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.

Introduction: Bone metastases lead to local bone destruction and skeletal complications. Bisphosphonates, particlulaly zoledronic acid (ZA), play a central role in the treatment of bone metastases. Some studies have shown that denosumab may delay and prevent SREs in metastatic bone disease more effectively than ZA; therefore, we systematically reviewed and assessed the safety of denosumab and ZA. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science with Conference Proceedings, Elsevier, and China National Knowledge Infrastructure (CNKI) databases were searched up to October 2015. 2 independent reviewers extracted data from each eligible study using a standard protocol, and both fixed-effects and random-effects models were used to analyze and evaluate the data extracted from eligible articles. Results: 6 randomized controlled trials enrolling 13,733 patients were included. Occurrences of adverse events were generally similar between the denosumab and ZA groups except anemia and anorexia in patients with bone metastases and back pain and bone pain. However, occurrences of serious adverse events such as hypocalcaemia , renal adverse events , and new primary malignancy were significantly different between the denosumab and ZA groups. Only the occurrence of osteonecrosis of the jaw showed no significant difference between the denosumab and ZA groups in patients with bone metastases. Conclusion: Denosumab was safer in delaying or preventing skeletal-related events in patients with bone metastases and prevented pain progression compared to ZA in this meta-analysis.

Natural immunity, the first line for the body to defense against the invasion of pathogen, serves as the body’s perception of the presence of pathogens depends on nucleic acid recognition mechanisms. The cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) signaling pathway is considered an essential pattern recognition and effector pathway in the natural immune system and is mainly responsible for recognizing DNA molecules present in the cytoplasm and activating downstream signaling pathways to generate type I interferons and some other inflammatory factors. STING, a crucial junction protein in the innate immune system, exerts an essential role in host resistance to external pathogen invasion. Also, STING, with the same character of inflammatory molecules, is inseparable from the body’s inflammatory response. In particular, when the expression of STING is upregulated or its related signaling pathways are overactivated, the body may develop serious infectious disorders due to the generation of excessive inflammatory responses, non-infectious diseases, and autoimmune diseases. In recent years, accumulating studies indicated that the abnormal activation of the natural immune cGAS-STING signaling pathway modulated by the nucleic acid receptor cGAS closely associated with the development and occurrence of autoimmune diseases (AID). Thereof, to explore an in-depth role of STING and its related signaling pathways in the diseases associated with inflammation may be helpful to provide new avenues for the treatment of these diseases in the clinic. This article reviews the activation process of the cGAS-STING signaling pathways and its related important roles, and therapeutic drugs in AID, aiming to improve our understanding of AID and achieve better diagnosis and treatment of AID.

Osteosarcoma (OS) is the most common primary malignancy of bone. Epigenetic regulation plays a pivotal role in cancer development in various aspects, including immune response. In this study, we studied the potential association of alterations in the DNA methylation and transcription of immune‐related genes with changes in the tumor microenvironment (TME) and tumor prognosis of OS. We obtained multi‐omics data for OS patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. By referring to curated immune signatures and using a consensus clustering method, we categorized patients based on immune‐related DNA methylation patterns (IMPs), and evaluated prognosis and TME characteristics of the resulting patient subgroups. Subsequently, we used a machine‐learning approach to construct an IMP‐associated prognostic risk model incorporating the expression of a six‐gene signature (MYC, COL13A1, UHRF2, MT1A, ACTB, and GBP1), which was then validated in an independent patient cohort. Furthermore, we evaluated TME patterns, transcriptional variation in biological pathways, somatic copy number alteration, anticancer drug sensitivity, and potential responsiveness to immune checkpoint inhibitor therapy with regard to our IMP‐associated signature scoring model. By integrative IMP and transcriptomic analysis, we uncovered distinct prognosis and TME patterns in OS. Finally, we constructed a classifying model, which may aid in prognosis prediction and provide a potential rationale for targeted‐ and immune checkpoint inhibitor therapy in OS.

As a DNA receptor in the cytoplasm, cyclic GMP-AMP synthase (cGAS) contributes to the recognition of abnormal DNA in the cytoplasm and contributes to the stimulator of interferon genes (STING) signaling pathway. cGAS could mediate the expression of interferon-related genes, inflammatory-related factors, and downstream chemokines, thus initiating the immune response. The STING protein is a key effector downstream of the DNA receptor pathway. It is widely expressed across cell types such as immune cells, tumor cells, and stromal cells and plays a role in signal transduction for cytoplasmic DNA sensing and immunity. STING agonists, as novel agonists, are used in preclinical research and in the treatment of various tumors via clinical trials and have displayed attractive application prospects. Studying the cGAS-STING signaling pathway will deepen our understanding of tumor immunity and provide a basis for the research and development of antitumor drugs.