Background Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study aims to investigate the protective effects of TUDCA in the SCI mouse model and the related mechanism involved. Methods The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on axon degeneration induced by oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added and immunostained with Tuj1. Mice were randomly divided into sham, SCI, and SCI+TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of the vertebra. TUDCA (200 mg/kg) or an equal volume of saline was intragastrically administrated daily post-injury for 14 days. Results We found that TUDCA attenuated axon degeneration induced by H2O2 treatment and protected primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis and promoted axon regeneration and remyelination in the lesion site of the spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated the recovery of limb function. Conclusions TUDCA treatment can alleviate secondary injury and promote functional recovery by reducing oxidative stress, inflammatory response, and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.

The extravagant osteoclast formation and resorption is the main cause of osteoporosis. Inhibiting the hyperactive osteoclastic resorption is considered as an efficient treatment for osteoporosis. Rhaponticin (RH) is a small molecule that has been reported to possess anti-inflammatory, anti-allergic, anti-fibrotic, and anti-diabetic activities. However, the influence of RH on osteoclasts differentiation and function is still unclear. To this end, an array of assays including receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL) induced osteoclastogenesis, tartrate-resistant acidic phosphatase (TRAcP) staining, immunofluorescence, and hydroxyapatite resorption were performed in this study. It was found that RH had significant anti-catabolic effects by inhibiting osteoclastogenesis and bone resorption without cytotoxicity. Mechanistically, the expression of NADPH oxidase 1 (Nox1) was found to be suppressed and antioxidant enzymes including catalase, superoxide dismutase 2 (SOD-2), and heme oxygenase-1(HO-1) were enhanced following RH treatment, suggesting RH exhibited antioxidant activity by reducing the generation of reactive oxygen species (ROS) as well as enhancing the depletion of ROS. In addition, MAPKs, NF-κB, and intracellular Ca2+ oscillation pathways were significantly inhibited by RH. These changes led to the deactivation of osteoclast master transcriptional factor-nuclear factor of activated T cells 1 (NFATc1), as examined by qPCR and Western blot assay, which led to the decreased expression of downstream integrin β3, c-Fos, cathepsin K, and Atp6v0d2. These results suggested that RH could effectively suppress RANKL-regulated osteoclast formation and bone resorption. Therefore, we propose that RH can represent a novel natural small molecule for the treatment of osteoporosis by inhibiting excessive osteoclast activity.

BackgroundIt is unclear whether common genetic variants of the RET proto-oncogene contribute to disease susceptibility, clinical severity, and thyroid function in differentiated thyroid cancer (DTC).MethodsA total of 300 DTC patients and 252 healthy controls were enrolled in this study. Seven RET tagging single nucleotide polymorphisms were genotyped using the KASPar platform.ResultsSubgroup analysis showed that concomitant thyroid benign diseases were less likely to occur in DTC subjects with the rs1799939 AG or AG plus AA genotypes (odds ratio (OR) = 1.93 and 1.88, P = 0.009 and 0.011, respectively). A rare haplotype, CGGATAA, was associated statistically with a reduced risk of DTC (OR = 0.18, P = 0.001). Concerning the aggressive features of DTC, higher level of N stage was more likely to occur in subjects carrying the wild-type genotypes at rs1800860 site (for dominant model: OR = 0.48, P = 0.008). Another rare haplotype, CAAGCGT, conferred increased risk for the occurrence of distant metastasis (OR = 7.57, P = 0.009). Notably, higher thyroid stimulating hormone levels and lower parathyroid hormone levels were found in patients with rs2075912, rs2565200, and rs2742240 heterozygotes and rare homozygotes; similar results were observed between PTH levels and rs1800858.ConclusionThis study provided useful information on RET variants that should be subjected to further study.

Background Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study is aim to investigate the protective effects of TUDCA in SCI mouse model and the related mechanism involved.Methods The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added. Mice were randomly divided into sham, SCI and TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of vertebra. TUDCA (200 mg/kg) or equal volume of saline was intragastrically administrated daily post injury for 14 days. ResultsWe found that TUDCA reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and restored superoxide dismutase (SOD) activity to protect primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis; promoted axon regeneration and remyelination in the lesion site of spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated recovery of limb function.ConclusionsTUDCA treatment can alleviate secondary injury and promote functional recovery through reducing oxidative stress, inflammatory response and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.