Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs

Our goal was to examine the anticancer effects of piperine against the resistant human ovarian cancer cells and to explore the molecular mechanisms responsible for its anticancer effects. Our study used drug-sensitive ovarian cancer cell line W1 and its sublines resistant to paclitaxel (PAC) and topotecan (TOP). We analyzed the cytotoxic effect of piperine and cytostatic drugs using an MTT assay. The impact of piperine on protein expression was determined by immunofluorescence and Western blot. We also examined its effect on cell proliferation and migration. We noticed a different level of piperine resistance between cell lines. Piperine increases the cytotoxic effect of PAC and TOP in drug-resistant cells. We observed an increase in PTPRK expression correlated with decreased pTYR level after piperine treatment and downregulation of P-gp and BCRP expression. We also noted a decrease in COL3A1 and TGFBI expression in investigated cell lines and increased COL3A1 expression in media from W1PR2 cells. The expression of Ki67 protein and cell proliferation rate decreased after piperine treatment. Piperine markedly inhibited W1TR cell migration. Piperine can be considered a potential anticancer agent that can increase chemotherapy effectiveness in cancer patients.     

Comprehensive Overview of Gene Rearrangements in Childhood T-Cell Acute Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) is a relevant form of childhood neoplasm, as it accounts for over 80% of all leukaemia cases. T-cell ALL constitutes a genetically heterogeneous cancer derived from T-lymphoid progenitors. The diagnosis of T-ALL is based on morphologic, immunophenotypic, cytogenetic, and molecular features, thus the results are used for patient stratification. Due to the expression of surface and intracellular antigens, several subtypes of T-ALL can be distinguished. Although the aetiology of T-ALL remains unclear, a wide spectrum of rearrangements and mutations affecting crucial signalling pathways has been described so far. Due to intensive chemotherapy regimens and supportive care, overall cure rates of more than 80% in paediatric T-ALL patients have been accomplished. However, improved knowledge of the mechanisms of relapse, drug resistance, and determination of risk factors are crucial for patients in the high-risk group. Even though some residual disease studies have allowed the optimization of therapy, the identification of novel diagnostic and prognostic markers is required to individualize therapy. The following review summarizes our current knowledge about genetic abnormalities in paediatric patients with T-ALL. As molecular biology techniques provide insights into the biology of cancer, our study focuses on new potential therapeutic targets and predictive factors which may improve the outcome of young patients with T-ALL.     

Ultrastructural and developmental toxicity of potato and tomato leaf extracts to beet armyworm,Spodoptera exigua (lepidoptera: noctuidae)

Beet Armyworm, Spodoptera exigua is a herbivorous moth and a serious pest of many economically important plants, which are used as food sources. Because of rigorous standards of food quality, usage of synthetic insecticides in crop protection, against pests, is limited. Solanaceae plant extracts may be a relatively cheap source of efficient natural insecticides that can limit usage of synthetic substances. Their biological activity is not fully known. In particular, ultrastructural studies, using transmission electron microscopy, are not usual. In the present article we describe the effects of sublethal concentrations of tomato and potato leaf extracts against S. exigua. Acute lethal effects were not observed. Both extracts exerted similar effects within midgut and fat body cells. Midgut cells were not significantly altered while fat body cells showed prominent swelling of nuclear envelope and endoplasmic reticulum, vacuolization of mitochondria and fusion of fat droplets. These changes were much more intensive within groups exposed to potato than tomato extracts at highest concentration at least. Light microscopy was used to observe and document developmental alterations of S. exigua exposed to potato and tomato leaf extracts. Potato leaf extracts significantly decreased hatching success and caused morphological malformations of imagoes. Among them, malformations of wings were the most prominent. Interestingly, these effects were not observed within populations exposed to tomato extracts at highest concentration at least.     

The effect of temperature and radiation on flavonol aglycones and flavonol glycosides of kale (Brassica oleracea var. sabellica)

The winter crop kale has a complex profile of different glycosylated and acylated flavonol glycosides which may be affected by global warming. To the best of our knowledge, compound–climate relationships for flavonol aglycones and flavonol glycosides were established for the first time. The investigated 10 major flavonol glycosides responded structure-dependent in the investigated temperature range between 0 and 12 °C and the photosynthetic active radiation range between 4 and 20 mol m⁻² d⁻¹, e.g. the decrease in temperature led to an increase in sinapic acid monoacylated and diacylated quercetin glycosides, while the sinapic acid monoacylated kaempferol glycosides showed a maximum at 4.5 °C. Furthermore, the hydroxycinnamic acid residues and the different number of glucose moieties in the 7-O position affected the response of kaempferol triglucosides. Consequently, global warming would result in lower concentrations of antioxidant-relevant quercetin glycosides in winter crops, suggesting a production at e.g. higher altitudes due to lower temperature.     

Chrysin,Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1) on Activated RAW264.7 Macrophages

Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4'' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.     

Fatigue lifetime study of piezoceramic patch transducers

This study investigates the loading limits and fatigue behavior of laminar piezoceramic patch transducers, based on monolithic lead zirconate titanate (PZT) plates encapsulated in epoxy resin matrix. Testing includes tensile and compressive mechanical loading, at different temperatures, as well as electric actuation. The objective is the identification of typical failure mechanisms and suitable models for failure and lifetime analysis. In tensile loading, which is observed to have the strongest influence on the patch lifetime, the relevant failure mechanism in quasi-static and cyclic loading is found to be cracking of the PZT plate, causing degradation of the patch performance. Based on the micro-structural investigations and FE simulation, the fracture toughness of the PZT plate is analyzed and a micro-crack-propagation-based fatigue lifetime model is derived. The effect of the fragmentation of the piezoceramic plate on the patch performance is analyzed by the presented functional length concept, based on the shear lag model, yielding very good quantitative agreement.