Toxins最新文献

This study aimed to assess the presence of ochratoxin A (OTA) residues in the blood serum of slaughtered pigs in Greece. Samples were obtained from 1695 healthy slaughtered pigs originating from 113 different farms located in 21 geographic regional units in 8 different geographic regions of Greece and were analyzed using an immunosorbent assay (ELISA) and high-performance liquid chromatography with fluorescence detector (HPLC-FD). OTA contamination assessment showed that 782 (46.1%) and 1233 (72.7%) samples were OTA-positive, with a concentration range of 0.20-5.38 μg/L and 0.15-5.96 µg/L according to ELISA and HPLC-FD analysis, respectively. Also, 88 (77.9%) and 108 (95.6%) of farms were found to be OTA-positive by ELISA and HPLC-FD analysis, respectively. The highest OTA serum positivity rate (>98%) and toxin level (5.96 µg/L) determined by HPLC-FD were observed in the Thessaly region, whereas a high prevalence of up to 100% (range 75-100%) was found on farms in the Crete Island region. The detection of OTA in the serum of slaughtered pigs in different regions in Greece poses a risk for animal and human health and highlights the need for constant OTA monitoring in the swine industry and pork meat production facilities.

OnabotulinumtoxinA (onabotA) is approved in the US for 12 therapeutic indications. Real-world data on onabotA multi-indication use are limited, often leading to delayed or reduced treatment. This study provides real-world evidence on the safety of onabotA when treating multiple indications concomitantly. SYNCHRONIZE was a multicenter, retrospective, chart-review study evaluating onabotA's safety for adults treated for ≥2 therapeutic indications within a 3-month period. The primary outcome was treatment-emergent adverse events (TEAEs) within 6 months post-treatment. A total of 279 patients were included. The most common concomitant indications treated were cervical dystonia and chronic migraine (43.4%). The average 3-month cumulative dose for multiple indications was 282.2 U. The treatment interval for multiple indications was ≤24 h for most patients (62.4%). Overall, 28.7% of patients reported ≥1 TEAE with no apparent trends in TEAEs and dose interval or cumulative dose. Reported TEAEs included UTI (5.7%), neck pain (5.0%), and headache (4.3%). No patient had a lack of effect according to clinical objective measurements. SYNCHRONIZE described the real-world safety of onabotA for patients treated concomitantly for ≥2 indications within a 3-month period. TEAEs were generally consistent with the known safety profiles of individual indications. No new safety signals were identified).

Aflatoxin B1 (AFB1) produced by some Aspergillus species belongs to the most dangerous contaminants of animal feeds. Development of safe and cost efficient decontamination methods saving feed quality and nutritional value are of paramount importance. The use of recombinant AFB1-detoxifying microbial enzymes represents a promising biotechnological approach meeting the aforementioned requirements. In this study, three AFB1-degrading oxidases (AFOs) from edible basidiomycetes Cantharellus cibarius, Lentinula edodes and Pleurotus eryngii as well as AFO from Armillaria tabescens were expressed in E. coli Rosetta (DE3) and purified by immobilized metal-chelate chromatography. The stabilizing effect of the addition of glycerol and β-mercaptoethanol during protein extraction is shown. The catalytic constants of the recombinant AFOs (rAFOs) and other characteristics, which might be important for their practical application (and optimal temperature and pH, thermolability, regulation of the activity by metal ions and chelating agents, storage stability) were investigated. Among the obtained enzymes, rAFO from P. eryngii (Pe-AFO), which was characterized by the highest specific activity, thermostability and pH stability (especially at acidic pH range), the lowest K_m, and relative resistance to the inhibition by phytate, showed the best AFB1-degrading efficacy. However, Pe-AFO and all other rAFOs significantly decreased the target activity during heating above 45 °C, storage frozen or lyophilization.

Aflatoxin constitutes a significant concern for food and feed safety, posing detrimental health risks to both animals and humans. This study aimed to examine the prevalence and concentration of aflatoxins in maize feed, total mixed ration, and wheat bran collected from specialized dairy farms and local markets in three major urban centers in eastern Ethiopia. A total of 180 feed samples were collected from September 2021 to January 2022 in Chiro town, Dire Dawa city, and Harar city. These samples underwent thorough extraction and immunoaffinity clean-up before aflatoxin analysis using HPLC/FLD. The results revealed that AFB₁, AFB₂, AFG₁, AFG₂, and TAF contamination was detected in 72.2%, 66.1%, 71.1%, 68.7%, and 82.8% of the feed samples, respectively. The corresponding mean levels of each aflatoxin were 28.15 ± 3.50, 3.3 ± 0.40, 19.87 ± 1.87, 2.7 ± 0.32, and 54.01 ± 4.72 µg/kg, respectively. The occurrence and levels of aflatoxin varied across different study sites and feed types. Notably, feeds from Dire Dawa city exhibited significantly higher mean levels of AFB₁ (43.98 ± 5.3 µg/kg), AFB₂ (5.69 ± 0.6 µg/kg), AFG₁ (32.25 ± 2.7 µg/kg), and AFG₂ (5.01 ± 0.5 µg/kg) than feeds from other urban centers did. Additionally, a significantly higher occurrence of AFB₁ (29.4%) and AFG₁ (28.3%) was detected in feed from Dire Dawa city. Similarly, the total mixed ration (TMR) displayed significantly higher levels of AFB₁ (50.67 ± 5.2 µg/kg), AFB₂ (4.74 ± 0.6 µg/kg), AFG₁ (32.87 ± 2.6 µg/kg), and AFG₂ (3.86 ± 0.5 µg/kg) compared to the other feed types. Moreover, a significantly higher occurrence of AFB₁ (30.7%) and AFG₁ (28.7%) was detected in the TMR. Furthermore, a moderate correlation was observed between the count of aflatoxigenic Aspergillus species and the levels of TAF in the feed samples. Overall, this study underscores the widespread presence of aflatoxin contamination in dairy feeds in eastern Ethiopia, highlighting the urgent need for stringent monitoring and mitigation measures to ensure food and feed safety, as well as public health.

Palytoxins are a group of highly potent and structurally complex marine toxins that rank among some of the most toxic substances known to science. Palytoxins are naturally synthesized by a variety of marine organisms, including Palythoa zoanthids, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria, and are widely distributed in tropical and temperate regions where they can bioaccumulate in marine life. The evolution of research on palytoxins has been an intricate exchange between interdisciplinary fields, drawing insights from chemistry, biology, medicine, and environmental science in efforts to better understand and mitigate the health risks associated with this family of toxins. In this review, we begin with a brief history covering the discovery of this group of toxins and the events that led to its isolation. We then focus on the chemical structure of these compounds and their proposed mechanism of action. Finally, we review in vitro, ex vivo, and in vivo studies related to their toxicity, with the aim to provide a broad overview of the current knowledge on palytoxin toxinology.

Parasporin PS2Aa1, recently renamed Mpp46Aa1, is an anti-cancer protein known for its selectivity against various human cancer cell lines. We genetically modified native PS2Aa1 to create a library of approximately 100 mutants. From this library, we selected promising mutants based on their half-maximal inhibitory concentration (IC₅₀) and sequence variations. In this study, Variant 3-35, with the G257V substitution, demonstrated increased cytotoxicity and selectivity against the colon cancer cell line SW480. Conversely, Variant N65, featuring substitutions N92D, K175R, and S218G, yielded the most favorable results against the cancer cell lines SW-620, MOLT-4, and Jurkat. The caspase 3/7 and 9, Annexin V-Cy3 and 6-GFDA activities, and, most notably, mitochondrial membrane permeabilization assays confirmed the apoptotic marker elevation. These findings indicate that residues 92, 175, 218, and 257 may play a critical role in the cytotoxic activity and selectivity. We successfully obtained genetically improved variants with substitutions at these key amino acid positions. Additionally, we conducted molecular dynamic simulations to explore the potential interactions between PS2Aa1 and the CD59 GPI-anchored protein. The simulation results revealed that residues 57, 92, and 101 were consistently present, suggesting their possible significance in the interactions between parasporin and the CD59 protein.

Background: Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix^®). The fecal microbiota composition was analyzed in a subgroup of patients (n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes, Lentisphaerae, and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota.

Ricin is a highly potent toxin that has been used in various attempts at bioterrorism worldwide. Although a vaccine for preventing ricin poisoning (RiVax™) is in clinical development, there are currently no commercially available prophylaxis or treatments for ricin intoxication. Numerous studies have highlighted the potential of passive immunotherapy using anti-ricin monoclonal antibodies (mAbs) and have shown promising results in preclinical models. In this article, we describe the neutralizing and protective efficacy of a new generation of high-affinity anti-ricin mAbs, which bind and neutralize very efficiently both ricin isoforms D and E in vitro through cytotoxicity cell assays. In vivo, protection assay revealed that one of these mAbs (RicE5) conferred over 90% survival in a murine model challenged intranasally with a 5 LD₅₀ of ricin and treated by intravenous administration of the mAbs 6 h post-intoxication. Notably, a 35% survival rate was observed even when treatment was administered 24 h post-exposure. Moreover, all surviving mice exhibited long-term immunity to high ricin doses. These findings offer promising results for the clinical development of a therapeutic candidate against ricin intoxication and may also pave the way for novel vaccination strategies against ricin or other toxins.

Potato is the fourth most consumed crop in the world. More than half of the crop is stored for three to nine months at cold temperatures (3-10 °C) for the fresh and seed market. One of the main causes of fresh potato waste in the retail supply chain is the processing of fungal and bacterial rots during storage. Dry rot is a fungal disease that mainly affects the potato crop during storage and is responsible for 1% of tuber losses in the UK. It is produced by Fusarium spp., such as Fusarium sambucinum and F. oxysporum, which can lead to the accumulation of mycotoxins in the potato tuber. Little is known about the impact of environmental factors on the accumulation of mycotoxins in potato tubers. Understanding the ecophysiology of these fungi is key to mitigating their occurrence under commercial storage conditions. Therefore, this work aimed to elucidate the effect of three different temperatures (5, 10, and 15 °C) and two different water activities (a_w; 0.97, 0.99) on the ecophysiology and mycotoxin accumulation of F. sambucinum and F. oxysporum in a potato-based semi-synthetic medium. The mycotoxin accumulation was then studied in vivo, in potato tubers cultivated under organic farming conditions, stored for 40 days at 8.5 °C. Results showed that higher temperatures and a_w enhanced fungal growth, lag time, and mycotoxin accumulation in vitro. Growth rate was 2 and 3.6 times higher when the temperature increased from 5 to 10 and 15 °C, respectively. Six different mycotoxins (T-2, HT-2, diacetoxyscirpenol, 15-acetoxyscirpenol, neosolaniol, and beauvericin) were detected in vitro and in vivo. T-2 was the most abundant mycotoxin detected in vitro, observing 10⁶ ng of T-2/g media after 21 days of incubation at 10 °C and 0.99 a_w. Due to the long period of time that potato tubers spend in storage, the fluctuations of environmental factors, such as temperature and relative humidity, could promote the development of fungal rot, as well as mycotoxin accumulation. This could result in important food and economic losses for the potato market and a threat to food safety.

With the increasing use of Botulinum toxin type A (BoNT-A) injections in the masseter muscles for both medical and aesthetic purposes, there is a constant need to continually enhance the efficacy of these treatments and reduce the risk of potential adverse events. This review provides an in-depth analysis of the masseter muscle's anatomical structure and essential landmarks and emphasizes the advantages of ultrasound (US) guidance in improving the precision of BoNT-A injections compared to conventional blind methods. The review is supplemented with comprehensive figures, including graphics, clinical images, and ultrasound visuals, to support the discussion. Potential complications such as paradoxical bulging, inadvertent injections into the risorius muscle or parotid gland, facial paralysis, and the risk of bone resorption are examined. Future research should aim at refining injection techniques and assessing the long-term effects of repeated treatments to ensure optimal patient care and safety.