Although chemotherapy-induced bone loss is well-recognized during breast cancer treatment, the underlying mechanism remains to be further elucidated, especially in patients with obesity. In this study, the objective was to investigate the impact of genomic silencing and pharmacological inhibition of S1P synthesis on bone loss in doxorubicin-induced obese breast cancer mice. In vitro study, upon the treatment of doxorubicin combined with palmitic acid, the S1P generated by 4T1 cells was significantly increased, resulting in an increase in osteoclastogenesis by activating the S1PR1/p-STAT3/NFATc-1 pathway in bone marrow-derived macrophages. In vivo study, pharmacological intervention with Sphingosine kinases (SPHK) antagonist SKI II or biological inhibition with SPHK1 and SPHK2 short hairpin RNA significantly reduced S1P production and rescued the obese breast cancer-bearing mice from doxorubicin-induced bone loss, manifested by the decreased osteoclastogenesis and recovered bone microarchitecture. Similarly, the administration of the S1PR1 antagonist FTY720 also alleviated bone loss in the breast cancer-bearing mice fed a high-fat diet. These studies indicate that genetic silencing and pharmacological inhibition can suppress S1P-dependent bone loss in doxorubicin-induced obese breast cancer mice. S1P shows promise as a potential drug target for preventing chemotherapy-induced bone loss in patients.

Neuroinflammation is a core pathological mechanism in neurodegenerative diseases. Although natural many compounds, derived from traditional Chinese medicine have shown promise in modulating neuroinflammation, conventional evaluation methods remain inefficient and fail to meet modern drug development needs. This study aimed to develop a neuroinflammation-on-a-chip for efficient and accurate evaluation of the anti-neuroinflammatory activity of such compounds. By integrating gelatin methacryloyl (GelMA) hydrogel with a microchamber array structure into a multi-channel concentration-gradient microfluidic chip, we constructed a functional neuroinflammation-on-a-chip suitable for high-throughput drug screening. Preliminary results demonstrated that the chip can successfully model lipopolysaccharide (LPS)-induced neuroinflammation and test the anti-inflammatory effects of curcumin (Cur) and resveratrol (RSV). Relative to traditional approaches, the chip offers the advantages of low sample consumption, rapid detection, and high data reliability. This study provides a novel tool for the efficient evaluation of anti-neuroinflammatory activity of traditional Chinese medicine active compounds and offers an innovative platform for research on neuroinflammation-related diseases.

Spinal cord injury (SCI), which is a severe complication of spinal fractures, often causes the dysfunction of the spinal cord and results in sensory and motor abnormalities. Current clinical treatments—including medication, decompression surgery, and bed rest—remain insufficient for complete functional recovery. It is necessary to reduce the early inflammatory reactions, rebuild the connections of neurons, and reduce the formation of the glial scar in order to restore spinal cord function. With the development of biomaterials discipline, hydrogel tissue engineering has become an effective and feasible method. Injectable and highly biocompatible hydrogel can directly fill the injured site as a scaffold material that can provide physical support to reduce scar formation and promote axon growth. In addition, hydrogels have the ability to regulate pathophysiological events. For example, it can reduce inflammatory reactions, inhibit glial scar formation, and promote axonal growth, so as to achieve the recovery of motor function after SCI. This review systematically correlates the four pathological phases of SCI with the stage-specific biological functions of hydrogels. It summarizes the current state of research in SCI and hydrogel-based tissue engineering, and discusses the key challenges and future directions in this evolving field.

Bone injuries, particularly those associated with an aging global population, pose a persistent and complex clinical challenge. Current gold-standard treatments such as autografts, allografts, and metal implants, are often limited by immune rejection and mechanical mismatch. In this context, hydrogels are promising biomaterials for bone regeneration, due not only to inherent biocompatibility, high hydration, and tunable elasticity but also to the ability to mimic the native bone micro environment. This review presents a critical and comprehensive analysis of how hydrogels for bone repair are designed, constructed, and functionalized to achieve the desired regenerative performance. It systematically examines multiple hydrogel types, centering on the design of their strength and biodegradation features to better align with the functional demands of bone healing. Furthermore, the review summarizes that by incorporating bioactive molecules, nanomaterials, or cells, advanced functionalization can orchestrate osteogenesis and angiogenesis. In vitro and in vivo studies evidenced the performance of hydrogels' applications ranging from bone fracture repair to smart, stimuli-responsive platforms for personalized regenerative medicine. This review finally identifies the prevailing translational challenges and suggests future research trajectories.