CI431, an Aqueous Compound from Ciona intestinalis L., Induces Apoptosis through a Mitochondria-Mediated Pathway in Human Hepatocellular Carcinoma Cells

In the present studies, a novel compound with potent anti-tumor activity from Ciona intestinalis L. was purified by acetone fractionation, ultrafiltration, gel chromatography and High Performance Liquid Chromatography. The molecular weight of the highly purified compound, designated CI431, was 431Da as determined by HPLC-MS analysis. CI431 exhibited significant cytotoxicity to several cancer cell types. However, only a slight inhibitory effect was found when treating the benign human liver cell line BEL-7702 with the compound. To explore its mechanism against hepatocellular carcinoma, BEL-7402 cells were treated with CI431 in vitro. We found that CI431 induced apoptotic death in BEL-7402 cells in a dose- and time-dependent manner. Cell cycle analysis demonstrated that CI431 caused cell cycle arrest at the G2/M phase, and a sub-G1 peak appeared after 24 h. The mitochondrial-mediated pathway was implicated in this CI431-induced apoptosis as evidenced by the disruption of mitochondrial membrane potential. The results suggest that the CI431 induces apoptosis in BEL-7402 human hepatoma cells by intrinsic mitochondrial pathway

Dynamic Interplay between the Co-Opted Fis1 Mitochondrial Fission Protein and Membrane Contact Site Proteins in Supporting Tombusvirus Replication

Plus-stranded RNA viruses have limited coding capacity and have to co-opt numerous pro-viral host factors to support their replication. Many of the co-opted host factors support the biogenesis of the viral replication compartments and the formation of viral replicase complexes on subverted subcellular membrane surfaces. Tomato bushy stunt virus (TBSV) exploits peroxisomal membranes, whereas the closely-related carnation Italian ringspot virus (CIRV) hijacks the outer membranes of mitochondria. How these organellar membranes can be recruited into pro-viral roles is not completely understood. Here, we show that the highly conserved Fis1 mitochondrial fission protein is co-opted by both TBSV and CIRV via direct interactions with the p33/p36 replication proteins. Deletion of FIS1 in yeast or knockdown of the homologous Fis1 in plants inhibits tombusvirus replication. Instead of the canonical function in mitochondrial fission and peroxisome division, the tethering function of Fis1 is exploited by tombusviruses to facilitate the subversion of membrane contact site (MCS) proteins and peroxisomal/mitochondrial membranes for the biogenesis of the replication compartment. We propose that the dynamic interactions of Fis1 with MCS proteins, such as the ER resident VAP tethering proteins, Sac1 PI4P phosphatase and the cytosolic OSBP-like oxysterol-binding proteins, promote the formation and facilitate the stabilization of virus-induced vMCSs, which enrich sterols within the replication compartment. We show that this novel function of Fis1 is exploited by tombusviruses to build nuclease-insensitive viral replication compartment

Role of MicroRNA-26b in Glioma Development and Its Mediated Regulation on EphA2

BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Deregulation of miRNAs is common in human tumorigenesis. Low level expression of miR-26b has been found in glioma cells. However, its underlying mechanism of action has not been determined. METHODOLOGY/PRINCIPAL FINDINGS: Real-time PCR was employed to measure the expression level of miR-26b in glioma patients and cells. The level of miR-26b was inversely correlated with the grade of glioma. Ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells. A binding site for miR-26b was identified in the 3'UTR of EphA2. Over-expression of miR-26b in glioma cells repressed the endogenous level of EphA2 protein. Vasculogenic mimicry (VM) experiments were performed to further confirm the effects of miR-26b on the regulation of EphA2, and the results showed that miR-26b inhibited the VM processes which regulated by EphA2. SIGNIFICANCE: This study demonstrated that miR-26b may act as a tumor suppressor in glioma and it directly regulates EphA2 expression. EphA2 is a direct target of miR-26b, and the down-regulation of EphA2 mediated by miR-26b is dependent on the binding of miR-26b to a specific response element of microRNA in the 3'UTR region of EphA2 mRNA

Functional Connectivity Within the Executive Control Network Mediates the Effects of Long-Term Tai Chi Exercise on Elders’ Emotion Regulation

Previous research has identified the effects of tai chi exercise on elders’ executive control or on their emotion regulation. However, few works have attempted to reveal the relationships between tai chi, executive control, and emotion regulation in the same study. The current resting-state study investigated whether the impact of tai chi on elders’ emotion regulation was mediated by the resting-state functional connectivity within the executive control network. A total of 26 elders with long-term tai chi experience and 26 demographically matched healthy elders were recruited. After the resting-state scan, both groups were required to complete a series of questionnaires, including the Five Facets Mindfulness Questionnaire (FFMQ), and a sequential decision task, which offered an index of the subjects’ emotion-regulation ability by calculating how their emotional response could be affected by the objective outcomes of their decisions. Compared to the control group, the tai chi group showed higher levels of non-judgment of inner experiences (a component of the FFMQ), stronger emotion-regulation ability, and a weaker resting-state functional connectivity between the dorsolateral prefrontal cortex (DLPFC) and the middle frontal gyrus (MFG). Moreover, the functional connectivity between the DLPFC and the MFG in the tai chi group fully mediated the impact of non-judgment of inner experience on their emotion-regulation ability. These findings highlighted that the modulation of non-judgment of inner experience on long-term tai chi practitioners’ emotion regulation was achieved through decreased functional connectivity within the executive control network

Ball-milling of titanium dioxide and zinc oxide for enhanced UV protection

Among various sunscreen materials, zinc oxide and titanium dioxide are excellent physical sunscreen components; however, these two materials tend to aggregate and form micrometer-sized particles that may impact their performance. This study utilizes fine grinding techniques to break up the aggregated oxide particles into small nanoparticles with a narrow size distribution averaging around 200 nm in diameter. The ground zinc oxide and titanium dioxide particles exhibit enhanced ability in absorbing and scattering ultraviolet radiation compared to their original state before grinding. Consequently, this research offers innovative concepts as well as approaches towards developing highly efficient yet low-toxic physical sunscreen components while significantly contributing to the preparation process optimization for mixed material performance