Yaohang Yue

Osteoarthritis (OA) is a degenerative disease linked to aging and obesity. The global aging population has led to an increasing number of OA patients, imposing a significant economic burden on society. Traditional drugs treatment methods often fail to achieve satisfactory outcomes. With the rapid advancement of nanomaterial delivery systems, numerous studies have focused on utilizing nanomaterials as carriers to achieve efficient OA treatment by effectively loading and delivering bioactive ingredients (e.g., drugs, nucleic acids) tailored to the unique pathological conditions, such as the weakly acidic microenvironment of synovial fluid in OA patients. This review highlights the latest advancements in the use of pH-responsive nanoparticles for OA treatment, emphasizing the principle of targeted drug delivery leveraging the acidic microenvironment of inflamed joints. It further discusses the composition, synthesis, response mechanism, target selection, application, and recent research findings of nanoparticles, while also addressing the challenges and future directions in this promising field.

UNLABELLED: BACKGROUND; Heavy ions represent the best tool for external radiotherapy (RT) of inoperable tumours. Heavy ion RT has been used in the treatment of various tumours, especially for radioresistant tumours mediated by hypoxia, localized near organs at risk. Most of these treatments are concentrated in deep-seated tumours such as those of the brain, head, lung, liver, rectum and urogenital organs, and treatment of skin carcinomas is limited. OBJECTIVES: To evaluate the outcome and toxicity after carbon ion RT for skin carcinomas at the Heavy Ion Research Facility in Lanzhou, China. METHODS: Between November 2006 and March 2009, 45 patients with skin carcinoma [squamous cell carcinoma (SCC) (n = 16), basal cell carcinoma (BCC) (n = 12), malignant melanoma (MM) (n = 7), Bowen disease (n = 8) and Paget disease (n = 2)] were treated with carbon ion RT within a clinical Phase I trial. Patients received total doses of 60-70 GyE for SCC and BCC, 61-75 GyE for MM, 60 GyE for Bowen disease and 42·5 GyE for Paget disease, administered in 6-11 fractions over 6-11 days, with a fraction dose of 7-10 GyE. RESULTS: The mean follow-up was 24 months, range 12-36 months. The actuarial local control rates at 1 and 3 years were 90·9% and 65·5% for SCC, 91·7% and 80·2% for BCC, 85·7% and 42·9% for MM, 90% and 90% for Bowen and Paget diseases, respectively. The actuarial 1- and 3-year overall survival rates for 45 patients were 88·9% and 86%, respectively. No severe side-effects greater than Common Toxicity Criteria grade 3 have been observed. CONCLUSIONS: The results demonstrated that heavy ion RT offers high local tumour control and progression-free survival rates without significant radiation-induced toxicity for patients with skin carcinomas.

Discovering an inhibitor for acyl-CoA synthetase long-chain family member 4 (ACSL4), a protein that triggers cell injury via ferroptosis, presents potential to minimize cellular damage. This study investigates paeonol (PAE), a traditional Chinese herbal medicine, as an ACSL4 inhibitor to prevent chondrocyte ferroptosis and protect against osteoarthritis (OA). We conducted in vitro experiments using mouse chondrocytes treated with PAE to mitigate ferroptosis induced by Interleukin-1 Beta (IL-1β) or ferric ammonium citrate (FAC), examining intracellular ferroptotic indicators, cartilage catabolic markers, and ferroptosis regulatory proteins. A mouse OA model was created via destabilized medial meniscus (DMM), followed by intra-articular PAE injections. After 8 weeks, micro-computed tomography and histological assessments evaluated PAE's protective and anti-ferroptotic effects in the OA model. In vitro results showed PAE significantly reduced IL-1β/FAC-induced damage by targeting ACSL4, including cell apoptosis, inflammatory responses, extracellular matrix degradation, and ferroptotic markers (oxidative stress, lipid peroxidation, and iron buildup). It also restored the expression of ferroptotic suppressors and mitigated mitochondrial damage. Additionally, PAE increased cartilage anabolic marker expression while reducing cartilage catabolic marker expression. Molecular docking, cellular thermal shift assay, and drug affinity responsive target stability analysis verified the binding interaction between PAE and ACSL4. Furthermore, the role of PAE in chondrocytes was further verified through ACSL4 knockdown and overexpression. In vivo , mice with OA showed increased cartilage degradation and ferroptosis, while intra-articular PAE injection alleviated these pathological changes. PAE significantly protects chondrocytes from ferroptosis induced by IL-1β/FAC in primary mouse chondrocytes and DMM surgery-induced OA mice through ACSL4 inhibition. These findings highlight the potential of targeting ACSL4 in chondrocytes as a treatment strategy for OA, positioning PAE as a promising drug candidate.