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Oligodendrocytes (OLs), myelin-producing glia in the central nervous system (CNS), produce a myelin extension that enwraps axons to facilitate action potential propagation. An effective approach to induce oligodendrogenesis and myelination is important to foster CNS development and promote myelin repair in neurological diseases. Hericium (H.) erinaceus, an edible and culinary-medicinal mushroom, has been characterized as having neuroprotective activities. However, its effect on OL differentiation has not yet been uncovered. In this study using oligodendrocyte precursor cell (OPC) cultures and an ex vivo cerebellar slice system, we found that the extract from H. erinaceus mycelium (HEM) not only promoted the differentiation of OPCs to OLs in the differentiation medium, but also increased the level of myelin basic protein (MBP) on neuronal fibers. Moreover, daily oral administration of HEM into neonatal rat pups for 7 days enhanced MBP expression and OLs in the corpus callosum of the postnatal rat brain. The effect of HEM-derived bioactive compounds, the diterpenoid xylosides erinacine A (HeA) and HeC and a sesterterpene with 5 isoprene units called HeS, were further evaluated. The results showed that HeA and HeS more potently stimulated MBP expression in OLs and increased the number of OLs. Moreover, overlap between MBP immunoreactivity and neuronal fibers in cultured cerebellar tissue slices was significantly increased in the presence of HeA and HeS. In summary, our findings indicate that HEM extract and its ingredients HeA and HeS display promising functional effects and promote OL maturation, providing insights into their potential for myelination in neurodevelopmental disorders.

Oligodendrocytes (OLs), myelin-producing glia in the central nervous system (CNS), produce a myelin extension that enwraps axons to facilitate action potential propagation. An effective approach to induce oligodendrogenesis and myelination is important to foster CNS development and promote myelin repair in neurological diseases. Hericium (H.) erinaceus, an edible and culinary-medicinal mushroom, has been characterized as having neuroprotective activities. However, its effect on OL differentiation has not yet been uncovered. In this study using oligodendrocyte precursor cell (OPC) cultures and an ex vivo cerebellar slice system, we found that the extract from H. erinaceus mycelium (HEM) not only promoted the differentiation of OPCs to OLs in the differentiation medium, but also increased the level of myelin basic protein (MBP) on neuronal fibers. Moreover, daily oral administration of HEM into neonatal rat pups for 7 days enhanced MBP expression and OLs in the corpus callosum of the postnatal rat brain. The effect of HEM-derived bioactive compounds, the diterpenoid xylosides erinacine A (HeA) and HeC and a sesterterpene with 5 isoprene units called HeS, were further evaluated. The results showed that HeA and HeS more potently stimulated MBP expression in OLs and increased the number of OLs. Moreover, overlap between MBP immunoreactivity and neuronal fibers in cultured cerebellar tissue slices was significantly increased in the presence of HeA and HeS. In summary, our findings indicate that HEM extract and its ingredients HeA and HeS display promising functional effects and promote OL maturation, providing insights into their potential for myelination in neurodevelopmental disorders.

B cell CLL/lymphoma 11B (Bcl11b), a C2H2 zinc finger transcription factor, not only serves as a critical regulator in development but also plays the controversial role in T cell acute lymphoblastic leukemia (T-ALL). We previously found that the enriched expression of Bcl11b was detected in high tumorigenic C6 glioma cells. However, the role of Bcl11b in glioma malignancy and its mechanisms remains to be uncovered. In this study, using the lentivirus-mediated knockdown (KD) approach, we found that Bcl11b KD in tumorigenic C6 cells reduced the cell proliferation, colony formation, and migratory ability. The results were further verified using two human malignant glioma cell lines, U87 and U251 cells. A cyclin-dependent kinase inhibitor p21, a known Bcl11b target, was significantly upregulated in tumorigenic C6, U87, and U251 cells after Bcl11b KD. Cellular senescence was observed by examination of the β-galactosidase activity in U87 and U251 cells with Bcl11b KD. Reduced expression of stemness gene Sox-2 and its downstream effector Bmi-1 was also observed in U87 and U251 cells with Bcl11b KD. These results suggest that the ablation of Bcl11b gene expression induced glioma cell senescence. Propidium iodide (PI) staining combined with flow cytometry analysis also showed that Bcl11b KD led to the cell cycle arrest of U87 and U251 cells at the G0/G1 or at the S phase, indicating that Bcl11b is required for glioma cell cycle progression. Together, this is the first study to show that the inhibition of Bcl11b suppresses glioma cell growth by regulating the expression of the cell cycle regulator p21 and stemness-associated genes (Sox-2/Bmi-1).

Present study tested a hypothesis that the seasonal reproductive pattern would be similar between two sympatric congeneric species of frogs, Buergeria japonica and B. robusta, by examining, fat body, liver and gonadal cycle. In total, 132 and 148 adult frogs, respectively, were collected from Taichung, Central Taiwan during July 1996 and July 1997. Both species were classified as prolonged breeders, breeding from March to August. This breeding season differs from those in conspecific populations from other localities. In both species, adult females attained larger snout-vent length (SVL), body mass (BM), head length (HL), and head width (HW) than males. The smaller size of male in these species is inconsistent with a previous energetic constraint hypothesis that smaller males are caused by the costs of advertising, maintaining territories, and lower food intake in prolonged breeding species. Neither B. japonica nor B. robusta showed a significant positive correlation between female ovary mass and...

Glioblastoma multiforme (GBM) is the most common primary brain tumor, and has poor prognosis and high recurrences. Pin1, a peptidyl-prolyl isomerase, can recognize phospho-Ser/Thr-Pro motifs and isomerize the cis/trans forms of its substrates. It has been known that Pin1 is involved in cell cycle regulation and cell proliferation, and has affected various protein stability and function, such as cyclin D1 and p53. Recent study has showed that cyclin D1 can directly bind to RAD51 upon radiation in addition to its role in cell cycle. This complex is recruited to DNA damage sites and helps DNA repair. Here, we investigated the role of Pin1 in regulating cyclin D1/RAD51 interaction and affecting the radiosensitivity in U87MG glioblastoma cells. We showed that no interaction was detected between cyclin D1 and RAD51 after ionic radiation in U87MG cells; interestingly, knockdown of Pin1 decreased both cyclin D1 and RAD51 expression and enhanced their sensitivities to radiation. Furthermore, knockdown of Pin1 with IR induced G1 and G2/M arrest which resulted in cell growth inhibition and apoptosis. Importantly, knockdown of Pin1 and combination with radiation yielded increased number of γ -H2AX foci than radiation control cells, suggesting that delayed repair occurred in pin1 knockdown cells. In summary, our results suggest that inhibition of Pin1 decreases RAD51 expression and enhances radiosenstivity in U87MG glioblastoma Cells. Citation Format: Edmund I. IT Chen, Chia-Hsin Ho. Inhibition of Pin1 reduces RAD51 expression and enhances radiosensitivity in U87MG glioblastoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 430. doi:10.1158/1538-7445.AM2013-430

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world. Metastases are resistant to conventional therapies and are responsible for 90% of tumour-related death. Better understanding on the molecular mechanism of metastasis may shed light on prevention and treatment of disease. We have established a systemic cellular model for metastases investigation. The parental SAS cells, a low tumorigenic HNSCC cell line; SASVO3 (VO3) cells, a highly tumorigenic cells derived from SAS; and SASVO3M-1 (M1) and SASVO3M-5 (M5) cells, two lines of pulmonary metastatic cells derived from SASVO3 cells using mice model. Transcriptome analysis revealed that M1 and M5 shared the most similar transcription signature and their common genes were designated common M. The profiles of VO3 and common M were distinct from that of parental SAS. Biological pathway analyses showed the signaling of cell movement such as integrin, RhoA, Cdc42, Rac, and actin polymerization were identified in metastatic cells. Of oncogenic properties, metastatic cells possess increased activities of foci formation, filopodia formation, wound healing, and in vivo pulmonary metastases. Interestingly, metabolism assay revealed that the glycolysis activity was increased in highly tumorigenic VO3 cells compare to parental SAS. Yet it was decreased in metastatic M5 cells compared to VO3 cells. “Reverse Warburg effect," which indicating a lowered glycolysis in tumor cells, has been demonstrated by others in metastatic breast cancer by in situ immunohistochemistry stain. The correlation of metabolism and metastasis of HNSCC cells will be discussed. Citation Format: Pei-Fen Su, Shu-Hao Chang, Chia-Hsin Ho, Wei-Li Huang. Increased Rho GTPase and reduced glycolysis activity in metastatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 397. doi:10.1158/1538-7445.AM2013-397