Cinnamaldehyde Alleviates Bone Loss by Targeting Oxidative Stress and Mitochondrial Damage via the Nrf2/HO-1 Pathway in BMSCs and Ovariectomized Mice.

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

A Novel Anti-Osteoporosis Mechanism of VK2: Interfering with Ferroptosis via AMPK/SIRT1 Pathway in Type 2 Diabetic Osteoporosis.

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients' risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as a pivotal mechanism of glucolipotoxicity-mediated death of osteocytes and osteoblast, a novel form of programmed cell death resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), a fat-soluble vitamin, is clinically applied to prevent osteoporosis and improve coagulation. This study aimed to clarify the role and mechanism of VK2 in HG-mediated ferroptosis. We established the mouse T2DOP model by intraperitoneal injection of streptozotocin solution and a high-fat and high-sugar diet. We also cultured bone marrow mesenchymal stem cells (BMSCs) in HG to simulate the diabetic environment in vitro. Based on our data, VK2 inhibited HG-mediated bone loss and ferroptosis, the latter manifested by decreased levels of mitochondrial reactive oxygen species, lipid peroxidation, and malondialdehyde and increased glutathione in vitro. In addition, VK2 treatment was capable of restoring bone mass and strengthening the expression of SIRT1, GPX4, and osteogenic markers in the distal femurs. As for further mechanism exploration, we found that VK2 could activate AMPK/SIRT1 signaling, and knockdown of SIRT1 by siRNA prevented the VK2-mediated positive effect in HG-cultured BMSCs. Summarily, VK2 could ameliorate T2DOP through the activation of the AMPK/SIRT1 signaling pathway to inhibit ferroptosis.

Development of a nomogram to predict surgical site infection after closed comminuted calcaneal fracture.

BACKGROUND: Compared with open comminuted calcaneal fractures, less emphasis is placed on postoperative surgical site infection (SSI) of closed comminuted calcaneal fractures. This study aimed to identify the risk factors associated with SSI and build a nomogram model to visualize the risk factors for postoperative SSI. METHODS: We retrospectively collected patients with closed comminuted calcaneal fractures from the Second Affiliated Hospital of Wenzhou Medical University database from 2017 to 2020. Risk factors were identified by logistics regression analysis, and the predictive value of risk factors was evaluated by ROC (receiver operating characteristic curve). Besides, the final risk factors were incorporated into R4.1.2 software to establish a visual nomogram prediction model. RESULTS: The high-fall injury, operative time, prealbumin, aspartate aminotransferase (AST), and cystatin-C were independent predictors of SSI in calcaneal fracture patients, with OR values of 5.565 (95%CI 2.220-13.951), 1.044 (95%CI 1.023-1.064), 0.988 (95%CI 0.980-0.995), 1.035 (95%CI 1.004-1.067) and 0.010 (95%CI 0.001-0.185) (Ps < 0.05). Furthermore, ROC curve analysis showed that the AUC values of high-fall injury, operation time, prealbumin, AST, cystatin-C, and their composite indicator for predicting SSI were 0.680 (95%CI 0.593-0.766), 0.756 (95%CI 0.672-939), 0.331 (95%CI 0.243-0.419), 0.605 (95%CI 0.512-0.698), 0.319 (95%CI 0.226-0.413) and 0.860 (95%CI 0.794-0.926), respectively (Ps < 0.05). Moreover, the accuracy of the nomogram to predict SSI risk was 0.860. CONCLUSIONS: Our study findings suggest that clinicians should pay more attention to the preoperative prealbumin, AST, cystatin C, high-fall injury, and operative time for patients with closed comminuting calcaneal fractures to avoid the occurrence of postoperative SSI. Furthermore, our established nomogram to assess the risk of SSI in calcaneal fracture patients yielded good accuracy and can assist clinicians in taking appropriate measures to prevent SSI.

[Effects of nitrogen management on maize nitrogen utilization and residual nitrate nitrogen in soil under maize/soybean and maize/sweet potato relay strip intercropping systems].

A large amount of nitrogen (N) fertilizers poured into the fields severely pollute the environment. Reasonable application of N fertilizer has always been the research hotpot. The effects of N management on maize N utilization and residual nitrate N in soil under maize/soybean and maize/ sweet potato relay strip intercropping systems were reported in a field experiment in southwest China. It was found that maize N accumulation, N harvest index, N absorption efficiency, N contribution proportion after the anthesis stage in maize/soybean relay strip intercropping were increased by 6.1%, 5.4%, 4.3%, and 15.1% than under maize/sweet potato with an increase of 22.6% for maize yield after sustainable growing of maize/soybean intercropping system. Nitrate N accumulation in the 0-60 cm soil layer was 12.9% higher under maize/soybean intercropping than under maize/sweet potato intercropping. However, nitrate N concentration in the 60-120 cm soil layer when intercropped with soybean decreased by 10.3% than when intercropped with sweet potato, indicating a decrease of N leaching loss. Increasing of N application rate enhanced N accumulation of maize and decreased N use efficiency and significantly increased nitrate concentration in the soil profile except in the 60-100 cm soil layer, where no significant difference was observed with nitrogen application rate at 0 to 270 kg · hm(-2). Further application of N fertilizer significantly enhanced nitrate leaching loss. Postponing N application increased nitrate accumulation in the 60-100 cm soil layer. The results suggested that N application rates and ratio of base to top dressing had different influences on maize N concentration and nitrate N between maize/soybean and maize/sweet potato intercropping. Maize N concentration in the late growing stage, N harvest index and N use efficiency under maize/soybean intercropping increased (with N application rate at 180-270 kg · hm(-2) and ratio of base to top dressing = 3:2:5) and decreased nitrate leaching loss with yield reaching 7757 kg · hm(-2) on average. However, for maize/sweet potato, N concentration and use efficiency and maize yield increased significantly with N application rate at 180 kg · hm(-2) and ratio of base to top dressing = 5:5 than that under other treatments with yield reaching 6572 kg · hm(-2). Under these circumstances, it would be possible to realize maize high yield, high efficiency and safety of N man- agement under maize/soybean and maize/sweet potato relay strip intercropping systems.