Cytoprotective effect of Fufang Lurong Jiangu capsule against hydrogen peroxide-induced oxidative stress in bone marrow stromal cell-derived osteoblasts through the Nrf2/HO-1 signaling pathway.

OBJECTIVE: Oxidative stress is increasingly recognized as a risk factor associated with the development and progression of osteoporosis. Fufang Lurong Jiangu Capsule (FLJC) has a known anti-osteoporotic effect, but its pharmacological effect on osteoblasts is not clearly understood. This study was designed to investigate FLJC effects/mechanisms on in vitro hydrogen peroxide (H2O2)-induced oxidative damage of osteoblasts and on in vivo lipopolysaccharide (LPS)-induced mice bone loss. FLJC alleviates osteoporosis via unknown pharmacological mechanisms. METHODS: Chemical compositions of FLJC preparations were analyzed using high-performance liquid chromatographic fingerprinting. After rat bone marrow mesenchymal stem cell differentiation induction, resulting osteoblasts received various 48 h FLJC pretreatments before H2O2-based (200 µM) oxidative stress exposure. FLJC effects were measured on osteoblast cell viability, morphological changes, levels of intracellular reactive oxygen species (ROS), localization of mitochondria, activity of antioxidant enzymes, alkaline phosphatase (ALP) and mineralization, the secretion of Col I and expression of osteogenic markers. The percentages of apoptosis were determined by flow cytometric analysis; apoptosis-related protein levels, including nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) with or without Nrf2 inhibitor were analyzed via western blot. Hematoxylin and eosin (H&E) and ALP staining revealed in vivo FLJC effect on mice LPS-induced bone loss. RESULTS: Five chemical components in FLJC were identified, and fingerprint analysis showed good reproducibility. FLJC pretreatment significantly reduced H2O2-induced ROS levels in osteoblasts and increased antioxidant enzyme activities to reduce oxidative damage. With regard to osteoblast differentiation, FLJC pretreatment increased ALP expression, as well as levels of mineralization and osteoblast markers. Additionally, FLJC protected against H2O2-induced apoptosis by inhibiting changes in expression of major Bcl-2 family effector proteins of the mitochondrial apoptosis pathway. Furthermore, FLJC protected cells from H2O2-induced oxidative damage by up-regulating Nrf2 and HO-1 protein levels. Finally, we confirmed that FLJC administration could reverse the bone loss in LPS-induced mice. CONCLUSION: These results indicate that FLJC may significantly attenuate oxidative damage of osteoblasts induced by H2O2 via the Nrf2/HO-1 signaling pathway, providing new insights to guide development of treatments for osteoporosis induced by oxidative injury.

Risk factors associated with failed sonographically guided saline hydrostatic intussusception reduction in children.

OBJECTIVES: The aim of this study was to explore the risk factors associated with failed sonographically guided saline hydrostatic intussusception reduction in children. METHODS: We retrospectively reviewed the medical records and sonograms of 288 cases of intussusception over a 3-year period. Logistic regression was used for the analysis of the clinical data (sex, age, duration of symptoms, and presence or absence of emesis or bloody stool) and sonographic features (initial location and intussusception length, presence or absence of free peritoneal fluid, and trapped fluid in the intussusception). RESULTS: The sex, age, and duration of symptoms showed no significant impact on the hydrostatic reducibility. The success rate became significantly lower for the intussusception cases with the presence of bloody stool, free peritoneal fluid, and trapped fluid in the intussusception (P < .05). The success rate was also lower when the intussusceptions were located in the left side of the abdomen (P < .05). For the above risk factors, the odds ratios from multivariate logistic regression analysis were 174.68 for initial intussusception location in the descending colon/rectum, 36.06 for the presence of peritoneal fluid, 13.22 for trapped fluid in the intussusception, and 9.27 for the presence of bloody stool. CONCLUSIONS: An initial intussusception location in the descending colon/rectum, the presence of peritoneal fluid, trapped fluid in the intussusception, and bloody stool are the most important risk factors for failure of sonographically guided saline hydrostatic intussusception reduction.