ABSTRACT
Alzheimer' s disease (AD) is an age-related neurodegenerative disease which seriously damages the physical and mental health of the elderly and causes huge economic pressure to the society. However, the pathogenesis of AD is not completely elucidated. There is still no effective drug to cure AD in clinical practice. Tau protein is a soluble and non-aggregating microtubule-related protein, which can stabilize microtubule structure. The structure and function of Tau protein are abnormal in AD' s brain while under pathological conditions, and the abnormal Tau protein aggregates to insoluble neurofibrillary tangles which damages microtubules and leads to cognitive dysfunction. These changes of Tau protein are regulated by a variety of post-translational modifications, which directly change the properties and functions of proteins by attaching specific chemical moieties to Tau protein's C-terminus or N-terminus. It's confirmed that a variety of Tau post-translational modifications, like phosphorylation, glycosylation, acetylation and sumoylation is abnormal in AD's brain, which is closely related to Tau degradation and the accumulation of toxic substances. In this review, we summarized the latest progress supporting the role of exercise regulated Tau post-translational modification in the prevention and treatment of Alzheimer's disease. Firstly, exercise inhibits tau protein hyperphosphorylation by suppressing the activity of GSK-3β and MAPKs and possibly by up-regulating the activity of PP2A. Secondly, exercise increases tau protein O-GlcNAcylation by up-regulating the expression of GLUT1 and GLUT3, also possibly by regulating the balance of activity of OGT and OGA. Thirdly, exercise decreases tau protein acetylation possibly by inhibiting p300 and activating SIRT1; exercise regulates the acetylation of Tau KXGS possibly by inhibiting HDAC6. Lastly, exercise inhibits abnormal Tau sumoylation possibly by regulating the co-location sites of phosphorylation and sumoylation.
ABSTRACT
<p><b>OBJECTIVE</b>To study the clinicopathologic and immunohistochemical features of mesenchymal chondrosarcoma.</p><p><b>METHODS</b>The clinical and histologic features of 23 cases of mesenchymal chondrosarcoma were analyzed. Immunohistochemical study was also performed in 14 of the cases.</p><p><b>RESULTS</b>The age of patients ranged from 12 to 47 years. Fourteen of them occurred in males. Thirteen cases involved the bony skeleton and 5 cases affected the soft tissue. The patients presented with pain and/or swelling. Histologically, the tumor consisted of a mixture of undifferentiated small round cells and hyaline cartilage. Transition between the two components was demonstrated and growth plate-like cartilage was observed. Immunohistochemical study showed that the small round cells were positive for Sox9 (14/14), CD99 (12/14), vimentin (6/14), CD56 (4/14), CD57 (4/14), neuron-specific enolase (3/14) and desmin(1/14). They were negative for Coll-II, S-100 protein, epithelial membrane antigen, pan-cytokeratin, synaptophysin, chromogranin A, CD34 and c-erbB2.</p><p><b>CONCLUSIONS</b>Mesenchymal chondrosarcoma is a rare malignant tumor. Thorough histologic examination, when coupled with immunohistochemical findings, is helpful in arriving at a correct diagnosis.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , 12E7 Antigen , Antigens, CD , Metabolism , Bone Neoplasms , Diagnostic Imaging , Metabolism , Pathology , General Surgery , Cell Adhesion Molecules , Metabolism , Chondrosarcoma, Mesenchymal , Diagnostic Imaging , Metabolism , Pathology , General Surgery , Follow-Up Studies , Immunohistochemistry , Lung Neoplasms , Mediastinal Neoplasms , Diagnostic Imaging , Metabolism , Pathology , General Surgery , Neoplasm Recurrence, Local , Orbital Neoplasms , Diagnostic Imaging , Metabolism , Pathology , General Surgery , Radiography , SOX9 Transcription Factor , Metabolism , Vimentin , MetabolismABSTRACT
<p><b>BACKGROUND</b>Myofibroblastic sarcoma was used to be a controversial neoplasm. This study investigated the clinicopathological features of 20 cases of myofibroblastic sarcoma arising in different locations.</p><p><b>METHODS</b>The paraffin-embedded tissue samples from 20 cases of patients with myofibroblastic sarcoma were stained immunohistochemically, and 5 cases examined by electron microscopy. Student's t test was used to analyze the difference of Ki-67 labeling index between grade 1 and grade 2 myofibroblastic sarcomas.</p><p><b>RESULTS</b>Histologically, the tumors were composed of slender spindle cells with eosinophilic cytoplasm, and fusiform, tapering, wavy, or plump ovoid; vesicular nuclei and a small central eosinophilic nucleoli. Immunohistochemically, the tumor cells expressed smooth muscle actin (18/20), muscle specific actin (16/20), fibronectin (20/20) and desmin (2/20). Ultrastructurally, the tumor cells revealed abundant rough endoplasmic reticulum and longitudinally arranged fine filaments with focal densities in the cytoplasm. A clinical follow-up of 19 patients showed that 2 cases experienced local recurrence and distant metastasis 6 months to 4 years after the initial operation. Nine cases recurred locally 17 to 46 months after the initial excision, and 9 cases were alive with no evidence of disease.</p><p><b>CONCLUSIONS</b>Myofibroblastic sarcomas, which exhibit diverse histological appearance, can easily be misdiagnosed as benign tumors. Myofibroblastic sarcomas are local destructive lesions with frequent recurrence, and may metastase distantly.</p>