Toxins最新文献

Fusarium neocosmosporiellum is the main pathogen of peanut pod rot in China. To investigate the type of F. neocosmosporiellum toxin and its pathogenic mechanism, a macrolide, brefeldin A, was isolated. The structure of the compound was identified by 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). At the same time, the content of the compound in healthy and diseased peanut capsules was detected, and its plant toxicity to radish, mung bean, rice, and peanut seed radicle elongation and pathogenicity to peanut pod rot were evaluated. The results showed that brefeldin A at 50 μg/mL could significantly inhibit the radicle elongation of rice seeds. Brefeldin A was detected only in pods with peanut rot. Injecting 2 mg/mL brefeldin A solution into peanut pods caused the severe decay of peanut pods at the R3R4 stage, which is consistent with the symptoms of peanut rot.

Microcystin-leucine arginine (MC-LR) poses a serious threat to aquatic animals during cyanobacterial blooms. Recently, biochar (BC), derived from rice straw, has emerged as a potent adsorbent for eliminating hazardous contaminants from water. To assess the joint hepatotoxic effects of environmentally relevant concentrations of MC-LR and BC on fish, male adult zebrafish (Danio rerio) were sub-chronically co-exposed to varying concentrations of MC-LR (0, 1, 5, and 25 μg/L) and BC (0 and 100 μg/L) in a fully factorial experiment. After 30 days exposure, our findings suggested that the existence of BC significantly decreased MC-LR bioavailability in liver. Furthermore, histopathological analysis revealed that BC mitigated MC-LR-induced hepatic lesions, which were characterized by mild damage, such as vacuolization, pyknotic nuclei, and swollen mitochondria. Compared to the groups exposed solely to MC-LR, decreased malondialdehyde (MDA) and increased catalase (CAT) and superoxide dismutase (SOD) were noticed in the mixture groups. Concurrently, significant changes in the mRNA expression levels of Nrf2 pathway genes (cat, sod1, gstr, keap1a, nrf2a, and gclc) further proved that BC reduces the oxidative damage induced by MC-LR. These findings demonstrate that BC decreases MC-LR bioavailability in the liver, thereby alleviating MC-LR-induced hepatotoxicity through the Nrf2 signaling pathway in zebrafish. Our results also imply that BC could serve as a potentially environmentally friendly material for mitigating the detrimental effects of MC-LR on fish.

Oromandibular dystonia (OMD) is a focal dystonia characterized by contractions of the masticatory, lingual, and other muscles of the stomatognathic system. We conducted a systematic review and meta-analysis to elucidate the impact and safety of botulinum toxin in OMD. The eligibility criteria were full-length original articles that provided data evaluating the efficacy and adverse effects of onabotulinumtoxinA injections in patients with OMD. PubMed and Embase were searched for articles published before 31 May 2023. We analyzed cases that showed a favorable response (>0% improvement), moderate or greater response (>50% improvement), and adverse effects. A fixed-model meta-analysis of 26 studies involving 1103 patients revealed that an overall favorable effect of onabotulinumtoxinA injection was observed in 96.2% (95% confidence interval [CI], 95-97.5%, p < 0.00001) of patients, with significant heterogeneity (p < 0.00001, I² = 85%). A moderate response (>50% improvement) was observed in 88.9% of patients (95% CI, 87-90.8%, p < 0.00001) with significant heterogeneity (p < 0.00001, I² = 85%). Adverse effects were detected in 17.8% of patients, and the most common event was dysphagia (10.1%). Our systematic review found that onabotulinumtoxinA injection was effective, with a low rate of side effects. Further randomized controlled trials are required to clarify the evidence-based efficacy and adverse effects.

Pain is a frequent and disturbing symptom among hemodialysis patients. Protein-bound uremic toxins (PBUTs) are related to cardiovascular and overall mortality, and they are difficult to remove with current hemodialysis treatments. The PBUT displacers, such as furosemide, tryptophan, or ibuprofen, may be promising new strategies for improving their clearance. This study aims to compare ibuprofen versus other analgesic drugs in PBUT removal. A prospective study was carried out in 23 patients. Patients underwent four dialysis sessions with routine dialysis parameters, except for analgesic drugs administered (lysine acetylsalicylic acid, acetaminophen, dexketoprofen, and ibuprofen). The reduction ratios (RRs) of a wide range of molecular weight molecules were assessed, including total p-cresyl sulfate and total indoxyl-sulfate. There were no complications related to the administered drug, and pain was controlled independently of the drug. There were no differences in the RR of small-size and medium-sized molecules between all four study treatments. However, indoxyl sulfate and p-cresyl sulfate RRs when ibuprofen was administered were significantly higher than lysine acetylsalicylic acid, acetaminophen, and dexketoprofen treatments. In conclusion, patients with pain may benefit from treatment with ibuprofen instead of lysine acetylsalicylic acid, paracetamol, or dexketoprofen, since in addition to improving pain, it increases the removal of PBUTs.

The therapeutic benefit of the oral adsorbent drug AST-120 in chronic kidney disease (CKD) is related to an indoxyl sulfate (IS)-lowering action. Diabetes and dyslipidemia might worsen kidney damage in CKD. However, it is not known whether AST-120 influences lipid abnormalities as well as renal function in patients with CKD and diabetes. The objective of the present meta-analysis was to evaluate the efficacy of AST-120 treatment in CKD using data from preclinical studies. Mixed-effect or random-effect models were used to estimate the standardized mean difference (SMD) and the 95% confidence interval (CI). Publication bias was assessed with a funnel plot and Egger's test. The potential influence of some variables (the dose and duration of AST-120 treatment, the animal species, and the CKD model's diabetic status) was evaluated in subgroup analyses. Treatment with AST-120 was associated with a significantly lower IS level in animals with CKD (SMD = -1.75; 95% CI = -2.00, -1.49; p < 0.001). Significant improvements in markers of renal function and the lipid profile were also observed. In subgroup analyses of the cholesterol level, the diabetic status, the AST-120 dose, and the animal species were found to be influential factors. AST-120 lowered serum IS and triglyceride levels and improved renal function in animal models of CKD independent of diabetes status. However, AST-120's ability to lower the total cholesterol level was more prominent in animals with diabetic CKD.

A growing body of evidence indicates that microcystins (MCs) exposure may cause metabolic diseases. However, studies exploring the effects of MCs exposure on the risk of metabolic syndrome (MetS) in humans are currently lacking, and the underlying mechanisms remain unclear. Here, we conducted a cross-sectional study in central China to explore the effect of serum MCs on MetS, and assessed the mediation effects of the inflammation biomarker, white blood cell (WBC) level, in this relationship. The relationships among MCs and WBC level and risk of MetS were assessed using binary logistic and linear regression. Mediation analysis was used to explore possible mechanisms underlying those associations by employing R software (version 4.3.1). Compared to the lowest quartile of MCs, the highest quartile had an increased risk of MetS (odds ratio [OR] = 2.10, 95% confidence interval [CI]: 1.19, 3.70), with a dose-response relationship (p for trend < 0.05). WBCs mediated 11.14% of the association between serum MCs and triglyceride (TG) levels, but did not mediate the association of MCs exposure with MetS. This study firstly reveals that MCs exposure is an independent risk factor for MetS in a dose-response manner, and suggests that WBC level could partially mediate the association of MCs exposure with TG levels.

Hemolytic-uremic syndrome (HUS) is a systemic complication of an infection with Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli, primarily leading to acute kidney injury (AKI) and microangiopathic hemolytic anemia. Although free heme has been found to aggravate renal damage in hemolytic diseases, the relevance of the heme-degrading enzyme heme oxygenase-1 (HO-1, encoded by Hmox1) in HUS has not yet been investigated. We hypothesized that HO-1, also important in acute phase responses in damage and inflammation, contributes to renal pathogenesis in HUS. The effect of tamoxifen-induced Hmox1 gene deletion on renal HO-1 expression, disease progression and AKI was investigated in mice 7 days after HUS induction. Renal HO-1 levels were increased in Stx-challenged mice with tamoxifen-induced Hmox1 gene deletion (Hmox1^R26Δ/Δ) and control mice (Hmox1^lox/lox). This HO-1 induction was significantly lower (-43%) in Hmox1^R26Δ/Δ mice compared to Hmox1^lox/lox mice with HUS. Notably, the reduced renal HO-1 expression was associated with an exacerbation of kidney injury in mice with HUS as indicated by a 1.7-fold increase (p = 0.02) in plasma neutrophil gelatinase-associated lipocalin (NGAL) and a 1.3-fold increase (p = 0.06) in plasma urea, while other surrogate parameters for AKI (e.g., periodic acid Schiff staining, kidney injury molecule-1, fibrin deposition) and general disease progression (HUS score, weight loss) remained unchanged. These results indicate a potentially protective role of HO-1 in the pathogenesis of Stx-mediated AKI in HUS.

Kojic acid is a secondary metabolite with strong chelating and antioxidant properties produced by Aspergillus flavus and A. oryzae. Although antioxidants and chelators are important virulence factors for plant pathogens, the ecological role of kojic acid remains unclear. We previously observed a greater gene expression of antioxidants, especially kojic acid, by non-aflatoxigenic A. flavus when co-cultured with aflatoxigenic A. flavus. Aflatoxin production was also reduced. In this study, we investigated kojic acid production in 22 A. flavus isolates from Louisiana and compared them to four common A. flavus strains in liquid medium and on corn kernels. Corn kernel infection was assessed by quantifying the maize beta tubulin DNA content of the kernels using drop digital PCR (ddPCR). Maize beta tubulin DNA content decreased with increased corn kernel infection. Greater kojic acid production by A. flavus isolates coincided with greater levels of corn kernel infection. All isolates produced 60 and 700 times more kojic acid than aflatoxin and cyclopiazonic acid (a known virulence factor), respectively, which varied among sclerotial size categories. A. flavus strains with small sclerotia, which were rarely isolated from corn, produced the least kojic acid and infected corn kernels the least, while medium and large sclerotia strains-mainly isolated from corn-produced the most kojic acid and were more infectious. Non-aflatoxigenic isolates from Louisiana produced the most kojic acid. These results suggest that kojic acid is a potential virulence factor and may increase the pathogenic success of medium and large sclerotia-producing A. flavus, which could ultimately lead to more effective A. flavus biocontrol strains. Further studies are required to determine the effects that kojic acid has on the redox environment during corn infection and how the altered redox environment decreases aflatoxin production.

An acidic shift in the pH profile of Clonostachys rosea zearalenone hydrolase (ZHD), the most effective and well-studied zearalenone-specific lactone hydrolase, is required to extend the range of applications for the enzyme as a decontamination agent in the feed and food production industries. Amino acid substitutions were engineered in the active center of the enzyme to decrease the pKa values of the catalytic residues E126 and H242. The T216K substitution provided a shift in the pH optimum by one unit to the acidic region, accompanied by a notable expansion in the pH profile under acidic conditions. The engineered enzyme demonstrated enhanced activity within the pH range of 3-5 and improved the activity within the pH ranging from 6 to 10. The D31N and D31A substitutions also resulted in a two-unit shift in the pH optimum towards acidic conditions, although this was accompanied by a significant reduction in the enzyme activity. The D31S substitution resulted in a shift in the pH profile towards the alkaline region. The alterations in the enzyme properties observed following the T216K substitution were consistent with the conditions required for the ZHD application as decontamination enzymes at acidic pH values (from 3.0 to 6.0).

Pyrrolizidine alkaloids (PAs) are common phytotoxins that are found worldwide. Upon hepatic metabolic activation, the reactive PA metabolites covalently bind to DNAs and form DNA adducts, causing mutagenicity and tumorigenicity in the liver. However, the molecular basis of the formation and removal of PA-derived DNA adducts remains largely unexplored. In the present study, Sprague Dawley (SD) rats were exposed to retrorsine (RTS), a representative PA, at a human-relevant dose of 3.3 mg/kg/day for 28 days. The rats were divided into three groups: control, RTS-28 (sacrificed after continuous RTS exposure), and RTS-161 (sacrificed at 133 days post-RTS-exposure). The multi-omics analyses demonstrated the involvement of homologous recombination (HR) and non-homologous end joining (NHEJ) repair pathways as a response to PA-induced DNA damage. Additionally, the characteristic guanine adducts induced by RTS exposure were in accordance with the higher expression of XPA and XPC, indicating that nucleotide excision repair (NER) and base excision repair (BER) also contributed to repairing RTS-induced DNA damage. Furthermore, we also showed that DNA damage persisted after PA exposure, and mutagenically related repair errors might occur due to the prolonged genotoxic effects. The present study lays the foundation for bridging PA-derived DNA adducts, DNA damage, DNA repair, and the follow-up mutagenesis and carcinogenesis associated with PA exposure.