This work has implications for the development of therapeutic treatments of genetic disorders, and it demonstrates that significant technical issues remain to be addressed. We advocate preventing any application of genome editing on the human germline until after a rigorous and thorough evaluation and discussion are undertaken by the global research and ethics communities.

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Treatment of hepatocellular carcinomas (HCCs) with chemotherapy has generally been disappointing and it is most desirable to have more effective new drugs. We extracted and purified 6 xanthone compounds from the rinds (peel) of the fruits of Garcinia mangostana L., using partitioned chromatography and then tested the cytotoxic effects of these compounds on a panel of 14 different human cancer cell lines including 6 hepatoma cell lines, based on the MTT method. Several commonly used chemotherapeutic agents were included in the assay to determine the relative potency of the potential new drugs. Our results have shown that one of the xanthone derivatives which could be identified as garcinone E has potent cytotoxic effect on all HCC cell lines as well as on the other gastric and lung cancer cell lines included in the screen. We suggest that garcinone E may be potentially useful for the treatment of certain types of cancer.

Mechanical interaction between the cell and its extracellular matrix (ECM) regulates cellular behaviors, including proliferation, differentiation, adhesion, and migration. Cells require the three dimensional (3D) architectural support of the ECM to perform physiologically realistic functions. However, current understanding of cell-ECM and cell-cell mechanical interactions is largely derived from 2D cell traction force microscopy, in which cells are cultured on a flat substrate. 3D cell traction microscopy is emerging for mapping traction fields of single animal cells embedded in either synthetic or natively derived fibrous gels. We discuss here the development of 3D cell traction microscopy, its current limitations, and perspectives on the future of this technology. Emphasis is placed on strategies for applying 3D cell traction microscopy to individual tumor cells migration within collagen gels.

Investigating the constituents of the roots of Vitis thunbergii led to the isolation of four new resveratrol derivatives, vitisinols A-D (1-4), together with (+)-epsilon-viniferin, (-)-viniferal, ampelopsin C, miyabenol A, (+)-vitisin A, and (+)-vitisin C. The structures of these 10 compounds were established by spectroscopic (NMR and MS) analyses. All of the isolated compounds, except 1, were tested for their antiplatelet and antioxidative activities.

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone formation. Here, we examined the effects of betulinic acid on cell proliferation, differentiation, and mineralization of MC3T3-E1 osteoblasts. Then, the impact of betulinic acid on signaling pathways known to be implicated in osteoblastogenesis was explored. Betulinic acid (1-20 microM) markedly increased alkaline phosphatase (ALP) activity and calcium nodule formation, although without a notable effect on cell proliferation. Stimulation with betulinic acid not only increased the osteopontin level and osteocalcin mRNA expression but also upregulated the osteoprotegerin (OPG)/RANKL ratio. Noggin, but not ICI 182780, significantly repressed betulinic acid-induced ALP activity, suggesting a possible action of betulinic acid through the bone morphogenetic protein (BMP) pathway. This was strengthened by the induction of BMP-2 expression, increases in Smad1/5/8 phosphorylation, and Runx2 expression. Furthermore, betulinic acid increased the nuclear level of the active form beta-catenin. These results suggested that betulinic acid has the potential to enhance osteoblastogenesis probably through the activation of BMP/Smad/Runx2 and beta-catenin signal pathways. Furthermore, upregulation of the OPG/RANKL ratio to repress bone catabolism may also indirectly contribute to the bone anabolic effect of betulinic acid.

The Asian citrus psyllid, Diaphorina citri is the principal vector of huanglongbing, which transmits Candidatus Liberibacter asiaticus. Trehalase is a key enzyme involved in trehalose hydrolysis and plays an important role in insect growth and development. The specific functions of this enzyme in D. citri have not been determined. In this study, three trehalase genes (DcTre1-1, DcTre1-2, and DcTre2) were identified based on the D. citri genome database. Bioinformatic analysis showed that DcTre1-1 and DcTre1-2 are related to soluble trehalase, whereas DcTre2 is associated with membrane-bound trehalase. Spatiotemporal expression analysis indicated that DcTre1-1 and DcTre1-2 had the highest expression levels in the head and wing, respectively, and DcTre2 had high expression levels in the fat body. Furthermore, DcTre1-1 and DcTre1-2 expression levels were induced by 20-hydroxyecdysone and juvenile hormone Ⅲ, but DcTre2 was unaffected. The expression levels of DcTre1-1, DcTre1-2, and DcTre2 were significantly upregulated, which resulted in high mortality after treatment with validamycin. Trehalase activities and glucose contents were downregulated, but the trehalose content increased after treatment with validamycin. In addition, the expression levels of chitin metabolismrelated genes significantly decreased at 24 and 48 h after treatment with validamycin. Furthermore, silencing of DcTre1-1, DcTre1-2, and DcTre2 reduced the expression levels of chitin metabolism-related genes and led to a malformed phenotype of D. citri. These results indicate that D. citri trehalase plays an essential role in regulating chitin metabolism and provides a new target for control of D. citri.

Investigation of the constituents of Garcinia mangostana has led to the isolation of four new compounds: three minor xanthones, garcimangosone A (1), garcimangosone B (2), and garcimangosone C (3), and a benzophenone glucoside, garcimangosone D (4). The structures of these four compounds were established by spectral (NMR and MS) and chemical methods.