Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.

Recently, microRNA-20a (miR-20a) has been reported to influence the clinical features and may have prognostic value in human cancers. The present meta-analysis assessed the prognostic role of miR-20a in various carcinomas. Literature searches of seven electronic databases were performed for eligible articles of the prognostic role of miR-20a in human cancers. Hazard ratios (HR) for overall survival (OS), disease free survival (DFS), progression-free survival (PFS) as well as their 95% confidence intervals (95%CIs) were used to assess the influence of miR-20a expression on patient prognosis. Odds ratio (OR) and 95%CIs were applied to evaluate the correlation between miR-20a expression and clinicopathological characteristics. Based on the OS analyzed by log rank tests, there was a significant association between miR-20a levels and OS by fixed effects model. By subgroup analyses, the significance was also observed in the studies of specimen derived from blood and gastrointestinal cancer group. The independent prognostic role of miR-20a expression for the OS was observed significantly by fixed effects model. In addition, we observed significant association between miR-20a expression levels and DFS of log rank tests, DFS of cox regression. Significant relation of gender/differentiation and the expression level of miR-20a was identified. Base on the findings, the elevated miR-20a expression level is related to poor prognosis of gastrointestinal cancer patients. As for other types of carcinomas, the results are still not stable and more studies are required to further identify miR-20a prognostic values. In addition, miR-20a expression level is relatively higher in women than that in men, and increased miR-20a expression level is linked to poor tumor differentiation.

Ewing sarcoma, the second most prevalent malignant bone tumor with potential occurrence in soft tissues, exhibits a high level of aggressiveness, primarily afflicting children and adolescents. It is characterized by fusion proteins arising from chromosomal translocations. The fusion proteins induce aberrations in multiple signaling pathways and molecules, constituting a key event in oncogenic transformation. While diagnostic and therapeutic modalities have advanced in recent decades and multimodal treatments, including surgery, radiotherapy, and chemotherapy, have significantly improved survival of patients with localized tumors, patients with metastatic tumors continue to face poor prognoses. There persists a pressing need for novel alternative treatments, yet the translation of our understanding of Ewing sarcoma pathogenesis into improved clinical outcomes remains a critical challenge. Here, we provide a comprehensive review of Ewing sarcoma, including fusion proteins, various signaling pathways, pivotal pathogenetic molecules implicated in its development, and associated targeted therapies and immunotherapies. We summarize past endeavors, current advancements, and deliberate on limitations and future research directions. It is envisaged that this review will furnish novel insights into prospective treatment avenues for Ewing sarcoma.

Background: Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory disease. When AS is complicated by intervertebral disc degeneration (IVDD), disease complexity increases substantially, often resulting in poor long-term outcomes. Although previous studies have explored the mechanisms linking AS and IVDD, reliable tools for precise risk prediction and early intervention remain scarce.Methods: In this retrospective study, we enrolled 144 patients with AS (60 with and 84 without IVDD). Their clinical features, immune status, and inflammatory cytokine levels were analyzed. A nomogram prediction model was constructed using multivariable logistic regression. Model performance was evaluated via receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).Results: Multivariable analysis identified body mass index (BMI), peripheral blood Th2 cell percentage (Th2%), and serum IL-4 levels as independent risk factors for IVDD in patients with AS. All associations remained statistically significant after Benjamini–Hochberg correction (BMI: BH-adjusted P = 0.001; Th2%: BH-adjusted P = 0.019; IL-4: BH-adjusted P = 0.019). Incorporation of these factors into a nomogram yielded excellent discriminative performance (area under the curve, AUC = 0.83) and calibration, outperforming a simplified model based solely on BMI (AUC = 0.74). This improvement in predictive accuracy was statistically significant, as determined by DeLong’s test (P = 0.018). DCA revealed that at a threshold probability of 60.8%, the nomogram effectively distinguished high-risk patients, underscoring its strong clinical applicability.Conclusions: This study is the first to highlight the critical roles of Th2 cells and IL-4 in AS complicated by IVDD, and establishes a nomogram that accurately predicts the risk of IVDD in AS. Beyond offering a tool for early detection and personalized management, these findings open avenues for investigating overlapping pathogenic mechanisms and potential immunotherapeutic targets in AS-IVDD.

Discogenic lower back pain (DLBP) is a prevalent lumbar disorder. Functional Anesthetic Discography (FAD) is the primary diagnostic method for DLBP, with a high positivity rate. However, the mechanism by which lidocaine, a local anesthetic commonly used in FAD, induces damage to intervertebral disc cells remains unclear. This study aimed to investigate how lidocaine causes intervertebral disc cell damage and exacerbates the process of intervertebral disc degeneration (IVDD). We conducted primary nucleus pulposus cell (NPC) isolation and culture, and divided the cells into groups by lidocaine concentration (2.0 %, 1.0 %, 0.5 %, and 0 %). The cytotoxic effect of lidocaine on NPCs was evaluated using the CCK-8 colorimetric assay. We then created a mouse IVDD model, and conducted X-ray, magnetic resonance imaging (MRI), and mRNA-seq analysis. Assays, immunofluorescence detection, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were also performed. Lidocaine-induced oxidative stress damage in NPCs, leading to DNA double-strand breaks and triggering the transition of NPCs into a senescent state. Furthermore, treatment with an ROS inhibitor significantly alleviated both DNA damage and senescence. RNA-seq analysis revealed a marked upregulation in the MYC-DUSP1 axis expression. By employing si-RNA to inhibit the MYC-DUSP1 axis, the expression of senescence-related phenotypes was effectively reduced. Additionally, dasatinib (DASA) administration effectively mitigated the lidocaine-induced senescence of NPCs and alleviated the detrimental effects of lidocaine on IVDD. This study demonstrated that lidocaine exacerbates oxidative stress reactions within NPCs, leading to DNA double-strand breaks and promoting cellular senescence, thereby further aggravating IVDD progression. Moreover, an effective anti-senescence drug was identified, suggesting that DASA could be utilized as an intervention during FAD to reduce further pharmacological damage to NPCs. These findings provide an experimental foundation for optimizing the diagnostic approaches for DLBP.

Intervertebral disc degeneration (IVDD) is an age‐related degenerative spinal disorder, with age as the primary independent risk factor. To investigate the key pathogenic mechanisms of IVDD, we conducted biochemical analyses on IVD specimens from elderly and young groups. In this study, we found that methylmalonic acid (MMA) levels are significantly elevated within the discs of the elderly group, suggesting that MMA may be a critical metabolite involved in aging‐induced IVDD. In in vitro experiments, we observed that MMA treatment of nucleus pulposus cells (NPCs) upregulated the expression of extracellular matrix catabolic markers and downregulated the expression of anabolic markers. Further validation in an in vivo mouse model of needle puncture‐induced IVDD confirmed that MMA accelerates IVDD progression. Mechanistically, we demonstrated that MMA upregulates the expression of C‐C motif chemokine ligand 7 (CCL7) in NPCs. CCL7 acts as a chemoattractant, further enhancing Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling transduction, ultimately leading to upregulated vascular endothelial growth factor (VEGF) expression. This promotes abnormal growth of vascular endothelial cells, resulting in disc vascularization. Additional in vivo and in vitro experiments confirmed that disc vascularization is a key progression factor in IVDD. As a rescue strategy, we administered lenvatinib, a VEGF receptor inhibitor, which delayed IVDD progression. Therefore, VEGF and disc vascularization represent a promising therapeutic target for IVDD, offering an innovative approach to addressing IVDD treatment in clinical practice.