👤 Eser Orhan

Glyphosate (GLY) is a widely used herbicide, particularly in agriculture, and its residues in plants and soil can induce toxic effects in various organisms, including humans, with the brain being especially vulnerable. Eugenol (EU), a natural antioxidant found in cloves, has demonstrated protective effects against different toxic substances. This experimental study explored whether eugenol could mitigate neurological damage triggered by glyphosate exposure in rats. A total of forty male Sprague-Dawley rats were allocated into five experimental groups consisting of control, eugenol (100 mg/kg), glyphosate (150 mg/kg), EU50 combined with glyphosate (50 mg/kg + 150 mg/kg), and EU100 combined with glyphosate (100 mg/kg + 150 mg/kg). Animals received the respective treatments by oral gavage for a period of seven days. Motor and anxiety-related behaviors were evaluated using behaviour tests, after which brain tissues were processed for histopathological analysis. Biochemical analyses included ELISA assessment of oxidative stress markers (MDA, SOD1, GSH, and GPx1), RT-PCR analysis of endoplasmic reticulum (ER) stress- and apoptosis-related genes (GRP78, ATF4, CHOP, PI3K/AKT/mTOR, BAX, and Bcl-2), Western blot evaluation of inflammatory and antioxidant signaling pathways (TLR4/NF-κB and Nrf2/HO-1/SIRT1), and immunohistochemical and immunofluorescence analyses of neuroplasticity, circadian rhythm, and autophagy markers (BDNF, BMAL1, CLOCK, Beclin-1, and LC3A/B). GLY exposure significantly increased lipid peroxidation (MDA), ER stress markers (GRP78 and CHOP), pro-inflammatory mediators (TLR4, NF-κB, TNF-α, and IL-1β), apoptotic signaling (BAX and caspase-3), and autophagy-related proteins, while suppressing antioxidant pathway components. Glyphosate exposure induced behavioral impairments accompanied by increased oxidative stress, inflammatory activation, endoplasmic reticulum stress, apoptosis, and dysregulated autophagy in cerebral cortex tissue. EU treatment dose-dependently attenuated these molecular and histopathological alterations, restored antioxidant and cellular stress responses, and significantly improved behavioral performance, indicating a protective role against GLY-induced neurotoxicity. Overall, EU may represent a promising therapeutic candidate for mitigating herbicide-induced brain injury. Show less

Pediatric AML with KMT2A::MLLT10 accounts for 10%-15% of KMT2A-rearranged AML and is associated with poor prognosis. Lately, the assessment of measurable residual disease (MRD) by reverse transcription quantitative polymerase chain reaction (RT-qPCR) has become an important tool for disease management; however, in the pediatric setting, it lacks standardized protocols. Therefore, we investigated the prognostic relevance of MRD monitoring by RT-qPCR during high-dose polychemotherapy in pediatric patients with AML expressing KMT2A::MLLT10. Using RNA sequencing, we determined the fusion breakpoints and designed RT-qPCR assays for MRD monitoring. Bone marrow samples collected from 41 patients, who were treated in the AML-BFM or AIEOP study, were analyzed for MRD by RT-qPCR. MRD positivity after the second treatment course resulted in a significantly worse probability of overall survival (pOS) compared to MRD negative patients (33.3% ± 19.2% vs. 80.6% ± 7.8%, p = 0.032). Moreover, the probability of event-free survival (pEFS) (16.7% ± 15.2% vs. 76.9% ± 8.3%, p = 0.003) and cumulative incidence of relapse (CIR) (83.3% ± 40.8% vs. 19.2% ± 40.2%, p = 0.001) were significantly worse for patients in complete morphologic remission who remained MRD positive after the second treatment course. Thus, MRD monitoring enables the identification of a subgroup of pediatric patients with AML carrying KMT2A::MLLT10 in complete morphologic remission with a dismal prognosis despite the current intensive therapy regimen. AML-BFM study 2004: ClinicalTrials.gov Identifier: NCT00111345; AML-BFM registry 2012 and AML-BFM study 2012: EudraCT 2013-000018-39; AML-BFM registry 2017: DRKS number: DRKS00013030. Show less