Activity

Radiotherapy is an important modality for the local control of human cancers, but the radioresistance induced by aberrant apoptotic signaling is a hallmark of cancers. Restoring the aberrant apoptotic pathways is an emerging strategy for cancer radiotherapy. In this study, we determined that targeting cell division cycle 20 (CDC20) radiosensitized colorectal cancer (CRC) cells through mitochondrial-dependent apoptotic signaling. CDC20 was overexpressed in CRC cells and upregulated after radiation. Inhibiting CDC20 activities genetically or pharmacologically suppressed the proliferation and increased radiation-induced DNA damage and intrinsic apoptosis in CRC cells. Mechanistically, knockdown of CDC20 suppressed the expression of antiapoptotic protein Mcl-1 but not other Bcl-2 family proteins. The expressions of CDC20 and Mcl-1 respond to radiation simultaneously through direct interaction, as evidenced by immunoprecipitation and glutathione S-transferase (GST) pull-down assays. Subsequently, decreased Mcl-1 expression inhibited the expression level of phosphorylated checkpoint kinase 1 (p-Chk1), thereby resulting in impaired DNA damage repair through downregulating the homologous recombination repair protein Rad51 and finally causing apoptotic signaling. In addition, both CDC20 and Chk1 inhibitors together, through in vivo studies, confirmed the radiosensitizing effect of CDC20 via inhibiting Mcl-1 and p-Chk1 expression. In summary, our results indicate that targeting CDC20 is a promising strategy to improve cancer radiotherapy.Guided bone regeneration was studied to establish protocols and develop new biomaterials that revealed satisfactory results. The present study aimed to comparatively evaluate the efficiency of the bacterial cellulose membrane (Nanoskin®) and collagen membrane Bio-Gide® in the bone repair of 8-mm critical size defects in rat calvaria. Seventy-two adult male rats were divided into three experimental groups (n = 24) the CG-membrane-free control group (only blood clot, negative control), BG-porcine collagen membrane group (Bio-Guide®, positive control), and BC-bacterial cellulose membrane group (experimental group). The comparison periods were 7, 15, 30, and 60 days postoperatively. Histological, histometric, and immunohistochemical analyses were performed. The quantitative data were subjected to 2-way ANOVA and Tukey’s post-test, and p less then 0.05 was considered significant. At 30 and 60 days postoperatively, the BG group showed more healing of the surgical wound than the other groups, with a high amount of newly formed bone (p less then 0.001), while the BC group showed mature connective tissue filling the defect. The inflammatory cell count at postoperative days 7 and 15 was higher in the BC group than in the BG group (Tukey’s test, p = 0.006). At postoperative days 30 and 60, the area of new bone formed was greater in the BG group than in the other groups (p less then 0.001). Immunohistochemical analysis showed moderate and intense immunolabeling of osteocalcin and osteopontin at postoperative day 60 in the BG and BC groups. Thus, despite the promising application of the BC membrane in soft-tissue repair, it did not induce bone repair in rat calvaria.Even though casein has an intrinsic potential ability to act as a flame retardant (FR) additive, the research regarding the FR performance of casein filled polymeric composites has not been thoroughly conducted. In the present work, two commercial casein products, such as lactic casein 720 (LAC) and sodium casein 180 (SC), were chosen to investigate their effects on the performances of the polypropylene (PP) composites. The melt compounding and compression moulding processes were employed to fabricate these casein-based composites. Ammonium polyphosphate (APP) was also selected to explore its combined effects in conjunction with casein on the composite’s flammability. The cone calorimeter results showed that the addition of casein significantly reduced (66%) the peak heat release rate (PHRR) of the composite compared to that of neat PP. In particular, the combination of LAC and APP led to the formation of more compact and rigid char compared to that for SC based sample; hence, a further reduction (80%) in PHRR and self-extinguishment under a vertical burn test were accomplished. Moreover, the tensile modulus of the composite improved (23%) by the combined effects of LAC and APP. The overall research outcome has established the potential of casein as a natural protein FR reducing a polymer’s flammability.A combination of calcination and hydrothermal processing was used to prepare a g-C3N4/UiO-66-NH2/CdS photocatalyst, and the degradation of tetracycline (TC) over this material was assessed. The photocatalytic performance of this nanocomposite was approximately 4.4 and 2.3 times those of CdS and g-C3N4, respectively, and was found to be affected by the CdS loading amount, the pH of the reaction solution and the initial TC concentration. This catalyst also exhibited stable performance over four consecutive reaction cycles. The highly enhanced photoactivity of the g-C3N4/UiO-66-NH2/CdS is attributed to the introduction of CdS, which widens the range over which the material absorbs visible light and inhibits the recombination of electron-hole pairs. The results of this study suggest further applications for this material in the treatment of contaminated wastewater powered by solar energy.Breast cancer (BC) is a heterogeneous and complex disease as witnessed by the existence of different subtypes and clinical characteristics that poses significant challenges in disease management. The complexity of this tumor may rely on the highly interconnected nature of the various biological processes as stated by the new paradigm of Network Medicine. We explored The Cancer Genome Atlas (TCGA)-BRCA data set, by applying the network-based algorithm named SWItch Miner, and mapping the findings on the human interactome to capture the molecular interconnections associated with the disease modules. To characterize BC phenotypes, we constructed protein-protein interaction modules based on “hub genes”, called switch genes, both common and specific to the four tumor subtypes. Transcriptomic profiles of patients were stratified according to both clinical (immunohistochemistry) and genetic (PAM50) classifications. 266 and 372 switch genes were identified from immunohistochemistry and PAM50 classifications, respectively. Moreover, the identified switch genes were functionally characterized to select an interconnected pathway of disease genes. By intersecting the common switch genes of the two classifications, we selected a unique signature of 28 disease genes that were BC subtype-independent and classification subtype-independent. Data were validated both in vitro (10 BC cell lines) and ex vivo (66 BC tissues) experiments. Results showed that four of these hub proteins (AURKA, CDC45, ESPL1, and RAD54L) were over-expressed in all tumor subtypes. Moreover, the inhibition of one of the identified switch genes (AURKA) similarly affected all BC subtypes. In conclusion, using a network-based approach, we identified a common BC disease module which might reflect its pathological signature, suggesting a new vision to face with the disease heterogeneity.Bone and soft-tissue sarcomas are relatively rare tumors both in children and adults […].The state diagram, which is defined as a stability map of different states and phases of a food as a function of the solid content and temperature, is regarded as fundamental approach in the design and optimization of processes or storage procedures of food in the low-, intermediate-, and high-moisture domains. Therefore, in this study, the effects of maltodextrin addition on the freezing points (Tm’, Tm) and glass transition temperatures (Tg’, Tg) required for the construction of state diagrams of fruit juice model systems by using differential scanning calorimetry methods was investigated. A D-optimal experimental design was used to prepare a total of 25 anhydrous model food systems at various dry mass fractions of fructose, glucose, sucrose, pectin, citric acid, and maltodextrin, in which this last component varied between 0 and 0.8. It was found that maltodextrin mass fractions higher than 0.4 are required to induce significant increases of Tg’, Tm’, Tg, and Tm curves. From this perspective, maltodextrin is a good alternative as a cryoprotectant and as a carrier agent in the food industry. Furthermore, solute-composition-based mathematical models were developed to evaluate the influence of the chemical composition on the thermal transitions and to predict the state diagrams of fruit juices at different maltodextrin mass fractions.Cowpea is a well-known nutrition rich African leafy vegetable that has potential to sustain food and nutrition insecurity in sub-Saharan Africa. Consumption of cowpea legumes is associated with reduced risk of type 2 diabetes mellitus. Therefore, the present study was designed to evaluate the (i) variation in phenolic metabolites in seven cowpea cultivars (VOP1, VOP2, VOP3, VOP4, VOP5, VOP7, and VOP8 using UHPLC coupled with high resolution Q-TOF-MS technique, (ii) in vitro antioxidant activity using ferric reducing/antioxidant capacity (FRAP) assay (iii) in vitro anti-diabetic effects and (iv) composition of carotenoids and amino acids of theses cowpea cultivars. The results of this study demonstrated that gentisic acid 5-O-glucoside, quercetin 3-(2G-xylosylrutinoside) and Quercetin 3-glucosyl-(1->2)-galactoside were highest in VOP1 VOP4 and VOP5, respectively. High inhibition (>50%) of α-glucosidase and α-amylase activities was shown by the leaf extracts (50 and 25 mg/mL) of VOP1 and VOP4. Cowpea cultivars VOP1 and VOP4 demonstrated the highest gene expression levels of regulation of glucose transporter GLUT4 in C2C12 skeletal muscle cells, similar to insulin. A positive correlation exited between the phenolic components and the inhibitory effect of antidiabetic enzymes and FRAP activity. Cytotoxic effect was not detected in vitro in any cowpea cultivar. Selleck 2-Aminoethanethiol Lutein (124.6 mg/100 g) and all-trans-beta-carotene (92.6 mg/100 g) levels were highest in VOP2 and VOP1, respectively. Cowpea cultivars VOP3 and VOP4 showed potential to fulfil the daily requirements of essential amino acids. Thus, based on this information, cowpea (leaves) genotypes/cultivars can be selected and propagated for the further development of supplementary foods or functional food ingredients.The inherent degradation property of most dental resins in the mouth leads to the long-term release of degradation by-products at the adhesive/tooth interface. The by-products increase the virulence of cariogenic bacteria, provoking a degradative positive-feedback loop that leads to physicochemical and mechanical failure. Photoinduced free-radical polymerization and sol‒gel reactions have been coupled to produce a novel autonomous-strengthening adhesive with enhanced hydrolytic stability. This paper investigates the effect of network structure on time-dependent mechanical properties in adhesives with and without autonomous strengthening. Stress relaxation was conducted under 0.2% strain for 8 h followed by 40 h recovery in water. The stress‒time relationship is analyzed by nonlinear least-squares data-fitting. The fitted Prony series predicts the sample’s history under monotonic loading. Results showed that the control failed after the first loading‒unloading‒recovery cycle with permanent deformation. While for the experimental sample, the displacement was almost completely recovered and the Young’s modulus increased significantly after the first test cycle.