Showing papers in "Toxins in 2021"

Zearalenone and Its Metabolites-General Overview, Occurrence, and Toxicity

Abstract: Mycotoxins are secondary metabolites of filamentous fungi and represent one of the most common groups of food contaminants with low molecular weight. These toxins are considered common and can affect the food chain at various stages of production, harvesting, storage and processing. Zearalenone is one of over 400 detected mycotoxins and produced by fungi of the genus Fusarium; it mainly has estrogenic effects on various organisms. Contaminated products can lead to huge economic losses and pose risks to animals and humans. In this review, we systemize information on zearalenone and its major metabolites.

The Food Poisoning Toxins of Bacillus cereus

Abstract: Bacillus cereus is a ubiquitous soil bacterium responsible for two types of food-associated gastrointestinal diseases While the emetic type, a food intoxication, manifests in nausea and vomiting, food infections with enteropathogenic strains cause diarrhea and abdominal pain Causative toxins are the cyclic dodecadepsipeptide cereulide, and the proteinaceous enterotoxins hemolysin BL (Hbl), nonhemolytic enterotoxin (Nhe) and cytotoxin K (CytK), respectively This review covers the current knowledge on distribution and genetic organization of the toxin genes, as well as mechanisms of enterotoxin gene regulation and toxin secretion In this context, the exceptionally high variability of toxin production between single strains is highlighted In addition, the mode of action of the pore-forming enterotoxins and their effect on target cells is described in detail The main focus of this review are the two tripartite enterotoxin complexes Hbl and Nhe, but the latest findings on cereulide and CytK are also presented, as well as methods for toxin detection, and the contribution of further putative virulence factors to the diarrheal disease

The Impact of CKD on Uremic Toxins and Gut Microbiota.

Abstract: Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Abstract: Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.

Phthalic Acid Esters: Natural Sources and Biological Activities.

Abstract: Phthalic acid esters (PAEs) are a class of lipophilic chemicals widely used as plasticizers and additives to improve various products’ mechanical extensibility and flexibility. At present, synthesized PAEs, which are considered to cause potential hazards to ecosystem functioning and public health, have been easily detected in the atmosphere, water, soil, and sediments; PAEs are also frequently discovered in plant and microorganism sources, suggesting the possibility that they might be biosynthesized in nature. In this review, we summarize that PAEs have not only been identified in the organic solvent extracts, root exudates, and essential oils of a large number of different plant species, but also isolated and purified from various algae, bacteria, and fungi. Dominant PAEs identified from natural sources generally include di-n-butyl phthalate, diethyl phthalate, dimethyl phthalate, di(2-ethylhexyl) phthalate, diisobutyl phthalate, diisooctyl phthalate, etc. Further studies reveal that PAEs can be biosynthesized by at least several algae. PAEs are reported to possess allelopathic, antimicrobial, insecticidal, and other biological activities, which might enhance the competitiveness of plants, algae, and microorganisms to better accommodate biotic and abiotic stress. These findings suggest that PAEs should not be treated solely as a “human-made pollutant” simply because they have been extensively synthesized and utilized; on the other hand, synthesized PAEs entering the ecosystem might disrupt the metabolic process of certain plant, algal, and microbial communities. Therefore, further studies are required to elucidate the relevant mechanisms and ecological consequences.

Occurrence, Impact on Agriculture, Human Health, and Management Strategies of Zearalenone in Food and Feed: A Review.

Abstract: Mycotoxins represent an assorted range of secondary fungal metabolites that extensively occur in numerous food and feed ingredients at any stage during pre- and post-harvest conditions. Zearalenone (ZEN), a mycotoxin categorized as a xenoestrogen poses structural similarity with natural estrogens that enables its binding to the estrogen receptors leading to hormonal misbalance and numerous reproductive diseases. ZEN is mainly found in crops belonging to temperate regions, primarily in maize and other cereal crops that form an important part of various food and feed. Because of the significant adverse effects of ZEN on both human and animal, there is an alarming need for effective detection, mitigation, and management strategies to assure food and feed safety and security. The present review tends to provide an updated overview of the different sources, occurrence and biosynthetic mechanisms of ZEN in various food and feed. It also provides insight to its harmful effects on human health and agriculture along with its effective detection, management, and control strategies.

Botulinum Toxin in Movement Disorders: An Update

Abstract: Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved into a therapeutic modality for a variety of neurological and non-neurological disorders. With respect to neurologic movement disorders, BoNT has been reported to be effective for the treatment of dystonia, bruxism, tremors, tics, myoclonus, restless legs syndrome, tardive dyskinesia, and a variety of symptoms associated with Parkinson’s disease. More recently, research with BoNT has expanded beyond its use as a powerful muscle relaxant and a peripherally active drug to its potential central nervous system applications in the treatment of neurodegenerative disorders. Although BoNT is the most potent biologic toxin, when it is administered by knowledgeable and experienced clinicians, it is one of the safest therapeutic agents in clinical use. The primary aim of this article is to provide an update on recent advances in BoNT research with a focus on novel applications in the treatment of movement disorders. This comprehensive review of the literature provides a critical review of evidence-based clinical trials and highlights recent innovative pilot studies.

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments.

Abstract: Staphylococcus aureus is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. S. aureus has a high level of antibiotic resistance and is a common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA), combined with the important severity of S. aureus infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant S. aureus continues to be a major health concern, necessitating the development of novel therapeutic strategies. S. aureus uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize S. aureus toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.

Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation.

Abstract: In the early 1960s the discovery of aflatoxins began when a total of 100,000 turkey poults died by hitherto unknown turkey "X" disease in England. The disease was associated with Brazilian groundnut meal affected by Aspergillus flavus. The toxin was named Aspergillus flavus toxin-aflatoxin. From the point of view of agriculture, aflatoxins show the utmost importance. Until now, a total of 20 aflatoxins have been described, with B1, B2, G1, and G2 aflatoxins being the most significant. Contamination by aflatoxins is a global health problem. Aflatoxins pose acutely toxic, teratogenic, immunosuppressive, carcinogenic, and teratogenic effects. Besides food insecurity and human health, aflatoxins affect humanity at different levels, such as social, economical, and political. Great emphasis is placed on aflatoxin mitigation using biocontrol methods. Thus, this review is focused on aflatoxins in terms of historical development, the principal milestones of aflatoxin research, and recent data on their toxicity and different ways of mitigation.

Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses.

Abstract: For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC). The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body. Cannabis is used as a therapeutic agent for treating pain and emesis. Some cannabinoids are clinically applied for treating chronic pain, particularly cancer and multiple sclerosis-associated pain, for appetite stimulation and anti-emesis in HIV/AIDS and cancer patients, and for spasticity treatment in multiple sclerosis and epilepsy patients. Medical cannabis varies from recreational cannabis in the chemical content of THC and cannabidiol (CBD), modes of administration, and safety. Despite the therapeutic effects of cannabis, exposure to high concentrations of THC, the main compound that is responsible for most of the intoxicating effects experienced by users, could lead to psychological events and adverse effects that affect almost all body systems, such as neurological (dizziness, drowsiness, seizures, coma, and others), ophthalmological (mydriasis and conjunctival hyperemia), cardiovascular (tachycardia and arterial hypertension), and gastrointestinal (nausea, vomiting, and thirst), mainly associated with recreational use. Cannabis toxicity in children is more concerning and can cause serious adverse effects such as acute neurological symptoms (stupor), lethargy, seizures, and even coma. More countries are legalizing the commercial production and sale of cannabis for medicinal use, and some for recreational use as well. Liberalization of cannabis laws has led to increased incidence of toxicity, hyperemesis syndrome, lung disease cardiovascular disease, reduced fertility, tolerance, and dependence with chronic prolonged use. This review focuses on the potential therapeutic effects of cannabis and cannabinoids, as well as the acute and chronic toxic effects of cannabis use on various body systems.

Possibilities for the Biological Control of Mycotoxins in Food and Feed.

Abstract: Seeking useful biological agents for mycotoxin detoxification has achieved success in the last twenty years thanks to the participation of many multidisciplinary teams. We have recently witnessed discoveries in the fields of bacterial genetics (inclusive of next-generation sequencing), protein encoding, and bioinformatics that have helped to shape the latest perception of how microorganisms/mycotoxins/environmental factors intertwine and interact, so the road is opened for new breakthroughs. Analysis of literature data related to the biological control of mycotoxins indicates the ability of yeast, bacteria, fungi and enzymes to degrade or adsorb mycotoxins, which increases the safety and quality of susceptible crops, animal feed and, ultimately, food of animal origin (milk, meat and eggs) by preventing the presence of residues. Microbial detoxification (transformation and adsorption) is becoming a trustworthy strategy that leaves no or less toxic compounds and contributes to food security. This review summarizes the data and highlights the importance and prospects of these methods.

Mycotoxin Occurrence, Toxicity, and Detoxifying Agents in Pig Production with an Emphasis on Deoxynivalenol.

Abstract: This review aimed to investigate the occurrence of mycotoxins, their toxic effects, and the detoxifying agents discussed in scientific publications that are related to pig production. Mycotoxins that are of major interest are aflatoxins and Fusarium toxins, such as deoxynivalenol and fumonisins, because of their elevated frequency at a global scale and high occurrence in corn, which is the main feedstuff in pig diets. The toxic effects of aflatoxins, deoxynivalenol, and fumonisins include immune modulation, disruption of intestinal barrier function, and cytotoxicity leading to cell death, which all result in impaired pig performance. Feed additives, such as mycotoxin-detoxifying agents, that are currently available often combine organic and inorganic sources to enhance their adsorbability, immune stimulation, or ability to render mycotoxins less toxic. In summary, mycotoxins present challenges to pig production globally because of their increasing occurrences in recent years and their toxic effects impairing the health and growth of pigs. Effective mycotoxin-detoxifying agents must be used to boost pig health and performance and to improve the sustainable use of crops.

Physical and Chemical Methods for Reduction in Aflatoxin Content of Feed and Food.

Abstract: Aflatoxins (AFs) are among the most harmful fungal secondary metabolites imposing serious health risks on both household animals and humans. The more frequent occurrence of aflatoxins in the feed and food chain is clearly foreseeable as a consequence of the extreme weather conditions recorded most recently worldwide. Furthermore, production parameters, such as unadjusted variety use and improper cultural practices, can also increase the incidence of contamination. In current aflatoxin control measures, emphasis is put on prevention including a plethora of pre-harvest methods, introduced to control Aspergillus infestations and to avoid the deleterious effects of aflatoxins on public health. Nevertheless, the continuous evaluation and improvement of post-harvest methods to combat these hazardous secondary metabolites are also required. Already in-use and emerging physical methods, such as pulsed electric fields and other nonthermal treatments as well as interventions with chemical agents such as acids, enzymes, gases, and absorbents in animal husbandry have been demonstrated as effective in reducing mycotoxins in feed and food. Although most of them have no disadvantageous effect either on nutritional properties or food safety, further research is needed to ensure the expected efficacy. Nevertheless, we can envisage the rapid spread of these easy-to-use, cost-effective, and safe post-harvest tools during storage and food processing.

Acute Hepatopancreatic Necrosis Disease (AHPND): Virulence, Pathogenesis and Mitigation Strategies in Shrimp Aquaculture.

Abstract: Shrimp, as a high-protein animal food commodity, are one of the fastest growing food producing sectors in the world. It has emerged as a highly traded seafood product, currently exceeding 8 MT of high value. However, disease outbreaks, which are considered as the primary cause of production loss in shrimp farming, have moved to the forefront in recent years and brought socio-economic and environmental unsustainability to the shrimp aquaculture industry. Acute hepatopancreatic necrosis disease (AHPND), caused by Vibrio spp., is a relatively new farmed penaeid shrimp bacterial disease. The shrimp production in AHPND affected regions has dropped to ~60%, and the disease has caused a global loss of USD 43 billion to the shrimp farming industry. The conventional approaches, such as antibiotics and disinfectants, often applied for the mitigation or cure of AHPND, have had limited success. Additionally, their usage has been associated with alteration of host gut microbiota and immunity and development of antibiotic resistance in bacterial pathogens. For example, the Mexico AHPND-causing V. parahaemolyticus strain (13-306D/4 and 13-511/A1) were reported to carry tetB gene coding for tetracycline resistance gene, and V. campbellii from China was found to carry multiple antibiotic resistance genes. As a consequence, there is an urgent need to thoroughly understand the virulence mechanism of AHPND-causing Vibrio spp. and develop novel management strategies to control AHPND in shrimp aquaculture, that will be crucially important to ensure food security in the future and offer economic stability to farmers. In this review, the most important findings of AHPND are highlighted, discussed and put in perspective, and some directions for future research are presented.

Phytotoxic Secondary Metabolites from Fungi

Abstract: Fungal phytotoxic secondary metabolites are poisonous substances to plants produced by fungi through naturally occurring biochemical reactions. These metabolites exhibit a high level of diversity in their properties, such as structures, phytotoxic activities, and modes of toxicity. They are mainly isolated from phytopathogenic fungal species in the genera of Alternaria, Botrytis, Colletotrichum, Fusarium, Helminthosporium, and Phoma. Phytotoxins are either host specific or non-host specific phytotoxins. Up to now, at least 545 fungal phytotoxic secondary metabolites, including 207 polyketides, 46 phenols and phenolic acids, 135 terpenoids, 146 nitrogen-containing metabolites, and 11 others, have been reported. Among them, aromatic polyketides and sesquiterpenoids are the main phytotoxic compounds. This review summarizes their chemical structures, sources, and phytotoxic activities. We also discuss their phytotoxic mechanisms and structure–activity relationships to lay the foundation for the future development and application of these promising metabolites as herbicides.

Zearalenone and the Immune Response.

Abstract: Zearalenone (ZEA) is an estrogenic fusariotoxin, being classified as a phytoestrogen, or as a mycoestrogen. ZEA and its metabolites are able to bind to estrogen receptors, 17β-estradiol specific receptors, leading to reproductive disorders which include low fertility, abnormal fetal development, reduced litter size and modification at the level of reproductive hormones especially in female pigs. ZEA has also significant effects on immune response with immunostimulatory or immunosuppressive results. This review presents the effects of ZEA and its derivatives on all levels of the immune response such as innate immunity with its principal component inflammatory response as well as the acquired immunity with two components, humoral and cellular immune response. The mechanisms involved by ZEA in triggering its effects are addressed. The review cited more than 150 publications and discuss the results obtained from in vitro and in vivo experiments exploring the immunotoxicity produced by ZEA on different type of immune cells (phagocytes related to innate immunity and lymphocytes related to acquired immunity) as well as on immune organs. The review indicates that despite the increasing number of studies analyzing the mechanisms used by ZEA to modulate the immune response the available data are unsubstantial and needs further works.

Wasp Venom Biochemical Components and Their Potential in Biological Applications and Nanotechnological Interventions

Abstract: Wasps, members of the order Hymenoptera, are distributed in different parts of the world, including Brazil, Thailand, Japan, Korea, and Argentina. The lifestyles of the wasps are solitary and social. Social wasps use venom as a defensive measure to protect their colonies, whereas solitary wasps use their venom to capture prey. Chemically, wasp venom possesses a wide variety of enzymes, proteins, peptides, volatile compounds, and bioactive constituents, which include phospholipase A2, antigen 5, mastoparan, and decoralin. The bioactive constituents have anticancer, antimicrobial, and anti-inflammatory effects. However, the limited quantities of wasp venom and the scarcity of advanced strategies for the synthesis of wasp venom's bioactive compounds remain a challenge facing the effective usage of wasp venom. Solid-phase peptide synthesis is currently used to prepare wasp venom peptides and their analogs such as mastoparan, anoplin, decoralin, polybia-CP, and polydim-I. The goal of the current review is to highlight the medicinal value of the wasp venom compounds, as well as limitations and possibilities. Wasp venom could be a potential and novel natural source to develop innovative pharmaceuticals and new agents for drug discovery.

Botulinum Toxin: An Update on Pharmacology and Newer Products in Development

Abstract: Since its introduction as a treatment for strabismus, botulinum toxin (BoNT) has had a phenomenal journey and is now recommended as first-line treatment for focal dystonia, despite short-term clinical benefits and the risks of adverse effects. To cater for the high demand across various medical specialties, at least six US Food and Drug Administration (FDA)-approved formulations of BoNT are currently available for diverse labelled indications. The toxo-pharmacological properties of these formulations are not uniform and thus should not be used interchangeably. Synthetic BoNTs and BoNTs from non-clostridial sources are not far from clinical use. Moreover, the study of mutations in naturally occurring toxins has led to modulation in the toxo-pharmacokinetic properties of BoNTs, including the duration and potency. We present an overview of the toxo-pharmacology of conventional and novel BoNT preparations, including those awaiting imminent translation from the laboratory to the clinic.

Aflatoxin Detoxification Using Microorganisms and Enzymes

Abstract: Mycotoxin contamination causes significant economic loss to food and feed industries and seriously threatens human health. Aflatoxins (AFs) are one of the most harmful mycotoxins, which are produced by Aspergillus flavus, Aspergillus parasiticus, and other fungi that are commonly found in the production and preservation of grain and feed. AFs can cause harm to animal and human health due to their toxic (carcinogenic, teratogenic, and mutagenic) effects. How to remove AF has become a major problem: biological methods cause no contamination, have high specificity, and work at high temperature, affording environmental protection. In the present research, microorganisms with detoxification effects researched in recent years are reviewed, the detoxification mechanism of microbes on AFs, the safety of degrading enzymes and reaction products formed in the degradation process, and the application of microorganisms as detoxification strategies for AFs were investigated. One of the main aims of the work is to provide a reliable reference strategy for biological detoxification of AFs.

Key Global Actions for Mycotoxin Management in Wheat and Other Small Grains.

Abstract: Mycotoxins in small grains are a significant and long-standing problem. These contaminants may be produced by members of several fungal genera, including Alternaria, Aspergillus, Fusarium, Claviceps, and Penicillium. Interventions that limit contamination can be made both pre-harvest and post-harvest. Many problems and strategies to control them and the toxins they produce are similar regardless of the location at which they are employed, while others are more common in some areas than in others. Increased knowledge of host-plant resistance, better agronomic methods, improved fungicide management, and better storage strategies all have application on a global basis. We summarize the major pre- and post-harvest control strategies currently in use. In the area of pre-harvest, these include resistant host lines, fungicides and their application guided by epidemiological models, and multiple cultural practices. In the area of post-harvest, drying, storage, cleaning and sorting, and some end-product processes were the most important at the global level. We also employed the Nominal Group discussion technique to identify and prioritize potential steps forward and to reduce problems associated with human and animal consumption of these grains. Identifying existing and potentially novel mechanisms to effectively manage mycotoxin problems in these grains is essential to ensure the safety of humans and domesticated animals that consume these grains.

Biological Control and Mitigation of Aflatoxin Contamination in Commodities.

Abstract: Aflatoxins (AFs) are toxic secondary metabolites produced mostly by Aspergillus species. AF contamination entering the feed and food chain has been a crucial long-term issue for veterinarians, medicals, agroindustry experts, and researchers working in this field. Although different (physical, chemical, and biological) technologies have been developed, tested, and employed to mitigate the detrimental effects of mycotoxins, including AFs, universal methods are still not available to reduce AF levels in feed and food in the last decades. Possible biological control by bacteria, yeasts, and fungi, their excretes, the role of the ruminal degradation, pre-harvest biocontrol by competitive exclusion or biofungicides, and post-harvest technologies and practices based on biological agents currently used to alleviate the toxic effects of AFs are collected in this review. Pre-harvest biocontrol technologies can give us the greatest opportunity to reduce AF production on the spot. Together with post-harvest applications of bacteria or fungal cultures, these technologies can help us strictly reduce AF contamination without synthetic chemicals.

Bacterial Toxins Active against Mosquitoes: Mode of Action and Resistance

Abstract: Larvicides based on the bacteria Bacillus thuringiensis svar. israelensis (Bti) and Lysinibacillus sphaericus are effective and environmentally safe compounds for the control of dipteran insects of medical importance. They produce crystals that display specific and potent insecticidal activity against larvae. Bti crystals are composed of multiple protoxins: three from the three-domain Cry type family, which bind to different cell receptors in the midgut, and one cytolytic (Cyt1Aa) protoxin that can insert itself into the cell membrane and act as surrogate receptor of the Cry toxins. Together, those toxins display a complex mode of action that shows a low risk of resistance selection. L. sphaericus crystals contain one major binary toxin that display an outstanding persistence in field conditions, which is superior to Bti. However, the action of the Bin toxin based on its interaction with a single receptor is vulnerable for resistance selection in insects. In this review we present the most recent data on the mode of action and synergism of these toxins, resistance issues, and examples of their use worldwide. Data reported in recent years improved our understanding of the mechanism of action of these toxins, showed that their combined use can enhance their activity and counteract resistance, and reinforced their relevance for mosquito control programs in the future years.

Old World Vipers—A Review about Snake Venom Proteomics of Viperinae and Their Variations

Abstract: Fine-tuned by millions of years of evolution, snake venoms have frightened but also fascinated humanity and nowadays they constitute potential resources for drug development, therapeutics and antivenoms. The continuous progress of mass spectrometry techniques and latest advances in proteomics workflows enabled toxinologists to decipher venoms by modern omics technologies, so-called 'venomics'. A tremendous upsurge reporting on snake venom proteomes could be observed. Within this review we focus on the highly venomous and widely distributed subfamily of Viperinae (Serpentes: Viperidae). A detailed public literature database search was performed (2003-2020) and we extensively reviewed all compositional venom studies of the so-called Old-World Vipers. In total, 54 studies resulted in 89 venom proteomes. The Viperinae venoms are dominated by four major, four secondary, six minor and several rare toxin families and peptides, respectively. The multitude of different venomics approaches complicates the comparison of venom composition datasets and therefore we differentiated between non-quantitative and three groups of quantitative workflows. The resulting direct comparisons within these groups show remarkable differences on the intra- and interspecies level across genera with a focus on regional differences. In summary, the present compilation is the first comprehensive up-to-date database on Viperinae venom proteomes and differentiating between analytical methods and workflows.

Multi-Mycotoxin Contamination of Maize Silages in Flanders, Belgium: Monitoring Mycotoxin Levels from Seed to Feed

Abstract: Maize silage, which in Europe is the main feed for dairy cattle in winter, can be contaminated by mycotoxins. Mycotoxigenic Fusarium spp. originating from field infections may survive in badly sealed silages or re-infect at the cutting edge during feed-out. In this way, mycotoxins produced in the field may persist during the silage process. In addition, typical silage fungi such as Penicillium spp. and Aspergillus spp. survive in silage conditions and produce mycotoxins. In this research, 56 maize silages in Flanders were sampled over the course of three years (2016-2018). The concentration of 22 different mycotoxins was investigated using a multi-mycotoxin liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the presence of DNA of three Fusarium spp. (F. graminearum, F. culmorum and F. verticillioides) was analyzed in a selection of these samples using quantitative polymerase chain reaction (qPCR). Every maize silage contained at least two different mycotoxins. Nivalenol (NIV) and deoxynivalenol (DON) were the most prevalent (both in 97.7% of maize silages), followed by ENN B (88.7%). Concentrations often exceeded the EU recommendations for DON and zearalenone (ZEN), especially in 2017 (21.3% and 27.7% of the maize silages, respectively). No correlations were found between fungal DNA and mycotoxin concentrations. Furthermore, by ensiling maize with a known mycotoxin load in a net bag, the mycotoxin contamination could be monitored from seed to feed. Analysis of these net bag samples revealed that the average concentration of all detected mycotoxins decreased after fermentation. We hypothesize that mycotoxins are eluted, degraded, or adsorbed during fermentation, but certain badly preserved silages are prone to additional mycotoxin production during the stable phase due to oxygen ingression, leading to extremely high toxin levels.

Chronic Kidney Disease-Associated Pruritus.

Abstract: Pruritus is a distressing condition associated with end-stage renal disease (ESRD), advanced chronic kidney disease (CKD), as well as maintenance dialysis and adversely affects the quality of life (QOL) of these patients. It has been reported to range from 20% to as high as 90%. The mechanism of CKD-associated pruritus (CKD-aP) has not been clearly identified, and many theories have been proposed to explain it. Many risk factors have been found to be associated with CKD-aP. The pruritus in CKD presents with diverse clinical features, and there are no set features to diagnose it.The patients with CKD-aP are mainly treated by nephrologists, primary care doctors, and dermatologists. Many treatments have been tried but nothing has been effective. The search of literature included peer-reviewed articles, including clinical trials and scientific reviews. Literature was identified through March 2021, and references of respective articles and only articles published in the English language were included.

Antiviral Activity of Ribosome-Inactivating Proteins.

Abstract: Ribosome-inactivating proteins (RIPs) are rRNA N-glycosylases from plants (EC 3.2.2.22) that inactivate ribosomes thus inhibiting protein synthesis. The antiviral properties of RIPs have been investigated for more than four decades. However, interest in these proteins is rising due to the emergence of infectious diseases caused by new viruses and the difficulty in treating viral infections. On the other hand, there is a growing need to control crop diseases without resorting to the use of phytosanitary products which are very harmful to the environment and in this respect, RIPs have been shown as a promising tool that can be used to obtain transgenic plants resistant to viruses. The way in which RIPs exert their antiviral effect continues to be the subject of intense research and several mechanisms of action have been proposed. The purpose of this review is to examine the research studies that deal with this matter, placing special emphasis on the most recent findings.

Macrolides: From Toxins to Therapeutics.

Abstract: Macrolides are a diverse class of hydrophobic compounds characterized by a macrocyclic lactone ring and distinguished by variable side chains/groups. Some of the most well characterized macrolides are toxins produced by marine bacteria, sea sponges, and other species. Many marine macrolide toxins act as biomimetic molecules to natural actin-binding proteins, affecting actin polymerization, while other toxins act on different cytoskeletal components. The disruption of natural cytoskeletal processes affects cell motility and cytokinesis, and can result in cellular death. While many macrolides are toxic in nature, others have been shown to display therapeutic properties. Indeed, some of the most well known antibiotic compounds, including erythromycin, are macrolides. In addition to antibiotic properties, macrolides have been shown to display antiviral, antiparasitic, antifungal, and immunosuppressive actions. Here, we review each functional class of macrolides for their common structures, mechanisms of action, pharmacology, and human cellular targets.

Shining a Light on Colibactin Biology.

Abstract: Colibactin is a secondary metabolite encoded by the pks gene island identified in several Enterobacteriaceae, including some pathogenic Escherichia coli (E. coli) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. E. coli harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of pks+ E. coli in cancer etiology, the biological mechanisms governing production and delivery of colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin’s structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine.

Quantitative Modeling of Climate Change Impacts on Mycotoxins in Cereals : A Review

Abstract: Our climate is projected to change gradually over time. Mycotoxin occurrence in cereal grains is both directly and indirectly related to local weather and to climate changes. Direct routes are via the effects of precipitation, relative humidity, and temperatures on both fungal infection of the grain and mycotoxin formation. Indirect routes are via the effects of the wind dispersal of spores, insect attacks, and shifts in cereal grain phenology. This review aimed to investigate available modeling studies for climate change impacts on mycotoxins in cereal grains, and to identify how they can be used to safeguard food safety with future climate change. Using a systematic review approach, in total, 53 relevant papers from the period of 2005-2020 were retrieved. Only six of them focused on quantitative modeling of climate change impacts on mycotoxins, all in pre-harvest cereal grains. Although regional differences exist, the model results generally show an increase in mycotoxins in a changing climate. The models do not give an indication on how to adapt to climate change impacts. If available models were linked with land use and crop models, scenario analyses could be used for analyzing adaptation strategies to avoid high mycotoxin presence in cereal grains and to safeguard the safety of our feed and food.

Occurrence of Fusarium Mycotoxins and Their Modified Forms in Forage Maize Cultivars

Abstract: Forage maize is often infected by mycotoxin-producing Fusarium fungi during plant growth, which represent a serious health risk to exposed animals. Deoxynivalenol (DON) and zearalenone (ZEN) are among the most important Fusarium mycotoxins, but little is known about the occurrence of their modified forms in forage maize. To assess the mycotoxin contamination in Northern Germany, 120 natural contaminated forage maize samples of four cultivars from several locations were analysed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) for DON and ZEN and their modified forms deoxynivalenol-3-glucoside (DON3G), the sum of 3- and 15-acetyl-deoxynivalenol (3+15-AcDON), α- and β-zearalenol (α-ZEL, β-ZEL). DON and ZEN occurred with high incidences (100 and 96%) and a wide range of concentrations, reaching levels up to 10,972 and 3910 µg/kg, respectively. Almost half of the samples (46%) exceeded the guidance value in complementary and complete feeding stuffs for ZEN (500 µg/kg), and 9% for DON (5000 µg/kg). The DON related mycotoxins DON3G and 3+15-AcDON were also present in almost all samples (100 and 97%) with amounts of up to 3038 and 2237 µg/kg and a wide range of concentrations. For the ZEN metabolites α- and β-ZEL lower incidences were detected (59 and 32%) with concentrations of up to 423 and 203 µg/kg, respectively. Forage maize samples were contaminated with at least three co-occurring mycotoxins, whereby 95% of all samples contained four or more mycotoxins with DON, DON3G, 3+15-AcDON, and ZEN co-occurring in 93%, together with α-ZEL in 57% of all samples. Positive correlations were established between concentrations of the co-occurring mycotoxins, especially between DON and its modified forms. Averaged over all samples, ratios of DON3G/DON and 3+15-AcDON/DON were similar, 20.2 and 20.5 mol%; cultivar-specific mean ratios ranged from 14.6 to 24.3 mol% and 15.8 to 24.0 mol%, respectively. In total, 40.7 mol% of the measured DON concentration was present in the modified forms DON3G and 3+15-AcDON. The α-ZEL/ZEN ratio was 6.2 mol%, ranging from 5.2 to 8.6 mol% between cultivars. These results demonstrate that modified mycotoxins contribute substantially to the overall mycotoxin contamination in forage maize. To avoid a considerable underestimation, it is necessary to analyse modified mycotoxins in future mycotoxin monitoring programs together with their parent forms.