This study aimed to detect and characterize microplastics in intervertebral disc and investigate their effects and molecular mechanism on intervertebral disc degeneration. We collected intervertebral disc tissues from cervical, lumbar, and thoracolumbar segments and used Raman spectroscopy to identify and characterize microplastics. Among 80 samples, 47 contained microplastics, with polyethylene being the most prevalent type. To explore the effects of polyethylene microplastics (PE-MPs), we established a mouse model and a nucleus pulposus cell model. Reactive oxygen species (ROS) levels were assessed via immunofluorescence staining, cell viability was measured using the CCK-8 assay, and protein expression related to the Toll-like receptor 4 (TLR4)/NADPH oxidase 2 (NOX2) axis, oxidative stress, and nucleus pulposus degeneration were evaluated through western blotting and immunofluorescence staining. Results showed that PE-MPs exposure led to intervertebral disc degeneration by inducing oxidative stress and activating the TLR4 / NOX2 axis, which increased the senescence of nucleus pulposus cells. These effects were mitigated by TLR4 and NOX2 inhibitors. This research highlights the existence of microplastics in human intervertebral disc tissue and unveils a novel mechanism of nucleus pulposus cell senescence induced by PE-MPs, offering new avenues for clinical treatment of microplastic-related disc degeneration.

Rheumatoid arthritis (RA) is a multifaceted, chronic, progressive autoimmune disease. This study aims to explore the potential benefits of an enhanced drug delivery system utilizing optimized Gelatin Methacryloyl (GelMA) vectors in RA management. We evaluated the levels of miR-1124-3p and AGO1 in RA tissues and cell lines using qPCR, WB, and immunofluorescence. The effects of osthole on inflammatory response and joint morphology were determined by qPCR, H&E staining, and micro-CT. The data showed that miR-1224-3p was downregulated in RA tissues and HUM-iCell-s010RA cells, while the overexpression of miR-1224-3p in HUM-iCell-s010RA cells reduced the expression of IL-6 and IL-1β. Luciferase assay demonstrated that AGO1 was a direct target gene of miR-1224-3p. Additionally, osthole treatment increased miR-1224-3p levels and decreased AGO1 expression. The release data showed that osthole loaded on GelMA was released at a slower rate than free osthole. Further studies in a mouse model of CIA confirmed that osthole-loaded GelMA was more effective in attenuating osteopenia in RA as well as alleviating autoimmune arthritis. These findings suggest that osthole can regulate the miR-1224-3p/AGO1 axis in RASFs cells and has the potential to be developed as a clinical anti-RA drug. GelMA could provide a new approach to long-term RA treatment.

The demands for novel and efficient therapies have gradually increased with the rising concerns of osteoporosis (OP). The most popular method in promoting bone regeneration during osteoporotic conditions consists of loading bioactive materials with different drugs to treat osteoporotic bones by either promoting the process of osteogenesis, or by inhibiting the activity of osteoclasts. By analyzing single cell sequencing results, we found that divalent metal transporter 1 (DMT1) played a role in OP. Based on our previous results, we found that melatonin (MT) suppressed expression of DMT1 induced by high glucose during OP, so we determined the efficacy of MT for the treatment of OP. However, the clinical effects of MT on OP were unsatisfactory. To enhance its biological efficacy, we combined MT with porous gelatin chitosan (chitosan) and the conductive material, PLA-b-AP-b-PLA (PAP), then determined how MT incorporation in chitosan@PAP nanoparticles affected the ability to promote MC3T3-E1 osteogenesis and mineralization, both in vitro and in vivo. The results confirmed the effect of MT on DMT1. We then prepared and characterized composites prepared as nanofibers, and determined the efficacy of MT combined with chitosan-PAP modified hydrogels as a slow-release system in a femur model of osteoporosis mice, with associated properties suitable for bone tissue engineering. The results indicated that MT-loaded chitosan@PAP nanospheres showed favorable osteogenic functions, both in vivo and in vitro, providing a practical solution for bone regeneration for OP patients.

Intervertebral disc degeneration (IVDD) serves as the fundamental pathological basis for low back pain. Microplastics influence the organisms through exosomes-mediated communication. Our study aimed to investigate the roles and underlying mechanisms of polyethylene microplastics (PE-MPs) in intervertebral disc degeneration. We isolated exosomes(exo) from PE-MPs-treated macrophages (M0-MPs-exo), and investigated whether PE-MPs could be translocated to nucleus pulposus cells (NPCs) via M0-MPs-exo, triggering ferroptosis and cellular senescence cascades that ultimately exacerbate IVDD progression. Then, the roles and underlying mechanisms of NAT10/SLC7A11 in IVDD were further explored in vitro and in vivo. M0-MPs-exo were successfully isolated, and PE-MPs could be transported to NPCs through M0-MPs-exo. Compared with the control NPCs, PE-MPs significantly up-regulated MMP13, P53 and P21 while down-regulated COL2A1, NAT10, GPX4 and SLC7A11 (P < 0.05). Besides, the increased levels of ROS and ac4C modification were also observed in NPCs treated with PE-MPs. Further, our in vitro and in vivo experiments displayed that NAT10 overexpression combined with ferrostatin-1 could significantly improve the PE-MPs-induced degenerative phenotypes, and ameliorate ferroptosis-related proteins, oxidative stress-related proteins, extracellular matrix (ECM) metabolism, and ac4C modification. Meanwhile, the effects of NAT10 in NPCs could be reversed by SLC7A11. Additionally, NAT10 overexpression could increase SOD and GSH levels, and reduce the levels of MDA, lipid peroxidation and Fe²⁺ in the PE-MPs-treated NPCs, which could be reversed by SLC7A11 knockdown. PE-MPs could be transported to NPCs via M0-MPs-exo, and trigger lipid peroxidation and ferroptosis through regulating NAT10/SLC7A11 and ac4C modification, thereby promoting IVDD.

Introduction: Postoperative comprehensive treatment has become increasingly important in recent years. This study was to repair tissue defects resulting from the removal of diseased tissue and to eliminate or inhibit the recurrence and metastasis of residual tumors under the condition of reducing the systemic side effects of chemotherapeutic drugs. To address these challenges, multifunctional scaffolds based local drug delivery systems will be a promising solution.Methods: An optimal drug-loaded scaffold material PHBV-mPEG5k (PP5) was prepared, which is biocompatible, hydrophilic and biodegradable. Furthermore, this material showed to promote bone healing, and could be conveniently prepared into porous scaffold by freeze-drying the solution. By means of introducing melatonin (MT) into the porous surfaces, the MT loaded PP5 scaffold with desirable sustained release ability was successfully prepared. The effectiveness of the MT loaded PP5 scaffold in promoting bone repair and anti-tumor properties was evaluated through both in vivo and in vitro experiments.Results and Discussion: The MT loaded PP5 scaffold is able to achieve the desired outcome of bone tissue repair and anti-bone tumor properties. Furthermore, our study demonstrates that the PP5 scaffold was able to enhance the anti-tumor effect of melatonin by improving cellular autophagy, which provided a therapeutic strategy for the comprehensive postoperative treatment of osteosarcoma.

This study seeks to elucidate the molecular mechanisms by which polyethylene microplastics (PE-MPs) facilitate the progression of osteosarcoma through the modulation of the ITGA5/FAPα/LGMN protein complex. Initially, tumor tissues were obtained from patients diagnosed with osteosarcoma, and Raman spectroscopy was employed to identify and characterize the presence of microplastics. Subsequent observations revealed that PE-MPs were internalized by osteosarcoma cells, exhibiting a pronounced promotive effect on cancer progression at a concentration of 10 mg/L. High-throughput sequencing analysis revealed that PE-MPs specifically upregulated the expression level of the ITGA5 gene. Immunofluorescence staining and co-immunoprecipitation (Co-IP) experiments further confirmed that ITGA5, FAPα, and LGMN interact to form a complex within osteosarcoma cells, and their protein expression levels increased in a dose-dependent manner with increasing polyethylene particle concentration. Furthermore, in vivo animal experiments demonstrated that polyethylene particle treatment significantly enhanced tumor growth, while administration of inhibitors targeting ITGA5, FAPα, or LGMN partially alleviated this pro-carcinogenic effect. This study first discovered the presence of microplastic particles in human osteosarcoma and elucidated the molecular mechanism by which PE-MPs promote osteosarcoma progression through interaction with ITGA5/FAPα/LGMN complex. This discovery provides new insights into the mechanism of action of environmental carcinogens and important theoretical support for the development of precise treatment strategies and prognostic biomarkers in the microenvironment of osteosarcoma.