Claudia Ciancarella, Fulvia Ceccarelli, Licia Picciariello, Francesco Natalucci, Alessandra Ida Celia, Cristina Garufi, Silvia Mancuso, Giuseppe Tripodi, Simona Truglia, Angelica Gattamelata, Francesca Romana Spinelli, Cristiano Alessandri, Fabrizio Conti
{"title":"Evolutionary trajectory of undifferentiated connective tissue disease and impact of 2019 EULAR/ACR systemic lupus erythematosus classification criteria: insights from a longitudinal study.","authors":"Claudia Ciancarella, Fulvia Ceccarelli, Licia Picciariello, Francesco Natalucci, Alessandra Ida Celia, Cristina Garufi, Silvia Mancuso, Giuseppe Tripodi, Simona Truglia, Angelica Gattamelata, Francesca Romana Spinelli, Cristiano Alessandri, Fabrizio Conti","doi":"10.1007/s10238-025-01668-1","DOIUrl":"https://doi.org/10.1007/s10238-025-01668-1","url":null,"abstract":"<p><p>Undifferentiated connective tissue disease (UCTD) is a condition characterized by serological evidence of autoimmunity and occurrence of clinical symptoms suggestive for systemic autoimmune diseases, yet not fulfilling specific classification/diagnostic criteria. In the present longitudinal, observational, retrospective study, we aimed at analysing the evolution of UCTD course, focussing on the impact of 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE). Since 2008 we consecutively collected data about UCTD patients. All subjects were evaluated every six months, to record the development of clinical and laboratory features suggestive for specific autoimmune diseases. Finally, we retrospectively applied the 2019 EULAR/ACR SLE classification criteria at the first and last visit in our outpatient clinic. All the patients included in the study had been evaluated at our Lupus Clinic before the release of 2019 EULAR/ACR criteria. We included 201 UCTD patients [F/M 191/10, median age at first visit 46 years (IQR 21), median disease duration at first visit 3 years (IQR 9)]. At the first visit, 27 patients (13.4%) already met 2019 EULAR/ACR SLE classification criteria. Logistic regression analysis demonstrated the association between SLE classification and thrombocytopenia, anti-dsDNA/anti-Sm positivity, low C4 levels, joint involvement. During a mean observation period of 45.9 ± 35.6 months, 18.9% of patients were lost to follow-up, while 141 patients were followed. At last visit, additional 11 patients (7.8%) could be classified as having SLE. A relevant proportion of UCTD patients could be reclassified as having SLE according to the most recent classification criteria. Thrombocytopenia, anti-DNA/anti-Sm positivity and low C4 levels represent the most associated factors.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"134"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A unifying model for multiple sclerosis.","authors":"Daniel Jonathan Park","doi":"10.1007/s10238-025-01666-3","DOIUrl":"https://doi.org/10.1007/s10238-025-01666-3","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a complex neurodegenerative disorder with unresolved cause that has been the subject of intensive research. A variety of putative models have been proposed to explain the course of disease. The preeminent mechanisms are suggested to be based on autoimmunity, including via viral epitope mimicry, although difficulties with a classical autoimmunity model for MS have been described. One prior idea that incorporates consideration of viral-self-cross-reactivity is that reactivated HHV-6A virus might induce subsequent reactivation of another virus, EBV, in a relay, resulting in a cascade of downstream consequences. Here, an alternative model for MS is proposed. This posits a viral reactivation relay in which EBV reactivation in the brain precedes HHV-6A reactivation in oligodendrocytes and neurons. At this juncture, relapsing-remitting MS (RRMS) can ensue to generate characteristic lesions, dominated by outbreaks of viral reactivation and CD8+T-cell-mediated cytotoxicity and inflammation. Additionally, self-targeting antibodies can be raised to mark the onset of progressive MS in a subset of patients. This model harmonises a plethora of prior evidence from diverse fields. It is suggested that future studies should challenge this new model for MS and that it provides direction for future approaches to prevention and therapy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"133"},"PeriodicalIF":3.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Iodinated contrast media (ICM)-induced thyroid dysfunction: a review of potential mechanisms and clinical management.","authors":"Yaxi Hu, Xia Zhong, Dan Peng, Lihong Zhao","doi":"10.1007/s10238-025-01664-5","DOIUrl":"https://doi.org/10.1007/s10238-025-01664-5","url":null,"abstract":"<p><p>Iodinated contrast media (ICM) are extensively utilized in medical imaging to enhance tissue contrast, yet their impact on thyroid function has attracted increasing attention in recent years. ICM can induce thyroid dysfunction, with reported prevalence ranging from 1 to 15% and a higher incidence observed in individuals with pre-existing thyroid conditions or other risk factors like age, gender, underlying health issues, and repeated ICM exposure. This review summarized the classification of ICM and the potential mechanisms, risk assessment, and clinical management of ICM-induced thyroid dysfunction, especially in vulnerable populations such as pregnant women and elderly patients. Despite advancements that have enriched our understanding of the pathophysiology and treatment of ICM-induced thyroid dysfunction, critical knowledge gaps remain, such as the long-term effects of ICM on thyroid function, the dose-response relationship between ICM volume and thyroid dysfunction risk, and the ecological impacts of ICM. Therefore, further exploration of the underlying mechanisms of ICM-induced thyroid dysfunction and optimization of the management strategies will be crucial for the safe and effective use of ICM in clinical practice, and collaborative efforts between clinicians and researchers are essential to ensure that the risks of thyroid dysfunction do not outweigh the benefits of imaging.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"132"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LingZhi Meng, JinXia Wang, Hui Yang, YiXuan Hu, ZongLi Yang
{"title":"Ultrasound-derived fat fraction to assess liver steatosis in obese patients with polycystic ovary syndrome.","authors":"LingZhi Meng, JinXia Wang, Hui Yang, YiXuan Hu, ZongLi Yang","doi":"10.1007/s10238-025-01635-w","DOIUrl":"https://doi.org/10.1007/s10238-025-01635-w","url":null,"abstract":"<p><p>This study aims to explore the characteristics and influencing factors of ultrasound-derived fat fraction (UDFF) in obese patients with polycystic ovary syndrome (PCOS). Evaluate the diagnostic value of UDFF for MAFLD. This study included 124 obese PCOS patients and 106 age- and body mass index (BMI)-matched obese women, collecting clinical data from both groups. Compare the characteristics and related factors of hepatic steatosis between two groups. A total of 124 obese PCOS patients were divided into MAFLD group (n = 64) and no MAFLD group (n = 60). Binary logistic regression was used to analyze the independent risk factors for MAFLD in obese PCOS patients, and Spearman correlation analysis was used to examine the correlation between UDFF and various variables. The MAFLD group was further divided into mild group (S1, n = 16), moderate group (S2, n = 24), and severe group (S3, n = 24). Based on the ultrasound results, draw a receiver operating characteristic curve (ROC) for diagnosing the degree of hepatic steatosis in obese PCOS patients using UDFF. MAFLD was more common in the obese PCOS group than in the simple obese group (51.61% vs. 40.57%, P < 0.05). UDFF is positively correlated with the severity of MAFLD (r = 0.603, P < 0.01). The AUC for diagnosing liver steatosis with S ≥ 1, S ≥ 2, and S = 3 using UDFF is 0.935, 0.951, and 0.916. UDFF has certain diagnostic value for metabolic-related fatty liver disease in obese PCOS patients, and UDFF levels gradually increase with the severity of MAFLD.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"130"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"m6A hypermethylation of TCF-1 regulated by METTL16 promotes acute myeloid leukemia.","authors":"Jingyi Li, Hui Kang","doi":"10.1007/s10238-025-01669-0","DOIUrl":"https://doi.org/10.1007/s10238-025-01669-0","url":null,"abstract":"<p><strong>Background: </strong>Methyltransferase 16 (METTL16) functions as an oncogene in various cancer, including leukemia. However, the role of METTL16 in acute myeloid leukemia (AML) is scarcely reported. The present study aimed to investigate the potential of METTL16 in AML.</p><p><strong>Methods: </strong>RT-qPCR was used to METTL16 expression in AML patients and healthy control. m6A levels was determined using m6A assay. Methylated RNA immunoprecipitation (MeRIP) assay applied for determining m6A hypermethylation of T cell factor 1 (TCF-1) transcripts in AML cells. Chimeric antigen receptor (CAR)-T-cell functions were analyzed using flow cytometry.</p><p><strong>Results: </strong>METTL16 is upregulated in AML patients. High levels of METTL16 were associated with poor prognosis of AML patients. Functionally, METTL16 deficiency promoted the persistence and tumor-killing ability of CAR-T cells. Moreover, METTL16 deficiency promoted the differentiation of CAR-T cells into TCF-1 precursor exhausted T cells (T<sub>PEX</sub>). METTL16 mediated the m6A modification of TCF-1 and inhibited its mRNA expression and stability. TCF-1 deficiency promoted the exhaustion and inhibited the self-renewal ability of T cells.</p><p><strong>Conclusion: </strong>Collectively, METTL16 deficiency promoted the persistence of CAR-T cells and memory formation in AML. Therefore, targeting METTL16 may stimulate the anti-tumor immunity in AML.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"129"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A comprehensive review of pathology and treatment of staphylococcus aureus osteomyelitis.","authors":"Muguo Song, Jian Sun, Kehan Lv, Junyi Li, Jian Shi, Yongqing Xu","doi":"10.1007/s10238-025-01595-1","DOIUrl":"https://doi.org/10.1007/s10238-025-01595-1","url":null,"abstract":"<p><p>Osteomyelitis (OM) is an inflammation of the bone and bone marrow triggered by infectious pathogens which may induce progressive bone destruction. The majority of OM cases, especially the chronic OM cases, are induced by the most prevalent and devastating pathogen Staphylococcus aureus (S. aureus), partially due to its resistance mechanisms against the immune system and antibiotic therapies. Regarding the high rate of morbidity and recurrence in patients, it is pivotal to elucidate underlying mechanisms that how S. aureus enter and survive in hosts. The accumulated discoveries have identified multiple distinct strategies associated with chronicity and recurrence include biofilm development, small colony variants (SCVs), staphylococcus abscess communities (SACs), the osteocyte lacuno-canalicular network invasion (OLCN) of cortical bones, and S. aureus protein A (SpA). Unfortunately, little clinical progress has been achieved for the diagnosis and therapeutic treatment for OM patients, indicating that numerous questions remain to be solved. Therefore, we still have a long way to obtain the clear elucidation of the host-pathogen interactions which could be applied for clinical treatment of OM. In this review, we provide insights of current knowledge about how S. aureus evades immune eradication and remains persistent in hosts with recent discoveries. The common and novel treatment strategies for OM are also described. The purpose of this review is to have in-dept understanding of S. aureus OM and bring new perspectives to therapeutic fields which may be translated to the clinic.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"131"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahdi Masrour, Aysan Moeinafshar, Amirhossein Poopak, Sepideh Razi, Nima Rezaei
{"title":"The role of CXC chemokines and receptors in breast cancer.","authors":"Mahdi Masrour, Aysan Moeinafshar, Amirhossein Poopak, Sepideh Razi, Nima Rezaei","doi":"10.1007/s10238-025-01662-7","DOIUrl":"https://doi.org/10.1007/s10238-025-01662-7","url":null,"abstract":"<p><p>CXC chemokines are a class of cytokines possessing chemotactic properties. Studies indicate that CXC chemokines exhibit dysregulation in miscellaneous cancer categories and are significantly associated with the advancement of tumors. Breast cancer is a commonly diagnosed and fatal cancer among the female population. Breast cancer pathogenesis and progression involve various mechanisms, including invasion, metastasis, angiogenesis, and inflammation. Chemokines and their receptors are involved in all of these processes. The CXC chemokine receptors (CXCRs) and their related ligands have attracted considerable attention due to their multifaceted functions in facilitating and controlling tumor proliferation. CXCRs are expressed by both cancer cells and immune cells, and they play a crucial role in regulating the tumor microenvironment and the immune response. This review aims to assess the potential of CXCRs and CXC chemokines as therapeutic targets or biomarkers for personalized therapy. Additionally, it provides an overview of the current understanding of the expression, function, and prognostic relevance of CXCRs in breast cancer. Furthermore, the challenges and potential prospects pertaining to CXCR investigation in breast cancer are deliberated.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"128"},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exosome-based immunotherapy in hepatocellular carcinoma.","authors":"Hong Liu, GuoWei Wang, ZhaoYi Li, XianTu Zhang, WeiDong Zhang, Xia Zhang, Fang Liu, Jing Gao","doi":"10.1007/s10238-025-01659-2","DOIUrl":"https://doi.org/10.1007/s10238-025-01659-2","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a significant global health concern and ranks as the third leading cause of cancer-associated mortality. Systemic therapy faces the emergence of resistance, which hinders the clinical benefits. Recent evidence suggests that exosomes, measuring between 30 and 150 nm in size, which impact the antitumor immune responses, making them a promising candidate for cancer immunotherapy. Owing to their unique physical and chemical characteristics, exosomes can be tailored and engineered for a range of therapeutic objectives. In the present review, we outline the immunomodulatory functions of exosomes in the tumor microenvironment (TME) of HCC, aiming to decipher the underlying mechanisms of exosomes in remodeling suppressive TME. Moreover, we provide detailed and intuitive resource for leveraging the potential of exosomes in immunotherapy, presenting valuable strategies to improve and optimize HCC treatment. Despite the huge therapeutic potential of exosomes, significant challenges persist, including the need for standardization in exosome production, optimization of cargo loading techniques, and the assurance of safety and effectiveness in clinical applications. Addressing these challenges may pave the way for exosome-based immunotherapy for HCC patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"127"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DOCK9 as a predictive biomarker linked to angiogenesis and immune response in esophageal squamous cell carcinoma.","authors":"Yaqiang Pan, Yangyong Sun, Ying Xiao, Jifei Ding, Ge Hu, Zhiqiang Lin, Chang Chen","doi":"10.1007/s10238-025-01653-8","DOIUrl":"https://doi.org/10.1007/s10238-025-01653-8","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) remains a serious health concern due to its high prevalence and mortality rates. Identifying prognostic biomarkers is essential to improving patient outcomes and treatment strategies. DOCK9, a gene implicated in various cellular functions, may play a significant role in ESCC progression and prognosis. We analyzed RNA microarray datasets and single-cell RNA sequencing data to identify survival-associated genes in ESCC. Using protein expression analysis, we examined DOCK9 in ESCC tissues and assessed its functional impact on human umbilical vein endothelial cells to understand its role in angiogenesis. Additionally, we developed a 21-gene prognostic risk model, focusing on the relevance of DOCK9. Our findings revealed that DOCK9 expression is significantly reduced in ESCC tissues and correlates with poor survival outcomes. Functionally, DOCK9 was found to regulate angiogenesis and modulate the tumor-associated fibroblast environment in ESCC. Furthermore, the DOCK9/CD31 ratio emerged as a potential marker to predict immune therapy response in ESCC. DOCK9 serves as a prognostic biomarker in ESCC, influencing both angiogenesis and immune response, and could guide future therapeutic strategies, particularly in immunotherapy. This study highlights DOCK9's relevance in ESCC prognosis, supporting its potential role in tailored therapies aimed at angiogenesis and immune modulation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"126"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Sun, Hui Cai, Xiaoyi Duan, Ya Yang, Min Li, Jingkun Qu, Xu Zhang, Jiansheng Wang
{"title":"Editorial Expression of Concern: Aberrant expression and potential therapeutic target of lysophosphatidic acid receptor 3 in triple-negative breast cancers.","authors":"Kai Sun, Hui Cai, Xiaoyi Duan, Ya Yang, Min Li, Jingkun Qu, Xu Zhang, Jiansheng Wang","doi":"10.1007/s10238-025-01656-5","DOIUrl":"https://doi.org/10.1007/s10238-025-01656-5","url":null,"abstract":"","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"123"},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}