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Mitochondria-mediated apoptosis (MMA) is a preferential option for cancer therapy due to the presence of cell-suicide factors in mitochondria, however, low permeability of mitochondria is a bottleneck for targeting drug delivery. In this paper, glycyrrhetinic acid (GA), a natural product from Glycyrrhiza glabra, is found to be a novel mitochondria targeting ligand, which can improve mitochondrial permeability and enhance the drug uptake of mitochondria. GA-functionalized graphene oxide (GO) is prepared and used as an effective carrier for targeted delivery of doxorubicin into mitochondria. The detailed in vitro and in vivo mechanism study shows that GA-functionalized GO causes a decrease in mitochondrial membrane potential and activates the MMA pathway. The GA-functionalized drug delivery system demonstrates highly improved apoptosis induction ability and anticancer efficacy compared to the non-GA-functionalized nanocarrier delivery system. The GA-functionalized nanocarrier also shows low toxicity, suggesting that it can be a useful tool for drug delivery.

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BackgroundA retrospective study of staged surgery for severe rigid scoliosis. The purpose of this study was to evaluate the result of staged surgery in treatment of severe rigid scoliosis and to discuss the indications.MethodsFrom 1998 to 2006, 21 cases of severe rigid scoliosis with coronal Cobb angle more than 80° were treated by staged surgeries including anterior release and halo-pelvic traction as first stage surgery and posterior instrumentation and spinal fusion as second stage. Pedicle subtraction osteotomy(PSO) was added in second stage according to spine rigidity. Among the 21 patients, 8 were male and 13 female with an average age of 15.3 years (rang from 4 to 23 years). The mean pre-operative Cobb angle was 110.5° (80°-145°) with a mean spine flexibility of 13%. Radiological parameters at different operative time points were analyzed (mean time of follow-up: 51 months).ResultsExternal appearance of all patients improved significantly. The average correction rate was 65.2% (ranging from 39.8% to 79.5%) with mean correction loss of 2.23° at the end of follow-up. No decompensation of trunk has been found. Mean distance between the midline of C7 and midsacral line was 1.19 cm ± 0.51. Two patients had neurological complications: one patient had motor deficit and recovered incompletely.ConclusionStaged operation and halo-pelvic traction offer a safe and effective way in treatment of severe rigid scoliosis. Patients whose Cobb angle was more than 80° and the flexibility of the spine was less than 20% should be treated in this way, and those whose flexibility of the spine was less than 10% and the Cobb angle remained more than 70° after 1st stage anterior release and halo-pelvic traction should undergo pedicle subtraction osteotomy (PSO) in the second surgery.

BACKGROUND AND PURPOSESublesional osteoporosis predisposes individuals with spinal cord injury (SCI) to an increased risk of low-trauma fracture. The aim of the present work was to investigate the effect of treatment with resveratrol (RES) on sublesional bone loss in spinal cord-injured rats. EXPERIMENTAL APPROACHComplete SCI was generated by surgical transaction of the cord at the T10-12 level. Treatment with RES (400 mg·kg −1 body mass per day −1 , intragastrically) was initiated 12 h after the surgery for 10 days. Then, blood was collected and femurs and tibiae were removed for evaluation of the effects of RES on bone tissue after SCI. KEY RESULTSTreatment of SCI rats with RES prevented the reduction of bone mass including bone mineral content and bone mineral density in tibiae, preserved bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in tibiae, and preserved mechanical strength including ultimate load, stiffness, and energy in femurs. Treatment of SCI rats with RES enhanced femoral total sulfhydryl content, reduced femoral malondialdehyde and IL-6 mRNA levels. Treatment of SCI rats with RES suppressed the up-regulation of mRNA levels of PPARγ, adipose-specific fatty-acid-binding protein and lipoprotein lipase, and restored mRNA levels of Wnt1, low-density lipoprotein-related protein 5, Axin2, ctnnb1, insulin-like growth factor 1 (IGF-1) and receptor for IGF-1 in femurs and tibiae. CONCLUSIONS AND IMPLICATIONSTreatment with RES attenuated sublesional bone loss in spinal-cord-injured rats, associated with abating oxidative stress, attenuating inflammation, depressing PPARγ signalling, and restoring Wnt/β-catenin and IGF-1 signalling.Abbreviations 25(OH)D, 25-hydroxyvitamin D; aP2, adipose-specific fatty-acid-binding protein; BFR/BS, bone formation rate/bone surface; BMD, bone mineral density; BV/TV, trabecular bone volume fraction; DPD, deoxypyridinoline; ES/BS, eroded surface/bone surface; IGF-1, insulin-like growth factor 1; IGF-1R, receptor for insulin-like growth factor; IGFBP5, insulin-like growth-factor-binding-protein 5; LPL, lipoprotein lipase; Lrp5, low-density lipoprotein-related protein 5; MAR, mineral apposition rate; MDA, malondialdehyde; Oc.S/BS, osteoclast surface/bone

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has aroused great public health concern worldwide. Currently, COVID-19 epidemic is spreading in many countries and regions around the world. However, the study of SARS-CoV-2 is still in its infancy, and there is no specific therapeutics. Here, we summarize the genomic characteristics of SARS-CoV-2. In addition, we focus on the mechanisms of SARS-CoV-2 infection, including the roles of angiotensin converting enzyme II (ACE2) in cell entry, COVID-19 susceptibility and COVID-19 symptoms, as well as immunopathology such as antibody responses, lymphocyte dysregulation, and cytokine storm. Finally, we introduce the research progress of animal models of COVID-19, aiming at a better understanding of the pathogenesis of COVID-19 and providing new ideas for the treatment of this contagious disease.

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