Search Results (4,021)

Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder that is characterized by progressive muscle weakness, musculoskeletal limitations, and pulmonary involvement, with cardiomyopathy and cardiovascular complications being a primary cause of morbidity and mortality. With advances in respiratory care, cardiac involvement has become the leading cause of death. There is growing interest in systemic inflammatory indices as potential predictors of cardiovascular involvement. This study aimed to evaluate the prognostic value of inflammatory markers—neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and pan-immune inflammation value (PIV)—in children with DMD and to explore their association with cardiac findings. Methods: In this retrospective study, 25 male patients diagnosed with DMD and 25 age-matched healthy male controls were evaluated between January 2021 and July 2024. Demographic and clinical data, hematologic and biochemical parameters, and inflammatory indices were recorded. Cardiovascular involvement was assessed using electrocardiography (ECG) and transthoracic echocardiography (TTE). Group comparisons were performed using independent t-tests, while ROC and Pearson correlation analyses were used for diagnostic performance and associations. Results: Pathological Q waves were the most frequent ECG abnormality (24%), and 16% of patients had echocardiographic abnormalities. While most systemic inflammatory indices (NLR, MLR, SIRI, SII, PIV) did not significantly distinguish cardiovascular involvement, PLR demonstrated a strong positive correlation with Pro-BNP levels (r = 0.86, p < 0.05), suggesting a potential link between systemic inflammation and subclinical cardiac stress. Conclusions: Although the overall diagnostic utility of inflammatory indices in predicting cardiovascular complications in DMD was limited, PLR showed a correlation with Pro-BNP in our cohort. However, given the small sample size and limited number of patients with ventricular dysfunction, this finding should be interpreted with caution. PLR may warrant further investigation as a potential marker of cardiovascular involvement in DMD, but larger prospective studies are needed to validate its clinical significance. Full article

Background: Type 1 diabetes (T1D) is an autoimmune disorder characterized by destruction of insulin-producing β-cells. While conventional insulin therapy manages hyperglycemia, it fails to halt autoimmunity. Oral immunotherapy targeting autoantigens like GAD65 offers potential for antigen-specific tolerance; however, its efficacy is limited by gastrointestinal degradation and poor mucosal uptake. Lactococcus lactis (L. lactis), a food-grade delivery vector, enables sustained antigen release and intestinal tract immune modulation, yet the differential transcriptomic mechanisms underlying mucosal versus systemic immune responses remain uncharacterized. Methods: Non-obese diabetic (NOD) mice were randomized into control and GAD65 groups, receiving oral PBS or the GAD65 recombinant L. lactis vaccine, respectively. Fasting blood glucose was monitored weekly. GAD65-specific IgA and IgG, along with immune tolerance-related factors, were quantified using ELISA. Lymphocyte subsets were analyzed by flow cytometry, alongside RNA sequencing and transcriptional profiling. Results: The study demonstrated that the orally administered GAD65-L. lactis vaccine could significantly induce GAD65-specific IgA antibody and TGF-β cytokine and alleviate hyperglycemia and diabetes symptoms in NOD mice. Our study facilitated the induction of GAD65-specific regulatory T cells within both intestinal lamina propria lymphocytes (LPLs) and splenic lymphocytes. Notably, antigen-specific tolerance was mainly observed in intestinal LPLs. Crucially, the immune responses elicited by the vaccine demonstrated significant disparities between intestinal LPLs and splenic lymphocytes, with intestinal LPLs exhibiting unique local immune tolerance transcriptomic profiles. Conclusions: Our findings have enhanced the comprehension of the mechanisms by which oral vaccines influence the interplay between mucosal and systemic immune responses, thereby establishing a foundational framework for the design of oral vaccines. This understanding is instrumental in advancing antigen-specific immune tolerance strategies for autoimmune diseases such as Type 1 Diabetes (T1D). Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) do not provide promising benefits to patients with advanced epithelial ovarian cancer (EOC). This study analyzed preoperative peripheral blood mononuclear cells (PBMCs) from these patients to evaluate the prognostic and therapeutic checkpoints. Methods: Preoperative PBMCs of 69 advanced EOC cases were collected to analyze the correlation between IC-expressing immune cells and survivals of patients. Co-expression of various ICs on the T lymphocytes from these patients was examined. Activation potential of programmed cell death 1 (PD-1)⁺herpes virus entry mediator (HVEM)⁺ T cells in PBMCs from the healthy donors and tumoricidal abilities of PMBCs treated with various ICIs were evaluated in vitro. Impact of respective ICIs on activation of T cells in PMBCs was investigated. Results: Percentages of PD-1⁺ CD4⁺ and CD8⁺ T cells in the PBMCs of patients could positively correlate with disease-free or overall survival. HVEM was highly co-expressed on these T lymphocytes. Prediction potential for overall survival of patients by the subpopulation of PD-1⁺ CD4⁺ or CD8⁺ T cells was higher than that by other parameters. The PD-1⁺HVEM⁺ CD4+ and CD8⁺ T cells showed characteristics of activated phenotype under activation signals. PBMCs receiving anti-B and T lymphocyte attenuator (BTLA) plus anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) or anti-PD-1 Ab had potent tumor-killing ability. Anti-BTLA Ab can drive T cells in the PBMCs toward an effector status. Conclusions: Percentages of PD-1⁺ T cells in the PBMCs could predict survival of EOC patients. Targeting HVEM-BTLA axis may be considered for ICI treatment of EOCs. Full article

Viruses cause a large number of diseases. After penetrating into a host, the virus starts infecting healthy cells. Then it uses the RNA or DNA of the cell to replicate and afterward it explodes the infected cell, letting out many copies of the virus that can infect new cells. The innate and adaptive parts of the immune system defend the body by eliminating both the free viruses and the infected cells. Neutrophils, macrophages, natural killer cells, helper T cells (CD4+) and cytotoxic T lymphocytes (CD8+) are among the participating immune cells. The interactions are complex and not fully understood. In this paper, we present and study three mathematical models based on ordinary differential equations of virus and immune system interactions with different complexities, and also introduce possible treatments. We discuss the advantages and disadvantages of each model. We do global sensitivity analysis and numerical simulations. Finally, we present conclusions including comments about the complexity of mathematical models. Full article

Background/Objectives: Plasma cell gingivitis (PCG) is a rare, benign, non-dental-plaque-induced inflammatory condition characterized by dense subepithelial infiltration of polyclonal plasma cells. Due to its nonspecific clinical presentation, PCG represents a diagnostic challenge. This case report aims to describe a clinical case of PCG, highlighting the diagnostic process, histopathological correlation, and therapeutic approach. Methods: A 57-year-old male presented with a polypoid, erythematous, and edematous gingival lesion in the anterior maxillary region, with spontaneous bleeding on probing. Following clinic assessment, an incisional biopsy was performed, alongside complete hematological and inflammatory profiling. Histological and immunohistochemical analyses revealed the presence of an inflammatory infiltrate. Results: Histological evaluation revealed spongiotic squamous epithelium characterized by a dense plasma cell infiltrate with a liquenoid pattern of CD3-positive T and CD20-positive B lymphocytes. A polytypic expression of kappa and lambda light chains was also detected. The patient underwent topical corticosteroid therapy, showing progressive clinical improvement and resolution of symptoms, although minor mucosal involvement persisted. Conclusions: PCG remains a rare and underdiagnosed condition requiring integration of clinical, hematological, and histopathological data for accurate diagnosis. While corticosteroids remain the first-line therapy, emerging treatments, including photobiomodulation, may offer future adjunctive strategies to improve outcomes and reduce recurrence. Full article

Thrombospondin-1 potently inhibits T cell activation by engaging its cell surface receptor CD47. This inhibitory signal requires glycosaminoglycan modification of CD47. CD47 also regulates the composition of RNAs in extracellular vesicles released by T cells and their functional activities. Because CD47 is also present in extracellular vesicles, we examined the effect of T cell activation on CD47 glycoforms in T cells and extracellular vesicles released by these cells. Activation increased both heparan and chondroitin sulfate biosynthesis by globally inducing mRNA levels of the respective glycosaminoglycan synthases and sulfotransferases. T cell activation in the presence of thrombospondin-1 inhibited induction of these biosynthetic enzymes, but not in cells lacking CD47. Therefore, CD47 signaling controls its own post-translational modification by glycosaminoglycans that are required for thrombospondin-1 signaling. Activation of Jurkat T lymphoblasts and primary CD4 and CD8 T cells increased the release of proteoglycan isoforms of CD47 and amyloid precursor-like protein-2 associated with extracellular vesicles and smaller macromolecular complexes. However, cell surface levels of CD47 were minimally changed during activation. BJAB and RAJI B cell lines also produced CD47⁺ extracellular vesicles and showed increased release of highly glycosylated CD47 following B cell receptor engagement. Therefore, T and B lymphocyte activation results in a selective increase in the synthesis and release of extracellular vesicles containing proteoglycan isoforms of CD47. Full article

Wenchang Chickens (WCCs) and Recessive White Feather Chickens (RWFCs) are two important broiler breeds in China, although their susceptibility to E. tenella has not been compared. This study explores these differences in susceptibility. The results showed that WCCs exhibited lower susceptibility, as evidenced by no mortality and significantly reduced oocyst production compared to RWFCs. Additionally, WCCs had higher levels of CD3⁺CD4⁺ T lymphocytes and lower levels of CD3⁺CD8α⁺ T lymphocytes, both before and after infection, compared to RWFCs. Notably, serum IgA and IgG antibody levels in WCCs were significantly higher than those in RWFCs. RNA−seq analysis at 2, 4, and 7 days post-infection (dpi) revealed a consistent upward trend in gene expression in WCCs, while RWFCs exhibited a fluctuating pattern. Functional analysis indicated that the stable immune response, as annotated by the differentially expressed genes (DEGs) in WCCs, along with distinct metabolic alterations, may contribute to their enhanced resistance. Several hub genes, including SLC7A11, CCL19, CD4, HSPA5, and HSP90AA1, were identified within gene interaction networks specific to each breed. These findings provide valuable insights into the molecular mechanisms underlying the differential susceptibility of WCCs and RWFCs, offering potential targets for new coccidiosis control strategies. Full article

Cerebral ischemia–reperfusion injury (CIRI) is a complex pathological process that arises when blood flow is restored to the brain after ischemia, often resulting in significant neuronal damage and triggering secondary inflammatory responses. This review explores the immune mechanisms underlying CIRI, focusing on the activation and polarization of resident central nervous system (CNS) cells—particularly microglia and astrocytes—and the infiltration of peripheral immune cells such as neutrophils, monocytes/macrophages, and T lymphocytes. We discuss the central role of microglia in the neuroinflammatory cascade, their polarization between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, and how this process influences neuronal damage and tissue repair. This review highlights the roles of the complement system, inflammasome activation, and blood–brain barrier disruption as key drivers of inflammation and neuronal injury. Additionally, we elaborate on the dynamic interactions between resident and infiltrating immune cells, which amplify inflammation and impede post-ischemic recovery. Finally, we discuss emerging therapeutic strategies targeting immune modulation, including cytokine regulation, microglial reprogramming, and targeted drug delivery systems, which offer promising avenues for improving outcomes in ischemic stroke. Full article

Cannabinoid receptor 1 (CB1) has been implicated in multiple inflammatory diseases by regulating pro-inflammatory mediators or altering immune cell polarization. However, the expression and direct functional role of CB1 in T cells remain largely unexplored. Here, we demonstrate that primary murine T cells express CB1 and that its novel agonist, BI-5756, directly increases the frequencies of regulatory T cells (Tregs) in primary murine pan T cells after activation. In addition, BI-5756 exhibits an in vivo protective effect against graft-versus-host disease (GvHD), an allogeneic T cell-mediated inflammatory complication after allogeneic hematopoietic cell transplantation (allo-HCT), resulting in an improved overall survival with enhanced platelet recovery and reconstitution of bone marrow-derived B and T cells. BI-5756 also directly suppresses tumor cell growth and upregulates MHC I, MHC II, and CD80 on tumor cells, which may subsequently enhance T cell-mediated anti-tumor responses in mixed lymphocyte reaction with A20 cells. The ability of BI-5756 to increase Tregs was significantly abrogated by rimonabant, a potent and selective CB1 antagonist, suggesting that the immunomodulatory effect of BI-5756 is mediated via CB1. In summary, BI-5756, a potent CB1 agonist, increases Tregs while preserving anti-tumor responses in vitro and effectively reduces GvHD in vivo. Full article

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T cells, driven by dysregulated transcriptional networks and oncogenic signaling pathways. Here, we present the first comprehensive analysis of the expression and regulation of TSPAN32, a tetraspanin implicated in lymphocyte homeostasis, in T-ALL. Methods: Transcriptomic data from the Leukemia MILE study (GSE13159) were analyzed to assess TSPAN32 expression across leukemic subtypes. Gene Set Enrichment Analysis (GSEA) was performed to explore biological pathways associated with TSPAN32-correlated genes. For mechanistic validation, HPB-ALL cells were used as a model, with NOTCH signaling inhibited by γ-secretase inhibitor (GSI) treatment and TAL1–LMO1 overexpression induced through doxycycline-inducible lentiviral vectors. Gene expression changes were quantified by RT-qPCR. Results: TSPAN32 was frequently downregulated in T-ALL compared to healthy bone marrow, although expression was retained in a subset of cases. GSEA revealed that TSPAN32-correlated genes were inversely associated with cell cycle–related programs, consistent with its established role as a negative regulator of T cell proliferation. Mechanistically, TAL1–LMO1 overexpression strongly induced TSPAN32, while GSI-mediated NOTCH inhibition partially reactivated its expression. Interestingly, GSI treatment also increased TAL1 levels despite downregulating LMO1. Conversely, TAL1–LMO1 overexpression suppressed NOTCH1 and NOTCH3, highlighting a reciprocal regulatory interplay between NOTCH and TAL1/LMO1 oncogenic circuits that shapes TSPAN32 expression dynamics in T-ALL. Conclusions: This study identifies TSPAN32 as a novel transcriptional target under the influence of key leukemogenic pathways and suggests its potential role as a modulator of leukemic T cell proliferation, with implications for therapeutic strategies targeting TAL1 and NOTCH signaling. Full article

Postpartum uterine involution in cattle involves complex morphological and immunological changes essential for restoring uterine health and fertility. This study evaluated endometrial biopsies collected at four postpartum time points to characterize tissue remodeling and immune cell dynamics during involution. Histology revealed intact luminal columnar epithelium in 92.98% of samples, with stable stromal architecture. Stromal edema decreased by Day 7 but increased again by Day 35, while endometrial gland numbers significantly rose at Day 35, suggesting glandular recovery linked to resumed cyclicity. Subepithelial collagen deposition peaked on Day 21, indicating active extracellular matrix remodeling. Immunologically, early postpartum was marked by increased PMNs and macrophages, whereas Day 21 showed peak infiltration of natural killer (NK) cells and T and B lymphocytes, sometimes forming lymphoid aggregates. Manual and automated immune cell quantifications correlated well. These findings demonstrate a dynamic shift from acute neutrophil-dominated inflammation to a lymphocyte-rich environment during uterine involution. This immune modulation may contribute to the earlier diagnosis of subclinical endometritis, typically identified at later stages of postpartum period. Overall, this study provides insight into the temporal immunomorphological events supporting uterine recovery, with potential implications for reproductive management in dairy cattle. Full article

Background and Objectives: Prognostic stratification in trauma patients admitted to the intensive care unit (ICU) remains a clinical challenge. While conventional scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) are widely used, the utility of biochemical biomarkers in predicting mortality is still evolving. This study aimed to evaluate the prognostic value of key inflammatory and metabolic biomarkers: platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), serum lactate, base deficit, and neutrophil-to-lymphocyte ratio (NLR) in relation to ICU mortality in trauma patients. Materials and Methods: In this retrospective cohort study, data from 240 ICU-admitted trauma patients were analyzed. Group comparisons between survivors and non-survivors were conducted using t-tests or Mann–Whitney-U tests. Pearson correlation and ROC analyses were performed to assess relationships and discriminatory performance of biomarkers alongside clinical scores. Results: Non-survivors (n = 50) exhibited significantly higher CAR, lactate, and base-deficit values, and lower PLR (p < 0.05) compared to survivors (n = 190). CAR strongly correlated with CRP (r = 0.96), while lactate and base deficit were inversely correlated (r = –0.69). ROC analysis revealed that ISS (AUC = 0.86) and APACHE II (AUC = 0.77) had the highest discriminatory power, followed by lactate (AUC = 0.75). NLR did not demonstrate significant prognostic utility (p > 0.05). Conclusion: PLR, CAR, lactate, and base deficit are accessible, cost-effective biomarkers with significant prognostic value in ICU trauma care. Their integration with established scoring systems can enhance early risk stratification. NLR, however, may require time-sensitive and context-specific evaluation. Full article

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a complex immune response. Given the considerable heterogeneity of the clinical phenotype of HS, this study aimed to analyse the immunohistochemical pattern of interstitial inflammation. Methods: Immunohistochemical analysis was performed on skin samples from 49 patients with HS. The immunohistochemical markers CD3, CD4 and CD8 for T-cells, CD20 for B-cells, CD138 for plasma cells and CD30, CD56, Bcl-2 and Bcl-6 were stained on lesional skin. Results: The analysis of immune cell dominance in patients with HS revealed that 33.3% of the cohort exhibited B-cell dominance, defined as a ratio of the sum of CD20+ and CD138+ cells to CD3+ cells greater than 1, while the majority (66.7%) demonstrated T-cell dominance, defined as a ratio of CD3+ cells to the sum of CD20+ and CD138+ cells greater than 1. B-cell-dominant HS is associated with a significantly elevated probability of mammary involvement (13.3% vs. 0%; p = 0.041). T-cell-dominant HS patients tended to demonstrate a higher mean tobacco consumption, but not significantly (20 vs. 5 tobacco pack-years; p = 0.06). CD4-dominant HS patients exhibited a significantly greater involvement of the mons pubis (62.5% vs. 28.6%, p = 0.023) compared to CD8-dominant patients, who demonstrated a significantly higher number of abscesses (p = 0.027). Conclusions: For the first time, we describe the clinical and immunohistochemical characteristics of T-cell- and B-cell-dominant HS. Although HS seems to be more dominated by T-cells, a B-cell dominance was found in 33% of cases. Full article

Background/Objectives: Non-Hodgkin lymphoma (NHL) is a group of blood cancers that arise in the lymphatic nodes and other tissues after an injury to the DNA of B/T lineage and NK lymphocytes. Recently, we reported that incomptine A (IA) has in vivo antilymphoma properties. This research aimed to evaluate the effects of IA in the treatment of NHL using antilymphoma activity, Tandem Mass Tag (TMT), and bioinformatics approaches. Methods: The antilymphoma activity of IA was tested on male Balb/c mice inoculated with U-937 cells. Also, TMT, gene ontology enrichment, Reactome pathway, Kyoto Encyclopedia of Gene and Genomes pathway, molecular docking, toxicoinformatic, and pharmaceutical analyses were performed. Results: By TMT analysis of the altered levels of proteins present in the lymph nodes of Balb/c mice with NHL and treated with IA, we identified 106 significantly differentially expressed proteins (DEPs), including Il1rap, Ifi44, Timd4, Apoa4, and Fabp3 as well as Myh3, Eno 2, and H4c11. Among these, the Fhl1 result was the most important cluster altered and a potential core target of IA for the treatment of NHL. Network pharmacology studies have revealed that DEPs are associated with processes such as muscle contraction, glycolysis, hemostasis, epigenetic regulation of gene expression, transport of small molecules, neutrophil extracellular trap formation, adrenergic signaling in cardiomyocytes, systemic lupus erythematosus, alcoholism, and platelet activation, signaling, and aggregation. Computational studies revealed strong binding affinities with six proteins associated with cancer, positive pharmacokinetic properties, and no toxicity. Conclusions: Our contribution suggests that IA may be a compound with potential therapeutic effects against NHL. Full article

Chimeric antigen receptor (CAR) T-cell therapy directed to CD19 and B-cell maturation antigen has revolutionized treatment of B-cell leukemia and lymphoma, and multiple myeloma. However, identifying suitable targets for acute myeloid leukemia (AML) remains challenging due to concurrent expression of potential target antigens on normal hematopoietic stem cells or tissues. As the stress-induced B7H6 molecule is rarely found on normal tissues but expressed on many cancers including AML and melanoma, the NKp30-ligand B7H6 emerges as a promising target for NKp30-based CAR T therapy for these tumors. In this study, we report a comprehensive B7H6 expression analysis on primary AML and melanoma as well as on different tumor cell-lines examined by RT-qPCR and flow cytometry, and efficient anti-tumor reactivity of NKp30-CAR T cells to AML and melanoma. To overcome limitations of autologous CAR T-cell fitness-dependent efficacy and patient-tailored production, we generated CRISPR/Cas9-mediated TCR-knockout (TCR^KO) NKp30-CAR T cells as an off-the-shelf approach for CAR T therapy. Functional studies comparing NKp30-CD28 CAR or NKp30-CD137 CAR TCR⁺ and TCR^KO T lymphocytes revealed superior anti-tumoral immunity of NKp30-CD28 CAR TCR^KO T cells to AML and melanoma cell lines in vitro, and effective control of tumor burden in an NSG melanoma-xenograft mouse model. In conclusion, these findings highlight the therapeutic potential of NKp30 CAR TCR^KO T cells for adoptive T-cell therapy to B7H6-expressing cancers, including melanoma and AML. Full article