Search Results (187)

The Arabian Gulf, bordered by major energy-producing nations, harbors diverse microalgal communities with strong potential for the bioremediation of environmental pollutants, particularly petroleum hydrocarbons. This review evaluates two key microalgal groups—micro-green algae and dinoflagellates—highlighting their distinct physiological traits and ecological roles in pollution mitigation. Dinoflagellates, including Prorocentrum and Protoperidinium, have demonstrated hydrocarbon-degrading abilities but are frequently linked to harmful algal blooms (HABs), marine toxins, and bioluminescence, posing ecological and health risks. The toxins produced by these algae can be hemolytic or neurotoxic and include compounds such as azaspiracids, brevetoxins, ciguatoxins, okadaic acid, saxitoxins, and yessotoxins. In contrast, micro-green algae such as Oedogonium and Pandorina are generally non-toxic, seldom associated with HABs, and typically found in clean freshwater and brackish environments. Some species, like Chlorogonium, indicate pollution tolerance, while Dunaliella has shown promise in remediating contaminated seawater. Both groups exhibit unique enzymatic pathways and metabolic mechanisms for degrading hydrocarbons and remediating heavy metals. Due to their respective phycoremediation capacities and environmental adaptability, these algae offer sustainable, nature-based solutions for pollution control in coastal, estuarine, and inland freshwater systems, particularly in mainland Qatar. This review compares their remediation efficacy, ecological impacts, and practical limitations to support the selection of effective algal candidates for eco-friendly strategies targeting petroleum-contaminated marine environments. Full article

Alzheimer’s disease (AD), a prevalent neurodegenerative disorder in the elderly, poses significant humanistic and economic burdens worldwide. Previously, we identified Trp-Leu-Pro (WLP), a novel antioxidant peptide derived from the sea squirt (Halocynthia roretzi); however, its effects on AD remained unexplored. In this study, we developed a rapid and efficient method to generate AD cerebral organoids with consistent quality using okadaic acid (OKA) exposure. This study aimed to evaluate the protective effects of WLP on OKA-induced AD pathology in cerebral organoids and elucidate its underlying mechanisms. Our results demonstrated that cerebral organoids exposed to 25 nM OKA successfully recapitulated hallmark AD pathologies, including amyloid-beta (Aβ) plaque deposits, neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau proteins, and neuronal loss. WLP treatment significantly enhanced cell viability, increased the proportion of neuronal progenitor cells, and reduced Aβ plaques and NFTs in OKA-induced cerebral organoids. Furthermore, transcriptomic analysis revealed that the neuroprotective effects of WLP are primarily mediated through the regulation of synapse-related and oxidative stress pathways. These findings highlight the potential of WLP as a promising nutraceutical candidate for AD prevention. Full article

As emerging contaminants, microplastics (MPs) may pose a threat to human health. Their co-exposure with the widespread phycotoxin okadaic acid (OA), a marine toxin known to cause gastrointestinal toxicity, may exacerbate health risk and raise public safety concern. In this study, the toxicity mechanisms of MPs and OA on intestinal microenvironment was explored using human Caco-2 cells as the model, which was combined with an in vitro fecal fermentation experiment. Our results showed that co-exposure to MPs (80 μg/mL) and OA (20 ng/mL) significantly decreased cell viability, increased intracellular reactive oxygen species (ROS) production, elevated lactate dehydrogenase release, impaired ABC transporter activity, promoted OA accumulation, and triggered inflammatory response compared to the control, MPs, and OA groups, indicating that co-exposure directly compromises intestinal epithelial integrity. In vitro fermentation experiments revealed that co-exposure disrupted gut microbial composition, decreasing the relative abundance of some bacteria, such as Parasutterella and Adlercreutzia, while increasing opportunistic pathogens, such as Escherichia-Shigella, increased. These findings provide new insights into the impact and underlying mechanisms of MPs and OA co-exposure on intestinal homeostasis, highlighting the potential health risks associated with MPs. Full article

Among aquatic organisms, marine dinoflagellates are essential sources of bioactive metabolites. The benthic dinoflagellate Coolia malayensis produces metabolites that have exhibited substantial and specific cytotoxicity on cancer cells; however, isolation and identification of the purified compounds remain a challenge. This study reports C. malayensis biomass multi-step extraction plus chemical analyses for identifying compounds with antineoplastic activity. Through bio-directed fractionation, the cytotoxicity of extracts and fractions was tested on H1299 (lung), PC-3 (prostate), HeLa (cervical), and MCF-7 (breast) cancer cell lines. Dichloromethane (DCM) phase, hydroalcoholic (HYD) secondary extract, and methanolic (MET) extract showed cytotoxic effects on all cell lines. Active extracts and fractions were analyzed by HPLC-QTOF-MS, ¹H, and ¹³C NMR. Cell lines H1299 and PC-3 treated with fractions F4, F7, and DCM2-AQ-Ch sub-extract showed morphological changes resembling those observed in the apoptosis control, and no signs of necrosis were observed. The selectivity of fraction F7 was above 100 μg mL⁻¹ for healthy cells, while cytotoxic activity was observed in cancer cells. This fraction was identified as mostly fatty acids (FA) by NMR. Seventeen compounds with reported biological activities, such as antioxidant, analgesic, antiviral, and anticancer, were identified from C. malayensis extracts and fractions. Among them, the phycotoxins gambieric acid A and B, okadaic acid, and dinophysistoxin-1 were detected. Further studies are needed to reveal more significant anti-cancer potential from C. malayensis. Full article

The knowledge of the routes of excretion of the toxins accumulated by molluscs is a key step in designing methods that accelerate depuration. In this work, the excretion route, in mussels and cockles, of the main diarrhetic shellfish poisoning (DSP) toxins in Europe (okadaic acid and dinophysistoxin-2) after natural intoxication were studied. During depuration, the amounts of free toxins and their derivatives were quantified in bivalves, faeces, and water. Most toxins (>98%) were excreted through faeces as acyl derivatives (most likely 7-O-acyl esters), independent of the ratio between these derivatives and free toxins in soft tissues. The small proportion of toxins excreted into water mostly constituted the free forms of the toxins. Both species shared the same route even though they contained very different proportions of free toxins in their soft tissues. No substantial changes in this general pattern were observed during the experiment. The esters of fatty acids with 16 carbon atoms were the most abundant in both soft tissues and faeces, but they were not the same in mussels and cockles. Most of the variability in ester proportions can be attributed to the species more than to their differential excretion (water or faeces) suggesting that there are not large differences in the depuration of the different esters. Full article

The binding interactions between okadaic acid (OA) aptamers and OA molecules are crucial for developing effective detection methods. This study aims to identify the recognition site and establish a reliable detection protocol through computational simulations and experimental validations. After determining the target sequence (OA-2), molecular docking simulations using Sybyl-X and H-dock were conducted to predict the binding affinity and interaction sites of OA aptamers with their targets. These predictions were subsequently validated through experiments based on the Förster resonance energy transfer (FRET) principle. The combined approach not only confirmed the computational predictions, identifying the “major region” as the recognition basis of OA-2, but also provided deeper insights into the binding mechanisms. Subsequently, a classical AuNPs-aptamer colorimetric detection method was established based on the OA-2 sequence and applied to the detection of real shellfish samples, achieving a limit of quantification (LOQ) of 5.0 μg kg⁻¹. The recoveries of OA in spiked samples ranged from 79.0% to 122.9%, with a relative standard deviation (RSD) of less than 14.7%. The results of this study contribute to the development of robust detection methods for OA aptamer–target interactions, enhancing the potential for practical applications in toxin detection and monitoring. Full article

AdipoRon is a selective adiponectin receptor agonist that inhibits vascular remodeling by promoting the differentiation of arterial smooth muscle cells (SMCs). Our recent studies have demonstrated that activation of TFEB and its downstream autophagy–lysosomal signaling contribute to adipoRon-induced differentiation of SMCs. The present study was designed to examine whether acid sphingomyelinase (ASM; gene symbol Smpd1) is involved in mediating adipoRon-induced activation of TFEB–autophagy signaling and inhibition of proliferation/migration in arterial SMCs. Our results showed that adipoRon induced ASM expression and ceramide production in Smpd1^+/+ SMCs, which were abolished in Smpd1^−/− SMCs. Compared to Smpd1^+/+ SMCs, Smpd1^−/− SMCs exhibited less TFEB nuclear translocation and activation of autophagy signaling induced by adipoRon stimulation. SMC differentiation was further characterized by retarded wound healing, reduced proliferation, F-actin reorganization, and MMP downregulation. The results showed that Smpd1^−/− SMCs were less responsive to adipoRon-induced differentiation than Smpd1^+/+ SMCs. Mechanistically, adipoRon increased the expression of protein phosphatases such as calcineurin and PP2A in Smpd1^+/+ SMCs. The calcineurin inhibitor FK506/cyclosporin A or PP2A inhibitor okadaic acid significantly attenuated adipoRon-induced activation of TFEB–autophagy signaling. In addition, adipoRon-induced expressions of calcineurin and PP2A were not observed in Smpd1^−/− SMCs. However, activation of calcineurin by lysosomal TRPML1-Ca²⁺ channel agonist ML-SA1 rescued the activation of TFEB–autophagy signaling and the effects of adipoRon on cell differentiation in Smpd1^−/− SMCs. Taken together, these data suggested that ASM regulates adipoRon-induced SMC differentiation through TFEB activation. This study provided novel mechanistic insights into the therapeutic effects of adipoRon on TFEB signaling and pathological vascular remodeling. Full article

Harmful algal blooms are an expanding phenomenon negatively impacting human health, socio-economic welfare, and ecosystems. Such events increase the risk of marine organisms’ exposure to algal toxins with consequent ecological effects. In this frame, the objective of this study was to investigate the ecotoxicological potential of three globally distributed dinoflagellate toxins (okadaic acid, OA; dinophysistoxin-1, DTX-1; dinophysistoxin-2, DTX-2) using Artemia franciscana as a model organism of marine zooplankton. Each toxin (0.1–100 nM) was evaluated for its toxic effects in terms of cyst hatching, mortality of nauplii Instar I and adults, and biochemical responses related to oxidative stress. At the highest concentration (100 nM), these toxins significantly increased adults’ mortality starting from 24 h (DTX-1), 48 h (OA), or 72 h (DTX-2) exposures, DTX-1 being the most potent one, followed by OA and DTX-2. The quantitation of oxidative stress biomarkers in adults, i.e., reactive oxygen species (ROS) production and activity of three endogenous antioxidant defense enzymes (glutathione S-transferase, superoxide dismutase, and catalase) showed that only DTX-2 significantly increased ROS production, whereas each toxin affected the antioxidant enzymes with a different activity profile. In general, the results indicate a negative impact of these toxins towards A. franciscana with potential consequences on the marine ecosystem. Full article

Prorocentrum, a dinoflagellate responsible for producing diarrhetic shellfish poisoning (DSP) toxins, poses significant threats to marine ecosystems, aquaculture industries, and human health. DSP toxins, including okadaic acid (OA), dinophysis toxin (DTX), and their diverse derivatives, continue to be identified and characterized. In this study, we report the isolation of four new diol esters of OA/DTX-1 from large-scale cultures of Prorocentrum lima. Their chemical structures were elucidated through comprehensive NMR and MS analyses, along with structural comparisons with the well-known OA. Notably, compound 1 featured an additional ester group within the diol unit, while compound 2 was revealed to be a C11 diol ester. The cytotoxicity of these newly isolated derivatives was evaluated against three cell lines: Neuro2a (mouse), HCT116 (human), and HepG2 (human). All diol esters exhibited cytotoxic effects, with compound 3 displaying toxicity comparable to OA. These results expand our understanding of DSP toxin diversity and provide valuable insight into the structural variations and biological activity of diol esters of OA/DTX-1. Full article

Background/Objectives: Alzheimer’s disease (AD) remains incurable, highlighting the need for new and diverse animal models to better understand its complex mechanisms. This study compares various injected animal models of AD, focusing on the main theories that explain the disease; Methods: Female Wistar rats (10-months old) were administered intracebroventricularly by artificial cerebrospinal fluid (aCSF) (Control), beta amyloid Aβ1-42 (BA), okadaic acid (OKA), lipopolysaccharides (LPS), buthionine sulfoximine (BSO) or by a mixture of these different molecules (MLG). Cognitive performance was assessed one week or one month after stereotaxic surgery; Results: Our results, show that only the Aβ and the MLG induced a persistence and progressive deficits in the working memory, recognition memory and spatial memory in rats. As the hippocampus (HIP) and the prefrontal cortex (PFC) are particularly involved in memory behavior, we analyzed long-term neuroadaptations in these brain subregions using spectrophotometric and histological methods to assess oxidative stress changes and neuronal loss, respectively. We found that the behavioral impairments in memory and learning were accompanied by irreversible oxidative stress changes and neurodegenerescence, particularly in the HIP; Conclusions: This study provides promising data on the modeling of AD in order to develop an effective therapeutic approach. Full article

Background/Objectives: Corema album berries are edible fruits from the Iberian Atlantic coast, characterized by a rich polyphenolic composition, which endows their juice with potential protective effects against neurodegeneration. This study aimed to evaluate the potential of the relatively lesser-known C. album berries as a novel neuroprotective agent against neurodegenerative diseases. Methods: The phenolic compounds of the juice were characterized using UHPLC-HRMS (Orbitrap). The SH-SY5Y neuroblastoma line was used to determine the preventive effect of the juice against H₂O₂-induced oxidative stress. Furthermore, neuronal cells were differentiated into dopaminergic and cholinergic lines and exposed to 6-hydroxydopamine and okadaic acid, respectively, to simulate in vitro models of Parkinson’s disease and Alzheimer’s disease. The ability of the juice to enhance neuronal viability under toxic conditions was examined. Additionally, its inhibitory effects on neuroprotective-related enzymes, including MAO-A and MAO-B, were assessed in vitro. Results: Phytochemical characterization reveals that 5-O-caffeoylquinic acid constitutes 80% of the total phenolic compounds. Higher concentrations of the juice effectively protected both differentiated and undifferentiated SH-SY5Y cells from H₂O₂-induced oxidative damage, reducing oxidative stress by approximately 20% and suggesting a dose-dependent mechanism. Moreover, the presence of the juice significantly enhanced the viability of dopaminergic and cholinergic cells exposed to neurotoxic agents. In vitro, the juice inhibited the activity of MAO-A (IC₅₀ = 87.21 µg/mL) and MAO-B (IC₅₀ = 56.50 µg/mL). Conclusions: While these findings highlight C. album berries as a promising neuroprotective agent, further research is required to elucidate its neuroprotective mechanisms in cell and animal models and, ultimately, in human trials. Full article

In this report, we describe a fluorescent assay for the detection of six marine toxins in water. The mechanism of detection is based on a duplex-to-complex structure-switching approach. The six aptamers specific to the targeted cyanotoxins were conjugated to a fluorescent dye, carboxyfluorescein (FAM). In parallel, complementary DNA (cDNA) sequences specific to each aptamer were conjugated to a fluorescence quencher BHQ1. In the absence of the target, an aptamer–cDNA duplex structure is formed, and the fluorescence is quenched. By adding the toxin, the aptamer tends to bind to its target and releases the cDNA. The fluorescence intensity is consequently restored after the formation of the complex aptamer–toxin, where the fluorescence recovery is directly correlated with the analyte concentration. Based on this principle, a highly sensitive detection of the six marine toxins was achieved, with the limits of detection of 0.15, 0.06, 0.075, 0.027, 0.041, and 0.026 nM for microcystin-LR, anatoxin-α, saxitoxin, cylindrospermopsin, okadaic acid, and brevetoxin, respectively. Moreover, each aptameric assay showed a very good selectivity towards the other five marine toxins. Finally, the developed technique was applied for the detection of the six toxins in spiked water samples with excellent recoveries. Full article

The Tam Giang-Cau Hai lagoon (TGCH) in Thua Thien Hue province (Vietnam) is a marsh/lagoon system and ranks among the largest waterbodies in Southeast Asia. It plays a significant role in terms of both socio-economic and environmental resources. However, anthropogenic stress, as well as the discharge of untreated domestic and industrial sewage with agricultural runoff from its three major tributaries, dramatically damages the water quality of the lagoon. Especially after heavy rain and flash floods, the continuous degradation of its water quality, followed by harmful algal and cyanobacterial bloom patterns (HABs), is more perceptible. In this study, several physicochemical factors, cyanotoxins (anatoxins (ATXs), saxitoxins (STXs), microcystins (MCs)), phycotoxins (STXs, okadaic acid (OA), and dinophysistoxins (DTXs)) were analyzed in water and shellfish samples from 13 stations in June 2023 from 13 stations, using enzyme-linked immunosorbent assay (ELISA) kits for the ATXs and STXs, and the serine/threonine phosphatase type 2A (PP2A) inhibition assay kit for the MCs, OA, and DTXs. The results showed for the first time the co-occurrence of freshwater cyanotoxins and marine phycotoxins in water and shellfish samples in this lagoon. Traces of ATXs and STXs were detected in the shellfish and the orders of magnitude were below the seafood safety action levels. However, toxins inhibiting the PP2A enzyme, such as MCs and nodularin (NODs), as well as OA and DTXs, were detected at higher concentrations (maximum: 130.4 μg equiv. MC-LR/kg shellfish meat wet weight), approaching the actionable level proposed for this class of toxin in shellfish (160 μg of OA equivalent per kg of edible bivalve mollusk meat). It is very important to note that due to the possible false positives produced by the ELISA test in complex matrices such as a crude shellfish extract, this preliminary and pilot research will be repeated with a more sophisticated method, such as liquid chromatography coupled with mass spectroscopy (LC-MS), in the upcoming research plan. Full article

In a constantly changing environment brought about by the climate crisis and escalated anthropogenic perturbations driven by the growing population, harmful algal bloom dynamics and their impacts are expected to shift, necessitating adaptive management strategies and comprehensive research efforts. Similar to primary productivity, HABs have been thought to be driven primarily by major nutrients such as N, P, and Si. However, recent investigations on the role and importance of micronutrients as limiting factors in aquatic environments have been highlighted. This paper provides a review of metal and phytoplankton interactions, with a specific emphasis on pertinent information on the influence of trace nutrients on growth, toxin production, and other underlying mechanisms related to the dynamics of HABs. Low to near-depleted levels of essential nutrients, including Fe, Cu, Zn, Se, Mn, Co, and Mo, negatively impact cell growth and proliferation of various marine and freshwater HAB species. However, evidence shows that at elevated levels, these trace elements, along with other non-essential ones, could still cause toxic effects to certain HAB species manifested by decreased photosynthetic activities, oxidative stress, ultrastructure damage, and cyst formation. Interestingly, while elevated levels of these metals mostly result in increased toxin production, Co (i.e., yessotoxins, gymnodimine, and palytoxins) and Mn (i.e., isodomoic acid, okadaic and diol esters) enrichments revealed otherwise. In addition to toxin production, releasing dissolved organic matter (DOM), including dissolved organic carbon (DOC) and humic substances, was observed as an adaptation strategy, since these organic compounds have been proven to chelate metals in the water column, thereby reducing metal-induced toxicity. Whilst current research centers on free metal toxicity of specific essential elements such as Cu and Zn, a comprehensive account of how trace metals contribute to the growth, toxin production, and other metabolic processes under conditions reflective of in situ scenarios of HAB-prone areas would yield new perspectives on the roles of trace metals in HABs. With the growing demands of the global population for food security and sustainability, substantial pressure is exerted on the agriculture and aquaculture sector, highlighting the need for effective communication of information regarding the interactions of macro- and micronutrients with HABs to improve existing policies and practices. Full article

GSK-3β, IKK-β, and ROCK-1 kinases are implicated in the pathomechanism of Alzheimer’s disease due to their involvement in the misfolding and accumulation of amyloid β (Aβ) and tau proteins, as well as inflammatory processes. Among these kinases, GSK-3β plays the most crucial role. In this study, we present compound 62, a novel, remarkably potent, competitive GSK-3β inhibitor (IC₅₀ = 8 nM, K_i = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC₅₀ = 2.3 µM) and demonstrates anti-inflammatory and neuroprotective properties. Compound 62 effectively suppresses the production of nitric oxide (NO) and pro-inflammatory cytokines in the lipopolysaccharide-induced model of inflammation in the microglial BV-2 cell line. Furthermore, it shows neuroprotective effects in an okadaic-acid-induced tau hyperphosphorylation cell model of neurodegeneration. The compound also demonstrates the potential for further development, characterized by its chemical and metabolic stability in mouse microsomes and fair solubility. Full article