Antimicrobial sensitisers: Gatekeepers to avoid the development of multidrug-resistant bacteria.

The resistance of multidrug-resistant bacteria to existing antibiotics forces the continued development of new antibiotics and antibacterial agents, but the high costs and long timeframe involved in the development of new agents renders the hope that existing antibiotics may again play a part. The "antibiotic adjuvant" is an indirect antibacterial strategy, but its vague concept has, in the past, limited the development speed of related drugs. In this review article, we put forward an accurate concept of a "non-self-antimicrobial sensitisers (NSAS)", to distinguish it from an "antibiotic adjuvant", and then discuss several scientific methods to restore bacterial sensitivity to antibiotics, and the sources and action mechanism of existing NSAS, in order to guide the development and further research of NSAS.

Dopaminergic and serotoninergic systems as preferential targets of the pyrethroid tefluthrin exposure in the rat brain.

The monoaminergic systems dopamine (DA) and serotonin (5-HT) play important roles in neuromodulation, such as motor control, cognitive, affective, and neuroendocrine functions. In the present research study, we addressed the hypothesis that exposure to Type I pyrethroid tefluthrin may specifically target the dopaminergic and serotoninergic systems. Tefluthrin could modify brain monoamine neurotransmitters, DA and 5-HT levels as well as dopaminergic and serotoninergic signaling pathways.

Oxidative stress and mitochondrial damage in lambda-cyhalothrin toxicity: A comprehensive review of antioxidant mechanisms.

Lambda-cyhalothrin, also known as cyhalothrin, is an efficient, broad-spectrum, quick-acting pyrethroid insecticide and acaricide and the most powerful pyrethroid insecticide in the world. However, there is increasing evidence that lambda-cyhalothrin is closely related to a variety of toxicity drawbacks (hepatotoxicity, nephrotoxicity, neurotoxicity and reproductive toxicity, among others) in non-target organisms, and oxidative stress seems to be the main mechanism of toxicity. This manuscript reviews the oxidative and mitochondrial damage induced by lambda-cyhalothrin and the signalling pathways involved in this process, indicating that oxidative stress occupies an important position in lambda-cyhalothrin toxicity.

Oxidative stress, the blood-brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants.

In recent years, growing awareness of the role of oxidative stress in brain health has prompted antioxidants, especially dietary antioxidants, to receive growing attention as possible treatments strategies for patients with neurodegenerative diseases (NDs). The most widely studied dietary antioxidants include active substances such as vitamins, carotenoids, flavonoids and polyphenols. Dietary antioxidants are found in usually consumed foods such as fresh fruits, vegetables, nuts and oils and are gaining popularity due to recently growing awareness of their potential for preventive and protective agents against NDs, as well as their abundant natural sources, generally non-toxic nature, and ease of long-term consumption.

Conjugated linoleic acid (CLA) as a functional food: Is it beneficial or not?

Conjugated linoleic acid (CLA) has attracted great attention in recent years as a popular class of functional food that is broadly used. It refers to a group of geometric and positional isomers of linoleic acid (LA) with a conjugated double bond. The main natural sources of CLA are dairy products, beef and lamb, whereas only trace amounts occur naturally in plant lipids.

Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells.

Cancer is a huge challenge for people worldwide. High reactive oxygen species (ROS) levels are a recognized hallmark of cancer and an important aspect of cancer treatment research. Abnormally elevated ROS levels are often attributable to alterations in cellular metabolic activities and increased oxidative stress, which affects both the development and maintenance of cancer.

Bifurcaria bifurcata extract exerts antioxidant effects on human Caco-2 cells.

The present research study investigated the potential protective effect of Bifurcaria bifurcata extract on cell viability and antioxidant defences of cultured human Caco-2 cells submitted to oxidative stress induced by tert-butylhydroperoxide (tert-BOOH). Aqueous extracts were firstly characterized in terms of total phenolic contents. Concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), generation of reactive oxygen species (ROS), nitric oxide (NO) production, antioxidant enzymes activities [NADPH quinone dehydrogenase 1 (NQO1) and glutathione S-transferase (GST)], caspase 3/7 activity and gene expression linked to apoptosis, proinflammation and oxidative stress signaling pathways were used as markers of cellular oxidative status.

The potential of CD38 protein as a target for autoimmune diseases.

Cluster of differentiation 38 (CD38) is a multifunctional cell surface protein involved in nicotinamide adenine dinucleotide (NAD) homeostasis in types of cells and tissues, which can be found in many immune cells and non-immune cells. Previous studies have shown that CD38 plays an important role in regulating innate immunity. Recently, many studies have revealed the importance of CD38 in autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes (T1D) and inflammatory bowel disease, among others.

Tefluthrin: metabolism, food residues, toxicity, and mechanisms of action.

Tefluthrin is a Type I pyrethroid insecticide widely used all over the world. Residues of tefluthrin in various agricultural and animal-derived products may be related to potential human health risks. Tefluthrin metabolism in mammals involves hydrolysis of the ester bond to form cyclopropane acid and 4-methylbenzyl alcohol moieties, followed by oxidation.

Neurotoxicity induced by the pyrethroid lambda-cyhalothrin: Alterations in monoaminergic systems and dopaminergic and serotoninergic pathways in the rat brain.

The effects of Type II pyrethroid lambda-cyhalothrin on dopamine (DA) and serotonin (5-HT) synthesis in rat brain regions (striatum, hippocampus, prefrontal cortex, hypothalamus and midbrain) were studied. Lambda-cyhalothrin (1, 4 and 8 mg/kg bw, oral gavage, 6 days) induced a decrease of DA, 5-HT and metabolites contents, in a brain regional- and dose-related manner. The major decreases in DA and 5-HT contents were observed in hippocampus and prefrontal cortex tissues.

The "steric-like" inhibitory effect and mechanism of doxycycline on florfenicol metabolism: Interaction risk.

Most of the studies on doxycycline (DOX) and florfenicol (FF) remain focused on the improvement of antimicrobial activity and antimicrobial spectrum, and there is no relevant report on whether there is interaction between the two drugs after the combination. This research study evaluated the effect of DOX on FF metabolism in vitro and its mechanisms. The findings of this study showed that DOX inhibits FF metabolism in two ways.

Nicotinamide N-methyltransferase protects against deoxynivalenol-induced growth inhibition by suppressing pro-inflammatory cytokine expression.

Deoxynivalenol (DON) is an inevitable contaminant in cereals for infants. Indeed, children's growth retardation caused by widespread DON pollution has become a global problem that cannot be ignored. Accumulating evidence has shown that DON stunts growth in children through pro-inflammatory cytokines.

Neonicotinoids: mechanisms of systemic toxicity based on oxidative stress-mitochondrial damage.

Neonicotinoids are the most widely used pesticides in the world. However, research studies have shown that it can affect the cognitive abilities and health of non-target bees and other wild pollinators by inducing DNA damage, apoptosis and mitochondrial damage, injure to its central nervous system, and it is even developmentally neurotoxic to mammals and humans, with mitochondria being an important target of neonicotinoids. Therefore, this article reviews the role of mitochondrial morphology, calcium ions (Ca) homeostasis, respiratory function, apoptosis, and DNA damage in neonicotinoids-induced systemic toxicity.

Toxicity induced by ciprofloxacin and enrofloxacin: oxidative stress and metabolism.

Ciprofloxacin (CIP) (human use) and enrofloxacin (ENR) (veterinary use) are synthetic anti-infectious medications that belong to the second generation of fluoroquinolones. They have a wide antimicrobial spectrum and strong bactericidal effects at very low concentrations via enzymatic inhibition of DNA gyrase and topoisomerase IV, which are required for DNA replication. They also have high bioavailability, rapid absorption with favorable pharmacokinetics and excellent tissue penetration, including cerebral spinal fluid.

Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications.

Metformin is the oldest and most commonly used first-line antidiabetic drug because of its good clinical efficacy, high safety, low cost and easy access. At the same time, in recent years, we have found that its role as a therapeutic drug is gradually expanding. A large number of basic studies have shown that metformin may become a promising attractive candidate for drug repurposing.

Oxidative Stress and Metabolism: A Mechanistic Insight for Glyphosate Toxicology.

Glyphosate (GLYP) is a widely used pesticide; it is considered to be a safe herbicide for animals and humans because it targets 5-enolpyruvylshikimate-3-phosphate synthase. However, there has been increasing evidence that GLYP causes varying degrees of toxicity. Moreover, oxidative stress and metabolism are highly correlated with toxicity.

Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats ().

When two drugs are combined, drug-drug interactions (DDI) often occur. Metabolic DDI usually occur due to inhibition of the metabolism of one drug by the other. This leads to an increase in the plasma concentration of the drug whose metabolism is inhibited.

The NO-dependent caspase signaling pathway is a target of deoxynivalenol in growth inhibition in vitro.

DON is commonly found in foods and feeds; it presents health risks, especially an increase of growth inhibition in humans, particularly infants and young children. However, there are relatively few research studies devoted to the mechanism of DON-mediated growth retardation. Interestingly, our results showed that DON does not cause any significant production of ROS but results in a persistent and significant release of NO with iNOS increasing activity, mitochondrial ultrastructural changes and decreasing ΔΨm.

A "Janus" face of the RASSF4 signal in cell fate.

RASSF4 (Ras-association domain family 4) is a protein-coding gene, regarded as a tumor suppressor regulated by DNA methylation. However, RASSF4 acts as a "Janus" in cell fate: death and survival. This review article focuses on the regulatory mechanisms of RASSF4 on cell death and cell survival and puts forward a comprehensive analysis of the relevant signaling pathways.

Brown marine algae Gongolaria baccata extract protects Caco-2 cells from oxidative stress induced by tert-butyl hydroperoxide.

Gongolaria baccata (S.G. Gmelin) is marine brown seaweed mainly found on the coasts of the Baltic Sea south to the Mediterranean Sea, Canary Islands, Mauritania and Western Sahara.

Environmental impact assessment of COVID-19 therapeutic solutions. A prospective analysis.

Several medicinal products for human use are currently under consideration as potential treatment for COVID-19 pandemic. As proposals cover also prophylactic use, the treatment could be massive, resulting in unprecedent levels of antiviral emissions to the aquatic environment. We have adapted previous models and used available information for predicting the environmental impact of representative medicinal products, covering the main groups under consideration: multitarget antiparasitic (chloroquines and ivermectin), glucocorticoids, macrolide antibiotics and antiviral drugs including their pharmacokinetic boosters.

Synthetic phenolic antioxidants: Metabolism, hazards and mechanism of action.

Synthetic phenolic antioxidants can interact with peroxides produced by food. This paper reviews correlation between BHA, BHT and TBHQ metabolism and harms they cause and provides a theoretical basis for rational use of BHA, BHT and TBHQ in food, and also put some attention on the transformation and metabolic products of PG. We introduce BHA, BHT, TBHQ, PG and their possible metabolic pathways, and discuss possible harms and their specific mechanisms responsible.