Mediators of Inflammation最新文献

{"title":"Gene Expression Signatures of Smoking and Acute Myocardial Infarction: A Blood Transcriptome Analysis.","authors":"Fang-Fang Liu, Yi-Xuan Yan, Hong-Feng Zhang, Ke Li","doi":"10.1155/mi/2431090","DOIUrl":"10.1155/mi/2431090","url":null,"abstract":"<p><p><b>Background:</b> Tobacco smoke is known to contain numerous harmful chemicals, and epidemiological evidence has firmly established smoking as a potent risk factor for hypertension and myocardial infarction (MI). However, the precise mechanisms by which smoking contributes to cardiovascular disease are not fully understood. The aim of this study is to identify common molecular signatures in blood that link smoking to acute MI (AMI). <b>Methods:</b> We extracted transcriptome data from seven blood microarray datasets in the Gene Expression Omnibus (GEO) database, encompassing a total of 403 patients. Employing both individual dataset analysis and a combined meta-analysis approach, we conducted a thorough examination of blood transcriptome profiles associated with AMI and smoking, uncovering numerous differentially expressed genes (DEGs). <b>Results:</b> Functional enrichment analysis indicated that DEGs associated with AMI and smoking were significantly enriched in overlapping biological processes, such as immune response and inflammation. Moreover, three genes-PTGDR, PYHIN1, and PRSS23-were consistently altered in both conditions and were validated as dysregulated in AMI using an independent GEO dataset. Furthermore, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) validation further confirmed the differential expression of PYHIN1 and PRSS23 in AMI patients. <b>Conclusions:</b> Our findings suggest that gene expression changes induced by smoking in blood may contribute to the heightened risk of AMI. These identified genes are likely to play critical roles in the pathogenesis of AMI. Given the accessibility of peripheral blood samples, the expression levels of these genes could potentially serve as biomarkers for assessing cardiovascular health, particularly in individuals with a history of long-term exposure to cigarette smoke.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2431090"},"PeriodicalIF":4.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024032","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":"Flavonoids of <i>Tetrastigma hemsleyanum</i> Diels et Gilg Against Acute Hepatic Injury by Blocking PI3K/AKT Signaling Pathway.","authors":"Lingling Li, Lianghui Zhan, Xiaojun Wu, Xuechun Jiang, Jinbao Pu","doi":"10.1155/mi/4302130","DOIUrl":"10.1155/mi/4302130","url":null,"abstract":"<p><p><b>Objective:</b> This study aims to investigate the mechanism of <i>Tetrastigma hemsleyanum</i> Diels et Gilg flavonoids (THF) on acute hepatic injury (AHI). <b>Methods:</b> First, high-performance liquid chromatography (HPLC) fingerprints were established to obtain the main chemical components of THF. According to the network pharmacology databases, collect active targets of AHI and potential targets. Using interaction targets to construct a protein-protein interaction (PPI) network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, the affinity between the core targets and the main active ingredients was verified by molecular docking. Next, verified network pharmacology predictions with animal experiments. Mice were treated with THF (20, 40, and 80 mg/kg) for 7 days, and then built an acute liver injury model (lipopolysaccharide [LPS], 10 mg/kg). Detecting the liver biochemical indices, observe the liver pathological changes, and verify the key signaling pathway targets. <b>Results:</b> HPLC showed that the main components of THF were quercetin and kaempferol. Seven active ingredients and 193 potential targets were screened, and 259 disease targets related to acute liver injury, quercetin, and kaempferol may be the main active ingredients in THF. PPI network analysis showed that tumor necrosis factor (TNF), interleukin-6 (IL-6), and tumor protein 53 (TP53) were potential targets of THF for the treatment of AHI. KEGG analysis showed that the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway might be one of the main pathways in the treatment of AHI. The molecular docking results showed that active compounds both have strong binding activity with potential targets in PPI. In vivo experiments showed that THF could reduce the fibrosis and inflammation of liver tissue etc. Meanwhile, it could downregulate the alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-6, tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) levels, and the protein expressions of phosphorylated phosphoinositide 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), and the ratio of BCL2-associated X (BAX)/B-cell lymphoma-2 (BCL-2) in the liver tissue of the mice with acute liver injury and upregulate the level of interleukin-10 (IL-10). <b>Conclusion:</b> The treatment of acute liver injury with THF is characterized by multicomponents and multitargets, and its mechanism may be related to the alleviation of the inflammatory response, reduction of apoptosis, and regulation of the PI3K/AKT signaling pathway.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4302130"},"PeriodicalIF":4.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007638","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":"A Retrospective Comparison of Aeroallergen Sensitization Among Different Allergic Diseases in Guangzhou, China.","authors":"Chao Yang, Qingxiang Zeng, Gen Lu, Haipian Li, Wenlong Liu","doi":"10.1155/mi/8896646","DOIUrl":"10.1155/mi/8896646","url":null,"abstract":"<p><p><b>Objective:</b> Numerous studies have reported on the types of aeroallergen sensitization in various pediatric allergic diseases, but limited data compared the types of aeroallergen sensitization across different pediatric allergic diseases. The aim of this study is to explore the nature and significance of aeroallergen sensitization in diverse pediatric allergic conditions. <b>Methods:</b> A comparative analysis was carried out on aeroallergen sensitization in children suffering from allergic diseases who visited the Otolaryngology, Respiratory, and Dermatology Departments between January 2019 and December 2023. The evaluation of the specific immunoglobulin E (IgE) response to various inhalant allergens was done using the ImmunoCAP 100 system. <b>Results:</b> Mites remain the main aeroallergen for skin and respiratory allergic diseases, especially respiratory diseases. Dog dander, grass pollen, and mold are more common in skin allergic diseases. The differences in dog dander and grass pollen among the three groups are more pronounced in children aged 1-6, while the differences in fungi are more pronounced in children aged 7 years and above. Seasonal changes have a greater impact on the sensitization rates of cockroaches, grass pollen, and molds. <b>Conclusions:</b> Our results demonstrate the distribution and differences of allergen types among common pediatric allergic diseases, providing a theoretical basis for preventing the development of different allergic diseases and avoiding aeroallergens.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"8896646"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951315","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":"Neutrophil-to-Lymphocyte and Platelet Ratio (N/LP Ratio), a Reliable Criterion for Predicting In-Hospital Mortality in Both Genders Infected With SARS-CoV-2.","authors":"Jafar Mohammadshahi, Hassan Ghobadi, Afshan Shargi, Hossein Moradkhani, Hamed Rezaei, Mahur Kazemy, Mohammad Reza Aslani","doi":"10.1155/mi/5720709","DOIUrl":"https://doi.org/10.1155/mi/5720709","url":null,"abstract":"<p><p><b>Background:</b> The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), neutrophil-to-lymphocyte and platelet ratio (N/LP ratio), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and systemic inflammation index (SII) have emerged as noteworthy determinants in evaluating the severity and mortality prognosis of inflammatory diseases. In order to predict mortality rate, this study aimed to assess the impact of systemic inflammatory markers on both men and women who were admitted to the hospital due to SARS-CoV-2 infection. <b>Methods:</b> The laboratory parameters of the 2007 COVID-19 patients were analyzed in a retrospective study (men = 1145 and women = 862). Receiver operating characteristic (ROC) analysis was used to determine the capability of inflammatory markers to differentiate the severity of COVID-19, while survival probability was determined using Kaplan-Meier curves, with the endpoint being death. To prevent any linear bias, the inflammatory indices were assessed separately using univariate analysis for Charlson comorbidity index (CCI), and adjustments were made for confounding factors if <i>p</i> < 0.2. <b>Results:</b> Adjusted-NLR, adjusted-MLR, N/LP ratio, adjusted-dNLR, adjusted-AISI, adjusted-SII, and adjusted-SIRI exhibited remarkably higher values in patients who did not survive as compared to those who did. The multivariate Cox regression models demonstrated significant association between survival and N/LP ratio (HR = 1.564, 95% CI = 1.161 to 2.107, <i>p</i> < 0.01) in men and N/LP ratio (HR = 1.745, 95% CI = 1.230 to 2.477, <i>p</i> < 0.01) and adjusted-SII (HR = 6.855, 95% CI = 1.454 to 32.321, <i>p</i> < 0.05) in women. <b>Conclusion:</b> A reliable predictor in the current study of men and women with COVID-19 was N/LP ratio.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"5720709"},"PeriodicalIF":4.4,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932307","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":"Causal Relationships Between Leukocyte Subsets and Adverse Fetal Outcomes: A Mendelian Randomization Study.","authors":"Hong Chen, Li-Zhen Shao, Ying-Xiong Wang, Zhi-Jie Han, Yong-Heng Wang, Xia Li, Jing-Yu Chen, Tai-Hang Liu","doi":"10.1155/mi/6349687","DOIUrl":"10.1155/mi/6349687","url":null,"abstract":"<p><p><b>Background:</b> The tolerance and dynamic regulation of the maternal immune system during pregnancy are pivotal for ensuring fetal health. Immune cell subsets play a complex and crucial role in this process, closely linked to the neonatal health status. Despite recognizing the significance of dysregulation in the quantity and activity of immune cells in neonatal disease occurrence, their specific roles remain elusive, resulting in a dearth of clinically viable interventions for immune-mediated neonatal diseases. <b>Materials and Methods:</b> Employing two-sample Mendelian randomization (MR) methodology, this study systematically investigated 446 leukocyte features (<i>N</i> = 500,675), including leukocyte subsets, absolute cell (AC) counts, and morphological parameters (MP) and their correlation with seven adverse fetal outcomes (<i>N</i> = 1,100,458), encompassing fetal growth restriction (FGR), preterm birth (PTB), neonatal jaundice (NNJ), digestive system disorders of fetus and newborn (DSDFN), hemorrhagic and hematological disorders of fetus and newborn (HDFN), respiratory distress of newborn (RDN), and transitory disorders of metabolism specific to fetus and newborn (TDMSFN). <b>Results:</b> The results unveiled significant causal relationships between 301 leukocyte subsets and these seven adverse fetal outcomes, with 259, 245, 15, 44, 11, 32, and 68 pairs of notable associations for each adverse outcome, respectively. Furthermore, the study highlighted potential pathogenic mechanisms underlying the mutual influence among neonatal diseases. MR results indicated FGR as a robustly correlated risk factor for PTB and NNJ and showed a reciprocal causal relationship between NNJ and FGR. PTB exhibited a positive correlation with HDFN. <b>Conclusions:</b> This study provided profound insights into the intricate regulatory mechanisms of leukocyte subsets in neonatal diseases, paving the way for new avenues in the diagnosis and treatment of associated disorders.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"6349687"},"PeriodicalIF":4.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922045","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":"Inhibiting Tyrosine Kinase 2 Ameliorates Antiphospholipid Syndrome Nephropathy.","authors":"Kuo-Tung Tang, Yu-Sin Chen, Tzu-Ting Chen, Ya-Hsuan Chao, Shu-Ping Kung, Der-Yuan Chen, Chi-Chien Lin","doi":"10.1155/mi/5568822","DOIUrl":"10.1155/mi/5568822","url":null,"abstract":"<p><p><b>Objective:</b> Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by the presence of <i>β</i>2-glycoprotein I (<i>β</i>2-GPI)-targeting antiphospholipid antibodies (aPLs) and vascular thrombosis or obstetrical complications. One of its severe manifestations is nephropathy. <b>Methods:</b> To examine the role of type I interferon (IFN) and therapeutic potential of tyrosine kinase 2 (Tyk2) inhibition, we administered BMS-986202, a novel Tyk2 inhibitor, in a mouse model of APS nephropathy. We administered BMS-986202 to BALB/c mice at a dose of 2 mg/kg. Biochemical and histological characteristics of APS nephropathy were then determined. The type I IFN signature in the kidney was also evaluated by real-time polymerase chain reaction (PCR). <b>Results:</b> The Tyk2 inhibitor reversed the elevation of blood urea nitrogen (BUN) and microalbuminuria in the murine model of APS nephropathy. In addition, the Tyk2 inhibitor reversed the pathological vascular changes in the kidney as judged in electron microscopy (EM), and fibrin and C3 deposition as revealed in immunohistochemistry (IHC). An increased expression levels of IFN signature (IFN regulatory factor 7 (IRF7) and Mx1) in the kidneys of APS mice were found. Tyk2 inhibition reversed such an upregulation. <b>Conclusion:</b> Our results demonstrated the key role of type I IFN in the pathogenesis of APS nephropathy. Furthermore, the therapeutic efficacy of Tyk2 inhibition was demonstrated in a murine model of APS nephropathy. Our results could provide a new treatment strategy for this debilitating disease.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"5568822"},"PeriodicalIF":4.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914934","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":"Enhancing Inflammatory Factors, Nitric Oxide, and Arterial Stiffness Through Aquatic Walking for Amelioration and Disease Prevention: Targeting in Obese Elderly Women.","authors":"Woo-Hyeon Son, Woo-Min Jeong, In Young Park, Min-Seong Ha","doi":"10.1155/mi/5520987","DOIUrl":"10.1155/mi/5520987","url":null,"abstract":"<p><p>In elderly women, hormonal changes lead to elevated body fat content, which results in elevated levels of vascular inflammatory factors, thereby increasing the risk of cardiovascular diseases (CVDs) associated with endothelial dysfunction. Regular physical exercises tend to keep these in check and are protective to the body. Aerobic exercise has been reported to improve CVD in obese elderly women; in this regard, aquatic exercises have been demonstrated to be more efficient in energy metabolism than land-based exercise. This study aimed to examine the effect of aquatic walking exercises on the levels of inflammatory factors, nitric oxide (NO), and brachial-ankle pulse wave velocity (baPWV) in obese elderly women. We measured these in 26 obese elderly women who were randomly assigned to control (<i>n</i> = 12) and aquatic walking exercise (<i>n</i> = 14) groups. After subjecting them to aquatic walking exercises thrice a week for 12 weeks, we specifically found a significant reduction in IL-6 levels and an increase in NO levels in these obese elderly women. This was paralleled with a reduction in the right baPWV (baPWV-R). Together, these results indicate that aquatic walking exercises can help improve vascular inflammatory factors, NO levels, and arterial stiffness.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"5520987"},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914919","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":"Correlation Between Neutrophil-Lymphocyte Ratio and Inhospital Cardiac Events in Geriatric Patients With Hip Fractures.","authors":"Miaomiao Yu, Zhen Cui, Ying Bai","doi":"10.1155/mi/5587265","DOIUrl":"10.1155/mi/5587265","url":null,"abstract":"<p><p><b>Background:</b> The novel inflammatory biomarker known as the neutrophil-lymphocyte ratio (NLR) has shown great potential in predicting and prognosing many diseases. However, its correlation with postoperative inhospital major adverse cardiac events (MACEs) in geriatric patients with hip fractures remains unclear. This study investigated the relationship between NLR and postoperative inhospital MACEs among geriatric patients with hip fractures. <b>Methods:</b> We enrolled geriatric patients with hip fractures who were hospitalized in the Department of Geriatric Traumatology and Orthopedics, Beijing Jishuitan Hospital, Capital Medical University, between January 2023 and November 2023. After surgery, the patients were transferred to the intensive care unit (ICU) for postoperative monitoring and treatment. Patients were assigned to the MACE or non-MACE group based on the occurrence of MACEs after surgery during their hospital stay. Clinical data were retrospectively analyzed. <b>Results:</b> In all, 216 patients were recruited into the study: 34 in the MACE group and 182 in the non-MACE group. Univariate and multivariate analyses revealed that a medical history of stroke (odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.18-6.01; <i>p</i>=0.018) and elevated preoperative NLR (OR = 1.09, 95% CI = 1.03-1.17; <i>p</i>=0.005) were significant risk factors for postoperative inhospital MACEs. The area under the curve (AUC) of preoperative NLR-predicted MACEs was 0.65 (0.55-0.75). Patients with a preoperative NLR <6.49 were less likely to experience inhospital MACEs, demonstrating a sensitivity of 61.8% and specificity of 64.8%. <b>Conclusion:</b> Elevated preoperative NLR is an independent risk factor for postoperative inhospital MACEs in geriatric patients with hip fractures.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"5587265"},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895814","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":"Hypoxia-Inducible Factor-1α Modulates the Toll-Like Receptor 4/Nuclear Factor Kappa B Signaling Pathway in Experimental Necrotizing Enterocolitis.","authors":"Yunfei Zhang, Mei Yan, Yingbin Yue, Yongfeng Cheng","doi":"10.1155/mi/4811500","DOIUrl":"10.1155/mi/4811500","url":null,"abstract":"<p><p>Necrotizing enterocolitis (NEC) is a devastating disease observed in premature infants, characterized by intestinal ischemia and inflammation. Hypoxia-inducible factor-1 alpha (HIF-1α), a master regulator of the cellular response to hypoxia and ischemia, plays a critical role in NEC pathogenesis. However, the precise mechanisms by which HIF-1α influences the intestines in NEC remain poorly understood. Herein, we aimed to explore the role of HIF-1α in NEC using a transgenic mouse model. We induced NEC in neonatal mice from postnatal day 5 to 9, and various parameters, including intestinal injury, oxidative stress, inflammatory responses, intestinal epithelial cell (IEC) proliferation, and apoptosis, were assessed. The results confirmed that the absence of intestinal epithelial HIF-1α increased the susceptibility of mice to NEC-induced intestinal injury, as evidenced by increased oxidative stress, inflammatory responses, apoptosis, and inhibition of proliferation. Additionally, we observed an upregulation of the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway specifically in the intestines of mice lacking HIF-1α in IECs (HIF-1α^ΔIEC) with NEC. These findings provide crucial insights into the role of HIF-1α in regulating intestinal oxidative stress and inflammation to maintain intestinal homeostasis, highlighting its association with the TLR4-NF-κB signaling pathway. Furthermore, these insights might lead to the identification of novel therapeutic targets for the treatment of NEC.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"4811500"},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885814","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":"Machine Learning and Mendelian Randomization Reveal Molecular Mechanisms and Causal Relationships of Immune-Related Biomarkers in Periodontitis.","authors":"Yuan Li, Bolun Zhang, Dengke Li, Yu Zhang, Yang Xue, Kaijin Hu","doi":"10.1155/mi/9983323","DOIUrl":"10.1155/mi/9983323","url":null,"abstract":"<p><p>This study aimed to investigate the molecular mechanisms of periodontitis and identify key immune-related biomarkers using machine learning and Mendelian randomization (MR). Differentially expressed gene (DEG) analysis was performed on periodontitis datasets GSE16134 and GSE10334 from the Gene Expression Omnibus (GEO) database, followed by weighted gene co-expression network analysis (WGCNA) to identify relevant gene modules. Various machine learning algorithms were utilized to construct predictive models, highlighting core genes, while MR assessed the causal relationships between these genes and periodontitis. Additionally, immune infiltration analysis and single-cell sequencing were employed to explore the roles of key genes in immunity and their expression across different cell types. The integration of machine learning, MR, and single-cell sequencing represents a novel approach that significantly enhances our understanding of the immune dynamics and gene interactions in periodontitis. The study identified 682 significant DEGs, with WGCNA revealing seven gene modules associated with periodontitis and 471 core candidate genes. Among the 113 machine learning algorithms tested, XGBoost was the most effective in identifying periodontitis samples, leading to the selection of 19 core genes. MR confirmed significant causal relationships between CD93, CD69, and CXCL6 and periodontitis. Further analysis showed that these genes were correlated with various immune cells and exhibited specific expression patterns in periodontitis tissues. The findings suggest that CD93, CD69, and CXCL6 are closely related to the progression of periodontitis, with MR confirming their causal links to the disease. These genes have potential applications in the diagnosis and treatment of periodontitis, offering new insights into the disease's molecular mechanisms and providing valuable resources for precision medicine approaches in periodontitis management. Limitations of this study include the demographic and sample size constraints of the datasets, which may impact the generalizability of the findings. Future research is needed to validate these biomarkers in larger, diverse cohorts and to investigate their functional roles in the pathogenesis of periodontitis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"9983323"},"PeriodicalIF":4.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882499","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}