NUCB2 inhibition antagonizes osteosarcoma progression and promotes anti-tumor immunity through inactivating NUCKS1/CXCL8 axis.

The oncogenic properties of Nucleobindin2 (NUCB2) have been observed in various cancer types. Nevertheless, the precise understanding of the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma remains limited. This investigation reported that NUCB2 was significantly increased upon glucose deprivation-induced metabolic stress. Elevated NUCB2 suppressed glucose deprivation-induced cell death and reactive oxygen species (ROS) increase. Depletion of NUCB2 resulted in a reduction in osteosarcoma cell proliferation as well as metastatic potential in vitro and in vivo. Mechanically, NUCB2 ablation suppressed C-X-C Motif Chemokine Ligand 8 (CXCL8) expression which then reduced programmed cell death 1 ligand 1 (PD-L1) expression and stimulated anti-tumor immunity mediated through cytotoxic T cells. Importantly, a combination of NUCB2 depletion with anti-PD-L1 treatment improved anti-tumor T-cell immunity in vivo. Moreover, we further demonstrated that NUCB2 interacted with NUCKS1 to inhibit its degradation, which is responsible for the transcriptional regulation of CXCL8 expression. Altogether, the outcome emphasizes the function of NUCB2 in osteosarcoma and indicates that NUCB2 elevates osteosarcoma progression and immunosuppressive microenvironment through the NUCKS1/CXCL8 pathway.

Holomycin, a novel NLRP3 inhibitor, attenuates cartilage degeneration and inflammation in osteoarthritis.

The contribution of the NLRP3 inflammasome in osteoarthritis (OA) pathogenesis has been uncovered in recent years. Holomycin (HL) has recently been identified as a novel NLRP3 inflammasome inhibitor. Herein, we aimed to explore the benefits of HL for OA. A chondrocyte-macrophage co-culture system and the destabilization of the medial meniscus (DMM) mouse model were established to study the effect of HL on OA in vitro and in vivo. ECM degradation-related proteins (MMP-13, aggrecan, and Collagen II) were detected by Western blot (WB) and immunohistochemistry (IHC). The chondrocyte senescence was determined by cell cycle, p16 and p21 expressions, and SA-ß-Gal staining. The cartilage degeneration was evaluated by OARSI score and Safranin O and H&E staining. Inflammation and NLRP3 inflammasome activation were investigated via RT-PCR, ELISA, WB, and IHC. In vitro studies showed that IL-1ß stimulation caused a significant increase of MMP13, p16, p21, and ß-galactosidase expressions, a G1-phase arrest, and a down-regulation of aggrecan and Collagen II in chondrocytes, and the increased expressions of IL-6, CXCL-1, IL-1ß, NLRP3, and Caspase 1 p20 in both chondrocyte and macrophage. Meanwhile, HL administration could partly reverse these effects induced by IL-1ß. In DMM mouse models, intra-articular administration of HL alleviated cartilage degeneration and inflammation, as evidenced by the decrease of OARSI score and MMP13, p16, p21, Collagen II, IL-6, and CXCL-1 expressions and the restoration of chondrocyte number, proteoglycan, and MMP13 expression in cartilage tissues. This study identified HL as a promising agent for OA.

[Comparison of full thread compression cannulated screw and partial thread cannulated screw in treatment of femoral neck fracture].

Objective: To compare the effectiveness of full thread compression cannulated screw and partial thread cannulated screw in the treatment of femoral neck fracture. Methods: A retrospective analysis was made on 152 patients with femoral neck fractures, who met the selection criteria, between April 2013 and February 2021. The fractures were fixed with the full thread compression cannulated screws in 74 cases (trial group) and the partial thread cannulated screws in 78 cases (control group). There was no significant difference in general data such as age, gender, body mass index, cause of injury, time from injury to operation, and the side, Garden typing, Pauwels typing of fracture between the two groups (P>0.05). The operation time, intraoperative blood loss, hospital stay, follow-up time, and Harris score were recorded in both groups. X-ray films were performed to evaluate the quality of fracture reduction and bone healing, the changes of neck-shaft angle, the changes of femoral neck, as well as the occurrence of internal fixation failure, screw back-out, and osteonecrosis of the femoral head. Results: There was no significant difference in operation time and hospital stay between the two groups (P>0.05). However, the intraoperative blood loss in the trial group was significantly lower than that in the control group (P<0.05). Patients in both groups were followed up, with the follow-up time of (24.11±4.04) months in the trial group and (24.10±4.42) months in the control group, and the difference was not significant (P>0.05). Postoperative X-ray films showed that there was no significant difference in fracture reduction grading between the two groups (P>0.05). Six cases in the trial group developed bone nonunion and 7 cases in the control group, the fractures of the other patients healed, and the healing time was significantly shorter in the trial group than in the control group (P<0.05). There was no significant difference in the incidence of bone nonunion between the two groups (P>0.05). During follow-up, 2 cases in the trial group and 5 cases in the control group had osteonecrosis of the femoral head, the difference was not significant (P>0.05), and the patients with osteonecrosis of the femoral head were treated with secondary operation. The screw back-out occurred in 3 cases of the trial group and in 9 cases of the control group, showing no significant difference (P>0.05). But the screw back-out distance was significantly shorter in the trial group than in the control group (P<0.05). The incidence of internal fixation failure in the trial group (4 cases) was significantly lower than that in the control group (14 cases) (P<0.05). The incidence of femoral neck shortening and the change of neck-shaft angle at 1 year after operation were significantly lower in the trial group than in the control group (P<0.05). The Harris score at last follow-up was significantly higher in the trial group than in the control group (P<0.05). Conclusion: Compared with the partial threaded cannulated screws, the full threaded cannulated compression screws can effectively maintain fracture reduction, avoid femoral neck shortening, and internal fixation failure. It is a better choice for femoral neck fracture.