A new class of potential magnetic resonance imaging contrast agents with nanosized mesoporous silica as the metal carrier is reported. Gadolinium-incorporated mesoporous silicas were synthesized by using longchain surfactant as a template. The products were characterized with X-ray powder diffraction, nitrogen adsorption-desorption isotherms, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, 29 Si-MAS NMR, and proton relaxivity. The materials showed much higher relaxivities, r 1 and r 2 , than Gd-DTPA. The particles are nanosized and can enter cells easily. This is a completely novel biomedical application of mesoporous silica materials.

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Osteoporosis is one of the most common bone pathologies. A number of novel molecules have been reported to increase bone formation including cysteine-rich protein 61 (CYR61), a ligand of integrin receptor, but mechanisms remain unclear. It is known that bone morphogenetic proteins (BMPs), especially BMP-2, are crucial regulators of osteogenesis. However, the interaction between CYR61 and BMP-2 is unclear. We found that CYR61 significantly increases proliferation and osteoblastic differentiation in MC3T3-E1 osteoblasts and primary cultured osteoblasts. CYR61 enhances mRNA and protein expression of BMP-2 in a time-and dose-dependent manner. Moreover, CYR61-mediated proliferation and osteoblastic differentiation are significantly decreased by knockdown of BMP-2 expression or inhibition of BMP-2 activity. In this study we found integrin ␣ v ␤ 3 is critical for CYR61-mediated BMP-2 expression and osteoblastic differentiation. We also found that integrin-linked kinase, which is downstream of the ␣ v ␤ 3 receptor, is involved in CYR61-induced BMP-2 expression and subsequent osteoblastic differentiation through an ERK-dependent pathway. Taken together, our results show that CYR61 up-regulates BMP-2 mRNA and protein expression, resulting in enhanced cell proliferation and osteoblastic differentiation through activation of the ␣ v ␤ 3 integrin/integrin-linked kinase/ ERK signaling pathway.Bone is a mineralized tissue that underlies multiple mechanical and metabolic functions of the skeleton (1). Bone functions include maintaining blood calcium levels, providing mechanical support to soft tissues and serving as levers for muscle action, supporting hematopoiesis, and housing the brain and spinal cord (2). Formation and maintenance of bone tissue are regulated in a sophisticated fashion by boneforming osteoblasts and bone-resorbing osteoclasts (3). Development and differentiation of these two cell types are under tight regulation by a number of endogenous substances such as hormones, growth factors, and cytokines (4). These factors are individually secreted through endocrine, paracrine/autocrine, and neurocrine systems, with subsequent interaction essential to the delicate balance between bone-forming and -resorbing cells in the marrow microenvironment. An imbalance between the two cell types leads to pathogenesis of certain bone diseases including osteopetrosis and osteoporosis (5, 6).Osteoporosis is the most common human metabolic bone disorder characterized by progressive and age-dependent bone loss and increasing bone fracture risk. It is an important public health issue in postmenopausal women; if untreated, more than half of white women will experience fractures during their lifetime. Between 30 and 50% of women and 15-30% of men will suffer a fracture related to osteoporosis in their lifetime (7). Fractures increase morbidity and mortality and impose a financial burden on the community (8). A most compelling therapeutic need for osteoporosis at the present time is a drug that will substantially increase bone formation...

Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.

A new isomalabaricane triterpenoid, stellettin A [1], was isolated from the sponge Stelletta tenuis collected off Hainan Island, People's Republic of China. Its structure and stereochemistry were established by analysis of its spectral data and reference to related compounds.

MicroRNAs (miRNAs) are a group of small noncoding RNAs capable of regulating specific gene expression. Let-7 miRNA was first discovered in Caenorhabditis elegans and it is highly conserved in human tissues. The human let- 7 family of miRNA contains 12 members of miRNA. Today, these members have become the most studied miRNAs and they have attracted attention of researchers in various fields, such as development, stem cell biology, aging, and metabolism. Furthermore, there is a large body of evidence linking the loss of let-7 expression and the development of poorly differentiated, aggressive cancers. In addition to the canonical biogenesis pathway, let-7 has been found to be regulated by protein factors, such as RNA binding proteins previously identified as regulators of protein-coding mRNAs. Moreover, the direct interaction between miRNAs has recently been identified as a novel pathway to control let-7 expression. In this review, we discuss the multifaceted roles of let-7 and provide an overview of its regulation at multiple levels.

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Therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib or erlotinib) significantly prolongs survival time for patients with tumors harboring an activated mutation on EGFR; however, up to 40% of lung cancer patients exhibit acquired resistance to EGFR-TKIs with an unknown mechanism. FOXO3a, a transcription factor of the forkhead family, triggers apoptosis, but the mechanistic details involved in EGFR-TKI resistance and cancer stemness remain largely unclear. Here, we observed that a high level of FOXO3a was correlated with EGFR mutation-independent EGFR-TKI sensitivity, the suppression of cancer stemness, and better progression-free survival in lung cancer patients. The suppression of FOXO3a obviously increased gefitinib resistance and enhanced the stem-like properties of lung cancer cells; consistent overexpression of FOXO3a in gefitinib-resistant lung cancer cells reduced these effects. Moreover, we identified that miR-155 targeted the 3′UTR of FOXO3a and was transcriptionally regulated by NF-κB, leading to repressed FOXO3a expression and increased gefitinib resistance, as well as enhanced cancer stemness of lung cancer in vitro and in vivo. Our findings indicate that FOXO3a is a significant factor in EGFR mutation-independent gefitinib resistance and the stemness of lung cancer, and suggest that targeting the NF-κB/miR-155/FOXO3a pathway has potential therapeutic value in lung cancer with the acquisition of resistance to EGFR-TKIs.