European Journal of Medical Research最新文献

{"title":"Remimazolam alleviates hippocampal neuronal injury in an in vitro Alzheimer's disease model by promoting PINK1/Parkin-mediated mitophagy.","authors":"Wei Zhang, Bowen Shi, Yuanyuan Xie, Yan Li, Jianke Yang, Ke Zhao","doi":"10.1186/s40001-025-03179-x","DOIUrl":"10.1186/s40001-025-03179-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the pathological accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau proteins. Remimazolam (RMZ), a novel ultra-short-acting benzodiazepine, exhibits neuroprotective effects by enhancing mitochondrial autophagy independently of traditional GABAergic mechanisms. This study investigates the protective role of RMZ against Aβ1-42-induced neuronal damage through PINK1/Parkin-mediated mitophagy. In hippocampal HT22 cells, RMZ significantly attenuated Aβ1-42-induced cytotoxicity, reduced apoptosis, suppressed reactive oxygen species (ROS) production, and decreased lactate dehydrogenase (LDH) release. Moreover, RMZ ameliorated mitochondrial membrane depolarization and tau hyperphosphorylation, while enhancing mitophagy, evidenced by an increased LC3-II/LC3-I ratio, elevated Beclin-1 expression, and decreased P62 levels. Mechanistically, RMZ upregulated PINK1 and Parkin expression, facilitating mitochondrial recruitment and clearance of damaged mitochondria. Importantly, knockdown of PINK1 abolished RMZ's protective effects, confirming the pathway's specificity. These findings suggest that RMZ promotes mitochondrial homeostasis and offers a promising strategy for AD therapy via PINK1/Parkin-mediated mitophagy.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"962"},"PeriodicalIF":3.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279231","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":"Unraveling the causality between carpal tunnel syndrome and trigger finger through genetic instrumental variables.","authors":"Junming Huang, Kui Deng, Shanhu Huang, Zhengtao Lv, Song Zhou, Mingxing Chen","doi":"10.1186/s40001-025-02833-8","DOIUrl":"10.1186/s40001-025-02833-8","url":null,"abstract":"<p><strong>Objective: </strong>Carpal tunnel syndrome (CTS) and trigger finger (TF) are the two most common non-traumatic connective tissue disorders of the hands. These conditions often manifest concurrently in certain patients; however, the mechanisms underlying this phenotypic association remain inadequately understood. In this study, we aimed to systematically investigate the causal relationship between CTS and TF using a large sample size and advanced methods.</p><p><strong>Method: </strong>In this study, comprehensive summary-level data on CTS and TF from genome-wide association studies (GWAS) were collected. The causal relationship between CTS and TF was investigated using two-sample Mendelian randomization (MR). Sensitivity analyses were conducted to evaluate the robustness of MR findings. Furthermore, multivariable Mendelian randomization (MVMR) was employed to examine the role of CTS in causation and adjust for potential confounding variables. Additionally, supplementary reverse MR analysis was performed to ascertain the causal effect of TF on CTS.</p><p><strong>Results: </strong>Univariate analysis indicated that CTS had a causative influence on TF (OR = 2.53, 95% CI = 1.52-4.23, P = 0.00039). Conversely, reverse MR analyses did not support TF as a causative factor of CTS. Furthermore, in the MVMR analysis, which accounted for potential confounding variables, such as body mass index and type 2 diabetes mellitus, the causal relationship between CTS and TF remained statistically significant and robust.</p><p><strong>Conclusion: </strong>This study established the genetic causality of CTS on TF, suggesting an elevated risk of TF development in individuals with CTS. These findings may inform evidence-based recommendations aimed at reducing the incidence of TF in patients with CTS.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"963"},"PeriodicalIF":3.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285961","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 lipid metabolism-related signature in nonalcoholic fatty liver: evidences from transcriptomics and single cell RNA-sequencing analysis.","authors":"Yanqing Sun, Minjie Hu, Jin Yang, Dong Jia, Chun Gao, Wei Wang","doi":"10.1186/s40001-025-03215-w","DOIUrl":"10.1186/s40001-025-03215-w","url":null,"abstract":"<p><strong>Background: </strong>Considering the complex and close-knit relationship between non-alcoholic fatty liver disease (NAFLD) and the metabolic status, this study aimed to identify lipid metabolism-related genes (LMGs), construct an effective diagnostic model, and uncover the underlying LMG-related mechanism in NAFLD.</p><p><strong>Methods: </strong>NAFLD datasets and the LMGs were downloaded from the GEO database and a previous publication. Key LMGs were identified through differential expression analysis, Venn diagrams, WGCNA, and three machine learning algorithms; and then nomogram models were constructed. To evaluate the model's performance, we employed calibration curves, decision curve analysis (DCA), clinical impact curve (CIC), and receiver operator characteristic (ROC) analysis. Additionally, we constructed immune infiltration analysis and scRNA-seq analysis to explore the immune infiltration patterns and underlying mechanisms. Finally, qRT-PCR and Western blotting were performed to validate the expression of the key genes.</p><p><strong>Results: </strong>The critical genes (PRKAA2 and ME1) were identified as significantly correlated with lipid metabolism in NAFLD. The nomogram model, based on the two key genes, demonstrated strong diagnostic performance for NAFLD, achieving an AUC of 0.945. The immune infiltration analysis revealed that PRKAA2 and ME1 were significantly associated with immune cells, particularly NK cells and T cells. scRNA-seq analysis classified cells into six subtypes: NK cells, monocytes and macrophages, T cells, B cells, proliferating cells, and plasmacytoid dendritic cells. Among these, T cells and NK cells were the most functionally relevant, with ME1 showing predominant expression and a strong correlation with NK cells. Experimental validation via qRT-PCR and Western blotting confirmed that only ME1 was significantly up-regulated in NAFLD.</p><p><strong>Conclusion: </strong>A lipid metabolism-related signature was successfully constructed, offering clinical potential for predicting NAFLD status.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"964"},"PeriodicalIF":3.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285940","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":"Predictors of flexion contracture progression following total knee arthroplasty: role of global sagittal alignment and patient age.","authors":"Woo-Suk Lee, Byung Woo Cho, Hyuck Min Kwon, Tae Hyung Kim, Kwan Kyu Park, Jun Young Park","doi":"10.1186/s40001-025-03225-8","DOIUrl":"10.1186/s40001-025-03225-8","url":null,"abstract":"<p><strong>Background: </strong>Knee flexion contracture (KFC) progression after total knee arthroplasty (TKA) can significantly affect functional outcomes through disruption of the biomechanical knee-hip-spine kinetic chain. This study was conducted to investigate whether preoperative global sagittal alignment parameters, particularly the center of the acoustic meatus-sagittal vertical axis (CAM-SVA), could predict short-term KFC progression after TKA.</p><p><strong>Methods: </strong>A retrospective case-control study was performed on 760 consecutive TKA cases, with 347 knees meeting inclusion criteria. KFC progression was defined as > 5° increase in knee flexion angle between immediate postoperative and final follow-up radiographs. Demographic factors and radiographic parameters were analyzed using univariate and multivariate logistic regressions. Patient-reported outcomes were assessed using the American Knee Society Score (AKSS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Potential sources of bias were addressed through standardized measurement protocols and inter-observer reliability testing.</p><p><strong>Results: </strong>KFC progression was observed in 39 knees (11.2%), with mean progression of 8.0 ± 3.8° over 23.5 ± 13.1 months. Multivariate analysis revealed that CAM-SVA and age were independently associated with KFC progression (odds ratio: 1.02 [95% CI 1.01-1.04], p < 0.05; and 1.09 [95% CI 1.02-1.17], p < 0.01, respectively). At 12 months, the KFC progression group demonstrated significantly lower AKSS scores and higher WOMAC scores (p < 0.05) as compared to the nonprogression group.</p><p><strong>Conclusions: </strong>CAM-SVA and advanced age were identified as independent predictors of KFC progression following TKA, supporting the hypothesis that global sagittal malalignment contributes to compensatory knee flexion through biomechanical interdependence of the knee-hip-spine kinetic chain. Assessment of preoperative global sagittal alignment may help identify patients at risk for KFC progression and inform individualized treatment strategies.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"960"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274260","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":"Comparative impact of persistent and paroxysmal atrial fibrillation on myocardial strain: a retrospective cohort study.","authors":"Hongru Chen, Lei Cheng, Wen Gao, Guoqian Huang, Yikai Zhao, Jian Li","doi":"10.1186/s40001-025-03224-9","DOIUrl":"10.1186/s40001-025-03224-9","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) impairs cardiac structure and function, increasing adverse cardiovascular outcomes. Myocardial strain analysis provides a sensitive measure of myocardial deformation and has emerged as a valuable tool in detecting subclinical cardiac dysfunction. However, comparative data on myocardial strain between paroxysmal AF (PAF) and persistent AF (PsAF) remain limited. This study aimed to investigate the independent effects of different AF subtypes on myocardial strain.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 128 non-valvular AF patients between January 2023 and January 2025. Patients were classified into PAF (n = 77) and PsAF (n = 51) groups based on preoperative 24-h Holter monitoring. Speckle-tracking echocardiography was used to assess myocardial strain. Multivariate linear regression models were constructed to evaluate the association between AF subtype and the global longitudinal peak strain average (GLPS_AVG). Subgroup analyses were conducted across age, gender, BMI, hypertension, hypertriglyceridemia and diabetes.</p><p><strong>Results: </strong>Patients with PsAF exhibited significantly lower GLPS_AVG values compared to those with PAF (- 14.00 ± 3.24 vs. - 17.71 ± 3.07, P < 0.001). In multivariable-adjusted models, PsAF remained independently associated with reduced GLPS_AVG (Model III: β = 2.70, 95% CI 1.11 ~ 4.29, P < 0.001). Subgroup analysis confirmed that this association exists in every subgroups.</p><p><strong>Conclusion: </strong>Persistent AF is associated with more severe impairment in myocardial strain compared to paroxysmal AF. These findings suggest that myocardial strain analysis may aid in early detection of AF-related cardiac dysfunction and support the need for timely intervention in patients with PsAF.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"959"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274152","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":"Cigarette smoke extract promotes metastasis and oxaliplatin resistance in colon adenocarcinoma through GDF15/ERBB2/AKT pathway.","authors":"Wen Jiang, Ye Wang, Wei-Jie Wang, Bai-Chuan Zhou, Xiao-Si Hu, A-Man Xu","doi":"10.1186/s40001-025-03233-8","DOIUrl":"10.1186/s40001-025-03233-8","url":null,"abstract":"<p><strong>Background: </strong>Colon adenocarcinoma (COAD) exhibits high mortality due to metastasis and oxaliplatin (L-OHP) resistance. Cigarette, an established environmental risk factor, is linked to poor prognosis in COAD, yet the underlying molecular mechanisms have not been explored. Growth differentiation factor 15 (GDF15) can promote the occurrence and development of tumors. Here, we identified that GDF15 as a crucial mediator of cigarette smoke promoting the development of COAD.</p><p><strong>Methods: </strong>Cox regression and Kaplan-Meier analyses were utilized to evaluate association between smoking history and prognosis of COAD patients. HT29 and HCT116 cells were chronically exposed to cigarette smoke extract (CSE) to evaluate migration, invasion and L-OHP resistance via transwell, wound healing, CCK-8, and flow cytometry. Bioinformatics analysis was utilized to study the association between GDF15 expression, smoking history and prognosis of COAD. GDF15 overexpression/knockdown models were established to study the effect of cigarette-induced GDF15 on COAD metastasis and chemotherapy resistance. RNA sequencing, co-immunoprecipitation (Co-IP) and inhibitor treatment were utilized to analyze GDF15-mediated ERBB2/AKT/SLC7A11 signaling. Nude mice xenografts with CSE-exposed or GDF15-knockdown cells were used to assess the effect of cigarette-induced GDF15 on L-OHP resistance in vivo.</p><p><strong>Results: </strong>Smoking history was correlated with reduced overall survival (OS) in COAD patients (p = 0.0016). Chronic CSE exposure enhanced migration and invasion via epithelial-mesenchymal transition (EMT) and conferred L-OHP resistance. Cigarette smoke can elevate GDF15 expression in COAD and high GDF15 predicted poor OS and progression-free survival (PFS) in chemotherapy-treated cohorts. Functional experiments showed that CSE-induced GDF15 promoted COAD metastasis and L-OHP resistance. RNA-sequence showed that GDF15-related genes were significantly enriched in AKT and glutathione metabolic pathways. Mechanically, GDF15 can bind to ERBB2 and activate ERBB2/AKT phosphorylation, upregulate SLC7A11, and increase glutathione (GSH) levels, driving L-OHP resistance and metastasis. In vivo CSE-exposed xenografts showed reduced L-OHP sensitivity via GDF15.</p><p><strong>Conclusions: </strong>CSE promoted COAD metastasis and L-OHP resistance by upregulating GDF15, which activated the ERBB2/AKT/SLC7A11 axis. Targeting GDF15 may offer therapeutic potential to overcome cigarette-aggravated COAD progression.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"958"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274123","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":"From \"lysosomal addiction\" to targeted therapies: exploiting novel windows in colorectal cancer.","authors":"Xiaoyu Wang, Fan An, Benjun Wang, Tiantian Zhang, Yueting Fang, Liwei Yan, Chuan Jiang, Wenwen Cui, Weiwei Han","doi":"10.1186/s40001-025-03145-7","DOIUrl":"10.1186/s40001-025-03145-7","url":null,"abstract":"<p><p>Patients with advanced-stage or treatment-resistant colorectal cancer (CRC) face limited therapeutic options with conventional therapies, necessitating novel treatment strategies. CRC cells exhibit \"lysosomal addiction\" through enhanced autophagy-lysosomal flux and upregulated lysosome-associated genes including lysosomal-associated membrane protein 1/2 and cathepsin B/D, creating therapeutic windows for selective targeting. Lysosome-dependent cell death represents a distinct mode of regulated cell death characterized by lysosomal membrane permeabilization and cathepsin-mediated cytotoxic cascades, offering advantages over apoptosis-dependent mechanisms. Recent investigations have identified multiple druggable targets within lysosomal pathways, including autophagy modulators, cathepsin inhibitors, and innovative drug delivery systems. Lysosomes also play bidirectional roles in tumor immune microenvironment regulation, with implications for combination immunotherapy strategies. However, challenges remain in clinical translation, including autophagy's dual functionality and the need for reliable biomarkers. Targeting lysosomal dysfunction represents a promising therapeutic approach for CRC, particularly for overcoming resistance to traditional therapies. The unique metabolic dependency of cancer cells on lysosomal function provides exploitable therapeutic windows for precision medicine approaches.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"957"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274225","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-based integration of pericoronary adipose tissue and clinical risk factors for cardiovascular risk prediction in type 2 diabetes: a retrospective cohort study.","authors":"Yuqing Tang, Xuankun Zheng, Xiaofei Yang, Sien Guo, Qiyuan Luo, Meiyi Su, Huiqi Chen, Wu Zhou, Hongqin Wang, Yue Liu, Guoqing Liu, Lei Wang","doi":"10.1186/s40001-025-03237-4","DOIUrl":"10.1186/s40001-025-03237-4","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease remains the predominant cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). Traditional risk models are limited in predictive accuracy. Pericoronary adipose tissue (PCAT), a novel imaging biomarker of vascular inflammation, may offer additional prognostic value. Therefore, this study aimed to develop and validate a machine learning model that integrates PCAT parameters with clinical risk factors to improve the accuracy of cardiovascular risk prediction in individuals with T2DM.</p><p><strong>Methods: </strong>This study retrospectively enrolled 686 hospitalized T2DM patients from four branches of Guangdong Provincial Hospital of Chinese Medicine between January 2017 and December 2021. PCAT-FAI and volume index were measured using coronary CTA. Major adverse cardiovascular events (MACE) were recorded during follow-up. Eight machine learning algorithms were applied, and multiple evaluation metrics were used to compare the predictive performance of the models. Feature contributions in the best-performing model were interpreted using both feature importance ranking and SHapley Additive exPlanations (SHAP) values.</p><p><strong>Results: </strong>A total of 183 patients experienced MACE during the mean 38.4 months of follow-up. Among the eight machine learning models evaluated, the XGBoost model performed the best in predicting MACE in patients with T2DM. In the internal validation of the training set, the AUC was 0.818 (95% CI 0.777-0.858), and in the external test set, the AUC was 0.809 (95% CI 0.700-0.918). Additionally, the XGBoost model outperforms other models in all evaluation metrics (accuracy = 0.824, specificity = 0.882, F1 score = 0.654, Brier score = 0.248). In the feature importance analysis of the prediction model, RCA-FAI in the PCAT parameters consistently ranked among the top three in eight ML models. Further SHAP analysis indicated that RCA-FAI, body mass index (BMI), and the monocyte/high-density lipoprotein cholesterol ratio (MHR) were the most influential factors for MACE in patients with T2DM.</p><p><strong>Conclusion: </strong>This study demonstrates the independent predictive value of PCAT parameters for long-term cardiovascular risk in patients with T2DM. The XGBoost model showed promise as a potential clinical decision support tool. Integrating PCAT parameters with conventional risk factors may improve the identification of high-risk individuals and enhance the ability to predict MACE in this population. Clinical trial registration ChiCTR2400079869.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"961"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274244","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":"Conjoint analysis of single-cell sequencing and high-throughput virtual screening regarding DDR2 in osteoarthritis disease models.","authors":"Hongliang Mei, Jiheng Wang, Xiaohu Zheng, Rui Yan, Weihang Li, Peng Wang, Xiaomeng Wang, Liang Liu","doi":"10.1186/s40001-025-03197-9","DOIUrl":"10.1186/s40001-025-03197-9","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common degenerative joint disease, which is highly prevalent in the elderly, imposes a significant burden on patients and society. Aging, obesity, and inflammation are important factors contributing to the development of osteoarthritis. Currently, there are limited pharmaceutical treatment options for osteoarthritis: non-steroidal anti-inflammatory drugs or COX2 inhibitors are generally used for anti-inflammatory treatment of mild to moderate pain, and corticosteroid joint injections are used for severe pain. Discoidin domain receptor tyrosine kinase 2 (DDR2) is reported to be closely related to OA in recent studies. Single-cell RNA sequencing analysis in this study also proved that DDR2 was strongly expressed in some specific cell subsets. Current DDR2 inhibitor research focuses on developing antagonists to block type II collagen binding and receptor activation, thereby reducing MMP13 expression and promoting cartilage repair. At present, most of DDR2 inhibitors are still at the research stage in the laboratory and further development and improvement of these drug candidates are required. In this study, computer-aided drug design (CADD) techniques were used to screen potential lead compounds targeting DDR2. Candidate compounds were analyzed following different modules, such as Libdock, CDOCKER, TOPKAT, ADMET, and molecular dynamics simulation (MD) etc. Altogether, two natural lead compounds were ultimately identified with characterizations of high affinity and low drug toxicity in this study. One of the compounds ZINC000003874604 were selected for in vitro cell experiments. In-vitro experiments confirmed that the lead compound ZINC000003874604 could protect tBHP-induced primary chondrocytes of OA by inhibiting DDR2 expression. In summary, this study found that ZINC000003874604, as a lead compound, had potential therapeutic activity for OA, which may help provide more drug options in the pharmaceutical market.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"954"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274287","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 analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study.","authors":"Sema Hepşen, Cem Haymana, Burçak Cavnar Helvacı, Halil Durantaş, Bora Toros, Ramazan Çakmak, Mehmet Güven, İbrahim Demirci, Lezan Keskin, Sinem Kıyıcı, Zehra Yağmur Şahin Alak, Mehmet Sargın, Gonca Tamer, Damla Balcı, Berna İmge Aydoğan, Arzu Or Koca, Mustafa Aydemir, İlhan Tarkun, Pınar Köksal, Ayten Oğuz, Eda Demir Önal, Süleyman Baldane, Muhammed Kızılgül, Erman Çakal, Bekir Çakır, Şefika Burçak Polat, İlhan Yetkin, Emre Bozkırlı, Gülsüm Karaahmetli, Sevgül Fakı, Narimana Imanova Yaghji, Ayşin Öge, Burak Özbaş, Şenay Topsakal, Sevde Nur Fırat, Hayri Bostan, Barış Karagün, Okan Sefa Bakıner, Ayşe Kargılı Çarlıoğlu, Bahri Evren, Kader Uğur, Faruk Kılınç, Adnan Batman, Selin Çakmak Demir, Dilek Yazıcı, Oğuzhan Deyneli, Metin Arslan, Omercan Topaloğlu, Kübra Kocatepe, Kemal Karagözoğlu, Sakin Tekin, Taner Bayraktaroğlu, Sibel Ertek Yalçın, Ayşe Kubat Üzüm, Gökçem Yalın Kocamaz, Mehtap Şahin, Yusuf Aydın, Mustafa Kutlu, Tevfik Sabuncu, Mustafa Cesur, Volkan Demirhan Yumuk, Fahri Bayram, Alper Sönmez","doi":"10.1186/s40001-025-02836-5","DOIUrl":"10.1186/s40001-025-02836-5","url":null,"abstract":"<p><strong>Background: </strong>The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study.</p><p><strong>Methods: </strong>This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes.</p><p><strong>Results: </strong>At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment. The treatment duration was identified as an independent predictor for achieving 5% and 10% weight loss targets (B = 0.315, p < 0.001) and 10% weight loss (B = 0.216, p < 0.001).</p><p><strong>Conclusions: </strong>Liraglutide effectively results in clinically significant weight loss, achieves expected weight loss targets, and improves metabolic parameters in real-world clinical practice. Therefore, liraglutide is still a reasonable GLP-1 analogue in the obesity treatment. However, it may be associated with various side effects, necessitating close monitoring by clinicians.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"956"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274155","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}