In vitro testing of hazardous mineral fibres: The issue of the concentration metric.

This communication addresses the matter of the appropriate concentration metrics for the in vitro testing of mineral fibres, a specific technical issue affecting the correct determination of their toxic/carcinogenic potential. The exposure to certain mineral fibres (e.g.

TPP-Based Nanovesicles Kill MDR Neuroblastoma Cells and Induce Moderate ROS Increase, While Exerting Low Toxicity Towards Primary Cell Cultures: An In Vitro Study.

Neuroblastoma (NB) is a malignant childhood tumour, which originates from neuroblasts with an incidence of approximately 15,000 new cases per year worldwide. Therapy-induced secondary tumorigenesis and the emergency of drug resistance in its high-risk (HR-NB) forms drive to a survival rate of <50%, despite aggressive treatments. Our recent research is focused on testing in vitro the effects of synthetized triphenyl phosphonium (TPP)-based bola amphiphilic nanovesicles (BPPBs) against both drug-sensitive and multi-drug-resistant (MDR) cancer cell lines.

Microplastics as benzo-a-pyrene carriers: genotoxicity assessment simulating human gastric digestion.

Microplastic particles (MPs) are ubiquitous environmental pollutants that can remain in ecosystems for prolonged periods. Plastic materials undergo various degradation processes driven by chemical, physical, and biological factors that alter their size, shape, composition, and bioavailability. The gastrointestinal tract is the primary pathway through which MPs are absorbed, raising concerns as they can transport harmful pollutants and microorganisms into the body.

Tri-Phenyl-Phosphonium-Based Nano Vesicles: A New In Vitro Nanomolar-Active Weapon to Eradicate PLX-Resistant Melanoma Cells.

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer, with characteristics including a poor prognosis, chemotherapy-induced secondary tumorigenesis, and the emergence of drug resistance. Our recent study demonstrated that triphenyl phosphonium (TPP)-based nanovesicles (BPPB), which have amphiphilic properties, exert potent ROS-dependent anticancer effect against PLX4032 (PLX)-sensitive MeOV BRAF and MeTRAV BRAF mutant cell lines, evidencing more marked efficacy on MeOV cells. Here, taking advantage of this in vitro model, the antitumoral effect of BPPB was tested on PLX-resistant (PLX-R) MeOV BRAF and MeTRAV BRAF mutant cell lines to find a new potential strategy to fight melanoma therapy resistance.

Fibrous erionite modifications following THP-1 macrophage phagocytosis: An insight into the mechanisms of interaction with biological systems.

Erionite is a ubiquitous natural zeolite, often occurring with fibrous habit, whose strong tumorigenic activity to humans has been certified by its inclusion in the Group 1 Human-Carcinogenic list by the International Agency for Research on Cancer. To date, the reason(s) of erionite toxicity are still unclear, albeit several hypotheses have been proposed. The present work, based on the combined analysis of the chemical and structural modifications of erionite fibres following incubation in human THP-1 macrophages and evaluation of cellular response, indicates that, upon macrophage phagocytosis, a large release of cations is counterbalanced by a significant sequestration of hydronium ions from lysosomes provoking a quick pH dysregulation.

The cytotoxic/genotoxic role of impurities in soluble minerals: The case of natural (fibrous epsomite) versus synthetic (Epsom salt) magnesium sulphate.

Epsomite and Epsom salt are very common mineral phases, and many known uses are found in agriculture, and in food and pharmaceutical industries. Natural epsomite can be fibrous and inhalable, potentially reaching the digestive tract after dissolving in mucus and saliva. Epsom salt is a common food additive (E 518) to which humans can be exposed daily, although its health effects are still debated.

Toxicity of size separated chrysotile fibres: The relevance of the macrophage-endothelial axis crosstalk.

Asbestos minerals have been widely exploited due to their physical-chemical properties, and chrysotile asbestos has accounted for about 95% of all asbestos commercially employed worldwide. The exposure to chrysotile, classified like other five amphibole asbestos species as carcinogenic to humans, represents a serious occupational and environmental hazard. Nevertheless, this mineral is still largely employed in about 65% of the countries worldwide, which still allow its "safe use".

Thermal measurements support a role of the ABA/LANCL1-2 hormone/receptors system in thermogenesis.

Abscisic acid (ABA) is a conserved 'stress hormone' in unicellular organisms, plants and animals. In mammals, ABA and its receptors LANCL1 and LANCL2 stimulate insulin-independent cell glucose uptake and oxidative metabolism: overexpression of LANCL1/2 increases, and their silencing conversely reduces, mitochondrial number, respiration and proton gradient dissipation in muscle cells and in brown adipocytes. We hypothesized that the ABA/LANCL hormone/receptors system could be involved in thermogenesis.

Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre parameters to the key characteristics of carcinogens: A comprehensive model inspiring asbestos-induced cancer prevention strategies.

Background: Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising effective cancer prevention strategies and therapies. Along this research line, our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects leading to carcinogenesis.

Methods: toxicology tests that deliver information on the 10 key characteristics of carcinogens adopted by the International Association for Research on Cancer (IARC) have been systematically collected for a commercial chrysotile, standard UICC crocidolite and wollastonite.

In vitro cyto- and geno-toxicity of asbestiform erionite from New Zealand.

This work is an in vitro toxicity study of two asbestiform erionites from Kaipara and Gawler Downs in New Zealand. This study is the first, to the knowledge of the authors, to investigate the mechanisms that trigger adverse effects leading to carcinogenicity from New Zealand erionites. The effects induced by the erionite fibres from New Zealand were compared with those produced by positive (crocidolite) and negative (wollastonite) standards, and other erionite fibres described in the literature.

The ABA/LANCL1-2 Hormone/Receptors System Controls ROS Production in Cardiomyocytes through ERRα.

Rat H9c2 cardiomyocytes overexpressing the abscisic acid (ABA) hormone receptors LANCL1 and LANCL2 have an increased mitochondrial proton gradient, respiration, and vitality after hypoxia/reoxygenation. Our aim was to investigate the role of the ABA/LANCL1-2 system in ROS turnover in H9c2 cells. H9c2 cells were retrovirally infected to induce the overexpression or silencing of LANCL1 and LANCL2, without or with the concomitant silencing of the transcription factor ERRα.

Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System.

The orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose tissue, kidney, and brain. Abscisic acid (ABA), traditionally acknowledged as a plant stress hormone, is detected and actively functions in organisms beyond the land plant kingdom, encompassing cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. Its ancient, cross-kingdom role enables ABA and its signaling pathway to regulate cell responses to environmental stimuli in various organisms, such as marine sponges, higher plants, and humans.

Toxicity and inflammatory potential of mineral fibres: The contribute of released soluble metals versus cell contact direct effects.

Asbestos fibres have been considered an environmental hazard for decades. However, little is known about the attempts of circulating immune cells to counteract their toxicity. We addressed the early effects of fibre-released soluble factors (i.

New Insights into the LANCL2- Binding Mode towards the Evaluation of New LANCL Agonists.

The lanthionine synthetase C-like (LANCL) proteins include LANCL2, which is expressed in the central nervous system (CNS) and in peripheral tissues. LANCL2 exhibits glutathionylation activity and is involved in the neutralization of reactive electrophiles. Several studies explored LANCL2 activation as a validated pharmacological target for diabetes and inflammatory bowel disease.

Abscisic Acid and Its Receptors LANCL1 and LANCL2 Control Cardiomyocyte Mitochondrial Function, Expression of Contractile, Cytoskeletal and Ion Channel Proteins and Cell Proliferation via ERRα.

The cross-kingdom stress hormone abscisic acid (ABA) and its mammalian receptors LANCL1 and LANCL2 regulate the response of cardiomyocytes to hypoxia by activating NO generation. The overexpression of LANCL1/2 increases transcription, phosphorylation and the activity of eNOS and improves cell vitality after hypoxia/reoxygenation via the AMPK/PGC-1α axis. Here, we investigated whether the ABA/LANCL system also affects the mitochondrial oxidative metabolism and structural proteins.

The ABA/LANCL1/2 Hormone/Receptor System Controls Adipocyte Browning and Energy Expenditure.

The abscisic acid (ABA)/LANC-like protein 1/2 (LANCL1/2) hormone/receptor system regulates glucose uptake and oxidation, mitochondrial respiration, and proton gradient dissipation in myocytes. Oral ABA increases glucose uptake and the transcription of adipocyte browning-related genes in rodent brown adipose tissue (BAT). The aim of this study was to investigate the role of the ABA/LANCL system in human white and brown adipocyte thermogenesis.

CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NAD-Lowering Agents.

Cancer cells fuel growth and energy demands by increasing their NAD biosynthesis dependency, which therefore represents an exploitable vulnerability for anti-cancer strategies. CD38 is a NAD-degrading enzyme that has become crucial for anti-MM therapies since anti-CD38 monoclonal antibodies represent the backbone for treatment of newly diagnosed and relapsed multiple myeloma patients. Nevertheless, further steps are needed to enable a full exploitation of these strategies, including deeper insights of the mechanisms by which CD38 promotes tumorigenesis and its metabolic additions that could be selectively targeted by therapeutic strategies.

Oxidative stress-induced MMP- and γ-secretase-dependent VE-cadherin processing is modulated by the proteasome and BMP9/10.

Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by HO exposure induced efficient VE-cadherin proteolysis by MMPs and γ-secretase in human umbilical endothelial cells (HUVECs). The cytoplasmic domain of VE-cadherin produced by γ-secretase, VE-Cad/CTF2-a fragment that has eluded identification so far-could readily be detected after HO treatment.

Citicoline Eye Drops Protect Trabecular Meshwork Cells from Oxidative Stress Injury in a 3D In Vitro Glaucoma Model.

Intraocular pressure (IOP) is considered an important modifiable risk factor for glaucoma, which is known as the second leading cause of blindness worldwide. However, lowering the IOP is not always sufficient to preserve vision due to other non-IOP-dependent mechanisms being involved. To improve outcomes, adjunctive therapies with IOP-independent targets are required.

The ABA-LANCL1/2 Hormone-Receptors System Protects H9c2 Cardiomyocytes from Hypoxia-Induced Mitochondrial Injury via an AMPK- and NO-Mediated Mechanism.

Abscisic acid (ABA) regulates plant responses to stress, partly via NO. In mammals, ABA stimulates NO production by innate immune cells and keratinocytes, glucose uptake and mitochondrial respiration by skeletal myocytes and improves blood glucose homeostasis through its receptors LANCL1 and LANCL2. We hypothesized a role for the ABA-LANCL1/2 system in cardiomyocyte protection from hypoxia via NO.

LncRNA EPR-induced METTL7A1 modulates target gene translation.

EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription. Here, we report on Mettl7a1 as a direct target of EPR. We show that EPR induces Mettl7a1 transcription by rewiring three-dimensional chromatin interactions at the Mettl7a1 locus.

HO-1 Limits the Efficacy of Vemurafenib/PLX4032 in BRAF Mutated Melanoma Cells Adapted to Physiological Normoxia or Hypoxia.

Induction of heme oxygenase 1 (HO-1) favors immune-escape in BRAF melanoma cells treated with Vemurafenib/PLX4032 under standard cell culture conditions. However, the oxygen tension under standard culture conditions (~18 kPa O) is significantly higher than the physiological oxygen levels encountered in vivo. In addition, cancer cells in vivo are often modified by hypoxia.

Heterodimer of A2A and Oxytocin Receptors Regulating Glutamate Release in Adult Striatal Astrocytes.

Background: Roles of astrocytes in the modulatory effects of oxytocin (OT) in central nervous system are increasingly considered. Nevertheless, OT effects on gliotransmitter release have been neglected.

Methods: In purified astrocyte processes from adult rat striatum, we assessed OT receptor (OTR) and adenosine A2A receptor expression by confocal analysis.