Glucagon-like peptide-1 regulates mitochondrial biogenesis and tau phosphorylation against advanced glycation end product-induced neuronal insult: Studies in vivo and in vitro.

Our previous study has proved that glucagon-like peptide-1 (GLP-1), which is developed to treat type 2 diabetes, has a significant effect on neuroprotection against advanced glycation end product (AGE)-induced neuronal insult in vitro models of diabetes-related Alzheimer's disease (AD). However, the molecular mechanisms remain to be elucidated and it is not clear whether GLP-1 receptor mediates the down-regulation effects on AGE-induced AD-like changes in vivo. This study aims to explore the effect and mechanisms of GLP-1 receptor agonists (GLP-1RA) against the AGE-dependent signaling pathway both in vitro and in vivo. In this study, we demonstrated that GLP-1RA could inhibit oxidative stress and repair mitochondrial damage in addition to decreasing tau hyperphosphorylation in PC12 cells treated with AGEs. Importantly, we first observed AGEs in the circulatory system could induce tau hyperphosphorylation after we injected AGEs (1µg/kg bodyweight) into the mice tail vein. We found GLP-1RA could promote mitochondrial biogenesis and antioxidant system via regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway in vivo besides down-regulating the activity of glycogen synthase kinase 3ß (GSK-3ß) to reverse tau hyperphosphorylation directly. Collectively, our results suggest that GLP-1RA protects neurons against AGE-induced tau hyperphosphorylation via regulating GSK-3ß and PGC-1α two cooperative signaling pathways.

Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation.

We have previously demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist ameliorated neurodegenerative changes in rat models of diabetes-related Alzheimer's disease (AD), and protected neurons from glucose toxicity in vitro. Herein, we investigated the effects of GLP-1 receptor mediates on cell toxicity and tau hyperphosphorylation induced by advanced glycation end products (AGEs), which are associated with glucose toxicity, and the molecular mechanism in PC12 cells and the primary hippocampal neurons. Our study demonstrated that the similar protection effects of GLP-1 existed in PC12 cells treated with glucose-bovine serum albumin (BSA) in hyperglycemic conditions or with glycoaldehyde-BSA alone. Additionally, glucose-BSA alone did not induce significant cytotoxicity in PC12 cells, but resulted in tau hyperphosphorylation in primary hippocampal neurons in 24h. And we found that GLP-1 could reduce cell tau phosphorylation induced by high glucose or glucose-BSA. Furthermore, our data in the present study suggested that GLP-1 regulated tau phosphorylation induced by AGEs through a signaling pathway involving glycogen synthase kinase 3ß (GSK-3ß), similarly to the GSK-3ß inhibitor, lithium chloride. Our findings suggest that GLP-1 can protect neurons from diabetes-associated AGE insults in vitro, and provide new evidence for a potential therapeutic value of GLP-1 receptor agonist in the treatment of AD especially diabetes-related AD.

[The synergistic action of guanghuoxiang volatile oil and sodium artesunate against Plasmodium berghei and reversal of SA-resistant Plasmodium berghei].

OBJECTIVE: To study the synergistic action of a combination of guanghuoxiang volatile oil (B) and sodium artesunate (SA) against Plasmodium berghei (P. b) and the resistance-reversal activity against SA-resistant P. b (P. b SA-R). METHODS: Mice infected with P. b N or P. b R were treated with a combination of B and SA respectively by 4-day suppressive test method and linear regression to calculate the SD50 of B and SA for each drug alone and in combination (equally effective dose compatibility). RESULTS: B alone, N:SD50 = 87.64 +/- 19.58(GKD), R:SD50 = 43.24 +/- 7.71(GKD); SA alone, N:SD50 = 0.88 +/- 0.01(MGKD), R:SD50 = 27.69 +/- 0.93(MGKD). B and SA combination, N:B SD50 = 36.89 +/- 4.57(GKD), SA SD50 = 0.39 +/- 0.05 (MGKD); R:B SD50 = 7.40 +/- 1.30(GKD), SA SD50 = 4.21 +/- 0.74(MGKD). The synergistic indexes of B and SA in combination were 2.2 for N and 6.6 for R, respectivly. The multiple of resistance reversal of B vs SA was 6.6. The relative reversal rate was 87.6%. CONCLUSION: A combination of B and SA may enhance the antimalarial effect against P. b and reverse the SA-resistance of P. b and delay the occurrence of resistance to SA in N.

Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members.

In a series of 111 patients with squamous cell carcinoma (SCC), we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor (EGFR) family members (EGFR, HER-2/neu, HER-3, and HER-4). Expression of the EGFR members was not significantly associated with tumor size. However, their expressions (except for HER-4) were significantly associated with the presence of lymph node metastasis, and all of them were significantly associated with distant metastasis. We further examined the association between the expression levels of the EGFR members and the survival rates in 47 oral SCC patients whose detailed clinical follow-ups were available. The expression of all EGFR members was significantly associated with shortened patient survival, and the association was strongest for HER-2/neu. Furthermore, the combination of HER-2, HER-3, and EGFR but not HER-4 significantly improved the predicting power. The expression level of HER-2/neu was significantly correlated with that of EGFR or HER-3. Similar coexpression patterns were also observed in three oral SCC cell lines studied, but not in four other head and neck SCC cell lines. Taken together, these results indicated that expression levels of EGFR, HER-2/ neu, and HER-3 may help predict the outcome of patients with oral SCC.

Neoplastic odontogenic epithelial cells express bone sialoprotein.

Bone sialoprotein (BSP) is synthesized and secreted by bone-, dentine- and cementum-forming cells and has been implicated in de novo bone formation and mineralization. In this study, we used histological sections of odontogenic neoplasms and performed immunohistochemical and in situ hybridization analyses. In ameloblastoma, BSP mRNA signals were seen in the neoplastic epithelial cells forming nests, strips and islands. BSP deposition was also seen in the stellate reticulum of the tumour masses revealed by immunohistochemistry using human BSP antibodies. In calcifying epithelial odontogenic tumour, the calcified masses demonstrated positive immunoreactivity to the human BSP antibodies, and the hybridization signals for BSP were located in the cells near the calcified particles. In the calcifying odontogenic cyst, strong BSP signals were seen in cells surrounding the characteristic nests of ghost cells, which often calcify subsequently. BSP protein was also found in these cells by immunohistochemistry. The active expression of BSP in the epithelial elements of the odontogenic tumours of adult patients suggests the activation of this matrix protein gene in the neoplastic process, and that BSP may play an important role in tumour formation and differentiation with respect to pathological calcification.

[HPLC determination of six flavonoid constituents in Ginkgo biloba leaves].

Six flavonoid constituents (quercetin, isorhamnetin, kaempferol, bilobetin, ginkgetin and sciadopitysin) were isolated from Ginkgo biloba leaves and determined by reversed phase HPLC using salvianolic acid B as internal standard. The column employed was Zorbax ODS (150 mm x 4 mm ID, 5 microns). The mobile phase consisted of solvent A (methanol) and solvent B [tetrahydrofuran--water--formic acid (34:65:1)] for gradient elution. The flow rate was 1 ml.min-1 and detection was effected at 350 nm. This method is accurate, rapid and reproducible. Analytical data for various samples were given.

[Study in the combining quantity of Con A-binding sites on membrane surface of artesunate-resistance strain of Plasmodium berghei].

OBJECTIVE: To study the production mechanism of plasmodium berghei (PB) in resisting artesunate. METHODS: The combining quantity of Con A-binding sites on membrane surface of PB trophozoite labelled with fluorescein isothiocyanate (FITC) of Con A was determined by fluoromicrospectrophotometer. RESULTS: The combining quantity of PB artesunate-resistance strain (PBAR) was reduced significantly than that of PB normal strain (P < 0.01). CONCLUSIONS: The type of glucose in surface membrane of PBAR has changed and the changes of membrane fluidity could be one of the causes of the change in the combining quantity of Con A-binding sites on membrane of PBAR.

[The influences of lanthanum,cerium and fluorine ions to the activity of collagenase degrading cemental collagens]

The influences of trace elements lanthanum,cerium and fluorine to the activity of clostridium histolyticum collagenase(CHC) during the period of CHC degrading the cemental root collagen in vitro is studied.The results reveal that La(3+) can significantly inhibit the activity of the CHC than Ce(3+) and F(-). Therefore it suggests that lanthanum may be used as a new kind of element in preventing root caries.The mechanisms of above functions are also discussed.

Strong correlation between c-erbB-2 overexpression and overall survival of patients with oral squamous cell carcinoma.

Overexpression of c-erbB-2 (also known as HER-2/neu) has been found in many human cancers, including head and neck squamous cell carcinoma (SCC). We therefore examined expression of the oncoprotein in oral SCC primary tumor samples and compared its relationship with clinical stages and survival rate. Out of 80 cases of oral SCC, high expression level (++ or +++) of c-erbB-2 was found in 41 cases. Of the 80 cases with follow-up information, 39 were further investigated for the correlation of expression level of c-erbB-2 and survival rate. Overexpression of the oncoprotein was significantly correlated with shorter overall survival, and the patients with low and no expression of c-erbB-2 had much higher survival rates. Overexpression of c-erbB-2 was also significantly correlated with nodal stage and metastasis. We found that high expression level of c-erbB-2 was frequently detected in oral cancer cell lines but not in the other head and neck SCC cell lines. Thus, we conclude that overexpression of c-erbB-2 is a frequent event in oral SCC and is correlated with poor survival and may be used as a poor prognostic factor.

[The effects of LTA and plaque on the periodontal tissue of the Guinea pig]

40 Guinea pigs were divided into 4 groups.The gingival sulcus of 2 mandibular incisors were irrigated with LPS(Lipopolysaccharide),LTA (Lipoteichoicacid),PL(Subgingival plaque) and NS(Normal saline solution) respectively.2 animals were sacrificed in group of 5 successively at 1,2,3,6,8 week after irrigation.Microscopic examination demonstrated:Only a few penetration of inflammatory cells lay in the gingival tissue in NS control group.Significant infiltrate associated with evident crystal resorption were noted at 1st week and active remodeling took place at 4th,5th week in LPS group.Enhancing accumulations of plaque calculus with weak inflammation could be seen in LTA group.Not only accumulations of plaque and calculus but also penetration of inflammation with resorption of bone were seen in PL group.Their effects on the periodontal tissue of Guinea pig showed evident different.These findings served further expression the possible mechanisms of periodontal diseases.

[Recurrent fetal cellular rhabdomyoma:histopathological and ultrastructural observations]

A mass of the neck in an 8-year-old boy diagnosed with recurrent fetal cellular rhabdomyoma was reported.The recurrent tumor consisted of undifferentiated round and short spindle cells and immature striated muscle cells,which was similar to the primary tumor occured in five years ago.However,there were more large round myoblasts which mainly located at the periphery of the tumor and osteoid stroma in the recurrent case immuno-histochemistry stain and ultrstructure observation suggested that these were undifferntiated mesenchymal cell and myoblasts.The differential diagnosis from fibrosarcoma,highly differentiated rhabdomyosarcoma,and hemangiopericytoma were dicussed.Author considered FRMs has a recurrent and malignant change tendency though it belongs to benign tumor.

[Malignant pleomorphic adenoma of salivary glands:A clinicopathologic study of 83 cases]

This paper presented the clinicopathologic features of 83 cases of malignant pleomorphic adenomas(MPA) of the salivary glands.The average age of the patients was 53 years old.The ratio from male to female was 1.24 to 1.Thirty nine tumors located in parotid glands,twenty in submandibular glands and seventeen in palate.Histopathologically,the malignant component of 76 tumors was identified as carcinoma and 7 tumours as carcinosarcoma both in various types.The statistic analysis showed the factors which influenced the prognosis(P>0.05) included 1. location,2. histologic subtype of malignant component,3.differentiation grade,4.infiltration status,and 5.with or without lymph node metastasis in the initial operation.The prognosis of MPA was more ominous than that of/the conventional types of carcinoma,with only 52.7% of year survival rate.The authors concluded that the pleomorphic adenoma was the pre-cancerous lesion of MPA.Therefore,it is necessary to resect the pleomorphic adenoma as early as possible in order to prevent the occurence of the MPA.

[Histopathological and ultrastructural studies of melanomatic neuroectodermal tumor of infancy]

Three cases of melanomatic neuroectodermal tumor of infancy(MNTI) were studied.The tumor mainly consisted of small neuroblastic-like cells and pigmented large cuboidal cell,and infiltrated adjacent tissues.The main ultrastructural charactristics were the presence of some membranebound dense-core secretory granules,numerous free ribosomes and polysomes aggregaed in rosettes,occasional mitoses in the small cells;and four types of membranebound pigment granules corresponding to melanosomes at different stages of maturation in the pigment cell.immunohistochemical results indicated that both of main cells were positive reaction for NSE,negative for S-100.These facts suggested they are immature in and malignancy.Further,the isogenesis of the tumor cells and embryo optic cup cells were discussed.

[Effects of demineral-resistant of Lanthanum,Cerium and Fluoride on human root surface:A comparative study in vitro]

An in vitro acid-resistant and remineralized study on human root surface with 500ppm lanthanum,Cerium and Fluoride accidulate buffer was carried out in a pH-cy-cling system.The results of quantitative chemical and energy spectrometry analyses showed that all these three elements had the demineral-resistant effects,although fluoride showed a better effect,Furthermore,the mechanisms of lanthanum,Cerium and Fluoride on demineral-resistant were discussed from the viewpoint of crystal physicochemistry.

[Primary non-Hodgkin's lymphoma on parotid gland clinicopathologic and immunohistochemical study.].

A clinico-pathologic and immunohistochemical study of 20 cases of primary non-Hodgkin's lymphoma on the parotid gland was made.The result showed 45% of the cases originated from B cells,white 40% from T cells,the rest 15% from the small lymphocytes.Immunohistochemical study was made on 11 cases,the result of immunophenotype was in concordance with the histopathologic diagnosis in 10 cases,except in one case which was initially diagnosed as plasmocytoid lymphocytic lymphoma,but the immunmophenotype suggested that it was T cell type of malignant lymphoma(ML).Follow-up data can be collected in 16 cases(80%).Three of the 16 cases(18.75%) died of the tumor within one year,they were diagnosed initially as B cleaved cell,lymphoplastic cell and polymorphic T cell type of ML,each in 1 case.Other cases survived from 15 months to 9.25 years,among them 2 were diagnosed as low-grade ML(both of small lymphocyte type),7 cases as middle-grade ML(5 of B cleaved cell,2 of B mixed type),and 4 cases as high-grade ML (2 of clear T cell,2 of polymorphic T cell type).They were treated by surgical removal and combined western and traditional Chinese medicine,their prognosis was quite good.