Mangiferin suppresses allergic asthma symptoms by decreased Th9 and Th17 responses and increased Treg response.

Mangiferin is the major bioactive ingredient in the leaves of Mangifera indica L., Aqueous extract of such leaves have been traditionally used as an indigenous remedy for respiratory diseases including cough and asthma in Traditional Chinese Medicine. Mangiferin was shown to exert its anti-asthmatic effect by modulating Th1/Th2 cytokines imbalance via STAT6 signaling pathway. However, compelling evidence indicated that subtypes of T helpers and regulatory T cells other than Th1/Th2 were also involved in the pathogenesis of asthma. In current study, we investigated the effects of mangiferin on the differentiation and function of Th9, Th17 and Treg cells in a chicken egg ovalbumin (OVA)-induced asthmatic mouse model. Mangiferin significantly attenuated the symptoms of asthma attacks, reduced the total number of leukocytes, EOS and goblet cells infiltration in lung. Simultaneously, treatment with mangiferin remarkably decreased the proportion of Th9 and Th17 cells; reduced the levels of IL-9, IL-17A; inhibited the expression of PU.1 and RORγt in lung. However, the proportion of Treg cells, the expression of IL-10, TGF-ß1 and Foxp3 were increased by mangiferin. Our data suggest that mangiferin exerted anti-asthmatic effect through decreasing Th9 and Th17 responses and increasing Treg response in OVA-induced asthmatic mouse model.

Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone.

BACKGROUND: The processes of prostate cancer (PCa) invasion and metastasis are facilitated by proteolytic cascade involving multiple proteases, such as matrix metalloproteinases, serine proteases and cysteine proteases including cathepsin K (CatK). CatK is predominantly secreted by osteoclasts and specifically degrades collagen I leading to bone destruction. PCa and breast cancer preferentially metastasize to the bone. Importantly, CatK expression level is greater in PCa bone metastatic sites compared to primary tumor and normal prostate tissues. However, the underlying mechanism of CatK during PCa metastases into the bone remains to be elucidated. We investigated the functional role of CatK during the PCa establishment and growth process in the murine bone. METHODS: CatK mRNA expression was validated by RT-PCR, protein expression by immunoblotting in PCa LNCaP, C4-2B, and PC3 cells as well as in PCa tissues. Its protein production was measured using ELISA assay. The effect of both knockdowns via siRNA and CatK inhibitor was compared in regard to PCa cell invasion. We further studied the dose-dependent CatK inhibitor effect on conditioned media-induced bone resorption. In setting up an animal model, C4-2B cells were injected into the tibiae of SCID mice. The animals treated with either vehicle or CatK inhibitor for 8 weeks at the time of tumor cell injection (tumor establishment model; protocol I) or 4 weeks after tumor cell injection (tumor progression model; protocol II) were applied to histological and histomorphometric analyses. RESULTS: We confirmed CatK expression in PCa LNCaP, C4-2B, and PC3 cells as well as in PCa tissues. Furthermore, we observed the inhibitory effects of a selective CatK inhibitor on PCa cell invasion. The CatK inhibitor dose-dependently inhibited PCa-conditioned media-induced bone resorption. Upon injection of C4-2B cells into the tibiae of SCID mice, the selective CatK inhibitor significantly prevented the tumor establishment in protocol I, and reduced the tumor growth in bone in protocol II. It also decreased serum PSA levels in both animal models. The inhibitory effects of the CatK inhibitor were enhanced in combination with zoledronic acid (ZA). CONCLUSION: The selective CatK inhibitor may prevent the establishment and progression of PCa in bone, thus making it a novel therapeutic approach for advanced PCa.

Patients with old age or proximal tumors benefit from metabolic syndrome in early stage gastric cancer.

BACKGROUND: Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. METHODS: Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. RESULTS: Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P=0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P=0.009 in multivariate analysis) or patients with proximal gastric cancer (P=0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P=0.052 in univariate analysis). CONCLUSIONS: Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

[The clinical study of multi-slice helical CT three-dimensional reconstruction in the sphenopalatine foramen].

OBJECTIVE: Used multi-slice helical CT to observe the reconstruction of the surface structure of nasal lateral wall "sphenopalatine foramen" and compared with anatomical specimens to verify the dependability of 3D data. METHOD: The position, shape, size and their correlational data of sphenopalatine foramen of 5 cadaver heads (10 sides) in adults fixed with formalin were dissected and measured. RESULT: Multi-slice helical CT has more rapid speed of 3D reconstruction and clearer imaging. The technique of Shade surface display and Volume rendering can give very clear structure of nasal lateral wall "sphenopalatine foramen". The 3D data makes no statistic difference with anatomical measurement. The 3D data can instruct the clinic directly. CONCLUSION: Multi-slice helical CT three-dimensional reconstruction can be used to orientation of surgery.

[The study of microdissection of endoscopic transnasal surgery in the sphenopalatine foramen].

OBJECTIVE: To provide anatomy evidence for endoscopic transnasal surgery in the sphenopalatine foramen by measuring and dissecting corpses. METHOD: The position, shape, size and their correlational data of sphenopalatine foramen of 40 sides skulls in adults were measured. RESULT: Classification of the sphenopalatine foramen were as three types: I 35%; II 5%; III 60%. The mean distance from upper edge of the sphenopalatine foramen to the base of the sphenopalatine sinus was male (1.75 +/- 1.10) mm, female (1.13 +/- 0.55) mm, and to the apertura sphenopalatine sinus was male (9.80 +/- 3.27) mm, female (8.30 +/- 3.45) mm. The mean distance from the posterior edge of the sphenopalatine foramen to the rhinopharynx was male (11.12 +/- 3.30) mm, female (10.85 +/- 3.12) mm. The mean distance from the anterior edge of the sphenopalatine foramen to the apertura maxillaris was male (18.50 +/- 6.80) mm, female (14.57 +/- 5.07) mm, and to the apex of nose was male (69.54 +/- 6.98) mm, female (66.57 +/- 5.07) mm, and to the nasospinale was male (56.69 +/- 5.70) mm, female (53.25 +/- 8.80) mm. The horizontal diameter of the sphenopalatine foramen was female (4.61 +/- 1.80) mm, male (5.12 +/- 2.05) mm. The vertical diameter was male (5.37 +/- 2.67) mm, female (0.35 +/- 0.07) mm. The surface diameter of the sphenopalatine artery and nerves was male (2.12 +/- 0.66) mm, female (1.61 +/- 0.70) mm, and male (0.65 +/- 0.49) mm, female (0.35 +/- 0.07) mm. The mean angle from the sphenopalatine foramen to the horizontal plate of palatine bone was male (22.83 +/- 4.71) degrees, female (22.73 +/- 3.81) degrees. Nasal lateral walls were controlled by lateral posterior nasal arteries and nerves, which were classified into three types: I 70%, II 20%, III 10%. CONCLUSION: The observation and survey about the sphenopalatine foramen will supply clinic with anatomy homological.

Modeling and Analysis of Structures of Phospholipase A(2)'s from Venom of Agkistrodon haly Pallas.

We have modeled three-dimensional structures of basic-acidic hybrid phospholipase A(2)-II and neutral phospholipase A(2) from venom of snake Agkistrodon halys Pallas, based on the known structures of basic and acidic phospholipase A(2)'s from the same source. We have compared these structures of phospholipase A(2)'s, explained the results of fluorescent spectrum study on the phospholipase A(2)'s and calculated the electrostatic potential maps on the catalytic active site. We suggest that the electrostatic potential around the catalytic active site of PLA(2) containing a calcium ion favors the binding of the PLA(2) to its substrate with negative charge.