[Expression pattern of beta-amyloid in the peri-infarct area and ipsilateral thalamus of rats after focal cerebral cortex infarction].

Objective: To investigate the expression pattern of beta-amyloid (Aß) in rats after focal cerebral cortex infarction, and to identify whether the Aß expression in the ipsilateral thalamus was directly related to focal cerebral ischemia. Methods: The distal middle cerebral artery occlusion (MCAO) was performed by electrocoagulation in rats. The rats were divided randomly into sham group (n=18) and MCAO group (n=30) . We used 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining to detect the location of cerebral infarction and Aß expression, respectively. Results: TTC staining showed that the cerebral infarction was consistently restricted to the frontal and temporoparietal cortex. In the peri-infarct area of the MCAO group, Aß expression began at day 2, reached the maximum level at day 7, and disappeared almost completely at day 28 after MCAO. The Aß appeared as diffuse small dots, and was located in neurons and astrocytes at day 2 and day 28, respectively. Meanwhile, in the ipsilateral thalamus, Aß expression began at day 3, increased markedly at day 7, and remained until day 28 after MCAO. The Aß was located constantly in the extracellular region of the ipsilateral thalamus, and aggregated gradually from small dots to dense plaque-like deposits with the time of ischemia. Conclusions: There are dynamic changes of Aß expression in both the peri-infarct area and the ipsilateral thalamus following MCAO. The Aß expression in the ipsilateral thalamus is not directly related to focal cerebral ischemia.

Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming.

Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of the electron transport chain component cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage-dependent growth and acquired invasive phenotypes. Disruption of the CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling includes activation of PI3-kinase, IGF1R and Akt, Ca2(+)-sensitive transcription factors and also TGFß1, MMP16 and periostin, which are involved in oncogenic progression. Whole-genome expression analysis showed the upregulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mitochondrial DNA depletion, although distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be the hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in the CcO complex can potentially induce tumor progression.

Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers.

Arginylation is an emerging post-translational modification mediated by arginyltransferase (ATE1) that is essential for mammalian embryogenesis and regulation of the cytoskeleton. Here, we discovered that Ate1-knockout (KO) embryonic fibroblasts exhibit tumorigenic properties, including abnormally rapid contact-independent growth, reduced ability to form cell-cell contacts and chromosomal aberrations. Ate1-KO fibroblasts can form large colonies in Matrigel and exhibit invasive behavior, unlike wild-type fibroblasts. Furthermore, Ate1-KO cells form tumors in subcutaneous xenograft assays in immunocompromised mice. Abnormal growth in these cells can be partially rescued by reintroduction of stably expressed specific Ate1 isoforms, which also reduce the ability of these cells to form tumors. Tumor array studies and bioinformatics analysis show that Ate1 is downregulated in several types of human cancer samples at the protein level, and that its transcription level inversely correlates with metastatic progression and patient survival. We conclude that Ate1-KO results in carcinogenic transformation of cultured fibroblasts, suggesting that in addition to its previously known activities Ate1 gene is essential for tumor suppression and also likely participates in suppression of metastatic growth.

[An autopsy study of 7 sudden death cases due to acute hemorrhagic enteritis].

7 sudden death cases due to acute hemorrhagic enteritis were analyzed to investigate the age, sex, clinical symptoms, medical diagnosis and anatomic results. The results showed that, because the pathological changes were not typical and clinical symptoms were varid, It was easy to come to erroneous diagnosis and cause medical disputes.