To develop a scaffold suitable for simultaneous repair of both spinal cord injury (SCI) and sciatic nerve injury (SNI), we designed a multilayer composite membrane capable of unidirectional and sustained release of two factors: nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). The membrane's morphology, mechanical properties, cytocompatibility, drug release kinetics, swelling, and degradation behavior were thoroughly characterized. Additionally, its ability to promote the differentiation of PC-12 cells was assessed. The findings indicated that the composite membrane featured a tri-layered structure and exhibited robust mechanical strength, enabling it to protect and regulate the release of NGF and BDNF. This regulation ensured the appropriate timing and concentration of the factors necessary for cell differentiation and growth. Moreover, the membrane demonstrated excellent cell compatibility and significantly fostered the differentiation of PC-12 cells into axons. In rat models of SCI and SNI, the composite membrane markedly enhanced axon and neuron regeneration, myelination, neural stem cell proliferation, and nerve fiber clustering, while reducing astrocyte formation. It also improved the integrity of spinal cord tissue and motor function recovery, suggesting that this scaffold holds promise for the repair of both SCI and SNI.

To overcome the drawbacks of oral administration of insulin, a surface-modified insulin-loaded nanocomposite was designed and prepared in this work. Halloysite nanotubes (HNTs) were employed to improve the insulin encapsulation, PEG-CS and hydroxypropyl methyl cellulose phthalate (HPMCP) were selected to surface modify the insulin-loaded HNTs to adjust the release of insulin. As a result, the insulin-loaded HNTs/PEG-CS/HPMCP NCs had good biocompatibility, relatively high drug loading, and pH-sensitive release properties. Oral administration of the NCs produced an effective and relative long-time hypoglycemic effect. Therefore, these NCs can be a promising delivery system to improve the oral bioavailability of insulin.

Osteoarthritis (OA) is a chronic disease common in the elderly population and imposes significant health and economic burden. Total joint replacement is the only currently available treatment but does not prevent cartilage degeneration. The molecular mechanism of OA, especially the role of inflammation in disease progression, is incompletely understood. We collected knee joint synovial tissue samples of eight OA patients and two patients with popliteal cysts (controls), measured the expression levels of lncRNAs, miRNAs, and mRNAs in these tissues by RNA-seq, and identified differentially expressed genes (DEGs) and key pathways. In the OA group, 343 mRNAs, 270 lncRNAs, and 247 miRNAs were significantly upregulated, and 232 mRNAs, 109 lncRNAs, and 157 miRNAs were significantly downregulated. mRNAs potentially targeted by lncRNAs were predicted. Nineteen overlapped miRNAs were screened based on our sample data and GSE 143514 data. Pathway enrichment and functional annotation analyses showed that the inflammation-related transcripts CHST11, ALDH1A2, TREM1, IL-1β, IL-8, CCL5, LIF, miR-146a-5p, miR-335-5p, lncRNA GAS5, LINC02288, and LOC101928134 were differentially expressed. In this study, inflammation-related DEGs and non-coding RNAs were identified in synovial samples, suggesting that competing endogenous RNAs have a role in OA. TREM1, LIF, miR146-5a, and GAS5 were identified to be OA-related genes and potential regulatory pathways. This research helps elucidate the pathogenesis of OA and identify novel therapeutic targets for this disorder.

This study aims to prepare a nanodrug system for insulin delivery and controlled release with Poly(lactic acid-glycolic acid) (PLGA) as the shell and polyethylene glycol-chondroitin sulfate as the core to enhance its oral administration bioavailability. The insulin/CS-PLGA nanoparticles (NPs) with an average size of about 150 nm and regular spherical shape were obtained and showed good biocompatibility and relative high drug loading. Insulin can be controlled release according to the environmental pH and retained its original structure. The oral administration of insulin/CS-PLGA NPs showed a relatively higher hypoglycemic effect than that of insulin, indicating the NPs is a potential oral delivery system to enhance insulin bioavailability.

In this work, multifunctional thiolated chitosan derivatives (DCA-CS-PEG-FA-NAC) were synthesized, and arsenic trioxide (ATO) was loaded onto the derivatives through glutathione (GSH)-sensitive AsIII-S bonds, and stable CS-ATO nanodrugs were prepared by simple self-assembly method. By adjusting the thiol substitution degree of CS, the drug loading capacity of the nanodrugs was significantly improved, which could reach 20 ATO per CS molecule (DCA10.7-CS-PEG3.1-FA-NAC20.2-ATO). In vitro release studies obviously showed the low leakage of ATO under physiological conditions while over 95 % ATO was released after 24 h under GSH. In vitro and in vivo investigations demonstrated that the DCA10.7-CS-PEG3.1-FA-NAC20.2-ATO nanodrug could significantly enhance the tumor intracellular accumulation of ATO, reduce the toxic and side effects of ATO on healthy organs, and improve the therapeutic effect of ATO on the HepG2 mice tumor model (tumor inhibition rate was as high as 86.4 %), indicating the potential application of ATO in clinical treatment of liver cancer.

Osteosarcoma (OS) is the most prevalent malignant bone tumour with high morbidity in children and adolescents. Increasing evidence indicates that microRNAs (miRNAs) play essential roles in OS occurrence and progression. This study aimed to investigate the expression and biological role of microRNA-608 (miR-608) in OS. Here, we found that miR-608 expression was consistently downregulated in OS tissues compared with the matched adjacent normal tissues, and its expression was significantly correlated with overall (P=0.0247) and disease-free survival rate (P=0.0107), tumour size (P=0.0004) and Tumour Node Metastasis (TNM) stage (P=0.0005). Functional study revealed that miR-608 overexpression in the OS cell lines and U2OS MG-63 inhibited cell proliferation and induced apoptosis. Furthermore, we demonstrated that macrophage migration inhibitory factor (MIF) was directly regulated by miR-608 which mediated the biological effects of miR-608 in OS. Restoration of MIF significantly reversed the inhibitory proliferation effect of miR-608. Taken together, our data provide compelling evidence that miR-608 functions as a tumour proliferation suppressor gene in OS by targeting MIF.