Impaired bone formation is the main characteristics of glucocorticoid (GC)-induced osteoporosis (GIO), which can be ameliorated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. However, the underlying mechanism is still not entirely clear. In the present study, we determined the parameters related to microstructure and function of bone tissue, bone microcirculation, and TXNIP signaling to investigate the beneficial effects of tanshinol on skeleton and its molecular mechanism in GIO rats. Male Sprague-Dawley rats aged 4 months were administrated orally with distilled water (Con), tanshinol (Tan, 25 mg kg-1 d-1), prednisone (GC, 5 mg kg-1 d-1) and GC plus tanshinol (GC + Tan) for 14 weeks. The results demonstrated that tanshinol played a significant preventive role in bone loss, impaired microstructure, dysfunction of bone metabolism and poor bone quality, based on analysis of correlative parameters acquired from the measurement by using Micro-CT, histomorphometry, ELISA and biomechanical assay. Tanshinol also showed a significant protective effect in bone microcirculation according to the evidence of microvascular perfusion imaging of cancellous bone in GIO rats, as well as the migration ability of human endothelial cells (EA.hy926, EA cells). Moreover, tanshinol also attenuated GC-elicited the activation of TXNIP signaling pathway, and simultaneously reversed the down-regulation of Wnt and VEGF pathway as manifested by using Western-blot method in GIO rats, EA cells, and human osteoblast-like MG63 cells (MG cells). Collectively, our data highlighted that tanshinol ameliorated poor bone health mediated by activation of TXNIP signaling via inhibiting microcirculation disturbance and the following impaired bone formation in GIO rats.

OBJECTIVE: To analyse the clinicopathological, immunohistochemical and β-catenin (CTNNB1) mutation characteristics of six cases of microcystic stromal tumour of the ovary (MCST).
RESULTS: Six Chinese patients with MCST who ranged in age from 29 to 69 years (mean 50 years) were included in the study. Five patients were detected with a pelvic mass during routine health examinations and one patient presented initially with opsomenorrhoea. All tumours involved the left ovary, with solid-cystic cut surface in five cases and cystic cut surface in one case. Microscopically, microcysts, solid nests and hyaline degenerated fibrous stroma were variably mixed. Immunohistochemically, the tumour cells in all cases were diffusely positive for CD10, vimentin and WT-1 and negative for α-inhibin and calretinin. β-catenin expression was observed in both the nucleus and the cytoplasm in five cases and only in the cytoplasm in one case. The results of CTNNB1 mutation analysis revealed four missense point mutations in four cases, which were c.97T>C, c.101G>A, c.110C>G and c.122C>T.
CONCLUSIONS: MCST shows a unique morphology with characteristic immunophenotype. β-catenin expression in the nucleus and β-catenin mutations were identified in the majority of cases, which suggests that the Wnt/β-catenin pathway may play a crucial role in the tumorigenesis of MCST.

Glioblastoma (GBM) is the malignant form of glioma, and the interplay of different pathways working in concert in GBM development and progression needs to be fully understood. Wnt signaling and sonic hedgehog (SHH) signaling pathways, having basic similarities, are among the major pathways aberrantly activated in GBM, and hence, need to be targeted. It becomes imperative, therefore, to explore the functioning of these pathways in context of each other in GBM. An integrative approach may help provide new biological insights, as well as solve the problem of identifying common drug targets for simultaneous targeting of these pathways. The beauty of this approach is that it can recapitulate several known facts, as well as decipher new emerging patterns, identifying those targets that could be missed when relying on one type of data at a time. This approach can be easily extended to other systems to discover key patterns in the functioning of signaling molecules. Studies were designed to assess the relationship between significant differential expression of genes of the Wnt (Wnt/β-catenin canonical and Wnt non-canonical) and SHH signaling pathways and their connectivity patterns in interaction and signaling networks. Further, the aim was to decipher underlying mechanistic patterns that may be involved in a more specific way and to generate a ranked list of genes that can be used as markers or drug targets. These studies predict that Wnt pathway plays a relatively more pro-active role than the SHH pathway in GBM. Further, CTNNB1, CSNK1A1, and Gli2 proteins may act as key drug targets common to these pathways. While CTNNB1 is a widely studied molecule in the context of GBM, the likely roles of CSNK1A1 and Gli2 are found to be relatively novel. It is surmised that Gli2 may be antagonistic to CSNK1A1, preventing the phosphorylation of CTNNB1 and SMO proteins in Wnt and SHH signaling pathway, respectively, by CSNK1A1, and thereby, aberrant activation. New insights into the possible behavior of these pathway molecules relative to each other in GBM reveal some key interesting patterns.