-
Toxins Apr 2024In Western Europe, the incidence of DST is likely the highest globally, posing a significant threat with prolonged bans on shellfish harvesting, mainly caused by species...
In Western Europe, the incidence of DST is likely the highest globally, posing a significant threat with prolonged bans on shellfish harvesting, mainly caused by species of the dinoflagellate genus . Using a time series from 2014 to 2020, our study aimed (i) to determine the concentration of in water at which shellfish toxin levels could surpass the regulatory limit (160 µg OA equiv kg) and (ii) to assess the predictability of toxic events for timely mitigation actions, especially concerning potential harvesting bans. The analysis considered factors such as (i) overdispersion in the data, (ii) distinct periods of presence and absence, (iii) the persistence of cells, and (iv) the temporal lag between cells in the water and toxins in shellfish. Four generalized additive models were tested, with the Tweedie (TW-GAM) model showing superior performance (>85%) and lower complexity. The results suggest existing thresholds currently employed (200 and 500 cells L) are well-suited for the Portuguese coast, supported by empirical evidence (54-79% accuracy). The developed algorithm allows for thresholds to be tailored on a case-by-case basis, offering flexibility for regional variations.
Topics: Dinoflagellida; Marine Toxins; Shellfish Poisoning; Shellfish; Animals; Portugal; Environmental Monitoring; Food Contamination
PubMed: 38787056
DOI: 10.3390/toxins16050204 -
Journal of Cellular Biochemistry May 2024J. Kong, D. Li, S. Zhang, H. Zhang, Y. Fu, B. Qian, C. Bei, S. Tan, X. Zhu, "Okadaic acid promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by...
J. Kong, D. Li, S. Zhang, H. Zhang, Y. Fu, B. Qian, C. Bei, S. Tan, X. Zhu, "Okadaic acid promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting protein phosphatase 2A," Journal of Cellular Biochemistry 122, no. 9 (2021): 993-1002, https://doi.org/10.1002/jcb.29629 The above article, published online on 6 January 2020 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the authors; the journal's Editor in Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by third parties. During the investigation, several flaws and inconsistencies were found within the provided data. The authors admitted substantial mistakes during figure compilation for this manuscript. Thus, the conclusions of this article are considered invalid by the editors.
PubMed: 38775121
DOI: 10.1002/jcb.30607 -
Environmental Science & Technology Jun 2024Tropical small island developing states (SIDS), with their geographical isolation and limited resources, heavily rely on the fisheries industry for food and revenue. The...
Tropical small island developing states (SIDS), with their geographical isolation and limited resources, heavily rely on the fisheries industry for food and revenue. The presence of marine lipophilic phycotoxins (MLPs) poses risks to their economy and human health. To understand the contamination status and potential risks, the Republic of Kiribati was selected as the representative tropical SIDS and 55 species of 256 coral reef fish encompassing multiple trophic levels and feeding strategies were collected to analyze 17 typical MLPs. Our results showed that the potential risks of ciguatoxins were the highest and approximately 62% of fish species may pose risks for consumers. Biomagnification of ciguatoxins was observed in the food web with a trophic magnification factor of 2.90. Brevetoxin-3, okadaic acid, and dinophysistoxin-1 and -2 were first reported, but the risks posed by okadaic acid and dinophysistoxins were found to be negligible. The correlation analysis revealed that fish body size and trophic position are unreliable metrics to indicate the associated risks and prevent the consumption of contaminated fish. The potential risks of MLPs in Kiribati are of concern, and our findings can serve as valuable inputs for developing food safety policies and fisheries management strategies specific to tropical SIDS contexts.
Topics: Animals; Marine Toxins; Fishes; Food Chain; Islands; Humans; Risk Assessment; Tropical Climate; Ciguatoxins
PubMed: 38768015
DOI: 10.1021/acs.est.4c00512 -
EXCLI Journal 2024Phycotoxins are responsible for foodborne intoxications. Symptoms depend on the ingested toxins but mostly imply gastro-intestinal and neurological disorders....
Phycotoxins are responsible for foodborne intoxications. Symptoms depend on the ingested toxins but mostly imply gastro-intestinal and neurological disorders. Importantly, humans are exposed to combinations of several phycotoxins, resulting in possible mixture effects. Most previous studies, however, have been focused on single toxin effects. Thus, the aim of this study was to examine the effects of binary mixtures of three main phycotoxins, okadaic acid (OA), azaspiracid-1 (AZA1) and yessotoxin (YTX), on human intestinal Caco-2 cells. The focus was placed on cell viability studies and inflammation responses using a multi-parametric approach to assess cell population (nuclei staining), cell metabolism/viability (reductase activity and lysosomal integrity), and release of inflammation markers (e.g., interleukins). Mixture effects were evaluated using the concentration addition (CA) and independent action (IA) models. Our assays show that none of the toxins had an impact on the cell population in the tested concentration range. Only OA modulated reductase activity, while all three toxins had strong effects on lysosomal integrity. Furthermore, all toxins triggered the release of interleukin 8 (IL-8), with OA being most potent. Mixture effect analysis showed additivity in most cases. However, supra-additivity was observed in regards to IL-6 and IL-8 release for combinations implying high concentrations of OA. This study extends the knowledge on mixture effects of phycotoxins in human cells.
PubMed: 38741723
DOI: 10.17179/excli2023-6884 -
Biochimica Et Biophysica Acta.... Aug 2024Alzheimer's disease (AD) research started several decades ago and despite the many efforts employed to develop new treatments or approaches to slow and/or revert disease...
Alzheimer's disease (AD) research started several decades ago and despite the many efforts employed to develop new treatments or approaches to slow and/or revert disease progression, AD treatment remains an unsolved issue. Knowing that mitochondria loss of function is a central hub for many AD-associated pathophysiological processes, there has been renewed interest in exploring mitochondria as targets for intervention. In this perspective, the present study was aimed to investigate the possible beneficial effects of 2,4 dinitrophenol (DNP), a mitochondrial uncoupler agent, in an in vitro model of AD. Retinoic acid-induced differentiated SH-SY5Y cells were incubated with okadaic acid (OA), a neurotoxin often used as an AD experimental model, and/or with DNP. OA caused a decrease in neuronal cells viability, induced multiple mitochondrial anomalies including increased levels of reactive oxygen species, decreased bioenergetics and mitochondria content markers, and an altered mitochondria morphology. OA-treated cells also presented increased lipid peroxidation levels, and overactivation of tau related kinases (GSK3β, ERK1/2 and AMPK) alongside with a significant augment in tau protein phosphorylation levels. Interestingly, DNP co-treatment ameliorated and rescued OA-induced detrimental effects not only on mitochondria but also but also reinstated signaling pathways homeostasis and ameliorated tau pathology. Overall, our results show for the first time that DNP has the potential to preserve mitochondria homeostasis under a toxic insult, like OA exposure, as well as to reestablish cellular signaling homeostasis. These observations foster the idea that DNP, as a mitochondrial modulator, might represent a new avenue for treatment of AD.
Topics: Alzheimer Disease; Okadaic Acid; Humans; 2,4-Dinitrophenol; Mitochondria; Reactive Oxygen Species; Cell Line, Tumor; Cell Survival; tau Proteins; Neurons; Lipid Peroxidation; Glycogen Synthase Kinase 3 beta; Tretinoin
PubMed: 38729530
DOI: 10.1016/j.bbadis.2024.167222 -
Journal of Traditional and... May 2024Royal jelly is an anti-inflammatory, antioxidant, and neuroprotective bee product. There are several sources for royal jelly and one of them is Indian Royal Jelly (IRJ)....
BACKGROUND
Royal jelly is an anti-inflammatory, antioxidant, and neuroprotective bee product. There are several sources for royal jelly and one of them is Indian Royal Jelly (IRJ). However, the neuroprotective actions of IRJ and the underlying molecular mechanisms involved are not well known.
OBJECTIVE
To evaluate the neuroprotective effect of IRJ in the okadaic acid (OKA)-induced Alzheimer's disease (AD) model in rats.
METHODS
In male Wistar rats, OKA was intracerebroventricularly (ICV) administered, and from day 7, they were treated orally with IRJ or memantine for 21 days. Spatial and recognition learning and memory were evaluated from days 27-34; employing the Morris water maze (MWM) and the novel object recognition tests (NORT), respectively. biochemical measurements were taken of the cholinergic system and oxidative stress markers. In silico docking was used to find the role of tau protein kinase and phosphatase in the pharmacological action.
RESULTS
In OKA-induced rats, IRJ decreased the escape latency and path length in MWM and increased the exploration time for novel objects and the discrimination index in NORT. ICV-OKA rats had higher free radicals and cytokines that caused inflammation and their level of free radical scavengers was back to normal with IRJ treatment. IRJ increased the level of acetylcholine and inhibited acetylcholinesterase. Moreover, the in silico docking study revealed the strong binding affinity of 10-hydroxy-2-decenoic acid (10-HDA), a bioactive constituent of IR, to the tau protein kinases and phosphatases.
CONCLUSION
IRJ may serve as a nootropic agent in the treatment of dementia, and owing to its capacity to prevent oxidative stress and neuroinflammation, and increase cholinergic tone; it has the potential to be explored as a novel strategy for the treatment of dementia and AD. More studies may be needed to develop 10-HDA as a novel drug entity for AD.
PubMed: 38707922
DOI: 10.1016/j.jtcme.2023.11.005 -
Marine Pollution Bulletin Jun 2024An efficient and sensitivity approach, which combines solid-phase extraction or ultrasonic extraction for pretreatment, followed by ultra-performance liquid...
An efficient and sensitivity approach, which combines solid-phase extraction or ultrasonic extraction for pretreatment, followed by ultra-performance liquid chromatography-tandem mass spectrometry, has been established to simultaneously determine eight lipophilic phycotoxins and one hydrophilic phycotoxin in seawater, sediment and biota samples. The recoveries and matrix effects of target analytes were in the range of 61.6-117.3 %, 55.7-121.3 %, 57.5-139.9 % and 82.6 %-95.0 %, 85.8-106.8 %, 80.7 %-103.3 % in seawater, sediment, and biota samples, respectively. This established method revealed that seven, six and six phycotoxins were respectively detected in the Beibu Gulf, with concentrations ranging from 0.14 ng/L (okadaic acid, OA) to 26.83 ng/L (domoic acid, DA) in seawater, 0.04 ng/g (gymnodimine-A, GYM-A) to 2.75 ng/g (DA) in sediment and 0.01 ng/g (GYM-A) to 2.64 ng/g (domoic acid) in biota samples. These results suggest that the presented method is applicable for the simultaneous determination of trace marine lipophilic and hydrophilic phycotoxins in real samples.
Topics: Marine Toxins; Environmental Monitoring; Seawater; Solid Phase Extraction; Biota; Geologic Sediments; Water Pollutants, Chemical; Tandem Mass Spectrometry; Hydrophobic and Hydrophilic Interactions; Kainic Acid; Heterocyclic Compounds, 3-Ring; Hydrocarbons, Cyclic; Imines
PubMed: 38705002
DOI: 10.1016/j.marpolbul.2024.116444 -
International Journal of Biological... Jun 2024Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) plays an essential role in Tau and Aβ pathology closely related to Alzheimer's disease (AD)....
Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) plays an essential role in Tau and Aβ pathology closely related to Alzheimer's disease (AD). Accumulative evidence has demonstrated DYRK1A inhibition is able to reduce the pathological features of AD. Nevertheless, there is no approved DYRK1A inhibitor for clinical use as anti-AD therapy. This is somewhat due to the lack of effective and safe chemotypes of DYRK1A inhibitors. To address this issue, we carried out in silico screening, in vitro assays and in vivo efficacy evaluation with the aim to discover a new class of DYRK1A inhibitors for potential treatment of AD. By in silico screening, we selected and purchased 16 potential DYRK1A inhibitors from the Specs chemical library. Among them, compound Q17 (Specs ID: AO-476/40829177) potently inhibited DYRK1A. The hydrogen bonds between compound Q17 and two amino acid residues named GLU239 and LYS188, were uncovered by molecular docking and molecular dynamics simulation. The cell-based assays showed that compound Q17 could protect the SH-SY5Y human neuroblastoma cell line from okadaic acid (OA)-induced injury by targeting DYRK1A. More importantly, compound Q17 significantly improved cognitive dysfunction of 3 × Tg-AD mice, ameliorated pathological changes, and attenuated Tau hyperphosphorylation as well as Aβ deposition. In summary, our computational modeling strategy is effective to identify novel chemotypes of DYRK1A inhibitors with great potential to treat AD, and the identified compound Q17 in this study is worthy of further study.
Topics: Dyrk Kinases; Protein-Tyrosine Kinases; Alzheimer Disease; Protein Serine-Threonine Kinases; Humans; Protein Kinase Inhibitors; Animals; Mice; Molecular Docking Simulation; Molecular Dynamics Simulation; Cell Line, Tumor; tau Proteins; Drug Discovery; Computer Simulation; Disease Models, Animal
PubMed: 38704072
DOI: 10.1016/j.ijbiomac.2024.132024 -
Toxins Apr 2024Okadaic acid (OA) is one of the most potent marine biotoxins, causing diarrheal shellfish poisoning (DSP). The proliferation of microalgae that produce OA and its...
Okadaic acid (OA) is one of the most potent marine biotoxins, causing diarrheal shellfish poisoning (DSP). The proliferation of microalgae that produce OA and its analogues is frequent, threatening human health and socioeconomic development. Several methods have been tested to remove this biotoxin from aquatic systems, yet none has proven enough efficacy to solve the problem. In this work, we synthesized and characterized low-cost composites and tested their efficacy for OA adsorption in saltwater. For the synthesis of the composites, the following starting materials were considered: chitosan of low and medium molecular weight (CH-LW and CH-MW, respectively), activated carbon (AC), and montmorillonite (MMT). Characterization by vibrational spectroscopy (FTIR), X-ray diffraction (XRD), and microscopy revealed differences in the mode of interaction of CH-LW and CH-MW with AC and MMT, suggesting that the interaction of CH-MW with MMT has mainly occurred on the surface of the clay particles and no sufficient intercalation of CH-MW into the MMT interlayers took place. Among the composites tested (CH-LW/AC, CH-MW/AC, CH-MW/AC/MMT, and CH-MW/MMT), CH-MW/MMT was the one that revealed lower OA adsorption efficiency, given the findings evidenced by the structural characterization. On the contrary, the CH-MW/AC composite revealed the highest average percentage of OA adsorption (53 ± 11%). Although preliminary, the results obtained in this work open up good perspectives for the use of this type of composite material as an adsorbent in the removal of OA from marine environments.
Topics: Adsorption; Chitosan; Okadaic Acid; Bentonite; Charcoal; Marine Toxins; Shellfish Poisoning
PubMed: 38668625
DOI: 10.3390/toxins16040200 -
Scientific Reports Apr 2024Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation...
Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation of α-synuclein (α-syn) and Tau, which are major components of cytosolic protein inclusions called Lewy bodies, in the brain. Currently, there is a lack of effective methods that preventing PD progression. It has been suggested that the plasminogen activation system, which is a major extracellular proteolysis system, is involved in PD pathogenesis. We investigated the functional roles of plasminogen in vitro in an okadaic acid-induced Tau hyperphosphorylation NSC34 cell model, ex vivo using brains from normal controls and methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and in vivo in a widely used MPTP-induced PD mouse model and an α-syn overexpression mouse model. The in vitro, ex vivo and in vivo results showed that the administered plasminogen crossed the blood‒brain barrier (BBB), entered cells, and migrated to the nucleus, increased plasmin activity intracellularly, bound to α-syn through lysine binding sites, significantly promoted α-syn, Tau and TDP-43 clearance intracellularly and even intranuclearly in the brain, decreased dopaminergic neurodegeneration and increased the tyrosine hydroxylase levels in the substantia nigra and striatum, and improved motor function in PD mouse models. These findings indicate that plasminogen plays a wide range of pivotal protective roles in PD and therefore may be a promising drug candidate for PD treatment.
Topics: Animals; Mice; alpha-Synuclein; Disease Models, Animal; DNA-Binding Proteins; Dopamine; Neurodegenerative Diseases; Parkinson Disease; Plasminogen; Serine Proteases; tau Proteins; Dopaminergic Neurons
PubMed: 38615036
DOI: 10.1038/s41598-024-59090-8