Vitamin D Attenuates Fibrotic Properties of Fibrous Dysplasia-Derived Cells for the Transit towards Osteocytic Phenotype.

Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells.

A Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects.

Fibrous dysplasia (FD) is a rare, non-hereditary skeletal disorder characterized by its chronic course of non-neoplastic fibrous tissue buildup in place of healthy bone. A myriad of factors have been associated with its onset and progression. Perturbation of cell-cell signaling networks and response outputs leading to disrupted building blocks, incoherent multi-level organization, and loss of rigid structural motifs in mineralized tissues are factors that have been identified to participate in FD induction. In more recent years, novel insights into the unique biology of FD are transforming our understandings of its pathology, natural discourse of the disease, and treatment prospects. Herein, we built upon existing knowledge with recent findings to review clinical, etiologic, and histological features of FD and discussed known and potential mechanisms underlying FD manifestations. Subsequently, we ended on a note of optimism by highlighting emerging therapeutic approaches aimed at either halting or ameliorating disease progression.

Massive sedimentation of fine sediment with organic matter and enhanced benthic-pelagic coupling by an artificial dyke in semi-enclosed Chonsu Bay, Korea.

To assess the impact of an artificial dyke in Chonsu Bay (CBD) on the organic carbon (C(org)) cycle, we measured excess (210)Pb activities, C(org) and nitrogen content in sediment cores. The C(org) oxidation rates (C(ox)) on the surface sediment and benthic nutrient fluxes were also quantified with an in situ benthic chamber. The higher excess (210)Pb inventory, C(org) and nitrogen in cores near the CBD indicated lateral transport and local, massive deposition of particulate matter due to tidal circulation altered by artificial dyke construction. The C(ox) in sediment near the CBD was about twice as high as that out of the bay, suggesting the importance of benthic remineralization of organic matter. The benthic fluxes of dissolved inorganic nitrogen and phosphate were four to six times higher than those outside the bay, corresponding to 141% and 131% respectively, of the requirements for primary production.

Up-regulation of Idh3alpha causes reduction of neuronal differentiation in PC12 cells.

The PC12 is the widely used cell line to study neuronal differentiation. We had extensively investigated the details of protein expression in differentiated PC12 cells by proteomic analysis. The cells were incubated at the presence of nerve growth factor. We had analyzed the expression changes in the differentiating PC12 cells by 2-dimensional electrophoresis and the identification of the proteins using MALDI-TOF MS. By comparing expression pattern in the time course, we identified the candidate genes which are associated with neuronal differentiation. Among these genes, we performed real-time PCR analysis to validate Idh3alpha expression by the time course. To identify the function of Idh3alpha in neuronal differentiation stage, the transfection of Idh3alpha to PC12 cells was performed. As a result, we proved that up-regulation of Idh3alpha causes reduction in neural differentiation of PC12 cells. Based on these data, we suggest that Idh3alpha plays a role to the neuronal differentiation.

The time-dependent serial gene response to Zeocin treatment involves caspase-dependent apoptosis in HeLa cells.

Zeocin, a member of the bleomycin/phleomycin family of antibiotics, is known to bind DNA and to induce apoptosis in cervical cancer cells, but the mechanism underlying this apoptotic response is poorly understood. The present study was undertaken to elucidate time-dependent serial transcript patterns in the HeLa cervical carcinoma cell line, following treatment with Zeocin. The HeLa cell proliferation rate was found to gradually decrease following Zeocin exposure, in a time-and dose-dependent manner. RNA transcript level measurements, for time-dependent serial gene expression profiling, were determined at 0, 6, 12, 18 and 24 hr using a 0.5 k apoptosis functional microarray chip. Further statistical analysis, using a significance test at a 95% confidence level, for transcripts with a greater than 2-fold change on the array chips, identified 49 up-regulated and 57 down-regulated genes. Our gene expression profile data indicate that Zeocin treatment induces an initial release of cytochrome c, the down-regulation of Bcl-X (L), ENDOG, DAXX and MDM2, and the up-regulation of CASP and BID. This suggests that a p53-independent mitochondrial caspase cascade pathway is primarily involved in Zeocin-induced apoptosis. Such caspasedependent cytotoxic activity also implies that this cell death pathway occurs via the caspase 8 and BID genes. However, disruption of either FAS or TNFR1 signaling did not interfere with the Zeocin induced apoptotic response in our experimental system. We hypothesize that Zeocin could be active against cervical cancer cell resistance to conventional chemotherapy and postulate that Zeocin is a novel candidate for the development of new chemotherapeutic treatments of gynecological cancers.