Therapeutic Effects of PEG-Modified Polyamide Amine Dendrimer for Cell Free DNA Adsorption in Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by the degeneration of cartilage and subchondral bone. In this study, we observed a significant increase in cell-free DNA (cfDNA) levels during the progression of TMJ OA. Bioinformatics analysis identified TLR9 as a pivotal molecule in TMJ OA pathogenesis. The polyamidoamine (PAMAM) dendrimer characterized by a well-structured, highly branched, and reactive nature, exhibits robust binding and clearance capabilities for cfDNA. However, the abundant amino groups on the surface of PAMAM lead to its inherent toxicity. To mitigate this, PEG-5000 was conjugated to the surface of PAMAM dendrimers, enhancing safety. Our results indicate that PEG-PAMAM effectively inhibits the upregulation of the TLR9 protein in TMJ OA, significantly suppressing the activation of the p-IκBα/p-NF-κB signaling pathway and subsequently decreasing chondrocyte inflammation and apoptosis, as evidenced by both in vivo and in vitro experiments. We conclude that PEG-PAMAM is a safe and effective material for in vivo applications, offering a promising therapeutic strategy for TMJ OA by targeting cfDNA clearance.

Advancements in neoadjuvant immune checkpoint inhibitor therapy for locally advanced head and neck squamous Carcinoma: A narrative review.

The prevalent treatment paradigm for locally advanced head and neck squamous carcinoma (HNSCC) typically entails surgery followed by adjuvant radiotherapy and chemotherapy. Despite this, a significant proportion of patients experience recurrence and metastasis. Immune checkpoint inhibitors (ICIs), notably pembrolizumab and nivolumab, have been established as the first and second lines of treatment for recurrent and metastatic HNSCC (R/M HNSCC). The application of ICIs as neoadjuvant immunotherapy in this context is currently under rigorous investigation. This review synthesizes data from clinical trials focusing on neoadjuvant ICIs, highlighting that the pathological responses elicited by these treatments are promising. Furthermore, it is noted that the safety profiles of both monotherapy and combination therapies with ICIs are manageable, with no new safety signals identified. The review concludes by contemplating the future direction and challenges associated with neoadjuvant ICI therapy, encompassing aspects such as the refinement of imaging and pathological response criteria, selection criteria for adjuvant therapies, evaluation of the efficacy and safety of various combination treatment modalities, and the identification of responsive patient cohorts.