Toxins最新文献

Scorpion venom is a rich source of diverse bioactive molecules with medicinal importance. While the venoms of many Buthidae scorpions have been extensively studied for their toxicity and therapeutic potential, Hottentotta judaicus scorpion venom (HjSV) remains poorly explored. In this study, using LC-ESI-MS, we show that HjSV has a complex composition. We find that HjSV has no significant cytotoxic effects on three human cancer cell lines, even at concentrations of up to 1000 µg/mL. However, it exerts a dose-dependent insecticidal effect against Drosophila melanogaster, a well-established genetic model organism, and two medically relevant mosquito species, Aedes albopictus and Culex pipiens. These findings highlight the venom's selective activity and reveal a species-dependent susceptibility in insects, with mosquitoes being more sensitive than Drosophila. Furthermore, we show that at sub-lethal doses, HjSV alters D. melanogaster behavioral patterns, significantly reducing locomotor activity and increasing sleep duration. Altogether, our results provide new insights into the dual role of HjSV as both an insecticidal agent and behavioral modulator, shedding light on its ecological function in prey subduing and its potential application in pest control strategies.

Background: This study, designed by the Greek Research Alliance for the Study of Headache and Pain (GRASP), sought to prospectively examine whether the treatment with two consecutive OnabotulinumtoxinA (BoNTA) cycles might improve the frequency and severity of chronic migraine (CM) with comorbid bruxism. We also explored whether the potential BoNTA-related alleviation of bruxism can directly influence the improvements in migraine efficacy outcomes.

Methods: A total of 58 CM patients with comorbid bruxism at baseline, attaining two consecutive (quarterly given) BoNTA cycles, were studied. The changes in bruxism-related pain were assessed with the 0-10 numeric scale PI-NRS. Bruxism was clinically diagnosed using the self-report Bruxscreen-Q questionnaire. Any phenotypic changes in bruxism, according to Bruxscreen-Q, from baseline (T0) to the last efficacy evaluation follow-up (T1), were analyzed and then compared. Migraine-related efficacy and disability outcomes, mostly mean headache days (MHD), were also compared between T0 and T1.

Results: BoNTA exerted significant improvements in bruxism-related pain, with PI-NRS median scores being significantly reduced from 7 at T0 to 3 at T1 (p < 0.001). The rates of masseter hypertrophy at T1 significantly dropped, compared to T0 (chi-square: 16; p < 0.001). Patients also self-reported significant improvements in the Bruxscreen-Q items at T1, compared to T0. At T1, 41/58 (70.7%) patients responded to BoNTA. The significant decrease in MHD frequency at T1 was positively correlated with improvements in bruxism-related pain severity (Pearson's correlation: 0.710; p < 0.001).

Conclusions: BoNTA exerts dual beneficial effects towards both the reduction of migraine frequency and the alleviation of bruxism-related pain and disability. Both of these effects seem closely interrelated in our study.

Aflatoxin M1 (AFM1), a hepatocarcinogenic metabolite of aflatoxin B1, poses significant risks to human health through its presence in milk and dairy products. This study investigates AFM1 contamination in raw milk produced in Serbia from 2021 to 2025, assessing annual and seasonal variations and associated health risks. A total of 907 milk samples were analyzed using enzyme-linked immunosorbent assay (ELISA), revealing contamination in 70.1% of samples, with mean concentrations exceeding the EU regulatory limit of 50 ng/kg. Seasonal analysis identified the highest contamination levels during winter, attributed to increased use of contaminated feed during colder months. Health risk assessments estimated the daily intake of AFM1 and associated health risks, with high-exposure individuals showing notably reduced margins of safety. The research demonstrates the essential requirement for better feed quality management alongside enhanced regulatory oversight along with health programs that reduce AFM1 exposure in Serbian populations.

Semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist, is widely prescribed for weight loss in non-diabetic populations. Given the link between obesity and overactive bladder (OAB), we explored whether GLP-1 use would improve adverse urinary events beyond its weight loss benefit for non-diabetic adults undergoing onabotulinumtoxin A (BTX-A) treatment for OAB. Using the TriNetX database, we conducted a retrospective cohort study of non-diabetic OAB patients treated with BTX-A alone or with concurrent GLP-1 therapy. Propensity score matching (1:1) was adjusted for age, race, ethnicity, hypertension, and BMI/obesity. After matching, 992 patients were included in each group. GLP-1 use was associated with a lower incidence of urinary retention (8.6% vs. 4.9%, risk difference 3.66%, p = 0.0044) and urinary tract infection (13.3% vs. 8.8%, risk difference 4.54%, p = 0.00224), with corresponding improved one-year retention-free and UTI-free survival on Kaplan-Meier (KM) analysis. Antispasmodic initiation rates were similar (11.8% vs. 10.3%, risk difference 1.55%, p = 0.6921), and KM analysis showed no significant difference. These findings suggest that GLP-1 receptor agonist use may improve select urinary adverse events in non-diabetic adults undergoing BTX-A treatment for OAB and support further investigation into its potential adjunctive role in OAB management with longer follow-up.

Pediatric torticollis, predominantly resulting from congenital muscular torticollis, is characterized by unilateral shortening of the sternocleidomastoid muscle, leading to head tilt and limited cervical mobility. Conventional management primarily involves physical therapy and repositioning strategies, with most infants achieving full recovery. However, a subset of patients exhibits persistent symptoms despite conservative treatment. Botulinum toxin type A (BoNT-A) has emerged as a minimally invasive adjunct intervention that targets muscular hypertonicity by inhibiting acetylcholine release at neuromuscular junctions. This scoping review synthesizes clinical evidence from six studies, including randomized controlled trials and case reports, assessing the efficacy and safety of BoNT-A in pediatric torticollis. Results indicate consistent improvements in range of motion, head posture correction, and patient satisfaction, with rare and mild adverse events such as local bruising and transient muscle weakness. Despite promising outcomes, variability in dosing, injection protocols, and follow-up durations underscores the need for standardized treatment guidelines and further high-quality research. These findings support BoNT-A as a valuable therapeutic option for refractory pediatric torticollis, warranting integration into multidisciplinary care frameworks.

Furosemide appears to contribute to the accumulation of protein-bound uremic toxins (PBUTs) and to induce adverse drug reactions. We investigated the extent to which the association between the furosemide dose and serum PBUT concentrations mediates the relationship between the furosemide dose and the symptom burden in patients with chronic kidney disease (CKD). This cross-sectional analysis included patients with CKD stages 2 to 5 from the CKD-REIN cohort and with data on the baseline serum concentrations of the free fractions of indoxyl sulphate (IS), kynurenine (KYN), p-cresyl sulphate (PCS), and indole-3-acetic acid (IAA), as measured by liquid chromatography-tandem mass spectrometry. The symptom burden was also assessed with a modified (8-item) symptom subscale from the Kidney Disease Quality of Life-36 (e.g., muscle soreness, cramps, itchy skin, dry skin, dizziness, appetite, numbness, and nausea). We used beta regressions to model the association between the furosemide dose and the symptom burden and used structural equation models to quantify the mediating effect of PBUT on this association. Among the 2053 included patients (males: 66%, median age: 68; mean estimated glomerular filtration rate: 35 mL/min/1.73 m²), those prescribed high-dose furosemide (>120 mg/day) had higher symptom burden than those not prescribed furosemide (i.e., a 5.67-point lower symptom score, 95%CI 1.41-9.93). The sum of PBUTs explained 3.78% (95%CI 0.10-18.01%) of this association. Similar results were observed for IS, KYN, and IAA, considered separately, but not for PCS, whose estimated mediation effect was nearly null. Although high-dose furosemide was associated with a greater symptom burden in patients with CKD, mediation by PBUT accumulation appeared to be minimal.

Almonds are an essential crop for the economy of California. However, mold and mycotoxin contamination of this commodity has a serious impact on food safety and international trade. The contamination levels of molds and the aflatoxigenic potential of Aspergillus section Flavi isolates were studied on almonds collected at a processing plant in California. The mean total fungal count for 80 samples was 1.0 × 10⁴ CFU/g, while 62 samples (77.5%) had a total mold count less than 1.0 × 10⁴ CFU/g. The most common fungal contaminants were Aspergillus section Nigri (100% of samples), followed by Penicillium (57.5%) and Cladosporium (52.5%) species. Rhizopus, Fusarium and Alternaria spp. were less frequent. A total of 26 A. section Flavi strains were identified, with most strains (23) belonging to the L morphotype of A. flavus. In addition, two S morphotypes of A. flavus, and one A. tamarii strain were observed. Other Aspergillus species, including A. terreus and A. ochraceus were rare. High Performance Liquid Chromatography (HPLC) analysis revealed that 9 out of 13 isolated A. flavus strains produced aflatoxin B₁ (AFB₁) on yeast extract sucrose media. The highest levels of AFB₁ were produced by two A. flavus isolates belonging to the S morphotype (78 and 260 µg/kg). Increasing temperatures and drought conditions may change the population dynamics of toxigenic mold strains on almonds, emphasizing the need to continue monitoring these fungal populations.

Bruxism, defined as a repetitive jaw-muscle activity characterized by clenching or grinding of teeth and/or by bracing or thrusting of the mandible, is a prevalent behavior affecting up to 22% of adults worldwide. While traditionally viewed as a disorder, current understanding recognizes bruxism as a behavior that may have both positive and negative consequences. Objective assessment methods for evaluating the effectiveness of interventions in symptomatic patients remain limited. This article presents the first longitudinal study using myotonometry to quantify changes in masseter muscle following botulinum toxin type A (BoNT-A) treatment in patients with symptoms of bruxism. In total, 57 patients were recruited and their masseter muscle tone, stiffness, elasticity, relaxation time, and creep parameters were measured. Measurements were performed at baseline, 3 weeks, and 3 months post-injection during both rest and maximum voluntary contraction. BoNT-A treatment produced significant improvements in all biomechanical parameters, with the greatest effects observed in patients with the highest baseline muscle values. The objective biomechanical changes correlated with the duration of BoNT-A's therapeutic effects. These findings establish myotonometry as a valuable tool for objective assessment of masticatory muscle function and demonstrate that BoNT-A produces measurable, long-lasting biomechanical changes in masseter muscle parameters, supporting its possible clinical application in this challenging condition.

Snakebite envenomation by Bothrops species is a neglected tropical disease and a major cause of local tissue damage and disability in Latin America. Antivenom therapy is effective against systemic effects but fails to prevent local myonecrosis, inflammation, and pain. This study evaluated photobiomodulation therapy (PBMT) using infrared (808 nm) alone or in combination with red (660 nm) laser in a murine model of Bothrops leucurus envenomation. A single PBMT session was applied, and animals were evaluated at 24 and 72 h. Combined treatment significantly reduced edema, hyperthermia, plasma CK and LDH, restored nociceptive thresholds, and improved motor recovery compared with infrared alone. Principal component analysis demonstrated clustering of combined-treatment animals with negative controls, supporting a synergistic therapeutic effect. These findings highlight dual-wavelength PBMT as a promising adjunctive approach to antivenom, directly targeting local venom-induced pathology.

Uremic toxins accumulate as kidney disease progresses, contributing to diverse systemic disorders. Despite numerous studies, no comprehensive mapping has been performed. In this study, keywords related to uremic toxins were quantitatively analyzed using bibliometric methods to clarify research trends, key molecules, and unresolved challenges. Literature and molecular data on uremic toxins and chronic kidney disease were retrieved from the Web of Science and the European Uremic Toxin Work Group (EUTox) databases. Network, citation burst, and keyword frequency analyses were performed using KeyWords Plus. In total, 3302 articles were identified, showing an increasing trend. Citation burst analysis revealed a growing interest in gut microbiota-related topics (burst strength = 15.21), whereas keyword frequency analysis indicated that indoxyl sulfate (566 articles) and p-cresyl sulfate (537 articles) were the most studied toxins. Toxins such as trimethylamine-N-oxide have gained attention over the past 5 years. Analysis of the EUTox database identified 24 protein-bound uremic toxins; among the 94 toxins with unreported clinical toxicity, 15 molecules, including osteocalcin and quinolinic acid, were investigated in <5 studies. These findings suggest that the gut microbiota and related uremic toxins are current research focuses; however, further investigation of underreported uremic toxins is required to define their clinical significance.