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Ovarian cancer is a lethal malignant tumour characterised by activated invasion, distant metastasis, anti-cancer drug resistance, angiogenesis and metabolism. CD147, an extracellular matrix metalloproteinase inducer, is overexpressed in most ovarian tumours and plays an important role in the progression of ovarian cancer and other malignant tumours. However, the factor(s) initiating this overexpression is unknown. Because of rapid reproduction and their hypoxic microenvironment, malignant tumours use glycolysis for energy, and lactic acid produced is harmful to the cells. For survival, excessive lactate needs to be transported by monocarboxylate transporters (MCTs). Functioning of MCT1 and MCT4 require the ancillary of CD147. The gene for CD147 possesses two hypoxia-inducible factors binding sites in its 3′-flank. It is logical to postulate that the hypoxic microenvironment is a major initiator of the overexpression of CD147, thus conferring on ovarian cancers their malignant properties. A model that can represent spontaneous ovarian cancer is necessary to verify this hypothesis. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a deadly and common primary brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity. Sex differences may play a role in patient outcome. Previous studies showed that ER‐α36, a variant of the estrogen receptor (ER), mediated non‐genomic estrogen signaling and is highly expressed in many ER‐negative malignant tumors. ER‐α36 also associates with epidermal growth factor receptor (EGFR). The primary purpose of this study is to investigate the cross talk between ER‐α36 and EGFR in estrogen‐mediated GBM cell proliferation. Here, we showed that ER‐α36 was highly expressed and confirmed that ER‐α36 co‐labels with EGFR in human GBM samples using immunohistochemical techniques. We also investigated the mechanisms of estrogen‐induced proliferation in ER‐α‐negative cell lines. We found that GBM cells showed varying responsive to mitogenic estrogen signaling which correlated with ER‐α36 expression, and knockdown of ER‐α36 diminished the response. Exposure to estrogen also caused upregulation of cyclin protein expression in vitro. We also found that low concentration of estrogen promoted SRC‐Y‐416 and inhibited SRC‐Y‐527 phosphorylation, corresponding with activated SRC signaling. Inhibiting SRC or EGFR abolished estrogen‐induced mitogenic signaling, including cyclin expression and MAPK phosphorylation. Cumulatively, our results demonstrate that ER‐α36 promotes non‐genomic estrogen signaling via the EGFR/SRC/MAPK pathway in GBM. This may be important for the treatment of ER‐α‐negative GBMs that retain high level of ER‐α36, since estrogen may be a viable therapeutic target for these patients. [ABSTRACT FROM AUTHOR]

Arecoline, a major alkaloid of the areca nut, has potential toxicity to the nervous system. Our previous study reveals that the neurotoxicity of arecoline involves in inhibited endogenous hydrogen sulfide (H2S) generation. Therefore, the present study investigated whether exogenous H2S protects against arecoline‐induced neurotoxicity and further explore the underlying mechanisms focusing on leptin/leptin receptor signaling pathway. The cell viability was measured by CCK‐8 kit. The apoptosis were detected by Hoechst 33258 and Annexin V/PI (propidium iodide) staining. The protein expressions were determined by Western blot analysis. Our results demonstrated that NaHS, an exogenous H2S donor, significantly increases the cell viability, decreases apoptosis ratio, and reduces caspase‐3 activity as well as Bax/Bcl‐2 ratio in PC12 cells exposed to arecoline, indicating the protection of H2S against arecoline‐induced cytotoxicity and apoptosis. Also, NaHS attenuated arecoline‐induced endoplasmic reticulum (ER) stress, as evidenced by the decreases in the expressions of glucose‐regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and Cleaved caspase‐12. Meanwhile, NaHS promoted leptin/leptin receptor signaling pathway in arecoline‐exposed PC12 cells, as illustrated by upregulations of leptin and leptin receptor expressions. Furthermore, leptin tA, an antagonist of leptin receptor, obviously abolished the inhibitory effects of NaHS on arecoline‐induced cytotoxicity, apoptosis, and ER stress in arecoline‐exposed PC12 cells. Taken together, these results suggested that H2S prevents arecoline‐induced neurotoxicity via enhancing the leptin/leptin receptor signaling pathway. [ABSTRACT FROM AUTHOR]

Cell labeling and tracking are becoming increasingly important areas within the field of stem cell transplantation. The ability to track the migration and distribution of implanted cells is critical to understanding the beneficial effects and mechanisms of stem cell therapy. The present study investigated the effects of amine-surface-modified superparamagnetic iron oxide (SPIO) nanoparticles on the biological properties of human adipose tissue-derived stem cells (hADSCs). Monodisperse hydrophobic magnetite (Fe3O4) nanoparticles were prepared using silicon and surface-modified with amine coating. Cell viability, proliferation, differentiation potential, and surface marker expression were evaluated. The magnetic particles (10-18 nm) displayed high labeling efficiency and stability in hADSCs. SPIO-labeled cells produced a hypointense signal and were effectively visualized by MRI for up to 21 days. The results of MTT proliferation assays and flow cytometry analysis demonstrated that SPIOs were biocompatible, viz. the labeling process did not cause cell death or apoptosis and had no side effects on cell proliferation. In vivo experiments showed that the magnetic particles did not affect liver and kidney function. The successful and stable labeling of hADSCs combined with efficient magnetic tropism demonstrates that SPIOs are promising candidates for hADSC tracking in hADSC-based cell therapy applications. [ABSTRACT FROM AUTHOR]

To simulate brain microenvironment, adipose-derived mesenchymal stem cells (AMSC) were induced to differentiate to neuronal-like cells in rat cortex and hippocampus medium (Cox + Hip). First, isolated AMSC were characterized by flow cytometer and the capacity of adipogenesis and osteogenesis. After induction in rat cortex and hippocampus conditioned medium, the cell morphological change was examined and neural marker proteins (β-Ш-Tubulin, NSE, Nissl body) expression was detected by immunofluorescence staining. A variety of synaptic marker proteins, including GAP43, SHANK2, SHANK3 and Bassoon body, were detected. ELISA was used to measure brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) secretion at different time-points. AMSCs positively expressed CD13, CD44 and CD90 and could differentiate into osteoblasts or adipocytes. After induction in Cox + Hip medium for 14 days, cells had a typical neuronal perikaryal appearance, which was suggestive of neuronal differentiation. After 14 days of Cox + Hip treatment, the percentage of cells expressing β-Ⅲ-Tubulin, NSE and Nissl was 53.9 ± 0.8%, 51.3 ± 1.7% and 16.4 ± 2.1%, respectively. Expression of GAP43, SHANK2, SHANK3 and Bassoon body was detected, indicating synapse formation after treatment in Cox + Hip medium. Differentiated AMSCs secreted neurotrophic factors NGF and BDNF. Thus rat cortex and hippocampus-derived soluble factors can induce AMSCs to a neuronal-like phenotype, suggesting that AMSCs have a dual role in supplementing newborn neurons and secreting neurotrophic factors, and therefore could be help as a potential treatment for nervous system diseases. [ABSTRACT FROM AUTHOR]