Polydopamine-coated biomimetic bone scaffolds loaded with exosomes promote osteogenic differentiation of BMSC and bone regeneration.

Introduction: The repair of bone defects is ideally accomplished with bone tissue engineering. Recent studies have explored the possibility of functional modification of scaffolds in bone tissue engineering. We prepared an SF-CS-nHA (SCN) biomimetic bone scaffold and functionally modified the scaffold material by adding a polydopamine (PDA) coating loaded with exosomes (Exos) of marrow mesenchymal stem cells (BMSCs). The effects of the functional composite scaffold (SCN/PDA-Exo) on BMSC proliferation and osteogenic differentiation were investigated. Furthermore, the SCN/PDA-Exo scaffolds were implanted into animals to evaluate their effect on bone regeneration. Methods: SCN biomimetic scaffolds were prepared by a vacuum freeze-drying/chemical crosslinking method. A PDA-functionalized coating loaded with BMSC-Exos was added by the surface coating method. The physical and chemical properties of the functional composite scaffolds were detected by scanning electron microscopy (SEM), energy spectrum analysis and contact angle tests. In vitro, BMSCs were inoculated on different scaffolds, and the Exo internalization by BMSCs was detected by confocal microscopy. The BMSC proliferation activity and cell morphology were detected by SEM, CCK-8 assays and phalloidin staining. BMSC osteogenic differentiation was detected by immunofluorescence, alizarin red staining and qRT‒PCR. In vivo, the functional composite scaffold was implanted into a rabbit critical radial defect model. Bone repair was detected by 3D-CT scanning. HE staining, Masson staining, and immunohistochemistry were used to evaluate bone regeneration. Results: Compared with the SCN scaffold, the SCN/PDA-Exo-functionalized composite scaffold had a larger average surface roughness and stronger hydrophilicity. In vitro, the Exos immobilized on the SCN/PDA-Exo scaffolds were internalized by BMSCs. The BMSC morphology, proliferation ability and osteogenic differentiation effect in the SCN/PDA-Exo group were significantly better than those in the other control groups (p < 0.05). The effects of the SCN/PDA-Exo functional composite scaffold on bone defect repair and new bone formation were significantly better than those of the other control groups (p < 0.05). Conclusions: In this study, we found that the SCN/PDA-Exo-functionalized composite scaffold promoted BMSC proliferation and osteogenic differentiation in vitro and improved bone regeneration efficiency in vivo. Therefore, combining Exos with biomimetic bone scaffolds by functional PDA coatings may be an effective strategy for functionally modifying biological scaffolds.

Arthroscopic percutaneous pullout suture transverse tunnel technique repair for tibial spine fractures in skeletally immature patients.

PURPOSE: We introduce an arthroscopic percutaneous pullout suture transverse tunnel (PP-STT) technique for repair tibial spine fractures (TSF) in skeletally immature patients (SIPs) to avoid damage to the tibial epiphyseal and evaluate the clinical and radiological outcomes of the PP-STT technique for repair TSF in SIPs. METHODS: Between February 2013 and November 2019, 41 skeletally immature patients were diagnosed with TSF; 21 patients were treated using the conventional transtibial pullout suture (TS-PLS) technique (group 1), and 20 patients were treated using the PP-STT technique (group 2). We compared clinical outcomes using the International Knee Documentation Committee (IKDC), Lysholm, Tegner, and visual analog scale (VAS) scores and participant sport levels, after a minimum of two year follow-up. Residual knee laxity was evaluated using Lachman and anterior drawer tests. Fracture healing and displacement were compared using X-ray. RESULTS: Significant improvements in clinical and radiological outcomes between preoperative and final follow-up (Lysholm, Tegner, IKDC, and VAS scores; Lachman and anterior drawer tests; and fracture displacement; p = 0.001) were achieved in both groups, with no significant between-group differences. Groups 1 and 2 exhibited no significant difference in time to radiographic healing (12.2 ± 1.3 weeks vs 13.1 ± 1.5 weeks, respectively; p = 0.513) or in the rate of return to sports level (19 (90.4%) vs 18 (90.0%), respectively; p = 0.826). CONCLUSION: Both surgical techniques provided satisfactory clinical and radiological outcomes. PP-STT may be a suitable alternative to protect the tibial epiphyseal for repair TSP in SIPs.

Aptamer-conjugated gold nanoparticles and their diagnostic and therapeutic roles in cancer.

The burden of incidence rate and mortality of cancer is increasing rapidly, and the development of precise intervention measures for cancer detection and treatment will help reduce the burden and pain of cancer. At present, the sensitivity and specificity of tumor markers such as CEA and CA-125 used clinically are low, while PET, SPECT, and other imaging diagnoses with high sensitivity possess shortcomings, including long durations to obtain formal reports and the inability to identify the molecular pathological type of cancer. Cancer surgery is limited by stage and easy to recur. Radiotherapy and chemotherapy often cause damage to normal tissues, leading to evident side effects. Aptamers can selectively and exclusively bind to biomarkers and have, therefore, gained attention as ligands to be targeted for cancer detection and treatment. Gold nanoparticles (AuNPs) are considered as promising nano carriers for cancer diagnosis and treatment due to their strong light scattering characteristics, effective biocompatibility, and easy surface modification with targeted agents. The aptamer-gold nanoparticles targeting delivery system developed herein can combine the advantages of aptamers and gold nanoparticles, and shows excellent targeting, high specificity, low immunogenicity, minor side effects, etc., which builds a bridge for cancer markers to be used in early and efficient diagnosis and precise treatment. In this review, we summarize the latest progress in the application of aptamer-modified gold nanoparticles in cancer targeted diagnosis and delivery of therapeutic agents to cancer cells and emphasize the prospects and challenges of transforming these studies into clinical applications.

Quantification of the major circulating metabolite of BS1801, an ebselen analog, in human plasma.

BS1801 contains two selenium atoms in its structure, which is a specific inhibitor of thioredoxin reductase intended to treat fibrotic interstitial pneumonia (control pulmonary fibrosis) and liver fibrosis. It is currently in phase I clinical trial. However, there was no report about the metabolic transformation and pharmacokinetics of BS1801. In this study, BS1801 metabolites were characterized in the hepatocytes of different species (monkey, dog, mouse, rat, and human) and plasma specimens using the ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC/Q-TOF MS) method. After incubation, BS1801 could not be detected in the hepatocytes of different species and human plasma. Five metabolites were identified based on the characteristic peak clusters of selenium atoms in the mass spectrum, combined with the product ions obtained by MS-MS through collision-induced-dissociation (CID), including M1 (reduction metabolite), M2 (reduction and Se-methylation metabolite), M4 (M2 further oxidized metabolite) and M5 (Se-methylation and Se-glucuronidation conjugation metabolite), of which the amount of M2 was the highest. By comparing the LC-MS information with the synthesized reference substance, the structure of M2 was confirmed. The principal BS1801 metabolic pathways were identified as reduction and Se-methylation in humans. Subsequently, an accurate and fast LC-MS/MS method was established to verify the major metabolite M2 in human plasma. Acetonitrile-induced protein precipitation was employed to extract M2 from human plasma. The metabolite was separated through XDB-C18 (4.6 × 50 mm, 1.8 µm) under isocratic elution with ammonium acetate (5 mM) containing 0.1% formic acid solution (A) and acetonitrile (B) as the mobile phases. A deuterated internal standard for M2 was prepared to overcome the influence of matrix effects during the detection. The bioanalytical method was shown to be precise, specific, accurate, and good linearity over the range of 3.00-3000 ng/mL, and was implemented to assess the pharmacokinetic profiles of M2 in healthy volunteers following a single oral administration of 450 mg BS1801. This is the first-ever study to identify and quantify the major circulating metabolite of ebselen analogs in human plasma.

Crokonoids A-C, A Highly Rearranged and Dual-Bridged Spiro Diterpenoid and Two Other Diterpenoids from Croton kongensis.

Crokonoid A (1), a highly rearranged diterpenoid featuring a dual-bridged tricyclo[4.4.1.11,4]dodecane-2,11-dione ring system and its two possible ent-kaurene diterpenoid precursors (2 and 3), was isolated and structurally characterized by solid data from Croton kongensis. Compound 1 exhibited significant cytotoxicity against HL-60 and A-549 cell lines with IC50 values of 1.24 ± 0.56 and 1.92 ± 0.60 µM, respectively.

Evaluation of the adjuvant properties of Astragalus membranaceus and Scutellaria baicalensis GEORGI in the immune protection induced by UV-attenuated Toxoplasma gondii in mouse models.

Human vaccines are not available and current anti-toxoplasma treatment is disappointing. To investigate the possible adjuvant effect of aqueous extracts obtained from medicinal herbs of Astragalus membranaceus (Am) and Scutellaria baicalensis GEORGI (Sb) on the immune response to Toxoplasma gondii in the mouse models induced by ultraviolet (UV)-attenuated T. gondii, this paper studies the possible vaccination strategies to help combat infections with Toxoplasma and looking towards developing new vaccine and approaches. We used UV-attenuated T. gondii (UV-T.g) of RH strain as a vaccine and the extracts of Am (AmE) and Sb (SbE) as adjuvant. Mice were infected by intraperitoneal (i.p.) injection of 10(2) RH tachyzoites alone (infected controls), infected and treated with AmE (T.g+AmE) and SbE (T.g+SbE), respectively; and mice immunized i.p. with UV-T.g alone, UV-T.g co-administrated with AmE (UV-T.g+AmE) or SbE (UV-T.g+SbE), and then challenged with T.g, respectively. The animal survival time, parasite burden in peritoneal lavage fluids, liver histopathological analysis, and levels of serum antibodies among the groups were compared after either infection or challenge. The results showed that, compared to infected controls, infected mice treated with AmE or SbE, or vaccinated mice and then challenged, had significantly prolonged survival time, decreased parasite burden, improved liver histopathological score, and increased Th1-type cellular immune response; furthermore, vaccinated mice co-administrated with AmE or SbE had even longer survival, lower parasite burden, lower liver histopathological score, and higher Th1 response after challenge. Our data demonstrated that the protective immunity of UV-attenuated T. gondii could be markedly enhanced by AmE or SbE co-administration, which suggests that both AmE and SbE may have the potential to be used as effective vaccine adjuvant.