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22 pages, 10734 KB  
Article
Analgesic and Anti-Inflammatory Activity of Ambroxol in the Treatment of Endometriosis: An Experimental Study in Wistar Rats
by Gustavo Medeiros Frota, Wilwana Guimarães Barbalho Santos, Joana Tenório-Meireles, Eduardo Rodrigues Silva, Amanda Tissore Forwille Reis, Rennan Abud Pinheiro Santos, Larissa Rodrigues de Sousa, Rafael Antônio Freire Carvalho, Joicy Cortez de Sá Sousa, Eduardo Martins de Sousa, Rafael de Abreu Lima, Rafael Cardoso Carvalho, Marcelo Souza de Andrade, João Batista Santos Garcia and Maria do Socorro de Sousa Cartágenes
Pharmaceuticals 2026, 19(4), 641; https://doi.org/10.3390/ph19040641 (registering DOI) - 18 Apr 2026
Abstract
Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A [...] Read more.
Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A medroxyprogesterone-treated group (Progesterone) was included as a positive control. Pain was assessed using validated behavioral tests, including the Rat Grimace Scale (RGS), the von Frey test, and the rotarod test. Additionally, interleukin-1β (IL-1β) levels and total leukocyte counts were measured in peritoneal lavage fluid. The volumetric reduction in endometriotic implants was evaluated by ultrasonography, while histopathological analysis characterized inflammatory infiltrate and epithelial layer integrity using a standardized scoring system. Results: All ambroxol doses reduced spontaneous pain manifestations throughout the treatment. The mechanical withdrawal threshold significantly increased from the second week onward, and motor quality improved over the course of the study. A significant reduction in IL-1β levels compared with the negative control (Control(−)) was observed on day 21. Abx 50 and Abx 100 significantly reduced implant volumes (48.2% and 56.2%, respectively) and promoted marked disruption of the endometriotic epithelial layer. When compared with Progesterone, higher doses—particularly 100 mg/kg—demonstrated comparable efficacy. Conclusions: Taken together, these pleiotropic effects support the potential for drug repurposing in endometriosis. Full article
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24 pages, 1124 KB  
Review
Modulatory Effects of Polyphenols on Altered Leukocyte Functions in Thromboinflammation and Diabetes Mellitus
by Dina Muharib, Xinyi Wu, Christine Boesch, Robert A. S. Ariëns and Julia S. Gauer
Int. J. Mol. Sci. 2026, 27(8), 3585; https://doi.org/10.3390/ijms27083585 - 17 Apr 2026
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent low-grade inflammation and a markedly increased risk of cardiovascular diseases (CVD). Leukocytes play an important role not only in host defense but are also increasingly recognized as key contributors to haemostasis and [...] Read more.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent low-grade inflammation and a markedly increased risk of cardiovascular diseases (CVD). Leukocytes play an important role not only in host defense but are also increasingly recognized as key contributors to haemostasis and thromboinflammatory processes. In DM, chronic hyperglycaemia, oxidative stress and inflammation lead to leukocyte dysfunction, including enhanced cell activation, impaired mitochondrial function, and dysregulated interactions with platelets and endothelial cells. These alterations promote the thromboinflammatory state that contributes to vascular complications in DM. Thus, the modulation of oxidative stress and inflammation are important. Polyphenols are a class of plant secondary metabolites widely studied for their antioxidant and anti-inflammatory properties. This review comprehensively explores leukocyte dysfunction in DM, its contribution to thromboinflammation, and the mechanistic role of polyphenols in modulating these processes. The evidence presented suggests that polyphenols may contribute to the modulation of thromboinflammatory pathways. Further research in this area is required to enhance our understanding of thromboinflammation in DM and to translate these findings into effective adjunctive strategies, alongside standard pharmacological therapies to reduce CVD risk in individuals with DM. Full article
(This article belongs to the Special Issue Molecular Insights in Diabetes)
17 pages, 1236 KB  
Article
Synergistic Effects of Achyranthes aspera and Ricinus communis Seed Extracts with an Inactivated Vaccine Enhance Growth, Immunity, and Disease Resistance in Labeo rohita
by Aiman Nadeem, Farkhanda Asad, Asma Ashraf and Tayyaba Ali
Fishes 2026, 11(4), 239; https://doi.org/10.3390/fishes11040239 - 17 Apr 2026
Abstract
Feed nutrition and rise in antibiotic resistance are growing global challenges in aquaculture, with Aeromonas hydrophila causing significant losses in the carp family. This 60-day study evaluated the potential of combining herbal seed extract (Achyranthes aspera and Ricinus communis) with inactivated [...] Read more.
Feed nutrition and rise in antibiotic resistance are growing global challenges in aquaculture, with Aeromonas hydrophila causing significant losses in the carp family. This 60-day study evaluated the potential of combining herbal seed extract (Achyranthes aspera and Ricinus communis) with inactivated vaccine (A. hydrophila) to enhance growth and immunity in Labeo rohita. A total of 540 fish were randomly assigned in six groups (T0-untreated control, T1-A. aspera seed extract (ASE), T2-R. communis seed extract (RSE), T3-vaccinated control, T4-vaccine plus ASE, T5-vaccine plus RSE). Results revealed that herbal–vaccine combinations, particularly T4, showed highest growth performance (p < 0.05). Furthermore, this group showed improved metabolic profiles, indicated by reduced serum cholesterol, triglycerides, and glucose, along with significantly elevated albumin and globulin concentrations. In terms of immune response, neutrophil counts were significantly higher in T4 and T5. Crucially, following a challenge with A. hydrophila, survival rates were higher in T4:90% and T5:85% compared with positive control’s meager 20% survival. Post-challenge hematology confirmed that groups T4 and T5 maintained an enhanced immune status. These findings suggest that combining medicinal plants extract with vaccine effectively enhances growth, immunity, and disease resistance in L. rohita, presenting an environment friendly alternative to traditional antibiotics in aquaculture. Full article
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28 pages, 23970 KB  
Article
Expression of Human CEACAM Receptors Promotes Inflammation and Organ Damage During Systemic Candida albicans Infection in Mice
by Esther Klaile, Mario Marco Müller, Johannes Sonnberger, Anne-Katrin Bothe, Saskia Brehme, Juliet Ehrenpfordt, Tilman Eike Klassert, Sabina Kuhn, Kristina Dietert, Olivia Kershaw, Jan-Philipp Praetorius, Marc Thilo Figge, Torsten Bauer, Andreas Gebhardt, Gita Mall, Ilse Denise Jacobsen and Hortense Slevogt
Cells 2026, 15(8), 707; https://doi.org/10.3390/cells15080707 - 16 Apr 2026
Abstract
Invasive candidiasis is a fungal infection characterized by a high mortality rate. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family receptors play a crucial role in regulating innate responses of both leukocytes and epithelia. Human CEACAM3, CEACAM5 and CEACAM6 receptors recognize Candida albicans and [...] Read more.
Invasive candidiasis is a fungal infection characterized by a high mortality rate. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family receptors play a crucial role in regulating innate responses of both leukocytes and epithelia. Human CEACAM3, CEACAM5 and CEACAM6 receptors recognize Candida albicans and are expressed in transgenic CEABAC10 mice. In a murine C. albicans infection model, CEABAC10 mice exhibited a shortened survival period attributed to an early cytokine storm, an exacerbated acute phase response, and heightened systemic inflammation compared to their wild-type littermates. The livers and kidneys of CEABAC10 mice displayed intensified purulent necrotizing inflammation, accompanied by increased infiltration of neutrophils and macrophages. Our in vivo and in vitro data indicated that the expression of CEACAM6 on monocytes of CEABAC10 mice caused the elevated cytokine levels and the subsequent exacerbation of the acute phase response upon C. albicans infection, resulting in decreased survival. Full article
(This article belongs to the Special Issue Host–Pathogen Interactions and Immune Responses)
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14 pages, 2814 KB  
Article
Intraoperative Contamination of Sterile Fields and Postoperative Implications in Total Hip and Knee Arthroplasty: A Prospective Observational Study
by Nicolas Catalin Ionut Ion, Sorin Radu Fleaca, Bogdan Axente Bocea, Cosmin-Ioan Mohor, Mihai-Dan Roman, Calin-Ilie Mohor, Alexandru Florin Diconi, Alexandru Turcu, Vicentiu Vasile Veres, Iustin-Ilie Tutuianu, Mihai Faur, Vanesa-Maria Veres and Victoria Birlutiu
J. Clin. Med. 2026, 15(8), 2986; https://doi.org/10.3390/jcm15082986 - 14 Apr 2026
Viewed by 254
Abstract
Introduction: Periprosthetic joint infections (PJI) are among the most serious and costly complications in orthopedic surgery, significantly affecting patient prognosis and healthcare systems. Despite rigorous aseptic measures, intraoperative contamination of sterile fields, instruments, and air remains a persistent source of potential infection. This [...] Read more.
Introduction: Periprosthetic joint infections (PJI) are among the most serious and costly complications in orthopedic surgery, significantly affecting patient prognosis and healthcare systems. Despite rigorous aseptic measures, intraoperative contamination of sterile fields, instruments, and air remains a persistent source of potential infection. This study investigates the relationship between the microbial contamination of sterile fields during arthroplasty and postoperative inflammatory markers, with the objective of determining whether the contamination of sterile fields correlates with the presence of periprosthetic joint infection (PJI). Material and Methods: This prospective observational study included 33 patients undergoing total hip or knee arthroplasty in a university-affiliated orthopedic center. Intraoperative samples were collected from sterile fields and equipment to detect microbial contamination, while postoperative monitoring involved the C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); leukocyte count; temperature; and wound assessment on days 1, 3 and 7. All patients received 48 h of prophylactic cefuroxime. Statistical analysis was conducted using the International Business Machines (IBM) Statistical Product and Service Solutions (SPSS) software for Windows, version 30.0 (IBM Corporation, Armonk, New York, United States of America) with significance set at p ≤ 0.05. Results: Postoperative inflammatory markers showed distinct patterns depending on the isolated microorganism, with Proteus vulgaris and Staphylococcus hominis ssp. consistently associated with higher CRP and leukocyte values, indicating a more intense systemic response. Staphylococcus epidermidis was the most frequently isolated species but showed moderate inflammatory profiles, suggesting its potential role in subclinical colonization. A strong correlation between CRP on day 3 and leukocyte count (r = 0.81) confirms their combined utility in the early detection of infectious complications, while ESR appeared less dynamic and more complementary in nature. Discussion: This study highlights the significant role of intraoperative contamination and microbial virulence in shaping the postoperative inflammatory response after arthroplasty. Elevated CRP and leukocyte levels, particularly on day 3, were closely associated with pathogens known for biofilm formation and chronic infections. Despite prophylactic antibiotic use, confirmed infections still occurred, suggesting the need to reassess current protocols and enhance intraoperative contamination control. Conclusions: Pathogen presence in sterile fields during arthroplasty increases the risk of periprosthetic joint infections, often without early clinical symptoms. CRP on day 3 and leukocyte count were the most reliable early indicators of persistent inflammation. Full article
(This article belongs to the Section Orthopedics)
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19 pages, 2981 KB  
Article
A Comparative Bioinformatics Analysis of the Transcriptomic Profiles of Peri-Implantitis and Periodontitis and Their Common Signaling Pathways with Atherosclerosis
by Aleksandr V. Guskov, Anatoliy S. Utyuzh, Aleksandr A. Oleynikov, Aleksandr A. Nikiforov and Stanislav N. Kotlyarov
Curr. Issues Mol. Biol. 2026, 48(4), 401; https://doi.org/10.3390/cimb48040401 - 14 Apr 2026
Viewed by 134
Abstract
(1) Objective. To conduct a comparative bioinformatics analysis of the transcriptomic profiles of peri-implantitis and periodontitis to identify common and specific molecular signatures underlying their pathogenesis, as well as molecular parallels with atherosclerosis. (2) Methods: We used datasets from the Gene Expression Omnibus [...] Read more.
(1) Objective. To conduct a comparative bioinformatics analysis of the transcriptomic profiles of peri-implantitis and periodontitis to identify common and specific molecular signatures underlying their pathogenesis, as well as molecular parallels with atherosclerosis. (2) Methods: We used datasets from the Gene Expression Omnibus (GEO) database: dataset GSE223924 (30 gingival tissue samples from patients with peri-implantitis, periodontitis, and healthy subjects) and GSE100927 (atherosclerotic and control tissue; n = 104). Differentially expressed genes (DEGs) were identified based on the criteria: |logFC| > 1 and FDR < 0.05. To quantitatively assess the relative abundance of immune cells, we used the xCell deconvolution algorithm. (3) Results: In the peri-implantitis group, 3669 DEGs with upregulated expression and 3106 with downregulated expression were identified; in the periodontitis group, 1968 and 1250 DEGs, respectively. Functional analysis of the upregulated DEGs revealed activation of inflammatory processes, cell adhesion, and angiogenesis in both diseases. Key differences lay in the activation of adaptive immune mechanisms in peri-implantitis (enrichment of the “graft rejection” and “T-cell receptor signaling”) and innate immunity in periodontitis (enrichment of the “lipopolysaccharide response” and “Toll-like receptors (TLR) signaling” pathways). Analysis of downregulated DEGs revealed more profound disruptions in cytoskeletal organization and epithelial differentiation in periodontitis, as well as suppression of xenobiotic and lipid metabolism in both diseases. xCell deconvolution confirmed a significant increase in B cells, neutrophils, monocytes, M1 macrophages, and dendritic cells in peri-implantitis, and also revealed a trend toward an increase in these cells in periodontitis (p > 0.05), which is consistent with the activation of TLR signaling. In periodontitis, a significant increase in M2 macrophages and a decrease in Th1 cells were observed. Comparison with atherosclerosis revealed 272 common DEGs with peri-implantitis and 173 common DEGs with periodontitis. Functional analysis of the common genes confirmed their role in leukocyte transendothelial migration, cytokine production, and the “Lipids and Atherosclerosis” pathway. (4) Conclusions: Functional analysis and immune deconvolution consistently demonstrate that peri-implantitis is characterized by statistically significant activation of both adaptive and innate immunity, whereas in periodontitis, the activation of innate immunity manifests primarily at the level of signaling pathways. The significant overlap found between the transcriptional profiles of both diseases and atherosclerosis may indicate the presence of common pathogenetic links. Full article
(This article belongs to the Special Issue Bioinformatics in Human Disease Network Analysis)
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15 pages, 3662 KB  
Article
Cellular and Molecular Profiling of Native Heart Valves in Infective Endocarditis: A Comparative Study with Calcific Aortic Valve Disease
by Anna Sinitskaya, Maria Khutornaya, Alyona Poddubnyak, Maxim Asanov, Alexander Kostyunin, Alexey Tupikin, Marsel Kabilov and Maxim Sinitsky
Biomedicines 2026, 14(4), 890; https://doi.org/10.3390/biomedicines14040890 - 14 Apr 2026
Viewed by 198
Abstract
Background: Infective endocarditis (IE) affects both native and prosthetic heart valves, the endocardial surface, as well as cardiac implantable electronic devices. Identifying specific IE biomarkers for its early risk stratification remains crucial, particularly in cases with blood culture-negative endocarditis. Methods: Eleven native heart [...] Read more.
Background: Infective endocarditis (IE) affects both native and prosthetic heart valves, the endocardial surface, as well as cardiac implantable electronic devices. Identifying specific IE biomarkers for its early risk stratification remains crucial, particularly in cases with blood culture-negative endocarditis. Methods: Eleven native heart valves obtained from IE and calcific aortic valve disease (CAVD) patients were analyzed. Immunohistochemical analysis of a pan-leukocyte marker (CD45), macrophage marker (CD68), T-lymphocyte marker (CD3), B-lymphocyte marker (CD19), neutrophil myeloperoxidase (MPO), and marker of vascular endothelial cells (CD31) was performed. Differentially expressed genes (DEGs) were identified by whole-transcriptome sequencing; proteomic profiling was performed by dot-blotting. Results: The immunophenotyping demonstrates the infiltration of macrophages and neutrophils, as well as occasional T-lymphocytes in the IE-affected aortic valves, and the CAVD-affected heart valves were characterized by the absence of neutrophils. For the whole-transcriptome sequencing, 157 DEGs were identified: 124 DEGs were upregulated, and 33 genes were downregulated in the IE-affected heart valves compared to the CAVD-affected ones. According to the dot-blotting, 35 cytokines were identified in the studied heart valves, but only 21 molecules were expressed in both IE and CAVD-affected heart valves. Analysis of proteases and their inhibitors allowed the identification of 13 protease molecules and 18 enzyme inhibitor molecules in all examined heart valves. Conclusions: The results of the present study can help to improve our understanding of the IE pathogenesis. In addition, we identified the candidate cellular and molecular-genetic features of IE-affected native heart valves. Full article
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33 pages, 448 KB  
Review
From Regenerative Mechanisms to Clinical Practice: Current Status, Controversies, and Future Perspectives of Platelet-Rich Plasma in Urology and Sexual Medicine
by Rui Qu, Jiaqi Gu, Yi Luo, Luo Yang and Yi Dai
J. Clin. Med. 2026, 15(8), 2949; https://doi.org/10.3390/jcm15082949 - 13 Apr 2026
Viewed by 271
Abstract
Background/Objectives: Platelet-rich plasma (PRP) is an autologous blood-derived biologic enriched in platelets and bioactive mediators. In urology and sexual medicine, PRP has been promoted for erectile dysfunction (ED) and a growing range of urogenital disorders on the premise that it may support angiogenesis, [...] Read more.
Background/Objectives: Platelet-rich plasma (PRP) is an autologous blood-derived biologic enriched in platelets and bioactive mediators. In urology and sexual medicine, PRP has been promoted for erectile dysfunction (ED) and a growing range of urogenital disorders on the premise that it may support angiogenesis, neuroregeneration, immune modulation, and tissue remodeling. However, clinical uptake has outpaced high-quality evidence, while heterogeneity in PRP preparation, characterization, and delivery limits interpretability and reproducibility. This structured narrative review aims to critically integrate mechanistic, preclinical, and clinical evidence regarding PRP use in ED, Peyronie’s disease (PD), stress urinary incontinence (SUI), interstitial cystitis/bladder pain syndrome (IC/BPS), and selected emerging indications. We further aim to identify sources of heterogeneity and propose an actionable minimum reporting framework (PRP-Uro Checklist) to guide future research. Methods: A structured search of PubMed/MEDLINE was conducted for studies published between 2021 and 2025. The relevant literature on PRP use in ED, PD, SUI, IC/BPS, and related indications was included for critical narrative synthesis. Emphasis was placed on PRP classification and preparation variables, outcome measure validity, and sources of heterogeneity across studies. Results: Mechanistic and preclinical evidence supports PRP’s potential to modulate nerve repair, angiogenesis, extracellular matrix remodeling, and immune polarization through a complex secretome of growth factors, cytokines, and extracellular vesicles (EVs). Clinical evidence suggests that intracavernosal PRP may improve erectile function in selected populations, but effect size, durability, and superiority over placebo remain uncertain due to small trials, substantial placebo effects, short follow-up, and incomplete biologic characterization. Evidence for PRP in PD, SUI, and IC/BPS remains preliminary and is derived largely from small cohorts, proof-of-concept studies, or uncontrolled designs, although early findings suggest potential symptom benefit and acceptable short-term tolerability. Across indications, inconsistent PRP reporting, particularly the absence of absolute platelet dose, leukocyte quantification, activation method, and standardized treatment protocols, represents a major barrier to reproducibility and evidence synthesis. Conclusions: PRP is biologically plausible and appears broadly safe, but its role in urology and sexual medicine remains investigational and is not yet supported by guideline-level evidence. To enhance reproducibility and interpretation, we propose a Minimum PRP Reporting Checklist for Urology and Sexual Medicine Trials (PRP-Uro Checklist). Future progress requires rigorous standardized reporting, indication-specific biologic characterization, rigorously designed sham-controlled trials, clinically meaningful endpoints, and longer-term follow-up. Full article
(This article belongs to the Section Nephrology & Urology)
14 pages, 2446 KB  
Article
Fibrinogen-to-Platelet Ratio and Hematologic Inflammatory Indexes in Spondylarthritis
by Roxana Doina Ungureanu, Cristina Elena Bita, Mirela Nicoleta Voicu, Adina Turcu-Stiolica, Sineta Cristina Firulescu, Mihai Turcu-Stiolica, Andreea Lili Bărbulescu, Stefan Cristian Dinescu and Florentin Ananu Vreju
J. Clin. Med. 2026, 15(8), 2926; https://doi.org/10.3390/jcm15082926 - 12 Apr 2026
Viewed by 249
Abstract
Background/Objectives: Spondylarthritis (SA) is characterized by high clinical heterogeneity, often resulting in a discrepancy between systemic inflammation and patient-reported symptoms. While hematologic indices are emerging as cost-effective biomarkers, their role in phenotypic differentiation remains unclear. We investigated the utility of traditional inflammatory [...] Read more.
Background/Objectives: Spondylarthritis (SA) is characterized by high clinical heterogeneity, often resulting in a discrepancy between systemic inflammation and patient-reported symptoms. While hematologic indices are emerging as cost-effective biomarkers, their role in phenotypic differentiation remains unclear. We investigated the utility of traditional inflammatory markers, including the novel fibrinogen-to-platelet ratio (FPR), in differentiating SA subtypes and predicting patient-reported disease activity. Methods: This cross-sectional study included 64 patients with spondylarthritis: axial SA (n = 32), peripheral SA (n = 8), and psoriatic SA (n = 24). Clinical assessments included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI). Systemic inflammation was evaluated via C-reactive protein (CRP), fibrinogen, and calculated ratios (NLR, PLR, MLR, and FPR). Principal Component Analysis (PCA) was employed to map the inflammatory architecture, while Receiver Operating Characteristic (ROC) curves evaluated the predictive power for high disease activity (BASDAI ≥ 4). Results: Significant phenotypic differences were observed with the FPR demonstrating superior discriminative capacity (p = 0.003). Patients with peripheral SA exhibited significantly higher FPR (median 1.88) compared to axial (1.33) and psoriatic (1.32) subtypes, and the dedicated ROC analysis for phenotypic discrimination yielded an AUC of 0.866 (95% CI: 0.745–0.987) (1.36, p = 0.039). HLA-B27 prevalence was low overall (31.3%) and in psoriatic SA (4.2%, p = 0.012). Correlation analysis revealed strong associations between BASDAI and BASFI (ρ = 0.79), NLR and MLR (ρ = 0.78), and CRP and fibrinogen (ρ = 0.66). PCA identified two independent inflammatory dimensions explaining 74.8% of variance: neutrophil-hypercoagulable axis (41.4%, driven by NLR, PLR, and MLR), and an acute-phase/fibrinogen axis (33.4%, driven by CRP, fibrinogen, and FPR). Notably, FPR clustered with acute-phase reactants rather than leukocyte-derived ratios, supporting its role as a marker of systemic inflammatory burden. Although fibrinogen is involved in the coagulation cascade, the absence of direct coagulation markers precludes definitive characterization of this component as hypercoagulable. ROC analysis revealed that fibrinogen showed the highest discriminative ability for disease activity (BASDAI ≥ 4), with an AUC of 0.690 (95% CI: 0.519–0.861), followed by NLR (0.621), MLR (0.592), and FPR (0.583). However, overall discriminative performance remained modest, with most 95% confidence intervals crossing 0.5. Conclusions: FPR emerges as a robust phenotypic biomarker capable of discriminating against SA subtypes, particularly identifying peripheral SA with high accuracy and excellent negative predictive value. In contrast, its ability to predict patient-reported disease activity remains limited, reinforcing the distinction between trait and state biomarkers. Exploratory PCA revealed that FPR clusters with acute-phase reactants rather than leukocyte-derived ratios, supporting its biological link to systemic inflammatory burden. These findings advocate for a dual-purpose biomarker approach in SA: FPR for phenotypic stratification and fibrinogen for activity assessment, while clinical indices remain indispensable for symptom monitoring. Validation in larger, prospective cohorts is warranted. Full article
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19 pages, 7039 KB  
Article
Morphological Characterization and Immunomodulatory Properties of Five Tolypothrix Strains
by Katerina Mladenova, Tsvetelina Batsalova, Dzhemal Moten, Balik Dzhambazov, Detelina Belkinova and Ivanka Teneva
Phycology 2026, 6(2), 40; https://doi.org/10.3390/phycology6020040 - 12 Apr 2026
Viewed by 285
Abstract
Different cyanobacterial species have been shown to be a valuable source of biologically active compounds with immunomodulatory activity. To date, little is known about members of the genus Tolypothrix (Cyanophyceae). Therefore, the present study focuses on five Tolypothrix strains (T. tenuis PACC [...] Read more.
Different cyanobacterial species have been shown to be a valuable source of biologically active compounds with immunomodulatory activity. To date, little is known about members of the genus Tolypothrix (Cyanophyceae). Therefore, the present study focuses on five Tolypothrix strains (T. tenuis PACC 5497, T. tenuis PACC 8648, T. distorta SAG 1482-2, T. distorta CCALA 194, Tolypothrix sp. PACC 5501) that were not previously evaluated for specific morphological characteristics and immunomodulatory potential toward human immune cells. Cyanobacterial cultures were studied by light and transmission electron microscopy (TEM). Peripheral blood leukocytes were isolated from patients with inflammatory conditions and treated ex vivo with Tolypothrix non-polar extract fractions. Following treatment, the cells were analyzed by flow cytometry, and cytokine concentrations in culture supernatants were quantified by ELISA. Light microscopy observations showed that the cultures established from four of the strains have morphological features that correspond to T. tenuis Kützing (1843) ex Bornet et Flahault 1887 and T. distorta Kützing (1843) ex Bornet et Flahault. TEM analyses indicated parietal arrangement of cellular thylakoids in all strains, but T. distorta CCALA194 and Tolypothrix sp. PACC 5501 also displayed fascicular thylakoid arrangement. Immunophenotypic analyses revealed significantly increased proportions of T, NK, and B lymphocytes in leukocyte cultures treated with Tolypothrix extracts compared to the untreated controls. The concentrations of proinflammatory cytokines were lower in the culture medium of treated cells, while levels of the anti-inflammatory cytokine interleukin-10 remained stable, except in cultures treated with T. distorta SAG 1482-2 extract. The present study provides the detailed morphological characteristics of five strains of the genus Tolypothrix and indicate that non-polar extract fractions derived from the strains exert immunomodulatory effects on human leukocytes. Full article
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26 pages, 1104 KB  
Review
Infection-Triggered Immune Dysregulation and Immunopathology in Lyme Disease: Mechanisms and Clinical Implications
by Klavio Pine, Vivian Pine, Nicoleta Negrut, Anca Ferician and Paula Marian
J. Clin. Med. 2026, 15(8), 2922; https://doi.org/10.3390/jcm15082922 - 11 Apr 2026
Viewed by 339
Abstract
Lyme disease (LD) is classically defined as a tick-borne infection caused by Borrelia burgdorferi sensu lato (Bbsl). However, accumulating evidence indicates that, beyond microbial persistence, Bbsl infection can initiate sustained immune dysregulation and post-infectious inflammatory phenotypes in a subset of patients. This narrative [...] Read more.
Lyme disease (LD) is classically defined as a tick-borne infection caused by Borrelia burgdorferi sensu lato (Bbsl). However, accumulating evidence indicates that, beyond microbial persistence, Bbsl infection can initiate sustained immune dysregulation and post-infectious inflammatory phenotypes in a subset of patients. This narrative review integrates open-access experimental, translational, and clinical data and discusses LD within the spectrum of infection-triggered, immune-mediated processes. We review key immunopathogenic mechanisms, including dysregulated innate immune activation, type I interferon (IFN-I) signaling, T helper 1 and T helper 17 (Th1/Th17) polarization with regulatory T-cell (Treg) insufficiency, antigen persistence (notably borrelial peptidoglycan), and pathways linking infection to autoimmunity such as molecular mimicry, epitope spreading, and human leukocyte antigen (HLA)-restricted susceptibility. These mechanisms are integrated with immune-mediated clinical manifestations affecting the central nervous system (CNS), peripheral nervous system (PNS), musculoskeletal system, heart, skin, and hematologic compartment. Finally, we discuss translational implications for diagnosis, biomarker-guided stratification, and emerging therapeutic strategies that extend beyond antimicrobial therapy, while addressing current controversies and limitations. This framework supports a mechanistic model in which Lyme disease-associated morbidity in selected patients reflects persistent immune activation and dysregulated host responses triggered by infection. Full article
11 pages, 383 KB  
Article
Monitoring Parameters During the Immediate Postnatal Transition Period and Inflammatory Markers in the First Two Days After Birth—A Retrospective Data Analysis
by Christina H. Wolfsberger, Andreas Hierz, Magdalena Holter, Nariae Baik-Schneditz, Ena Suppan, Bernhard Schwaberger and Gerhard Pichler
Children 2026, 13(4), 529; https://doi.org/10.3390/children13040529 - 10 Apr 2026
Viewed by 221
Abstract
Objective: The fetal-to-neonatal transition is marked by profound cardio-respiratory changes. Infections emerging within the first 48 h after birth may influence early cardiovascular adaptation. We aimed to evaluate the association between early infection/inflammation markers and vital parameters in neonates during the first 15 [...] Read more.
Objective: The fetal-to-neonatal transition is marked by profound cardio-respiratory changes. Infections emerging within the first 48 h after birth may influence early cardiovascular adaptation. We aimed to evaluate the association between early infection/inflammation markers and vital parameters in neonates during the first 15 min after birth. Methods: This is a secondary outcome parameter post-hoc analysis of data derived from a prospective observation study. Preterm and term neonates with cerebral oxygen saturation (crSO2) monitoring (INVOS 5100C) during the first 15 min after birth and available inflammatory markers (C-reactive protein [CRP], leukocytes, immature-to-total neutrophils ratio [IT ratio]) within 48 h after birth were included. Heart rate (HR) and arterial oxygen saturation (SpO2) were continuously recorded during the first 15 min. Inflammatory markers obtained at 16–24 and 24–48 h after birth were correlated with crSO2, SpO2, and HR at minute 5, 10 and 15. Results: Sixty-eight neonates were included (median (IQR) gestational age 34.0 (32.0; 35.9) weeks, birth weight 1900 (1488; 2542) grams). CRP within the first 24 h correlated negatively with crSO2 (r = −0.314; p = 0.011) and with SpO2 (r = −0.393; p = 0.001) at minute 15. IT ratio within 24 h correlated negatively with crSO2 at minute 5 (r = −0.367; p = 0.005), 10 (r = −0.273; p = 0.035), and 15 (r = −0.306; p = 0.013), and with SpO2 at minute 5 (r = −0.327; p = 0.008). IT ratio at 24–48 h correlated negatively with crSO2 at minute 15 (r = −0.384, p = 0.012). No significant correlations were observed with HR. Leukocytes within the first 24 h after birth correlated negatively with crSO2 at minute 5 (r = −0.265; p = 0.046). Conclusions: Early inflammatory markers, particularly CRP and the IT ratio, are associated with cerebral and systemic oxygenation during immediate postnatal transition. These findings suggest a potential association between early inflammatory activation and oxygenation dynamics; however, given the observational design and modest correlation strength, the results should be interpreted cautiously and do not allow conclusions regarding causality or underlying mechanisms. Full article
(This article belongs to the Special Issue Neonatal Resuscitation: Current Updates and Global Perspectives)
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12 pages, 1117 KB  
Review
Transient Glycocalyx Remodeling by Intravenous Hyaluronidase in Atherosclerosis: A Hypothesis-Generating Review
by Andreas Pfützner, Tobias Gantner, Harald Burgard, Tilman Steinmeier, Eduard Stappler, Julia Jantz and Petra Wiechel
Pathophysiology 2026, 33(2), 26; https://doi.org/10.3390/pathophysiology33020026 - 10 Apr 2026
Viewed by 200
Abstract
Atherosclerosis remains the leading cause of death worldwide and imposes a major healthcare burden. Physiologically, elimination of cholesterol from the arterial wall depends on reverse cholesterol transport (RCT). RCT requires access to HDL and apolipoprotein A-I (ApoA-I) to lesional macrophages/foam cells. The endothelial [...] Read more.
Atherosclerosis remains the leading cause of death worldwide and imposes a major healthcare burden. Physiologically, elimination of cholesterol from the arterial wall depends on reverse cholesterol transport (RCT). RCT requires access to HDL and apolipoprotein A-I (ApoA-I) to lesional macrophages/foam cells. The endothelial glycocalyx is a dynamic and injury-sensitive layer of proteoglycans and glycosaminoglycans (including hyaluronan). It contributes to vascular barrier properties, leukocyte adhesion, mechanotransduction, and macromolecular transport. In atherosclerosis, glycocalyx structure and function are altered; this may facilitate entry/retention of atherogenic lipoproteins and may also alter transport conditions relevant to cholesterol efflux pathways. This article presents a mechanistic hypothesis: short, transient, systemic hyaluronidase exposure could temporarily remodel glycocalyx/extracellular matrix components and thereby facilitate conditions permissive for regulated transport processes relevant to RCT. However, the proposed link between glycocalyx remodeling and improved lesional cholesterol efflux remains theoretical. Direct in vivo evidence that the endothelial glycocalyx is a dominant barrier limiting HDL- or ApoA-I-mediated cholesterol efflux from plaque macrophages is currently limited. Moreover, glycocalyx degradation is widely associated with endothelial dysfunction, increased permeability, inflammation, and thrombosis, all of which could aggravate rather than ameliorate atherosclerosis. Human pharmacokinetic data indicate a very short plasma half-life of circulating hyaluronidase activity, suggesting that any systemic enzymatic effect is brief. Nevertheless, the biological consequences of repeated degradation–regeneration cycles, especially in high-risk states such as diabetes, inflammation, oxidative stress, or chronic kidney disease, remain incompletely understood. Evidence supporting clinical benefit in atherosclerosis is currently limited to heterogeneous animal experiments, historical uncontrolled reports, and a small number of anecdotal case observations, whereas randomized trials have only been performed in other settings such as acute myocardial infarction and do not establish efficacy for plaque regression. We therefore provide a balanced evaluation of knowns, uncertainties, alternative interpretations, potential risks, dosing unknowns, and a translational research agenda including mechanistic preclinical studies, biomarker development, imaging, and carefully designed early-phase clinical investigation. Full article
(This article belongs to the Section Cardiovascular Pathophysiology)
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10 pages, 273 KB  
Article
Prevalence and Specificity of Anti-HPA and Anti-HLA Antibodies in Patients with Suspected Immune-Mediated Platelet Disorders: A Single-Center Study from Serbia
by Svetlana Vojvodić and Jasmina Grujić
Medicina 2026, 62(4), 725; https://doi.org/10.3390/medicina62040725 - 10 Apr 2026
Viewed by 207
Abstract
Background and Objectives: Alloantibodies directed against human platelet antigens and human leukocyte antigens are implicated in several immune-mediated platelet disorders, including platelet transfusion refractoriness, post-transfusion purpura and fetal and neonatal alloimmune thrombocytopenia. Reliable and simultaneous detection of these antibodies is essential for accurate [...] Read more.
Background and Objectives: Alloantibodies directed against human platelet antigens and human leukocyte antigens are implicated in several immune-mediated platelet disorders, including platelet transfusion refractoriness, post-transfusion purpura and fetal and neonatal alloimmune thrombocytopenia. Reliable and simultaneous detection of these antibodies is essential for accurate diagnosis and appropriate clinical management. The aim of this study was to determine the prevalence and specificity spectrum of anti-HLA and anti-HPA alloantibodies in patients with suspected immune-mediated platelet disorders using a multiplex bead-based assay, and to evaluate its diagnostic utility in a Serbian cohort. Materials and Methods: A bead-based glycoprotein-specific antibody detection assay was performed using monoclonal antibodies specific for platelet glycoproteins and HLA class I molecules, separately coupled to Luminex microbeads. Serum samples were collected from 259 patients, including 234 patients with thrombocytopenia, 11 with neonatal alloimmune thrombocytopenia, and 14 with suspected platelet transfusion refractoriness. All samples were tested using the PakLx Luminex assay, and results were interpreted with MatchIt! Antibody software. Results: Of the 259 tested samples, 72 (27.8%) were positive for HLA and/or platelet-specific antibodies. Among the positive samples, 29.2% contained HLA class I antibodies, 45.8% contained platelet-specific antibodies, and 25% showed combined HLA and platelet antibody positivity. The most frequently detected platelet-specific antibodies were directed against GPIIb/IIIa (HPA-1, -3, -4) and GPIa/IIa (HPA-5). Conclusions: This first analysis of platelet alloantibodies in a Serbian cohort demonstrates a high prevalence of antibody positivity in patients with neonatal alloimmune thrombocytopenia and platelet transfusion refractoriness, with anti-HPA-1a as the predominant specificity. The significant association between clinical presentation and antibody profile underscores the need for targeted diagnostic testing. Multiplex bead-based technology provides comprehensive alloantibody detection, facilitating optimized transfusion management in immune-mediated platelet disorders. Full article
(This article belongs to the Section Hematology and Immunology)
14 pages, 1125 KB  
Article
The Lectin from Schinus terebinthifolia Raddi Leaves (SteLL) Exhibited Anti-Inflammatory Activity in Lipopolysaccharide-Induced Acute Lung Injury in Mice
by Amanda de Oliveira Marinho, Maria Nívea Bezerra da Silva, Ana Karollina Viana Chagas, Alícia Natalie Silva dos Santos, Pedro Paulo Marcelino Neto, Patrícia Maria Guedes Paiva, Emmanuel Viana Pontual, Anderson Arnaldo da Silva, Leydianne Leite de Siqueira Patriota and Thiago Henrique Napoleão
Int. J. Mol. Sci. 2026, 27(8), 3394; https://doi.org/10.3390/ijms27083394 - 10 Apr 2026
Viewed by 274
Abstract
Acute lung injury (ALI) is a severe inflammatory condition associated with high morbidity and mortality, and there are currently no specific pharmacological treatments available. In this context, plants and natural products have emerged as promising therapeutic alternatives. SteLL (Schinus terebinthifolia Raddi leaf [...] Read more.
Acute lung injury (ALI) is a severe inflammatory condition associated with high morbidity and mortality, and there are currently no specific pharmacological treatments available. In this context, plants and natural products have emerged as promising therapeutic alternatives. SteLL (Schinus terebinthifolia Raddi leaf lectin) has demonstrated several biological activities, including anti-inflammatory and immunomodulatory effects. This study evaluated the anti-inflammatory effects of SteLL in a murine model of lipopolysaccharide (LPS)-induced ALI. Female BALB/c mice received intraperitoneal (i.p.) administration of SteLL (1, 5, or 10 mg/kg), dexamethasone (2 mg/kg), or vehicle (PBS). Sixty minutes later, ALI was induced by intranasal instillation of 25 µL of LPS (1 μg/μL). After 24 h, the animals were euthanized. Bronchoalveolar lavage fluid (BALF) was obtained to evaluate inflammatory parameters and lungs were collected for histopathological analysis. The tested doses of SteLL resulted in a 45–66% lower leukocyte infiltration. The group treated with 5 mg/kg exhibited a lower proportion of neutrophils and a higher proportion of mononucleated cells. Pre-treatment with SteLL also minimized plasma leakage and myeloperoxidase (MPO) activity. Furthermore, SteLL attenuated the release of pro-inflammatory cytokines at all tested doses as well as prevented nitric oxide (NO) production at the highest dose (10 mg/kg). Histopathological analysis showed that SteLL (5 and 10 mg/kg) attenuated LPS-induced lung injury. Overall, SteLL demonstrated significant anti-inflammatory effects, showing its potential as a plant-derived compound for modulating pulmonary inflammation. Full article
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