The roles of metastasis-related proteins in the development of giant cell tumor of bone, osteosarcoma and Ewing's sarcoma.

BACKGROUND: Giant cell tumor of bone (GC), osteosarcoma (OS) and Ewing's sarcoma (ES) are three different types of bone cancer with common and specific pathology features. OBJECTIVE: The purpose of the study was to examine the relationship and differences of the three bone tumors using clinical samples. METHODS: Through screening the profiles of clinical samples from GC, OS and ES patients using a humanoncology array, we found 26, 25 and 15 tumorigenesis factors significantly increased in GS, OS and ES tissues compared to normal individuals. eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF directly or indirectly involve in the metastasis Therefore, expression levels of the 6 factors were further determined by Western blot. RESULTS: The results showed levels of MCP1, MCP2, MCP3 or IL-6 in the GS, OS and ES significantly increased, and the expression levels of angiogenesis and anti-angiogenesis factors containing eNOS, endostatin, HIF-1α, Tie or VEGF were enhanced. CONCLUSIONS: Our results suggest that eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF may play important roles in tumorigenesis, reveal the expression differences of tumor-associated cytokines and angiogenesis related factors, and provide clinical evidence for studying the mechanisms on the metastasis in GC, OS and ES.

Studies on the Neuroprotection of Osthole on Glutamate-Induced Apoptotic Cells and an Alzheimer's Disease Mouse Model via Modulation Oxidative Stress.

In the present study, the neuroprotection of osthole (OST) was confirmed. In L-glutamic acid (L-Glu)-damaged HT22 cells, a 3-h pre-incubation with OST-enhanced cell viability suppressed the apoptosis rate; inhibited the activities of caspase-3, caspase-8, and caspase-9; reduced the over-accumulation of intracellular reactive oxygen species; restored the dissipated mitochondrial membrane potential; and regulated the expression levels of B cell lymphoma-2 (Bcl-2), Bax, cleaved poly (ADP-ribose) polymerase (PARP), NF-E2p45-related factor 2 (Nrf2), and its downstream proteins. In amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, an 8-week OST administration improved the pathological behaviors related to memory and cognition, and reduced the expression levels of 4-hydroxynonenal, the deposition of ß-amyloid peptides and neuronal fiber tangles formed by the high phosphor-Tau in the brain. OST enhanced the expression levels of Nrf2 and its downstream proteins including superoxide dismutase-1 (SOD-1) and heme oxygenase-1 (HO-1). The present data confirmed the protection of OST against AD-like symptoms via modulating oxidative stress, especially Nrf2 signaling.

Protective roles of isoastilbin against Alzheimer's disease via Nrf2­mediated antioxidation and anti­apoptosis.

By analyzing the L­glutamic acid (L­Glu)­induced apoptosis of PC12 cells and an AlCl3 combined with D­galactose (D­gal)­developed Alzheimer's disease (AD) mouse model, the protective effects of isoastilbin (IAB) against AD were systematically investigated in the present study. Pre­incubation with IAB for 3 h prior to treatment with 25 mM L­Glu decreased cell viability and inhibited apoptosis, suppressed the accumulation of intracellular reactive oxygen species, and restored mitochondrial membrane potential in PC12 cells induced by L­Glu. In mice with AD, the reduced escape latency time in the water maze test, suppressed chronic movement in the center area of an open field test and enhanced ability to seek hidden food in a Y maze test indicated that abnormal behaviors had improved after 28 days of treatment with IAB. Furthermore, IAB reduced the deposition of amyloid ß (Aß) and the expression of phosphorylated­Tau in the mouse brain and enhanced the serum levels of Aß. IAB ameliorated the oxidative stress via modulating the levels of associated enzymes and improved the functioning of the central cholinergic system, as indicated by an increase in acetylcholine and choline acetyltransferase concentrations. The expression levels of acetylcholine esterase were reduced in the mouse brain in response to IAB pre­treatment. In cells and brain tissue, IAB regulated the expression levels of pro­ and anti­apoptotic proteins and enhanced the nuclear levels of NF­E2p45­related factor 2 (Nrf2); subsequently, IAB further enhanced the expression of superoxide dismutase 1, catalase, and heme oxygenase­1 and ­2. The findings of the present study indicated that the protection of IAB against AD is at least partially associated with its antioxidation and anti­apoptotic properties.

Sarcodon imbricatus polysaccharides improve mouse hematopoietic function after cyclophosphamide-induced damage via G-CSF mediated JAK2/STAT3 pathway.

Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. We investigated the effects of S. imbricatus polysaccharides (SIPS) on hematopoietic function and identified the underlying mechanisms using in vitro experiments with CHRF, K562, and bone marrow mononuclear cells (BMMNCs) and in vivo experiments with a mouse model of cyclophosphamide-induced hematopoietic dysfunction. We found that SIPS induced proliferation and differentiation of CHRF and K562 cells and upregulated the expression of hematopoietic-related proteins, including p90 ribosomal S6 kinases (RSK1p90), c-Myc, and ETS transcription factor, in the two cell lines. After 28 days of treatment, SIPS enhanced the bodyweight and thymus indices of the mice, alleviated enlargement of the spleen and liver, and contributed to the recovery of peripheral blood to normal levels. More importantly, the percentages of B lymphocytes and hematopoietic stem cells or hematopoietic progenitor cells were significantly elevated in bone marrow. Based on an antibody chip analysis and enzyme-linked immunosorbent assay, SIPS were found to successfully regulate 12 cytokines to healthy levels in serum and spleen. The cytokines included the following: interleukins 1Ra, 2, 3, 4, 5, and 6, tumor necrosis factor α, interferon-γ, granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), C-C motif chemokine1, and monocyte chemoattractant protein-1. Moreover, SIPS upregulated the phosphorylation levels of janus kinase 2 (JAK2) and the signal transducer and activator of transcription 3 (STAT3) in the spleen, and similar results were validated in CHRF cells, K562 cells, and BMMNCs. The data indicate that SIPS activated the JAK2/STAT3 pathway, possibly by interactions among multiple cytokines, particularly G-CSF. We found that SIPS was remarkably beneficial to the bone marrow hematopoietic system, and we anticipate that it could improve myelosuppression induced by long-term radiotherapy or chemotherapy.

The anti-fatigue activities of Tuber melanosporum in a mouse model.

Tuber melanosporum (TM) is an edible fungus that exhibits antioxidant and anti-tumor activity via its unique bioactive metabolites. The present study analyzed the anti-fatigue effects of TM using a BALB/c mouse model. The anti-fatigue properties of TM were evaluated by assessing the endurance of mice by performing forced swimming, rotary rod and running tests. Following 2 weeks TM treatment, hepatic and muscular ATP, and glycogen levels were increased in mice subjected to 30 min swimming, compared with controls. Similarly, levels of serum lactic acid and lactic dehydrogenase were decreased in the same group, compared with the control. Additionally, TM treatment reduced reactive oxygen species and malondialdehyde levels, and increased superoxide dismutase and glutathione peroxidase levels in the muscle, liver and/or serum. The effect of TM on hormone levels was also investigated in the present study, as different efficacies of TM were observed in male and female mice. TM treatment increased serum levels of progesterone, estradiol and testosterone in female and male mice, whereas a decrease in serum luteinizing hormone levels was only observed in females. A decrease in serum follicle-stimulating hormone levels was identified in females, whereas an increase was observed in males. The current study demonstrated that the anti-fatigue effects of TM occur via the regulation of oxidative stress, energy metabolism and hormone levels.

Investigation of the neuroprotective effects of Lycium barbarum water extract in apoptotic cells and Alzheimer's disease mice.

Alzheimer's disease (AD) affects people worldwide and is caused by chronic and progressive damage to the central nervous system. Lycium barbarum (LB), a renowned functional food and medicinal plant in Southeast Asia, may possess protective effects against nerve injury. The present study aimed to investigate the neuroprotective effects of LB water extract in a differentiated (D)PC12 cellular apoptosis model induced by L­glutamic acid (L­Glu), and a mouse model of AD, induced by the combination of AlCl3 and D­galactose. LB markedly increased DPC12 cell survival against L­Glu induced damage by increasing cell viability, reducing the apoptosis rate and G1 phase arrest, suppressing intracellular reactive oxygen species accumulation, blocking Ca2+ overload and preventing mitochondrial membrane potential depolarization. LB additionally normalized the expression levels of apoptosis regulator Bcl­2, apoptosis regulator BAX, and cleaved caspase­3, ­8 and ­9 in L­Glu exposed cells. In the AD mouse model, LB increased the amount of horizontal and vertical movement in the autonomic activity test, improved endurance time in the rotarod test and decreased escape latency time in the Morris water maze test. Additionally, the levels of acetylcholine and choline acetyltransferase were significantly increased in the serum and hypothalamus in the LB­treated AD mice. These data suggested that LB may exert neuroprotective effects and may aid in preventing neurodegenerative disease.