Human & experimental toxicology最新文献

IntroductionAccurate determinations of the cause of death are crucial for public health, crime investigations, and social justice. In the Netherlands, cause-of-death determinations rely heavily on external examinations, which can miss substance-related deaths. This study investigates the added value of toxicological blood testing in the determination of the cause and manner of death by forensic physicians in the Netherlands.MethodsCollected blood samples of 642 decedents that were examined by a forensic physician in Amsterdam and surrounding regions underwent toxicological testing. Findings and concluding remarks from the external examination and toxicological testing were compared using descriptive statistics.ResultsBlood samples of 69% of cases tested positive for one or more pharmaceuticals, and 36% tested positive for illicit drugs and/or alcohol. In 55% of cases, toxicological testing revealed substances that were not indicated by the external examination. Its findings also prompted a revision of the initial cause and manner of death in 18 cases (3%).DiscussionKey limitations in this study include that not all detected substances were quantified and a verification bias of the included cases, which may have led to an underrepresentation of unsuspected detections. Nonetheless, despite the constraints of (routine) screening capabilities and the effects of post-mortem degradation and redistribution, this study presented the importance of toxicological blood testing within a multifaceted approach that combines toxicological findings with scene evidence, medical history and the external examination, which is essential for improving the accuracy of cause-of-death determinations by the forensic physician.

BackgroundGold nanoparticles (Au NPs) have emerged as major contributors for innovative technologies and have been used extensively in various biomedical and industrial fields with little, if any, known about their neurotoxicity.ObjectiveThe current study aims to explore the nanotoxicity of Au NPs on the brain tissues.Materials and methodsTwo experimental groups, a control one and an Au NPs-treated group, each comprising 10 adult male Wistar albino rats, were used. Nanoparticle-treated rats received 28 intraperitoneal injections of 10 nm Au NPs at a daily dosage of 2 mg/kg.ResultsBrain tissue specimen for each rat under study was subjected to histological, immunohistochemical, and morphometric examination for alterations that might be induced by Au NPs exposure. Compared with control animals, brain tissue of rats treated with Au NPs exhibited neuronal shrinkage and pyknosis, perineuronal spacing, glial cell proliferation, vascular congestion, and neurons with lipofuscin pigmentation. Moreover, the hippocampus exhibited shrunken neurons, vascular congestion, and perivascular edema. Furthermore, the cerebellum showed degenerated Purkinje cells, cerebellar congestion, and perivascular spacing. In addition, the neuronal tissue demonstrated decreased autophagy, astrogliosis, and apoptosis presented by substantially decreased immunohistochemical protein expression of Beclin 1, increased expression of GFAP and caspase 3, respectively.ConclusionThe findings suggest that exposure to Au NPs has the potential to cause histological, immunohistochemical, and morphometric changes in brain tissue, which could impact the function of this vital organ. Further endeavors are necessary for more understanding of the potential risks of Au NPs to human health.

ObjectiveTo investigate the mechanism of tumor-associated macrophages (TAM) in the invasive migration of lung adenocarcinoma (LUAD) cells.MethodsThe single-cell sequencing data of lung adenocarcinoma (GSE131907) were initially analyzed. Kaplan-Meier curve analysis, univariate as well as multivariate Cox analysis, and immunofluorescence staining were performed. The analysis of fibroblast-macrophage interactions using Single-cell CellChat revealed their relationship. Subsequently, we screened and validated the target proteins in macrophages that interact with SEMA3C. The effects of these interactions on lung cancer cell migration and invasion were evaluated in vitro through Western blot analysis to assess phenotypic changes in macrophages, as well as through Transwell migration and invasion assays.ResultsSEMA3C was predominantly expressed in fibroblasts of patients with high-grade lung adenocarcinoma at high levels. SEMA3C exhibited independent prognostic significance in determining the overall survival outcome among individuals diagnosed with lung adenocarcinoma. Lung adenocarcinoma fibroblasts had elevated SEMA3C. CellChat demonstrated enhanced interactions between TAM as well as T cells. A high expression of vascular non-inflammatory molecule 1 (VNN1) in fibroblast macrophages during Stage II-III, and this elevated VNN1 was also an independent prognostic factor. The interaction between cancer-associated fibroblasts (CAFs) and VNN1 on macrophage membranes mediated by SEMA3C. Furthermore, these experiments demonstrated that SEMA3C regulates the polarization of TAM through VNN1, thereby influencing lung cancer.ConclusionThe phenotype of TAM is regulated by SEMA3C, which in turn influences the migration as well as invasion of lung cancer cells through VNN1.

IntroductionMethanol toxicity is a significant health concern with potentially severe outcomes. This study aimed to investigate the prognostic factors of patients with methanol toxicity referred to Tabriz Sina Hospital.MethodsA descriptive-analytical retrospective study was conducted in methanol toxicity patients admitted in Tabriz Sina Hospital since 2019 to 2021. Demographic characteristics and management methods were extracted from the patients' medical records.ResultsPatients were predominantly male (91.3%) with a median age of 30-40 years. Winter accounted for 48.7% of cases. Coma (OR = 8.0, 95% CI: 3.2-19.9) and arrhythmia (OR = 5.5, 2.0-15.1) at admission, pH <7.1 (OR = 4.2, 2.0-8.9), elevated creatinine (OR = 1.3/mg/dL, 1.1-1.6), opiate co-use (OR = 2.8, 1.2-6.5), and delayed ethanol therapy (>3 h, OR = 2.3, 1.1-4.8) independently increased mortality risk. Bicarbonate, Eprex, and methylprednisolone reduced complications. Time from ingestion to admission (48-72 h) did not affect mortality, but delayed hemodialysis initiation worsened outcomes.ConclusionEarly presentation and providing early therapeutic modalities have a significant impact on the mortality rate and the patients' outcome.

Introduction: Quercetin has been reported to inhibit the growth of oral squamous cell carcinoma (OSCC), but the mechanism remains unclear. Therefore, our study aimed to investigate the involvement of sirtuin 3 (SIRT3) and the autophagy-dependent form of cell death, ferroptosis, in the pathogenesis of OSCC, and observe the impacts of quercetin on ferroptosis and SIRT3/AMPK/mTOR-mediated autophagy.

Methods: SIRT3 knock out or overexpressing SCC15 cell line was generated, treated with indicated drugs, and malondialdehyde (MDA) and ROS levels were measured. Roles of SIRT3 in regulating autophagy-mediated ferroptosis were assessed by immunoprecipitation and Western blotting.

Results: SIRT3 overexpression increased levels of MDA and ROS, reducing cell viability, and SIRT3 knockout produced the opposing effect. SIRT3 overexpression upregulated ATG16L1 expression and the conversion of LC3-Ⅰ to LC3-Ⅱ, triggering autophagy. Suppression of autophagy by ATG16L1 knockout impaired SIRT3-triggered ferroptosis. Use of an AMPK inhibitor antagonized the induction of ferroptosis by SIRT3 in SCC15 cells, indicating the involvement of the AMPK/mTOR pathway. Additionally, quercetin significantly increased the levels of SIRT3, p-AMPK, ATG16L1, and the ratio of LC3-Ⅱ/Ⅰ, but reduced cell viability and p-mTOR in SCC15 cells. Autophagy and AMPK inhibitors, or SIRT3 deletion significantly antagonized the impacts of quercetin on the autophagy-mediated ferroptosis in cancer cells.

Discussion: SIRT3 overexpression activated the AMPK/mTOR pathway and triggered ATG16L1-mediated autophagy, promoting ferroptosis in SCC15 cells, and we proposed that quercetin may be a promising therapeutic drug for OSCC.

IntroductionThis study examined the cardioprotective effects of Pelargonidin-3-O-glucoside (Pg3G) against myocardial infarction induced by isoproterenol (ISO) in male Wistar rats.MethodsAnimals were divided into four groups each groups contain six animals. Group 1 control; Group 2 Pg3G treated control; Group 3 ISO-control; Group 4 Pg3G + ISO treated rats. At the end of the experiment period the animals were sacrificed and collected the serum, heart tissue used for the experimental work.ResultsAccording to the network pharmacology analysis, Prostaglandin-endoperoxide Synthase 2 (PTGS2), Matrix metallo proteins -9 (MMP-9), and tumour necrosis factor-alpha (TNF-α) were identified as potential targets among the 97 common targets between Pg3G and myocardial injury. Further, we investigated that prominent cardiac indicator such creatine kinase (CK), CK-MB, cardiac troponin T (cTnT), and cardiac troponin I (cTnI) were not elevated by ISO in the presence of Pg3G administration. Additionally, Pg3G administration decreased the pro-inflammatory cytokines generated by ISO, including as interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and TNF-α, suggesting its anti-inflammatory qualities. Additionally, Pg3G increased levels of reduced glutathione (GSH) and restored the activity of important antioxidant enzymes that were depleted by ISO-induced oxidative stress, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD).DiscussionPg3G capacity to reduce ISO-induced inflammatory, fibrotic, and cardiac toxicity markers in myocardial tissue was demonstrated by gene expression investigations. Therefore, Pg3G may be considered for ISO-induced cardiac injury since it provides significant cardioprotection by reducing oxidative stress, inflammation, and fibrosis.

BackgroundCisplatin (CIS) is a widely used chemotherapeutic agent; however, it is associated with ovarian toxicity. Tribulus Terrestris (TT) is recognized for its antioxidant and anti-inflammatory properties. This study aims to evaluate the effects of TT extract on ovarian tissue damage induced by cisplatin.Material and MethodTwenty-five female BALB/c mice were divided into five groups (n = 5): Control, CIS (Cisplatin only), CIS + TT100 (100 mg/kg TT extract daily + CIS), CIS + TT300 (300 mg/kg TT + CIS), and CIS + TT500 (500 mg/kg TT daily + CIS). After 15 days, blood samples were collected for hormonal analysis, and ovaries were harvested for histopathological, immunohistochemical, and biochemical assessments.ResultsThe CIS group exhibited a significant decline in follicle count compared to the control group (P < 0.001). In contrast, the CIS + TT groups showed a notable increase in follicle count (P < 0.05). TT treatment also resulted in significant improvements in antioxidant markers (SOD, CAT) and a reduction in oxidative stress (MDA) compared to the CIS group. Moreover, E2, AMH, and progesterone concentrations were decreased in the CIS group, while these levels were restored in the TT-treated groups (P < 0.001). The expression of inflammatory markers TNF-α and IL-1β was higher in the CIS group and decreased in the TT-treated groups.ConclusionTribulus Terrestris extract effectively mitigates cisplatin-induced ovarian toxicity by enhancing follicular count, improving antioxidant activity, and reducing oxidative stress. TT treatment also elevated AMH and progesterone levels while decreasing inflammatory markers, underscoring its potential as a protective agent against cisplatin-induced ovarian damage.

IntroductionSodium dodecyl sulfate (SDS), a widely used surfactant in detergents, has raised concerns due to its potential health risks, particularly in children. This study evaluates the impact of SDS exposure on GH secretion in GH3 cells, focusing on oxidative stress as a key mechanism.MethodsGH3 cells were treated with varying concentrations of SDS (0.001-10 mM) for 24 or 48 h. Cell viability was assessed using the MTT assay, while GH secretion was quantified via ELISA. Oxidative stress levels were evaluated through ROS fluorescence assays, and gene expression of Nrf2, IL-6, TNF-α, and caspase-3 was analyzed using qPCR. Additionally, the antioxidant N-acetylcysteine (NAC) was used to determine its protective effects against SDS-induced oxidative stress.ResultsSDS exposure led to a dose-dependent decrease in GH secretion and cell viability, with oxidative stress identified as a primary driver. Nrf2 exhibited a biphasic response, showing transient upregulation at low doses but suppression at higher concentrations, exacerbating oxidative damage. NAC treatment reduced ROS levels and partially restored GH secretion, confirming the role of oxidative stress in SDS-induced toxicity.DiscussionThese findings suggest that SDS exposure may disrupt endocrine function, warranting further risk assessment of its safety in consumer products. Given SDS's prevalence in household products, future research should focus on the long-term effects of SDS exposure to children and potential therapeutic interventions to mitigate oxidative damage.