Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, first approved CAR product, has demonstrated therapeutic potential treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach immune particularly solid highlighting feasibility using macrophages to eliminate pathogens abnormal cells.

Язык: Английский

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Artesunate: attenuating TLR4/MD2 signaling to alleviate cardiac fibrosis

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 30, 2025

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Deep-DPC: Deep learning-assisted label-free temporal imaging discovery of anti-fibrotic compounds by controlling cell morphology

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Fibrosis can damage the normal function of many organs, such as cardiac function, for which no effective clinical therapies exist. However, traditional approaches to anti-fibrosis drug discovery have primarily focused on final biological indicators, often overlooking dynamic morphological changes during fibrosis progression. Here, we present a novel approach, deep-DPC, integrates label-free, time-series digital phase contrast (DPC) imaging with cell morphology analysis and unsupervised machine learning dynamically control monitor morphology. This method enables discrimination between resting activated fibrocytes facilitates non-invasive labeled anti-fibrotic lead compounds. The deep-DPC comprises two major steps: (1) preliminary by Harmony 4.9 software (2) image classification via neural network. For experiment dataset, label-free was acquired from each well at 10 × magnification using high-content system, equipped high-speed charge-coupled device (CCD) camera. Dual-channel output images were generated through one channel bright-field other DPC imaging, captured 30-minute intervals Firstly, applying model case, developed combining deep learning, its stability verified training 12,000 images. Furthermore, Application in Using platform, over 100,000 1,400 compounds processed, identifying Neo-Przewaquinone A potent agent. exerts effects inhibiting TGF-β receptor I, thereby maintaining cells state arresting cycle. offers promising strategy assessment based Additionally, platform holds potential therapeutic approach anti-myocardial regulating

Язык: Английский

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From injury to repair: the therapeutic potential of induced pluripotent stem cells in heart failure

Regenerative medicine reports ., Год журнала: 2025, Номер 2(1), С. 22 - 30

Опубликована: Март 1, 2025

Heart failure is a complex clinical syndrome characterized by the heart’s inability to pump sufficient blood meet body’s metabolic demands, resulting in symptoms such as dyspnea, fatigue, and fluid retention. Despite significant advances pharmacological treatments device therapies, prognosis for patients with advanced heart remains poor. This underscores urgent need innovative regenerative therapies aimed at restoring cardiac function improving quality of life suffering from this debilitating condition. article provides comprehensive overview pathophysiologic mechanisms underlying end-stage failure, which include myocardial systolic diastolic dysfunction, neuroendocrine activation, inflammation, oxidative stress. Collectively, these lead progressive deterioration structure function, culminating failure. The also examines differences between ischemic non-ischemic cardiomyopathies their implications treatment strategies prognosis. Furthermore, review explores application medicine focusing on its potential repair functional recovery. In field medicine, induced pluripotent stem cells derived cardiomyocytes are considered cutting-edge technologies repair. Induced can differentiate into cardiomyocytes, thereby offering new hope regeneration. However, current research faces several challenges, including maturity integration immunogenicity concerns, difficulties scaling up production applications. Additionally, ethical issues related cell technology, sourcing tumorigenic risks, must be carefully addressed. highlights technology treating while emphasizing complexities involved transitioning laboratory practice.

Язык: Английский

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Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3038 - 3038

Опубликована: Март 26, 2025

Cardiovascular diseases (CVD), the leading cause of death worldwide, and their strong association with fibrosis highlight pressing need for innovative antifibrotic therapies. In vitro models have emerged as valuable tools replicating cardiac 'in a dish', facilitating study disease mechanisms serving platforms drug testing development. These in systems encompass 2D 3D models, each its own limitations advantages. offer high reproducibility, cost-effectiveness, high-throughput capabilities, but they oversimplify complex fibrotic environment. On other hand, provide greater biological relevance are more complex, harder to reproduce, less suited screening. The choice model depends on specific research question stage Despite significant progress, challenges remain, including integration immune cells optimizing scalability throughput highly biomimetic systems. Herein, we review recent focus shared characteristics remaining challenges, explore how organs could inspire novel approaches research, showcasing potential strategies that be adapted refine myocardial models.

Язык: Английский

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Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure

Circulation Research, Год журнала: 2025, Номер 136(7), С. 773 - 802

Опубликована: Март 27, 2025

Cardiac fibrosis, a hallmark of heart failure and various cardiomyopathies, represents complex pathological process that has long challenged therapeutic intervention. High-throughput omics technologies have begun revolutionizing our understanding the molecular mechanisms driving cardiac fibrosis are providing unprecedented insights into its heterogeneity progression. This review provides comprehensive analysis how techniques—encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics—are insight fibrosis. Genomic studies identified novel genetic variants regulatory networks associated with susceptibility progression, single-cell transcriptomics unveiled distinct fibroblast subpopulations unique signatures. Epigenomic profiling revealed dynamic chromatin modifications controlling activation states, proteomic analyses biomarkers potential targets. Metabolomic uncovered important alterations in energetics substrate utilization during fibrotic remodeling. The integration these multi-omic data sets led to identification previously unrecognized pathogenic targets, including cell-type-specific interventions metabolic modulators. We discuss advances development precision medicine approaches for while highlighting current challenges future directions translating effective strategies. systems-level perspective on may inform more effective, personalized related cardiovascular diseases.

Язык: Английский

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Paeonol Suppresses Bladder Cancer Progression via Apoptotic Pathways: Insights from In Vitro and In Vivo Studies

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 472 - 472

Опубликована: Март 27, 2025

Background/Objectives: Bladder cancer (BC), a highly heterogeneous and mutation-prone malignancy, remains significant therapeutic challenge due to its propensity for recurrence, metastasis, drug resistance. Natural products, particularly paeonol, bioactive compound derived from Moutan Cortex in traditional Chinese medicine, have shown promising potential therapy. This study aims evaluate the anti-BC effects of paeonol elucidate underlying molecular mechanisms. Methods: In vitro experiments were conducted using T24 J82 BC cell lines assess paeonol’s on viability, migration, apoptosis, cycle progression via CCK-8, scratch, flow cytometry, RT-qPCR, Western blot analyses. vivo efficacy was evaluated xenograft mouse model, with tumor growth monitored histopathological analysis performed. Results: Paeonol significantly inhibited proliferation migration dose- time-dependent manner, IC50 values 225 μg/mL (T24) 124 (J82) at 48 h. It induced apoptosis arrested G1 phase, accompanied by upregulation pro-apoptotic proteins (BID, BAX, BIM, p53). vivo, reduced volume weight without abnormalities vital organs. Conclusions: exhibits potent activity apoptotic pathways arresting phase inhibiting growth. Its favorable safety profile multi-target mechanisms highlight as candidate BC. These findings provide foundation further clinical development paeonol-based therapies.

Язык: Английский

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Diverse potential of chimeric antigen receptor‐engineered cell therapy: Beyond cancer

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(4)

Опубликована: Апрель 1, 2025

Язык: Английский

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Antimalarial drug hits cardiac fibrosis

Nature Reviews Drug Discovery, Год журнала: 2024, Номер 23(12), С. 893 - 893

Опубликована: Ноя. 5, 2024

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State of the ART: Drug Screening Reveals Artesunate as a Promising Anti-Fibrosis Therapy

Deleted Journal, Год журнала: 2024, Номер 2(1), С. 10023 - 10023

Опубликована: Дек. 16, 2024

Fibrosis is a progressive pathological process that severely impairs normal organ function. Current treatments for fibrosis are extremely limited, with no curative approaches available. In recent article published in Cell, Zhang and colleagues employed drug screening using ACTA2 reporter iPSC-derived cardiac fibroblasts identified artesunate as potent antifibrotic by targeting MD2/TLR4 signaling. This study provides new insights into strategies exploiting existing drugs to treat fibrosis.

Язык: Английский

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