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Cyanobacteria are photoautotrophic organisms which occur in aquatic and terrestrial environments. They have the potential to produce toxins which pose a threat to human and animal health. This review covers the global distribution of the common cyanotoxins and related poisoning cases. A total of 468 selected articles on toxic cyanobacteria, dating from the earliest records until 2018, were reviewed. Most of the articles were published after 2000 (72%; 337 out of 468), which is consistent with the recent growth in interest in the analysis, toxinology and ecotoxicology of cyanotoxins. Animal and/or human poisoning cases were described in more than a third of the overall publications (38%; 177 out of 468). The reviewed publications showed that there were 1118 recorded identifications of major cyanotoxins in 869 freshwater ecosystems from 66 countries throughout the world. Microcystins were the most often recorded cyanotoxins worldwide (63%; 699 out of 1118), followed by cylindrospermopsin (10%; 107 out of 1118), anatoxins (9%; 100 out of 1118), and saxitoxins (8%; 93 out of 1118). Nodularins were the most rarely recorded cyanotoxins (2%; 19 out of 1118); however, there were also reports where cyanotoxins were not analysed or specified (9%; 100 out of 1118). The most commonly found toxic cyanobacterial genera were Microcystis spp. (669 reports), Anabaena spp. (397 reports), Aphanizomenon spp. (100 reports), Planktothrix spp. (98 reports), and Oscillatoria spp. (75 reports). Furthermore, there were 183 recorded cyanotoxin poisonings of humans and/or animals. Out of all toxic cyanobacterial blooms reviewed in this paper, the highest percentage of associated poisonings was found in North and Central America (39%; 69 cases out of 179), then Europe (20%; 35 out of 179), Australia including New Zealand (15%; 27 out of 179), and Africa (11%; 20 out of 179), while the lowest percentage was related to Asia (8%; 14 cases out of 179) and South America (8%; 14 cases out of 179). Events where only animals were known to have been affected were 63% (114 out of 182), whereas 32% (58 out of 182) of the investigated events involved only humans. A historical overview of human and animal poisoning episodes associated with cyanobacterial blooms is presented. Further, geographical data on the occurrence of cyanotoxins and related poisonings based on the available literature are shown. Some countries (mainly European) have done very intensive research on the occurrence of toxic cyanobacteria and cyanotoxins, and reported related ecotoxicological observations, while in some countries the lack of data is apparent. The true global extent of cyanotoxins and associated poisonings is likely to be greater than found in the available literature, and it can be assumed that ecotoxicological and hygienic problems caused by toxic cyanobacteria may occur in more environments.

The impacts of climate change on cyanobacterial harmful algal blooms (cHABs) are paramount, promoting the widespread distribution, intensity, and toxicity of these phenomena in major freshwater bodies across the globe. Microcystins (MCs) and nodularins (NODs) are monocyclic peptides that produce hepatotoxic effects in living organisms. Despite efforts in understanding their molecular toxicological mechanisms, we do not fully have a grasp on the human health impacts associated with these toxins derived from freshwater cHABs. We seek to provide a current update on the toxicity and epidemiology of MCs and NODs, integrating key evidence from in vitro, in vivo, and epidemiological studies. The primary objective of this work is to understand the human health impacts of MC and NOD-producing cHABs.

Global warming and human-induced eutrophication drive the occurrence of various cyanotoxins in aquatic environments. These metabolites reveal diversified mechanisms of action, encompassing cyto-, neuro-, hepato-, nephro-, and neurotoxicity, and pose a threat to aquatic biota and human health. In the present paper, we review data on the occurrence of the most studied cyanotoxins, microcystins, nodularins, cylindrospermopsin, anatoxins, and saxitoxins, in the aquatic environment, as well as their potential bioaccumulation and toxicity in fish. Microcystins are the most studied among all known cyanotoxins, although other toxic cyanobacterial metabolites are also commonly identified in aquatic environments and can reveal high toxicity in fish. Except for primary toxicity signs, cyanotoxins adversely affect the antioxidant system and anti-/pro-oxidant balance. Cyanotoxins also negatively impact the mitochondrial and endoplasmic reticulum by increasing intracellular reactive oxygen species. Furthermore, fish exposed to microcystins and cylindrospermopsin exhibit various immunomodulatory, inflammatory, and endocrine responses. Even though cyanotoxins exert a complex pressure on fish, numerous aspects are yet to be the subject of in-depth investigation. Metabolites other than microcystins should be studied more thoroughly to understand the long-term effects in fish and provide a robust background for monitoring and management actions.

The review summarizes the available knowledge on toxins and their producers from rather disparate algal assemblages of aeroterrestrial, airborne and other versatile extreme environments (hot springs, deserts, ice, snow, caves, etc.) and on phycotoxins as contaminants of emergent concern in soil and plants. There is a growing body of evidence that algal toxins and their producers occur in all general types of extreme habitats, and cyanobacteria/cyanoprokaryotes dominate in most of them. Altogether, 55 toxigenic algal genera (47 cyanoprokaryotes) were enlisted, and our analysis showed that besides the “standard” toxins, routinely known from different waterbodies (microcystins, nodularins, anatoxins, saxitoxins, cylindrospermopsins, BMAA, etc.), they can produce some specific toxic compounds. Whether the toxic biomolecules are related with the harsh conditions on which algae have to thrive and what is their functional role may be answered by future studies. Therefore, we outline the gaps in knowledge and provide ideas for further research, considering, from one side, the health risk from phycotoxins on the background of the global warming and eutrophication and, from the other side, the current surge of interest which phycotoxins provoke due to their potential as novel compounds in medicine, pharmacy, cosmetics, bioremediation, agriculture and all aspects of biotechnological implications in human life.

Cyanotoxins have gained global public interest due to their potential to bioaccumulate in food, which threatens human health. Bloom formation is usually enhanced under Mediterranean, subtropical and tropical climates which are the dominant climate types in developing countries. In this context, we present an up-to-date overview of cyanotoxins (types, toxic effects, analysis, occurrence, and mitigation) with a special focus on their contamination in (sea)food from all the developing countries in Africa, Asia, and Latin America as this has received less attention. A total of 65 publications have been found (from 2000 until October 2021) reporting the contamination by one or more cyanotoxins in seafood and edible plants (five papers). Only Brazil and China conducted more research on cyanotoxin contamination in food in comparison to other countries. The majority of research focused on the detection of microcystins using different analytical methods. The detected levels mostly surpassed the provisional tolerable daily intake limit set by the World Health Organization, indicating a real risk to the exposed population. Assessment of cyanotoxin contamination in foods from developing countries still requires further investigations by conducting more survey studies, especially the simultaneous detection of multiple categories of cyanotoxins in food.

ABSTRACT Interactions between climate change and ultraviolet radiation (UVR) have a substantial impact on aquatic ecosystems, especially on photosynthetic organisms. To counteract the damaging effects of UVR, cyanobacteria developed adaptive strategies such as the biosynthesis of secondary metabolites. This study aimed to evaluate the effects of UVR on the metabolomic profiles of potentially toxic cyanobacteria. Twelve strains were irradiated with ultraviolet A and ultraviolet B radiation and parabolic aluminized reflector lamps for 3 days, followed by liquid chromatography–tandem mass spectometry (LC-MS/MS) analysis to assess changes in metabolomic profiles. Matrices were used to generate principal component analysis biplots, and molecular networks were obtained using the Global Natural Products platform. Most strains showed significant changes in their metabolomic profiles after UVR exposure. On average, 7% of MS features were shown to be exclusive to metabolomic profiles before UVR exposure, while 9% were unique to metabolomic profiles after UVR exposure. The identified compounds included aeruginosins, spumigins, cyanopeptolins, microginins, namalides, pseudospumigins, anabaenopeptins, mycosporine-like amino acids, nodularins and microcystins. Data showed that cyanobacteria display broad metabolic plasticity upon UVR exposure, including the synthesis and differential expression of a variety of secondary metabolites. This could result in a competitive advantage, supporting cyanobacterial blooms under various UVR light exposures. This study revealed the differential expression of cyanobacterial secondary metabolites induced by UVR.

Clinically, most prostate cancer (PCa) patients inevitably progress to castration‐resistant prostate cancer (CRPC) with poor prognosis after androgen deprivation therapy (ADT), including abiraterone, the drug of choice for ADT. Therefore, it is necessary to explore the resistance mechanism of abiraterone in depth. Genome‐wide CRISPR/Cas9 knockout technology was used to screen CRPC cell line 22Rv1 for abiraterone‐resistant genes. Combined with bioinformatics, a key gene with high expression and poor prognosis in CRPC patients was screened. Then, the effects of target gene on abiraterone‐resistant 22Rv1 cell function were explored by silencing and overexpression. Further, a natural product with potential targeting effect was identified and validated by molecular docking and protein expression. Molecular dynamics simulations revealed potential mechanism for the natural product affecting target protein expression. Finally, the combined anti‐CRPC effects of the natural product and abiraterone were validated by cellular and in vivo experiments. Five common resistance genes (KCNJ3, COL2A1, PPP1CA, MDH2 and EXOSC5) were identified successfully, among which high PPP1CA expression had the worst prognosis for disease‐free survival. Moreover, PPP1CA was highly expressed in abiraterone‐resistant 22Rv1 cells. Silencing PPP1CA increased cell sensitivity to abiraterone while promoting apoptosis and inhibiting clone formation. Overexpressing PPP1CA exerted the opposite effects. Molecular docking revealed the binding mode of the natural product nodularin‐R to PPP1CA with a dose‐dependent manner for inhibition. Mechanistically, nodularin‐R attenuates the interaction between PPP1CA and USP11 (deubiquitinating enzyme), potentially promoting PPP1CA degradation. Additionally, combination of 2.72 μM nodularin‐R and 54.5 μM abiraterone synergistically inhibited the resistant 22Rv1 cell function. In vivo experiments also revealed that combination therapy significantly inhibited tumour growth and reduced inducible expression of PPP1CA. PPP1CA is a key driver for abiraterone resistance, and nodularin‐R enhances the anti‐CRPC effects of abiraterone by inhibiting PPP1CA.

Cyanobacterial harmful algal blooms (cyanoHABs) are a natural phenomenon produced mainly by the interaction between natural and anthropogenic events. CyanoHABs are characterized by the production of cyanotoxins that can have harmful effects on different species within the food web and even affect human health. Among the most prevalent toxin groups worldwide are microcystins (MCs), anatoxins (ATXs), cylindrospermopsins (CYNs) and nodularins (NODs), which are characterized as toxins with hepatotoxic, neurotoxic, and cytotoxic effects. This review summarizes and analyzes research on the influence of cyanoHABs, the main toxin-producing cyanobacteria and the most prevalent cyanotoxins in freshwater and marine bodies, highlighting their global occurrence, toxicology, and bioaccumulation dynamics in vectors of the food web, and the main cases of acute and chronic intoxications in humans. This review is useful for understanding the dynamics of cyanoHABs’ interaction with the ecosystem and their impact on human health, and how the implementation of a surveillance and management framework for cyanobacteria and cyanotoxins could generate vital information for stakeholders to establish health guidelines on the risks and hazards of cyanoHABs for the ecosystem and humans.

This review is focused on the mechanisms that regulate health, disease and aging redox status, the signal pathways that counteract oxidative and reductive stress, the role of food components and additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), and the role of the hormones irisin and melatonin in the redox homeostasis of animal and human cells. The correlations between the deviation from optimal redox conditions and inflammation, allergic, aging and autoimmune responses are discussed. Special attention is given to the vascular system, kidney, liver and brain oxidative stress processes. The role of hydrogen peroxide as an intracellular and paracrine signal molecule is also reviewed. The cyanotoxins β-N-methylamino-l-alanine (BMAA), cylindrospermopsin, microcystins and nodularins are introduced as potentially dangerous food and environment pro-oxidants.

Benthic cyanobacterial proliferations in rivers are have been reported with increasing frequency worldwide. In the Eel and Russian rivers of California, more than a dozen dog deaths have been attributed to cyanotoxin toxicosis since 2000. Periphyton proliferations in these rivers comprise multiple cyanobacterial taxa capable of cyanotoxin production, hence there is uncertainty regarding which taxa are producing toxins. In this study, periphyton samples dominated by the cyanobacterial genera Anabaena spp. and Microcoleus spp. and the green alga Cladophora glomerata were collected from four sites in the Eel River catchment and one site in the Russian River. Samples were analysed for potential cyanotoxin producers using polymerase chain reaction (PCR) in concert with Sanger sequencing. Cyanotoxin concentrations were measured using liquid chromatography tandem-mass spectrometry, and anatoxin quota (the amount of cyanobacterial anatoxins per toxigenic cell) determined using droplet digital PCR. Sequencing indicated Microcoleus sp. and Nodularia sp. were the putative producers of cyanobacterial anatoxins and nodularins, respectively, regardless of the dominant taxa in the mat. Anatoxin concentrations in the mat samples varied from 0.1 to 18.6 μg g-1 and were significantly different among sites (p < 0.01, Wilcoxon test); however, anatoxin quotas were less variable (< 5-fold). Dihydroanatoxin-a was generally the most abundant variant in samples comprising 38% to 71% of the total anatoxins measured. Mats dominated by the green alga C. glomerata contained both anatoxins and nodularin-R at concentrations similar to those of cyanobacteria-dominated mats. This highlights that even when cyanobacteria are not the dominant taxa in periphyton, these mats may still pose a serious health risk and indicates that more widespread monitoring of all mats in a river are necessary.