-
Marine Drugs Apr 2024The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the...
The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the potential of hydroxybenzoic acid derivatives, specifically protocatechuic acid (PCA) and gentisic acid (DHB), for alleviating Nematocyst Venom (NnNV)-induced injuries. By employing an in vivo mouse model, the study delves into the therapeutic efficacy of these compounds. Through a combination of ELISA and Western blot analyses, histological examinations, and molecular assays, the study scrutinizes the inflammatory response, assesses skin damage and repair mechanisms, and investigates the compounds' ability to counteract venom effects. Our findings indicate that PCA and DHB significantly mitigate inflammation by modulating critical cytokines and pathways, altering collagen ratios through topical application, and enhancing VEGF and bFGF levels. Furthermore, both compounds demonstrate potential in neutralizing NnNV toxicity by inhibiting metalloproteinases and phospholipase-A, showcasing the viability of small-molecule compounds in managing toxin-induced injuries.
Topics: Animals; Hydroxybenzoates; Mice; Cnidarian Venoms; Skin; Gentisates; Nematocyst; Disease Models, Animal; Cytokines
PubMed: 38786596
DOI: 10.3390/md22050205 -
Marine Drugs Apr 2024nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The...
nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The nAChR has high Ca permeability and can be quickly activated and desensitized, and is closely related to Alzheimer's disease (AD), epilepsy, schizophrenia, lung cancer, Parkinson's disease (PD), inflammation, and other diseases. α-conotoxins from marine cone snail venom are typically short, disulfide-rich neuropeptides targeting nAChRs and can distinguish various subtypes, providing vital pharmacological tools for the functional research of nAChRs. [Q1G, ΔR14]LvΙB is a rat nAChRs selective antagonist, modified from α-conotoxin LvΙB. In this study, we utilized three types of fluorescein after N-Hydroxy succinimide (NHS) activation treatment: 6-TAMRA-SE, Cy3 NHS, and BODIPY-FL NHS, labeling the N-Terminal of [Q1G, ΔR14]LvΙB under weak alkaline conditions, obtaining three fluorescent analogs: LvIB-R, LvIB-C, and LvIB-B, respectively. The potency of [Q1G, ΔR14]LvΙB fluorescent analogs was evaluated at rat nAChRs expressed in oocytes. Using a two-electrode voltage clamp (TEVC), the half-maximal inhibitory concentration (IC) values of LvIB-R, LvIB-C, and LvIB-B were 643.3 nM, 298.0 nM, and 186.9 nM, respectively. The stability of cerebrospinal fluid analysis showed that after incubation for 12 h, the retention rates of the three fluorescent analogs were 52.2%, 22.1%, and 0%, respectively. [Q1G, ΔR14]LvΙB fluorescent analogs were applied to explore the distribution of nAChRs in the hippocampus and striatum of rat brain tissue and it was found that Cy3- and BODIPY FL-labeled [Q1G, ΔR14]LvΙB exhibited better imaging characteristics than 6-TAMARA-. It was also found that nAChRs are widely distributed in the cerebral cortex and cerebellar lobules. Taking into account potency, imaging, and stability, [Q1G, ΔR14]LvΙB -BODIPY FL is an ideal pharmacological tool to investigate the tissue distribution and function of nAChRs. Our findings not only provide a foundation for the development of conotoxins as visual pharmacological probes, but also demonstrate the distribution of nAChRs in the rat brain.
Topics: Animals; alpha7 Nicotinic Acetylcholine Receptor; Conotoxins; Rats; Brain; Xenopus laevis; Oocytes; Nicotinic Antagonists; Fluorescent Dyes; Rats, Sprague-Dawley; Male; Female
PubMed: 38786593
DOI: 10.3390/md22050200 -
Marine Drugs Apr 2024The Drinking Water Directive (EU) 2020/2184 includes the parameter microcystin LR, a cyanotoxin, which drinking water producers need to analyze if the water source has...
The Drinking Water Directive (EU) 2020/2184 includes the parameter microcystin LR, a cyanotoxin, which drinking water producers need to analyze if the water source has potential for cyanobacterial blooms. In light of the increasing occurrences of cyanobacterial blooms worldwide and given that more than 50 percent of the drinking water in Sweden is produced from surface water, both fresh and brackish, the need for improved knowledge about cyanotoxin occurrence and cyanobacterial diversity has increased. In this study, a total of 98 cyanobacterial blooms were sampled in 2016-2017 and identified based on their toxin production and taxonomical compositions. The surface water samples from freshwater lakes throughout Sweden including brackish water from eight east coast locations along the Baltic Sea were analyzed for their toxin content with LC-MS/MS and taxonomic composition with 16S rRNA amplicon sequencing. Both the extracellular and the total toxin content were analyzed. Microcystin's prevalence was highest with presence in 82% of blooms, of which as a free toxin in 39% of blooms. Saxitoxins were found in 36% of blooms in which the congener decarbamoylsaxitoxin (dcSTX) was detected for the first time in Swedish surface waters at four sampling sites. Anatoxins were most rarely detected, followed by cylindrospermopsin, which were found in 6% and 10% of samples, respectively. As expected, nodularin was detected in samples collected from the Baltic Sea only. The cyanobacterial operational taxonomic units (OTUs) with the highest abundance and prevalence could be annotated to NIES-81 and the second most profuse cyanobacterial taxon to PCC 7914. In addition, two correlations were found, one between NIES-81 and saxitoxins and another between PCC 7914 and microcystins. This study is of value to drinking water management and scientists involved in recognizing and controlling toxic cyanobacteria blooms.
Topics: Sweden; Cyanobacteria; Microcystins; Lakes; Marine Toxins; Saxitoxin; Environmental Monitoring; RNA, Ribosomal, 16S; Bacterial Toxins; Cyanobacteria Toxins; Tandem Mass Spectrometry
PubMed: 38786590
DOI: 10.3390/md22050199 -
Frontiers in Immunology 2024envenomation causes severe cutaneous symptoms known as jellyfish dermatitis. The potential molecule mechanisms and treatment efficiency of dermatitis remain elusive...
BACKGROUND
envenomation causes severe cutaneous symptoms known as jellyfish dermatitis. The potential molecule mechanisms and treatment efficiency of dermatitis remain elusive because of the complicated venom components. The biological activity and molecular regulation mechanism of Troxerutin (TRX) was firstly examined as a potential treatment for jellyfish dermatitis.
METHODS
We examined the inhibit effects of the TRX on tentacle extract (TE) obtained from and using the mice paw swelling models and corresponding assays for Enzyme-Linked Immunosorbent Assay (ELISA) Analysis, cell counting kit-8 assay, flow cytometry, respectively. The mechanism of TRX on HaCaT cells probed the altered activity of relevant signaling pathways by RNA sequencing and verified by RT-qPCR, Western blot to further confirm protective effects of TRX against the inflammation and oxidative damage caused by TE.
RESULTS
TE significantly induced the mice paw skin toxicity and accumulation of inflammatory cytokines and reactive oxygen species in vivo and vitro. Moreover, a robust increase in the phosphorylation of mitogen-activated protein kinase (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways was observed. While, the acute cutaneous inflammation and oxidative stress induced by TE were significantly ameliorated by TRX treatment. Notablly, TRX suppressed the phosphorylation of MAPK and NF-κB by initiating the nuclear factor erythroid 2-related factor 2 signaling pathway, which result in decreasing inflammatory cytokine release.
CONCLUSION
TRX inhibits the major signaling pathway responsible for inducing inflammatory and oxidative damage of jellyfish dermatitis, offering a novel therapy in clinical applications.
Topics: Animals; Oxidative Stress; Mice; NF-E2-Related Factor 2; Signal Transduction; Dermatitis; Humans; Hydroxyethylrutoside; Scyphozoa; Cnidarian Venoms; Heme Oxygenase-1; Disease Models, Animal; Inflammation; Male; Cytokines; Anti-Inflammatory Agents; HaCaT Cells; Reactive Oxygen Species; Membrane Proteins
PubMed: 38779681
DOI: 10.3389/fimmu.2024.1369849 -
The Science of the Total Environment Aug 2024To innovate the design of water treatment technology for algal toxin removal, this research investigated the mechanisms of cyanotoxin microcystin-LR (MC-LR) removal by a...
To innovate the design of water treatment technology for algal toxin removal, this research investigated the mechanisms of cyanotoxin microcystin-LR (MC-LR) removal by a coupled adsorption-biodegradation. Eight types of woody carbonaceous adsorbents with and without Sphingopyxis sp. m6, a MC-LR degrading bacterium, were tested for MC-LR removal in water. All adsorbents showed good adsorption capability, removing 40 % to almost 100 % of the MC-LR (4.5 mg/L) within 48 h in batch experiments. Adding Sphingopyxis sp. m6 continuously promoted MC-LR biological removal, and successfully broke the barrier of adsorption capacity of tested adsorbents, removing >90 % of the MC-LR in most of the coupled adsorption-biodegradation tests, especially for those adsorbents had low physiochemical adsorption capacity. Variance partitioning analysis indicated that mesopore was the dominant contributor to adsorption capacity of MC-LR in pure adsorption treatments, which acted synergistically with electrical conductivity, polarity and total functional groups on the absorbent. Pore structure was the key factor beneficial for the growth of Sphingopyxis sp. m6 (51% contribution) and subsequent MC-LR biological removal rate (80 % contribution). Overall, pinewood-based carbonaceous adsorbents (especially pinewood activated carbon) exhibited the highest adsorption capacity towards MC-LR and provided the most favorable conditions for biological removal of MC-LR, largely because of their high mesopore volume, total functional groups and electric conductivity. The research outcomes not only deepened the quantitative understanding of mechanisms for MC-LR removal by the coupled process, but also provided theoretical basis for future materials' selection and modification during the practical application of coupled process.
Topics: Microcystins; Marine Toxins; Adsorption; Biodegradation, Environmental; Water Purification; Water Pollutants, Chemical; Sphingomonadaceae
PubMed: 38772489
DOI: 10.1016/j.scitotenv.2024.173370 -
Ecotoxicology and Environmental Safety Jul 2024Microcystins (MCs) are toxic to the central nervous system of mammals. However, the direct toxicity of MCs on mammalian brain cells and the involved molecular mechanisms...
Microcystins (MCs) are toxic to the central nervous system of mammals. However, the direct toxicity of MCs on mammalian brain cells and the involved molecular mechanisms are not fully elucidated. Here, we incubated primary astrocytes, the major glial cell-type in the brain, with 0-12.5 μM concentrations of MC-LR for 48 h, and the impairment was evaluated. We found that MC-LR caused significant increases in the cell viability at the range of 0.05-1 μM concentrations with the highest density at 0.1 μM concentration. Treatment with 0.1 μM MC-LR induced YAP nuclear translocation and decreased the ratio of p-YAP to YAP. It also decreased mRNA levels of the upstream regulator (AMOT), and enhanced expressions of YAP interacted genes (Egfr, Tead1, and Ctgf) in primary astrocytes. Overexpression of AMOT significantly attenuated the increase of MC-LR-induced astrocyte proliferation and the expression of YAP downstream genes. These results indicate that Hippo signaling contributed to MC-LR-caused astrocyte proliferation. Further, reactive astrogliosis was observed in the mice brain after MC-LR exposure to environmentally relevant concentrations (20 or 100 μg/L) through drinking water for 16 weeks. Pathological observations revealed that 100 μg/L MC-LR exposure caused neuronal damages with characteristics of shrunken or vacuolation in the region of the cerebral cortex, striatum and cerebellum. These results were accompanied with increased oxidative stress and inflammatory response. Our data reveal the potential astrocytic mechanisms in MC-induced neurotoxicity and raise an alarm for neurodegenerative disease risk following daily exposure to MC-LR.
Topics: Microcystins; Animals; Astrocytes; Marine Toxins; Hippo Signaling Pathway; Signal Transduction; Cell Proliferation; Mice; Protein Serine-Threonine Kinases; YAP-Signaling Proteins; Cell Survival; Transcription Factors; ErbB Receptors; TEA Domain Transcription Factors; DNA-Binding Proteins
PubMed: 38772146
DOI: 10.1016/j.ecoenv.2024.116480 -
JCI Insight May 2024Pathogenic variants in SCN8A, which encodes the voltage-gated sodium (NaV) channel NaV1.6, associate with neurodevelopmental disorders, including developmental and...
Pathogenic variants in SCN8A, which encodes the voltage-gated sodium (NaV) channel NaV1.6, associate with neurodevelopmental disorders, including developmental and epileptic encephalopathy. Previous approaches to determine SCN8A variant function may be confounded by use of a neonatally expressed, alternatively spliced isoform of NaV1.6 (NaV1.6N) and engineered mutations rendering the channel tetrodotoxin (TTX) resistant. We investigated the impact of SCN8A alternative splicing on variant function by comparing the functional attributes of 15 variants expressed in 2 developmentally regulated splice isoforms (NaV1.6N, NaV1.6A). We employed automated patch clamp recording to enhance throughput, and developed a neuronal cell line (ND7/LoNav) with low levels of endogenous NaV current to obviate the need for TTX-resistance mutations. Expression of NaV1.6N or NaV1.6A in ND7/LoNav cells generated NaV currents with small, but significant, differences in voltage dependence of activation and inactivation. TTX-resistant versions of both isoforms exhibited significant functional differences compared with the corresponding WT channels. We demonstrated that many of the 15 disease-associated variants studied exhibited isoform-dependent functional effects, and that many of the studied SCN8A variants exhibited functional properties that were not easily classified as either gain- or loss-of-function. Our work illustrates the value of considering molecular and cellular context when investigating SCN8A variants.
Topics: NAV1.6 Voltage-Gated Sodium Channel; Humans; Protein Isoforms; Alternative Splicing; Tetrodotoxin; Neurons; Patch-Clamp Techniques; Mutation; Cell Line; Animals
PubMed: 38771640
DOI: 10.1172/jci.insight.177530 -
Journal of Cellular and Molecular... May 2024Fermented foods play a significant role in the human diet for their natural, highly nutritious and healthy attributes. Our aim was to study the effect of yeast extract,...
Fermented foods play a significant role in the human diet for their natural, highly nutritious and healthy attributes. Our aim was to study the effect of yeast extract, a fermented substance extracted from natural yeast, on colonic motility to better understand its potential therapeutic role. A yeast extract was given to rats by gavage for 3 days, and myogenic and neurogenic components of colonic motility were studied using spatiotemporal maps made from video recordings of the whole colon ex vivo. A control group received saline gavages. The yeast extract caused excitation of the musculature by increasing the propagation length and duration of long-distance contractions, the major propulsive activity of the rat colon. The yeast extract also evoked rhythmic propulsive motor complexes (RPMCs) which were antegrade in the proximal and mid-colon and retrograde in the distal colon. RPMC activity was evoked by distention-induced neural activity, but it was myogenic in nature since we showed it to be generated by bethanechol in the presence of tetrodotoxin. In conclusion, ingestion of yeast extract stimulates rat colon motility by exciting neurogenic and myogenic control mechanisms.
Topics: Animals; Colon; Gastrointestinal Motility; Rats; Male; Yeasts; Rats, Sprague-Dawley; Tetrodotoxin
PubMed: 38760903
DOI: 10.1111/jcmm.18343 -
Scientific Reports May 2024The present study assessed the effective use of biochar for the adsorption of two potent HAB toxins namely, Microcystin-LR (MCLR) and Saxitoxin (STX) through a...
The present study assessed the effective use of biochar for the adsorption of two potent HAB toxins namely, Microcystin-LR (MCLR) and Saxitoxin (STX) through a combination of dosage, kinetic, equilibrium, initial pH, and competitive adsorption experiments. The adsorption results suggest that biochar has excellent capabilities for removing MCLR and STX, with STX reporting higher adsorption capacities (622.53-3507.46 µg/g). STX removal required a minimal dosage of 0.02 g/L, while MCLR removal needed 0.4 g/L for > 90%. Similarly, a shorter contact time was required for STX removal compared to MCLR for > 90% of toxin removed from water. Initial pH study revealed that for MCLR acidic conditions favored higher uptake while STX favored basic conditions. Kinetic studies revealed that the Elovich model to be most suitable for both toxins, while STX also showed suitable fittings for Pseudo-First Order and Pseudo-Second Order in individual toxin systems. Similarly, for the Elovich model the most suited kinetic model for both toxins in presence of each other. Isotherm studies confirmed the Langmuir-Freundlich model as the best fit for both toxins. These results suggest adsorption mechanisms including pore filling, hydrogen bonding, π-π interactions, hydrophobic interactions, electrostatic attraction, and dispersive interactions.
Topics: Microcystins; Charcoal; Saxitoxin; Marine Toxins; Adsorption; Kinetics; Water Purification; Hydrogen-Ion Concentration; Water Pollutants, Chemical
PubMed: 38745050
DOI: 10.1038/s41598-024-61802-z -
The Journal of Medical Investigation :... 2024Vibrio vulnificus (V. vulnificus) is a halophilic gram-negative bacterium that inhabits coastal warm water and induce severe diseases such as primary septicemia. To...
Vibrio vulnificus (V. vulnificus) is a halophilic gram-negative bacterium that inhabits coastal warm water and induce severe diseases such as primary septicemia. To investigate the mechanisms of rapid bacterial translocation on intestinal infection, we focused on outer membrane vesicles (OMVs), which are extracellular vesicles produced by Gram-negative bacteria and deliver virulence factors. However, there are very few studies on the pathogenicity or contents of V. vulnificus OMVs (Vv-OMVs). In this study, we investigated the effects of Vv-OMVs on host cells. Epithelial cells INT407 were stimulated with purified OMVs and morphological alterations and levels of lactate dehydrogenase (LDH) release were observed. In cells treated with OMVs, cell detachment without LDH release was observed, which exhibited different characteristics from cytotoxic cell detachment observed in V. vulnificus infection. Interestingly, OMVs from a Vibrio Vulnificus Hemolysin (VVH) and Multifunctional-autoprocessing repeats-in -toxin (MARTX) double-deletion mutant strain also caused cell detachment without LDH release. Our results suggested that the proteolytic function of a serine protease contained in Vv-OMVs may contribute to pathogenicity of V. vulnificus by assisting bacterial translocation. This study reveals a new pathogenic mechanism during V. vulnificus infections. J. Med. Invest. 71 : 102-112, February, 2024.
Topics: Vibrio vulnificus; Humans; Extracellular Vesicles; Hemolysin Proteins; L-Lactate Dehydrogenase; Bacterial Outer Membrane; Epithelial Cells
PubMed: 38735705
DOI: 10.2152/jmi.71.102