The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis. Increasing evidence focuses on the relationship between the bone microenvironment and osteosarcoma metastasis. Many elements exist in the bone microenvironment, such as acids, hypoxia, and chemokines, which have been verified to affect the progression and malignance of osteosarcoma through various signaling pathways. We thoroughly summarized all these regulators in the bone microenvironment and the transmission cascades, accordingly, attempting to furnish hints for inhibiting osteosarcoma metastasis via the amelioration of the bone microenvironment. In addition, analysis of the cross-talk between the bone microenvironment and osteosarcoma will help us to deeply understand the development of osteosarcoma. The cellular and molecular protagonists presented in the bone microenvironment promoting osteosarcoma metastasis will accelerate the exploration of novel therapeutic strategies towards osteosarcoma.

Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant diseases worldwide. Despite advances in the diagnosis and treatment of HCC, its overall prognosis remains poor. Recent studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in various pathophysiological processes, including liver cancer. In the current study, we report that lncRNA SLC2A1‐AS1 is frequently downregulated in HCC samples, as shown by quantitative real‐time polymerase chain reaction analysis. SLC2A1‐AS1 deletion is significantly associated with recurrence‐free survival in HCC. By performing glucose uptake, lactate production and ATP detection assays, we found that SLC2A1‐AS1‐mediated glucose transporter 1 (GLUT1) downregulation significantly suppressed glycolysis of HCC. In vitro Cell Counting Kit‐8, colony formation, transwell assays as well as in vivo tumorigenesis and metastasis assays showed that SLC2A1‐AS1 overexpression significantly suppressed proliferation and metastasis in HCC through the transcriptional inhibition of GLUT1. Results from fluorescence in situ hybridization, ChIP and luciferase reporter assays demonstrated that SLC2A1‐AS1 exerts its regulatory role on GLUT1 by competitively binding to transketolase and signal transducer and activator of transcription 3 (STAT3) and inhibits the transactivation of Forkhead box M1 (FOXM1) via STAT3, thus resulting in inactivation of the FOXM1/GLUT1 axis in HCC cells. Our findings will be helpful for understanding the function and mechanism of lncRNA in HCC. These data also highlight the crucial role of SLC2A1‐AS1 in HCC aerobic glycolysis and progression and pave the way for further research regarding the potential of SLC2A1‐AS1 as a valuable predictive biomarker for HCC recurrence.

Background: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term spaceflight, which results in decreased bone formation. Methods: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. Results: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (Alp), collagen type 1 alpha-1(ColIα1)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity. Conclusions: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.

Skeletal systems provide support, movement, and protection to the human body. It can be affected by several life suffering bone disorders such as osteoporosis, osteoarthritis, and bone cancers. It is not an easy job to treat bone disorders because of avascular cartilage regions. Treatment with non-specific drug delivery must utilize high doses of systemic administration, which may result in toxicities in non-skeletal tissues and low therapeutic efficacy. Therefore, in order to overcome such limitations, developments in targeted delivery systems are urgently needed. Although the idea of a general targeted delivery system using bone targeting moieties like bisphosphonates, tetracycline, and calcium phosphates emerged a few decades ago, identification of carrier systems like viral and non-viral vectors is a recent approach. Viral vectors have high transfection efficiency but are limited by inducing immunogenicity and oncogenicity. Although non-viral vectors possess low transfection efficiency they are comparatively safe. A number of non-viral vectors including cationic lipids, cationic polymers, and cationic peptides have been developed and used for targeted delivery of DNA, RNA, and drugs to bone tissues or cells with successful consequences. Here we mainly discuss such various non-viral delivery systems with respect to their mechanisms and applications in the specific targeting of bone tissues or cells. Moreover, we discuss possible therapeutic agents that can be delivered against various bone related disorders.