Toxins最新文献

In this paper, we examine the filamentous cyanobacterial strain NILCB16 and describe it as a new species within the genus Pegethrix. The original population was sampled from a mat growing in an irrigation canal in the Nile River, Egypt. Initially classified under Plectonema or Planktolyngbya, the strain is a potential producer of the toxins microcystin and β-N-Methylamino-L-Alanine (BMAA). Additionally, we reviewed the taxonomic relationships between the Oculatellales genera. To describe the new species, we conducted a polyphasic study, encompassing 16S rRNA gene phylogenetic analyses performed using both Maximum Likelihood and Bayesian methods, sequence identity (p-distance) analysis, 16S-23S ITS secondary structures, and morphological and habitat comparisons. The phylogenetic analysis revealed that strain NILCB16 clustered within the Pegethrix clade with strong phylogenetic support, but in a distinct position from other species in the genus. The strain shared a maximum 16S rRNA gene identity of 97.3% with P. qiandaoensis and 96.1% with the type species, P. bostrychoides. Morphologically, NILCB16 can be differentiated from other species in the genus by its lack of false branching. Our phylogenetic analyses also show that Pegethrix, Cartusia, Elainella, and Maricoleus are clustered with strong phylogenetic support. They exhibit high 16S rRNA gene identity and are morphologically indistinguishable, suggesting they could potentially be merged into a single genus in the future.

Recent studies have revealed that the coagulation system plays a role in mammalian innate defense by entrapping bacteria in clots and generating antibacterial peptides. So, it is very important for the survival of bacteria to defend against the host coagulation system, which suggests that bacterial exotoxins might be a new source of anticoagulants. In this study, we analyzed the genomic sequences of Acinetobacter baumannii and a new bacterial exotoxin protein, F6W77, with five Kunitz-domains, KABP1-5, was identified. Each Kunitz-type domain features a classical six-cysteine framework reticulated by three conserved disulfide bridges, which was obviously similar to animal Kunitz-domain peptides but different from plant Kunitz-domain peptides. Anticoagulation function evaluation showed that towards the intrinsic coagulation pathway, KABP1 and KABP5 had apparently inhibitory activity, KABP4 had weak inhibitory activity, and KBAP2 and KABP3 had no effect even at a high concentration of 20 μg/mL. All five Kunitz-domain peptides, KABP1-5, had no inhibitory activity towards the extrinsic coagulation pathway. Enzyme-inhibitor experiments showed that the high-activity anticoagulant peptide KABP1 had apparently inhibitory activity towards two key coagulation factors, Xa and XIa, which was further confirmed by pull-down experiments that showed that KABP1 can bind to coagulation factors Xa and XIa directly. Structure-function relationship analyses of five Kunitz-type domain peptides showed that the arginine of the P1 site of three new bacterial anticoagulants, KABP1, KABP4 and KABP5, might be the key residue for their anticoagulation activity. In conclusion, with bioinformatics analyses, peptide recombination, and functional evaluation, we firstly found bacterial-exotoxin-derived Kunitz-type serine protease inhibitors with selectively inhibiting activity towards intrinsic coagulation pathways, and highlighted a new interaction between pathogenic bacteria and the human coagulation system.

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies.

Cyanobacterial blooms have become a serious water pollution problem in many parts of the world, and the monitoring and study of the impacts of biotoxins on human health are of vital importance. In this study, the contents of microcystin-LR, 2-methylisoborneol, and geosmin were measured in water and sediment samples from Nanwan Reservoir, China, by means of bimonthly sampling between February and December 2023. The physicochemical and hydrochemical factors and phytoplankton dynamics in the reservoir were also investigated. The results showed that the overall mean concentration of microcystin-LR (0.729 μg/L) in summer approached the guiding standard (1 μg/L) set by the WHO for drinking water. Furthermore, the content of 2-methylisoborneol (143.5 ng/L) was 14 times higher than the national standard (10 ng/L). The results of laboratory cultures showed that lower light levels and medium temperatures were suitable for the growth of Microcystis and Planktothricoides but higher temperatures promoted the synthesis and release of microcystin-LR and 2-methylisoborneol. In addition, the results of co-cultures showed that the growth of Planktothricoides was inhibited by Microcystis. Our results suggest that cyanobacterial bloom and the presence of the metabolites 2-methylisoborneol and microcystin-LR can decrease the drinking water quality of Nanwan Reservoir.

A comprehensive LC-MS study examined the venom components of the solitary scoliid wasp Scolia oculata. Online mass fingerprinting showed that crude venom contains 25 small molecules (amino acids, biogenic amines, and nucleosides/nucleotides) and 45 peptides with MW 400-2700. The small molecules were identified by elemental composition analysis, and peptide sequences were determined by ESI-MS/MS and MALDI-TOF/TOF MS analyses. As major peptide components, a known peptide, β-scoliidine (DYVTVKGFSPLRKA), and three new peptides, γ-scoliidine (YVTVKGFSPLR), δ-scoliidine (YVTVKGFSPLREP) and ε-scoliidine (DYVTVKGFSPLREP) were identified, all of which are closely homologous to each other. Once the neuroprotective effects of β-scoliidine have already been described, the other three new scoliidine peptides were analyzed against oxidative stress-induced toxicity in PC12 neuronal cells by mitochondrial metabolism assay, and the structure-activity relationship was evaluated. Interestingly, pre-treatment with ε-scoliidine increased the mitochondrial metabolism of PC12 cells (106 ± 3.6%; p = 0.007) exposed to H₂O₂-induced oxidative stress in contrast to γ- and δ-scoliidines (77.6 ± 4.8 and 68.5 ± 4.1%, respectively) in compared to cells treated only H₂O₂ (75.8 ± 2.4%). These new peptides were also analyzed for enzyme inhibitor/substrate assays with angiotensin-converting enzyme (ACE), neprilysin (NEP), and acetylcholinesterase (AChE). In these assays, only δ- and ε-scoliidines increased the AChE activity (128.7 ± 3.8%; p = 0.01; and 116.8 ± 3.8% p = 0.03; respectively) in relation to basal activity (100.1 ± 1.6%). In addition, the four peptides were analyzed through in silico analysis, and none of them demonstrated possible hemolytic and toxic activities. In our study, the comprehensive LC-MS and MS/MS analyses of Scolia oculate venom identified four major peptide components of the venom β-, γ-, δ- and ε-scoliidines, and small differences in their primary structures are important to their neuroprotective properties.

Within the phylum Cnidaria, sea anemones (class Anthozoa) express a rich diversity of ion-channel peptide modulators with biomedical applications, but corollary discoveries from jellyfish (subphylum Medusozoa) are lacking. To bridge this gap, bioactivities of previously unexplored proteinaceous and small molecular weight (~15 kDa to 5 kDa) venom components were assessed in a mouse dorsal root ganglia (DRG) high-content calcium-imaging assay, known as constellation pharmacology. While the addition of crude venom led to nonspecific cell death and Fura-2 signal leakage due to pore-forming activity, purified small molecular weight fractions of venom demonstrated three main, concentration-dependent and reversible effects on defined heterogeneous cell types found in the primary cultures of mouse DRG. These three phenotypic responses are herein referred to as phenotype A, B and C: excitatory amplification (A) or inhibition (B) of KCl-induced calcium signals, and test compound-induced disturbances to baseline calcium levels (C). Most notably, certain Alatina alata venom fractions showed phenotype A effects in all DRG neurons; Physalia physalis and Chironex fleckeri fractions predominantly showed phenotype B effects in small- and medium-diameter neurons. Finally, specific Physalia physalis and Alatina alata venom components induced direct excitatory responses (phenotype C) in glial cells. These findings demonstrate a diversity of neuroactive compounds in jellyfish venom potentially targeting a constellation of ion channels and ligand-gated receptors with broad physiological implications.

The global prevalence of aflatoxin B1 (AFB1) and zearalenone (ZEN) contamination in food and feed poses a serious health risk to humans and animals. Recently, enzymatic detoxification has received increasing attention, yet most enzymes are limited to degrading only one type of mycotoxin, and free enzymes often exhibit reduced stability and activity, limiting their practicality in real-world applications. In this study, the laccase CotA gene from ZEN/AFB1-degrading Bacillus subtilis ZJ-2019-1 was cloned and successfully expressed in Escherichia coli BL21, achieving a protein yield of 7.0 mg/g. The recombinant CotA (rCotA) completely degraded AFB1 and ZEN, with optimal activity at 70 °C and pH 7.0. After rCotA treatment, neither AFB1 nor ZEN showed significantly cytotoxicity to mouse macrophage cell lines. Additionally, the AFB1/ZEN degradation efficiency of rCotA was significantly enhanced by five natural redox mediators: acetosyringone, syringaldehyde, vanillin, matrine, and sophoridin. Among them, the acetosyringone-rCotA was the most effective mediator system, which could completely degrade 10 μg of AFB1 and ZEN within 1 h. Furthermore, the chitosan-immobilized rCotA system exhibited higher degradation activity than free rCotA. The immobilized rCotA degraded 27.95% of ZEN and 41.37% of AFB1 in contaminated maize meal within 12 h, and it still maintained more than 40% activity after 12 reuse cycles. These results suggest that media-assisted or immobilized enzyme systems not only boost degradation efficiency but also demonstrate remarkable reusability, offering promising strategies to enhance the degradation efficiency of rCotA for mycotoxin detoxification.

Specialized metabolites, also known as secondary metabolites, produced by plants and microbes possess several biological activities [...].

Introduction: Botulinum neurotoxin A (BoNT-A) is a treatment option for neurogenic lower urinary tract dysfunctions (NLUTD) and idiopathic overactive bladder (OAB) in adults. Recently, its use has gained popularity in paediatric urology. Transitional urology deals with adolescents affected by congenital urological issues, who mature into adulthood. The aim of this systematic review was to update the current knowledge on the use of BoNT-A in children and adolescents.

Methods: A comprehensive search in PubMed, Scopus, and Web of Science databases was performed from articles published up to September 2024. Both prospective and retrospective single-cohort or comparative studies evaluating outcomes of interest were included. These consisted of the amelioration of urinary incontinence (UI), continence rates, improvement of urodynamic parameters (maximum detrusor pressure during voiding, maximum bladder capacity, and bladder compliance), and type and prevalence of adverse/side effects. Qualitative and quantitative data syntheses were provided. Moderators and meta-regression analyses were carried out as well.

Results: Forty-one full-text manuscripts were selected of which 26 focused on children with NLUTD, 13 on idiopathic OAB, and two on both conditions. Overall, 1521 patients were included of whom 715 were male, 646 female, and 160 of unknown sex. Mean age varied between 5.6 and 15.6 years. No studies specifically focused on transitional urology, despite patients up to at least 17 years of age being included. Several differences existed in design, type, dose, way of administration, outcomes measured and follow-up time; however, all studies independently showed an improvement of UI and urodynamic parameters with no major side/adverse events. Pooled analysis showed a mean rate of improvement in UI scores/episodes of 75.87% within a period of 3-6 months following BoNT-A treatment. Meta-regression analyses demonstrated a significant correlation between dryness rate and both patients' age (negative) and bladder compliance (positive).

Conclusions: Several uncontrolled or comparative studies provided significative evidence of the clinical benefit and safety of BoNT-A administration in children in terms of UI relief and improvement of urodynamic parameters, with neurogenic aetiologies being the most investigated conditions. A reduced bladder compliance was identified as one of the potential predictors of poor response to BoNT-A. Moreover, the earlier the treatment was started the higher the success rate that was reached in terms of dryness/urinary continence achievement.

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R²) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R² = 0.74; muscle weakness = 0.096, R² = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY^®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.