauryl sulfate), Irrisept (chlorhexidine gluconate), and Betadine^® (povidone-iodine) on nascent S. aureus biofilms alone and in the presence of human neutrophils were assessed at manufactured and diluted concentrations. All three solutions, at a 10% dilution, inhibited bacterial growth as demonstrated by culture assays and confocal video microscopy of bacterial aggregate formation. The effects of 10% dilutions of each of these solutions on neutrophil membrane integrity (by flow cytometry and propidium iodide staining) and motility (by confocal video microscopy of neutrophil track length) were investigated with differing outcomes for each irrigation solution. At this concentration only Irrisept preserved neutrophil membrane integrity and motility. Together, this study examines an overlooked aspect of surgical irrigation solutions by investigating their impact on innate immunity and highlights the feasibility of formulations wherein solution effectiveness is complemented by neutrophil function to reduce risks of infection. Full article

Background/Objectives: Neutrophils, as the first line of defense in the immune response, produce neutrophil extracellular traps (NETs) upon activation, which are significant in the pathogenesis and organ damage in sepsis. This study aims to explore the clinical value of myeloperoxidase-DNA (MPO-DNA) and cell-free DNA (cf-DNA) in sepsis patients. Methods: Clinical data were collected from 106 sepsis patients, 25 non-sepsis patients, and 51 healthy controls. Sequential Organ Failure Assessment (SOFA) scores were calculated, and levels of MPO-DNA) complexes and cf-DNA were measured using specific kits. Correlation analyses assessed relationships between indicators, while logistic regression identified independent risk factors. Receiver operating characteristic (ROC) curves calculated the area under the curve (AUC) to evaluate the diagnostic value of the biomarkers. Results: Sepsis patients exhibited significantly elevated levels of MPO-DNA and cf-DNA compared to non-sepsis patients and healthy controls. In sepsis patients, MPO-DNA and cf-DNA levels correlated with inflammation, coagulation, and organ damage indicators, as well as procalcitonin (PCT) levels and SOFA scores. Both C-reactive protein (CRP) and cf-DNA were identified as independent risk factors for sepsis, demonstrating moderate diagnostic value. ROC analysis showed that the combination of MPO-DNA and CRP (AUC: 0.837) enhances the AUC value of CRP (0.777). Conclusions: In summary, elevated serum levels of MPO-DNA and cf-DNA in sepsis patients correlate with SOFA scores and PCT levels, providing reference value for sepsis diagnosis in clinical settings. Full article

Introduction: Patients undergoing hemodialysis (HD) often exhibit an impaired cellular immune response, which may contribute to an increased susceptibility to infections and other complications. Th1 cells, a subset of T-helper cells, play a crucial role in cellular immunity. However, the modulation of Th1 cells by HD treatment remains unclear. Objective: This study aims to investigate the levels of circulating T cells, especially Th1 cells, and the neutrophil-to-lymphocyte ratio (NLR) in HD patients. Methods: We recruited 26 HD patients and 10 healthy volunteers. Demographical data were collected, and peripheral blood samples were analyzed. Absolute blood cell counts were determined, and T-cell populations were identified using flow cytometry. Th1 cells were defined as IFN-γ-producing CD4⁺ T cells after in vitro activation, and NLR was calculated through the ratio between the neutrophil and lymphocyte counts measured in peripheral blood. Results: We have observed a significant decrease in Th1 subpopulation frequency in HD patients, as well as significant correlations between immunological and demographic parameters, among which are the NLR values and the absolute values of T-cell subsets. Conclusions: These results seem to clarify the role of Th1 cells in modulating the immune responses of hemodialysis-treated patients, potentially considering its frequency as an indicator for CKD development. Full article

Traumatic brain injury (TBI) can cause major disability and increases the risk of neurodegeneration. Post-TBI, there is infiltration of peripheral myeloid and lymphoid cells; there is limited information on the peripheral immune response post-TBI in the immature brain—where injury may interfere with neurodevelopment. We carried out two injury types in juvenile mice: invasive TBI with a controlled cortical impact (CCI) and repetitive mild TBI (rmTBI) using weight drop injury and analysed the response at 5- and 35-days post-injury. In the two models, we detected the brain infiltration of immune cells (e.g., neutrophils, monocytes, dendritic cells, CD4+ T cells, and NK cells). There were increases in macrophages, neutrophils, and dendritic cells in the spleen, increases in dendritic cells in blood, and increases in CD8+ T cells and B cells in lymph nodes. These results indicate a complex peripheral immune response post-TBI in the immature brain, with differences between an invasive injury and a repetitive mild injury. Full article

Background/Objectives: Neutrophils are emerging as promising candidates for cell-based nanodrug delivery to tumors due to their unique biological properties. This study aims to investigate the mechanisms of nanoparticle internalization by neutrophils, specifically focusing on liposomes, poly(lactic-co-glycolic acid) (PLGA), and magnetite nanoparticles. Understanding these mechanisms could enhance the efficiency of neutrophil-based nanodrug delivery for cancer treatment. Methods: Neutrophils were isolated from the peripheral blood of mice bearing 4T1 mammary adenocarcinoma. Confocal microscopy, transmission electron microscopy, and flow cytometry were employed to evaluate the uptake of liposomes, PLGA, and magnetite nanoparticles by neutrophils. The effects of cultivation conditions, such as the presence or absence of plasma in the growth medium, were also examined. Additionally, the roles of immunoglobulins (IgG/IgM) and cell surface receptors (Fc and scavenger receptors) in nanoparticle internalization were explored. Results: All types of nanoparticles were successfully internalized by neutrophils, though the mechanisms of uptake varied. Plasma presence in the medium significantly influenced nanoparticle binding, particularly for PLGA nanoparticles. Internalization of PLGA nanoparticles was found to depend on the presence of IgG/IgM in the medium and Fc receptors on neutrophil surfaces, while scavenger receptors were not involved. Conclusions: Understanding the distinct endocytosis pathways for different nanoparticles can improve the efficacy of neutrophil loading with nanodrugs, potentially advancing the development of neutrophil-based cancer therapies. The findings underscore the importance of the extracellular environment in modulating nanoparticle uptake. Full article

Background/Objectives: Periprosthetic joint infection (PJI) is a disastrous complication after joint replacement procedures as the diagnosis remains a significant challenge. The objective of this study is to assess the accuracy and test the interdependency of the proposed compound serum biomarkers for the diagnosis of PJI after total hip arthroplasties (THA). Methods: From January 2019 to December 2023, 77 consecutive cases that underwent revision total hip arthroplasties (rTHA) were included in a single−retrospective, observational cohort study. A total of 32 arthroplasties were classified as having septic complications using the European Bone and Joint Infection Society (EBJIS) definition from 2021, while the other 45 cases were assigned as aseptic failures (AF). Results: In the univariate analysis between the two groups created, statistically significant differences (p < 0.005) were found for the following variables: time from primary arthroplasty to symptom onset (Time PA−SO), neutrophil count, Lymphocyte count, haematocrit level (HCT) and haemoglobin level (HGB), C−reactive protein (CRP), the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI). The ROC curve analysis showed that the SII (sensitivity 90.6% and specificity 62.2%) and the NLR (sensitivity 84.4% and specificity 64.4%) are the most accurate biomarkers. The multivariate analysis confirmed that NLR > 2.63 (p = 0.006), PLR > 147 (p = 0.021), MLR > 0.31 (p = 0.028), SII > 605.31 (p = 0.002), SIRI > 83.34 (p = 0.024), and AISI > 834.86 (p = 0.011) are all closely related to PJI diagnosis independently. Conclusions: The proposed serum biomarkers can be correlated with PJI diagnosis with the reserve of relatively low specificities. Full article

Nuclear imaging modalities can detect somatostatin receptor type 2 (SSTR2) in vivo as a potential marker of local post-MI inflammation. SSTR2+ macrophages are thought to be the main substrate for SSTR-targeted radioimaging. However, the distribution of SSTR2+ cells in the MI patients’ myocardium is unknown. Using immunohistochemistry, we investigated the distribution of SSTR2+ cells in the myocardium of patients who died during the MI inflammatory phase (n = 7) compared to the control group of individuals with fatal trauma (n = 3). Inflammatory cellular landscapes evolve in a wave front-like pattern, so we divided the myocardium into histological zones: the infarct core (IC), the border zone (BZ), the remote zone (RZ), and the peri-scar zone (PSZ). The number of SSTR2+ neutrophils (NPs), SSTR2+ monocytes/macrophages (Mos/MPs), and SSTR2+ vessels were counted. In the myocardium of the control group, SSTR2+ NPs and SSTR2+ Mos/MPs were occasional, SSTR2+ vessels were absent. In the RZ, the picture was similar to the control group, but there was a lower number of SSTR2+ Mos/MPs in the RZ. In the PSZ, SSTR2+ vessel numbers were highest in the myocardium. In the IC, the median number of SSTR2+ NPs was 200 times higher compared to the RZ or control group myocardium, which may explain the selective uptake of SSTR-targeted radiotracers in the MI area during the inflammatory phase of MI. Full article

Background and Objectives: Traumatic spinal cord injury (SCI) is a devastating condition that occurs in two phases: primary and secondary injury. These phases contribute to changes in blood vessels and the influx of inflammatory cells such as neutrophils and lymphocytes. The biomarker known as the neutrophil-to-lymphocyte ratio (NLR) has been suggested as being highly valuable in predicting outcomes for patients with traumatic brain injury, acute ischemic stroke, and traumatic spinal cord injury. Therefore, this review study aims to investigate the prognostic value of the NLR in predicting outcomes for patients with SCI. Materials and Methods: A thorough review of relevant articles was conducted using Mesh keywords in Medline via Embase, PubMed, Google Scholar, and Scopus from 2000 to 2023. The search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. After reviewing the articles and applying inclusion and exclusion criteria, only relevant articles were included in the study. Results: In the initial search, 41 papers were identified. After applying exclusion criteria, only three clinical studies remained for review. It is still debatable whether the NLR can serve as a cost-effective, readily available, and independent predictive factor for both mortality and recovery outcomes in patients with traumatic spinal cord injuries. Conclusions: Our study demonstrates that NLR, a readily available and inexpensive marker, can serve as an independent predictor of both mortality and recovery outcomes in patients with traumatic spinal cord injury. To reach a conclusive decision, additional data are required. Full article