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13 pages, 9825 KB  
Article
Comparison of Complete Blood Count Results Between K3-EDTA- and MgSO4-Anticoagulated Samples Using a DxH800 Analyzer
by Aurélie Védrenne, Florence Habarou, Tiffany Pascreau and Marc Vasse
J. Clin. Med. 2026, 15(12), 4607; https://doi.org/10.3390/jcm15124607 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: In case of EDTA-induced pseudothrombocytopenia (PTCP), MgSO4-anticoagulated tubes are recommended for platelet counting, requiring the collection of an additional tube. The aim of this study was to analyze whether complete blood count (CBC) and differential performed on MgSO4 [...] Read more.
Background/Objectives: In case of EDTA-induced pseudothrombocytopenia (PTCP), MgSO4-anticoagulated tubes are recommended for platelet counting, requiring the collection of an additional tube. The aim of this study was to analyze whether complete blood count (CBC) and differential performed on MgSO4-anticoagulated tubes were comparable to the results obtained on K3-EDTA samples, and to characterize the stability of the CBC over a 24 h period. Methods: In 355 patients (70 with a confirmed PTCP and 285 without PTCP), we compared CBC results obtained on K3-EDTA- and MgSO4-anticoagulated tubes, using DxH800 analyzers. In 33 cases, a differential was available for both anticoagulants, and for 10 patients, samples were re-analyzed 6, 12, and 24 h after the first determination. Results: In the presence or absence of clumps, white blood cell (WBC) count, hematocrit, and mean corpuscular volume (MCV) were slightly lower in MgSO4 than in K3-EDTA tubes, whereas mean corpuscular hemoglobin concentration (MCHC) was slightly higher. Mean platelet volume (MPV) was significantly lower on MgSO4- than on K3-EDTA-anticoagulated tubes. Values were highly correlated between both anticoagulants, and mean relative biases (MRBs) were below Ricos’s recommendations, except for MCHC and MPV. For differential, neutrophils were significantly lower on MgSO4- in comparison to K3-EDTA-anticoagulated tubes (MRB = −2.9%, below Ricos’s optimal bias). The morphology of white blood cells (WBCs) was similar on both anticoagulants. During storage at room temperature, MCV and red cell distribution width increased slightly, but the increase was more pronounced in K3-EDTA than in MgSO4 tubes. Conclusions: CBC and differentials obtained with the DxH 800 analyzer on MgSO4-anticoagulated samples are similar to those obtained with K3-EDTA, except for MPV. Full article
(This article belongs to the Section Hematology)
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24 pages, 2514 KB  
Review
Oral Barrier Immunometabolism in Chronic Low-Grade Inflammation: Molecular Mechanisms and Systemic Implications
by Aferdita Ademi, Skender Topi, Mitilda Gugu, Alessia Ciafarone, Maria Grazia Cifone, Davide Pietropaoli and Serena Altamura
Int. J. Mol. Sci. 2026, 27(12), 5356; https://doi.org/10.3390/ijms27125356 (registering DOI) - 13 Jun 2026
Abstract
Chronic low-grade inflammation is a hallmark of aging and a major driver of metabolic and degenerative diseases. While systemic immune dysfunction has been widely investigated, the contribution of barrier tissues to persistent inflammatory signaling remains incompletely defined. The oral mucosa represents a uniquely [...] Read more.
Chronic low-grade inflammation is a hallmark of aging and a major driver of metabolic and degenerative diseases. While systemic immune dysfunction has been widely investigated, the contribution of barrier tissues to persistent inflammatory signaling remains incompletely defined. The oral mucosa represents a uniquely exposed barrier, continuously challenged by microbial, mechanical, and metabolic stressors and characterized by a specialized immune architecture. Here, we synthesize current evidence supporting the oral barrier as an active immunometabolic interface linking local immune activation to systemic inflammatory tone. Spatially organized epithelial, neutrophil, and antigen-presenting cell (APC) compartments coordinate immune responses tightly coupled to metabolic reprogramming, including hypoxia-inducible factor-1α (HIF-1α)-dependent glycolysis and mitochondrial reactive oxygen species (mtROS) production. In parallel, the oral microbiota provides ligands and metabolites such as lipopolysaccharide (LPS), short-chain fatty acids (SCFAs), and succinate, which activate pattern-recognition receptors (PRRs), including toll-like receptors (TLRs) and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, thereby sustaining nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-mediated inflammatory signaling. Barrier disruption and dysbiosis promote microbial translocation and persistent innate immune activation, while saliva and gingival crevicular fluid facilitate systemic dissemination of inflammatory mediators. Overall, sustained immunometabolic engagement at the oral barrier emerges as a key driver of chronic low-grade systemic inflammation and a potential therapeutic target in inflammaging. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Oral Immunology)
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24 pages, 7603 KB  
Article
Lobenzarit Attenuates DSS-Induced Colitis by Reprogramming Immune Microenvironment and Mitochondrial Homeostasis
by Ali Khaled, Manar A. Nader and Marwa E. Abdelmageed
Pharmaceuticals 2026, 19(6), 926; https://doi.org/10.3390/ph19060926 (registering DOI) - 12 Jun 2026
Abstract
Background: The incidence of inflammatory bowel disease (IBD) is growing in the population. At present, the etiology of inflammatory bowel disease remains unclear, and there is no effective and low-toxic therapeutic drug. This study aimed to investigate the role of Lobenzarit (Lbz) in [...] Read more.
Background: The incidence of inflammatory bowel disease (IBD) is growing in the population. At present, the etiology of inflammatory bowel disease remains unclear, and there is no effective and low-toxic therapeutic drug. This study aimed to investigate the role of Lobenzarit (Lbz) in the treatment of colitis in mice as well as the underlying mechanism. Methods: In this experiment, colitis was induced in mice with dextran sulphate sodium (Dss). Subsequently, the role of Lbz in colitis and its underlying mechanisms were examined using H&E staining, TEM, ELISA, PCR, and other assays. Results: Lbz significantly attenuated the related symptoms of Dss-induced colitis in mice. In addition, Lbz suppressed neutrophil infiltration and restored macrophage polarization towards an anti-inflammatory state. Lbz also inhibited (p < 0.05) the activation of signaling pathways TLR4 and MAPK (51.61% decrease for TLR4 and 56.94% decrease for MAPK), reduced the release of inflammatory factors as it significantly decreased (p < 0.05) colonic IL-1β, TNF-α, IFN-γ, COX2, and VEGF (47.63, 42.49, 53.42, 58.74, and 61.28% decreases respectively) thereby attenuating the inflammatory response in mice. Lbz administration also restored the permeability of the intestinal barrier by increasing (p < 0.05) tight junction-associated proteins (claudin-1, occludin, and ZO-1 with a 5.36- and 2.26-fold increase for claudin-1 and ZO-1, respectively) and decreasing (p < 0.05) MALK levels by 53.51%. In addition, Lbz upregulated colonic Cytochrome C oxidase II, PDH, and ATP synthase levels and upregulated CD163, CD206, c-Maf, and PPAR-γ levels as compared to the DSS-treated group. Conclusions: Lbz has a repairing effect on Dss-induced colitis and may alleviate Dss-induced colitis by targeting the TLR4 pathway and promoting intestinal stem cell proliferation. Full article
(This article belongs to the Section Pharmacology)
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13 pages, 337 KB  
Article
Longitudinal Changes in Neutrophil-to-Lymphocyte and Monocyte-to-Lymphocyte Ratios During Multiple Sclerosis Relapse
by Marta Konieczna, Przemysław Puz, Michał Gałuszewski, Jan Olszewski, Karolina Jankowska, Alicja Gierlach, Krzysztof Wójcik and Anetta Lasek-Bal
J. Clin. Med. 2026, 15(12), 4539; https://doi.org/10.3390/jcm15124539 - 11 Jun 2026
Viewed by 49
Abstract
Background: The neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) reflect the balance between innate and adaptive immunity and may indicate systemic inflammation. Objectives: To evaluate longitudinal changes in NLR and MLR in MS patients during relapse compared with relapse-free controls. Methods: In this [...] Read more.
Background: The neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) reflect the balance between innate and adaptive immunity and may indicate systemic inflammation. Objectives: To evaluate longitudinal changes in NLR and MLR in MS patients during relapse compared with relapse-free controls. Methods: In this retrospective single-center observational study, patients with MS were followed for 2 years. Individuals with at least one relapse and complete blood count data at predefined time points were included. Controls without relapse were selected in a 2:1 ratio and matched for age, sex, disease duration, EDSS score, and disease-modifying therapy category. NLR and MLR were assessed 3 months before relapse (or index date), during relapse, and 3 months after. Results: The study included 34 patients with relapse and 68 controls. During relapse, patients showed higher neutrophil and monocyte counts, lower lymphocyte counts, and elevated NLR and MLR compared with controls (all p < 0.001). NLR increased from 2.75 pre-relapse to 3.62 during relapse, then decreased to 2.67 (p = 0.0002). MLR rose from 0.45 to 0.54 and declined to 0.40 (p = 0.002). No significant changes were observed in controls. Conclusions: NLR and MLR demonstrated dynamic changes during MS relapse. These non-specific indices may serve as exploratory, complementary markers of relapse-associated inflammation, but require validation in larger prospective studies including MRI correlates. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Current Diagnosis, Treatment, and Future Options)
16 pages, 800 KB  
Article
Clinical, Microbiological, and Hematological Characteristics of Pediatric Brucellosis in Saudi Arabia: A Single-Center Retrospective Study
by Nawaf R. R. Alshammari, Fahaad S. Alenazi, Mohd Saleem, Nahed Fathallah Fahmy Mohamed, Saada A. Alogla, Najd B. Albalawi, Noor Munawer Alrashidi, Layan Zaid Alhamashi, Abdulelah Ghazi AlHarbi, Khalid Ata Alshammari, Misheal Ayed Alshammeri and Azharuddin Sajid Syed Khaja
Diagnostics 2026, 16(12), 1807; https://doi.org/10.3390/diagnostics16121807 - 11 Jun 2026
Viewed by 45
Abstract
Background and Objectives: Brucellosis remains a significant zoonotic disease in endemic regions such as Saudi Arabia, with children being particularly vulnerable. Pediatric brucellosis often presents with nonspecific symptoms, and hematological abnormalities can serve as important yet underrecognized diagnostic clues. This study aimed to [...] Read more.
Background and Objectives: Brucellosis remains a significant zoonotic disease in endemic regions such as Saudi Arabia, with children being particularly vulnerable. Pediatric brucellosis often presents with nonspecific symptoms, and hematological abnormalities can serve as important yet underrecognized diagnostic clues. This study aimed to evaluate the demographic, clinical, microbiological, treatment, and hematological characteristics of patients with pediatric brucellosis in the Hail region of Saudi Arabia and to assess the diagnostic value of hematological parameters. Methods: This retrospective observational study included children aged ≤15 years who were diagnosed with brucellosis at a tertiary care hospital in Hail between 2014 and 2025. Demographic, clinical, laboratory, microbiological, and treatment data were analyzed. Hematological parameters were compared between culture-confirmed and non-culture-confirmed brucellosis cases using multivariate and receiver operating characteristic (ROC) analyses. Results: A total of 38 pediatric patients were included (mean age 8.6 years; 57.9% male). Positive culture results were observed in 42.1% of the cases, with Brucella melitensis being the predominant species (68.75%). Fever (89.5%) and bone/joint pain (71.1%) were the most frequent symptoms. Culture-confirmed brucellosis patients had significantly lower hemoglobin levels (10.8 vs. 12.1 g/dL; p = 0.020), white blood cell counts (p = 0.046), and absolute neutrophil counts (p = 0.037). ROC analysis revealed a fair diagnostic performance for hemoglobin (AUROC = 0.695), WBC (0.699), and ANC (0.680). Leukopenia demonstrated high specificity (95.5%) and positive predictive value. Conclusions: Pediatric brucellosis is commonly associated with anemia, leukopenia, and neutropenia. Although no single hematological parameter independently predicts infection, the combination of these abnormalities may support early clinical suspicion, particularly in resource-limited endemic settings. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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20 pages, 3403 KB  
Article
Discovery of Rhubarb Anthraquinones Physcion and Rhein as Functional Inhibitors of TRPV1 Against Lipopolysaccharide-Induced Neuroinflammation
by Shuli Li, Yulin He, Hiotong Kam, Hanbin Chen, Jin-Song Bian, Nan Xu, Guiyi Gong, Qiwen Liao, Chen Zhao, Binrui Yang, Liang Chen, Kit Ieng Kuok and Simon Ming Yuen Lee
Molecules 2026, 31(12), 2049; https://doi.org/10.3390/molecules31122049 - 11 Jun 2026
Viewed by 125
Abstract
Neuroinflammation, mediated by microglia and astrocytes, is an abnormal immune reaction in central nervous system (CNS) disorders. Stimulation of TRPV1 has been found to enhance microglial activation, resulting in a pro-inflammatory response. Natural anthraquinones such as physcion and rhein are commonly found in [...] Read more.
Neuroinflammation, mediated by microglia and astrocytes, is an abnormal immune reaction in central nervous system (CNS) disorders. Stimulation of TRPV1 has been found to enhance microglial activation, resulting in a pro-inflammatory response. Natural anthraquinones such as physcion and rhein are commonly found in rhubarb, a medicinal plant recognized for its dual role in culinary and therapeutic applications. The therapeutic potential and mechanisms of these anthraquinones remain largely unexplored. This research aims to examine how anthraquinones protect against neuroinflammation and delineate the underlying mechanisms in lipopolysaccharide (LPS)-mediated cellular and zebrafish models. Among the representative anthraquinone analogs, physcion and rhein showed potent functional inhibitory activity against the TRPV1 channel. The production of nitric oxide (NO) and secretion of pro-inflammatory factors triggered by LPS were significantly reduced in BV-2 cells through regulation of iNOS, IL-6, IL-1β, and TNF-α mRNA expression. Moreover, physcion and rhein inhibited calcium influx and exerted anti-neuroinflammatory effects, which were closely associated with the suppression of Ca2+/CAMKK2/AKT and the PI3K/AKT-mediated NF-κB activation pathways. Furthermore, physcion and rhein reduced LPS-driven neutrophil recruitment to the brain and ameliorated locomotor deficits in zebrafish larvae, with the restoration of IL-1β, IL-6, and TNF-α transcript levels to baseline. In conclusion, natural-derived anthraquinones from rhubarb, physcion and rhein, acted as functional inhibitors of TRPV1-mediated calcium dynamics and significantly reduced LPS-mediated neuroinflammation in microglial cells and zebrafish larvae, suggesting promise as therapeutics for neurological disorders. Full article
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17 pages, 856 KB  
Article
Larger Acute Phase Reactions Are Associated with Immunogenicity of an Adjuvanted Recombinant Receptor Binding Domain Protein Vaccine Against SARS-CoV-2 in Rhesus Monkeys
by Christopher L. Coe, Gabriele R. Lubach, Francesca Nimityongskul, Kimberly Luke, Eva G. Rakasz, David M. Rancour and Fritz M. Schomburg
Vaccines 2026, 14(6), 523; https://doi.org/10.3390/vaccines14060523 - 11 Jun 2026
Viewed by 153
Abstract
Background: Although prolonged inflammatory symptoms are an infrequent and problematic adverse effect of vaccination that can occur in some people, the transient activation of acute phase reactants (APRs) is expected with adjuvanted vaccines and helps to potentiate immune responses. Methods: This experiment examined [...] Read more.
Background: Although prolonged inflammatory symptoms are an infrequent and problematic adverse effect of vaccination that can occur in some people, the transient activation of acute phase reactants (APRs) is expected with adjuvanted vaccines and helps to potentiate immune responses. Methods: This experiment examined the association between vaccine reactogenicity and immunogenicity in monkeys immunized with an adjuvanted recombinant protein including a receptor binding domain–human IgG1-Fc fusion protein (RBD-Fc) sequenced from the ancestral Wuhan strain of SARS-CoV-2. The acute inflammatory reaction to immunization was assessed by determining the decline in serum iron levels at 24 h and the increase in the neutrophil-to-lymphocyte ratio (NLR) as the adherent neutrophil pool trafficked into circulation. Results: Robust primary and secondary antibody responses were elicited. Larger decreases in serum iron and higher NLRs were associated with a stronger inhibition of RBD binding with angiotensin-converting enzyme (ACE2) when five early viral variants of SARS-CoV-2 were tested, including Wuhan, Alpha, Beta, Gamma and Delta. Inhibition of ACE2-RBD binding was less evident when the Omicron variant was tested. Individual variation in the APR was also predictive of the persistence of cell-mediated immunity based on the number of interferon-expressing mononuclear cells activated by viral antigen in ELISpot assays. Conclusions: Rapid antibody responses to primary immunization and large secondary responses to booster immunizations were elicited by this adjuvanted recombinant RBD-Fc vaccine, and our analysis affirmed the view that a transient APR can enhance antibody binding with antigen proteins. Full article
(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)
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14 pages, 519 KB  
Article
Diagnostic Performance of Hematological Blood Ratios in Revision Surgery for Periprosthetic Joint Infections: A Retrospective Cohort Analysis of CRP/Hb Ratio, NLR, and MLR
by Diana-Elena Vulpe, Serban Dragosloveanu, Rares-Mircea Birlutiu, Victoria Birlutiu, Radu Josanu, Andrei Larie, Calina Maier, Cristian Scheau, Javad Parvizi and Oana Sandulescu
Prosthesis 2026, 8(6), 57; https://doi.org/10.3390/prosthesis8060057 - 11 Jun 2026
Viewed by 121
Abstract
Objectives: Periprosthetic joint infections represent a serious complication following joint arthroplasty, often leading to significant morbidity, with an economic and social impact on the health system. Timely diagnosis of periprosthetic joint infections remains a major challenge. Our study aimed to investigate the diagnostic [...] Read more.
Objectives: Periprosthetic joint infections represent a serious complication following joint arthroplasty, often leading to significant morbidity, with an economic and social impact on the health system. Timely diagnosis of periprosthetic joint infections remains a major challenge. Our study aimed to investigate the diagnostic value and accuracy of several markers, including the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and C-reactive protein-to-serum-hemoglobin ratio in revision surgery for periprosthetic joint infections. Methods: A total of 251 revision arthroplasty cases, including 137 cases of periprosthetic joint infections and 114 cases of aseptic revision arthroplasty, were included from the time span January 2016 to May 2025. The diagnostic value and accuracy of the C-reactive protein-to-hemoglobin ratio, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio were evaluated using sensitivity, specificity, and receiver operating characteristic (ROC) analysis with area under the curve analysis. Results: The highest diagnostic performance was obtained by the C-reactive protein-to-hemoglobin ratio, yielding an AUC of 0.859 (SE = 0.0263, 95% CI: 0.809–0.899). This ratio also demonstrated a strong discriminative capacity, with a threshold of >0.0667, sensitivity of 80.45%, and specificity of 85.96%. For the neutrophil-to-lymphocyte count ratio and monocyte-to-lymphocyte count ratio, we obtained an AUC of 0.615 (95% CI: 0.551–0.676) and 0.620 (95% CI: 0.556–0.680), respectively, demonstrating lower sensitivity and specificity than the C-reactive protein-to-hemoglobin ratio. Conclusions: The C-reactive protein-to-hemoglobin ratio demonstrated better diagnostic strength in detecting periprosthetic joint infections, with superior sensitivity and specificity compared to the neutrophil-to-lymphocyte count ratio and monocyte-to-lymphocyte count ratio. Our findings offer new insights into the accurate and early diagnosis of periprosthetic joint infections in cases requiring revision surgery and suggest incorporating these new biomarkers and ratios into the diagnostic algorithm. Future large-scale studies are further needed to validate these results and facilitate their clinical use. Full article
(This article belongs to the Special Issue Managing the Challenge of Periprosthetic Joint Infection)
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15 pages, 636 KB  
Article
A Derivation Study of a Cardio-Nutrition-Inflammation-Oxygen Index and 3-Month Functional Outcomes After Outpatient Pulmonary Rehabilitation
by Sae Rom Kim, Jinkyeong Park, Ga Yang Shim, Seung Don Yoo and Eo Jin Park
Nutrients 2026, 18(12), 1879; https://doi.org/10.3390/nu18121879 - 11 Jun 2026
Viewed by 143
Abstract
Background/Objectives: Short-term functional outcomes after outpatient pulmonary rehabilitation are heterogeneous. We examined whether a study-derived cardio-nutrition-inflammation-oxygen (CNIO) index integrating echocardiographic filling pressure, nutritional status, inflammation, and oxygen requirement was associated with 3-month functional outcomes in chronic respiratory disease. Methods: This single-center retrospective cohort [...] Read more.
Background/Objectives: Short-term functional outcomes after outpatient pulmonary rehabilitation are heterogeneous. We examined whether a study-derived cardio-nutrition-inflammation-oxygen (CNIO) index integrating echocardiographic filling pressure, nutritional status, inflammation, and oxygen requirement was associated with 3-month functional outcomes in chronic respiratory disease. Methods: This single-center retrospective cohort study included 60 adults with chronic obstructive pulmonary disease, interstitial lung disease, or bronchiectasis who completed outpatient pulmonary rehabilitation and had baseline and 3-month functional assessments. The CNIO index was calculated as standardized E/e′ plus standardized ln(neutrophil-to-lymphocyte ratio) plus standardized resting oxygen flow rate minus standardized Geriatric Nutritional Risk Index, and the summed score was then standardized to mean 0 and SD 1. The primary outcome was 3-month 6 min walk test (6MWT) distance, and the exploratory secondary outcome was 3-month Short Physical Performance Battery (SPPB) score. The primary 6MWT analysis used multivariable analysis of covariance adjusted for baseline 6MWT, age, sex, body mass index, and diagnosis, whereas the exploratory SPPB analysis used ordinal logistic regression adjusted for baseline SPPB and the same covariates. Results: Mean 6MWT increased from 340.3 ± 61.0 m to 368.0 ± 102.0 m, corresponding to a mean change of 27.7 ± 90.3 m. Each 1-SD increase in CNIO was associated with a lower 3-month 6MWT distance (β = −43.42 m; 95% confidence interval [CI], −77.55 to −9.30; p = 0.014). In the exploratory ordinal logistic regression model for SPPB, each 1-SD increase in CNIO was associated with lower odds of being in a higher 3-month SPPB category, although the estimate was fragile and the confidence interval was close to the null (odds ratio = 0.39; 95% CI, 0.15 to 0.99; p = 0.048). Bootstrap internal stability analysis for the primary 6MWT model showed a wide percentile bootstrap 95% CI of −76.05 to −13.97 m per 1-SD increase in CNIO, supporting the need for cautious interpretation. Conclusions: In this hypothesis-generating derivation study, a higher standardized CNIO index was associated with lower 3-month 6MWT distance among adults with chronic respiratory disease who completed outpatient pulmonary rehabilitation. The association with SPPB was weaker and should be interpreted cautiously. These findings are not generalizable to patients who discontinue rehabilitation or are hospitalized for exacerbation during follow-up, and prospective external validation in larger, diagnostically stratified cohorts is required before CNIO can be considered for clinical risk stratification or rehabilitation planning. Full article
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15 pages, 21454 KB  
Article
Disrupted Neutrophil and Myeloid Cell Homeostasis and Effector Dysfunction Drive Vasculopathy in Idiopathic Inflammatory Myopathies
by Daniel Alberto Carrillo-Vázquez, Beatriz Alcalá-Carmona, Jennifer Tiaré Balderas Miranda, Yatzil Reyna-Juárez, María José Ostos-Prado, Fabiola Cassiano-Quezada, Samuel Govea-Peláez, Nancy R. Mejía-Domínguez, Guillermo Juárez-Vega, Karina Santana-De Anda, Jiram Torres-Ruiz and Diana Gómez-Martín
Cells 2026, 15(12), 1062; https://doi.org/10.3390/cells15121062 - 10 Jun 2026
Viewed by 159
Abstract
Background: Neutrophils play a role in idiopathic inflammatory myopathies (IIMs), especially in vasculopathic manifestations. While neutrophil extracellular traps (NETs) and low-density granulocytes (LDGs) have been described, the functional relevance of other subsets—such as naïve neutrophils, reverse transendothelial migration neutrophils (rTEM), myeloid-derived suppressor cells [...] Read more.
Background: Neutrophils play a role in idiopathic inflammatory myopathies (IIMs), especially in vasculopathic manifestations. While neutrophil extracellular traps (NETs) and low-density granulocytes (LDGs) have been described, the functional relevance of other subsets—such as naïve neutrophils, reverse transendothelial migration neutrophils (rTEM), myeloid-derived suppressor cells (MDSCs), and regulatory neutrophils—and their association with vasculopathy remains unknown. Objective: We aimed to characterize the phenotypic and functional profile of neutrophil subsets and their association with vasculopathic manifestations in IIM, adjusting for disease activity. Methods: We conducted a cross-sectional, single-center study including 59 IIM patients diagnosed by muscle biopsy and fulfilling 2017 ACR/EULAR criteria. Flow cytometry was used to immunophenotype myeloid subsets, and functional assays assessed phagocytosis and respiratory burst. Patients were stratified by clinical activity and presence of vasculopathy. Results: Vasculopathic patients showed expansion of LDGs (p = 0.0092), granulocytic and monocytic MDSCs expressing Arginase-1 (p = 0.0078, p = 0.0003) and PD-L1 (p = 0.0258, p = 0.0087), and rTEM neutrophils (p = 0.0775). In contrast, they exhibited a reduction in naïve neutrophils (p = 0.0004), phagocytosis (p < 0.0001) and respiratory burst (p = 0.0006). Multivariate analysis identified naïve neutrophils and activated CD177+ neutrophils as independent predictors of vasculopathy. A positive correlation between activated and naïve neutrophils were observed in patients with vasculopathic features (r = 0.43; p < 0.05). Conclusions: IIM patients with vasculopathic features display a distinct immune profile characterized by an imbalance between proinflammatory and regulatory neutrophil subsets, alongside persistent functional impairment. Full article
(This article belongs to the Section Cellular Immunology)
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15 pages, 1669 KB  
Article
Low-Molecular-Weight Versus Protein Inhibitors for the CXCL8/Glycosaminoglycan Interaction: Biophysical Characterization and Cellular Activity
by Tanja Gerlza, Paula Peinsipp, Birgit Müller, Klaus Thirring and Andreas J. Kungl
Chemistry 2026, 8(6), 80; https://doi.org/10.3390/chemistry8060080 - 10 Jun 2026
Viewed by 124
Abstract
CXCL8, a pro-inflammatory chemokine, which can be induced by TNF-α or IL-1, is responsible for the recruitment and activation of neutrophils. Chemokines interact with glycosaminoglycans on endothelial cells and are thus protected from degradation and sequestration, holding them in an optimal position for [...] Read more.
CXCL8, a pro-inflammatory chemokine, which can be induced by TNF-α or IL-1, is responsible for the recruitment and activation of neutrophils. Chemokines interact with glycosaminoglycans on endothelial cells and are thus protected from degradation and sequestration, holding them in an optimal position for recruiting immune cells. Inhibiting the interaction of chemokines with their glycosaminoglycan co-receptors represents an attractive approach for the treatment of chemokine-mediated diseases. Two polyketide-pyrone compounds, PA501 and PA502 were synthesized, which bind to CXCL8 with affinities higher than the natural glycosaminoglycan ligand heparan sulfate, and in a similar range as heparin. Significant structural changes were induced in the chemokine by interacting with the two compounds, as expressed in fluorescence and far-UV CD experiments. In filter binding assays, both compounds were found to displace heparan sulfate efficiently from CXCL8, with PA501 displaying the highest competition efficacy. Using a C-terminally truncated form of the chemokine, CXCL81-58, which lacks the main glycosaminoglycan-binding α-helical domain, the two compounds are suggested to use—to a varying degree—different binding sites on the protein, which have also been proposed for the natural heparan sulfate ligand. In a transmigration assay, PA501 and PA502 exhibited dose-dependent modulation of CXCL8-induced neutrophil mobilization and migration. The compounds PA501 and PA502 may thus be regarded as early novel lead compounds in the quest for anti-inflammatory, chemokine-targeting drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
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13 pages, 266 KB  
Article
Associations of Serum Zinc and Iron with Systemic Inflammatory Indices in Pediatric Obesity: An Exploratory Cross-Sectional Study
by Mehmet Cengiz
Children 2026, 13(6), 800; https://doi.org/10.3390/children13060800 - 10 Jun 2026
Viewed by 146
Abstract
Background/Objectives: Childhood obesity is associated with chronic low-grade systemic inflammation. This exploratory cross-sectional study aimed to evaluate associations between a comprehensive panel of serum micronutrient levels and four systemic inflammatory indices—neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio [...] Read more.
Background/Objectives: Childhood obesity is associated with chronic low-grade systemic inflammation. This exploratory cross-sectional study aimed to evaluate associations between a comprehensive panel of serum micronutrient levels and four systemic inflammatory indices—neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio (MLR)—in a pediatric cohort, with iron as the primary focus and zinc as a secondary exploratory analysis. Methods: We included 410 children (mean age 7.2 ± 3.8 years; 205 male) attending a tertiary pediatric clinic. Of these, 399 had complete BMI percentile data and were included in obesity-stratified analyses; patients were classified as having obesity (BMI ≥ 95th percentile; n = 56) or not having obesity (n = 343). The remaining 11 children lacked BMI percentile data and were included only in full-cohort analyses. Serum iron, ferritin, folate, zinc, vitamin D, vitamin B12, magnesium, and phosphorus were measured alongside complete blood count parameters. Spearman correlations and multivariable ordinary least squares regression were performed. Benjamini–Hochberg false discovery rate (FDR)-adjusted q-values were computed for all Spearman correlations; all remaining analyses are exploratory and all findings should be interpreted with caution. Results: All four inflammatory indices were significantly higher in children with obesity (SII: 487.1 vs. 332.1, p < 0.001; NLR: 1.30 vs. 1.03, p = 0.001). Low serum iron was more prevalent in the group with obesity (42.9% vs. 27.1%, p = 0.025). In multivariable regression, serum iron was significantly associated with NLR (β = −0.009, 95% CI [−0.012, −0.005], p < 0.001) and SII (β = −3.268, 95% CI [−4.404, −2.132], p < 0.001) after adjustment for age and BMI percentile. In an exploratory analysis restricted to children with obesity and complete data (n = 39), zinc was associated with SII (β = −11.912, 95% CI [−21.836, −1.988], p = 0.025); however, the overall model was non-significant (p = 0.067), zinc showed no association in the full cohort, and—given the small sample and absence of multiple comparison correction—this finding must be considered strictly hypothesis-generating. Conclusions: Systemic inflammatory burden is elevated in children with obesity. Iron shows consistent associations with inflammatory indices independent of age and BMI. Zinc shows a potentially relevant, exploratory association with inflammation, specifically in the subgroup with obesity, warranting replication in adequately powered prospective studies. These findings are consistent with a role for iron status assessment in the clinical evaluation of pediatric obesity and warrant further prospective investigation of zinc-related inflammatory associations. Full article
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16 pages, 13040 KB  
Article
When Protection Turns Pathogenic: Dual Compartment Functions of Myeloid YB-1 in Renal IRI
by Anna Leitz, Yili Chen, Xiyang Liu, Yingying Gao, Jialin Wang, Ina Verena Martin, Rafaela Rawinski, Rafael Kramann, Tammo Ostendorf and Ute Raffetseder
Int. J. Mol. Sci. 2026, 27(12), 5239; https://doi.org/10.3390/ijms27125239 - 10 Jun 2026
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Abstract
Acute kidney injury (AKI) caused by ischemia–reperfusion injury (IRI) involves rapid activation of innate immune responses, in which myeloid-derived immune cells critically shape injury severity. Y-box binding protein 1 (YB-1) regulates pro-inflammatory gene expression intracellularly and can be secreted to function extracellularly, yet [...] Read more.
Acute kidney injury (AKI) caused by ischemia–reperfusion injury (IRI) involves rapid activation of innate immune responses, in which myeloid-derived immune cells critically shape injury severity. Y-box binding protein 1 (YB-1) regulates pro-inflammatory gene expression intracellularly and can be secreted to function extracellularly, yet how these two compartments jointly influence early IRI pathology remains poorly understood. To dissect the roles of intracellular myeloid versus extracellular YB-1, we subjected myeloid-specific Ybx1 knockout, Ybx1fl/fl × LysMcre, mice and wild-type (WT) littermates to unilateral renal IRI following administration of either a neutralizing anti-YB-1 antibody or control IgG. Kidney injury, inflammation, immune cell recruitment, neutrophil extracellular trap (NET) formation, antibody localization, and Fcγ receptor expression were assessed by qRT-PCR, histology, immunostaining, Western blotting, and flow cytometry. Myeloid-specific knockout of Ybx1 markedly reduced renal inflammation, neutrophil infiltration, NET formation, and tubular injury. This protective phenotype was lost when extracellular YB-1 was simultaneously reduced: anti-YB-1 treatment in knockout mice restored pro-inflammatory cytokine expression, increased tubular damage markers such as NGAL and KIM-1, exacerbated neutrophil recruitment and NET formation, and led to luminar accumulation of YB-1/anti-YB-1 immune complexes in tubular cells. Mechanistically, Ybx1-deficient myeloid cells exhibited significantly reduced CD16 expression, pointing to impaired Fcγ receptor-mediated phagocytosis as the cause of defective immune complex clearance. In contrast, wild-type mice efficiently cleared extracellular YB-1 complexes and showed no injury aggravation upon antibody treatment. Our findings identify myeloid YB-1 as a central regulator of early inflammatory injury in renal IRI and reveal that its protective depletion becomes pathogenic when extracellular YB-1 is simultaneously neutralized, likely due to unmasked defects in immune complex clearance. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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16 pages, 1103 KB  
Article
Correlation of Age and Laboratory Parameters with Urine Flow Cytometry and Culture Results in Patients with Urinary Tract Infections
by Alma Trnacevic, Emir Trnacevic, Merjema Mahmutovic, Amra Serak, Humera Porobic Jahic, Jasminka Petrovic, Dilista Piljic, Rahima Jahic, Danijel Bijedic and Amela Becirovic
Infect. Dis. Rep. 2026, 18(3), 56; https://doi.org/10.3390/idr18030056 - 9 Jun 2026
Viewed by 125
Abstract
Background: The diagnosis of urinary tract infection (UTI) remains a clinical challenge, with urine culture as the gold standard. In developing countries like Bosnia and Herzegovina, a high prevalence of antimicrobial resistance and frequent empirical treatment pose significant clinical challenges. Automated urine flow [...] Read more.
Background: The diagnosis of urinary tract infection (UTI) remains a clinical challenge, with urine culture as the gold standard. In developing countries like Bosnia and Herzegovina, a high prevalence of antimicrobial resistance and frequent empirical treatment pose significant clinical challenges. Automated urine flow cytometry has emerged as a rapid tool to optimize diagnostic processes. Objectives:To determine the correlation of age, gender, and laboratory parameters—such as white blood cell (WBC) count, neutrophil count, and C-reactive protein (CRP)—with both urinary bacterial counts and urine culture results. Methods: This retrospective study analyzed 200 adult patients (≥18 years) with symptoms suggestive of UTI at the University Clinical Center Tuzla. Data on age, gender, WBC, neutrophils, CRP, and urine flow cytometry (Sysmex UF-4000) were collected. Statistical analysis was performed using R software (version 4.5.1), utilizing logistic regression models via the ‘glm’ function to identify independent predictors, with statistical significance set at p< 0.05.Results: The mean age of the population was 68.61 ± 15.19 years. Logistic regression demonstrated that WBC count (OR = 1.06, p = 0.004), neutrophil count (OR = 1.04, p = 0.014), and patient age (OR = 1.03, p = 0.001) were significant independent predictors of UTI. Furthermore, patients with a urinary bacterial count >1200/μL had 83 times higher odds of a positive urine culture (OR = 83, 95% CI 32.25–200, p< 0.001). Conversely, CRP levels and gender were not significant predictors (p> 0.05). Conclusions: Patient age, WBC, and neutrophil counts are key factors for predicting UTIs. Integrating these parameters with urine flow cytometry bacterial counts can significantly enhance diagnostic accuracy and rapid screening in clinical practice. Full article
(This article belongs to the Section Bacterial Diseases)
27 pages, 2796 KB  
Review
Osteoimmunology of Natural and Synthetic Biomaterials Used in Dentistry for Bone Remodeling
by Karla Lizeth Santana-Arenas, Tanya A. Camacho-Villegas and Pavel H. Lugo-Fabres
Macromol 2026, 6(2), 41; https://doi.org/10.3390/macromol6020041 - 9 Jun 2026
Viewed by 75
Abstract
Bone loss in the maxillofacial region arises from multiple causes, including periodontal disease, trauma, surgical procedures, infection, congenital anomalies, and cancer. Traditional treatment relies on bone grafting, either alone or in combination with biomaterials. Advances in tissue engineering have introduced synthetic or natural [...] Read more.
Bone loss in the maxillofacial region arises from multiple causes, including periodontal disease, trauma, surgical procedures, infection, congenital anomalies, and cancer. Traditional treatment relies on bone grafting, either alone or in combination with biomaterials. Advances in tissue engineering have introduced synthetic or natural scaffolds to mimic the mineralized bone matrix. Natural scaffolds offer excellent biocompatibility and similarity to native tissue but often lack sufficient mechanical strength and exhibit poor degradation rates. Synthetic scaffolds provide tunable porosity and mechanical stability; however, their biological inertness makes them poor sources of osteogenic signaling. A key factor in the success of any scaffold is its interaction with the host immune system. Upon implantation, the innate immune response is initiated, with neutrophils and macrophages being the first cells to contact the scaffold. Macrophage polarization toward proinflammatory (M1) or anti-inflammatory (M2) phenotypes determines whether the microenvironment favors inflammation or remodeling. The adaptive immune response also plays a critical role: T and B lymphocytes may promote tolerance and integration through Th2/Treg pathways and antibody-mediated regulation, or they may trigger chronic inflammation and rejection through Th1/Th17 activation. This review examines the natural and synthetic materials used for bone remodeling and their biological properties. It then outlines the sequence of immune events occurring from the moment a scaffold is implanted to its potential integration or failure. Finally, this study highlights the relevance of cellular models and in vitro assays for the early evaluation of immunogenicity and biocompatibility, which are essential for optimizing scaffold design and improving outcomes in maxillofacial bone regeneration. Full article
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