Xiangyu Chu

Diabetic wounds are characterized by drug-resistant bacterial infections, biofilm formation, impaired angiogenesis and perfusion, and oxidative damage to the microenvironment. Given their complex nature, diabetic wounds remain a major challenge in clinical practice. Reactive oxygen species (ROS), which have been shown to trigger hyperinflammation and excessive cellular apoptosis, play a pivotal role in the pathogenesis of diabetic wounds. ROS-scavenging nanosystems have recently emerged as smart and multifunctional nanomedicines with broad synergistic applicability. The documented anti-inflammatory and pro-angiogenic ability of ROS-scavenging treatments predestines these nanosystems as promising options for the treatment of diabetic wounds. Yet, in this context, the therapeutic applicability and efficacy of ROS-scavenging nanosystems remain to be elucidated. Herein, the role of ROS in diabetic wounds is deciphered, and the properties and strengths of nanosystems with ROS-scavenging capacity for the treatment of diabetic wounds are summarized. In addition, the current challenges of such nanosystems and their potential future directions are discussed through a clinical-translational lens.

Abstract Diabetic foot ulcer (DFU) is one of the most common complications of diabetes, bringing physical and mental challenges for patients due to the lack of efficient curative therapy. Despite considerable advances in pharmacological and surgical approaches, clinical trials for DFU patients remain disappointing due to the local overactive and excessive inflammation. Immunomodulatory hydrogels has significant advantages to overcome the clinical challenge of DFUs therapy. Here, recent fabrication and regenerative advances in the utilization of functional hydrogels for altering the immune microenvironment of DFUs are comprehensively reviewed. The pathological features and the healing processes of DFUs, followed by summarizing the physicochemical properties essential for the design of regenerative hydrogels for immunomodulation in DFUs, are briefly introduced. Then, the potential immuno‐therapeutic modalities of hydrogels and emerging trends used to treat DFUs via multitherapeutic approaches and enhanced efficacy and safety are discussed. Taken together, by linking the structural properties of hydrogels to their functions in DFU therapy with a particular focus on immunomodulatory stimuli, this review can promote further advances in designing advanced hydrogels for DFUs, resulting in improved diabetic wound repair through translation into clinical setting in the near future.

Metabolic reprogramming provides tumors with an energy source and biofuel to support their survival in the malignant microenvironment. Extensive research into the intrinsic oncogenic mechanisms of the tumor microenvironment (TME) has established that cancer-associated fibroblast (CAFs) and metabolic reprogramming regulates tumor progression through numerous biological activities, including tumor immunosuppression, chronic inflammation, and ecological niche remodeling. Specifically, immunosuppressive TME formation is promoted and mediators released via CAFs and multiple immune cells that collectively support chronic inflammation, thereby inducing pre-metastatic ecological niche formation, and ultimately driving a vicious cycle of tumor proliferation and metastasis. This review comprehensively explores the process of CAFs and metabolic regulation of the dynamic evolution of tumor-adapted TME, with particular focus on the mechanisms by which CAFs promote the formation of an immunosuppressive microenvironment and support metastasis. Existing findings confirm that multiple components of the TME act cooperatively to accelerate the progression of tumor events. The potential applications and challenges of targeted therapies based on CAFs in the clinical setting are further discussed in the context of advancing research related to CAFs.

Osteoarthritis (OA) is a highly prevalent joint disorder blamed for pain and disability in older individuals. It's commonly accepted that inflammation, apoptosis, autophagy and cellular senescence participate in the progress of OA. Protease activated receptor 2 (PAR2), a member of the G-protein coupled receptors, is involved in the regulation of various inflammation diseases. Previous studies have identified PAR2 as a potential therapeutic target for the treatment of OA. Here, we investigated the role of PAR2 antagonist AZ3451 in inflammation response, apoptosis, autophagy and cellular senescence during OA. We confirmed that PAR2 expression was significantly up-regulated in OA articular cartilage tissues as well as in interleukin 1β (IL-1β) stimulated chondrocytes. We demonstrated AZ3451 could prevent the IL-1β-induced inflammation response, cartilage degradation and premature senescence in chondrocytes. Further study showed that AZ3451 attenuated chondrocytes apoptosis by activating autophagy in vitro. The P38/MAPK, NF-κB and PI3K/AKT/mTOR pathways were involved in the protective effect of AZ3451. In vivo, we found that intra-articular injection of AZ3451 could ameliorate the surgery induced cartilage degradation in rat OA model. Our work provided a better understanding of the mechanism of PAR2 in OA, and indicated that PAR2 antagonist AZ3451 might serve as a promising strategy for OA treatment.