3D-Printed Biomimetic Hydroxyapatite Composite Scaffold Loaded with Curculigoside for Rat Cranial Defect Repair.

The treatment of various large bone defects has remained a challenge for orthopedic surgeons for a long time. Recent research indicates that curculigoside (CUR) extracted from the curculigo plant exerts a positive influence on bone formation, contributing to fracture healing. In this study, we employed emulsification/solvent evaporation techniques to successfully fabricate poly(ε-caprolactone) nanoparticles loaded with curculigoside (CUR@PM). Subsequently, using three-dimensional (3D) printing technology, we successfully developed a bioinspired composite scaffold named HA/GEL/SA/CUR@PM (HGSC), chemically cross-linked with calcium chloride, to ensure scaffold stability. Further characterization of the scaffold's physical and chemical properties revealed uniform pore size, good hydrophilicity, and appropriate mechanical properties while achieving sustained drug release for up to 12 days. In vitro experiments demonstrated the nontoxicity, good biocompatibility, and cell proliferative properties of HGSC. Through alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, cell migration assays, tube formation assays, and detection of angiogenic and osteogenic gene proteins, we confirmed the HGSC composite scaffold's significant angiogenic and osteoinductive capabilities. Eight weeks postimplantation in rat cranial defects, Micro-computed tomography (CT) and histological observations revealed pronounced angiogenesis and new bone growth in areas treated with the HGSC composite scaffold. These findings underscore the scaffold's exceptional angiogenic and osteogenic properties, providing a solid theoretical basis for clinical bone repair and demonstrating its potential in promoting vascularization and bone regeneration.

Lumbar Apex Position as an Independent Risk Factor for Adjacent Segment Diseases in Patients Undergoing Short-level Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate whether lumbar apex position had an impact on the development of adjacent segment disease (ASD) following transforaminal lumbar interbody fusion (TLIF). SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated that solely concentrating on lumbar lordosis value is not suitable and neglecting the significance of lumbar apex can lead to mechanical complications. However, the relationship between lumbar apex and ASD is still not well understood. METHODS: In this retrospective study, 234 consecutive patients who underwent L3-5 or L4-5 TLIF for degenerative diseases were reviewed. The study evaluated the associations between sagittal parameters and pelvic incidence (PI). Patients were labeled "matched" when lumbar apex position aligned with the theoretical target, and "mismatched" when it did not. Multivariate analysis was applied to find the independent risk factors of ASD. Additionally, a focused sub-analysis was performed based on the lumbar apex position (ideal match, cranial from ideal, and caudal from ideal). RESULTS: After an average follow-up period of 70.6 months, 68 cases were identified as having ASD. Postoperatively, 64.7% (44 out of 68) of the patients with ASD exhibited a mismatched lumbar apex, compared to 41% (68 out of 166) of those without ASD (p < 0.001). PI correlated significantly with proximal lordosis (PL) and lordosis distribution index (LDI), but not with distal lordosis (DL). Multivariate analysis identified age, L3-5 fusion, postoperative DL, and postoperative mismatched lumbar apex as independent risk factors of ASD. Upon the sub-analysis, it was discovered that there were unique compensatory strategies in the cranial and caudal groups, with notable variations in postoperative DL, PL, and LDI among three groups (all p value<0.05). CONCLUSION: Lumbar apex position significantly influenced the risk of ASD. To restore the lumbar apex to its ideal position, a proper value and distribution of DL should be attained.

Validation of age-adjusted pelvic incidence minus lumbar lordosis and lordosis distribution index for assessing adjacent-segment disease after short-level lumbar fusion surgery: minimum 5 years of follow-up.

OBJECTIVE: The purpose of this study was to investigate the influence of sagittal alignment according to age-adjusted pelvic incidence minus lumbar lordosis (PI-LL) and lordosis distribution index (LDI) on the occurrence of adjacent-segment disease (ASD) after lumbar fusion surgery. METHODS: This study retrospectively reviewed 234 consecutive patients with lumbar degenerative diseases who underwent 1- or 2-level lumbar fusion surgery. Demographic and radiographic (preoperative and 3-month postoperative) data were collected and compared between ASD and non-ASD groups. Binary logistic regression analysis was performed to evaluate adjusted associations between potential variables and ASD development. A subanalysis was further conducted to assess their relationships in the range of different PI values. RESULTS: With a mean follow-up duration of 70.6 months (range 60-121 months), 118 patients (50.4%) were diagnosed as having cranial radiological ASD. Univariate analyses showed that older age, 2-level fusion, worse preoperative pelvic tilt and LL, lower pre- and postoperative LDI, and more improvement in sagittal vertical axis were significantly correlated with the occurrence of ASD. No significant differences in the PI-LL and age-adjusted PI-LL (offset) were detected between ASD and non-ASD groups. Multivariate analysis identified postoperative LDI (OR 0.971, 95% CI 0.953-0.989, p = 0.002); 2-level fusion (OR 3.477, 95% CI 1.964-6.157, p < 0.001); and improvement of sagittal vertical axis (OR 0.992, 95% CI 0.985-0.998, p = 0.039) as the independent variables for predicting the occurrence of ASD. When stratified by PI, LDI was identified as an independent risk factor in the groups with low and average PI. Lower segmental lordosis (OR 0.841, 95% CI 0.742-0.954, p = 0.007) could significantly increase the incidence of ASD in the patients with high LDI. CONCLUSIONS: Age-adjusted PI-LL may have limited ability to predict the development of ASD. LDI could exert an important effect on diagnosing the occurrence of ASD in the cases with low and average PI, but segmental lordosis was a more significant risk factor than LDI in individuals with high PI.

LncRNA-HOTAIRM1 promotes aerobic glycolysis and proliferation in osteosarcoma via the miR-664b-3p/Rheb/mTOR pathway.

Osteosarcoma (OS), which is a common and aggressive primary bone malignancy, occurs mainly in children and adolescent. Long noncoding RNAs (lncRNAs) are reported to play a pivotal role in various cancers. Here, we found that the lncRNA HOTAIRM1 is upregulated in OS cells and tissues. A set of functional experiments suggested that HOTAIRM1 knockdown attenuated the proliferation and stimulated the apoptosis of OS cells. A subsequent mechanistic study revealed that HOTAIRM1 functions as a competing endogenous RNA to elevate ras homologue enriched in brain (Rheb) expression by sponging miR-664b-3p. Immediately afterward, upregulated Rheb facilitates proliferation and suppresses apoptosis by promoting the mTOR pathway-mediated Warburg effect in OS. In summary, our findings demonstrated that HOTAIRM1 promotes the proliferation and suppresses the apoptosis of OS cells by enhancing the Warburg effect via the miR-664b-3p/Rheb/mTOR axis. Understanding the underlying mechanisms and targeting the HOTAIRM1/miR-664b-3p/Rheb/mTOR axis are essential for OS clinical treatment.

MicroRNA-324-3p inhibits osteosarcoma progression by suppressing PGAM1-mediated aerobic glycolysis.

Osteosarcoma (OS) is the most common primary malignant neoplasm of the bone. Recent studies have indicated that the inhibitory effects of microRNA (miR)-324-3p could affect the development of numerous cancers. However, its biological roles and underlying mechanisms in OS progression remain unexplored. In this study, miR-324-3p expression was markedly reduced in OS cell lines and tissues. Functionally, miR-324-3p overexpression suppressed OS progression and was involved in the Warburg effect. Mechanistically, miR-324-3p negatively regulated phosphoglycerate mutase 1 (PGAM1) expression by targeting its 3'-UTR. Moreover, high expression of PGAM1 promoted OS progression and aerobic glycolysis, which were associated with inferior overall survival in patients with OS. Notably, the tumor suppressor functions of miR-324-3p were partially recovered by PGAM1 overexpression. In summary, the miR-324-3p/PGAM1 axis plays an important role in regulating OS progression by controlling the Warburg effect. Our results provide mechanistic insights into the function of miR-324-3p in glucose metabolism and subsequently on the progression of OS. Targeting the miR-324-3p/PGAM1 axis could be a promising molecular strategy for the treatment of OS.

Sensing and monitoring of edifenphos molecules based on the quantum chemical approach.

The tendency of edifenphos (EDF) species toward boron carbide nanotube (BC3NT) was investigated through density functional theory (DFT) calculations with perfect and defected forms. It was found that perfect BC3NT tube is not capable to adsorb the EDF molecules appropriately. Introducing defects in BC3NT lattice resulted in a noticeable enhancement of interaction with EDF providing the adsorption energy of - 25.66 kcal/mol. It was predicted that the conductivity of complex formed of single vacancy BC3NT tube, SV-BC3NT, and EDF complexes is enhanced by 91.37 times compared with BC3NT tube with no defects. As the solvent dielectric constant increases, a significant change in adsorption energy was reported while slighter variation was observed at dielectric constant values lower than 15. Similar to electric conductivity, the magnetic properties of BC3NT are remarkably enhanced after single vacancy defect and EDF adsorption leads to a highly significant change in magnetic property compared with perfect BC3NT. Graphical abstract.