Biomedicines最新文献

{"title":"Early Renal Dysfunction and Reduced Retinal Vascular Density Assessed by Angio-OCT in Hypertensive Patients.","authors":"Caterina Carollo, Maria Vadalà, Alessandra Sorce, Emanuele Cirafici, Miriam Bennici, Massimo Castellucci, Vincenza Maria Elena Bonfiglio, Giuseppe Mulè, Giulio Geraci","doi":"10.3390/biomedicines13051176","DOIUrl":"10.3390/biomedicines13051176","url":null,"abstract":"<p><p><b>Background:</b> The eye and kidney share embryological, structural, and pathophysiological similarities, suggesting potential interconnections between retinal and renal microvascular changes. Hypertension, a major risk factor for renal impairment, also affects retinal microvasculature. This study investigates the relationship between retinal vascular density, assessed by Optical Coherence Tomography Angiography (OCT-A), and early renal dysfunction in hypertensive patients. <b>Methods:</b> A total of 142 hypertensive patients (mean age 47 ± 13 years; 74% male) were enrolled from the Nephrology and Hypertension Unit at the University of Palermo. Retinal vascular density was measured using OCT-A, and renal function was assessed using estimated glomerular filtration rate (eGFR). Clinical and hemodynamic parameters, including 24-h aortic blood pressure, were also analyzed. <b>Results</b>: Patients with eGFR < 60 mL/min/1.73 m² exhibited significantly lower retinal vascular densities, particularly in the parafoveal region. Superficial parafoveal density was inversely associated with aortic pulse pressure (<i>p</i> = 0.012) and directly correlated with eGFR (<i>p</i> = 0.012). Deep parafoveal density was independently associated with eGFR (<i>p</i> = 0.001). Multiple linear regression confirmed that lower retinal vascular density was significantly linked to reduced renal function, independent of age and blood pressure. <b>Conclusions:</b> Retinal vascular density, particularly in the parafoveal region, is associated with renal function decline in hypertensive patients. These findings suggest that retinal microvascular changes could serve as a non-invasive biomarker for kidney dysfunction, with potential applications in early risk stratification and disease monitoring. Further research is needed to establish causality and clinical utility.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Epigenetic Therapies for the Treatment of Cardiac Fibrosis.","authors":"Nerea Garitano, Laura Pilar Aguado-Alvaro, Beatriz Pelacho","doi":"10.3390/biomedicines13051170","DOIUrl":"10.3390/biomedicines13051170","url":null,"abstract":"<p><p>Fibrosis is a pathological process characterized by excessive extracellular matrix (ECM) deposition, leading to tissue stiffening and organ dysfunction. It is a major contributor to chronic diseases affecting various organs, with limited therapeutic options available. Among the different forms of fibrosis, cardiac fibrosis is particularly relevant due to its impact on cardiovascular diseases (CVDs), which remain the leading cause of morbidity and mortality worldwide. This process is driven by activated cardiac fibroblasts (CFs), which promote ECM accumulation in response to chronic stressors. Epigenetic mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, are key regulators of fibroblast activation and fibrotic gene expression. Enzymes such as DNA methyltransferases (DNMTs), histone methyltransferases (HMTs), histone acetyltransferases (HATs), and histone deacetylases (HDACs) have emerged as potential therapeutic targets, and epigenetic inhibitors have shown promise in modulating these enzymes to attenuate fibrosis by controlling fibroblast function and ECM deposition. These small-molecule compounds offer advantages such as reversibility and precise temporal control, making them attractive candidates for therapeutic intervention. This review aims to provide a comprehensive overview of the mechanisms by which epigenetic regulators influence cardiac fibrosis and examines the latest advances in preclinical epigenetic therapies. By integrating recent data from functional studies, single-cell profiling, and drug development, it highlights key molecular targets, emerging therapeutic strategies, and current limitations, offering a critical framework to guide future research and clinical translation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Umbilical Cord MSC-Derived Exosomes in a Severe Dry Eye Rat Model: Enhancing Corneal Protection and Modulating Inflammation.","authors":"Sze-Min Chan, Chris Tsai, Tai-Ping Lee, Zih-Rou Huang, Wei-Hsiang Huang, Chung-Tien Lin","doi":"10.3390/biomedicines13051174","DOIUrl":"10.3390/biomedicines13051174","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with immunomodulatory and regenerative properties. This study investigates the therapeutic effects of umbilical cord MSC-derived exosomes (UCMSC-exos) in a severe dry eye model, induced by a surgical resection of the infra-orbital (ILG) and extra-orbital lacrimal gland (ELG) in rats. <b>Methods</b>: Clinical evaluations, including tear volume measurement, slit lamp biomicroscopy, fluorescein staining, and spectral domain optical coherence tomography (SD-OCT), were performed to assess corneal neovascularization, corneal abrasion, and epithelial/stromal thickness. Histopathological analysis, immunohistochemistry, and mRNA gene expression were conducted to evaluate corneal tissue changes and inflammatory marker expression. <b>Results</b>: The results show that the treatment group exhibited significantly reduced corneal neovascularization compared to the control group (<i>p</i> = 0.030). During the first month, the Exo group also had a significantly lower corneal fluorescein staining area (<i>p</i> = 0.032), suggesting accelerated wound healing. SD-OCT analysis revealed that the corneal epithelial thickness in the treatment group was closer to normal levels compared to the control group (<i>p</i> = 0.02 and <i>p</i> = 0.006, respectively). UCMSC-exos treatment also modulated the expression of α-SMA and apoptosis in the cornea. Additionally, the gene expression of inflammatory cytokines (IL-1β and TNF-α) were downregulated. <b>Conclusions</b>: These findings suggest that MSC-exosome therapy offers a novel, cell-free regenerative approach for managing severe DED, modulating inflammatory response.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-Occurrence of <i>Helicobacter pylori</i> and <i>Candida</i> spp. Infections in the Pathogenesis of Gastrointestinal Diseases.","authors":"Joanna Braksator, Anna Kofla-Dłubacz, Katarzyna Antosz-Popiołek, Hubert Szyller, Joanna Koga-Batko, Martyna Wrześniewska, Maciej Dyda, Tomasz Pytrus","doi":"10.3390/biomedicines13051172","DOIUrl":"10.3390/biomedicines13051172","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> and <i>Candida</i> spp. are widespread microorganisms found in the human gastrointestinal tract, often coexisting in the same ecological niche. <i>H. pylori</i>, a Gram-negative bacterium, is a well-known pathogen responsible for gastritis, peptic ulcers, and gastric cancer. In contrast, <i>Candida</i> fungi, often detected in food, particularly <i>Candida albicans</i>, are generally considered commensal organisms, but can become opportunistic pathogens under certain conditions. Recent studies suggest a possible link between these microorganisms, highlighting a new survival strategy of <i>H. pylori</i>, that is, its ability to internalize in <i>Candida</i> vacuoles. This phenomenon, confirmed by various microscopic and molecular techniques, may provide <i>H. pylori</i> with protection against adverse environmental conditions, especially clinically important antibiotic therapy. The basic premise of this theory is the ability of <i>H. pylori</i> to penetrate vacuoles in fungal cells, which then become a reservoir of infection, allowing the infection to recur. Understanding the interaction between <i>H. pylori</i> and <i>Candida</i> may offer new insights into the pathogenesis of gastrointestinal diseases and may lead to the development of treatments targeting both organisms simultaneously. The purpose of this article is to review the literature, considering the first observations on this problem in the literature and the current state of knowledge, and to suggest a direction for further research.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of First-Line Pembrolizumab Monotherapy in Metastatic NSCLC with High PD-L1 Expression (TPS ≥ 50%): A Multicenter Study from Serbia.","authors":"Filip Marković, Mihailo Stjepanović, Milan Rančić, Marina Cekić, Milica Kontić","doi":"10.3390/biomedicines13051175","DOIUrl":"10.3390/biomedicines13051175","url":null,"abstract":"<p><p><b>Background:</b> Pembrolizumab monotherapy is the standard first-line treatment for metastatic non-small cell lung cancer (NSCLC) patients whose tumors express a PD-L1 tumor proportion score (TPS) of ≥50%. However, real-world data regarding its effectiveness outside of clinical trials, particularly in Eastern European populations, are limited. <b>Methods:</b> We conducted a retrospective, multicenter study including 225 patients with metastatic NSCLC and PD-L1 TPS ≥ 50% who received first-line pembrolizumab monotherapy in Serbia between 2019 and 2022. Patient demographics, clinical characteristics, and treatment outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards regression was performed to identify predictors of outcomes. <b>Results:</b> The median PFS was 9.7 months (95% CI: 7.979-11.421), and the median OS was 17.0 months (95% CI: 12.813-20.187) at a median follow-up of 18.1 months. The overall response rate (ORR) was 36.4%, and the disease control rate (DCR) was 73.4%. Multivariable analysis identified good performance status (ECOG PS 0-1), PD-L1 TPS ≥ 90%, and the occurrence of immune-related adverse events (irAEs) as independent predictors of improved PFS and OS. <b>Conclusions:</b> Our study highlights the efficacy and safety of first-line pembrolizumab monotherapy in a real-world Serbian population with metastatic NSCLC and high PD-L1 expression. Furthermore, it confirms the prognostic value of ECOG PS, high PD-L1 expression, and the development of irAEs in predicting favorable clinical outcomes.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular Nucleic Acids Act as an Oncogenic MicroRNA Sponge to Inhibit Hepatocellular Carcinoma Progression.","authors":"Qianyi Zhang, Pengcheng Sun, Guang Hu, Xuanyao Yu, Wen Zhang, Xuan Feng, Lan Yu, Pengfei Zhang","doi":"10.3390/biomedicines13051171","DOIUrl":"10.3390/biomedicines13051171","url":null,"abstract":"<p><p><b>Background:</b> Aberrant expression of microRNAs in neoplastic lesions may serve as potential personalized therapeutic targets. To inhibit oncogenic microRNAs (oncomiRs) expression and restore tumor suppressor proteins, linear miRNA sponges have been developed, leading to several drugs in clinical trials. Despite their efficacy, chemically synthesized miRNA inhibitors face challenges with sustained inhibition and high production costs, hindering widespread clinical adoption. Additionally, single-stranded circular RNAs (circRNAs) act as miRNA sponges, enhancing protein expression and demonstrating stability and therapeutic potential in cancer treatment. Our approach involves the use of synthetic single-stranded circular nucleic acids, including circDNA and circRNA, to selectively target and inhibit a variety of aberrantly overexpressed oncomiRs in tumors. The objective of this strategy is to restore the expression levels of multiple tumor suppressor factors and to suppress the malignant progression of tumors. <b>Methods:</b> Our methodology comprises a two-step process. First, we identified tumor suppressor genes (TSGs) with abnormally low expression in hepatocellular carcinoma (HCC) tumor cells by transcriptomic analysis and targeted the upstream cancer miRNA clusters of these TSGs. Second, we designed and validated a fully complementary circDNA or circRNA construct, ligated by T4 DNA ligase or T4 RNA ligase, respectively, that specifically targets the sponge oncomiRs both in vitro and in vivo to inhibit the malignant progression of HCC. <b>Results:</b> CircNAs demonstrated superior, long-lasting therapeutic efficacy against HCC compared to inhibitors. Furthermore, we compared the immune effects in vivo of three different nucleic acid adsorption carriers, including commercial miRNA inhibitor, circDNA, and circRNA. We found that the miRNA inhibitor activates a more robust inflammatory response compared to circDNA and circRNA. <b>Conclusions:</b> These findings underscore the substantial therapeutic potential of circDNA in tumorigenesis and provide novel insights for the formulation of personalized treatment plans for malignant tumors, such as HCC.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Tregs in the Tumor Microenvironment.","authors":"Yohei Sato","doi":"10.3390/biomedicines13051173","DOIUrl":"10.3390/biomedicines13051173","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a unique ecosystem that surrounds tumor tissues. The TME is composed of extracellular matrix, immune cells, blood vessels, stromal cells, and fibroblasts. These environments enhance cancer development, progression, and metastasis. Recent success in immune checkpoint blockade also supports the importance of the TME and immune cells residing in the tumor niche. Although the TME can be identified in almost all cancer types, the role of the TME may not be similar among different cancer types. Regulatory T cells (Tregs) play a pivotal role in immune homeostasis and are frequently found in the TME. Owing to their suppressive function, Tregs are often considered unfavorable factors that allow the immune escape of cancer cells. However, the presence of Tregs is not always linked to an unfavorable phenotype, which can be explained by the heterogeneity and plasticity of Tregs. In this review, the current understanding of the role of Tregs in TME is addressed for each cancer cell type. Moreover, recently a therapeutic approach targeting Tregs infiltrating in the TME has been developed including drug antibody conjugate, immunotoxin, and FOXP3 inhibiting peptide. Thus, understanding the role of Tregs in the TME may lead to the development of novel therapies that directly target the TME.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Immunological and Inflammation Proteomic Changes in Elderly COVID-19 Patients Predict Severe Disease Progression.","authors":"Shiyang Liu, Wen Xu, Bo Tu, Zhiqing Xiao, Xue Li, Lei Huang, Xin Yuan, Juanjuan Zhou, Xinxin Yang, Junlian Yang, De Chang, Weiwei Chen, Fu-Sheng Wang","doi":"10.3390/biomedicines13051162","DOIUrl":"10.3390/biomedicines13051162","url":null,"abstract":"<p><p><b>Background:</b> Elderly patients infected with SARS-CoV-2 are at higher risk of developing cytokine storm and severe outcomes; however, specific immunological and proteomic biomarkers for early prediction remain unclear in this vulnerable group. <b>Methods:</b> We enrolled 182 elderly COVID-19 patients from the Chinese PLA General Hospital between November 2022 and April 2023, categorizing them based on progression to respiratory failure requiring mechanical ventilation (defined as severe progression). Olink proteomic analysis was performed on admission serum from 40 propensity score-matched samples, with differentially expressed proteins (DEPs) validated by cytometric bead array (CBA) in 178 patients. To predict severe progression, a model was developed using a 70% training set and validated on a 30% validation set. LASSO regression screened features followed by logistic regression and receiver operating characteristic (ROC) analysis to optimize the model by incrementally incorporating features ranked by random forest importance. <b>Results:</b> Elderly patients progressing to severe COVID-19 exhibited early immune dysregulation, including neutrophilia, lymphopenia, monocytopenia, elevated procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as coagulation dysfunction and multi-organ injury. Proteomics identified a set of biomarkers, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and revealed disruptions in signaling pathways, including the mTOR and VEGF signaling pathways. The optimal predictive model, which incorporated PCT, IL-6, monocyte percentage, lymphocyte count, and TRAIL, achieved an area under curve (AUC) of 0.870 (0.729-1.000) during validation. TRAIL levels negatively correlated with fibrinogen (<i>p</i> < 0.05). <b>Conclusions:</b> Elderly COVID-19 patients with severe progression demonstrate early immune dysregulation, hyperinflammation, coagulation dysfunction, and multi-organ injury. The model we proposed effectively predicts disease progression in elderly COVID-19 patients, providing potential biomarkers for early clinical risk stratification in this vulnerable population.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies for Anticancer Treatment in p53-Mutated Head and Neck Squamous Cell Carcinoma.","authors":"Bi-He Cai, Chia-Chi Chen, Yu-Te Sung, Yu-Chen Shih, Ching-Feng Lien","doi":"10.3390/biomedicines13051165","DOIUrl":"10.3390/biomedicines13051165","url":null,"abstract":"<p><p>This Opinion summarizes the strategies for anticancer treatment in p53-mutated head and neck squamous cell carcinoma (HNSCC). It examines six strategies for anticancer treatment in p53-mutated HNSCC: 1. direct reactivation of mutated p53; 2. activation of p63; 3. activation of p73; 4. degradation of mutated p53; 5. blocking the p53-regulated oncogenic microRNA; and 6. blocking the p53-regulated oncogenic long non-coding RNA. Since HNSCC has a high p53 mutation rate compared to other types of cancers, these strategies for combating p53-mutated HNSCC may prove useful for generating new ideas or methods for developing treatments for other cancers with p53 mutations. This article also explores other factors that may impact the effectiveness of anticancer therapies in p53-mutated HNSCC.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engagement of CD300c by a Novel Monoclonal Antibody Ameliorates Behavioral Deficits in a 5xFAD Mouse Model of Alzheimer's Disease.","authors":"Suin Lee, Chang Ki Lim, Jongyeob Kim, Joon Kim, Hee Kyung Jin, Jae-Sung Bae, Jae-Won Jeon","doi":"10.3390/biomedicines13051169","DOIUrl":"10.3390/biomedicines13051169","url":null,"abstract":"<p><p><b>Background</b>: Current treatment modalities for Alzheimer's disease (AD), which is characterized by the accumulation of amyloid β (Aβ), have limitations with regard to their efficacy and safety, posing significant challenges for advances in healthcare. However, recent studies indicated that AD can be treated using monocyte-derived macrophages (MDMs). Reportedly, the protein CD300c regulates monocyte differentiation, indicating that targeting CD300c could offer a treatment for AD. <b>Methods</b>: To confirm this, we developed CB201, a fully human anti-CD300c antibody, and demonstrated its strong and specific binding to CD300c using surface plasmon resonance and binding ELISAs. <b>Results</b>: Treatment of THP-1 and human peripheral blood mononuclear cells with CB201 led to increased levels of pro-inflammatory cytokines and the differentiation of macrophages to MDMs. Moreover, the CB201-differentiated macrophages expressed cytokines and chemokines in a pattern that alleviates AD symptoms. In a 5xFAD mouse model, CB201 treatment improved memory and behavior in both the early and late stages of AD and reduced cerebral Aβ plaque load. <b>Conclusions</b>: These results indicate that CB201 promotes the differentiation of macrophages to MDMs and modulates AD-related inflammatory responses, thereby ameliorating the pathological features of AD. These findings identify CD300c as a potential therapeutic target for AD and indicate that CB201 is a promising candidate for its treatment.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}