International Journal of Immunopathology and Pharmacology最新文献

Objective: This study aimed to investigate the effect of rapamycin on inflammatory pain in rats.

Introduction: Inflammatory pain is a kind of pathological pain caused by inflammatory mediators or factors such as TNF-α (Tumor Necrosis Factor-α), IL-1β (Interleukin-1β), and IL-6 (Interleukin-6). NSAIDs and opioid analgesics are commonly used for relieving inflammatory pain, but the side effects limit their clinical application. New drugs based on new mechanisms for inflammatory pain are urgently needed. Autophagy is an evolutionarily conserved homeostatic process for lysosomal degradation of intracellular components. Recent reports indicate the involvement of autophagy in the development and maintenance of neuropathic pain, but the role of autophagy in inflammatory pain still needs to be explored.

Methods: The pain-related behaviors of rats were studied by paw withdrawal threshold and paw withdrawal latency. The autophagy level of the rat spinal cord was detected by western blots. The concentrations of TNF-α, IL-1β, and IL-6 were detected by ELISA.

Results: We found that the paw withdrawal threshold and paw withdrawal latency were both significantly decreased after CFA (Complete Freund's Adjuvant) injection, accompanied by the activation of mTOR signaling pathway and the inhibited autophagy flux in the spinal cord. And inflammatory cytokines were increased in the spinal cord after CFA injection. Then, we studied the effect of rapamycin on CFA-induced inflammatory pain in rats, and found that rapamycin restored the autophagy flux and significantly reduced mechanical allodynia and thermal hyperalgesia. In addition, rapamycin significantly decreased the levels of TNF-α, IL-1β, and IL-6 after CFA injection in the spinal cord.

Conclusion: Our results suggested that rapamycin might be a promising candidate for the treatment of inflammatory pain by restoring the autophagy flux in the spinal cord.

Objective: The effect of the cGAS/STING pathway on antitumor immunity and its connection to senescence in vivo necessitates further investigation.

Introduction: Cellular senescence and its secretory phenotype (the SASP) are implicated in modulating the immune microenvironment of cancer possibly through the cGAS/STING pathway.

Methods: Gene expression data from paired colon cancer and adjacent non-malignant mucosa (98 patients, n = 196 samples; 65 patients, n = 130 samples) were analyzed for cGAS/STING and a senescence signature. Immunohistochemistry assessed cGAS/STING protein expression in 124 colorectal samples.

Results: Approximately one-quarter of patients displayed senescence profiles in both gene sets, yet without significantly correlating with cGAS/STING expression. Notably, cGAS expression was higher than STING in tumor tissue compared to non-malignant colonic mucosa. Protein analysis showed 83% positive cGAS expression and 39% positive STING expression, with discrepancies in expression patterns. Additionally, 15% of samples lacked both markers, while 35% exhibited positive staining for both. No significant correlations were found between cGAS/STING status and tumor stage, patient age, lymphovascular invasion, or lymph node involvement.

Conclusions: Our findings demonstrate significant senescence marker expression in colorectal cancer samples but with no correlation with cGAS/STING.

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.

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.

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.

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.

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.

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.