{"title":"Correlation between human papillomavirus protein expression and clinicopathological features in oral squamous cell carcinoma.","authors":"Lin Wang, Nian Jiang, Chijen Lee Chen","doi":"10.1177/03946320241272527","DOIUrl":"10.1177/03946320241272527","url":null,"abstract":"<p><strong>Objective: </strong>Given the implications of concurrent human papilloma viral infection (HPV) in the prognostic course and implications on therapeutic approached of patients with oral squamous cell carcinoma (OSCC), we seek to investigate the implications that P16 expression has on the clinical course and pathological appearance of patients with OSCC and concurrent infection.</p><p><strong>Methods: </strong>Using S-P immunohistochemistry, we examined the expression of P16 and Ki67 in 460 patients with OSCC. We compared the expression of the protein between the tumor cells and normal epithelial mucosa within the same patient. The clinical and pathological characteristics (including gender, age, histological grade, lymph node metastasis, clinical stage, clinical recurrence, tumor diameter, Ki67 proliferation index) were analyzed by stratification statistically.</p><p><strong>Results: </strong>In total 460 cases of OSCC were identified and expression of P16 was significantly higher in the OSCC group compared to the normal mucosal epithelial group (X2 = 60.545, <i>p</i> = .000). There also appear to be a gender predilection as the expression was higher in females compared to males (0.218 vs. 0.144, X2 = 3.921, <i>p</i> = .048). Younger age also appears to be a predictive factor as those under 35 years old had higher expression of the protein compared to those over 35 years old (0.294 vs. 0.157, X2 = 4.230, <i>p</i> = .040). P16 positivity showed a significant positive correlation with histologic grade (X2 = 4.114, <i>p</i> = .043). In addition, the positive rate of P16 was higher in patients with ki67 over 85% (0.455 vs. 0.160, X2 = 6.667, <i>p</i> = .023).</p><p><strong>Conclusion: </strong>OSCC with HPV infection tends to occur more frequently in female patients and those under 35 years of age. HPV infection with expression of the P16 and ki67 protein may promote the proliferation and growth of OSCC at a higher frequency.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241272527"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976994","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}
Ali Tavakoli Pirzaman, Ghazaleh Sadeghnezhad, Zahra Azmoun, Amirreza Eslami, Razieh Mansoori, Sohrab Kazemi, Seyed Mohammad Hosseini
{"title":"The effect of <i>geraniol</i> on nickel-induced embryotoxicity and cardiotoxicity in rats.","authors":"Ali Tavakoli Pirzaman, Ghazaleh Sadeghnezhad, Zahra Azmoun, Amirreza Eslami, Razieh Mansoori, Sohrab Kazemi, Seyed Mohammad Hosseini","doi":"10.1177/03946320241272693","DOIUrl":"10.1177/03946320241272693","url":null,"abstract":"<p><strong>Background: </strong>Nickel (Ni), commonly-used heavy metals in industrial activities, can lead to embryo and organ toxicity, especially cardiovascular damage. Geraniol (GER) has various beneficial effects such as anti-oxidant, anti-inflammatory, anti-tumor, anti-ulcer, anti-microbial, and neuroprotective activities.</p><p><strong>Objective: </strong>The objective of this study was to investigate the effect of GER on Ni-induced embryotoxicity and cardiotoxicity in rats.</p><p><strong>Methods: </strong>40 mother Wistar rats were randomly divided into five groups: Control, GER 250, Ni, Ni + GER 100, and Ni + GER 250. On the 20<sup>th</sup> day of pregnancy, the animals were sacrificed and fetuses along with blood and tissue samples were collocated for morphological, serological, biochemical, and histopathologic analysis.</p><p><strong>Results: </strong>Morphological assessments revealed GER's capacity to mitigate the incomplete ossification of fetal skeletons, indicating a potential safeguarding against the impact of Ni-induced embryotoxicity. Serological and biochemical analyses further affirm GER's role, with noteworthy reductions in cardiac injury markers, such as CRP, CKMB, CPK, LDH, and troponin, in response to GER administration, thereby suggesting its cardioprotective potential. Moreover, treatment with GER 250 could significantly reduce the level of MDA and increase the level of TAC compared to the Ni group. Histopathological examinations corroborated these findings, underscoring GER's ability to counteract cardiac injury and diminish structural damage in affected tissue.</p><p><strong>Conclusions: </strong>These multidimensional analyses indicate the protective prowess of GER against Ni-induced embryotoxic and cardiotoxic effects, shedding light on its potential therapeutic significance in combating adverse impacts stemming from Ni exposure.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241272693"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407066","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}
Wael Em Barakat, Fatma Sm Moawed, Esraa Sa Ahmed, Omayma Ar Abo-Zaid
{"title":"The hepatotoxicity of γ-radiation synthesized 5-fluorouracil nanogel versus 5-fluorouracil in rats model.","authors":"Wael Em Barakat, Fatma Sm Moawed, Esraa Sa Ahmed, Omayma Ar Abo-Zaid","doi":"10.1177/03946320241227099","DOIUrl":"10.1177/03946320241227099","url":null,"abstract":"<p><strong>Introduction: </strong>The clinical use of 5-fluorouracil (5-FU), a routinely used chemotherapy medication, has a deleterious impact on the liver. Therefore, it is necessary to find a less harmful alternative to minimize liver damage. This study was designed to see how 5-fluorouracil nanogel influenced 5-FU-induced liver damage in rats.</p><p><strong>Methods: </strong>To induce liver damage, male albino rats were injected intraperitoneally with 5-FU (12.5 mg/kg) three doses/week for 1 month. The histopathological examination together with measuring the activities of serum alanine and aspartate aminotransferase enzymes (ALT and AST) were used to evaluate the severity of liver damage besides, hepatic oxidative stress and antioxidant markers were also measured. The hepatic gene expression of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α) and interleukins (IL-1β, IL-6) were detected.</p><p><strong>Results: </strong>5-Fu nanogel effectively attenuated 5-FU-induced liver injury by improving the hepatic structure and function (ALT and AST) besides the suppression of the hepatic inflammatory mediators (TNF- α, IL-1β and IL-6). Additionally, 5-FU nanogel alleviated the impaired redox status and restored the antioxidant system via maintaining the cellular homeostasis Keap-1/Nrf2/HO-1 pathway.</p><p><strong>Conclusion: </strong>Consequently, 5-Fu nanogel exhibited lower liver toxicity compared to 5-FU, likely due to the alleviation of hepatic inflammation and the regulation of the cellular redox pathway.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241227099"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425791","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":"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}
Rasha Ahmed Ghorab, Shaimaa H Fouad, Yara Elsaadawy, Marwa Hamdy, Sara I Taha
{"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 PM<sub>10</sub>-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 PM<sub>10</sub> 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), PM<sub>10</sub> 100 μL (100 μg/mL), PM<sub>10</sub> 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 PM<sub>10</sub> decreased water content in disrupted skin, all antioxidants preserved skin hydration in the skin barrier-disrupted mice, regardless of the presence of PM<sub>10</sub>. 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 PM<sub>10</sub> in skin barrier-disrupted mice. This study elucidated the protective effects of antioxidants-namely, punicalagin, dieckol, EGCG, and resveratrol-in mitigating the impact of PM<sub>10</sub> 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}
Mariam Mansouri, Ghyzlane ElHaddoumi, Ilham Kandoussi, Lahcen Belyamani, Azeddine Ibrahimi, Naima El Hafidi
{"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}
Li Wang, Lulu Tang, Lingna Zhou, Yingtao Lai, Hui Li, Xiaojun Wang, Xiaoyi Liu
{"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 (I<sup>2</sup> = 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}
Ling Xu, Ying Jiang, Fuping Xu, Jun Liu, Yuhong Jiang, Fang Fang, Lin Luo
{"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<sup>th</sup> 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}