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Abstract: Colonic perforation is an extremely rare complication following ventriculoperitoneal (VP) shunting. The common treatment is to remove the perforating catheter and replace it with a new one. Here we report a case of colonic perforation from VP shunting in a 2-year, 8-month-old boy who presented with the distal end of the shunt catheter protruding out of his anus. The distal catheter was removed via the anus and the perforation repaired transanally. The patient's postoperative course was uneventful. This case reminds us that we should not make another rush to perform a new shunt operation unless there are some manifestations of hydrocephalus. Potential mechanisms of migration and its management strategy are discussed. [Copyright &y& Elsevier]

Summary: Gliomas are malignant primary brain tumors with high morbidity. This tumor has a feature of resistance to chemotherapy and radiotherapy and the underlying mechanism is not yet clear. Autophagy is an evolutionarily conserved process of cytoplasm and cellular organelle in lysosome degradation. Under poor conditions, cells use autophagy to recycle cellular components to sustain metabolism and to prevent the accumulation of damaged, toxic proteins and organelles. More and more recent experimental results suggest that autophagy allows tumor cells survive gene therapy, chemotherapy or nutrient deficient environment. Therefore, we propose the hypothesis that autophagy may be one of the factors influencing on malignant glioma’s resistance to therapy. Although there is not yet reaching an agreement about the effects of autophagy on tumor cells survival and death and much more studies are needed to prove the effects of autophagy on malignant gliomas, it gives us a new direction to investigate the mechanism underlying therapy resistance of malignant gliomas. [Copyright &y& Elsevier]

Abstract: We describe a rare scalp malignant peripheral nerve sheath tumor (MPNST) with cranial destruction and intracranial extension in a 52-year-old male with neurofibromatosis type 1 (NF1). The scalp tumor measured 22cm×18cm, with local surface ulceration. Skin examination revealed many café-au-lait spots and small, hard dermal nodules on the trunk. CT scans revealed the scalp tumor to have heterogeneous density with partial destruction of the right parietal cranium; on T1-weighted MRI the scalp tumor displayed heterogeneous hypointensity, whereas on T2-weighted and fluid-attenuated inversion recovery MRI it was hyperintense. The tumor was excised totally and the scalp reconstructed using a skin flap isolated from the lateral aspect of the left thigh. Histological examination confirmed that the tumor was an MPNST. The patient recovered uneventfully and was well at the 6-month follow-up, with no local or other tumor recurrence noted. [ABSTRACT FROM AUTHOR]

Summary: Brain ischemia has been an important risk factor for human being health, there is no effective medicine can be used to protect delayed neuronal injury or death secondary to blood reperfusion following ischemia. Recent discovery shows protein aggregation is an important factor resulting in ischemia-induced neuron death. Therefore, we propose the hypothesis that inhibiting protein aggregation may be an effective way to prevent delayed neuronal death after transient ischemia. At present, in vitro studies show some chemicals such as 4PBA (sodium 4-phenylbutyrate) and trehalose have the features of antagonizing protein aggregation in vitro. Moreover, polyQ-binding peptide (QBP1), geldanamycin, amino acids and amino acid derivatives have been also used in vitro to decrease aggregation and to increase protein stability. Although in vivo and systematical study should be performed to evaluate their effects of anti-protein aggregation, this enlightening us on using them to protect ischemic-induced neuronal death, and find new potential chemicals or methods which could be effective in keeping protein stable and prevent forming aggregates. [Copyright &y& Elsevier]

Chromatinolysis refers to enzymatic degradation of nuclear DNA and is regarded as one of the crucial events leading to cell death. Mixed-lineage kinase domain-like protein (MLKL) has been identified as a key executor of necroptosis, but it remains unclear whether MLKL contributes to necroptosis via regulation of chromatinolysis. In this study, we find that shikonin induces MLKL activation and chromatinolysis in glioma cells in vitro and in vivo, which are accompanied with nuclear translocation of AIF and γ-H2AX formation. In vitro studies reveal that inhibition of MLKL with its specific inhibitor NSA or knockdown of MLKL with siRNA abrogates shikonin-induced glioma cell necroptosis, as well as chromatinolysis. Mechanistically, activated MLKL targets mitochondria and triggers excessive generation of mitochondrial superoxide, which promotes AIF translocation into nucleus via causing mitochondrial depolarization and aggravates γ-H2AX formation via improving intracellular accumulation of ROS. Inhibition of nuclear level of AIF by knockdown of AIF with siRNA or mitigation of γ-H2AX formation by suppressing ROS with antioxidant NAC effectively prevents shikonin-induced chromatinolysis. Then, we found that RIP3 accounts for shikonin-induced activation of MLKL, and activated MLKL reversely up-regulates the protein level of CYLD and promotes the activation of RIP1 and RIP3. Taken together, our data suggest that MLKL contributes to shikonin-induced glioma cell necroptosis via promotion of chromatinolysis, and shikonin induces a positive feedback between MLKL and its upstream signals RIP1 and RIP3. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of programmed cell death decided by iron-dependent lipid peroxidation, but its role in glioma cell death remains unclear. In this study, we found Pseudolaric acid B (PAB) inhibited the viabilities of glioma cells in vitro and in vivo, which was accompanied by abnormal increases of intracellular ferrous iron, H2O2 and lipid peroxidation, as well as depletion of GSH and cysteine. In vitro studies revealed that the lipid peroxidation and the cell death caused by PAB were both inhibited by iron chelator deferoxamine, but exacerbated by supplement of ferric ammonium citrate. Inhibition of lipid peroxidation with ferrostatin-1 or GSH rescued PAB-induced cell death. Morphologically, the cells treated with PAB presented intact membrane, shrunken mitochondria with increased membrane density, and normal-sized nucleus without chromatin condensation. Mechanistically, PAB improved intracellular iron by upregulation of transferrin receptor. The increased iron activated Nox4, which resulted in overproduction of H2O2 and lipid peroxides. Moreover, PAB depleted intracellular GSH via p53-mediated xCT pathway, which further exacerbated accumulation of H2O2 and lipid peroxides. Thus, PAB triggers ferroptosis in glioma cells and is a potential medicine for glioma treatment. [ABSTRACT FROM AUTHOR]

RIP1 and RIP3 are necroptosis initiators, but their roles in regulation of glycolysis remain elusive. In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA. Moreover, shikonin also triggered accumulation of intracellular H2O2 and depletion of GSH and cysteine. Mitigation of intracellular H2O2 via supplement of GSH reversed shikonin-induced glycolysis suppression. The role of intracellular H2O2 in regulation of glycolysis suppression was further confirmed in the cells treated with exogenous H2O2. Notably, inhibition of RIP1 or RIP3 prevented intracellular H2O2 accumulation, which was correlated with preventing shikonin-induced downregulation of x-CT and depletion of GSH and cysteine. In addition, supplement of pyruvate effectively inhibited shikonin- or exogenous H2O2-induced accumulation of intracellular H2O2 and glioma cell death. Taken together, we demonstrated in this study that RIP1 and RIP3 contributed to shikonin-induced glycolysis suppression via increasing intracellular H2O2. [ABSTRACT FROM AUTHOR]