Peripheral CD3+CD4+ T cells as indicators of disease activity in thyroid eye disease: age-dependent significance.

PURPOSE: To provide an in-depth analysis of the association of peripheral lymphocytes and the disease activity of thyroid eye disease (TED). METHODS: This retrospective study enrolled 65 active TED patients and 46 inactive TED patients. Comparative analyses of peripheral lymphocyte subsets were conducted between active and inactive patients. Subgroup analyses were performed based on sex, age, disease duration, and severity. Correlation analyses explored the associations between lymphocyte subsets and TED activity indicators. Prediction models for TED activity were established using objective indicators. RESULTS: Significantly elevated levels of CD3+CD4+ T cells were observed in active TED patients compared to inactive patients (P = 0.010). Subgroup analyses further revealed that this disparity was most prominent in females (P = 0.036), patients aged 50 years and younger (P = 0.003), those with long-term disease duration (P = 0.022), and individuals with moderate-to-severe disease (P = 0.021), with age exerting the most substantial impact. Subsequent correlation analysis confirmed the positive association between CD3+CD4+ T cells and the magnetic resonance imaging indicator of TED activity among patients aged 50 years and younger (P = 0.038). The combined prediction models for TED activity, established using objective indicators including CD3+CD4+ T cells, yielded areas under curve of 0.786 for all patients and 0.816 for patients aged 50 years and younger. CONCLUSIONS: Peripheral CD3+CD4+ T cells are associated with disease activity of TED, especially in patients aged 50 years and younger. Our study has deepened the understanding of the peripheral T cell profiles in TED patients.

Development and application of animal models to study thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO), also known as Graves' ophthalmopathy, is an autoimmune disease that is usually accompanied by hyperthyroidism. Its pathogenesis involves the activation of autoimmune T lymphocytes by a cross-antigen reaction of thyroid and orbital tissues. The thyroid-stimulating hormone receptor (TSHR) is known to play an important role in the development of TAO. Because of the difficulty of orbital tissue biopsy, the establishment of an ideal animal model is important for developing novel clinical therapies of TAO. To date, TAO animal modeling methods are mainly based on inducing experimental animals to produce anti-thyroid-stimulating hormone receptor antibodies (TRAbs) and then recruit autoimmune T lymphocytes. Currently, the most common methods are hTSHR-A subunit plasmid electroporation and hTSHR-A subunit adenovirus transfection. These animal models provide a powerful tool for exploring the internal relationship between local and systemic immune microenvironment disorders of the TAO orbit, facilitating the development of new drugs. However, existing TAO modeling methods still have some defects, such as low modeling rate, long modeling cycles, low repetition rate, and considerable differences from human histology. Hence, the modeling methods require further innovation, improvement, and in-depth exploration.

Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis.

Osteoarthritis (OA) is a highly prevalent whole-joint disease that causes disability and pain and affects a patient's quality of life. However, currently, there is a lack of effective early diagnosis and treatment. Although stem cells can promote cartilage repair and treat OA, problems such as immune rejection and tumorigenicity persist. Extracellular vesicles (EVs) can transmit genetic information from donor cells and mediate intercellular communication, which is considered a functional paracrine factor of stem cells. Increasing evidences suggest that EVs may play an essential and complex role in the pathogenesis, diagnosis, and treatment of OA. Here, we introduced the role of EVs in OA progression by influencing inflammation, metabolism, and aging. Next, we discussed EVs from the blood, synovial fluid, and joint-related cells for diagnosis. Moreover, we outlined the potential of modified and unmodified EVs and their combination with biomaterials for OA therapy. Finally, we discuss the deficiencies and put forward the prospects and challenges related to the application of EVs in the field of OA.

Immune modulating nanoparticles for the treatment of ocular diseases.

Ocular diseases are increasingly influencing people's quality of life. Complicated inflammatory mechanisms involved in the pathogenic process of ocular diseases make inflammation-targeting treatment a potential therapeutic approach. The limited efficacy of conventional anti-inflammatory therapeutic strategies, caused by various objective factors, such as complex ocular biological barriers, and subjective factors, such as poor compliance, are promoting the development of new therapeutic methods. With the advantages of considerable tissue permeability, a controllable drug release rate, and selective tissue targeting ability, nanoparticles have successfully captured researchers' attention and have become a research hotspot in treating ocular diseases. This review will focus on the advantages of nanosystems over traditional therapy, the anti-inflammation mechanisms of nanoparticles, and the anti-inflammatory applications of nanoparticles in different ocular diseases (ocular surface diseases, vitreoretinopathy, uveal diseases, glaucoma, and visual pathway diseases). Furthermore, by analyzing the current situation of nanotherapy and the challenges encountered, we hope to inspire new ideas and incentives for designing nanoparticles more consistent with human physiological characteristics to make progress based on conventional treatments. Overall, some progress has been made in nanoparticles for the treatment of ocular diseases, and nanoparticles have rather broad future clinical translation prospects. Graphical abstract.