In Vitro Toxicity Testing of Nanomaterials

Cell culture-based techniques are employed world-wide to assess risks to optimize design and handling of materials. Nano-scale particles particularly pose a challenge to the predictability of toxicity. This is due to the interplay of several factors including size, shape, surface properties, micro-environment, charge, electronic species etc., that affect the degree of cellular stress. Numerous assays could be employed to understand the nature of toxicity. Some of these include cytotoxicity, metabolic kinetics, modulation in cellular morphology. Various models such as primary cell culture and cell lines can also be employed that best suits a study. Signaling cascades could also be monitored in better understanding cellular responses holistically. Fluorescence microscopy can further be attempted in studying spatial and temporal variations of bio-markers. Ultimately any plethora of dose-response data, need to be streamlined for developing toxicity evaluation protocols that are accurate, cost effective and time saving

Nucleoporin98-96 Function Is Required for Transit Amplification Divisions in the Germ Line of Drosophila melanogaster

Production of specialized cells from precursors depends on a tightly regulated sequence of proliferation and differentiation steps. In the gonad of Drosophila melanogaster, the daughters of germ line stem cells (GSC) go through precisely four rounds of transit amplification divisions to produce clusters of 16 interconnected germ line cells before entering a stereotypic differentiation cascade. Here we show that animals harbouring a transposon insertion in the center of the complex nucleoporin98-96 (nup98-96) locus had severe defects in the early steps of this developmental program, ultimately leading to germ cell loss and sterility. A phenotypic analysis indicated that flies carrying the transposon insertion, designated nup98-962288, had dramatically reduced numbers of germ line cells. In contrast to controls, mutant testes contained many solitary germ line cells that had committed to differentiation as well as abnormally small clusters of two, four or eight differentiating germ line cells. This indicates that mutant GSCs rather differentiated than self-renewed, and that these GSCs and their daughters initiated the differentiation cascade after zero, or less than four rounds of amplification divisions. This phenotype remained unaffected by hyper-activation of signalling pathways that normally result in excessive proliferation of GSCs and their daughters. Expression of wildtype nup98-96 specifically in the germ line cells of mutant animals fully restored development of the GSC lineage, demonstrating that the effect of the mutation is cell-autonomous. Nucleoporins are the structural components of the nucleopore and have also been implicated in transcriptional regulation of specific target genes. The nuclear envelopes of germ cells and general nucleocytoplasmic transport in nup98-96 mutant animals appeared normal, leading us to propose that Drosophila nup98-96 mediates the transport or transcription of targets required for the developmental timing between amplification and differentiation

Repurposing of Anti-Malarial Drug Quinacrine for Cancer Treatment: A Review

Quinacrine (QC), a synthetic drug belonging to the 9-aminoacridine family, has been used extensively to treat malaria and multiple ailments over the past several decades. Following its discovery in the 1920s and extensive use for the treatment of malaria for nearly two decades, numerous studies have explored its antineoplastic potential in both preclinical and clinical settings. Multiple studies spanning over seven decades have examined a wide range of QC anticancer activities across various types of cancers, along with the underlying mechanisms. Many of these mechanisms, including activation of the p53 signaling cascade and simultaneous NF-κB signaling inhibition, have been reported in various studies, bringing QC to a unique polypharmacological category drug possessing the potential to treat a wide variety of diseases, including cancer. This article summarizes most of the research conducted over several decades to uncover new molecular mechanisms activated or inactivated and directly correlate with antineoplastic activity QC

Hemotoxic and wound healing potential of coelomic fluid of sea-star Astropecten indicus

Abstract Background The coelomic fluid of echinoderms bathes all the internal organs and is a natural reservoir of various bio-active compounds. However, coelomic fluid from Indian sea-star Astropecten indicus is not well characterized for its biochemical and pharmacological profiles. Sea-star (or starfish) Astropecten indicus was collected from the coast of Goa, India during low tides. Sea-star coelomic fluid (SCF) extracted from the sea-stars was concentrated, filtered, and assayed for various hemotoxic activities such as fibrinogenolysis, fibrinolysis, hemolysis, and effects on platelet aggregation. Results Studies on effects of SCF on A-549 human lung cancer cell line showed its non-cytotoxic and wound healing abilities in vitro. SCF was found to possess fibrinogen and fibrin digesting ability at a dose of 4 μg/ml within 30 min of incubation with the substrate. Additionally, SCF could hemolyze goat RBC by 50% and human RBC by only 5%. SDS-PAGE analysis showed that SCF contains various proteins and peptides. Two protein components of SCF yielded strong fibrinolytic, fibrinogenolytic, caseinolytic, and gelatinase activities as revealed by zymography. SCF enhanced the aggregation of ADP and collagen-activated platelets in a dose-dependent manner and had a specific proteolytic activity of 2.5 μg/ml in 30 min at 37 °C as assayed using azocasein as substrate. Conclusion This study focuses on the anticoagulant, pro-platelet aggregation and cell proliferative potential of SCF in vitro and is the first report on hemotoxic and wound healing potential of coelomic fluid of Astropecten indicus

Microstructure, mechanical, and corrosion properties of electron beam-welded commercially pure titanium after laser shock peening

Surface properties play a critical role in the structural integrity of any component and this becomes even more critical for weld joints. Laser shock peening (LSP) is one of the non-contact methods which is getting popular in industries to enhance surface properties for improving service life, mainly fatigue of engineering components. In the present study, electron beam welding (EBW) of commercially pure (cp) titanium was carried out at constant line energy with varying scan speeds ranging from 1000 to 1600 mm/min and welding currents from 25 to 40 mA. The influence of the EBW parameters on microstructure, surface micro-hardness, tensile, and fatigue strength was investigated. The effect of LSP on mechanical and corrosion properties of EBW cp titanium was studied. LSP induced a significant amount of compressive residual stresses at the surface through plastic deformation and led to significant improvement in micro-hardness (7–10%) at the sub-surface region of the fusion zone due to finer grain structure. Further, appreciable enhancement in tensile strength (~ 15%) and fatigue life (~ 43%) due to strain hardening and changes in microstructure like twinning within grains was realized. © 2021, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature