Mechanical study of alisol B 23-acetate on methionine and choline deficient diet-induced nonalcoholic steatohepatitis based on untargeted metabolomics.

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.

Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion).

Lymphoepithelial lesions (LELs, or epi-myoepithelial islands) in lymphoepithelial sialadenitis (LESA, or benign lymphoepithelial lesion) of the salivary gland are known to be mainly composed of duct epithelial cells. However, other constituent cells are poorly characterized. Formalin-fixed paraffin sections obtained from six surgical specimens of LESA were examined using immunohistochemistry for cytoskeletal proteins, inflammatory cells, vascular endothelial cells, and extracellular matrix (ECM) molecules as well as by in situ hybridization for ECM molecules. In addition to keratin-immunopositive (+) duct-like epithelial cells, there were CD31/CD34+ vascular endothelial cells-which were either scattered in a singular fashion, in formed sheets, or in tubular structures-, CD20+ B lymphocytes, CD45RO+ T lymphocytes, and CD68 macrophages in the LELs. ECM molecules, such as heparan sulfate proteoglycan and tenascin, were immunolocalized in hyaline materials in the LELs. Their mRNAs were demonstrated mainly in endothelial cells and, to a lesser extent, in lympho-monocytic cells around hyaline materials, but were not as evident in epithelial constituent cells of LELs. The results indicate that endothelial cells as well as inflammatory cells are important constituents of the LELs, and the hyaline ECM cores mainly result from the intra-LEL angiogenesis by endothelial cells with the assistance of inflammatory cells. This intra-LEL vasculature seems to support regeneration and proliferation of salivary epithelial remnant cells.

[Determination of chlorogenic acid and eriodictyol-7-O-beta-D-glucuronide in Pyrrosia by RP-HPLC].

AIM: To develop a method for determination of chlorogenic acid and eriodictyol-7-O-beta-D-glucuronide in Pyrrosia of different species and different places of origin by RP-HPLC. METHODS: Chromatography was performed using a C18 column with mobile phase of methanol-water-phosphoric acid (50:200:0.2). The monitoring wavelength was 284 nm. RESULTS: The linear ranges were 0.01-5.0 micrograms (r = 0.9997) and 0.004-5.0 micrograms (r = 0.9997), the recoveries were 97.1% (n = 8, RSD = 2.7%) and 98.8% (n = 9, RSD = 2.5%) for chlorogenic acid and eriodictyol-7-O-beta-D-glucuronide, respectively. CONCLUSION: The method was employed to the analysis of 21 samples of Pyrrosia. The contents of compounds vary greatly depending on the species used, place of collection and time of harvesting. The HPLC method is sensitive, rapid and can be used to control the quality of Pyrrosia and to guide reasonable season of harvesting.

[Activation of auto-mesenchymal stem cells of skeletal muscle by bone morphogenetic protein for rescuing bone marrow failure].

OBJECTIVE: To explore the effect of bone morphogenetic protein (BMP) to activate mesenchymal stem cells of skeletal muscle for rescuing bone marrow failure. METHODS: The study was performed on lethal rat acute aplastic anemia model induced by combined 5-fluorouracil (5-FU) and busulfan. The rh-BMP-2 was implanted into the thigh muscle of the rats at 3 days before aplastic anemia was induced. In the control group the rats were implanted with agar into the thigh muscle. The blood picture, pathologic changes and the mortality in two groups were observed. At the same time, rh-BMP-2 were implanted into the thigh muscle of normal Kun-min mice for dynamic control observation of the implantation local morphological changes, colony forming units-spleen (CFU-S) and stem cell growth factor (SCF) expression of the stroma cells of ectopic ossicles induced by BMP. RESULTS: At 7 days after BMP implantation in the mice the mesenchymal cells around BMP in muscle proliferated, and appeared in bone marrow to form an ectopic ossicles. The SCF expression of stroma cells in ectopic ossicles were higher than that of self-bone marrow. 56.3% of BMP-treated aplastic rats were survived over 3 months and its hematopoiesis was completely reconstituted and the histo-morphological picture of the spleen and bone marrow were recovered to normal. But in the control group only one of 23 rats was survived, the remainder died of hematopoietic failure. CONCLUSIONS: BMP-implantation into the skeletal muscle could rescue the bone marrow hematopoietic failure. The mechanism might be related to the BMP activated auto-mesenchymal cells of skeletal muscles to direct hematopoietic cell differentiation. In our hands it might create a new pathway for utilization of auto-muscle derived mesenchymal cells to reconstitute hematopoiesis.

[De novo salivary malignant myoepithelioma: pathologic diagnosis of 19 cases].

OBJECTIVE: To study the pathological characteristics of salivary malignant myoepithelioma with characteristic multinodular architecture. METHODS: To observe the histologic and cytologic characteristics of 19 cases of de novo salivary malignant myoepithelioma with multinodular growth pattern. Immunohistochemistry of calponin, SMA, S-100, GFAP, cytokeratin, PCNA was done on 11 cases and ultrastructure was observed on 3 cases. RESULTS: 19 tumors presented characteristic multinodular growth pattern, mostly accompanied by central necrosis. Neoplastic nests invaded the surrounding normal tissue and tumor cells displayed a variety of pleomorphism. Epitheliod cell was the most predominant cell type. Tumor-related extracellular matrix formation was revealed among tumor cells. Immunohistochemical staining demonstrated that the tumor cells were positive for calponin, SMA, S-100, GFAP, AE1/AE3, CKH and PCNA. Myofilaments were found in neoplastic cell cytoplasm under the electron microscope. CONCLUSION: Histologic and cytologic observation, immunostaining and ultrastructural study all supported the myoepithelial and malignant nature of the tumor.