International Journal of Immunopathology and Pharmacology最新文献

Objectives: The objectives of this study were to determine the prevalence of anti-β2glycoprotein-1 antibodies (anti-β2GPI) in Pakistani patients clinically suspected to have antiphospholipid syndrome (APS) and assess their association with clinical manifestations.

Introduction: The antiphospholipid syndrome (APS) is a complex disorder characterized by recurrent thrombotic and obstetric complications.

Methods: An analytical cross-sectional study was conducted at Aga Khan University Hospital from January to June 2022, after obtaining ethical approval (ERC ID: 2021-6404-19580). A total of 133 patients aged 18-60 years, clinically suspected of having APS based on the updated international consensus (Sydney) classification criteria, were recruited. Anti-β2GPI antibodies were tested using the same blood samples provided for aCL testing, with verbal consent. Demographic, clinical, and biochemical data were collected via a structured questionnaire, while information on lupus anticoagulant testing was retrospectively obtained from prior records.

Results: The study included 120 females (90.2%) and 13 males (9.8%) with a mean age of 31.3 ± 8.8 years. Predominant clinical manifestations included unexplained miscarriages at >10 weeks of gestation (n = 77/120 female, 64.2%), while deep venous thrombosis (DVT) was a common non-obstetric clinical feature (n = 18/133, 13.5%). The median level of anti-β2GPI was 2.12 U/ml (1.34-7.04) and 7.5% (n = 10) were positive. Of the 10 positive patients, 2 displayed positive anti-β2GPI while concurrently testing negative for other aPL antibodies. A significant association was identified between the presence of anti-β2GPI and the occurrence of DVT and other venous thromboembolic events (VTE).

Conclusion: This study highlights the prevalence and diagnostic utility of anti-β2GPI in Pakistani patients suspected of APS, identifying cases missed by other aPL tests and showing significant associations with thrombotic manifestations like DVT and VTE. However, the cross-sectional design, lack of confirmatory testing, and absence of locally derived cut-offs limit causal inferences.

Background: Oral mucosal diseases manifest primarily as inflammatory conditions. These diseases affect approximately half a billion people worldwide.

Objective: Novel and effective strategies for treating inflammatory diseases of the oral mucosa have great potential for improving patient outcomes, and warrant study.

Methods: The impact of melatonin on inflammation was investigated using RAW264.7 macrophages and HOEC and HSC-3 oral epithelial cells.

Results: Melatonin decreased macrophage-induced inflammation by acting through the melatonin receptor MTNR1A. Additionally, melatonin mitigated macrophage-induced inflammation in oral epithelial cells. Importantly, the results demonstrated that the effects of melatonin on oral epithelial inflammation were mediated through the KEAP1/Nrf2 signaling pathway.

Conclusion: These findings will contribute to the development of innovative therapies for inflammatory conditions affecting the oral epithelium.

Currently, no glucocorticoid dose prediction model is available for clinical practice. This study aimed to utilise machine learning techniques to develop and validate personalised dosage models. Participants were patients with SLE who were registered at Nanfang Hospital and received prednisone. Univariate analysis was used to confirm the feature variables. Subsequently, the random forest (RF) algorithm was utilised to interpolate the absent values of the feature variables. Finally, we assessed the prediction capabilities of 11 machine learning and deep-learning algorithms (Logistic, SVM, RF, Adaboost, Bagging, XGBoost, LightGBM, CatBoost, MLP, and TabNet). Finally, a confusion matrix was used to validate the three regimens. In total, 129 patients met the inclusion criteria. The XGBoost algorithm was selected as the preferred method because of its superior performance, achieving an accuracy of 0.81. The factors exhibiting the highest correlation with the prednisone dose were CYP3A4 (rs4646437), albumin (ALB), haemoglobin (HGB), anti-double-stranded DNA antibodies (Anti-dsDNA), erythrocyte sedimentation rate (ESR), age, and HLA-DQA1 (rs2187668). Based on validation, the precision and recall rates for low-dose prednisone (⩾5 mg but <7.5 mg/d) were 100% and 40% respectively. Similarly, for medium-dose prednisone (⩾7.5 mg but <30 mg/d), the accuracy and recall rates were 88% and 88%, and for high-dose prednisone (⩾30 mg but ⩽100 mg/d), the accuracy and recall rates were 62% and 100% respectively. A robust machine learning model was developed to accurately predict prednisone dosage by integrating the identified genetic and clinical factors.

Introduction: Although, several studies have assessed the association of HLA Class I and II genes with inclusion body myositis (IBM), results were inconsistent and between-studies heterogeneity needs to be investigated.

Objectives: The aim of this review was to summarize existing data on the contribution of HLA-DRB1 and HLA-B alleles to IBM susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions.

Design: This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses.

Methods: An electronic literature search for eligible studies among all papers published prior to January 29, 2025, was conducted through PubMed, EMBASE, Web of science, and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the two following HLA genes: HLA-DRB1 and HLA-B.

Results: Combined analyses revealed a significant increase in IBM risk conferred by the HLA-DRB1*03 allele (9.21 (7.05-12.01)), the DRB*03:01 allele (8.44 (6.85-10.41)), the DRB1*01 allele (2.31 (1.82-2.93)), the DRB1*01:01 allele (2.63 (1.95-3.55)), the DRB1*15:02 allele (3.49 (2.12-5.75)), the B*08 allele (4.05 (2.58-6.38)), and the DQB1*02 allele (6.62 (4.5-9.74)), all p-values < 0.001. In addition, the DRB1*15:01 allele was found to be protective against IBM in all populations (0.48 (0.32-0.72)). Conversely, the DRB*11 allele was not associated with IBM risk, OR (95% CI) = 0.91 (0.54-1.51), p = 0.703.

Conclusion: This meta-analysis demonstrated that HLA-DRB1, DQB1, and B loci could play a major role in IBM pathogenesis.

Registration: This review has been registered on PROSPERO on June 25, 2024: CRD42024557948, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024557948.

This study aims to identify differentially upregulated ligand-receptor interactions between B-ALL cells and exhausted CD8⁺ T cells and to develop a multivariate Cox regression model for predicting the overall survival of pediatric B-ALL patients based on CCL3/CCL4/CCL5 expression levels. Pediatric B cell-acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy. T cell exhaustion has an important impact on the prognosis of leukemia. The interaction between tumor cells and T cells can influence the degree of T cell exhaustion. However, the effects of B-ALL cells on exhausted T cell subpopulations and how the interaction influences the prognosis of B-ALL patients remain unclear. Single-cell RNA sequencing (scRNA-Seq) data from pediatric B-ALL patients were downloaded from GEO. Cell interaction analysis identified ligand-receptor pairs between B-ALL cells and exhausted CD8⁺ T cell. To confirm the function of CCL3/CCL4/CCL5/CCR5 in prognosis prediction, quantitative real-time polymerase chain reaction (qRT-PCR) was employed. We further developed an innovative stratified model that integrates CCL3, CCL4, and CCL5 through multi-Cox regression. Clustering of scRNA-Seq data revealed an increased proportion of exhausted CD8⁺ T cells in relapsed B-ALL, especially terminal exhausted CD8⁺ T cells (CD8_Ex), with increased exhaustion and decreased proliferation scores. Moreover, the CCL3/CCL4/CCL5-CCR5 axis was upregulated in interactions between B-ALL cells and terminal CD8_Ex. Transcriptome data from 221 pediatric B-ALL samples revealed that high CCL3/CCL4/CCL5/CCR5 levels correlate with low overall survival (OS). A multivariate Cox regression model incorporating CCL3/CCL4/CCL5 predicted prognoses. Finally, a model based on the adult B-ALL patients from our center also accurately predicted prognoses. We report for the first time the crucial role of the CCL3/CCL4/CCL5-CCR5 axis in the differentiation of terminal exhausted CD8⁺ T cells in B-ALL. High expression of CCL3, CCL4, CCL5, and CCR5 correlates with poor prognosis in B-ALL, suggesting potential biomarkers and therapeutic targets.

To investigate whether obstructing the cysteinyl leukotriene receptor-1 (CYSLTR1) with zafirlukast diminishes experimentally induced gastric ulcer (GU) in rats by modulating inflammation and apoptosis. Gastric ulcers affect approximately 10% of the global population and can lead to serious complications such as gastrointestinal perforation and bleeding. Leukotrienes are proinflammatory compounds, and cysteinyl leukotrienes, such as LTC4, LTD4, and LTE4, that are potent proinflammatory mediators. Rats were orally administered a single oral dose of 80 mg/kg of indomethacin to induce GU. The rats were administered an oral dose of 20 mg/kg Zafirlukast. Gastric tissues were collected for macrostructural and microstructural analyses. A portion of gastric tissue was used to assess the genetic expression and protein levels of CYSLTR1, NFκB, TNF-α, IL-1β/4/10, JNK, PKB, and caspase-3. The gastric sections were subjected to hematoxylin/eosin and Masson trichrome staining and immunohistochemical staining with anti-TNF-α and anti-caspase-3 antibodies. Zafirlukast blocked the expression of CYSLTR1. Analysis of micro-images of GU rats revealed damage to surface cells and glandular epithelial cells caused by inflammatory cell infiltration, which was mitigated by Zafirlukast. Additionally, Zafirlukast treatment significantly reduced NFκB, TNF-α, IL-1β, JNK, PKB, and caspase-3 while increasing IL-4 and IL-10. Zafirlukast successfully reduced experimentally induced gastric ulcers in rats. Its mechanism of action includes inhibition of CYSLTR1, diminishing the inflammatory pathway. This is demonstrated by a decrease in the levels of NFκB, TNF-α, and IL-1β, along with an increase in the levels of IL-4 and IL-10. Additionally, Zafirlukast exerted anti-apoptotic effects by downregulating the expression of JNK, PKB, and caspase-3.

Objective: To investigate the involvement of oxidative and apoptotic mechanisms in the possible neuroprotective effect of Kaempferide (KPD) and Norbergenin (NRG) against AlCl₃-induced cognitive shutdown in rats.

Introduction: Aluminium chloride (AlCl₃) is widely known as a neurotoxic agent that induces memory and cognitive shutdown via induction of oxidative stress and apoptosis. KPD is an O-methylated flavonol that possesses anti-oxidant, anti-inflammatory, anti-dementia and anti-depression properties, whereas NRG, a demethylated compound derived from bergenin, possesses an anti-oxidant property and has neuroprotective effects. Both alleviate D-galactose-induced neurotoxicity in rats.

Methods: Eighty-four male Wistar rats were randomly divided into two experimental models: prophylactic (pre-treatment with donepezil, KPD or NRG; n = 42) and curative (post-treatment with donepezil, KPD, or NRG; n = 42). In each of these models, the animals were divided into seven groups (n = 6 per group): group 1 (normal saline), group 2 (200 mg/kg AlCl₃), group 3 (donepezil + AlCl₃), group 4 (5 mg/kg KPD + AlCl₃), group 5 (10 mg/kg KPD + AlCl₃), group 6 (5 mg/kg NRG + AlCl₃) and group 7 (10 mg/kg NRG + AlCl₃)Results:Kaempferide and Norbergenin averted the increase in TBARS, NO and AChE, and decrease in the number of crossings, time spent and distance moved in the target quadrant, latency of fall, speed, paw withdrawal threshold (PWT), SOD, CAT, GPx, GR and GSH induced by AlCl₃. These agents also averted the upregulation of Aβ_1-41, p-Tau, caspase-3, Bax and downregulation of Akt, p-CREB, SOD1 and BCl-2 induced by AlCl₃Conclusion:The neuroprotective effects of KPD and NRG against AlCl₃-induced Aβ accumulation and cognitive shutdown are mediated via suppression of oxidative stress and apoptosis.

Introduction & aims: Optimal neural activity in the central nervous system relies on the myelin sheath formed by oligodendrocytes. During demyelination, changes in the microenvironment can activate oligodendrocyte precursor cells (OPCs) and induce them to generate new oligodendrocytes. However, different demyelination models employ distinct pathways, targeting different cells and cytokines; these, in turn, have varying effects on OPCs. Therefore, it is reasonable to assume that OPCs derived from different pathologic environment may exhibit functional differences. This study aims to investigate the influence of the pre-activation of OPCs, isolated from lipopolysaccharide (LPS)-induced and cuprizone (CPZ)-induced demyelination models, on their regenerative capacity.

Methods: OPCs were isolated from mice subjected to LPS or CPZ-induced neurodegeneration. Characterization and activation assessment included immunostaining for PDGFRα, OLIG2, and ELISA analysis for IL-1, and SOX10 expression assessment. Then OPCs were intravenously transplanted into LPS-exposed mice. The migration patterns of transplanted OPCs were tracked using DiI labeling. After 7 days, spinal cords were assessed for myelin content and integrity (Luxol fast blue, Transmission electron microscopy, MBP and MOG analysis) and extracellular matrix changes (chondroitin sulfate proteoglycan-CSPG levels).

Results: Transplantation of LPS-OPCs significantly enhanced their migration to the demyelinated spinal cord, correlating with increased myelin content and integrity and a reduction in CSPG levels compared to the CPZ-pre-activated OPCs and control groups.

Conclusion: Our findings suggest that the pre-activation environment, determined by the source model, differentially affects the regenerative potential of transplanted OPCs.

The Coombs test is important in hematology for detecting erythrocyte-bound IgG antibodies or in serm through agglutination methods, but its sensitivity and specificity are limited. Flow cytometry provides a more precise and sensitive alternative for quantitatively assessing RBC-bound IgG antibodies. This assessment is crucial for evaluating the risk of hemolytic reactions and ensuring safe transfusions. This study aimed to explore a new method for the detection of RBC-bound IgG antibodies in rabbits following the injection of human red blood cells. Rabbits serum treated with 2-mercaptoethanol (2-ME) were serially diluted at ratios of 1:1, 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128, 1:256, 1:512, 1:1024, and 1:2048. These diluted samples were then reacted with O-type red blood cells (RBCs). Serum samples from healthy individuals were used as the control group. The tubes were kept in a water bath at 37°C for 30 min incubation. After incubation, the samples were analyzed using a flow cytometry-based assay. Additionally, the traditional Coombs tube method was used and the strength of IgG antibody and agglutination was graded. The results were analyzed using a flow cytometry-based assay, and the agglutination strength was determined using the Coombs traditional tube method for RBC-bound IgG antibodies. A significant difference was found between the rabbits serum and normal control groups (p < 0.001). IgG titers increased significantly after 1 month of immunization in rabbits compared to the titers observed after 1 week. The serum Anti-D stability test showed a coefficient of variation (CV) of 7.74%, indicating good stability of the test results. In this study, we concluded that the flow cytometry-based assay for detecting RBC-bound IgG antibodies was accurate, sensitive, and had positional value in clinical laboratories and research centers.

The skin serves as the primary defensive barrier of the human body against external stimuli and damage. Keratinocytes, which are the predominant cell type in the human epidermis, undergo a differentiation process that is crucial for the formation of the skin barrier. Myricetin, a dietary flavonoid present in various fruits and vegetables, is known to play a significant role in maintaining intestinal barrier function; however, its impact on the skin barrier remains inadequately understood. Consequently, this study investigates the effects of myricetin on the differentiation of epidermal keratinocytes and the integrity of the skin barrier. Differentiation of primary mouse keratinocytes was induced using 1.8 mM CaCl₂. tudy demonstrated that myricetin effectively suppresses cell proliferation and induces both cell cycle arrest and calcium ion (Ca²⁺) influx, without influencing apoptosis. Concurrently, myricetin enhances the expression of differentiation markers, including K10, TGase1, Filaggrin, and Involucrin, and facilitates the formation of tight junctions. Upon examining the underlying mechanisms, we discovered that myricetin activates the TRPV4 channel, and the promotion of keratinocyte differentiation by myricetin is contingent upon the activation of this channel. In summary, these findings suggested that myricetin could promote keratinocytes differentiation and have well-established skin barrier protective function.