Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma.

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

Transcriptome Analysis Reveals the Effects of Troxerutin and Cerebroprotein Hydrolysate Injection on Injured Spinal Cords in Rats.

Spinal cord injury (SCI) is a serious condition that results in disability and has a high morbidity rate; its treatment is very difficult. Although troxerutin and cerebroprotein hydrolysate (TCH) injections have been extensively used in clinics in China for the treatment of traumatic brain injury (TBI) and cerebral stroke, the potential efficacy of TCH injection in the treatment of SCI has never been revealed. In this study, the effects of administering TCH injections on neurological recovery in post-SCI rats were first tested with regard to the behavior and histology; subsequently, the specific expression profile of mRNAs and long noncoding RNAs (LncRNAs) in their spinal cords were conducted using RNA sequencing (RNA-seq). The LncRNA-mRNA networks were also elucidated. After SCI, we found that TCH injection with the right dose is effective for the recovery of locomotion function and repairing of the damaged tissue in the spinal cord; TCH injection is also discovered to have a role in the regulation of 443 differentially expressed genes (DEGs) and 27 differentially expressed LncRNAs (DELs) that are identified to have multiple functions, including locomotion, blood vessel morphogenesis, thiamine metabolism, Hippo signaling pathway, and axon guidance, by applying the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis. In addition, it is revealed that, after SCI, the highly expressed LncRNA AABR07071383.1 in the post-SCI cis/trans-regulates the expression of mRNA Acpp mRNA that encodes a key enzyme involved in the metabolic process of thiamine in the abirritation of the dorsal root ganglion (DRG), which implies that TCH injection may be more effective when administered with benfotiamine (a common treatment drug).

An effective treatment of experimental osteomyelitis using the antimicrobial titanium/silver-containing nHP66 (nano-hydroxyapatite/polyamide-66) nanoscaffold biomaterials.

Effective treatment of osteomyelitis remains a formidable clinical challenge. The rapid emergence of multidrug-resistant bacteria has renewed interest in developing antimicrobial biomaterials using antiseptic silver ions to treat osteomyelitis. However, inadequate local retention and severe cytotoxic effects have limited the clinical use of ionic silver for bone grafts. We recently developed novel porous nano-hydroxyapatite/polyamide 66 (nHP66)-based nanoscaffold materials containing varied concentrations of silver ions (Ag+) (TA-nHAPA66) and oxidized titanium (TiO2), which was added as a second binary element to enhance antibacterial activity and biocompatibility. In this study, we establish a large cohort of rabbit model of experimental osteomyelitis and investigate the in vivo antimicrobial and therapeutic effects of TA-nHP66 biomaterials and their in vivo silver release kinetics. We find the TA-nHP66 scaffolds exhibit potent antibacterial activities against E. coli and S. aureus, support cell adhesion and cell proliferation of pre-osteoblasts, and stimulate osteogenic regulator/marker expression. Moreover, the TA2-nHP66 scaffold exerts potent antibacterial/anti-inflammation effects in vivo and promotes bone formation at the lesion site of osteomyelitis. We further demonstrate that TA2-nHP66 exhibits excellent biosafety profile without apparent systemic toxicities. Therefore, the TA-nHP66 scaffold biomaterials may be further explored as an effective adjuvant therapy for infected bone defects and/or osteomyelitis debridement.