Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (772)

Search Parameters:
Keywords = N2 neutrophils

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
22 pages, 1924 KiB  
Article
Effects of Superground Pfaffia glomerata Leaves on Growth Performance and Immune Function in New Zealand Rabbits
by Yan-Jun Chen, Guang-Zhou Lv, Asim Muhammad, Xin-Yu Zheng, Jia-Hong Xie and Jin-Jun Chen
Animals 2025, 15(16), 2452; https://doi.org/10.3390/ani15162452 - 21 Aug 2025
Abstract
The rabbit industry urgently needs natural alternatives to maintain gut health. This need is growing due to the higher incidence of intestinal problems in antibiotic-free production systems. Pfaffia glomerata (Brazilian ginseng) is a medicinal plant rich in bioactive compounds. This study evaluated the [...] Read more.
The rabbit industry urgently needs natural alternatives to maintain gut health. This need is growing due to the higher incidence of intestinal problems in antibiotic-free production systems. Pfaffia glomerata (Brazilian ginseng) is a medicinal plant rich in bioactive compounds. This study evaluated the effects of dietary inclusion of P. glomerata leaf powder on growth performance, immune function, and gut microbiota in New Zealand rabbits. A total of 100 New Zealand rabbits (35 days old) were randomly assigned to five groups (n = 20 each). The groups comprised a blank control group (CON), an immunosuppressed group (CTX), and three treatment groups receiving low (L), medium (M), and high (H) doses of P. glomerata leaf powder at 0.5%, 1%, and 2% of the basal diet, respectively. Growth performance was assessed by average daily gain (ADG). Intestinal morphology was evaluated by measuring villus height and crypt depth in the duodenum, jejunum, and ileum. Immune parameters included thymus and spleen weight, serum immunoglobulin levels, and leukocyte counts. Cecal microbiota diversity and composition were analyzed. Compared to CON, Pfaffia supplementation improved growth performance: the L and H groups had significantly higher ADG and a lower feed conversion ratio (p < 0.05). In intestinal histology, groups L and M had reduced crypt depth in the duodenum (p < 0.05), and group L had an increased villus height to crypt depth ratio. In the jejunum and ileum, groups L and H exhibited increased villus height and villus height to crypt depth ratio (p < 0.05), indicating an enhanced absorptive surface. In the immunosuppressed model, rabbits in all Pfaffia groups showed significantly increased thymus and spleen weight compared to the CTX group (p < 0.05) and demonstrated elevated serum immunoglobulins and leukocyte counts (monocytes, lymphocytes, and neutrophils) (p < 0.05). Pfaffia supplementation also enhanced cecal microbiota diversity and increased the abundance of beneficial bacteria. In summary, dietary P. glomerata leaf powder enhanced growth performance, immune organ development, and healthy gut microbiota in growing rabbits. The 0.5% supplementation level (L group) yielded the most consistent benefits. These results suggest that P. glomerata is a promising natural feed additive to promote rabbit health and production in antibiotic-free systems. Full article
Show Figures

Figure 1

15 pages, 10651 KiB  
Article
Systemic Inflammatory Burden Causes Liver Injury in H1N1-Infected Mice
by Junbin Wang, Qing Huang, Yun Yang, Cong Tang, Wenhai Yu, Yanan Zhou, Daoju Wu, Bai Li, Hao Yang, Haixuan Wang, Lei Ma and Shuaiyao Lu
Viruses 2025, 17(8), 1132; https://doi.org/10.3390/v17081132 - 18 Aug 2025
Viewed by 103
Abstract
Clinical evidence has associated H1N1 influenza with liver impairment, yet the underlying mechanisms remain poorly understood. Here, we investigated H1N1-induced liver damage and its potential mechanisms using a BALB/c mouse infection model. Pathological examination and serum aspartate transaminase (AST) and alanine transaminase (ALT) [...] Read more.
Clinical evidence has associated H1N1 influenza with liver impairment, yet the underlying mechanisms remain poorly understood. Here, we investigated H1N1-induced liver damage and its potential mechanisms using a BALB/c mouse infection model. Pathological examination and serum aspartate transaminase (AST) and alanine transaminase (ALT) were assessed. Messenger ribonucleic acid-sequence was used to analyze the transcriptomic changes in tissues. Multiple inflammatory cytokines in tissues and inflammatory cells in the blood were detected on the fifth day post-infection. Our results showed that H1N1 infection caused significant liver pathology and elevated serum AST/ALT levels. Transcriptomic analysis revealed significant alterations in liver gene expression profiles following H1N1 infection, particularly in genes associated with inflammatory responses, including those involved in monocyte adhesion/activation and neutrophil/macrophage infiltration. Marked increases in inflammatory mediators were observed in lungs, serum, and liver, accompanied by systemic changes in circulating inflammatory cells, indicating H1N1 triggered a robust systemic inflammatory response. These findings suggest that H1N1-induced liver damage may be associated with the systemic inflammatory response induced by H1N1 and changes in liver gene regulation. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
Show Figures

Figure 1

15 pages, 3491 KiB  
Article
PARP Inhibition Shifts Murine Myeloid Cells Toward a More Tolerogenic Profile In Vivo
by Jose R. Pittaluga-Villarreal, Casey M. Daniels, Tara Capece, Pauline R. Kaplan, Martin Meier-Schellersheim and Aleksandra Nita-Lazar
Biomolecules 2025, 15(8), 1149; https://doi.org/10.3390/biom15081149 - 9 Aug 2025
Viewed by 427
Abstract
The human Poly ADP-ribose Polymerase (PARP) family comprises 17 enzymes responsible for the transfer of ADP-ribose to proteins, forming poly- or mono-ADP-ribosylation. This post-translational modification regulates DNA repair and programmed cell death, processes affecting cancer biology. PARP inhibitors, including the FDA-approved olaparib, are [...] Read more.
The human Poly ADP-ribose Polymerase (PARP) family comprises 17 enzymes responsible for the transfer of ADP-ribose to proteins, forming poly- or mono-ADP-ribosylation. This post-translational modification regulates DNA repair and programmed cell death, processes affecting cancer biology. PARP inhibitors, including the FDA-approved olaparib, are used to treat BRCA-dependent breast and ovarian cancers. Although therapies with use of PARP inhibitors are showing clinical success, their effects on the immune system remain understudied. Prior work has shown that PARP inhibition can modulate inflammatory responses and alter innate immunity. In this study, we evaluated the immunomodulatory effects of olaparib on myeloid cells in vivo, focusing on bone marrow and spleen. Olaparib treatment altered the composition and activation state of dendritic cells, neutrophils, and macrophages. In the bone marrow, olaparib increased the proportion of cDC2 population, mature neutrophils and inflammatory macrophages expressing CD80. In contrast, splenic myeloid cells exhibited enhanced expression of markers associated with tolerogenic phenotypes, including CD206 and CD124 in neutrophils and macrophages. The spleen also showed an increase in immature monocyte-derived dendritic cells (CD206+) and a bias toward the cDC2 subset. These findings indicate that PARP inhibition can induce short-term phenotypic remodeling of myeloid cell populations, promoting a more immunoregulatory profile, especially in the spleen. These changes may contribute to an altered immune landscape with implications for anti-tumor immunity. Full article
(This article belongs to the Special Issue PARPs in Cell Death and PARP Inhibitors in Cancers: 2nd Edition)
Show Figures

Figure 1

28 pages, 1748 KiB  
Review
Neutrophil Dynamics in Response to Cancer Therapies
by Huazhen Xu, Xiaojun Chen, Yuqing Lu, Nihao Sun, Karis E. Weisgerber, Manzhu Xu and Ren-Yuan Bai
Cancers 2025, 17(15), 2593; https://doi.org/10.3390/cancers17152593 - 7 Aug 2025
Viewed by 480
Abstract
Neutrophils are increasingly recognized as key players in the tumor microenvironment (TME), displaying functional plasticity that enables them to either promote or inhibit cancer progression. Depending on environmental cues, tumor-associated neutrophils (TANs) may polarize toward antitumor “N1” or protumor “N2” phenotypes, exerting diverse [...] Read more.
Neutrophils are increasingly recognized as key players in the tumor microenvironment (TME), displaying functional plasticity that enables them to either promote or inhibit cancer progression. Depending on environmental cues, tumor-associated neutrophils (TANs) may polarize toward antitumor “N1” or protumor “N2” phenotypes, exerting diverse effects on tumor growth, metastasis, immune modulation, and treatment response. While previous studies have focused on the pathological roles of TANs in cancer, less attention has been given to how cancer therapies themselves influence the behavior of TANs. This review provides a comprehensive synthesis of current knowledge regarding the dynamics of TANs in response to major cancer treatment modalities, including chemotherapy, radiotherapy, cell-based immunotherapies, and oncolytic viral and bacterial therapies. We discuss how these therapies influence TAN recruitment, polarization, and effector functions within the TME, and highlight key molecular regulators involved. By consolidating mechanistic and translational insights, this review emphasizes the potential to therapeutically reprogram TANs to enhance treatment efficacy. A deeper understanding of context-dependent TAN roles will be essential for developing more effective, neutrophil-informed cancer therapies. Full article
(This article belongs to the Special Issue The Role of Neutrophils in Tumor Progression and Metastasis)
Show Figures

Figure 1

11 pages, 782 KiB  
Article
Exploring the Association Between Platelet Count, the Systemic Immune Inflammation Index, and Fracture Risk in Postmenopausal Women with Osteoporosis: A Cross-Sectional Study
by Cecilia Oliveri, Anastasia Xourafa, Rita Maria Agostino, Valentina Corigliano, Antonino Botindari, Agostino Gaudio, Nunziata Morabito, Alessandro Allegra and Antonino Catalano
J. Clin. Med. 2025, 14(15), 5453; https://doi.org/10.3390/jcm14155453 - 2 Aug 2025
Viewed by 575
Abstract
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution [...] Read more.
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution width (PDW), platelet crit, percentage of large platelets (P-LCR), platelet–lymphocyte ratio, and the SII, calculated as (NxP)/L, where N, P, and L represented neutrophils, platelets and lymphocytes counts, respectively, were evaluated. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Results: A total of 124 women (mean age 68.4 ± 9 years) were stratified into two groups based on the median platelet count; the “lower platelet count group” (n = 58) had a count of 200,000 (174,000 to 226,000), while the “higher platelet count group” (n = 66) had a count of 281,500 (256,500 to 308,500). The higher platelet count group showed a higher hip fracture risk (7.4 vs. 4.5%, p = 0.08) and lower lumbar spine BMD (0.773 vs. 0.83 gr/cm2, p = 0.03). By dividing the participants into two groups with higher SSI (950,848.6 ± 746,097.99) (n = 61) and lower SII (355,751.2 ± 88,662.6) (n = 63), the group with the higher SII showed the higher hip fracture risk (7.4 vs. 3.6%, p = 0.01). Univariate regression analysis revealed correlations between chronological age and PDW (r = 0.188, p = 0.047), and P-LCR (r = 0.208, p = 0.03), as well as associations between vitamin D status and P-LCR (r = −0.301, p = 0.034), and between SII and hip fracture risk (r = 0.12, p = 0.007). Conclusions: Platelet count and SII were associated with fracture risk in postmenopausal women undergoing osteoporosis assessment. Given their reproducibility and cost-effectiveness, these markers warrant further investigation in future prospective studies focused on bone fragility. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, Prevention and Rehabilitation in Osteoporosis)
Show Figures

Figure 1

15 pages, 504 KiB  
Article
Long-Term Impact of Neonatal Acute Kidney Injury on Renal Function in Children Born Preterm: A Follow-Up Study
by Tuğba Barsan Kaya, Özge Aydemir, Ozge Surmeli Onay, Evin Kocaturk, Çiğdem Öztunalı, Aslı Kavaz Tufan, Nuran Cetin, Özkan Alataş and Ayşe Neslihan Tekin
Children 2025, 12(8), 1018; https://doi.org/10.3390/children12081018 - 1 Aug 2025
Viewed by 282
Abstract
Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In [...] Read more.
Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In this prospective cohort, preterm-born children (≤35 weeks’ gestation) with (n = 19) and without (n = 38) neonatal AKI were evaluated at 7–12 years. A term-born control group (n = 44) was included for biomarker comparison. Assessments included perinatal data, anthropometry, office and ambulatory blood pressure monitoring (ABPM), and renal ultrasonography. Kidney function was evaluated using serum creatinine (sCr), cystatin C, and estimated glomerular filtration rate (eGFR). Tubular injury was assessed using urinary kidney injury molecule-1/Cr (KIM-1/Cr), neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr), and trefoil factor 3/Cr (TFF3/Cr) ratios, as well as serum TFF3. Results: Conventional kidney function markers were similar among groups. However, the AKI group had higher serum cystatin C, lower cystatin C–based eGFR, and elevated urinary KIM-1/Cr and NGAL/Cr compared to no-AKI and term controls. Serum TFF3 was also higher in the AKI group. ABPM revealed higher nocturnal systolic blood pressure and blood pressure load in the AKI group. Kidney size did not differ between preterm subgroups. Conclusions: Neonatal AKI in preterm infants is associated with subtle alterations and potential renal stress or injury at school age, detectable only with sensitive biomarkers and ABPM. Further prospective studies are needed to validate these biomarkers and determine their role in predicting long-term outcomes in preterm infants with neonatal AKI. Full article
(This article belongs to the Section Pediatric Nephrology & Urology)
Show Figures

Figure 1

15 pages, 4972 KiB  
Article
In Vivo Biocompatibility Assessment of a Novel Cyanoacrylate–Polylactic Acid Hemostatic Patch
by Alexandru Ilie-Ene, Victor P. Tosa, Luciana M. Gherman, Lorena M. Hantig, Madalin M. Onofrei, Lavinia P. Mocan, Carmen M. Mihu, Catalin O. Popa and George C. Dindelegan
Materials 2025, 18(15), 3581; https://doi.org/10.3390/ma18153581 - 30 Jul 2025
Viewed by 390
Abstract
Background and Objectives: Although cyanoacrylate–polylactic acid (CA + PLA) patches shorten the time to hemostasis after partial hepatectomy, their long-term biocompatibility remains uncertain. We compared the 5-month histopathological footprint of a novel CA + PLA patch (Study group) with a licensed fibrinogen/thrombin matrix [...] Read more.
Background and Objectives: Although cyanoacrylate–polylactic acid (CA + PLA) patches shorten the time to hemostasis after partial hepatectomy, their long-term biocompatibility remains uncertain. We compared the 5-month histopathological footprint of a novel CA + PLA patch (Study group) with a licensed fibrinogen/thrombin matrix (TachoSil® group) and electrocautery (Control group). Methods: Thirty-three male Wistar rats underwent a 3 × 1.5 cm hepatic segment resection and were randomized to the Control (n = 5), Study (n = 14), or TachoSil® (n = 14) group. The animals were sacrificed on postoperative day (POD) 50, 100, or 150. Blinded semiquantitative scoring (0–3) was used to capture inflammation intensity, and the number of neutrophils (PMNs), lymphocytes (Ly’s), isolated histiocytes, and foreign-body giant cells (FBGCs). Results: The proportions of animals in each group across the different sacrifice time points were homogeneous (χ2 = 4.34, p = 0.36). The median inflammation remained mild (2 [IQR 1–2]) in the Control and Study groups but lower in the TachoSil® group (1 [1–2], p = 0.47). The FBGC scores differed markedly (score ≥ 2: 64% in Study, 0% in Control, 14% in TachoSil®; p < 0.001). Fibrosis occurred almost exclusively in the Study group (79% vs. 0%; χ2 = 22.4, p < 0.001). Mature vessels were most frequently observed in the TachoSil® group (50%, aOR = 5.1 vs. Study, p = 0.04). Abscesses only developed in the Study group (29%, p = 0.046). Within the TachoSil® group, inflammation (ρ = −0.62, p = 0.019) and Ly infiltration (ρ = −0.76, p = 0.002) declined with time; no significant temporal trends emerged in the Study group. Conclusions: At the five-month follow-up, there was an exuberant foreign-body reaction, dense collagen deposition, and a higher abscess rate around the CA + PLA patch compared with both TachoSil® and cautery. Conversely, TachoSil® evolved toward a mature, well-vascularized scar with waning inflammation. These findings underscore the importance of chronic-phase evaluation before clinical adoption of new hemostatic biomaterials. Full article
(This article belongs to the Special Issue Materials for Drug Delivery and Medical Engineering)
Show Figures

Figure 1

25 pages, 15118 KiB  
Article
CD45 and CD148 Are Critically Involved in Neutrophil Recruitment and Function During Inflammatory Arthritis in Mice
by Jan-Niklas Heming, Andreas Margraf, Karolina Najder, Giulia Germena, Mathis Richter, Anika Cappenberg, Katharina Henke, Bernadette Bardel, Lena Schemmelmann, Marina Oguama, Pia Lindental, Wida Amini, Jacqueline Sobocik, Georg Schett, Gerhard Krönke, Helena Block, Jan Rossaint, Oliver Soehnlein and Alexander Zarbock
Cells 2025, 14(15), 1169; https://doi.org/10.3390/cells14151169 - 29 Jul 2025
Viewed by 365
Abstract
Neutrophils play a key role in autoimmune diseases like rheumatoid arthritis, contributing to tissue damage through rapid recruitment and activation. In this study, we investigated the regulatory properties of two receptor-like tyrosine phosphatases (RPTPs), CD45 and CD148, in inflammatory arthritis. Using an in [...] Read more.
Neutrophils play a key role in autoimmune diseases like rheumatoid arthritis, contributing to tissue damage through rapid recruitment and activation. In this study, we investigated the regulatory properties of two receptor-like tyrosine phosphatases (RPTPs), CD45 and CD148, in inflammatory arthritis. Using an in vivo mouse model of K/BxN serum transfer-induced arthritis, we found that CD45 and CD148 feature distinct regulatory properties during inflammatory arthritis. CD45 is required for neutrophil infiltration, cytokine release, and reactive oxygen species production, whereas CD148 deficiency leads to a delayed onset of arthritis but unaltered overall neutrophil infiltration and reduced ROS production. Furthermore, we could demonstrate that activation of Src family kinases in neutrophils is differentially regulated by CD45 and CD148 in a stimulus-dependent manner. Summarizing, our results suggest that CD45 is positively involved, while CD148 is positively and negatively involved in neutrophil recruitment and function during inflammatory arthritis. Full article
Show Figures

Figure 1

17 pages, 5140 KiB  
Article
Comparative Analysis of Chitosan, Lipid Nanoparticles, and Alum Adjuvants in Recombinant SARS-CoV-2 Vaccine: An Evaluation of Their Immunogenicity and Serological Efficacy
by Majed Ghattas, Garima Dwivedi, Anik Chevrier, Trevor Scobey, Rakan El-Mayta, Melissa D. Mattocks, Dong Wang, Marc Lavertu and Mohamad-Gabriel Alameh
Vaccines 2025, 13(8), 788; https://doi.org/10.3390/vaccines13080788 - 24 Jul 2025
Viewed by 588
Abstract
Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following [...] Read more.
Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following administration of recombinant SARS-CoV-2 spike immunogen in adult mice. Mice received the adjuvanted recombinant protein vaccine in a prime-boost regimen with four weeks interval. Subsequent analyses included serological assessment of antibody responses, evaluation of T cell activity, immune cell recruitment and cytokine profiles at injection site. Results: Compared to alum, chitosan induced a more balanced Th1/Th2 response, akin to that observed with eLNPs, demonstrating its ability to modulate both the humoral and cellular immune pathways. Chitosan induced a different proinflammatory cytokine (e.g., IL-1⍺, IL-2, IL-6, and IL-7) and chemokine (e.g., Eotaxin, IP-10, MIP-1a) profile compared to eLNPs and alum at the injection site and in the draining lymph nodes. Moreover, chitosan potentiated the recruitment of innate immune cells, with neutrophils accounting for about 40% of the infiltrating cells in the muscle, representing a ~10-fold increase compared to alum and a comparable level to eLNPs. Conclusions: These findings collectively indicate that chitosan has the potential to serve as an effective adjuvant, offering comparable, and potentially superior, properties to those of currently approved adjuvants. Full article
(This article belongs to the Special Issue Advances in Vaccine Adjuvants)
Show Figures

Figure 1

73 pages, 19750 KiB  
Article
Transcriptomic Profiling of the Immune Response in Orthotopic Pancreatic Tumours Exposed to Combined Boiling Histotripsy and Oncolytic Reovirus Treatment
by Petros Mouratidis, Ricardo C. Ferreira, Selvakumar Anbalagan, Ritika Chauhan, Ian Rivens and Gail ter Haar
Pharmaceutics 2025, 17(8), 949; https://doi.org/10.3390/pharmaceutics17080949 - 22 Jul 2025
Viewed by 389
Abstract
Background: Boiling histotripsy (BH) uses high-amplitude, short-pulse focused ultrasound to disrupt tissue mechanically. Oncolytic virotherapy using reovirus has shown modest clinical benefit in pancreatic cancer patients. Here, reovirus and BH were used to treat pancreatic tumours, and their effects on the immune [...] Read more.
Background: Boiling histotripsy (BH) uses high-amplitude, short-pulse focused ultrasound to disrupt tissue mechanically. Oncolytic virotherapy using reovirus has shown modest clinical benefit in pancreatic cancer patients. Here, reovirus and BH were used to treat pancreatic tumours, and their effects on the immune transcriptome of these tumours were characterised. Methods: Orthotopic syngeneic murine pancreatic KPC tumours grown in immune-competent subjects, were allocated to control, reovirus, BH and combined BH and reovirus treatment groups. Acoustic cavitation was monitored using a passive broadband cavitation sensor. Treatment effects were assessed histologically with hematoxylin and eosin staining. Single-cell multi-omics combining whole-transcriptome analysis with the expression of surface-expressed immune proteins was used to assess the effects of treatments on tumoural leukocytes. Results: Acoustic cavitation was detected in all subjects exposed to BH, causing cellular disruption in tumours 6 h after treatment. Distinct cell clusters were identified in the pancreatic tumours 24 h post-treatment. These included neutrophils and cytotoxic T cells overexpressing genes associated with an N2-like and an exhaustion phenotype, respectively. Reovirus decreased macrophages, and BH decreased regulatory T cells compared to controls. The combined treatments increased neutrophils and the ratio of various immune cells to Treg. All treatments overexpressed genes associated with an innate immune response, while ultrasound treatments downregulated genes associated with the transporter associated with antigen processing (TAP) complex. Conclusions: Our results show that the combined BH and reovirus treatments maximise the overexpression of genes associated with the innate immune response compared to that seen with each individual treatment, and illustrate the anti-immune phenotype of key immune cells in the pancreatic tumour microenvironment. Full article
Show Figures

Figure 1

14 pages, 3307 KiB  
Article
Expanding the Spectrum of CSF3R-Mutated Myeloid Neoplasm Beyond Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia: A Comprehensive Analysis of 13 Cases
by Neha Seth, Judith Brody, Peihong Hsu, Jonathan Kolitz, Pratik Q. Deb and Xinmin Zhang
J. Clin. Med. 2025, 14(15), 5174; https://doi.org/10.3390/jcm14155174 - 22 Jul 2025
Viewed by 423
Abstract
Background: Genetic alterations in CSF3R, typically associated with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML), rarely occur in other myeloid neoplasms. Methods: This study characterized the clinical, morphologic, cytogenetic, and molecular features of 13 patients with non-CNL non-aCML myeloid [...] Read more.
Background: Genetic alterations in CSF3R, typically associated with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML), rarely occur in other myeloid neoplasms. Methods: This study characterized the clinical, morphologic, cytogenetic, and molecular features of 13 patients with non-CNL non-aCML myeloid neoplasms with CSF3R alterations. Patients (median age, 77 years) were categorized into groups with a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) (n = 5), acute leukemia (n = 4), and other myeloid neoplasms (n = 4) based on the WHO 2022 and ICC criteria. Results: The CSF3R p.Thr618Ile mutation was most frequent (11/13), with additional pathogenic variants including p.Gln743Ter and frameshift mutations affecting the cytoplasmic tail. Variant allele frequencies (VAFs) ranged from 2% to 49%, with the highest median VAF in the MDS/MPN group. Co-mutations varied by subtype; MDS/MPN, NOS, and CMML cases frequently harbored mutations in epigenetic regulators (ASXL1, TET2) and splicing factors (SF3B1, SRSF2, ZRSR2), while acute leukemia cases showed alterations in JAK3, STAT3, and NRAS. Survival analysis revealed distinct patterns across the three diagnostic groups, with MDS/MPN having the poorest prognosis. Conclusion: This study expands the recognized spectrum of CSF3R-related myeloid neoplasms and highlights the clinical and molecular heterogeneity associated with these mutations, emphasizing the need for comprehensive molecular profiling and the potential for targeted therapies. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies for Acute Myeloid Leukemia)
Show Figures

Figure 1

11 pages, 810 KiB  
Article
Pediatric Hematology–Oncology Provider Attitudes and Beliefs About the Use of Acupuncture for Their Patients
by Holly L. Spraker-Perlman, Kenneth M. Busby, Amy Ly, Maggi Meyer, Justin N. Baker and Deena R. Levine
Children 2025, 12(8), 961; https://doi.org/10.3390/children12080961 - 22 Jul 2025
Viewed by 435
Abstract
Background/Objectives: Children with cancer suffer due to the underlying disease and prescribed cancer-directed therapies, and non-pharmacologic modalities may offer improved symptom control without additional medications. We sought to elicit knowledge, attitudes, and beliefs of Pediatric Hematology Oncology (PHO) providers surrounding the incorporation [...] Read more.
Background/Objectives: Children with cancer suffer due to the underlying disease and prescribed cancer-directed therapies, and non-pharmacologic modalities may offer improved symptom control without additional medications. We sought to elicit knowledge, attitudes, and beliefs of Pediatric Hematology Oncology (PHO) providers surrounding the incorporation of acupuncture for symptom management for their patients. Methods: A cross-sectional survey instrument was created, formatted, and delivered to physicians and advanced practice providers (APPs) at a single US pediatric cancer center. Survey responses were summarized by descriptive statistics. Results: A total of 78 PHO clinicians participated (response rate 29%). Most participants were interested in learning more about acupuncture (n = 42, 56.0%), yet rarely (n = 17, 22.7%) or never (n = 46, 61.3%) recommend acupuncture to patients. Most (n = 51, 73.9%) noted that they would support institutional development of an acupuncture program. Over half (n = 37, 52.2%) indicated their threshold for minimum hematologic indices for acupuncture includes a platelet count greater than 20,000 and absolute neutrophil count (ANC) greater than 500 (n = 37, 54.4%). Approximately two-thirds (n = 52, 66.7%) of participants noted that acupuncture could improve their patient’s quality of life, and most (n = 46, 67.6%) were not worried about harm. Conclusions: Acupuncture for symptom management is an evidenced-based, guideline-concordant recommendation for adults with cancer, but robust data in the pediatric oncology population are lacking. PHO providers do not routinely recommend acupuncture for patients but note that it may improve quality of life. Given their high symptom burden, rigorous studies of non-pharmacologic strategies for pediatric symptom management are vital. Acupuncture should be examined as a potential beneficial adjunct. Full article
Show Figures

Figure 1

17 pages, 706 KiB  
Article
Hematological Parameter-Derived Inflammatory Scores in Non-Pancreatic Hyperlipasemia (NPHL)—The Prognosis Lies in the Blood
by Krisztina Eszter Feher, David Tornai and Maria Papp
Biomedicines 2025, 13(7), 1719; https://doi.org/10.3390/biomedicines13071719 - 14 Jul 2025
Viewed by 380
Abstract
Background/Objectives: Non-pancreatic hyperlipasemia (NPHL) is associated with high in-hospital mortality, with sepsis being one of the most common etiologies. The prognostic value of hematological parameter-derived inflammatory scores has not been extensively studied in NPHL to date. Methods: The prognostic value of eight inflammatory [...] Read more.
Background/Objectives: Non-pancreatic hyperlipasemia (NPHL) is associated with high in-hospital mortality, with sepsis being one of the most common etiologies. The prognostic value of hematological parameter-derived inflammatory scores has not been extensively studied in NPHL to date. Methods: The prognostic value of eight inflammatory scores for in-hospital mortality was assessed in a total of 545 NPHL patients from two hospitalized patient cohorts (COVID-19 [n = 144] and non-COVID-19 [n = 401], the latter stratified as bacterial sepsis [n = 111] and absence of systemic infection [n = 290]). We assessed the neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-lymphocyte and platelet ratio (N/(LP)), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), aggregate index of systemic inflammation (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), comparing their prognostic value among etiological groups. Results: Patients with bacterial sepsis were older, had more comorbidities, and experienced worse outcomes, including longer hospitalization (median: 15, 7, and 11 days; p < 0.001), higher ICU admission rates (75.7%, 33.8%, and 47.9%, p < 0.001), and increased mortality (45.0%, 13.8%, and 38.2%, p < 0.001), compared to those without systemic infection or with COVID-19-induced NPHL. Overall, NLR, dNLR, and N/(LP) were the most accurate predictors of in-hospital mortality at admission (AUROC: non-infection: 0.747; 0.737; 0.772; COVID-19: 0.810; 0.789; 0.773, respectively). The accuracy of NLR decreased in bacterial sepsis, and only N/(LP) and PLR remained associated with in-hospital mortality (AUROC: 0.653 and 0.616, respectively). Conclusions: The prognostic performance of hematological parameter-derived inflammatory scores in NPHL is etiology-dependent. NLR is the most accurate prognostic tool for mortality in the absence of bacterial sepsis, while N/(LP) is the best score in sepsis-induced NPHL. Full article
(This article belongs to the Section Molecular and Translational Medicine)
Show Figures

Figure 1

19 pages, 5784 KiB  
Article
Identification of Exosome-Associated Biomarkers in Diabetic Foot Ulcers: A Bioinformatics Analysis and Experimental Validation
by Tianbo Li, Lei Gao and Jiangning Wang
Biomedicines 2025, 13(7), 1687; https://doi.org/10.3390/biomedicines13071687 - 10 Jul 2025
Viewed by 538
Abstract
Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes and are characterized by impaired wound healing and a high amputation risk. Exosomes—which are nanovesicles carrying proteins, RNAs, and lipids—mediate intercellular communication in wound microenvironments, yet their biomarker potential in DFUs remains [...] Read more.
Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes and are characterized by impaired wound healing and a high amputation risk. Exosomes—which are nanovesicles carrying proteins, RNAs, and lipids—mediate intercellular communication in wound microenvironments, yet their biomarker potential in DFUs remains underexplored. Methods: We analyzed transcriptomic data from GSE134431 (13 DFU vs. 8 controls) as a training set and validated findings in GSE80178 (6 DFU vs. 3 controls). A sum of 7901 differentially expressed genes (DEGs) of DFUs were detected and intersected with 125 literature-curated exosome-related genes (ERGs) to yield 51 candidates. This was followed by GO/KEGG analyses and a PPI network construction. Support vector machine–recursive feature elimination (SVM-RFE) and the Boruta random forest algorithm distilled five biomarkers (DIS3L, EXOSC7, SDC1, STX11, SYT17). Expression trends were confirmed in both datasets. Analyses included nomogram construction, functional and correlation analyses, immune infiltration, GSEA, gene co-expression and regulatory network construction, drug prediction, molecular docking, and RT-qPCR validation in clinical samples. Results: A nomogram combining these markers achieved an acceptable calibration (Hosmer–Lemeshow p = 0.0718, MAE = 0.044). Immune cell infiltration (CIBERSORT) revealed associations between biomarker levels and NK cell and neutrophil subsets. Gene set enrichment analysis (GSEA) implicated IL-17 signaling, proteasome function, and microbial infection pathways. A GeneMANIA network highlighted RNA processing and vesicle trafficking. Transcription factor and miRNA predictions uncovered regulatory circuits, and DGIdb-driven drug repurposing followed by molecular docking identified Indatuximab ravtansine and heparin as high-affinity SDC1 binders. Finally, RT-qPCR validation in clinical DFU tissues (n = 5) recapitulated the bioinformatic expression patterns. Conclusions: We present five exosome-associated genes as novel DFU biomarkers with diagnostic potential and mechanistic links to immune modulation and vesicular transport. These findings lay the groundwork for exosome-based diagnostics and therapeutic targeting in DFU management. Full article
(This article belongs to the Section Cell Biology and Pathology)
Show Figures

Figure 1

12 pages, 800 KiB  
Article
The Role of Anti-Interferon-α Autoantibodies in Severe COVID-19: Implications for Vaccination Prioritization
by Xin Rong Lim, Shiyu Liu, Hwee Siew Howe, Khai Pang Leong, Elampirai Elangovan, Chiung-Hui Huang, Kok Ooi Kong, Bernard Yu Hor Thong, Shawn Vasoo and Bernard Pui Lam Leung
Vaccines 2025, 13(7), 742; https://doi.org/10.3390/vaccines13070742 - 9 Jul 2025
Viewed by 558
Abstract
Background/Objectives: Neutralizing autoantibodies against type I interferons, particularly interferon-alpha (IFN-α), have been implicated in severe COVID-19 outcomes. This study investigated the prevalence and functional significance of anti-IFN-α autoantibodies (AAbs) in hospitalized unvaccinated COVID-19 patients and their association with COVID-19 disease severity. Methods [...] Read more.
Background/Objectives: Neutralizing autoantibodies against type I interferons, particularly interferon-alpha (IFN-α), have been implicated in severe COVID-19 outcomes. This study investigated the prevalence and functional significance of anti-IFN-α autoantibodies (AAbs) in hospitalized unvaccinated COVID-19 patients and their association with COVID-19 disease severity. Methods: We retrospectively analyzed serum samples from 122 hospitalized COVID-19 patients (asymptomatic/mild: n = 69, moderate: n = 35, severe/critical: n = 18) and 32 healthy uninfected controls. Anti-IFN-α AAbs were quantified using a commercial enzyme-linked immunosorbent assay (ELISA) kit, with functional neutralization assessed via competitive ELISA and STAT1 phosphorylation inhibition. Statistical comparisons were performed using one-way ANOVA for parametric data and the Kruskal–Wallis test for non-parametric variables. Results: Anti-IFN-α AAbs were detected in 24.6% of COVID-19 patients, with all clinical subgroups showing significantly higher titers compared to healthy controls (p < 0.05). Although no significant differences in anti-IFN-α AAb levels were found between mild, moderate, and severe cases, patients with severe or critical COVID-19 had markedly higher mean titers (10,511.3 ng/mL) compared to non-severe (mild + moderate) cases (375.2 ng/mL, p < 0.001). Strongly neutralizing anti-IFN-α AAbs, with high titers (>20,000 ng/mL) and the ability to inhibit STAT1 phosphorylation, were identified in three severe COVID-19 cases. Anti-IFN-α AAb levels correlated positively with CRP (r = 0.80, p < 0.0001), LDH (r = 0.80, p = 0.001), and neutrophil count (r = 0.52, p = 0.003), and negatively with lymphocyte count (r = −0.59, p = 0.0006). Conclusions: Elevated and functionally neutralizing anti-IFN-α AAbs were associated with severe COVID-19. These findings support their role as a risk factor for poor outcomes and emphasize the importance of early COVID-19 vaccination. Screening may help identify high-risk individuals, particularly those unvaccinated or with immune vulnerabilities. Full article
Show Figures

Figure 1

Back to TopTop