European Journal of Medical Research最新文献

{"title":"Therapeutic effect of dihydroartemisinin on Alzheimer's disease model mice with senile macular degeneration.","authors":"Gao Han, Gong Xuewu, Zhang Meng, Wang Yuejing, Wang Yuchun, Zhang Keshuang, Yao Hongbo","doi":"10.1186/s40001-025-02315-x","DOIUrl":"10.1186/s40001-025-02315-x","url":null,"abstract":"<p><strong>Objectives: </strong>This study focuses on the preventive and therapeutic effects of Dihydroartemisinin (DHA) on Alzheimer's disease (AD) model mice and the effects of DHA and donepezil on amyloid β-protein deposition and autophagy in nerve cells.</p><p><strong>Methods: </strong>Six autophagy related targets were selected for molecular docking with DHA to predict the affinity between DHA and the target. The AD mouse model was established and treated with donepezil and DHA, respectively. Morris water maze was used to detect the spatial learning and memory ability of AD mice. Hematoxylin eosin (he) staining was used to observe the structural changes of cerebral cortical neurons and retina, and transmission electron microscope was used to observe the structural changes of mitochondria and synapses. Immunohistochemistry (IHC) and immunofluorescence staining were used to detect the deposition of amyloid beta protein. Western blot was used to detect the expression of apoptosis and autophagy related proteins in the brain tissue of mice in each group.</p><p><strong>Results: </strong>The results of molecular docking showed that the selected active compounds had good binding activity with the target. The binding energy between DHA and Aβ, Bcl-2, ATG5, LC3, Caspase3, LAMP1 is -5.7, -7.0, -5.8, -7.2, -6.9 kcal/mol. The water maze test showed that compared with the wild type (WT) group, the spatial memory ability of AD model group mice (5× FAD) was significantly decreased, and the search time (27.62 ± 6.51 s vs. 282.80 ± 17.15 s) and average path (106.30 ± 29.65 cm vs. 993.20 ± 135.80 cm) were significantly prolonged. The application of donepezil and DHA significantly shortened the exploration time and average path (donepezil: 116.10 ± 10.58 s, 529.40 ± 106.00 cm; DHA: 99.71 ± 14.22 s, 373.30 ± 60.97 cm). The path to find the platform in DHA treatment group was shorter than donepezil treatment group (P < 0.05). HE staining showed that the arrangement of nerve cells in 5× FAD mice was disordered, and IHC showed that amyloid β-protein deposition was obvious. DHA and donepezil could improve the damage of cerebral cortex structure and reduce the deposition of extracellular amyloid β-protein in AD mice. Transmission electron microscopy showed that DHA and donepezil could reduce mitochondrial vacuolation and synaptic edema. The above results showed that DHA treatment effect was better than donepezil. Compared with the conventional feeding group, autophagy and apoptosis related proteins B-cell lymphoma-2 (BCL2) and anti-thymocyte globulin (ATG) were significantly down regulated in the 5× FAD group, and the expressions of BCL2 and ATG were increased after treatment with DHA and donepezil.</p><p><strong>Conclusions: </strong>DHA combined with BCL2 and ATG protein, through promoting autophagy protein, can reduce the damage of cerebral cortex structure in AD mice, reduce the deposition of extracellular β-amyloid protein, and then improve the memory ability of","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"81"},"PeriodicalIF":2.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254966","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":"Construction and validation of risk prediction models for renal replacement therapy in patients with acute pancreatitis.","authors":"Fei Zuo, Lei Zhong, Jie Min, Jinyu Zhang, Longping Yao","doi":"10.1186/s40001-025-02345-5","DOIUrl":"10.1186/s40001-025-02345-5","url":null,"abstract":"<p><strong>Background: </strong>Renal replacement therapy (RRT) plays a crucial role in managing acute pancreatitis (AP). This study aimed to develop and evaluate predictive models for determining the need for RRT among patients with AP in the intensive care unit (ICU).</p><p><strong>Methods: </strong>A retrospective selection of patients with AP was made from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version V2.0). The cohort was randomly divided into a training set (447 patients) and a validation set (150 patients). The least absolute shrinkage and selection operator (LASSO) regression cross-validation method was utilized to identify key features for model construction. Using these features, four machine learning (ML) algorithms were developed. The optimal model was visualized and clarified using SHapley Additive exPlanations (SHAP) and presented as a nomogram.</p><p><strong>Results: </strong>The mean age of the cohort was 59.17 years, with an average Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 17.55. Acute kidney injury (AKI) was observed in 52.43% of patients with AP, and 9.05% required RRT. After feature selection, four of 41 clinical factors were ultimately chosen for use in model construction. The Lasso-Logistic Regression (Lasso-LR) model showed a high discriminative ability to predict RRT risk in patients with AP, with an area under the receiver operating characteristic (AUROC) of 0.955 (95% CI 0.924-0.987) in the training set. In the validation set, it maintained its discriminative performance, achieving an AUROC of 0.985 (95% CI 0.970-1.000). Calibration curves indicated an excellent fit in both sets (Brier scores: 0.039 and 0.032, respectively), suggesting high consistency. Decision curve analysis (DCA) highlighted the Lasso-LR model's significant clinical utility in predicting RRT likelihood in patients with AP.</p><p><strong>Conclusions: </strong>Developed via the LASSO regression cross-validation method, the Lasso-LR model significantly excels in predicting the requirement for RRT in patients with AP, demonstrating its potential for clinical application.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"70"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188661","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":"WNT3A promotes the cementogenic differentiation of dental pulp stem cells through the FOXO1 signaling pathway.","authors":"Dongmei Cheng, Yang Bao, Xue Wang, Haidong Xiang, Tianyuan Guo, Yong Du, Zhiyong Zhang, Han Guo","doi":"10.1186/s40001-024-02259-8","DOIUrl":"10.1186/s40001-024-02259-8","url":null,"abstract":"<p><strong>Background: </strong>Dental pulp stem cells (DPSCs) possess capability of multidirectional differentiation, and their cementogenic differentiation potential enables them to participate in cementum repair and regeneration. The molecular mechanisms underlying cementogenic differentiation of DPSCs remain unclear.</p><p><strong>Methods: </strong>DPSC data set GSE138179 was retrieved from gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was employed to identify significant modules. Pathway enrichment exploration was conducted utilizing gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Metascape tools. CIBERSORT was utilized to analyze immune cell infiltration analysis. The comparative toxicogenomics database (CTD) was utilized for the validation of core targets. Subsequently, cell experiments were conducted to validate the core targets. Changes in protein expression related to the FOXO1 signaling pathway, cell cycle, and apoptosis were evaluated using western blotting (WB).</p><p><strong>Results: </strong>Differentially expressed genes (DEGs) associated with DPSC cementogenic differentiation were predominantly enriched in crucial pathways such as the signaling pathway, cell apoptosis, and Wnt signaling pathway. Bioinformatics analysis confirmed WNT3A as a pivotal biomarker for DPSC cementogenic differentiation, and WNT3A was highly expressed in the cementogenic differentiation group. Western blotting results demonstrated that compared to the DPSC group, molecules such as Caspase-3, Caspase-9, FAS, P53, and BAX were downregulated in the CDDPSC group, suggesting reduced apoptosis. Furthermore, upregulation of WNT3A expression in CDDPSC-OE further suppressed the expression of these apoptotic molecules, suggesting a mitigated apoptotic response. Downregulation of WNT3A expression in CDDPSC-KO resulted in increased expression of apoptosis-related molecules, thereby enhancing apoptosis.</p><p><strong>Conclusions: </strong>WNT3A is highly expressed in the cementogenic differentiation of DPSC, and WNT3A mediates FOXO1 pathway to promote differentiation of dental pulp stem cells into cementogenic differentiation, thus realizing the formation and maintenance of cementum tissue.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"68"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188683","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":"Comparing survival outcomes of localized tumor destruction, sublobar resection, and pulmonary lobectomy in stage IA non-small cell lung cancer: a study from the SEER database.","authors":"Lin Cheng, Sheng-Wei Li, Xiao-Guang Li","doi":"10.1186/s40001-025-02325-9","DOIUrl":"10.1186/s40001-025-02325-9","url":null,"abstract":"<p><strong>Purpose: </strong>A large-scale comparative analysis was performed with the aim of comparing local tumor destruction (LTD), sublobar resection (SR), and pulmonary lobectomy (PL) for cancer-specific survival (CSS) and overall survival (OS) in stage IA non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>In the Surveillance, Epidemiology, and End Results (SEER) database (2000-2021), we included patients with pathologically confirmed stage IA non-small cell lung cancer who were treated with LTD, SR, or PL. Comparison between groups was performed separately after 1:1 proportional propensity score matching (PSM) with a caliper value of 0.1. Kaplan-Meier analysis was performed to compare survival outcomes between groups.</p><p><strong>Results: </strong>In the total cohort of 4437 LTD patients, 2425 SR patients, and 6386 PL patients, 84.18% of LTD-treated patients were older than 65 years, whereas 68.95% of SR-treated patients and 62.82% of PL-treated patients were older than 65 years. The CSS (HR = 0.756, 95% CI 0.398 ~ 1.436, P = 0.393) and OS (HR = 0.46, 95% CI 0.553 ~ 1.295, P = 0.442) of LTD were consistent with SR. Whereas LTD demonstrated lower CSS (HR = 0.603, 95% CI 0.378 ~ 0.940, P = 0.024) and OS (HR = 0.590, 95% CI 0.432 ~ 0.805, P < 0.001) than PL, but were consistent when the tumor size was ≤ 1 cm. The CSS (HR = 1.215, 95% CI 0.872 ~ 1.693, P = 0.249) of SR was consistent with PL, but OS (HR = 1.347, 95% CI 1.079 ~ 1.681, P = 0.008) was higher than PL, but were consistent when the tumor size was 1.1-3 cm.</p><p><strong>Conclusions: </strong>In patients with stage IA non-small cell lung cancer, the CSS and OS of LTD were no worse than those of SR. Compared with PL, the CSS and OS of LTD were lower, but when the tumor size was ≤ 1 cm, the CSS and OS of LTD were no worse than those of PL.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"76"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188627","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":"Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis.","authors":"Shasha Huang, Shumin He, Fei Xiao, Yang Zhou, Su Lyu","doi":"10.1186/s40001-025-02333-9","DOIUrl":"10.1186/s40001-025-02333-9","url":null,"abstract":"<p><strong>Background: </strong>Fulminant myocarditis (FM), a critical cardiac disease, is characterised by atypical initial symptoms and rapid progression and tends to lead to cardiomyocyte degeneration or necrosis. Reliable biological markers for FM screening remain lacking. Circular RNAs (circRNAs) are highly stable in peripheral blood due to their special closed-loop structure, and reports have described their involvement in regulating inflammatory responses and cell injury in cardiomyocytes. This study attempted to identify the abnormal expression of circRNAs in the peripheral blood of patients with FM and to evaluate the potential diagnostic value.</p><p><strong>Methods: </strong>Peripheral blood was collected from 5 children with FM and 5 sex- and age-matched healthy controls; total RNA was extracted from each sample, and the extracted RNA from each group was pooled. After RNase R treatment, high-throughput sequencing was performed to screen for differentially expressed circRNAs in the peripheral blood of patients. Biological function classification and enrichment analysis were used to explore the main action pathways involving differentially expressed circRNAs. A lipopolysaccharide (LPS)-induced cardiomyocyte inflammation model was used to explore the effect of inflammation on the expression of these dysregulated circRNAs. Receiver operating characteristic (ROC) curves were used to evaluate the potential clinical value of FM-related circRNAs as biomarkers in a large sample of patients.</p><p><strong>Results: </strong>CircRNA expression profiling of peripheral blood samples from patients revealed 6,435 and 3,678 circRNAs with upregulated and downregulated expression, respectively, compared with healthy controls. The expression of 1,749 circRNAs did not significantly differ between the groups. GO and KEGG analysis revealed that the genes encoding the dysregulated circRNAs were associated with various biological functions related to the risk of FM development, including infectious diseases, the immune system, and signal transduction. The high expression of hsa_circ_0064338 (circ_PPARG) was confirmed in both the myocardial cell inflammation model and peripheral blood from a large sample of FM patients. ROC curve analysis showed that the level of circ_PPARG in peripheral blood had a good ability to distinguish patients with FM from healthy controls.</p><p><strong>Conclusions: </strong>Large numbers of abnormally regulated circRNAs were identified in peripheral blood from patients with FM; among these, the highly expressed circ_PPARG could distinguish patients from healthy controls to a certain extent. It is expected to become a potential clinical biomarker of FM in the future.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"72"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188622","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":"L-shaped association between ankle-brachial index and coronary heart disease in Chinese adults with hypertension.","authors":"Wei Zhou, Yumeng Shi, Chao Yu, Tao Wang, Lingjuan Zhu, Huihui Bao, Xiaoshu Cheng","doi":"10.1186/s40001-025-02342-8","DOIUrl":"10.1186/s40001-025-02342-8","url":null,"abstract":"<p><strong>Background: </strong>Prior research has established that an ankle-brachial index (ABI) ≤ 0.9 is positively correlated with cardiovascular events, including coronary heart disease (CHD). The present study aimed to elucidate the dose-response relationship between ABI and CHD within a hypertensive population.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis involving 10,900 hypertensive patients, with CHD as the primary outcome. A generalized additive model (GAM) and fitted smoothing curve were employed to assess linearity and delineate the dose-response association between ABI and CHD.</p><p><strong>Results: </strong>The cohort had a mean (SD) age of 68.3 (9.25) years, with 5129 (47.06%) being male. CHD was present in 552 (5.06%) participants. The fully adjusted odds ratio (OR) for CHD associated with ABI levels was 0.75 (95%CI 0.33-1.71). An L-shaped relationship between ABI and CHD was identified, with an inflection point at 1.07. Below this threshold, ABI showed a negative correlation with CHD (OR: 0.27; 95%CI 0.08-0.84), whereas above it, the association was not significant (OR: 3.08; 95%CI 0.60-15.80).</p><p><strong>Conclusions: </strong>In Chinese adults with hypertension, ABI exhibits a nonlinear, L-shaped association with CHD, with the inflection point at 1.07.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"73"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188649","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":"The value of inflammation-related indicators in chemotherapy efficacy and disease-free survival of triple-negative breast cancer.","authors":"Jie Zhu, Jiale Cheng, Yuyuan Ma, Ying Wang, Zhonghua Zou, Wenjie Wang, Haihua Shi, You Meng","doi":"10.1186/s40001-025-02328-6","DOIUrl":"10.1186/s40001-025-02328-6","url":null,"abstract":"<p><strong>Background: </strong>Systemic inflammation is closely correlated with the progression of cancer. Inflammation-related indicators has been recognized as outcome predictors in triple-negative breast cancer (TNBC). Our study aimed to investigate the predictive value of several inflammation-related indicators in TNBC patients underwent chemotherapy (NAC).</p><p><strong>Methods: </strong>100 TNBC patients were enrolled in the study. Levels of interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assays (ELISAs). Platelet-to-lymphocyte ratio (PLR) and immune inflammatory index (SII) were obtained from blood routine. Levels of Ki-67 expression were detected by immunohistochemistry (IHC). Mentioned indicators were divided into two groups based on their median values. The correlation between these indicators and NAC efficacy was analyzed using t tests. Prognostic risk scores were calculated by univariate Cox regression analysis and Lasso-penalized Cox regression. The patients were divided into low- and high-risk groups based on the median risk score. Survival curves were obtained by Kaplan-Meier method. Models for univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. A nomogram was used for the prediction of 1-, 2-, and 3-year disease-free survival (DFS). Accuracy of the prognostic model was validated by receiver operating characteristic curve (ROC).</p><p><strong>Results: </strong>IL-6, PLR, SII, and Ki-67 levels were associated with neoadjuvant efficacy. IL-6, PLR, SII, Ki-67, and lymphocyte count were associated with DFS. The risk score for each TNBC patient was obtained using LASSO regression analysis to construct a prognostic model. In the prognostic model, patients in the high-risk score group showed worse DFS than those in the low-risk group. Risk score and tumor size were independently correlated with outcomes in multivariate Cox regression analysis. A nomogram was constructed using IL-6, PLR, SII, Ki-67, and Miller-Payne (MP) scores. Calibration curves demonstrated good consistency between the actual and predictive values of the nomogram.</p><p><strong>Conclusion: </strong>A prognostic model was established by combining four prognosis-related indicators in TNBC patients who underwent NAC.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"77"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188673","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 between blood-urea-nitrogen-to-albumin ratio and in-hospital mortality in patients diagnosed with coronavirus disease 2019: a retrospective cohort study.","authors":"Ruoqing Zhou, Dianzhu Pan","doi":"10.1186/s40001-025-02338-4","DOIUrl":"10.1186/s40001-025-02338-4","url":null,"abstract":"<p><strong>Background: </strong>The blood-urea-nitrogen-to-albumin ratio (BAR) is recognized as a novel prognostic indicator; however, there is a limited number of studies investigating the relationship between BAR and in-hospital mortality associated with coronavirus disease 2019 (COVID-19). Therefore, the present investigation aims to explore the correlation between BAR and in-hospital mortality in patients with COVID-19 in China.</p><p><strong>Methods: </strong>This retrospective observational study enrolled a cohort of 1027 patients diagnosed with COVID-19 between December 2022 and March 2023. Multivariate Cox regression analyses were used to ascertain the independent association between BAR and in-hospital mortality among patients with COVID-19. Furthermore, stratified analyses were used to investigate potential interaction effects with variables, such as age, sex, COVID-19 Severity, hypertension, coronary artery disease, and diabetes mellitus.</p><p><strong>Results: </strong>A total of 117 patients (11.4%) died from various causes during hospitalization. Subsequent to adjustment for confounding variables, patients in the highest BAR tertile exhibited an elevated risk for in-hospital mortality relative to those in the lowest tertile (hazard ratio [HR] 2.44 [95% confidence interval CI 1.24-4.79]) when BAR was treated as a categorical variable. When considering BAR as a continuous variable, a 6% increase in the prevalence of in-hospital mortality was observed for each 1-unit increase in BAR (adjusted HR 1.06 [95% CI 1.03-1.08]; P < 0.001). Stratified analyses revealed a consistent association between BAR and in-hospital mortality due to COVID-19.</p><p><strong>Conclusions: </strong>BAR exhibited a significant relationship with in-hospital mortality in patients with COVID-19, suggesting that a higher BAR is associated with a poorer prognosis. However, further research is required to confirm these findings.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"78"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188597","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":"Targeted intervention of tumor microenvironment with HDAC inhibitors and their combination therapy strategies.","authors":"Wanli Zhang, Luqi Ge, Yiwen Zhang, Zhentao Zhang, Wen Zhang, Feifeng Song, Ping Huang, Tong Xu","doi":"10.1186/s40001-025-02326-8","DOIUrl":"10.1186/s40001-025-02326-8","url":null,"abstract":"<p><p>Histone deacetylation represents a significant epigenetic mechanism that involves the removal of acetyl groups from histones, subsequently influencing gene transcription. Overexpression of histone deacetylases (HDACs) is prevalent across various cancer types, positioning HDAC inhibitors as broadly applicable therapeutic agents. These inhibitors are known to enhance tumor immune antigenicity, potentially slowing tumor progression. Furthermore, the tumor microenvironment, which is intricately linked to cancer development, acts as a mediator in the proliferation of numerous cancers and presents a viable target for oncological therapies. This paper primarily explores how HDAC inhibitors can regulate cancer progression via the tumor microenvironment and suppress tumor growth through multiple pathways, in addition to examining the synergistic effects of combined drug therapies involving HDAC inhibitors.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"69"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188671","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":"Comprehensive genomic and transcriptomic profiling of pulmonary nodules in synchronous multiple primary lung cancer.","authors":"Xingsheng Liu, Kun Qian, Lei Su, Xiaoru Tian, Xin Zhao, Tengteng Wang, Li Han, Zhenzhen Li, Peilong Zhang, Ruotian Wang, Baodong Liu, Yuanbo Li, Xiaogang Tan, Yi Zhang","doi":"10.1186/s40001-025-02327-7","DOIUrl":"10.1186/s40001-025-02327-7","url":null,"abstract":"<p><strong>Background: </strong>Synchronous multiple primary lung cancer (sMPLC) exhibits distinct histopathological characteristics among pulmonary nodules. However, a comprehensive understanding of the somatic mutation landscape and transcriptome heterogeneity is lacking. Therefore, our study aims to meticulously investigate genomic distinctions among multiple pulmonary nodules within individual patients.</p><p><strong>Methods: </strong>We performed targeted DNA sequencing on tumor specimens and conducted bulk RNA transcriptome analysis on 53 multiple nodules originating from 26 lung cancer patients. The multiple nodules from the same patient was determined as major nodule and minor nodule. Additionally, the tumor tissues underwent histopathological evaluation through H&E staining, complemented by a comprehensive series of immunohistochemistry (IHC) analyses to detect protein expression. The detected protein markers encompassed PD-L1, Ki67, and others.</p><p><strong>Results: </strong>For the 53 nodule samples from 26 MPLCs patients, EGFR was the mostly mutated genes, and the TP53 mutation frequency was notably different between major and minor nodules. Furthermore, pathway enrichment analysis based on the differentially expressed genes (DEGs) between major and minor nodules revealed the significantly active cell cycle and p53 pathways in the major nodules. Additionally, both major and minor nodules demonstrated mostly similar immune microenvironment and PD-L1 protein expression, and a significantly higher expression of Ki67. A noteworthy suppression was observed in the immune microenvironment in nodules, revealed by the expression of macrophage, neutrophils, and NK cells. Furthermore, minor nodules exhibited a modestly elevated expression of macrophages compared to major nodules. Additionally, among the significantly up-regulated cell cycle-related genes in the major nodules when compared with minor nodules, CCNE1 mRNA expression demonstrated significant correlation with poor prognosis in the lung cancer. Furthermore, the MYC inhibitor demonstrated more sensitivity for the major nodules than minor nodules.</p><p><strong>Conclusions: </strong>This study validated molecular distinctions between samples from major and minor nodules in patients with sMPLC at both genomic and transcriptomic levels. The major nodules exhibited heightened activity in tumor cell proliferation pathways and demonstrated malignancy-related biological characteristics, which correlated with pathological assessment results.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"74"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188632","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}