Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of NeuN-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.

Osteoporosis is a systemic metabolic disease, mainly characterized by reduced bone mineral density and destruction of bone tissue microstructure. However, the molecular mechanisms of osteoporosis need further investigation and exploration. Increasing studies have reported that circular RNAs (circRNAs), a novel type of RNA molecule, play crucial roles in various physiological and pathological processes and bone-related diseases. Based on an in-depth understanding of their roles in bone development, we summarized the multiple regulatory roles and underlying mechanisms of circRNA–miRNA–mRNA networks in the treatment of osteoporosis, associated with bone marrow mesenchymal stem cells (BMSCs), osteoblasts, and osteoclasts. Deeper insights into the vital roles of circRNA–miRNA–mRNA networks can provide new directions and insights for developing novel diagnostic biomarkers and therapeutic targets in the treatment of osteoporosis.

Summary: Aim: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI.Methods: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat. Hematoxylin and eosin staining (H&E staining) and Luxol fast blue (LFB) staining were used to observe the histological lesions. Apoptosis was examined by TUNEL staining, Annexin V‐FITC/PI, caspase‐3, and Bcl‐2. Cytokines and neurotrophins were tested by Western blot. Locomotion recovery assessed by hindlimb BBB score and the inclined plane test.Results: Nafamostat mesilate treatment significantly improved locomotion recovery as assessed by hindlimb BBB scores and the inclined plane test. H&E staining and LFB staining showed a significant increase in spared tissue in both gray matter and white matter. NM decreased the expression of the proinflammatory cytokines TNF‐α and IL‐6. In addition, apoptosis was also significantly decreased, as shown by TUNEL staining and Annexin V‐FITC/PI and by Western blotting for caspase‐3 and Bcl‐2 expression. Due to the mechanism of action of NM as a serine protease inhibitor, the drug decreased thrombin expression in the damaged spinal cord. Furthermore, NM increased the expression of neurotrophins (NT‐3, BDNF, and NGF).Conclusions: Upon NM treatment, the functional and histological outcomes were improved, and microenvironment upon SCI was modulated. As a clinically approved drug, NM holds promise for clinical use after spinal cord injury.

Background: Lung cancer is a leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. While immune checkpoint inhibitors (ICIs) have transformed treatment for advanced NSCLC, the role of bone metastasis in modulating ICI efficacy remains unclear. Bone metastasis, occurring in 30-40% of advanced NSCLC cases, is associated with worse outcomes. However, how this affects the therapeutic benefit of ICIs has not been fully elucidated, highlighting a critical knowledge gap in optimizing treatment for this patient population.Methods: A comprehensive literature search across multiple databases, including PubMed, Embase, and Cochrane, identified 13 studies with a total of 3,681 patients, of whom 37.6% had bone metastasis. Overall survival (OS) and progression-free survival (PFS) were compared between NSCLC patients with and without bone metastasis. Data were analyzed using a random-effects model to account for study heterogeneity.Results: The meta-analysis demonstrated that bone metastasis significantly worsened overall survival (OS) and progression-free survival (PFS) in NSCLC patients treated with ICIs. Specifically, bone metastasis was associated with a 45% increased risk of death (HR: 1.45, 95% CI: 1.30–1.62, p < 0.001) and a 40% increased risk of disease progression (HR: 1.40, 95% CI: 1.25–1.58, p < 0.001). No statistically significant impact on PFS was observed. (HR: 1.28, 95% CI: 0.77–2.10, p = 0.34). High heterogeneity was observed in some subgroup analyses (I² = 72%), indicating variability in the results.Conclusion: Bone metastasis is a significant negative prognostic factor for NSCLC patients treated with ICIs, associated with a higher risk of mortality and disease progression. These results underscore the importance of tailored treatment approaches for NSCLC patients with bone metastasis and call for further research to optimize therapy outcomes in this group.

Osteosarcoma (OS) is a type of malignant primary bone cancer, which is highly aggressive and occurs more commonly in children and adolescents. Thus, novel potential drugs and therapeutic methods are urgently needed. In the present study, we aimed to elucidate the effects and mechanism of melatonin on OS cells to provide a potential treatment strategy for OS. The cell survival rate, cell viability, proliferation, migration, invasion and metastasis were examined by trypan blue assay, MTT, colony formation, wound healing, transwell invasion and attachment/detachment assay, respectively. The expression of relevant lncRNAs in OS cells was determined by real‐time qPCR analysis. The functional roles of lncRNA JPX in OS cells were further examined by gain and loss of function assays. The protein expression was measured by western blot assay. Melatonin inhibited the cell viability, proliferation, migration, invasion and metastasis of OS cells (Saos‐2, MG63 and U2OS) in a dose‐dependent manner. Melatonin treatment significantly downregulated the expression of lncRNA JPX in Saos‐2, MG63 and U2OS cells. Overexpression of lncRNA JPX into OS cell lines elevated the cell viability and proliferation, which was accompanied by the increased metastasis. We also found that melatonin inhibited the OS progression by suppressing the expression of lncRNA JPX via regulating the Wnt/β‐catenin pathway. Our results suggested that melatonin inhibited the biological functions of OS cells by repressing the expression of lncRNA JPX through regulating the Wnt/β‐catenin signalling pathway, which indicated that melatonin might be applied as a potentially useful and effective natural agent in the treatment of OS.