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Topic Review
Toxic Effects of Pyrrolizidine Alkaloids
Pyrrolizidine alkaloids (PAs) are naturally occurring secondary metabolites of plants. More than 660 types of PAs have been identified from an estimated 6000 plants, and approximately 120 of these PAs are hepatotoxic. As a result of PAs being found in spices, herbal teas, honey, and milk, PAs are considered contaminants in foods, posing a potential risk to human health.
  • 174
  • 27 Feb 2024
Topic Review
Toxic Effects of Poly-Fluoroalkyl Substances in Organisms
More than 7000 synthetic compounds known as per- and poly-fluoroalkyl substances (PFAS) are applied to food packaging and other materials to provide fat, fire, and/or water resistance properties. These compounds have exceptional environmental stability and persistence due to the strong C-F chemical bond, earning them the moniker “forever chemicals”. Emission of PFAS from industrial waste leads to water, air, and soil contamination. Due to this ubiquitous nature, combined with the fact that PFAS in humans are known to have carcinogenic and reprotoxic effects and to cause vaccine resistance and depression of the immunity system, PFAS may constitute a major threat to human health. For this reason, the attention of the scientific community and of control bodies is increasing and as a consequence legislation and the scientific literature on PFAS are constantly evolving.
  • 309
  • 19 Jun 2023
Topic Review
Toll-like Receptor 4 Inflammatory Perspective on Doxorubicin-Induced Cardiotoxicity
Doxorubicin (Dox) is one of the most frequently used chemotherapeutic drugs in a variety of cancers, but Dox-induced cardiotoxicity diminishes its therapeutic efficacy. The underlying mechanisms of Dox-induced cardiotoxicity are still not fully understood. More significantly, there are no established therapeutic guidelines for Dox-induced cardiotoxicity. To date, Dox-induced cardiac inflammation is widely considered as one of the underlying mechanisms involved in Dox-induced cardiotoxicity. The Toll-like receptor 4 (TLR4) signaling pathway plays a key role in Dox-induced cardiac inflammation, and growing evidence reports that TLR4-induced cardiac inflammation is strongly linked to Dox-induced cardiotoxicity.
  • 249
  • 25 Jun 2023
Topic Review
TMDC Nanozymes: Application Perspective
Applications of TMDC NZs in different fields—starting from biosensing to different treatment fields like antibacterial, anti-inflammation activity and cancer therapy—are discussed in more details. 
  • 378
  • 29 Mar 2022
Topic Review
Three-Dimensional Liver Culture Systems
Drug-induced liver injury (DILI) is the major reason for failures in drug development and withdrawal of approved drugs from the market. Two-dimensional cultures of hepatocytes often fail to reliably predict DILI: hepatoma cell lines such as HepG2 do not reflect important primary-like hepatic properties and primary human hepatocytes (pHHs) dedifferentiate quickly in vitro and are, therefore, not suitable for long-term toxicity studies. More predictive liver in vitro models are urgently required in drug development and compound safety evaluation. This review discusses available human hepatic cell types for in vitro toxicology analysis and their usage in established and emerging three-dimensional (3D) culture systems. Generally, 3D cultures maintain or improve primary hepatic functions (including expression of drug metabolizing enzymes) of different liver cells for several weeks of culture, thus allowing long-term and repeated-dose toxicity studies. Spheroid cultures of pHHs have been comprehensively tested, but also other cell types such as HepaRG benefit from 3D culture systems. Emerging 3D culture techniques include usage of induced pluripotent stem-cell-derived hepatocytes and primary-like upcyte cells, as well as advanced culture techniques such as microfluidic liver-on-a-chip models. In-depth characterization of existing and emerging 3D hepatocyte technologies is indispensable for successful implementation of such systems in toxicological analysis.
  • 552
  • 10 Nov 2021
Topic Review Peer Reviewed
The Mysteries of the White Truffle: Its Biology, Ecology and Cultivation
Tuber magnatum Picco is the most expensive of the truffles and a great deal of research has been carried out in an attempt to solve the mysteries of its ecology and biology. However, considerable work remains to be done particularly on those secrets of its life cycle that remain a mystery. It is known that T. magnatum is heterothallic, but it has yet to be determined how fertilization occurs between the two strains of different mating types. It is also known that the white truffle is an ectomycorrhizal fungus, and its mycorrhizas can be produced in greenhouses, but then they seem to disappear in the field. The role of other soil microorganisms, fungi and bacteria, on its soil mycelial development and fructification is intriguing but is far from being completely understood. All these uncertainties have made the cultivation of T. magnatum extremely difficult and only recently have we had the scientific proofs that it is possible. Even so, many questions remain unanswered and the management practices of T. magnatum plantations are still to be better defined to also enable the taming of this truffle.
  • 686
  • 11 Jan 2023
Topic Review
The Gut–Liver–Brain Axis
The gut–liver–brain axis constitutes a multidirectional communication network that connects the enteric, hepatic, and central nervous systems. Through the complex interplay between the gut–liver, gut–brain, and liver–brain axes, this communication network extends to involve endocrine, immune (humoral), and metabolic routes of communication. Within the network, the gut and liver affect cognitive behaviors through the host’s immune responses and the regulation of microbiota, and the brain also influences intestinal and hepatic activities. Studies in animals have shown that an impaired gut–liver–brain axis is associated with diseases such as hepatic encephalopathy, Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, depression, and autism spectrum disorder (ASD).
  • 208
  • 01 Feb 2024
Topic Review
The Case of Hydroxychloroquine in COVID-19 Patients
Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this entry is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. 
  • 471
  • 14 Jan 2022
Topic Review
The Acute Toxicity of Mineral Fibres
To gain new insights into the different toxicity mechanisms of carcinogenic mineral fibres, the acute effects of fibrous erionite, crocidolite and chrysotile in the THP-1 M0, M1 and M2 macrophages were investigated. The three mineral fibres apparently act by different toxicity mechanisms. Crocidolite seems to exert its toxicity effects mostly thanks to its biodurability, ROS and cytokine production, and DNA damage. Chrysotile, due to its low biodurability, displays toxic effects related to the release of toxic metals, ROS and cytokine production. Other mechanisms are involved in explaining the toxicity of biodurable fibrous erionite with lower ROS and toxic metal release but exhibiting cation exchange capacity able to alter the intracellular homeostasis of important cations. Their results aim to fill the gap on understanding the fine bio-chemical interactions of different types of carcinogenic fibres inside the cells, hopefully helping in upgrading the existing models of toxicity/carcinogenicity of mineral fibres.
  • 329
  • 19 Apr 2022
Topic Review
Tetrodotoxin for Neuropathic&Cancer Pain Relief
Tetrodotoxin (TTX) is a potent neurotoxin found mainly in puffer fish and other marine and terrestrial animals. TTX blocks voltage-gated sodium channels (VGSCs) which are typically classified as TTX-sensitive or TTX-resistant channels. VGSCs play a key role in pain signaling and some TTX-sensitive VGSCs are highly expressed by adult primary sensory neurons. During pathological pain conditions, such as neuropathic pain, upregulation of some TTX-sensitive VGSCs, including the massive re-expression of the embryonic VGSC subtype NaV1.3 in adult primary sensory neurons, contribute to painful hypersensitization. In addition, people with loss-of-function mutations in the VGSC subtype NaV1.7 present congenital insensitive to pain. TTX displays a prominent analgesic effect in several models of neuropathic pain in rodents. According to this promising preclinical evidence, TTX is currently under clinical development for chemo-therapy-induced neuropathic pain and cancer-related pain.
  • 629
  • 21 Jul 2021
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