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Dietary exposure to aflatoxin B1 (AFB1) is harmful to the health and performance of domestic animals. The hepatic cytochrome P450s (CYPs), CYP1A1 and CYP2A6, are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide (AFBO) in chicks. However, the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown. Dual-luciferase reporter assay, bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region −1,063/−948, −606/−541 of the CYP1A1 promoter as well as −636/−595, −503/−462, −147/−1 of the CYP2A6 promoter. Furthermore, overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6. Moreover, bioactivation of AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion of AP-1, rather than SP1, stimulated by AFB1-induced reactive oxygen species. Additionally, nano-selenium could reduce ROS, downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6, thus alleviating the toxicity of AFB1. In conclusion, AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver, which could provide novel targets for the remediation of aflatoxicosis in chicks. [ABSTRACT FROM AUTHOR]

The increasing pollution of ecosystems by both biological and non-biological contaminants has recently fostered the rapid development of biosensors, thus opening a new investigation area in analytical sciences. Here, we review the applications of immunosensors in food safety, human health, environmental sciences, water pollution, and agriculture. We present the analysis of cancer markers, pathogens, antigens, antibiotics, pesticides, toxins, allergens, hormones, and phytohormones. Immunosensors comprise electrochemical, microgravimetric, optical, and thermometric immunosensors. Immunosensors have advantages such as enhanced sensitivity, selectivity, speed, and cost-effectiveness. In particular, antibody-based biosensors have outperformed traditional methods in identifying and analysing various compounds. Immunosensors are able to detect compounds at nanomolar to picomolar levels. [ABSTRACT FROM AUTHOR]

Key message: CitCAT1 and CitCAT2 were cloned and highly expressed in mature leaves. High temperatures up-regulated CitCAT1 expression, while low temperatures and Diversispora versiformis up-regulated CitCAT2 expression, maintaining a low oxidative damage. Catalase (CAT), a tetrameric heme-containing enzyme, removes hydrogen peroxide (H2O2) to maintain low oxidative damage in plants exposed to environmental stress. This study aimed to clone CAT genes from Citrus sinensis cv. “Oita 4” and analyze their expression patterns in response to environmental stress, exogenous abscisic acid (ABA), and arbuscular mycorrhizal fungal inoculation. Two CAT genes, CitCAT1 (NCBI accession: PP067858) and CitCAT2 (NCBI accession: PP061394) were cloned, and the open reading frames of their proteins were 1479 bp and 1539 bp, respectively, each encoding 492 and 512 amino acids predicted to be localized in the peroxisome, with CitCAT1 being a stable hydrophilic protein and CitCAT2 being an unstable hydrophilic protein. The similarity of their amino acid sequences reached 83.24%, and the two genes were distantly related. Both genes were expressed in stems, leaves, flowers, and fruits, accompanied by the highest expression in mature leaves. In addition, CitCAT1 expression was mainly up-regulated by high temperatures (37 °C), exogenous ABA, and PEG stress within a short period of time, whereas CitCAT2 expression was up-regulated by exogenous ABA and low-temperature (4 °C) stress. Low temperatures (0 °C) for 12 h just up-regulated CitCAT2 expression in Diversispora versiformis-inoculated plants, and D. versiformis inoculation up-regulated CitCAT2 expression, along with lower hydrogen peroxide and malondialdehyde levels in mycorrhizal plants at low temperatures. It is concluded that CitCAT2 has an important role in resistance to low temperatures as well as mycorrhizal enhancement of host resistance to low temperatures. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal fungi (AMF) in the soil have many positive effects on growth, nutrient acquisition, and stress tolerance of host plants, as well as soil fertility, soil structure, and soil ecology. Glomalin-related soil proteins (GRSP) are a mixture of humic substances and heat-stable glycoproteins, primarily of AMF origin. GRSP are as an important component of soil organic carbon (C) pools, which can stabilize and sequestrate C, thus reducing soil C emissions for slowing down global warming. Based on the CiteSpace software and the core collection of Web of Science as the database, this study made a visual analysis of GRSP's literature in the C field published from 1999 to 2022, including the number of publications, countries, institutions, co-cited literature, keywords, top cited papers, etc. The study regarding the GRSP in the C field could be divided into the initial stage (1999–2009), the steady stage (2010–2018), and the explosive stage (2019–2022). The Chinese Academy of Sciences is the organization with the most publications, and the United States, China, and India are the three leading nations in the C field of GRSP. However, there was little collaboration among the participating countries and the study's institutions. The focus of the research has shifted from the composition and content of GRSP in C to the question of whether C in GRSP affects soil properties. Future research was also prospected. [ABSTRACT FROM AUTHOR]

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals. [ABSTRACT FROM AUTHOR]

The misuse of novichok agents in assassination attempts has been reported in the international media since 2018. These relatively new class of neurotoxic agents is claimed to be more toxic than the agents of the G and V series and so far, there is no report yet in literature about potential antidotes against them. To shed some light into this issue, we report here the design and synthesis of NTMGMP, a surrogate of A-242 and also the first surrogate of a novichok agent useful for experimental evaluation of antidotes. Furthermore, the efficiency of the current commercial oximes to reactivate NTMGMP-inhibited acetylcholinesterase (AChE) was evaluated. The Ellman test was used to confirm the complete inhibition of AChE, and to compare the subsequent rates of reactivation in vitro as well as to evaluate aging. In parallel, molecular docking, molecular dynamics and MM-PBSA studies were performed on a computational model of the human AChE (HssAChE)/NTMGMP complex to assess the reactivation performances of the commercial oximes in silico. Experimental and theoretical studies matched the exact hierarchy of efficiency and pointed to trimedoxime as the most promising commercial oxime for reactivation of AChE inhibited by A-242. [ABSTRACT FROM AUTHOR]

Aging is a progressive, unalterable physiological degradation process of living organisms, which leads to deterioration of biological function and eventually to senescence. The most prevalent factor responsible for aging is the accumulation of damages resulting from oxidative stress and dysbiosis. D-galactose-induced aging has become a hot topic, and extensive research is being conducted in this area. Published literature has reported that the continuous administration of D-galactose leads to the deterioration of motor and cognitive skills, resembling symptoms of aging. Hence, this procedure is employed as a model for accelerated aging. This review aims to emphasize the effect of D-galactose on various bodily organs and underline the role of the Lactobacillus sp. in the aging process, along with its anti-oxidative potential. A critical consideration to the literature describing animal models that have used the Lactobacillus sp. in amending D-galactose-induced aging is also given. Key points: • D-Galactose induces the aging process via decreasing the respiratory chain enzyme activity as well as ATP synthesis, mitochondrial dysfunction, and increased ROS production. • D-Galactose induced aging primarily affects the brain, heart, lung, liver, kidney, and skin. • The anti-oxidative potential of Lactobacillus sp. in improving D-galactose-induced aging in animal models via direct feeding and feeding of Lactobacillus-fermented food. [ABSTRACT FROM AUTHOR]

An innovative amperometric immunosensor has been developed to detect antibiotic colistin from the chicken liver. Colistin is a antibacterial peptide that has been barred for human consumption, but it is being commonly used as a veterinary drug, and as a feed additive for livestock. In the present work, an immunosensor was developed by immobilizing an anti-colistin Ab onto the CNF/AuNPs surface of the screen-printed electrode. The sensor records electrochemical response in the chicken liver spiked with colistin with CV. Additionally, the characterization of electrode surface was done with FE-SEM, FTIR, and EIS at each step of fabrication. The lower LOD was 0.89 μgKg−1, with a R2 of 0.901 using CV. Further validation of the immunosensor was conducted using commercial chicken liver samples, by comparing the results to those obtained using traditional methods. The fabricated immunosensor showed high specificity towards colistin, which remained stable for 6 months but with a 13% loss in the initial CV current. [ABSTRACT FROM AUTHOR]

Presence and functional roles of arbuscular mycorrhizal (AM) fungi in wetland environment have gained a global importance in recent past. Wetlands build a low-oxygen atmosphere, forming a completely different ecological environment for AM fungi, known more to occur in terrestrial environment. Nevertheless, as many 101 of AM fungi species, belonging to 19 genera and 9 families have been observed in the rhizosphere of wetland plants. In order to obtain oxygen, AM fungi expand the aeration system of wetland plants, store oxygen through their own vesicles, or change the structure of AM to survive. Human activities negatively affect the wetland environment, thus, reducing the population of AM fungi, while certain AM fungi species still improved the survival and development of wetland plants. AM fungi regulate different physiological activities of wetland plants in response to waterlogging stress, including an enhancement of antioxidant defense system, increased proline accumulation, improved plant growth and root morphology, responses of nutrients and aquaporins, and suppression in ethanol accumulation. The current review briefly summarized different species of wetland plants forming AM structures, the population of AM fungi inhabiting the rhizosphere of wetland plant, AM fungi-colonization of wetland plants, and the effect of AM fungi on physiological functions of wetland plants to neutralize the negative impact of waterlogging in addition to outlook of researchable issues. This review also highlighted human impacts on AM fungi of wetland plants and the impact of AM fungi on wetland environments and wetland plants. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal fungi (AMF) reduce disease incidence of host plants through the competition of carbon sources and direct inhibition of pathogens, as well as through induction of biochemical and molecular responses. However, it is not known whether AMF enhance the resistance to Phytophthora parasitica-induced root rot in citrus and what the underlying mechanisms are. This study was carried out to analyze roles of Funneliformis mosseae (a mycorrhizal fungus) in plant defence responses of Poncirus trifoliata infected by P. parasitica. A week after the pathogen infection, mycorrhizal seedlings possessed higher expression of root mitogen-activated protein kinase 3 (PtMAPK3) regardless of P. parasitica infection. F. mosseae induced higher root salicylic acid (SA) concentrations, accompanied with up-regulation of SA synthesis genes (PtPAL1 and PtEPS1), regardless of being infected with P. parasitica or not. Jasmonic acid (JA) synthesis genes were down-regulated by mycorrhization in the absence of P. parasitica and up-regulated (except for PtAOC) by mycorrhization under P. parasitica infection. Moreover, F. mosseae stimulated higher expression of pathogenesis-related protein gene 1 (PtPR1), PtPR4, and PtPR5, especially under P. parasitica infection. F. mosseae inoculation increased levels of root lignin, calmodulin, and total soluble phenol and activities of root chitinase, phenylalanine ammonialyase, and β-1,3-glucanase, and decreased concentrations of root nitric oxide with or without P. parasitica infection. These results implied that F. mosseae elicited MAPKs cascades as well as SA- and calmodulin-mediated signal pathways to activate disease-defence genes, proteins, and compounds to early-warn P. parasitica infection for enhancing tolerance of root rot in trifoliate orange. [ABSTRACT FROM AUTHOR]

The role of the immune system as an integral component of the inflammatory response in the pathophysiology of migraine remains unclear. The aim of this study was to evaluate the differences in immune system parameters (acquired immunity parameters) in patients with episodic migraine (EM) and in healthy controls. In EM patients, we aimed to determine whether the changes found in peripheral blood parameters were related to migraine severity according to the standardised MIDAS and HIT-6 tests. Forty-nine patients with EM and 50 healthy controls were included in this study. The authors compared different lymphocyte parameters obtained by multicolor flow cytometry in the EM and control groups by performing statistical tests. The relationship between the changes in peripheral blood parameters and migraine severity in EM patients was investigated using correlation and regression analysis. EM patients showed higher values than healthy controls, especially in nine parameters: relative count of lymphocytes, relative and absolute counts of CD3 T cells, relative and absolute counts of CD8 suppressor cytotoxic T cells, relative and absolute counts of CD4 + TEMRA (terminally differentiated helper T lymphocytes), absolute count of CD8 naïve T cells, and absolute count of CD19 switched memory B cells. Among the lymphocyte parameters, CD4 + TEM (effector memory helper T lymphocytes) and CD8 + TEMRA (terminally differentiated cytotoxic T lymphocytes) were statistically significantly associated with HIT-6. Patients with a CD4 + TEM value below 15 had a high probability (90%) that the HIT-6 value would be higher than 60. The results of this study show that EM patients have changes in immune system parameters measured in the peripheral blood. Changes in the abundance of CD4 + TEM could be used as a biomarker for disease severity. [ABSTRACT FROM AUTHOR]

Current demographic trends indicate that there is a growing number of older population groups worldwide, which is associated with an increase of chronic neurological disorders such as Parkinson's disease that burdens the country's healthcare system. Therefore there is an urgent call for developing efficient strategies which could reduce the healthcare costs and meet the demand of older people affected by these chronic neurological diseases at affordable cost. One of such approaches is the exploitation of a new emerging platform in the form of Internet of Things (IoT), which takes advantage of the connection of any physical object, for example a smartphone, to the Internet. The purpose of this study is to explore the use of IoT in the management of Parkinson's disease (PD), specifically in its assessment, diagnostics, and treatment. The methods used in this study include a literature review of available sources found in the world's acknowledged databases Web of Science, Scopus, PubMed, and ScienceDirect, as well as the methods of comparison and evaluation of the findings from the selected studies. The findings show that IoT may serve as an appropriate healthcare platform. IoT seems to be efficient, cost-effective and affordable approach in the management of chronic neurological disorders such as PD. However, more research has to be done by conducting more randomized controlled trials with larger samples of subjects in the area of the use of IoT in PD, as well as in other chronic neurological diseases. [ABSTRACT FROM AUTHOR]

Background: In the sense of Act No. 123/2000 Coll., as amended (hereinafter referred to as "the Act"), a medical device is understood to be a wide range of resources, especially medical equipment. To implement innovative technologies in practice, it is becoming extremely important to be cost-conscious and effective. The aim of the article is to use an ultrasonographic device case study in a selected hospital to show the possibility of solving the use effectiveness of medical devices. Methods: Within the first step, a summary of the use of ultrasonographic devices is developed in terms of performance number and time. Also, a summary of all costs for the last 5 years has been created. The analyzed ultrasonographic device set is evaluated in terms of activity indicators, profitability, and Du Pont decomposition. Revenues from the operation of individual instruments and payroll productivity are taken into account. All of this is evaluated in the context of the requirements of the department and the spectrum of ultrasonographic devices. Results: The results show that the economic evaluation of device use efficiency, comparing the requirements of the department and spectrum of the devices, suggests a major revision in use of these devices and savings. Conclusion: The new design of the most profitable system differs significantly in the arrangement of individual ultrasonographic devices. The benefit of the study is not just a newly designed organization-specific arrangement, but it can be perceived as a modeling approach that can be used to analyze other sets of medical technology. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON), the most commonly occurring trichothecene in nature, may affect animal and human health through causing diarrhea, vomiting, gastrointestinal inflammation, and immunomodulation. DON-3-glucoside (DON-3G) as a major plant metabolite of the mycotoxin is another 'emerging' food safety issue in recent years. Humans may experience potential health risks by consuming DON-contaminated food products. Thus, it is crucial for human and animal health to study also the degradation of DON and DON-3G during thermal food processing. Baking, boiling, steaming, frying, and extrusion cooking are commonly used during thermal food processing and have promising effects on the reduction of mycotoxins in food. For DON, however, the observed effects of these methods, as reported in numerous studies, are ambiguous and do not present a clear picture with regard to reduction or transformation. This review summarized the influence of thermal processing on the stability of DON and the formation of degradation/conversion products. Besides this, also a release of DON and DON-3G from food matrix as well as the release of DON from DON-3G during processing is discussed. In addition, some conflicting findings as reported from the studies on thermal processing as well as cause-effect relationships of the different thermal procedures are explored. Finally, the potential toxic profiles of DON degradation products are discussed as well when data are available. [ABSTRACT FROM AUTHOR]

Spirulina is a species of filamentous cyanobacteria that has long been used as a food supplement. In particular, Spirulina platensis and Spirulina maxima are the most important. Thanks to a high protein and vitamin content, Spirulina is used as a nutraceutical food supplement, although its other potential health benefits have attracted much attention. Oxidative stress and dysfunctional immunity cause many diseases in humans, including atherosclerosis, cardiac hypertrophy, heart failure, and hypertension. Thus, the antioxidant, immunomodulatory, and anti-inflammatory activities of these microalgae may play an important role in human health. Here, we discuss the antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina in both animals and humans, along with the underlying mechanisms. In addition, its commercial and regulatory status in different countries is discussed as well. Spirulina activates cellular antioxidant enzymes, inhibits lipid peroxidation and DNA damage, scavenges free radicals, and increases the activity of superoxide dismutase and catalase. Notably, there appears to be a threshold level above which Spirulina will taper off the antioxidant activity. Clinical trials show that Spirulina prevents skeletal muscle damage under conditions of exercise-induced oxidative stress and can stimulate the production of antibodies and up- or downregulate the expression of cytokine-encoding genes to induce immunomodulatory and anti-inflammatory responses. The molecular mechanism(s) by which Spirulina induces these activities is unclear, but phycocyanin and β-carotene are important molecules. Moreover, Spirulina effectively regulates the ERK1/2, JNK, p38, and IκB pathways. This review provides new insight into the potential therapeutic applications of Spirulina and may provide new ideas for future studies. [ABSTRACT FROM AUTHOR]

Transition metal ions are key elements of various biological processes ranging from oxygen formation to hypoxia sensing, and therefore, their homeostasis is maintained within strict limits through tightly regulated mechanisms of uptake, storage and secretion. The breakdown of metal ion homeostasis can lead to an uncontrolled formation of reactive oxygen species, ROS (via the Fenton reaction, which produces hydroxyl radicals), and reactive nitrogen species, RNS, which may cause oxidative damage to biological macromolecules such as DNA, proteins and lipids. An imbalance between the formation of free radicals and their elimination by antioxidant defense systems is termed oxidative stress. Most vulnerable to free radical attack is the cell membrane which may undergo enhanced lipid peroxidation, finally producing mutagenic and carcinogenic malondialdehyde and 4-hydroxynonenal and other exocyclic DNA adducts. While redox-active iron (Fe) and copper (Cu) undergo redox-cycling reactions, for a second group of redox-inactive metals such as arsenic (As) and cadmium (Cd), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. While arsenic is known to bind directly to critical thiols, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. Redox-inert zinc (Zn) is the most abundant metal in the brain and an essential component of numerous proteins involved in biological defense mechanisms against oxidative stress. The depletion of zinc may enhance DNA damage by impairing DNA repair mechanisms. Intoxication of an organism by arsenic and cadmium may lead to metabolic disturbances of redox-active copper and iron, with the occurrence of oxidative stress induced by the enhanced formation of ROS/RNS. Oxidative stress occurs when excessive formation of ROS overwhelms the antioxidant defense system, as is maintained by antioxidants such as ascorbic acid, alpha-tocopherol, glutathione (GSH), carotenoids, flavonoids and antioxidant enzymes which include SOD, catalase and glutathione peroxidase. This review summarizes current views regarding the role of redox-active/inactive metal-induced formation of ROS, and modifications to biomolecules in human disease such as cancer, cardiovascular disease, metabolic disease, Alzheimer's disease, Parkinson's disease, renal disease, blood disorders and other disease. The involvement of metals in DNA repair mechanisms, tumor suppressor functions and interference with signal transduction pathways are also discussed. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a group B trichothecene and a common contaminant of crops worldwide. This toxin is known to cause a spectrum of diseases in animals and humans such as vomiting and gastroenteritis. Importantly, DON could inhibit the synthesis of protein and nucleonic acid and induce cell apoptosis in eukaryote cells. The transduction of signaling pathways is involved in the underlying mechanism of the cytotoxicity of DON. Mitogen-activated protein kinase and Janus kinase/signal transducer and activator of transcription seem to be two important signaling pathways and induce the inflammatory response by modulating the binding activates of specific transcription factors. This review mainly discussed the toxic mechanism of DON from the vantage point of signaling pathways and also assessed the profiles of DON and its metabolites in humans. Importantly, we conducted a human exposure risk assessment of DON from cereals, cereal-based foods, vegetables, water, and animal-derived foods in different countries. Some regular patterns of DON occurrence in these countries are suggested based on an analysis of global contamination with DON. This review should provide further insight for the toxic mechanism study of DON and human exposure risk assessment, thereby facilitating mycotoxin control strategies. [ABSTRACT FROM AUTHOR]

Aflatoxins are potent hepatocarcinogen in animal models and suspected carcinogen in humans. The most important aflatoxin in terms of toxic potency and occurrence is aflatoxin B1 (AFB1). In this review, we mainly summarized the key metabolizing enzymes of AFB1 in animals and humans. Moreover, the interindividual and the interspecies differences in AFB1 metabolism are highly concerned. In human liver, CYP3A4 plays an important role in biotransforming AFB1 to the toxic product AFB1-8,9-epoxide. In human lung, CYP2A13 has a significant activity in metabolizing AFB1 to AFB1-8,9-epoxide and AFM1-8,9-epoxide. The epoxide of AFB1-8,9-epoxide could conjugate with glutathione to reduce the toxicity by glutathione-S-transferase (GST). In poultry species, CYP2A6, CYP3A37, CYP1A5, and CYP1A1 are responsible for bioactivation of AFB1. There are interindividual variations in the rate of activation of aflatoxins in various species, and there are also differences between children and adults. The age and living regions are important factors affecting resistance of species to AFB1. The rate of AFB1-8,9-epoxide formation and its conjugation with glutathione are key parameters in interspecies and interindividual differences in sensitivity to the toxic effect of AFB1. This review provides an important information for key metabolizing enzymes and the global metabolism of aflatoxins in different species. [ABSTRACT FROM AUTHOR]

Trichothecenes are a large family of structurally related toxins mainly produced by Fusarium genus. Among the trichothecenes, T-2 toxin and deoxynivalenol (DON) cause the most concern due to their wide distribution and highly toxic nature. Trichothecenes are known for their inhibitory effect on eukaryotic protein synthesis, and oxidative stress is one of their most important underlying toxic mechanisms. They are able to generate free radicals, including reactive oxygen species, which induce lipid peroxidation leading to changes in membrane integrity, cellular redox signaling, and in the antioxidant status of the cells. The mitogen-activated protein kinases signaling pathway is induced by oxidative stress, which also induces caspase-mediated cellular apoptosis pathways. Several new metabolites and novel metabolic pathways of T-2 toxin have been discovered very recently. In human cell lines, HT-2 and neosolaniol (NEO) are the major metabolites of T-2 toxin. Hydroxylation on C-7 and C-9 are two novel metabolic pathways of T-2 toxin in rats. The metabolizing enzymes CYP3A22, CYP3A29, and CYP3A46 in pigs, as well as the enzymes CYP1A5 and CYP3A37 in chickens, are able to catalyze T-2 toxin and HT-2 toxin to form the C-3′-OH metabolites. Similarly to carboxylesterase, CYP3A29 possesses the hydrolytic ability in pigs to convert T-2 toxin to NEO. T-2 toxin is able to down- or upregulate cytochrome P-450 enzymes in different species. The metabolism of DON in humans is region-dependent. Free DON and DON-glucuronide are considered to be the biomarkers for humans. The masked mycotoxin DON-3-β- d-glucoside can be hydrolyzed to free DON in the body. This review will provide useful information on the progress of oxidative stress as well as on the metabolism and the metabolizing enzymes of T-2 toxin and DON. Moreover, the literature will throw light on the blind spots of metabolism and toxicological studies in trichothecenes that have to be explored in the future. [ABSTRACT FROM AUTHOR]

Highlights: The goal is to optimize the microsponge drug delivery system's preparation. Scaling up ensures product repeatability. FTIR, DSC, and SEM confirmed the drug-loaded microsponge particles' compatibility and porous shape. The final gel dosage had shear-thinning rheology, suggesting dermal use. Ultimately, it supports and advances the UN's sustainable development goals and G20. In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5–300 μm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative. [ABSTRACT FROM AUTHOR]

Certain AChE reactivators, asoxime, obidoxime, K027, K048, and K075, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the different organs. As a continuation of previously published data, in this study, Wistar rats have sacrificed 24 hrs and 7 days after single im application of 0.1LD50, 0.5LD50 and 1.0LD50 of each reactivator, and examinated tissue samples were obtained for pathohistological and semiquantitative analysis. A severity of tissue alteration, expressed as different tissue damage scores were evaluated. Morphological structure of examinated tissues treated with of 0.1LD50 of all reactivators was comparable with the control group of rats. Moderate injuries were seen in visceral tissues treated with 0.5LD50 of asoxime, obidoxime and K027. Acute damages were enlarged after treatment with 0.5LD50 and 1.0LD50 of all reactivators during the next 7 days. The most prominent changes were seen in rats treated with 1.0LD50 of K048 and K075 (P < 0.001 vs. control and asoxime-treated group). All reactivators given by a single, high, unitary dose regimen, have an adverse effect not only on the main visceral tissue, but on the whole rat as well, but the exact mechanism of cellular injury remains to be confirmed in further investigation. [ABSTRACT FROM AUTHOR]

Therapeutic application of newly developed oximes is limited due to their adverse effects on different tissues. Within this article, it has been investigated which morphological changes could be observed in Wistar rats after the treatment with increasing doses of selected acetyl cholinesterase reactivators - asoxime, obidoxime, K027, K048, and K075. Subsequently, heart, diaphragm and musculus popliteus were obtained for pathohistological and semiquantitative analysis 24 hrs and 7 days after im administration of a single dose of 0.1 LD50, 0.5 LD50, and 1.0 LD50 of each oxime. Different muscle damage score was based on an estimation scale from 0 (no damage) to 5 (strong damage). In rats treated with 0.1 LD50 of each oxime, muscle fibres did not show any change. The intensive degeneration was found in all muscles after treatment with 0.5 LD50 of asoxime and obidoxime, respectively. Acute toxic muscle injury was developed within 7 days following treatment with 0.5 LD50 and 1.0 LD50 of each oxime, with the highest values in K048 and K075 group (P < 0.001 vs. control and asoxime), respectively. The early muscle alterations observed in our study seem to contribute to the pathogenesis of the oxime-induced toxic muscle injury, which probably manifests as necrosis and/or inflammation. [ABSTRACT FROM AUTHOR]

This study is aimed to investigate whether simvastatin induces cardiomyocytes survival signaling in endotoxin (lipopolysaccharide, LSP)-induced myocardial injury, and if so, further to determine a role of survivin in simvastatin-anti-apoptotic effect. Wistar rats were pretreated with simvastatin (10-40 mg/kg po) before a single non-lethal dose of LPS. In myocardial tissue, LPS induced structural disorganization of myofibrils with significant inflammatory infiltrate (cardiac damage score, CDS = 3.87 ± 0.51, p < 0.05), whereas simvastatin dose-dependently abolished structural changes induced by LPS (p < 0.01). Simvastatin in 20 mg/kg and 40 mg/kg pretreatment, dose dependently, attenuated myocardial apoptosis determined as apoptotic index (28.8 ± 4.5% and 18.9 ± 3.5, p < 0.05), decreased cleaved caspase-3 expression (32.1 ± 5.8%, p < 0.01), along with significant Bcl-xL expression in the simvastatin groups (p < 0.01). Interestingly, in the simvastatin groups were determined significantly increased expression of survivin (p < 0.01), but in negative correlation with cleaved caspase-3 and apoptotic indices (p < 0.01). Simvastatin has a cardioprotective effects against LPS induced apoptosis. The effect may be mediated by up-regulation of survivin via activation of NF-κB, which leads to reduced activation of caspase-3 and consequent apoptosis of cardiomyocytes in experimental sepsis. [ABSTRACT FROM AUTHOR]

The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC “Annex on Chemicals” some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman’s assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed. [ABSTRACT FROM AUTHOR]

Both arsenic (As) and obesity are associated with brain disorders. However, long term studies to evaluate their concomitant adverse effects on the brain functions are lacking. Present study was conducted to evaluate the long term co-exposure of As and high fat diet (HFD) on memory and brain mitochondrial function in mice. Male mice were randomly divided into 7 groups fed with HFD or ordinary diet (OD) and instantaneously exposed to As (25 or 50 ppm) in drinking water for, 4, 8, 12, 16 or 20 weeks. Step-down passive avoidance method was used for memory assessment and post exposure various parameters including mitochondrial damage, level of reactive oxygen species (ROS), malondialdeid (MDA) and glutathione (GSH) were determined. Results indicated that the retention latency decreased in As (25 and 50 ppm) and HFD received mice after 12 and 16 weeks respectively. Same results were observed at significantly shorter duration (8th week) when As was administered along with HFD as compared to control group. In the HFD alone fed mice increased the mitochondrial membrane damage, levels of ROS and MDA were observed while GSH contents decreased significantly. Concomitant administration of HFD and As amplified those mentioned toxic effects (p < 0.001). In conclusion, our findings demonstrated that the simultaneous HFD and As impaired memory at least three times more than exposing each one alone. These toxic effects could be due to the mitochondria originated oxidative stress along with the depleted antioxidant capacity of the brain of mice. [ABSTRACT FROM AUTHOR]

The serine/threonine protein phosphatase type 5 (PP5) is a promising target for designing new antitumor drugs. This enzyme is a member of the PPP phosphatases gene family, which catalyzes a dephosphorylation reaction: a regulatory process in the signal transduction pathway that controls various biological processes. The aim of this work is to study and compare the inhibition of PP5 by ten cantharidin-like inhibitors in order to bring about contributions relevant to the better comprehension of their inhibitory activity. In this theoretical investigation, we used molecular dynamics techniques to understand the role of key interactions that occur in the protein active site; QM calculations were employed to study the interaction mode of these inhibitors in the enzyme. In addition, atoms in molecules (AIM) calculations were carried out to characterize the chemical bonds among the atoms involved and investigate the orbital interactions with their respective energy values. The obtained results suggest that the Arg275, Asn303, His304, His352, Arg400, His427, Glu428, Val429, Tyr451, and Phe446 residues favorably contribute to the interactions between inhibitors and PP5. However, the Asp271 and Asp244 amino acid residues do not favor such interactions for some inhibitors. Through the QM calculations, we can suggest that the reactional energy of the coordination mechanism of these inhibitors in the PP5 active site is quite important and is responsible for the inhibitory activity. The AIM technique employed in this work was essential to get a better comprehension of the transition states acquired from the mechanism simulation. This work offers insights of how cantharidin-like inhibitors interact with human PP5, potentially allowing the design of more specific and even less cytotoxic drugs for cancer treatments.Interactions of cantharidin-like inhibitors with human protein phosphatase-5 in a Mg2+ system [ABSTRACT FROM AUTHOR]