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Nickel compounds are Group 1 carcinogens and possibly cancer-causing in the pancreas. We examined the toxicity of nickel in both 2-D and 3-D pancreatic cell cultures, to determine the LD50 for organic and inorganic nickel in normal and cancerous cells. Assays with cadmium chloride were performed to be a comparison to potential nickel-induced toxicity. Cells were exposed to twelve concentrations of NiCl2 or Ni-(Ac)2 for 48h (2-D), or six concentrations for 48 hours (3-D). There was a significant (P=0.0016) difference between HPNE and AsPC-1 LD50values after cadmium exposure, at 69.9 μM and 29.2 μM, respectively. Neither form of nickel exhibited toxicity in 2-D or 3-D cultures, but after 48h, changes in spheroid morphology were observed. The inability of Ni to reduce viable cell numbers suggests a toxic mechanism that differs from cadmium, also a Group 1 carcinogen. The cell microenvironment was not a factor in nickel toxicity with no changes in viable cells in either 2-D or 3-D cultures. These studies only examined cytotoxicity, and not genotoxicity, a potential mechanism of nickel carcinogenicity. Alterations in DNA function or the expression of apoptotic proteins/processes would take longer to manifest. Current work focuses on cellular changes following extended nickel exposure., Uloga nikla, toksičnog metala, u nastanku karcinoma pankreasa još uvek nije u potpunosti ispitana. Cilj rada je da ispita toksičnost nikla (Ni) u 2-D i 3-D kulturi ćelija pankreasa, kako bi se utvrdila LD50 vrednost za organski i neorganski nikl u normalnim i tumorskim ćelijama. Ispitivanja su izvršena i sa kadmijumom (Cd), metalom čija je uloga u nastanku karcinoma pankreasa potvrđena u prethodnim istraživanjima, a u svrhu poređenja sa potencijalnom toksičnošću izazvanom Ni. Ćelije su bile tretirane sa 12 različitih koncentracija NiCl2 ili Ni-(Ac)2 tokom 48h (2-D), odnosno sa šest različitih koncentracija tokom 48 sati (3-D). Nijedan oblik Ni nije ispoljio toksičnost u 2-D ili 3-D kulturama, ali nakon 48h primećene su promene u sferoidnoj morfologiji. Nemogućnost Ni da smanji broj vijabilnih ćelija sugeriše mehanizam karcinogeneze različit od mehanizma koji ispoljava Cd. Ipak, da bi se uočile izmene u funkciji DNK ili izražavanju apoptotičkih proteina/procesa potrebno je duže vremena, pa su dalja istraživanja upravo fokusirana na ćelijske promene nakon produžene izloženosti nikla.

Toxic metals are extensively found in the environment, households, and workplaces and contaminate food and drinking water. The crosstalk between environmental exposure to toxic metals and human diseases has been frequently described. The toxic mechanism of action was classically viewed as the ability to dysregulate the redox status, production of inflammatory mediators and alteration of mitochondrial function. Recently, growing evidence showed that heavy metals might exert their toxicity through microRNAs (miRNA)-short, single-stranded, noncoding molecules that function as positive/negative regulators of gene expression. Aberrant alteration of the endogenous miRNA has been directly implicated in various pathophysiological conditions and signaling pathways, consequently leading to different types of cancer and human diseases. Additionally, the gene-regulatory capacity of miRNAs is particularly valuable in the brain-a complex organ with neurons demonstrating a significant ability to adapt following environmental stimuli. Accordingly, dysregulated miRNAs identified in patients suffering from neurological diseases might serve as biomarkers for the earlier diagnosis and monitoring of disease progression. This review will greatly emphasize the effect of the toxic metals on human miRNA activities and how this contributes to progression of diseases such as cancer and neurodegenerative disorders (NDDs).

Copyright © 2019 ASME. In product design courses, prototyping offers a way for students to develop physical intuition about materials while practicing techniques used by professional designers. A web-based platform was developed to explore the use of multimedia to provide students with additional support for prototyping activities. The result is Designy (www.productdesigny.com), a platform containing a series of photo- and video-based resources meant to help students prototype effectively. Students in two product design classes – 2.00b Toy Product Design and 2.744 Product Design – were given access to Designy to aid in their project work. To better understand whether the platform was utilized by students and if access to the platform contributed to student learning and project work, researchers analyzed website activity data and interviewed students (n=19) to collect data regarding their experiences with the platform. A core group of 24 students (27%) in 2.00b and 29 students (35%) in 2.744 generated the most activity on the platform. Interview data indicates that students used the platform to answer prototyping-related questions when designing, to better understand the landscape of prototyping tools available to them, and to increase a feeling of confidence working in a prototyping shop. Overall, results suggest that while in-person interactions with staff members can better help students in situations where the support students need is poorly identified, Designy was shown to provide efficient support in situations when students could clearly identify the type of support they needed.