Our previous studies proposed that Alzheimer's disease (AD) is a metabolic disorder and hypothesized that abnormal brain glucose metabolism inducing multiple pathophysiological cascades contributes to AD pathogenesis. Aging is one of the great significant risk factors for AD. Membrane aging is first prone to affect the function and structure of the brain by impairing glucose metabolism. We presume that risk factors of AD, including genetic factors (e.g., the apolipoprotein E ε4 allele and genetic mutations) and non-genetic factors (such as fat, diabetes, and cardiac failure) accelerate biomembrane aging and lead to the onset and development of the disease. In this review, we further modify our previous hypothesis to demonstrate "membrane aging" as an initial pathogenic factor that results in functional and structural alterations of membranes and, consequently, glucose hypometabolism and multiple pathophysiological cascades.
Aging ; pathology ; Alzheimer Disease ; etiology ; pathology ; Animals ; Brain ; pathology ; Cell Membrane ; pathology ; Humans

Research on peripheral nervous injuries, especially the stretched injuries, is important to improve the clinical effectiveness and alleviate the patients's pain. In recent years, the biological changes and mechanics of stretched axons have been hot topics. This article reviews the recent advances in the morphological changes of axons as well as changes in cellular membrane, cytoskeleton, cellular metabolism, and action potential after axonal stretch.
Action Potentials ; Animals ; Axons ; metabolism ; pathology ; Cell Membrane ; pathology ; Cytoskeleton ; pathology ; Humans ; Stress, Mechanical

Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury and/or apoptosis. Microparticles of various cellular origins, such as platelets, leukocytes, and endothelial cells, are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Recent studies show that endothelial microparticles, a kind of envelope particles derived from endothelial cells, not only constitute a marker of endothelial dysfunction, but also play a major biological role in the diagnostic and therapeutic approaches to erectile dysfunction.
Biomarkers ; Cell Membrane ; Endothelial Cells ; metabolism ; pathology ; Erectile Dysfunction ; metabolism ; pathology ; Humans ; Liposomes ; metabolism ; Male

OBJECTIVETo observe the change in the amount of sialic acids on hepatocellular carcinoma (HCC) cell membrane.

METHODSSurgical specimens of HCC and liver cirrhosis tissues were obtained from 28 patients to prepare carcinoma cell and hepatocyte suspensions by collagenase digestion. For assay of α2, 3 and α2, 6-sialic acids, the cells were suspended in the staining buffer containing either fluorescein isothiocyanate-Maackia amurensis lectin (FITC-MAL) or fluorescein isothiocyanate-Sambucus nigra bark lectin (FITC-SNA) and incubated for 1 h, respectively. Flow cytometric analysis was carried out to measure the mean fluorescence intensity (MFI) on the cell surface.

RESULTSIn both FITC-MAL- and FITC-SNA-incubated HCC cells, the MFI on the cell surface was greater than that of the hepatocytes.

CONCLUSIONBoth of α2, 3 and α2, 6- sialic acids increases significantly on the hepatocyte membrane after the carcinomatous change.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Membrane ; metabolism ; Humans ; Liver Cirrhosis ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Sialic Acids ; metabolism

Animals ; Arthritis, Experimental ; metabolism ; pathology ; Breast Neoplasms ; pathology ; Cadherins ; metabolism ; physiology ; Cell Movement ; Female ; Fibroblasts ; cytology ; pathology ; Humans ; Macrophages ; cytology ; pathology ; Neoplasm Invasiveness ; Synovial Membrane ; cytology ; metabolism ; pathology

OBJECTIVETo investigate the expression of cell surface E-cadherin in leukemia cell and the correlation of cell membrane localization of beta-catenin with E-cadherin expression.

METHODSBone marrow samples from 46 patients with acute leukemia and 17 normal donors were analyzed. Cell surface expression of E-cadherin and membrane localization of beta-catenin were labeled by immunofluorescence and analyzed with a laser scanning confocal fluorescence microscope in 14 specimens.

RESULTSCell surface E-cadherin expression level was significantly lower in leukemia cells (with the median fluorescent intensity of 16.78) than in normal hematopoietic progenitors (26.03). Correlation analysis showed that cell membrane localization of beta-catenin was correlated with E-cadherin expression (r = 0.74, P = 0.002). After E-cadherin was induced to express in leukemic cell by 5-Aza-CdR, membranous expression of beta-catenin was elevated while the nuclear expression reduced, indicating that E-cadherin-mediated adhesions could recruit beta-catenin to cell membrane.

CONCLUSIONThe loss of E-cadherin in leukemia cells may result in beta-catenin translocating to the nuclear and transcriptional activation of its target genes.

Cadherins ; metabolism ; Case-Control Studies ; Cell Membrane ; metabolism ; Humans ; Leukemia ; metabolism ; pathology ; beta Catenin ; metabolism

BACKGROUND: Airway hyperresponsiveness is expressed as the provocative dose or concentration of the stimulus required to achieve bronchoconstriction, a 20% fall in FEV1 (PD20 and PC20, respectively). A decrease in PC20 may be due to a steeper dose-response curve (hyperreactivity) or to a shift in the curve to the left (hypersensitivity), or both. It has been suggested that many factors, such as genetic factor, airway inflammation, epithelial damage or airway remodeling, are involved in the airway hyperresponsiveness in asthma. OBJECTIVE: In this study, we analyzed the relationship of airway sensitivity and reactivity with bronchial inflammation and structural change in asthmatics. METHOD: The PC20 for methacholine, as the airway sensitivity parameter, and the slope between PC20 and PC40, as the airway reactivity parameter, were measured. Total cell counts and differential cell counts in BAL fluid, percentage of epithelial shedding (ES), basement membrane thickness (BMT) and depth of submucosal collagen deposition (SMC) on bronchial tissue were measured. The patients (n=27) were divided into two groups by median values of ES, BMT, or SMC (32%, 7.3 micrometer, 68 micrometer, respectively). RESULTS: The PC20 showed a significant correlation with baseline FEV1% (r=0.498, p<0.05), and was significantly lower in patients with over 32% of ES than in those with under 32% of ES (2.89+/-1.05 mg/ml vs 5.70+/-3.70 mg/ml, p<0.05). The slope was significantly steeper in patients with thicker BMT or SMC. CONCLUSION: These results suggest that airway hypersensitivity is affected by airway caliber, and airway hyperreactivity is affected by bronchial remodeling in asthma.
Airway Remodeling ; Asthma ; Basement Membrane ; Bronchoconstriction ; Cell Count ; Collagen ; Humans ; Hypersensitivity ; Inflammation ; Methacholine Chloride ; Pathology*

The authors report a typical case of tenosynovial giant cell tumor of the right middle finger of a 31-year-old man. Histologically, this tumor is characterized by a discrete proliferation of rounded synovial-like cells accompanied by a variable number of multinucleated giant cells, inflammatory cells, and xanthoma cells. Clinicopathologically, this tumor is a benign lesion that nonetheless possesses a capacity for local recurrence. Local excision with a small cuff of normal tissue is the treatment of choice in this tumor.
Adult ; Case Report ; Fingers* ; Giant Cell Tumors/surgery ; Giant Cell Tumors/pathology* ; Histocytochemistry ; Human ; Male ; Muscle Neoplasms/surgery ; Muscle Neoplasms/pathology* ; Neoplasm Recurrence, Local ; Synovial Membrane/pathology*

OBJECTIVETo construct a small interfering RNA (siRNA) vector targeting p63 and observe its effect on the proliferation and invasiveness of human cholangiocarcinoma cells in vitro.

METHODSReal-time PCR was used to examine the expression of p63 in human cholangiocarcinoma QBC939 cells. The recombinant lentivirus shRNA-p63 vector was constructed and transfected into QBC939 cells via Lipofectamine 2000 to establish a cholangiocarcinoma cell line with stable expression of siRNA-p63. The interfering efficiency of the siRNA targeting p63 was assessed using Western blotting. MTT and soft agar colony formation assays were used to evaluate the changes in the cell proliferation, and Boyden test was employed to observe the cell invasiveness after the transfection.

RESULTSQBC939 cells showed a high expression of p63. The recombinant lentivirus shRNA-p63 vector was successfully constructed as verified by sequencing. Transfection with the vector significantly suppressed the proliferation and invasiveness of QBC939 cells.

CONCLUSIONDown-regulation of p63 can inhibit the proliferation and invasiveness of human cholangiocarcinoma QBC939 cells in vitro.

Bile Duct Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cholangiocarcinoma ; genetics ; pathology ; Humans ; Membrane Proteins ; genetics ; metabolism ; Neoplasm Invasiveness ; RNA, Small Interfering ; genetics ; Transfection

OBJECTIVETo investigate the influence of hypoxia induced microtubule damage on the opening of mitochondrial permeable transition pore (MPTP)of cardiac myocytes and on the decrease of respiratory function in rat.

METHODSPrimary cultured myocardial cells from 30 neonatal rats were randomized as normoxic group (A), hypoxia group (B), normoxia with microtubule destabilizing agent group (C, with treatment of 8 micromol/L colchicines for 30 minutes before normoxia), and hypoxia with microtubule stabilizing agent group (D, with treatment of 10 micromol/L taxol for 30 minutes before hypoxia). beta-tubulin immunofluorescence ,the opening of mitochondria permeability transition pore, and the mitochondrial inner membrane potential were detected at 0.5, 1, 3, 6 and 12 post-treatment hours (PTH), and the mitochondrial respiratory function was determined by MTT method. The changes in these indices were also determined in A group at the corresponding time-points.

RESULTSObvious damage of polymerized microtubule, opening of MPTP, mitochondrial inner membrane potential loss and decrease of myocardial respiratory activity were observed in both group B and C at 0.5 PTH, and they became more and more serious afterwards. However, the changes in the above indices in D group were much better than those in B group (P < 0.05 or 0.01), and no difference was found between D (92.8 +/- 4.0)% and C [(100.0 +/- 0.0) %, P > 0.05] groups.

CONCLUSIONHypoxia played a role in the myocardial microtubule damage as well as in the opening of MPTP. Moreover, hypoxia could also impair the mitochondrial respiratory function. Microtubule destabilizing agent could reproduce well the process of hypoxia induced microtubule damage, while the stabilizing agent exerted protective effect by improving the transition of mitochondrial permeability and the mitochondria respiratory function.

Animals ; Cell Hypoxia ; Cells, Cultured ; Hypoxia ; metabolism ; pathology ; Membrane Potential, Mitochondrial ; Microtubules ; pathology ; Mitochondria, Heart ; metabolism ; pathology ; Myocytes, Cardiac ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley