Kaempferide (KFD) is a naturally occurring flavonoid that exists in various medicinal plants. The pharmaceutical properties of KFD, including its anti-cancer, antioxidant and anti-diabetic effects, have been noted, but the effects of KFD on photoaging and their underlying molecular mechanism have yet to be elucidated. In this study, we investigated the effects of KFD on Ultraviolet-B (UVB)-mediated photoaging processes using in vitro and in vivo photoaging model systems. The topical administration of KFD on mouse dorsal areas suppressed UVB-mediated wrinkle formation and epidermal thickening. In addition, the UVB-mediated reduction of dermal collagen content, which was estimated by Masson’s trichrome staining, was recovered through KFD treatments. Furthermore, we found that UVB-induced abnormal values of procollagen type-1 (COL1A1), metalloproteinases (MMP-1a and MMP-3) and proinflammatory cytokines (IL-8, MCP-3 and IL-6) on mouse skin tissue as well as NIH-3T3 cells was recovered through KFD treatment. The administration of KFD to NIH-3T3 cells suppressed the UVB-mediated upregulation of reactive oxygen species (ROS), mitogen-activated protein kinases (MAPKs) and AKT phosphorylation. Furthermore, the treatment of ROS inhibitor restored the UVB-induced MAPKs and AKT phosphorylation as well as the abnormal expression of photoaging related genes. These findings indicate that KFD can attenuate UVB-induced ROS elevation to elicit anti-photoaging activity. Taken together, our data suggest that KFD could be developed as a potential natural anti-photoaging agent.

Gleditsia sinensis thorns (GST) have been used as a traditional medicine for carbuncles and skin diseases. The purpose of this study was to decide whether non-toxicological levels of water extract of GST (WEGST) are effective in inhibiting the progress of prostate cancer formation and to identify the target molecule involved in the WEGST-mediated inhibitory process of prostate cancer cell migration and in vivo tumor formation. Through the Boyden chamber migration assay, we found that non-toxic levels of WEGST could not attenuate the PC3 migration to the bottom area coated with serum but significantly inhibited PC3 cell migration to the collagen-coated bottom area. We also found that non-toxic levels of WEGST significantly attenuated collagen against adhesion. Interestingly, ectopic administration of WEGST could not affect the expression of α2β1 integrin, which is known as a receptor of collagen. However, when the PC3 cells adhered to a collagen-coated plate, the expression of α2 integrin but not that of β1 integrin was significantly inhibited by the administration of non-toxic levels of WEGST, leading to the inhibition of focal adhesion kinase (FAK) phosphorylation. Furthermore, oral administration of WEGST (25 mg/kg/day) significantly inhibited the size of a PC3 cell-xenografted tumor. Taken together, these results suggest a novel molecular mechanism for WEGST to inhibit prostate cancer progression at particular stages, such as collagen-mediated adhesion and migration, and it might provide further development for the therapeutic use of WEGST in the treatment of prostate cancer progression.

Many neurodegenerative diseases have several similar cellular dysregulations. We investigated the inhibitory role of Ishige okamurae, an edible brown alga, on neurodegenerative processes by estimating the effects of Ishige okamurae on excitotoxicity induced by glutamate in vitro and neurodegeneration induced by trimethyltin (TMT) in vivo. This study aimed to describe the molecular mechanisms responsible for the mediating anti-neurodegenerative effects of Ishige okamurae extract (IOE). The oral administration of IOE to TMT-injected mice impeded the TMT-mediated short- and long-term memory impairments investigated by the Morris water maze and Y-maze test. IOE attenuated TMT-mediated cellular apoptosis and the expression of brain-derived neurotrophic factor, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in mice brains. Glutamate-induced apoptosis and the expression of reactive oxygen species, Nrf2, and HO-1 in HT22 cells were also attenuated by IOE. In addition, TMT- and glutamate-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in mouse brain tissues and HT22 cells were attenuated by the treatment of IOE. In HT22 cells, administration of MAPK inhibitors recovered the glutamate induced by the expression of Nrf2, HO-1, and cellular dysregulation to the equal extent to IOE administration. Taken together, these results suggest that IOE could attenuate neurodegenerative processes, such as TMT- and glutamate-mediated neuronal dysregulation, by regulating MAPKs/Nrf-2/HO-1 antioxidant pathways.

Aims: Glioblastoma multiforme (GBM) is the most lethal tumor with a median patient survival of 14 to 15 months. Glioma stem cells (GSCs) play a critical role in tumor initiation and therapeutic resistance in GBM. B3GNT5 has been suggested as the key glycosyltransferase in the biosynthesis of the (neo‐) lacto series of glycosphingolipid. In this study, we evaluated the B3GNT5 expression in GSCs as well as the correlation with clinical data in GBM.Methods: The mRNA levels of B3GNT5 in normal astrocytes, four glioma cell lines, and four GSCs were evaluated using real‐time PCR. Small interference RNAs (siRNAs) were used to inhibit B3GNT5 expression and analyze its ability to form neurospheres. Statistical analyses were conducted to determine the association with B3GNT5 expression and tumor grade and GBM subtypes as well as patient survival using public datasets.Results: B3GNT5 expression was significantly elevated in GSCs compared with normal astrocytes, glioma cell lines, and their matched differentiated tumor cells. Knockdown of B3GNT5 in GSCs decreased the neurosphere formation. Patients with high B3GNT5 expression had a short overall survival. B3GNT5 is correlated with classical and mesenchymal GBM subtypes.Conclusion: The findings suggest the central role of B3GNT5 in regulating malignancy of GBM.

Overexpression of human epidermal growth factor receptor type 2 (HER2) is considered as a prognostic factor of breast cancer, which is positively associated with recurrence when cancer metastasizes to the lymph nodes. Here, we expressed the single variable domain on a heavy chain (VHH) form of anti-HER2 camelid single domain antibody in tobacco plants and compared its in vitro anticancer activities with the anti-HER2 full size antibody. The gene expression cassette containing anti-HER2 camelid single domain antibody VHH fused to human IgG Fc region with KDEL endoplasmic reticulum (ER) (VHH-FcK) was transferred into the tobacco plant via the Agrobacterium-mediated transformation. The transformants were screened with polymerase chain reaction and Western blot analyses. Enzyme-linked immunosorbent assay (ELISA) confirmed the binding of the purified anti-HER2 VHH-FcK to the HER2-positive breast cancer cell line, SK-BR-3. Migration assay results confirmed anticancer activity of the plant-derived anticancer camelid single chain antibody. Taken together, we confirmed the possibility of using anti-HER2 VHH-FcK as a therapeutic anticancer agent, which can be expressed and assembled and purified from a plant expression system as an alternative antibody production system.

Since mushrooms have many bioactive components, they have been used as components in folk medicine. Because mycelium has an advantage when it comes to large-scale production, this study aimed to evaluate the antioxidant properties and anti-tyrosinase activity from 55 mycelia in culture media. Relatively high 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity was detected from the ethanol extract of culture media including mycelium (EECiM) ofMorchella esculentavar.esculenta(MEVE),Auricularia polytricha(APO),Tremella aurantia(TAU),Volvariella bombycina(VBO), andOudemansiellasp. (Osp), which also showed strong reducing power and inhibitory activity in relation to the thiobarbituric acid (TBA) value. On the other hand, relatively high tyrosinase inhibitory activity was detected inInonotus mikadoi(IMI),Coriolus versicolor(CVE),Volvariella volvacea(VVO),Panellus serotinus(PSE),Auricularia auricula(AAU), andFomitopsissp. (Fsp). Interestingly, the APO EECiM exhibited the highest DPPH radical scavenging rate (77.5 ± 4.3%) and reducing power (1.18 ± 0.041), while the highest inhibitory power of the TBA value and antityrosinase activity were detected in that of TAU (64.5 ± 4.1%) and IMI (46.0 ± 7.5%), respectively. Overall, our study suggested potential candidates for EECiMs that exhibited powerful antioxidant and tyrosinase inhibitory properties and might be used as natural antioxidant tyrosinase inhibitor.