Toxins最新文献

Deoxynivalenol (DON) is a common mycotoxin in cereal crops such as corn, wheat, and their processed products. It can cause feed refusal and growth retardation in piglets. This study systematically evaluated the effects of dietary exposure to purified DON at low doses of 0.25, 0.5, 1.0, and 2.0 mg/kg on growth performance, blood biochemistry, antioxidant capacity, immune function, intestinal health, and reproductive development in female weaned piglets over a 42-day period. Although dietary exposure to 0.25-2.0 mg/kg of DON did not significantly affect growth performance, it induced subclinical multi-organ toxicity. Notably, decreased platelet count (PLT) at 0.25-2.0 mg/kg and increased serum alanine aminotransferase (ALT) activity at 2.0 mg/kg were observed. DON exposure also impaired antioxidant function with reduced serum total antioxidant capacity (T-AOC) at 0.25-2.0 mg/kg, and elevated malondialdehyde (MDA) content in the jejunum and ileum at 0.5-2.0 mg/kg. Furthermore, at all doses tested (0.25-2.0 mg/kg), DON suppressed anti-inflammatory cytokine interleukin-10 (IL-10) levels in both serum and intestine, reduced duodenal villus height (VH), and decreased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Additionally, histopathological injuries of liver, kidney, duodenum, jejunum, ileum, uterus and ovaries were also observed at doses of 1.0-2.0 mg/kg. In summary, this study confirms the multi-organ toxicity of low-dose DON in piglets. Our findings suggest that DON concentrations in pig feed should be more strictly controlled and highlight the importance of considering subclinical health endpoints, such as oxidative stress markers and immune parameters, in future risk assessments of mycotoxin exposure.

Chronic liver damage usually results in a pathological state of excessive deposition of extracellular matrix that is known as liver fibrosis. This study was designed to examine the potential preventive effect of the pentahydroxyglucosyl flavone, gossypin (GPN), against concanavalin A (Con A)-induced liver fibrosis in BALB/c albino mice. Methods: Liver fibrosis was induced by intravenous (IV) injection of Con A (10 mg/kg) once weekly for 4 weeks. GPN (10 and 20 mg/kg) was administered orally three times weekly for 4 weeks. At the end of the experiment, serum and liver tissue were obtained and used for different biochemical, histological, histochemical and molecular assessments. GPN (10 and 20 mg/kg) considerably ameliorated liver fibrosis induced by Con A. A marked decrease in serum levels of ALT, AST and LDH was observed upon GPN treatment, confirmed by histopathological analysis by H&E. GPN markedly reduced collagen deposition as confirmed by MT staining, reduced hepatic levels of Col-1 and TGF-β as well as inhibited α-SMA immunostaining. The hepatic oxidative stress biomarker, MDA, was markedly reduced, whereas hepatic antioxidant defense, TAC, was significantly enhanced. Furthermore, GPN effectively enhanced gene and protein expression of SIRT3. GPN downregulated hepatic proinflammatory biomarkers, NF-κB and TNF-α. Additionally, GPN caused a noticeable increase in the hepatic levels and expression of PI3K and Akt. GPN effectively attenuated Con A-induced liver fibrosis via reducing liver damage and collagen deposition majorly by lessening inflammation, oxidative stress and fibrosis. GPN modulated SIRT3, NF-κB/TNF-α and PI3K/Akt pathways.

The presence of Alternaria mycotoxins in hepatic tissue of both human and animal origin remains unexplored. This work describes the development of an analytical method based on salt-assisted liquid-liquid extraction (SALLE) and ultrahigh-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) for the determination of six main Alternaria mycotoxins and related metabolites. Sample treatment was fully optimized, including sample mass, extraction solvent, and volume and sodium chloride mass. The method was validated, achieving calibration curve R² values above 0.99 and limits of detection between 0.01 and 1.46 µg kg^-1. Moreover, satisfactory trueness (apparent recoveries between 84% to 111%) and precision (RSD values below 10%) were achieved, complying with EU requirements. Matrix effects in terms of signal suppression/enhancement varied between 53% for TeA and 78% for AME. Applied to real liver samples (20 human and 20 animal), alternariol monomethyl ether (AME) was found in pig liver, while alternariol (AOH) and tentoxin (TEN) were found in human forensic liver tissues. No other Alternaria mycotoxin metabolites were detected. This methodology is the first validated approach for determining Alternaria mycotoxins in liver tissue.

Chronic Kidney Disease (CKD) and Colorectal Cancer (CRC) share a profound epidemiological link, supported by Mendelian randomization studies suggesting causality. This review articulates a refined Gut-Kidney Axis, focusing on the pathophysiology of indole-derived uremic toxins. CKD-induced dysbiosis drives hepatic synthesis and systemic accumulation of indoxyl sulfate, which is proposed to promote carcinogenesis via Aryl Hydrocarbon Receptor (AhR) and Akt signaling, ultimately upregulating c-Myc and EGFR. We propose a two-compartment model: while systemic indoxyl sulfate reflects the total gut indole pool (mainly from planktonic bacteria), adherent bacteria like Fusobacterium nucleatum may create high-concentration indole hotspots within the tumor microenvironment. Clinically, we advocate for protein-independent DNA methylation biomarkers (SEPT9, SDC2) to avoid renal confounding. Furthermore, we propose a novel diagnostic panel integrating serum indoxyl sulfate (systemic load) and urinary indoxyl sulfate (gut production) to guide therapy. Therapeutically, targeting upstream drivers (AhR/Akt) may bypass resistance to anti-EGFR therapies in KRAS-mutated tumors. We also discuss the repurposing of the oral adsorbent AST-120 and emerging bacteriophage therapies as strategies to disrupt this oncogenic axis. This review offers a comprehensive framework for stratified management of CKD-associated CRC.

Although kidney transplantation (KT) restores renal function, residual uremic toxins, such as indoxyl sulfate (IS), may persist and contribute to vascular remodeling and aging. Aortic stiffness, reflected by carotid-femoral pulse wave velocity (cfPWV), is a strong predictor of cardiovascular events. This study enrolled KT recipients to examine the association of circulating IS with aortic stiffness. Using the SphygmoCor system, we assessed aortic stiffness, which was defined as cfPWV > 10 m/s. Serum IS concentrations were measured by liquid chromatography-tandem mass spectrometry. Of 94 KT recipients, 26 (27.7%) met the criteria for aortic stiffness. Compared with patients without aortic stiffness, those with aortic stiffness were older (p = 0.017) and had significantly higher systolic blood pressure (p = 0.011) and fasting glucose levels (p = 0.002), a higher prevalence of diabetes (p = 0.043), and higher IS levels (p = 0.002). According to multivariable logistic regression, serum IS remained independently associated with aortic stiffness (p = 0.017). According to stepwise linear regression, log-transformed IS further showed a positive correlation with cfPWV (p = 0.016). Serum IS remained an independent determinant of aortic stiffness in KT recipients, highlighting the burden of residual uremic toxins as a contributor to post-transplant vascular aging.

Clostridial toxins, involved in a wide range of serious diseases, affect humans and animals [...].

Background: Upper-limb spasticity involving the shoulder girdle and elbow flexors often impairs functional hand use, and although Botulinum toxin type A (BoNT-A) is a first-line therapy, severe proximal synergies may persist while higher doses risk distal weakness.

Methods: We report a case of a 47-year-old woman with neurodegenerative tetraparesis and marked shoulder and elbow flexor spasticity treated with bilateral percutaneous cryoneurolysis of the lateral pectoral, thoracodorsal, and musculocutaneous nerves, followed by distal BoNT-A injections, and we conducted a scoping review following Arksey and O'Malley, Levac, and PRISMA-ScR methods to contextualize the current evidence.

Results: At one-month follow-up, the patient showed a reduction in MAS from 4 to 1-2, complete resolution of pain, improved passive shoulder abduction and elevation, preserved distal dexterity, and high satisfaction with no adverse events. The scoping review identified consistent MAS and range-of-motion improvements across multiple case reports and small series involving similar proximal nerve targets.

Conclusions: The combined proximal cryoneurolysis-distal BoNT-A approach appears to be a feasible dual-modulation strategy for complex upper-limb spasticity when the preservation of hand function is essential, and the emerging literature supports its further investigation.

Alternaria alternata is a common postharvest mold affecting tomato products, including cherry tomatoes, and causing their contamination with mycotoxins. When consumers encounter moldy fruits, some may remove the visibly contaminated part and consume the rest, to reduce waste. However, the extent to which A. alternata toxins migrate beyond visible fungal growth remains unclear, potentially posing health risks. This study investigated (i) the within-fruit migration of A. alternata in cherry tomatoes together with the associated mycotoxin production, and (ii) the diffusion of purified Alternaria toxins in tomatoes in the absence of any fungal activity. Toxins were quantified using LC-MS/MS, while fungal colonization was assessed through visual inspection and DNA quantification across fruit sections. In the absence of fungal growth, toxins remained largely confined to the spiking site and were degraded over time. In contrast, in inoculated samples, Alternaria DNA was detected at notable levels even in sections lacking visible fungal growth, while Alternaria toxins were found both in these regions and in lower fruit sections where fungal DNA was below the qPCR detection limit. These findings highlight the limitations of relying solely on visual inspection to assess food safety. A consumer recommendation is proposed to help minimize health risks while reducing food waste.

This study evaluated the effect of time of botulinum toxin A (BoNT-A) treatment on clinical outcomes in adults with post-stroke spasticity (PSS). Individual data were pooled from five studies. Eligible patients received ≥1 BoNT-A injection(s) for PSS and had goal attainment scaling (GAS) scores measured at baseline and 12 weeks. Patients were grouped according to time of treatment post-stroke: early (<1 year) or late (≥1 year). The primary endpoint was the total GAS (GAS-T) score change from baseline to 12 weeks. Secondary outcomes included the proportion of patients with a GAS-T score ≥ 50. Overall, 968 patients were included (166 early and 802 late). Median time post-stroke to BoNT-A treatment was 0.5 (early) versus 5.4 (late) years. Mean (standard deviation [SD]) baseline GAS scores were similar between cohorts (early: 36.9 [3.5]; late: 36.9 [3.6]). The mean (SD) change in the GAS-T score from baseline to 12 weeks was greater in the early versus late cohort (15.7 [8.9] vs. 13.1 [8.9]; p < 0.001). More patients in the early versus late cohort had a GAS-T score ≥ 50 (63.9% vs. 47.4%; p < 0.001) at 12 weeks. No new safety concerns were reported. Early treatment of PSS with BoNT-A has a positive impact on patients' ability to achieve treatment goals. Plain Language Summary: After a stroke, people can experience muscle stiffness in their limbs, called post-stroke spasticity (PSS), which can lead to pain and make movement difficult. Treatment can include botulinum toxin A (BoNT-A) injections given directly into affected muscles. The aim of our study was to assess whether giving BoNT-A within a year after experiencing a stroke was more effective in treating PSS than delaying treatment. We combined data from 968 patients across five different studies. Most people (802 patients) received BoNT-A treatment 1 year or more after their stroke (late treatment group), while 166 people received treatment within a year of their stroke (early treatment group). In the studies, patients set treatment goals with their physician, for example being able to hold an object or walk a certain distance. After treatment, the extent to which each goal was achieved was assessed and scored based on whether the result was less than expected, as expected, or better than expected by the patient and physician. The scores from the two treatment groups were compared. People in the early treatment group did better in achieving their treatment goals compared with those in the late treatment group. We also looked at any side effects patients experienced. No unexpected side effects were reported. BoNT-A treatment of PSS can help patients achieve their treatment goals, and patients treated early (within 1 year after stroke) may do better than those treated later. This information may help in rehabilitation planning for stroke patients.

Currently, commercially available pain medications can cause adverse effects. Within this framework, researchers have been exploring new drug candidates derived from animal venoms and toxins. The objective of this study was to investigate the number of molecules with potential for pain relief derived from animal venoms and toxins, which could potentially contribute to the development of new biopharmaceuticals. We conducted a literature search in January 2025, covering the period from 1960 to 2025, in two Latin American and nine international scientific databases. The results consisted of 212 articles selected for review. From these articles, 152 toxins and venoms with analgesic potential were identified and classified into 14 different types of pharmacological targets. The peptides investigated, with masses between 500 Da and 5000 Da, are strong candidates for alternative biopharmaceuticals. Most of the toxins found interact with ion channels, representing an alternative to commercially available drugs.