Recombinant VP1, an Akt Inhibitor, Suppresses Progression of Hepatocellular Carcinoma by Inducing Apoptosis and Modulation of CCL2 Production

BACKGROUND: The application of viral elements in tumor therapy is one facet of cancer research. Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. Here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (HCC), one of the most common human cancers worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with rVP1 inhibited cell proliferation in two murine HCC cell lines, BNL and Hepa1-6, with IC₅₀ values in the range of 0.1-0.2 µM. rVP1 also induced apoptosis in these cells, which was mediated by Akt deactivation and dissociation of Ku70-Bax, and resulted in conformational changes and mitochondrial translocation of Bax, leading to the activation of caspases-9, -3 and -7. Treatment with 0.025 µM rVP1, which did not affect the viability of normal hepatocytes, suppressed cell migration and invasion via attenuating CCL2 production. The production of CCL2 was modulated by Akt-dependent NF-κB activation that was decreased after rVP1 treatment. The in vivo antitumor effects of rVP1 were assessed in both subcutaneous and orthotopic mouse models of HCC in immune-competent BALB/c mice. Intratumoral delivery of rVP1 inhibited subcutaneous tumor growth as a result of increased apoptosis. Intravenous administration of rVP1 in an orthotopic HCC model suppressed tumor growth, inhibited intra-hepatic metastasis, and prolonged survival. Furthermore, a decrease in the serum level of CCL2 was observed in rVP1-treated mice. CONCLUSIONS/SIGNIFICANCE: The data presented herein suggest that, via inhibiting Akt phosphorylation, rVP1 suppresses the growth, migration, and invasion of murine HCC cells by inducing apoptosis and attenuating CCL2 production both in vitro and in vivo. Recombinant protein VP1 thus has the potential to be developed as a new therapeutic agent for HCC

Exercise Behavior and Mood during the COVID-19 Pandemic in Taiwan: Lessons for the Future

The Coronavirus disease 2019 (COVID-19) pandemic and its associated governmental recommendations and restrictions have influenced many aspects of human life, including exercise and mental health. This study aims to explore the influence of COVID-19 on exercise behavior and its impact on mood states, as well as predict changes in exercise behavior during a similar future pandemic in Taiwan. A cross-sectional online survey was conducted between 7 April and 13 May 2020 (n = 1114). Data on exercise behavior pre and during the pandemic and mood states were collected. A cumulative link model was used to predict changes in exercise frequency during a similar future pandemic by exercise frequency during the pandemic. A linear model was used to predict the influence of exercise frequency before and during the pandemic on mood states during the pandemic. A total of 71.2%, 67.3%, and 58.3% of respondents maintained their exercise intensity, frequency, and duration, respectively, during the pandemic. Frequent exercisers are more likely to maintain their exercise frequency during a similar pandemic (p \u3c 0.001). Higher exercise frequencies during the pandemic were associated with better mood states (p \u3c 0.05). Moreover, the effects of prepandemic exercise frequency on mood states are moderated by changes in exercise frequency during the pandemic (p \u3c 0.05). Additionally, maintenance of exercise frequency during a pandemic specifically for frequent exercisers are recommended to preserve mood states. These results may provide evidence for health policies on exercise promotion and mental health before and during a future pandemic

Expert-Novice Differences in SMR Activity during Dart Throwing

Cheng M-Y, Hung C-L, Huang C-J, et al. Expert-Novice Differences in SMR Activity during Dart Throwing. Biological Psychology. 2015;110:212-218.Previous evidence suggests that augmented sensorimotor rhythm (SMR) activity is related to the superior regulation of processing cognitive-motor information in motor performance. However, no published studies have examined the relationship between SMR and performance in precision sports; thus, this study examined the relationship between SMR activity and the level of skilled performance in tasks requiring high levels of attention (e.g., dart throwing). We hypothesized that skilled performance would be associated with higher SMR activity. Fourteen dart-throwing experts and eleven novices were recruited. Participants were requested to perform 60 dart throws while EEG was recorded. The 2 (Group: Expert, Novice) x 2 (Time window: –2000 ms to –1000 ms, –1000 ms to 0 ms) ANOVA showed that the dart-throwing experts maintained a relatively higher SMR power than the novices before dart release. These results suggest that SMR might reflect the adaptive regulation of cognitive-motor processing during the preparatory period

Higher power of sensorimotor rhythm is associated with better performance in skilled air-pistol shooters

Cheng M-Y, Wang K-P, Hung C-L, et al. Higher power of sensorimotor rhythm is associated with better performance in skilled air-pistol shooters. Psychology of Sport and Exercise. 2017;32:47-53.Objectives Psychomotor efficiency has been linked with processing efficiency during sport performance. Reduced cortical activity in the sensorimotor area has been related to less variability in the movement preparation that is conducive to skilled motor performance. This study proposes sensorimotor rhythm (SMR), 12–15 Hz of the electroencephalography (EEG) in the sensorimotor area, may be used to investigate psychomotor efficiency in sports performance. Method Twenty-four skilled air pistol shooters were recruited to fire 40 shots while EEG and shooting accuracy were recorded. Results The data show that improved performance of skilled shooters is associated with higher SMR power during the last second and lower coherence on high alpha power at Fz-T3 before action initiation. A negative relationship is also exhibited between the SMR power and the shooting performance during the aiming. Conclusions This finding suggests that reduced interference from sensorimotor processing, as reflected by elevated SMR power, may be related to improved processing efficiency during the aiming period. We conclude that SMR may be used to understand psychomotor efficiency underlying air-pistol shooting performance

Learning Curve of ROSA ONE Spine System for Transpedicular Screw Placement

Objective The study investigated our institutional learning curve for the ROSA ONE spine system (ROSA) based on ROSA usage time. Methods ROSA was designed to provide high accuracy for spinal pedicle screw placement through a built-in tracking technique. This study was conducted from November 2018 to January 2021. The time taken to complete each step of the robotic workflow was recorded. Patient demographics, comorbidities, surgical indications, and number of screw placements were examined in subgroup analysis. The Curve Fitting-General package (a part of NCSS 2021 software) was used to fit a mathematical model to the learning curve. Patient demographics, imaging data, and surgical time were reviewed retrospectively. Results A total of 167 patients who had undergone surgery were included. The mean total ROSA usage time was 107.1 ± 27.3 minutes. The estimated learning rate was 90.4%, and the largest slope change occurred close to the time of the 20th surgery. The observed overall learning trend in the 4-screw group could be attributed to screw planning. The presence of scoliosis (p = 0.73) or spondylolisthesis (p = 0.70) did not significantly influence the mean total time (TT) for all patients; however, the mean TT differed significantly (p < 0.01) among subgroups stratified by body mass index, screw number placement, and thoracic spine involvement. Conclusion To the best of our knowledge, this is the first study to examine the learning curve for the various crucial steps of ROSA-guided pedicle screw placement. The indicative learning curve involved 20 patients who had undergone surgery

Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma

Kras activation and p16 inactivation are required to develop pancreatic ductal adenocarcinoma (PDAC). However, the biochemical mechanisms underlying these double alterations remain unclear. Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(P)H, is upregulated when p16 is inactivated by looking at gene expression profiling studies. Activation of NOX4 requires catalytic subunit p22phox, which is upregulated following Kras activation. Both alterations are also detectable in PDAC cell lines and patient specimens. Furthermore, we show that elevated NOX4 activity accelerates oxidation of NADH and supports increased glycolysis by generating NAD+, a substrate for GAPDH-mediated glycolytic reaction, promoting PDAC cell growth. Mechanistically, NOX4 was induced through p16-Rb-regulated E2F and p22phox was induced by KrasG12V-activated NF-κB. In conclusion, we provide a biochemical explanation for the cooperation between p16 inactivation and Kras activation in PDAC development and suggest that NOX4 is a potential therapeutic target for PDAC

Impacts of MicroRNA Gene Polymorphisms on the Susceptibility of Environmental Factors Leading to Carcinogenesis in Oral Cancer

BACKGROUND: MicroRNAs (miRNAs) have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC) remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC. METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48) of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94) and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79) in younger patients (age<60). CONCLUSIONS: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese