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This study investigated the microstructures, mechanical performances, corrosion resistances, and in vitro studies of porous Ti-xNb-10Zr (x: 10 and 20; at. %) alloys. The alloys were fabricated by powder metallurgy with two categories of porosities, i.e., 21–25% and 50–56%, respectively. The space holder technique was employed to generate the high porosities. Microstructural analysis was performed by using various methods including scanning electron microscopy, energy dispersive spectroscopy, electron backscatter diffraction, and x-ray diffraction. Corrosion resistance was assessed via electrochemical polarisation tests, while mechanical behavior was determined by uniaxial compressive tests. In vitro studies, such as cell viability and proliferation, adhesion potential, and genotoxicity, were examined by performing an MTT assay, fibronectin adsorption, and plasmid-DNA interaction assay. Experimental results showed that the alloys had a dual-phase microstructure composed of finely dispersed acicular hcp α-Ti needles in the bcc β-Ti matrix. The ultimate compressive strength ranged from 1019 MPa to 767 MPa for alloys with 21–25% porosities and from 173 MPa to 78 MPa for alloys with 50–56% porosities. Noted that adding a space holder agent played a more critical role in the mechanical behaviors of the alloys compared to adding niobium. The pores were largely open and exhibited irregular shapes, with uniform size distribution, allowing for cell ingrowth. Histological analysis showed that the alloys studied met the biocompatibility criteria required for orthopaedic biomaterial use.

INTRODUCTION: Numerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS-CoV-2. OBJECTIVE: The main objective of our study was to determine artemisinin content by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS), to investigate the in vitro biological activity of artemisinin from the A. annua plants grown in Turkey with various extracted methods, to elaborate in silico activity against SARS-CoV-2 using molecular modelling. METHODOLOGY: Twenty-one different extractions were applied. Direct and sequential extractions studies were compared with ultrasonic assisted maceration, Soxhlet, and ultra-rapid determined artemisinin active molecules by LC-ESI-MS/MS methods. The inhibition of spike protein and main protease (3CL) enzyme activity of SARS-CoV-2 virus was assessed by time resolved fluorescence energy transfer (TR-FRET) assay. RESULTS: Artemisinin content in the range 0.062-0.066%. Artemisinin showed significant inhibition of 3CL protease activity but not Spike/ACE-2 binding. The 50% effective concentration (EC50 ) of artemisinin against SARS-CoV-2 Spike pseudovirus was found greater than 50 µM (EC45 ) in HEK293T cell line whereas the cell viability was 94% of the control (P < 0.01). The immunosuppressive effects of artemisinin on TNF-α production on both pseudovirus and lipopolysaccharide (LPS)-induced THP-1 cells were found significant in a dose dependent manner. CONCLUSION: Further studies of these extracts for COVID-19 treatment will shed light to seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.

The COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to have high incidence and mortality rate globally. To meet the increasingly growing demand for new therapeutic drugs and vaccines, researchers are developing different diagnostic techniques focused on screening new drugs in clinical use, developing an antibody targeting a SARS-CoV-2 receptor, or interrupting infection/replication mechanisms of SARS-CoV-2. Although many prestigious research publications are addressing this subject, there is no open access platform where all experimental techniques for COVID-19 research can be seen as a whole. Many researchers have accelerated the development of in silico methods, high-throughput screening techniques, and in vitro assays. This development has played an important role in the emergence of improved, innovative strategies, including different antiviral drug development, new drug discovery protocols, combinations of approved drugs, and setting up new drug classes during the COVID-19 outbreak. Hence, the present review discusses the current literature on these modalities, including virtual in silico methods for instant ligand- and target-driven based techniques, nucleic acid amplification tests, and in vitro models based on sensitive cell cultures, tissue equivalents, organoids, and SARS-CoV-2 neutralization systems (lentiviral pseudotype, viral isolates, etc.). This pack of complementary tests informs researchers about the accurate, most relevant emerging techniques available and in vitro assays allow them to understand their strengths and limitations. This review could be a pioneer reference guide for the development of logical algorithmic approaches for new drugs and vaccine strategies against COVID-19.

The carbon-based nanomaterials (CNMs) such as graphene oxide (GO) and carbon nanofibers (CNFs) are generally considered safe materials. However, recent studies indicate that they can pose risk for human health and living systems depending on their exposure route and dose. The diversity in their lateral and longitudinal sizes and shape increase their potential risk. Although several studies demonstrate that surface chemistry can alter the toxic behavior of nanomaterials, it is not clear for every type of NMs. In order to implement the Safe-by Design approach, in this study, the influence of surface chemistry of carbon-based nanomaterials on their cytotoxicity and genotoxicity is investigated. Two CNMs, GO and CNFs, are modified with glycine, a simplest amino acid, and glucose, a monosaccharide, and evaluated for their cytotoxicity and genotoxicity using cell lines, HSF (human skin fibroblast), RAW264.7 (macrophage) and BEAS-2B (human bronchial lung epithelial). It was found that surface chemistry was a significant factor determining the cellular response.

Cardiac tissue engineering focusing on biomaterial scaffolds incorporating cells from different sources has been explored to regenerate or repair damaged area as a lifesaving approach.The aim of this study was to evaluate the cardiomyocyte differentiation potential of human adipose mesenchymal stem cells (hAD-MSCs) as an alternative cell source on silk fibroin (SF) scaffolds for cardiac tissue engineering. The change in surface morphology of SF scaffolds depending on SF concentration (1–6%, w/v) and increase in their porosity upon application of unidirectional freezing were visualized by scanning electron microscopy (SEM). Swelling ratio was found to increase 2.4 fold when SF amount was decreased from 4% to 2%. To avoid excessive swelling, 4% SF scaffold with swelling ratio of 10% (w/w) was chosen for further studies.Biodegradation rate of SF scaffolds depended on enzymatic activity was found to be 75% weight loss of SF scaffolds at the day 14. The phenotype of hAD-MSCs and their multi-linage potential into chondrocytes, osteocytes, and adipocytes were shown by flow cytometry and immunohistochemical staining, respectively.The viability of hAD-MSCs on 3D SF scaffolds was determined as 90%, 118%, and 138% after 1, 7, and 14 days, respectively. The use of 3D SF scaffolds was associated with increased production of cardiomyogenic biomarkers: α-actinin, troponin I, connexin 43, and myosin heavy chain. The fabricated 3D SF scaffolds were proved to sustain hAD-MSCs proliferation and cardiomyogenic differentiation therefore, hAD-MSCs on 3D SF scaffolds may useful tool to regenerate or repair damaged area using cardiac tissue engineering techniques.

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of SARS-CoV-2. In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist Montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of Montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of the Montelukast both on the main protease enzyme inhibition and virus entry into the host cell (Spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with Montelukast for 20 hours on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and if its effect is proven in clinical phase studies, it should be used against COVID-19., Graphical abstract, In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist Montelukast that simultaneously targets two important drug targets of SARS-CoV-2. Montelukast shows its effect both on the main protease and Spike/ACE2. The virus neutralization assay results showed that SARS-CoV-2 activity was delayed with Montelukast for 20 hours on the infected cells.

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of SARS-CoV-2. In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist Montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of Montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the Fluorescent Resonance Energy Transfer (FRET)-based main protease enzyme inhibition assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T / hACE2, and virus neutralization assay using xCELLigence MP real time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of the Montelukast both on virus entry into the host cell (Spike/ACE2) and on the main protease enzyme inhibition. The virus neutralization assay results showed that while no cytotoxicity of the Montelukast was observed at 12 μM concentration, the cell index time 50 (CIT50) value was delayed for 12 hours. Moreover, it was also shown that Favipiravir, a well-known antiviral used in COVID-19 therapy, should be used by 16-fold higher concentrations than Montelukast in order to have the same effect of Montelukast. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and if its effect is proven in clinical phase studies, it should be used against COVID-19.

Assessment of risk in the field of nanotechnology requires an integrated multidisciplinary approach due to the complex and cross-disciplinary framework for materials and activities at the nanoscale. The present paper summarizes the workshop "Governance of emerging nano-risk in the semiconductor industry" held on April 26, 2018 in Brussels, Belgium. The event targeted representatives of stakeholder communities involved in the risk assessment and governance of the engineered nanomaterials. Nanoelectronics was selected as an impactful use case for risk assessment approaches and comparison to bottom-up nanofabrication. The workshop outlined key data gaps impeding successful assessment of risks associated with nanoparticle use in the industry, using the semiconductor industry as an example. The workshop outlined mitigation strategies informing future regulatory decisions and identified some directions for future efforts. ispartof: FRONTIERS IN PUBLIC HEALTH vol:8 ispartof: location:Switzerland status: published

This work presents a titanium (Ti) - magnesium (Mg) composite as a novel material that is designed for application in biomedical devices that are subjected to intense and cyclic loading (such as dental implants). This study concentrates on how the mechanical properties, fatigue endurance, in-vitro corrosion response and cytotoxicity of TiMg composites depend on the use of high-purity regular-morphology plasma atomized (PA) Ti Grade 1 powders. It also compares the desired results with those obtained for composites fabricated using hydride–dehydride (HDH) Ti Grade 4 powders. The results showed that the as-processed Ti(PA)+17 vol% Mg composite exhibited an attractive combination of an ultimate tensile strength (UTS) of 450 ± 1 MPa, 0.2% strain offset yield stress (YS0.2) of 331 ± 5 MPa, and elongation (e) of 8.9 ± 1%), in addition to a reduced Young’s elastic modulus (E) of 88 ± 0.1 GPa. Moreover, the as-processed Ti(PA)+17 vol% Mg composite showed a reasonable fatigue life, while it reached a fatigue tensile stress of 260 MPa at 1.5·107 cycles. The advantageous mechanical properties of the Ti(PA)+17 vol% Mg composite, superior to those of Ti(HDH)+Mg counterparts, resulted from a specific ultrafine Ti grain structure. The corrosion behavior of the Ti(PA)+17 vol% Mg composite was systematically studied during immersion in a Hank’s balanced salt solution (HBSS) for up to 21 days. The elution of Mg enabled a further decrease of E down to 84.3 ± 0.3 GPa, while the tensile strengths remained unaffected, and e and fatigue stress decreased. Nevertheless, the mechanical performance of eluted Ti(PA)+17 vol% Mg remained appropriate for a specific application of dental implants with the addition of porosity induced osseointegration. Owing to a refined Mg grain structure, in-vitro corrosion tests confirmed a reduced elution rate of the Mg component from Ti(PA)+17 vol% Mg when compared with that of Ti(HDH)+Mg counterparts. The cytotoxicity assays demonstrated that as-extruded Ti(PA)+17 vol% Mg exhibited a nontoxic response upon culturing with resistant hAD-MSC cells, which was comparable with that of the commercial purity (CP) Ti Grade 4 reference material. For a highly sensitive L929 cell line, the metabolic activity of Ti(PA)+17 vol% Mg had to be increased by surface pretreatment of a TiMg sample. All results of this study indicate that the new Ti(PA)+17 vol% Mg composite is immensely promising for use in prosthodontic surgery.

This research focuses on synthesis and anticancer activity of trans-[(dichloro)bisdipyridlquinoxalino] and [(dichloro)bisdithienylquinoxalino]copper(II)/platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin (HSA) of the complexes were assessed with UV titration, thermal decomposition, viscometric, and fluorometric measurements. The nature of the binding of the complexes on DNA were revealed as electrostatic interaction between the cationic metal complexes ion and the negative phosphate groups of CT-DNA upon removal of the counter ion, chloride. In addition, our complexes induced a surface contact through the hydrophobic region of protein. Antitumor activity of the complexes against human glioblastoma A172, LN229, and U87 cell lines and human lung A549, human breast MDA-231, human cervix HeLa, and human prostate PC-3 cell lines were investigated by examining cell viability, oxidative stress, apoptosis, and migration/invasion. Cytotoxicity of the complexes was evaluated by MTT test. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of dipyridlquinoxalino and dithienylquinoxalino copper(II)/platinum(II) complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that trans-[(dichloro)bisdithenylquinoxalino]copper (II) (Cu(dtq)) has the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. Wound healing and invasion analysis results also supported the anticancer activity of Cu(dtq).

Here, we describe the characteristics of a Pt-blue complex [Pt-4(2-atp)(8)(H2O)(OH)] (2-atp: 2-aminothiophenol) as a prodrug for its DNA-binding properties and its use in cancer therapy. The nature of the interaction between the Pt-blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single- and double-stranded breaks (DBS) on DNA in vitro, but no DSBs in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species (ROS) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST-1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro-apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt-blue complex under study grants premise for further studies.

The aim of this study was to evaluate the In-vitro response, including cytotoxicity, genotoxicity, and oxidative stress, of a pretreated dental implant (DI) that was produced from a novel partially biodegradable Ti17Mg composite material. Viability and adhesion, and morphological alteration of Mouse fibroblast NCTC clone 929 cell line (L929) and human Dental Pulp Stem Cells (hDPSCs) were evaluated using MTT and live/dead assays. The genotoxic potential was investigated by comet and plasmid DNA interaction assays. The oxygen reactive species (ROS) formation was detected by Oxidative stress testing. The results showed surface pretreatment by 20 h prewashing in Hank's balanced salt solution (HBSS) at 20 mL.cm−2 concertation minimized the hypermagnesemia effect. Compared with the Ti Grade 4 (TiGR4) reference EDS analysis confirmed formation of a Ca/P-rich biomimetic layer on the surface of Ti17Mg DI after extraction in DMEM. The indirect MTT assay revealed that Ti17Mg DI extracts exerted a mild level of cytotoxicity without any induced morphological alteration of the incubated cells. The direct assays showed that the initial cell adhesion and proliferation were improved. No DNA damage was induced by Ti17Mg DI. No detection for smearing or loss of plasmid DNA was found. Oxidative stress confirmed no increase in ROS levels. In-vitro evaluation study confirmed a desirable In-vitro response of pretreated Ti17Mg that was comparable to that of the TiGR4 reference. The obtained results suggest the Ti17Mg composite exhibits a promising application potential as a material for the fabrication of DI.

The main aim of this study is to assess the safety and antitumor efficacy of a palladium(II) (Pd)-saccharinate complex with terpyridine. To characterize the Pd(II) complex in vitro, its cytotoxicity was evaluated using a water-soluble tetrazolium salt cell viability assay and the mechanism of cell death was assessed by DNA fragmentation/condensation and live cell imaging analyses. The antitumor efficacy and safety of the Pd(II) complex in-vivo were examined by analyzing reduction in tumor size, changes in body and organ weight, histopathological analysis of liver, kidney, and tumor sections, and biochemical analysis of serum in C57BL/6 mice. Our results showed that the Pd(II) complex was more cytotoxic to cancer cells than noncancer cell lines and caused cell death through apoptotic pathways. The treatment of the Pd(II) complex in tumor-bearing mice effectively reduced the tumor size at half the dose used for cisplatin. The Pd(II) complex appeared to exert less liver damage than the cisplatin-based complex on changes in the hepatic enzymes levels in the serum. Hence, the complex appears to be a potential chemotherapeutic drug with high antitumor efficacy and fewer hepatotoxic complications, providing an avenue for further studies. Anti-Cancer Drugs 28: 898-910 Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved. Scientific and Technological Research Institute of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) This work was supported by the internal funding of The Scientific and Technological Research Institute of Turkey (TUBITAK). WOS:000408162400009 28657910 Q3

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Epidemiological studies show that exposure to nickel (Ni) compounds is associated with a variety of pulmonary adverse health effects, such as lung inflammation, fibrosis, emphysema and tumours. However, the mechanisms leading to pulmonary toxicity are not yet fully elucidated. In the current study we used Calu-3, a well differentiated human bronchial cell line, to investigate in vitro the effect of Ni in soluble form (NiCl(2)) and in the form of micro-sized Ni particles on the airway epithelium. For this purpose, we evaluated the effect of Ni compounds on the epithelial barrier integrity by monitoring the transepithelial electrical resistance (TEER) and on oxidative stress pathways by measuring reactive oxygen species (ROS) formation and induction of stress-inducible genes. Our results showed that exposure to NiCl(2) and Ni particles resulted in a disruption of the epithelial barrier function observed by alterations in TEER, which occurred prior to the decrease in cell viability. Moreover, Ni compounds induced oxidative stress associated with ROS formation and up-regulation of the stress-inducible genes, Metallothionein 1X (MT1X), Heat shock protein 70 (HSP70), Heme oxygenase-1 (HMOX-1), and gamma-glutamylcysteine synthetase (γGCS). Furthermore, we have demonstrated that the induced effects by Ni compounds can be partially attributed to the increase in Ni ions (Ni(2+)) intracellular levels.

Epidemiological studies show that cadmium (Cd) exposure causes pulmonary damage, such as emphysema, pneumonitis, and lung cancer. However, the mechanisms leading to pulmonary toxicity are not yet fully elucidated. The aim of this study was to further investigate cadmium chloride (CdCl(2)) induced toxicity using Calu-3 cells as an in vitro model of human bronchial epithelial cells. CdCl(2) induced effects following either apical or basolateral exposure were evaluated by Neutral Red Uptake (NRU), Trans-Epithelial Electrical Resistance (TEER), and alteration in Metallothionein 1X (MT1X), Heat shock protein 70 (HSP70), and Heme oxygenase 1 (HMOX-1) genes. CdCl(2) exposure resulted in a collapse of barrier function and the induction of MT1X, HMOX-1 and HSP70 genes, prior to alterations in cell viability. These effects were more pronounced when the exposure was from the basolateral side. Co-administration of N-Acetylcysteine (NAC) exerted a strong protective effect against CdCl(2) induced barrier damage and stress related genes, while other antioxidants only attenuated CdCl(2) induced HSP70 and HMOX-1 and showed no protective effect on the barrier collapse. These findings indicate that CdCl(2) exposure is likely to impair Calu-3 barrier function at non cytotoxic concentrations by a direct effect on adherens junction proteins. The protective effect of NAC against CdCl(2) induced MT1X, HSP70 and HMOX-1 genes, demonstrates an anti-oxidant effect of NAC in addition to Cd chelation.

In October 2006, the European Centre for theValidation of Alternative Methods (ECVAM) spon-sored and hosted a three-day workshop to consideropportunities and challenges in the development ofalternative methods for the identification and char-acterisation of chemical respiratory allergens. Theproceedings, conclusions and recommendations ofthat workshop were subsequently made available asECVAM Workshop Report 60 (1).In April 2008, a second meeting was convenedby ECVAM to consider what progress has beenmade in the light of the recommendations derivedfrom the 2006 Workshop and the publishedreport. This meeting had as a second objective —to consider whether new opportunities for theidentification and characterisation of chemicalrespiratory allergens had emerged since 2006. Inaddition, the scope of the meeting was broadenedto also include an examination of new and emerg-ing approaches that may be appropriate for theevaluation of the respiratory sensitising potentialof proteins.

The objective of this study was to determine the loss of toxicity of deoxynivalenol in extruded cereal-based products by the tetrazolium salt (MTT) bioassay using a sensitive Chinese hamster ovary (CHO-K1) cell line and to compare the results to chemical (high-performance liquid chromatography, HPLC) and biochemical (enzyme-linked immunosorbant assay, ELISA) methods of analysis. A split-split plot design was used for the extrusion process experiments at temperatures of 150, 175, and 200 degrees C and screw speeds of 70 and 140 rpm. The initial mean deoxynivalenol concentration in the corn grits artificially contaminated with Fusarium graminearum was found to be 23.5 mug/g as measured by HPLC. The percent reductions of deoxynivalenol in the contaminated corn grits upon extrusion processing ranged from 22 to 35%, from 21 to 34%, and from 21 to 37% as measured by HPLC, ELISA, and MTT bioassay, respectively. The MTT bioassay results were more closely correlated with HPLC (r = 0.90) results than with ELISA results (r = 0.78). The MTT bioassay, using a sensitive mammalian cell line, was demonstrated to be a useful method for quantification of deoxynivalenol as well as a potential toxicity screening method for contaminated extruded cereal-based products.

Oral ingestion of pesticides can be a major exposure route. These compounds are frequently consumed in the presence of triacylglycerides, which are then hydrolyzed to free fatty acids. The purpose of this work was to examine the effect of two common fatty acids, palmitic (PA) and oleic (OA) acids, and the biological emulsifier sodium taurocholate (TC) on the absorption of three herbicides (trifluralin, alachlor and atrazine) by Caco-2 cell monolayers. Trifluralin's absorption was enhanced (p < 0.05) in the presence of OA whereas the greatest absorption of atrazine and alachlor occurred with PA and the control media, respectively. Trifluralin had significantly lower absorption through the monolayer than either alachlor or atrazine (p < 0.001). A mass balance study demonstrated that trifluralin accumulated within the cell monolayer (13.85% of the donor after 3 h of exposure), but alachlor and atrazine (1.27% and 0.85%, respectively) did not. This response was linear with time (21.89% trifluralin after 6 h of exposure), and demonstrated the potential for continued release of trifluralin after source removal. These experiments demonstrated that fatty acids and an emulsifier can influence absorption of herbicides across small intestinal epithelium.

Metal-based compounds represent promising anticancer therapeutic agents. In this study, the mechanism of action of a novel metal-based drug, a palladium(II) (Pd) complex ([PdCl(terpy)](sac)2H(2)O, terpy=2,2':6',2 ''-terpyridine and sac=saccharinate), was elucidated. The tested compound induced cytotoxicity in nine different human cancer cell lines that originated from various organs, suggesting a broad spectrum of activity. The IC50 values were significantly higher for noncancerous cells when compared with cancer cells. We found that cells treated with the Pd(II) complex exhibited increased caspase 3/7 activities and condensed/fragmented nuclei, as demonstrated by nuclear staining and DNA laddering. Morphological features, such as cellular shrinkage and blebbing, were also observed, indicating that apoptosis was the primary mechanism of cell death. Pd(II) treatment induced DNA double-stranded breaks both in vitro and in vivo, potentially accounting for the source of stress in these cells. Although caspase 3/7 activities were elevated after Pd(II) treatment, silencing or using inhibitors of caspase 3 did not block apoptosis. Other molecules that could potentially play a role in Pd(II)-induced apoptosis, such as p53 and Bax, were also tested using silencing technology. However, none of these proteins were essential for cell death, indicating either that these molecules do not participate in Pd(II)-induced apoptosis or that other pathways were activated in their absence. Hence, this new molecule might represent a promising anticancer agent that exhibits cytotoxicity in p53-mutant, Bax-mutant, and/or caspase 3-mutant cancer cells. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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The objective of this study was to determine loss of toxicity of zearalenone in extruded cereal-based products by the MTT (tetrazolium salt) cell proliferation assay using a sensitive MCF-7 human breast cancer cell line and to compare the results to chemical (high-performance liquid chromatography, HPLC) and biochemical (enzyme-linked immunosorbent assay, ELISA) methods of analysis. A split-split plot design was used for the extrusion process experiments at temperatures of 150, 175, and 200 degrees C and screw speeds of 70 and 140 rpm. The initial zearalenone concentration in the artificially contaminated corn grits with Fusarium graminearum was found at a mean concentration of 37.88 microg/g as measured by HPLC. The percent reductions of zearalenone in the contaminated corn grits upon extrusion processing were in the ranges of 67-81, 60-72, and 66-78% as measured by HPLC, ELISA, and the MTT cell proliferation assay, respectively. The MTT cell proliferation assay results were more closely correlated with HPLC results (r = 0.96) than ELISA results (r = 0.83). The MTT cell proliferation assay was demonstrated to be a useful method for quantification of zearalenone as well as a potential toxicity screening method for contaminated extruded cereal-based products.

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Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epithelia, which can alter their kinetic and metabolic profiles. It is, therefore, important to understand diffusion kinetics across barrier membranes when choosing a dosing regime that will elicit the greatest cellular response. An in vitro system that combines membrane transport studies with a downstream cell culture chamber has been developed. The system has been tested with skin and a small intestine model (Caco-2 cell monolayers) as barriers, the peroxovanadium compound [VO(O2)2 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumption as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in diabetic rats when administered transdermally. A dose of 10 mM bpV(phen) placed on the skin epidermis with a continuous iontophoretic current of 0.5 mA/cm2 for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23%. This system is highly versatile and can be used to study many other processes, involving a variety of biological membranes, cell types, chemicals and assays, making it a valuable research tool. © 2000 Biomedical Engineering Society.