International Journal of Immunopathology and Pharmacology最新文献

{"title":"Immunogenicity and adverse events of the COVID-19 vaccines in healthy and individuals with autoimmune diseases in an Iranian population.","authors":"Amin Moradi Hasan-Abad, Mohsen Arbabi, Hamidreza Gilasi, Hossein Motedayyen","doi":"10.1177/03946320241239202","DOIUrl":"10.1177/03946320241239202","url":null,"abstract":"<p><p><b>Introduction:</b> Recent studies have proposed various COVID-19 vaccines to control the disease and protect susceptible individuals. However, immunogenicity and safety of COVID-19 vaccines in various populations are not well identified yet. Therefore, this study aimed to elucidate the efficacy and safety of the BBIBP-CorV (Sinopharm) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in healthy subjects and patients with autoimmune diseases.<b>Methods:</b> Study population included 121 healthy subjects and 100 patients with autoimmune diseases. Immunization was performed based on the national vaccination protocols. Of the 221 volunteers, 201 subjects received Sinopharm and 20 cases were vaccinated with Oxford-AstraZeneca<b>.</b> During a 1-year follow-up, the immunogenicity was measured by ELISA before primary vaccination and 1 to 3 months after secondary immunization. Side effects were studied before entering the study and 1 week after the second dose.<b>Results:</b> Vaccination had a positive impact on the induction of immunogenic response (<i>p</i> < .0001). The rates of seropositive vaccine responses were 80% and 75% in subjects vaccinated with the Sinopharm and Oxford-AstraZeneca, respectively. The neutralizing antibody values were significantly higher in subjects with autoimmune diseases than those without autoimmunity (<i>p</i> < .05). The rate of adverse events were 38% and 42% in subjects vaccinated with the Sinopharm and Oxford-AstraZeneca, respectively. The rates of immunogenic responses induced with the Sinopharm and Oxford-AstraZeneca were, respectively, 76% and 81.5% in seropositive subjects, while they were 63.8% and 79.1% in seronegative subjects vaccinated with the Sinopharm and Oxford-AstraZeneca, respectively. Individuals previously infected with SARS-CoV-2 showed a significant reduction in the value of SARS-CoV-2 neutralizing antibodies compared with seronegative subjects (<i>p</i> < .01-.05). Seropositive individuals vaccinated with the Sinopharm had significantly higher the percentages of vaccine-related adverse events than seronegative persons (<i>p</i> < .05). There was no significant difference between seronegative and seropositive individuals vaccinated with the Oxford-AstraZeneca.<b>Conclusion:</b> Our findings revealed that the Sinopharm and Oxford-AstraZeneca vaccines are effective in the production of neutralizing antibodies in healthy subjects and patients with autoimmune disorders undergoing immunosuppressive therapies without considerable reactogenicity.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241239202"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of XRCC1 p. Arg194Trp gene polymorphism with the risk of hepatocellular carcinoma in HCV Egyptian population: A pilot case-control study.","authors":"Rasha Ahmed Ghorab, Shaimaa H Fouad, Yara Elsaadawy, Marwa Hamdy, Sara I Taha","doi":"10.1177/03946320241265263","DOIUrl":"10.1177/03946320241265263","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (HCC) is the most common and fatal primary liver cancer. Genetic variants of DNA repair systems can reduce DNA repair capability and increase HCC risk. <b>Objectives:</b> This study aimed to examine, in Egyptian hepatitis C virus (HCV) patients, the relationship between the X-ray repair cross-complementing group 1 (XRCC1) rs1799782 single nucleotide polymorphism (SNP) and HCC susceptibility. <b>Methods:</b> We included 100 adult HCV-positive patients with HCC and 100 adult HCV-positive patients with liver cirrhosis as pathological controls. XRCC1 rs1799782 SNP genotyping was done in both groups using quantitative real-time PCR (qPCR). The distribution of genotypes in patients and controls was compared using several inheritance models. <b>Results:</b> We found that the CT genotype, when analyzed under both the co-dominant (OR (95 % CI): 2.147 (1.184-3.893), <i>p</i> = .012) and the over-dominant (OR (95 % CI): 2.055 (1.153-3.660), <i>p</i> = .015) models, as well as the combined CT and TT genotypes under the dominant model (OR (95 % CI) of 1.991 (1.133-3.497), <i>p</i> = .017), were associated with increased susceptibility to HCC. The frequency of the T allele was higher among HCC participants (32%) compared to those with cirrhosis (23.5%) and carrying the T allele increased the risk of HCC by 1.532 times, however, these associations did not reach statistical significance (<i>p</i>-values >0.05). Moreover, the variant T allele was associated with worse clinical manifestations and laboratory results among the HCC group, but AFP levels were not affected significantly. <b>Conclusions:</b> Egyptians with XRCC1 rs1799782 SNP may have a higher risk of HCV-related HCC. More extensive multi-center prospective investigations must confirm this association.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241265263"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of antioxidants on skin hydration, inflammatory cytokines, and keratinocyte differentiation markers in a PM₁₀-exposed skin barrier-disrupted mouse model.","authors":"Jin Ho Kim, Mi Hee Kwack, Weon Ju Lee","doi":"10.1177/03946320241303860","DOIUrl":"10.1177/03946320241303860","url":null,"abstract":"<p><p>Given that particulate matter (PM) has an established role in inducing oxidative stress, inflammation, and skin aging, it is plausible that PM could exacerbate inflammatory skin conditions such as xerosis. Xerosis represents a significant dermatological concern among older adults within aging populations. We conducted an investigation into the efficacy of antioxidants, such as dieckol, punicalagin, epigallocatechin gallate (EGCG), and resveratrol, against PM₁₀ in a skin barrier-disrupted mouse model. A skin barrier-disrupted mouse model was induced by tape stripping. This study investigated the antioxidative and anti-inflammatory properties of antioxidants on PM-induced changes using the skin barrier-disrupted mouse model. Tape strips were attached to the back of 7-week-old nude mice and removed quickly. To investigate variations in skin hydration, levels of inflammatory cytokines, and indicators of keratinocyte differentiation, mice underwent treatment with several compounds: a control vehicle (100 μL), PM₁₀ 100 μL (100 μg/mL), PM₁₀ 100 μL (100 μg/mL) with antioxidants 100 μL (Punicalagin 5 μM, Dieckol 5 μM, EGCG 1 μM, resveratol 1 μM) for 1 week. To assess their effects, different analysis were conducted using measurements of skin moisture, real-time polymerase chain reaction, enzyme-linked immunosorbent assay for detecting inflammatory cytokines, and immunofluorescence staining to identify markers of keratinocyte differentiation. While PM₁₀ decreased water content in disrupted skin, all antioxidants preserved skin hydration in the skin barrier-disrupted mice, regardless of the presence of PM₁₀. All antioxidants also inhibited the upregulation of inflammatory cytokines, such as interleukin (IL)-1β, IL-4, IL-6, IL-8, and tumor necrosis factor-alpha and normalized the downregulation of keratinocyte differentiation markers against PM₁₀ in skin barrier-disrupted mice. This study elucidated the protective effects of antioxidants-namely, punicalagin, dieckol, EGCG, and resveratrol-in mitigating the impact of PM₁₀ on skin barrier integrity and inflammation in a disrupted skin barrier mouse model, highlighting their potential utility in dermatological treatments.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241303860"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Syk protein inhibitors treatment for the allergic symptoms associated with hyper immunoglobulin E syndromes: A focused on a computational approach.","authors":"Mariam Mansouri, Ghyzlane ElHaddoumi, Ilham Kandoussi, Lahcen Belyamani, Azeddine Ibrahimi, Naima El Hafidi","doi":"10.1177/03946320241282030","DOIUrl":"10.1177/03946320241282030","url":null,"abstract":"<p><p><b>Background:</b> Mutations in the Spleen tyrosine kinase (Syk) protein have significant implications for its function and response to treatments. Understanding these mutations and identifying new inhibitors can lead to more effective therapies for conditions like autosomal dominant hyper-IgE syndrome (AD-HIES) and related immunological disorders. <b>Objective:</b> To investigate the impact of mutations in the Syk protein on its function and response to reference treatments, and to explore new inhibitors tailored to the mutational profile of Syk. <b>Methods:</b> We collected and analyzed mutations affecting the Syk protein to assess their functional impact. We screened 94 deleterious mutations in the kinase domain using molecular docking techniques. A library of 997 compounds with potential inhibitory activity against Syk was filtered based on Lipinski and Veber rules and toxicity assessments. We evaluated the binding affinity of reference inhibitors and 14 eligible compounds against wild-type and mutant Syk proteins. Molecular dynamics simulations were conducted to evaluate the interaction of Syk protein complexes with the reference inhibitor and potential candidate inhibitors. <b>Results:</b> Among the analyzed mutations, 60.5% were identified as deleterious, underscoring their potential impact on cellular processes. Virtual screening identified three potential inhibitors (IDs: 118558008, 118558000, and 118558092) with greater therapeutic potential than reference treatments, meeting all criteria and exhibiting lower IC50 values. Ligand 1 (ID: 118558000) demonstrated the most stable binding, favorable compactness, and extensive interaction with solvents. A 3D pharmacophore model was constructed, identifying structural features common to these inhibitors. <b>Conclusion:</b> This study found that 60.5% of reported mutations affecting the Syk protein are deleterious. Virtual screening revealed three top potential inhibitors, with ligand 1 (ID: 118558000) showing the most stable binding and favorable interactions. These inhibitors hold promise for more effective therapies targeting Syk-mediated signaling pathways. The pharmacophore model provides valuable insights for developing targeted therapies for AD-HIES and related disorders, offering hope for patients suffering from Hyper IgE syndrome with allergic symptoms.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241282030"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of CGNL1 as a diagnostic marker in fibroblasts of diabetic foot ulcers: Insights from single cell RNA sequencing and bulk sequencing data.","authors":"Li Wang, Lulu Tang, Lingna Zhou, Yingtao Lai, Hui Li, Xiaojun Wang, Xiaoyi Liu","doi":"10.1177/03946320241265945","DOIUrl":"10.1177/03946320241265945","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to explore the unique transcriptional feature of fibroblasts subtypes and the role of ferroptosis in diabetic foot ulcers (DFUs).</p><p><strong>Methods: </strong>The GEO (Gene Expression Omnibus) was searched to obtain the DFUs single-cell and transcriptional datasets. After identifying cell types by classic marker genes, the integrated single-cell dataset was used to run trajectory inference, RNA velocity, and ligand-receptor interaction analysis. Next, bulk RNA-seq datasets of DFUs were analyzed to the key ferroptosis genes.</p><p><strong>Results: </strong>Here, we profile 83529 single transcriptomes from the foot samples utilizing single-cell sequencing (scRNA-seq) data of DFU from GEO database and identified 12 cell types, with fibroblasts exhibiting elevated levels of ferroptosis activity and substantial cellular heterogeneity. Our results defined six main fibroblast subsets that showed mesenchymal, secretory-reticular, secretory-papillary, pro-inflammatory, myogenesis, and healing-enriched functional annotations. Trajectory inference and cell-cell communication analysis revealed two major cell fates with subpopulations of fibroblasts and altered ligand-receptor interactions. Bulk RNA sequencing data identified CGNL1 as a distinctive diagnostic signature in fibroblasts. Notably, CGNL1 positively correlated with pro-inflammatory fibroblasts.</p><p><strong>Conclusions: </strong>Overall, our analysis delineated the heterogeneity present in cell populations of DFUs, showing distinct fibroblast subtypes characterized by their own unique transcriptional features and enrichment functions. Our study will help us better understand DFUs pathogenesis and identifies CGNL1 as a potential target for DFUs therapies.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241265945"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of HLA class II alleles and haplotypes with bullous and mucus membrane pemphigoid risk: A systematic review, a meta-analysis and a meta-regression.","authors":"Tarak Dhaouadi, Awatef Riahi, Taïeb Ben Abdallah, Yousr Gorgi, Imen Sfar","doi":"10.1177/03946320241296903","DOIUrl":"10.1177/03946320241296903","url":null,"abstract":"<p><p>Although, several studies have assessed the association of HLA Class II and genes with bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), results were inconsistent and between-studies heterogeneity needs to be investigated. An electronic literature search for eligible studies among all papers published prior to May 31, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the three following HLA genes: DRB1, DQA1 and DQB1. Combined analyses revealed a significant increase in pemphigoid risk conferred by the following alleles: DQB1*0301, DRB1*11, DRB1*1101 subtype and DQA1*0505, all <i>p</i>-values <.001. However, there was a moderate to high level of between-studies heterogeneity. Subgroup analyses revealed that the risk conferred by the aforementioned alleles was significantly higher in case of dipeptidyl peptidase-4 inhibitors induced BP (DBP) comparatively to idiopathic BP and MMP. In addition, the risk conferred by the DQB1*0301 was significantly higher in MMP (OR [95% CI] = 5.25 [4.03-6.84]) than in BP (OR [95% CI] = 2.22 [1.87-2.65]), <i>p</i> = .007. Besides, the DRB1*1101-DQB1*0301 and DRB1*11-DQA1*05-DQB1*0301 haplotypes were significantly associated with an increased pemphigoid risk, both <i>p</i>-values <.001. Conversely, the DQA1*0201 allele was significantly associated with reduced pemphigoid risk (OR [95% CI] = 0.3 [0.17-0.52]), with no between-studies heterogeneity (I² = 0%, <i>p</i> = .76). This meta-analysis demonstrated that the DRB1*1101, DQA1*0505 and DQB1*0301 were significantly associated with increased pemphigoid risk. These associations were found to be significantly stronger in case of DBP comparatively to idiopathic pemphigoid. The DQA1*0201 allele seems to play a protective role against pemphigoid. <b>Registration</b>: This review has been registered on PROSPERO: CRD42024552821, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024552821.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241296903"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deucravacitinib and shikonin combination therapy ameliorates imiquimod-induced psoriasis in mice.","authors":"Ling Xu, Ying Jiang, Fuping Xu, Jun Liu, Yuhong Jiang, Fang Fang, Lin Luo","doi":"10.1177/03946320241260262","DOIUrl":"10.1177/03946320241260262","url":null,"abstract":"<p><strong>Introduction: </strong>TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of JAK/STAT pathway, but it is currently unclear whether their combination will enhance the effect on psoriasis. In this study, we used imiquimod (IMQ)-induced psoriasis mouse model to investigate the therapeutic effects of the combined administration of deucravacitinib (TYK2 inhibitor) and shikonin.</p><p><strong>Methods: </strong>Aldara cream containing 5% IMQ was used to topically treat the dorsal skin of each mouse for a total of six consecutive days to induce psoriasis. The psoriasis area and severity index (PASI) scores were recorded every day. On the 7^th day, skin tissues were taken for histopathological examination and the content of cytokines in skin were evaluated. The frequency of immune cells in peripheral blood, spleen and skin were detected through flow cytometry.</p><p><strong>Results: </strong>Compared to the vehicle control group, the psoriasis symptoms and immune disorder improved significantly in the combination therapy group and deucravacitinib treatment group on the 7th day, and the expressions of p-STAT3 and Ki67 in skin were reduced as well. Moreover, the combined treatment of deucravacitinib and shikonin for psoriasis was superior to the monotherapy group, especially in inhibiting abnormal capillaries proliferation, reducing immune cells infiltration and decreasing the concentration of IL-12p70 in skin.</p><p><strong>Conclusion: </strong>The combination of deucravacitinib and shikonin is a promising clinical application.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241260262"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentagalloyl glucose induces anti-inflammatory macrophage polarization - suppressing macrophage mediated vascular cell dysfunction and TGF-β secretion.","authors":"Gregory Halsey, Fatema-Tuj Zohora, Shivani Arora, Holly Zimmerman, Naren Vyavahare","doi":"10.1177/03946320241276894","DOIUrl":"10.1177/03946320241276894","url":null,"abstract":"<p><p><b>Background:</b> Pentagalloyl glucose (PGG) is a polyphenol with vasoprotective properties. Targeted delivery of PGG reversed aortic aneurysm growth in several rodent models associated with decreased number of macrophages and transforming growth factor-β (TGF-β) expression. Thus, we sought to determine cellular mechanisms by which PGG reduces macrophage-induced aortic pathogenicity and its relationship to TGF-β. <b>Methods:</b> Using THP-1 cells, primary human aortic cells, and explanted rat aortas, we assessed the anti-inflammatory effect of PGG. Expression of pro/anti-inflammatory macrophage markers was analyzed. Adhesion of monocytes as well as oxidative stress status, viability, and TGF-β expression after primary aortic cell exposure to macrophage-conditioned medium with and without PGG were assessed. The release of TGF-β was also examined in elastase-treated cultured rat aortas. <b>Results:</b> PGG pre-treatment of human aortic cell monolayers reduced the adhesion of THP-1 monocytes. PGG enhanced the expression of anti-inflammatory markers in THP-1-derived macrophages, and increased mitochondrial reactive oxygen species as well as mitochondrial polarization. Conditioned medium from THP-1-derived macrophages induced reactive oxygen species, cell death, and TGF-β release from human aortic cells, which was suppressed by PGG. In explanted rat aortas, PGG reduced elastase mediated TGF-β release. <b>Conclusions:</b> Combining anti-inflammatory, cytotoxic, and oxidative effects, PGG has high cardiovascular therapeutic potential. We confirmed previous in vivo observations whereby PGG suppressed TGF-β response associated with disease resolution.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241276894"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin suppresses metastasis, invasion, and proliferation in osteosarcoma cells by regulating the EGFR/Src signaling axis.","authors":"Huiying Liu, Zhiqiang Li, Binwu Xu, Zhipeng Li, Xili Yang, Jun Luo","doi":"10.1177/03946320241308082","DOIUrl":"10.1177/03946320241308082","url":null,"abstract":"<p><p>We explored the biological mechanisms by which curcumin (Cur) confronts osteosarcoma (OS) tumorigenesis and potential drug gene targets based on network pharmacology and in vitro cell experiments. Cur has been recognized for its significant role in combating various types of tumors. However, the intrinsic molecular mechanisms through which it affects OS remain uncharted. In this study, we performed network pharmacology methods including protein-protein interaction (PPI) and core target screening, Functional Enrichment Analysis and Network Construction, Molecular Docking, which obtained the potential target of Cur. Meanwhile, cell experiments (wound healing assay, Transwell assay, Western blots, immunofluorescence, et al.) in vitro were performed to verify the targets, and reveal the biological mechanisms. A total of 18 hub genes were identified through our network pharmacological analysis. In vitro studies show that Cur inhibits the proliferation, migration, invasion capabilities of MG63 and U2OS cells. Western blot reveals a down-regulation of p-PI3K, PI3K, p-Akt, Akt, EGFR, Src, p-Src (Tyr416) and STAT3 expression when treated with Cur. Additionally, Cur upregulated epithelial proteins (E-cadherin and Occludin) while decreasing the expression of the mesenchymal protein (N-cadherin). In addition, Cur treatment decreases the EGFR/Src signaling pathway in the presence of active Src overexpression. Cur inhibits the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) by down-regulating EGFR/Src signaling axis, also resulting in coordinated weakening of its downstream regulatory genes, including Akt, STAT3, Bcl2, ERK1/2, among others signal axis (PI3K/Akt signaling pathway).</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241308082"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of cutaneous manifestations and myositis-specific antibodies in COVID-19 patients and Anti-PL7 antibodies association with pulmonary radiological severity: A retrospective study.","authors":"Giorgio Alberto Oddenino, Paola Canepa, Emanuele Cozzani, Giulia Gasparini, Alessandro Garlaschi, Luca Roccatagliata, Irene Schiavetti, Aurora Parodi","doi":"10.1177/03946320241260295","DOIUrl":"10.1177/03946320241260295","url":null,"abstract":"<p><strong>Background: </strong>Dermatomyositis (DM) is an idiopathic immune-mediated myopathy, and may involve many organs, including muscles, skin and lungs. Myositis-specific autoantibodies (MSAs) are a useful aid in diagnosis DM and identifying its clinical subtype. During the COVID-19 pandemic, several studies found clinical similarities regarding lung involvement in both COVID-19 and DM. Such similarities have prompted speculation of a common pathogenetic mechanism. Indeed, viral infections are well-known triggers of autoimmune diseases. This prompted us to investigate whether circulating MSAs could be markers of the severity of lung involvement and of clinical outcome in COVID-19 patients. Moreover, we investigated the presence of cutaneous signs of DM in COVID-19 patients.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study on 178 hospitalized patients affected by COVID-19. The diagnosis was confirmed by naso-pharyngeal swab positivity for SARS-CoV-2. The severity of lung involvement was assessed by assigning to each patient a radiological score ranging from 1 to 4, based on chest imaging (chest X-rays or CT scans). Serum samples were tested for MSAs.</p><p><strong>Results: </strong>Anti-PL-7 antibodies were detected in 10.1% of patients and were found to be associated with an increased risk of severe pulmonary involvement (<i>p</i> = 0.019) and a worse prognosis in COVID-19 patients. Cutaneous lesions were observed in 26.4% of patients. However, none were cutaneous manifestations of DM.</p><p><strong>Conclusions: </strong>The detection of anti-PL7 antibodies might predict severe pulmonary involvement and a worse prognosis in COVID-19 patients.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241260295"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}