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.

Preparation, characterization and anti-diabetic activity of polysaccharides from adlay seed.

Coix (Coix lachryma-jobi L.), commonly known as adlay, is a traditional Chinese medicine for thousands of years. A new water-soluble polysaccharide with anti-diabetic activity was extracted and purified from the adlay seed (PAS). The structure and physicochemical properties of PAS were determined by Fourier transform infrared spectrometer (FT-IR) and scanning electron microscopy (SEM). Structural analysis indicated that PAS had a porous surface and relatively loose distribution. After intragastric administered PAS for 4 weeks, biochemical analysis demonstrated dose dependent anti-diabetic activity. These results showed that PAS decreased blood glucose and insulin levels. In addition, mice fed the PAS showed significantly reduced the plasma levels of amyloid ß42 and glycated hemoglobin (HbA1c), while the expression of glucagon-like peptide-1 (GLP-1) was markedly increased. Our study introduced a new polysaccharide PAS with unique anti-diabetic activity, which can be used as a potential dietary supplement or functional food.

Hidden blood loss and the influential factors after percutaneous kyphoplasty surgery.

PURPOSE: Percutaneous kyphoplasty (PKP) is a minimally invasive procedure for the treatment of osteoporotic vertebral compression fractures (OVCFs). It is generally considered that there is little blood loss during the surgery. However, a significant perioperative hidden blood loss (HBL) is neglected. This study was to examine the amount of HBL and determine the influential factors during PKP. METHODS: From January 2015 to January 2016, 115 patients with OVCFs who were scheduled to have a PKP were enrolled in this study. The factors analyzed included gender, age, body mass index (BMI), percentage of vertebral height loss, percentage of vertebral height restoration, number of fracture levels, bone mineral density (BMD), duration of symptom, cement leakage, and other internal diseases (hypertension, diabetes mellitus). According to Gross's formula, each patient's height, weight, and pre-operative and post-operative hematocrit were recorded and used for calculating the blood loss. Influential factors were further analyzed by multivariate linear regression analysis and t test. RESULTS: The mean HBL was 282 ± 162 mL (mL) and the post-operative Hb loss was 8.7 ± 5.4 g per liter (g/L). According to multivariate linear regression analysis, patients with severe vertebral height loss (P = 0.016), better vertebral height restoration (P = 0.038), and multi-segmental vertebral fractures (P = 0.000) had a higher amount of HBL. Fresh fractures (P = 0.008) and cement leakage (P = 0.004) were also important factors to increase HBL, whereas gender (P = 0.642), age (P = 0.203), BMI (P = 0.075), hypertension (P = 0.099), diabetes mellitus (P = 0.905), and BMD (P = 0.521) were not correlate with HBL. When we compared the incidence of anemia between pre-operative and post-operative, we found that the incidence of anemia was significantly associated with HBL (P = 0.000). CONCLUSIONS: HBL cannot be ignored in perioperative period, especially for poor physical condition and multiple fractures patients. Having a correct understanding of HBL can help improve clinical assessment capabilities, ensuring patients' safety.