Understanding acrylamides in foods: mechanistic insights, exposure risks and technological approaches for reduction

Alzheimer’s disease (AD) is the most conspicuous chronic neurodegenerative syndrome, which has become a significant challenge for the global healthcare system. Multiple studies have corroborated a clear association of neurotoxicants with AD pathogenicity, such as Amyloid beta (Aβ) proteins and neurofibrillary tangles (NFTs), signalling pathway modifications, cellular stress, cognitive dysfunctions, neuronal apoptosis, neuroinflammation, epigenetic modification, and so on. This review, therefore, aimed to address several essential mechanisms and signalling cascades, including Wnt (wingless and int.) signalling pathway, autophagy, mammalian target of rapamycin (mTOR), protein kinase C (PKC) signalling cascades, cellular redox status, energy metabolism, glutamatergic neurotransmissions, immune cell stimulations (e.g. microglia, astrocytes) as well as an amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2) and other AD-related gene expressions that have been pretentious and modulated by the various neurotoxicants. This review concluded that neurotoxicants play a momentous role in developing AD through modulating various signalling cascades. Nevertheless, comprehension of this risk agent-induced neurotoxicity is far too little. More in-depth epidemiological and systematic investigations are needed to understand the potential mechanisms better to address these neurotoxicants and improve approaches to their risk exposure that aid in AD pathogenesis. Key messages Inevitable cascade mechanisms of how Alzheimer’s Disease-related (AD-related) gene expressions are modulated by neurotoxicants have been discussed. Involvement of the neurotoxicants-induced pathways caused an extended risk of AD is explicited. Integration of cell culture, animals and population-based analysis on the clinical severity of AD is addressed.

Titanium dioxide (TiO2) nanoparticles (NPs) are employed as an ultraviolet filter in sunscreen products because of their high ultraviolet absorptivity. However, sunscreen sprays may pose health risks due to the toxicity of inhaled TiO2 NPs. Therefore, we estimated the potential human health risk posed by inhaled TiO2 NPs emitted from sunscreen sprays. The physiology-based lung model was employed to predict the lung TiO2 NPs burden caused by long-term exposure. A Hill-based dose-response model described the relationship between lung inflammation and TiO2 NP accumulation. The Weibull threshold model was used to estimate the threshold amount of accumulation inducing 0.5% of the maximum increase in neutrophils. The potential health risk was assessed using a hazard quotient-based probabilistic risk model. All data obtained to date indicate that application of sunscreen sprays poses no significant health risk. However, using data simulations based on the threshold criterion, we discovered that in terms of practical strategies for preventing the risks posed by inhaled TiO2 NPs emitted from spray products, the suggested daily use amount and pressing number are 40 g (95% confidence interval: 11-146 g) and 66 (18-245), respectively. In this study, we successfully translated the potential health risk of long-term exposure to NP-containing sunscreen sprays and recommendations for daily application into mechanistic insights.

Humans are exposed to diverse hazardous chemicals daily. Although an exposure to these chemicals is suspected to have adverse effects on human health, mechanistic insights into how they interact with the human body are still limited. Therefore, acquisition of curated data and development of computational biology approaches are needed to assess the health risks of chemical exposure. Here we present HExpoChem, a tool based on environmental chemicals and their bioactivities on human proteins with the objective of aiding the qualitative exploration of human exposure to chemicals. The chemical-protein interactions have been enriched with a quality-scored human protein-protein interaction network, a protein-protein association network and a chemical-chemical interaction network, thus allowing the study of environmental chemicals through formation of protein complexes and phenotypic outcomes enrichment. HExpoChem is available at http://www.cbs.dtu.dk/services/HExpoChem-1.0/.

Enteric virus infection was boosted by the accumulation of micro- and nano-particles in host cells.

Droplet nuclei aerosol and Covid 19 - a risk to healthcare staff

Emerging flame retardants in the marine environment: A comprehensive review of occurrence, fate and analytical challenges

Cataracts are one of the most common eye diseases that can cause blindness. Discovering susceptibility factors in the proteome that contribute to cataract development would be helpful in gaining new insights in the molecular mechanisms of the cataract process. We used label-free nanoflow ultra-high-performance liquid chromatography–tandem mass spectrometry to compare aqueous humor protein expressions in cataract patients with different cataract risk factors such as diabetes mellitus (DM) and smoking and in controls (with cataract) without risk exposure. Eight patients with diabetes and who smoked (with double risk factors), five patients with diabetes and five patients who smoked (both with a single risk factor), and nine aged-matched cataract controls patients (non-risk exposure) were enrolled. In total, 136 aqueous humor proteins were identified, of which only alpha-2-Heremans–Schmid (HS)-glycoprotein was considered to be significantly risk-associated because it was differentially expressed in these three groups and exhibited increased expression with increasing risk factors. Significant changes in the aqueous humor level of alpha-2-HS-glycoprotein between DM and control samples and between smoking and control samples were confirmed using ELISA. The alpha-2-HS-glycoprotein, called fetuin-a, could be a potential aqueous biomarker associated with DM and smoking, which were cataract risk factors.

Overlooked environmental risks of type 2 diabetes: Evidence from a case-control study on the roles of dechlorane plus (DPs) and novel brominated flame retardants (NBFRs).

Pesticide exposure and spontaneous abortion risk: A comprehensive systematic review and meta-analysis

Rivaroxaban is an oral Factor Xa inhibitor. The primary objective of this communication was to quantitatively predict changes in rivaroxaban exposure when individuals with varying degrees of renal impairment are co-administered with another drug that is both a P-gp and a moderate CYP3A4 inhibitor. A physiologically based pharmacokinetic (PBPK) model was developed to simulate rivaroxaban pharmacokinetics in young (20-45 years) or older (55-65 years) subjects with normal renal function, mild, moderate and severe renal impairment, with or without concomitant use of the combined P-gp and moderate CYP3A4 inhibitor, erythromycin. The simulations indicate that combined factors (i.e., renal impairment and the use of erythromycin) have a greater impact on rivaroxaban exposure than expected when the impact of these factors are considered individually. Compared with normal young subjects taking rivaroxaban, concurrent mild, moderate or severe renal impairment plus erythromycin resulted in 1.9-, 2.4- or 2.6-fold increase in exposure, respectively in young subjects; and 2.5-, 2.9- or 3.0-fold increase in exposure in older subjects. These simulations suggest that a drug-drug-disease interaction is possible, which may significantly increase rivaroxaban exposure and increase bleeding risk. These simulations render more mechanistic insights as to the possible outcomes and allow one to reach a decision to add cautionary language to the approved product labeling for rivaroxaban.

Acrylamide (AA) is a well-known industrial chemical classified as a probable human carcinogen. Benign and malignant tumours at different sites, including the mammary gland, have been reported in rodents exposed to AA. This xenobiotic is also formed in many carbohydrate-rich foods prepared at high temperatures. For this reason, AA is an issue of concern in terms of human cancer risk. The epoxide glycidamide (GA) is thought to be the ultimate genotoxic AA metabolite. Despite extensive experimental and epidemiological data focused on AA-induced breast cancer, there is still lack of information on the deleterious effects induced by GA in mammary cells. The work reported here addresses the characterisation and modulation of cytotoxicity, generation of reactive oxygen species, formation of micronuclei (MN) and quantification of specific GA-DNA adducts in human MCF10A epithelial cells exposed to GA. The results show that GA significantly induces MN, impairs cell proliferation kinetics and decreases cell viability at high concentrations by mechanisms not involving oxidative stress. KU55933, an inhibitor of ataxia telangiectasia mutated kinase, enhanced the cytotoxicity of GA (P < 0.05), supporting a role of this enzyme in regulating the repair of GA-induced DNA lesions. Moreover, even at low GA levels, N7-GA-Gua adducts were generated in a linear dose-response manner in MCF10A cells. These results confirm that human mammary cells are susceptible to GA toxicity and reinforce the need for additional studies to clarify the potential correlation between dietary AA exposure and breast cancer risk in human populations.

Investigating the association between bisphenols and diabetes: Evidence from epidemiological and bioinformatics.

Perfluorooctanesulfonic acid (PFOS) exposure and multiple sclerosis: Evidence of association and mechanistic insights.

Revealing consensus gene pathways associated with respiratory functions and disrupted by PM2.5 nitrate exposure at bulk tissue and single cell resolution.

A scientifically sound estimation of low-dose radiation risk must take account of data coming from the full spectrum of radiological protection science including input from radiation energy deposition biophysics, molecular, cellular and animal radiation biology as well as epidemiological studies of exposed populations. One of the challenges in the field is to combine this input from different disciplines in a comprehensive description of cancer induced by ionising radiation. During the past decade, multi-step carcinogenesis models have been increasingly applied to achieve this goal and promise to provide a new approach to the estimation of low-dose radiation risks. The 20th L H Gray Conference, held in Ede, the Netherlands from 17-21 February 2002, was organised to review new insights in radiation mechanisms, carcinogenesis modelling and epidemiology, and these proceedings document that conference.The meeting aimed to provide a forum where radiation biologists, epidemiologists and radiation cancer modellers could meet, exchange results and views and consider the further development of their recent work. The focus of the meeting - as well as of these proceedings - was on the implications for low-dose radiation risks. The different issues were divided into topics such as `Basic Mechanisms and Bystander Effects'; `Cancer Modelling'; `Radon Exposure and Lung Cancer Risk'; `Cancer after Medical Exposure'; `Cancer Risk Estimation'; `Dose-Effect Relationships'; and `Application to Radiation Protection', and contained both review articles by keynote speakers and original contributions from participants.In the organisation of the conference, attention was given to stimulating the discussion and to this end all the participants were given the opportunity to `vote', in total confidentiality, on a series of pertinent questions using an interactive polling machine. The polling machine was used in the first session and participants were asked to respond to a series of questions, phrased to invite a `yes' or `no' answer, on important issues in radiological protection. In the last session some of these questions were repeated or slightly modified to form the basis for debate. The interested reader with internet access can review both the questions and the responses on http://www.rivm.nl/rca (click `Results' or `A question of opinion'). It should be borne in mind that polling was not done to find the true answers to the questions but to stimulate the discussion. It is interesting to note that although some 75% of the participants felt that a linear dose-effect relationship should not always be assumed for the evaluation of epidemiological data, about 75% also felt that the dose-effect for cancer induction does not have a threshold. There was a small swing in the voting on this last question from 70% to 80% during the meeting. It is also interesting that 70% felt that the bystander effect had been convincingly proven but 60% felt that it should not be taken into account in radiation risk assessment. Perhaps the most interesting responses were to questions about ICRP developments where 60% felt that the ICRP should not ignore the potential effects of very low doses and a large majority (85%) felt that an age-dependent risk should be incorporated into recommendations for radiological protection.The important and on-going discussion of low-dose radiation risk and the anticipated new recommendations from the ICRP provided the back-drop for the conference and it is hoped that these proceedings will stimulate further cooperative research between radiation biologists, epidemiologists and cancer modellers leading to improved insights into the estimation of low-dose radiation risks, and that these insights will soon be considered for inclusion in the recommendations of the ICRP.We wish to express our gratitude for the generous support provided for the meeting and the publication of these proceedings by the following organisations: the L H Gray Trust (seehttp://www.graylab.ac.uk/usr/lhgraytrust/ for more information about the L H Gray Trust and previous L H Gray conferences and workshops);the Nuclear Energy Programme of the Research Directorate General of the European Commission (Contract FIGH-CT-2001-06006);the Biological and Environmental Research Program (BER) of the US Department ofEnergy (Grant No DE-FG02-02ER63291); the Society for Radiological Protection (SRP) and the Dutch National Institute for Public Health and the Environment (RIVM). We would also like to acknowledge the indispensable assistance given by Mrs P Zahradnik in organising the practical and administrative aspects of the meeting and the proceedings. We would not have been able to finalise these proceedings for publication without the efficient cooperation of the Scientific Committee, the referees, the authors and the editorial and production team at Institute of Physics Publishing.