International Journal of Immunopathology and Pharmacology最新文献

Objective: The aim of this study was to investigate the role of glutathione peroxidase 7 (GPX7) in mitigating oxidative stress-induced cellular ageing and its contribution to intervertebral disc degeneration (IVDD).

Introduction: Human nucleus pulposus (NP) cells in degenerated intervertebral discs (IVDs) show signs of ageing, such as telomere shortening, DNA damage, and mitochondrial dysfunction. GPX7, known for its ability to protect against ageing in cancer cells, may also play a role in NP cell ageing.

Methods: Two datasets (GSE34095 and GSE147383) were analysed to compare GPX7 expression in normal and degenerated IVDs and used KEGG analysis to identify related pathways. An H₂O₂-induced cell model and a natural ageing model were used to simulate ageing. GPX7 was transfected into and overexpressed in NP cells, and its protective effects were examined. Molecular docking identified GNF-5837 as a potential compound to prevent GPX7 cleavage, which was tested in an IVDD rat model.

Results: The expression of GPX7 was increased in degenerated IVDs and H₂O₂-induced models. GPX7 overexpression reduced ageing in NP cells. GNF-5837 alleviated IVDD in rats by upregulating GPX7.

Conclusion: Our study demonstrates that GNF-5837 reduced the expression of ageing markers by upregulating GPX7, suggesting it could serve as a potential treatment for IVDD.

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children. It often follows a viral infection. Although it is a self-limiting disease, various acute, and chronic complications can occur. We describe a case of a 6-year-old boy presenting with HSP and secondary multi-organ involvement. Because of diffuse purpura and arthralgia associated with acute abdominal pain, oral corticosteroid was administered but with no clinical improvement. Despite steroid treatment, the child developed hematemesis and massive intestinal hemorrhage, so he was treated with one dose of intravenous immunoglobulin (IVIG). This produced significant improvement in the gastrointestinal, cutaneous, and articular symptoms. Our case report demonstrates that IVIG may be useful in the treatment of complicated HSP with gastrointestinal involvement, but more structured research and guidelines are necessary for a correct therapeutic approach.

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.

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.

Objectives: Baicalein, a flavonoid derived from the roots of Scutellaria baicalensis Georgi, demonstrates multifarious pharmacological effects due to its high antioxidant activity. However, the latent mechanisms remain insufficiently resolved. In the present research, we evaluated the therapeutic effects of baicalein on isoprenaline (ISO)-induced heart failure and investigated the possible underlying mechanisms.

Methods: Toxicity was analyzed in zebrafish embryos and mouse atrial myocytes HL-1. The MTT assay was used to evaluate the effectiveness of baicalein. DCFH-DA was used as a fluorescence probe to detect intracellular reactive oxygen species (ROS). Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured using SOD, MDA and GSH-Px commercial kits. Adult BALB/c mice were randomized into six groups of ten animals each. Cardiac function was analyzed by echocardiographic images. Structural changes were analyzed by hematoxylin & eosin (HE) staining, Masson staining and TUNEL staining. The mechanism of baicalein was investigated by analyzing relative signaling pathways through western blotting.

Results: Our studies show that baicalein both significantly reduces ISO-induced oxidative stress, apoptosis and cardiac fibrosis in vitro and vivo, this phenomenon was related to mitochondrial fusion/fission balance and inhibiting GRP78/CHOP pathway.

Conclusions: Our results suggested that baicalein controls mitochondrial fusion/fission balance and inhibits GRP78/CHOP pathway, thus exerting therapeutic effects in ISO-induced heart failure in HL-1 cells and BALB/c mice. These results suggested that baicalein may be a potential therapeutic agent for heart failure.

Knowledge about total RNA molecules in Parkinson's disease is limited. This gene expression profiling study was conducted with a preclinical experimental design using a mouse model to examine the molecular-biological characteristics and the pathological implication of total RNA gene interaction in Parkinson's disease in silico. In silico analysis of total RNA molecules, the Gene Expression Omnibus database, published results, and preliminary findings of available patient samples apply. The potential signaling network and the effect of the interaction of molecules with total RNA was predicted and confirmed. The research consists of four parts. At first, we analyzed the control and MPTP groups. In the second part, we analyzed FVB-N control and MPTP. In the third part, we analyzed controls. In the fourth part, we analyzed MTPT separately. The constructed network contains total RNA, where the Kyoto Encyclopedia of Genes and Genomes database analysis showed that genes from the signaling pathway are involved in the development and complications of Parkinson's disease in male and female rats. Identified total RNA and genes are involved in altered signaling. There is direct interconnection and interdependence of interactions in the signaling network. Results identified the significant total-RNA molecules of the signaling pathway that connect other molecules. In silico analysis shows upregulated and downregulated genes in Parkinson's disease rats. Preliminary data shows that total RNA molecules interact with other genes, and they are applicable in Parkinson's disease course monitoring, shedding light on how factors impact the expression of genes and offering strategies for management.