Novaluron impairs the silk gland and productive performance of silkworm Bombyx mori (Lepidoptera: Bombycidae) larvae.

This study investigates the effects of the insect growth regulator Novaluron on the silk gland (SG) and silk cocoon production in a nontarget insect, the silkworm Bombyx mori, which is a model research insect among Lepidoptera and of great economic importance for the commercial production of silk threads. Larvae were segregated into experimental groups: the control group (CG) and the treatment group (TG), which was exposed to a Novaluron concentration of 0.15 mL/L. Following exposure, we analyzed the cytotoxic effects on the epithelial cells of the anterior, middle and posterior regions of the SG of B. mori larvae in the 3rd, 4th, and 5th instars, as well as the quality of the cocoons from larvae in the 5th instar. Cytotoxic effects were observed in the TG, such as the dilation of cells, emission of cytoplasmic protrusions, extreme rarefaction of the cytoplasm and nuclei, dilation of the endoplasmic reticulum, intracellular and intercellular spaces, spacing between the epithelial cells and the basal lamina and detachment of some cells towards the lumen of the SG, and decreased protein in the lumen, with faults in its composition. In addition, we verified ultrastructural changes in the production of fibers and silk cocoons, including a reduction in the weight of the cocoons constructed by both males and females in the TG and the construction of defective cocoons. Novaluron exposure impairs the SG and may affect the physiological functions of this organ; additionally, it compromises the quality of silk cocoons, potentially causing serious damage to sericulture.

Live Cell Imaging Supports a Key Role for Histone Deacetylase as a Molecular Target during Glioblastoma Malignancy Downgrade through Tumor Competence Modulation.

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system, and the identification of the mechanisms underlying the biological basis of GBM aggressiveness is essential to develop new therapies. Due to the low prognosis of GBM treatment, different clinical studies are in course to test the use of histone deacetylase inhibitors (iHDACs) in anticancer cocktails. Here, we seek to investigate the impact of HDAC activity on GBM cell behavior and plasticity by live cell imaging. We pharmacologically knock down HDAC activity using two different inhibitors (TSA and SAHA) in two different tumor cell types: a commercial GBM cell line (U87-MG) and primary tumor (GBM011). Upon 72 hours of in vitro iHDAC treatment, GBM cells presented a very unusual elongated cell shape due to tunneling tube formation and independent on TGF-ß signaling epithelial to mesenchymal transition. Live cell imaging revealed that voltage-sensitive Ca++ signaling was disrupted upon HDAC activity blockade. This behavior was coupled to vimentin and connexin 43 gene expression downregulation, suggesting that HDAC activity blockade downgrades GBM aggressiveness mostly due to tumor cell competence and plasticity modulation in vitro. To test this hypothesis and access whether iHDACs would modulate tumor cell behavior and plasticity to properly respond to environmental cues in vivo, we xenografted GBM oncospheres in the chick developing the neural tube. Remarkably, upon 5 days in the developing neural tube, iHDAC-treated GBM cells ectopically expressed HNK-1, a tumor-suppressor marker tightly correlated to increased survivor of patients. These results describe, for the first time in the literature, the relevance of iHDACs for in vivo tumor cell morphology and competence to properly respond to environmental cues. Ultimately, our results highlight the relevance of chromatin remodeling for tumor cell plasticity and shed light on clinical perspectives aiming the epigenome as a relevant therapeutic target for GBM therapy.