Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis

Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC). Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 +/- 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 +/- 4% and 4 +/- 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis

Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress

Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy

Measurement of the production cross section for Z + b jets in proton-proton collisions at s\sqrt{s} = 13 TeV

The measurement of the cross section for the production of a Z boson, decaying to dielectrons or dimuons, in association with at least one bottom quark jet is performed with proton-proton collision data at √s=13  TeV. The data sample corresponds to an integrated luminosity of 137  fb$^{-1}$, collected by the CMS experiment at the LHC during 2016–2018. The integrated cross sections for Z+≥1 b jet and Z+≥2 b jets are reported for the electron, muon, and combined channels. The fiducial cross sections in the combined channel are 6.52±0.04(stat)±0.40(syst)±0.14(theo)  pb for Z+≥1 b jet and 0.65±0.03(stat)±0.07(syst)±0.02(theo)  pb for Z+≥2 b jets. The differential cross section distributions are measured as functions of various kinematic observables that are useful for precision tests of perturbative quantum chromodynamics predictions. The ratios of integrated and differential cross sections for Z+≥2b  jets and Z+≥1 b jet processes are also determined. The value of the integrated cross section ratio measured in the combined channel is 0.100±0.005(stat)±0.007(syst)±0.003(theo). All measurements are compared with predictions from various event generators

Validation of the Activity Preference Assessment: a tool for quantifying children’s implicit preferences for sedentary and physical activities

Background High levels of sedentary behavior and low physical activity are associated with poor health, and the cognitive determinants of these behaviors in children and adolescents are not well understood. To address this gap, we developed a novel, non-verbal, computer-based assessment to quantify the degree to which youth prefer to be sedentary relative to physically active in their leisure time. Methods The Activity Preference Assessment (APA) uses a forced-choice paradigm to understand implicit decision-making processes when presented with common sedentary and physical activities. The APA bias score ranges from − 100 to + 100, with positive scores indicating a relative preference for sedentary activities, and negative scores representing a preference for physical activities. In 60 children ages 8–17 years, we assessed the validity of this behavioral task against a free-choice play observation, accelerometry-measured activity, anthropometrics and body composition, and cardiorespiratory fitness. We explored neighborhood, family, and individual-level factors that may influence implicit activity preferences. Test-retest reliability was assessed over one week. Results The majority of children (67%) preferred sedentary relative to physical activities. APA bias scores were positively associated with sedentary time during free-choice play. In girls, bias scores were negatively associated with average daily MVPA. APA bias scores were positively associated with body fat and negatively associated with cardiorespiratory fitness. These findings were independent of age, sex, and race/ethnicity. Neighborhood access to physical activity spaces, the number of people in the home, perceived physical self-competence (e.g., coordination, strength), and self-reported depressive symptoms were associated with activity preferences. The intra-class correlation for test-retest reliability was r = 0.59. Conclusions The APA shows promise as a novel tool for quantifying children’s relative preference for sedentary versus physical activities. Implicit bias scores from the APA are clinically meaningful, as shown by significant associations with adiposity and cardiorespiratory fitness. Future longitudinal studies should examine the directionality of the association between preferences and health markers, and the degree to which implicit activity preferences are modifiable. Importantly, the task only takes an average of 10 min to complete, highlighting a potential role as an efficient screening tool for the propensity to be sedentary versus physically active