INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 4.7
Yan Song,Mi Chen,Chen Wu,Leiming Yang,Qiyu Sun,Shuang Guo,Huiting He,Qi Huang,Xiying Guo,Youzhi Zhang
Trimethyltin chloride (TMT) is a highly toxic organotin pollutant commonly found in the environment, posing serious risks to humans and animals. To explore the potential toxicity mechanism of TMT on vascular systems, we developed models exposing vascular smooth muscle cells (VSMCs) and male Balb/c mice to TMT. Levels of reactive oxygen species (ROS) and glutathione (GSH) were measured using fluorescence methods and assay kits, while the expression of genes related to glutathione peroxidase 4 (GPX4), Nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 (NRF2/HO-1) pathway, autophagy-lysosome, and ubiquitination proteasome pathway were analyzed through Western blot and immunofluorescence. The findings indicated that exposure to TMT activated the GPX4-dependent lipid peroxidation pathway, leading to cell death in VSMCs, rather than necrosis or apoptosis. This conclusion was supported by several key indicators: a dose-dependent increase in ROS levels, alongside a dose-dependent decrease in GSH and GPX4 levels. Further in-depth analysis elucidated that TMT-induced GPX4 degradation and subsequent cell death are primarily mediated by the ubiquitination-proteasome pathway. Notably, this process occurs independently of the NRF2/HO-1 signaling pathways or the autophagy-lysosome system. In conclusion, TMT exposure causes dose-dependent GPX4 degradation via the ubiquitination proteasome pathway, leading to cell death in VSMCs and vascular injury.
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TOXICOLOGY
·
2026
·
IF 4.6
Jin Chen,Hanwen Hu,Jing Fu,Yaolin He,Hui Zhou,Jingwei Lei,Ming Huang,Jianqi Wang,Anfei Liu,Zhenzhong Liu
Trimethyltin chloride (TMT), a pervasive environmental organic tin pollutant, has been implicated in cardiac injury, though its underlying mechanisms remain unclear. TMT exposure triggers excessive reactive oxygen species (ROS) generation, a key inducer of ferroptosis—a regulated form of cell death driven by iron-dependent lipid peroxidation. NADPH oxidase 4 (NOX4), highly expressed during cardiac development, plays a critical role in myocardial ROS production, while the Keap1/Nrf2 pathway regulates cellular ROS homeostasis. We hypothesized that TMT induces cardiac developmental defects by activating NOX4/Keap1/ROS-mediated ferroptosis. TMT exposure induced cardiac malformations, pericardial edema, and reduced heart rate in zebrafish embryos. Further studies revealed that TMT upregulated nox4 expression in embryonic hearts. Notably, pharmacological inhibition or genetic knockdown of nox4 markedly attenuated TMT-induced cardiac defects. Moreover, nox4 suppression antagonized TMT-triggered dysregulation of the Keap1/Nrf2 axis, ROS overaccumulation, mitochondrial damage, and ferroptosis-related abnormalities—including Fe²⁺ accumulation, elevated lipid peroxidation, and downregulated glutathione peroxidase 4 (GPX4) expression. Crucially, inhibition or knockdown of keap1 similarly mitigated TMT-induced ROS bursts, mitochondrial injury, and ferroptosis progression. Intervention with ferroptosis-specific inhibitors (Liproxstatin-1 and Myricetin) confirmed that ferroptosis directly contributes to TMT-induced cardiac developmental defects. This study demonstrates that TMT induces cardiac malformations by activating ferroptosis via the nox4/Keap1/Nrf2/ROS signaling axis. These findings reveal a novel mechanism underlying TMT cardiotoxicity, provide theoretical insights for assessing TMT exposure as a risk factor for congenital heart disease, and identify potential molecular targets for therapeutic intervention.
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TOXICOLOGY
·
2023
·
IF 4.5
Yuting Gao,Wenli Liao,Ruyi Zhang,Yining Lei,Tao Chen,Lingling Wu,Manqin Li,Xinran Liu,Fei Cai
Neuroinflammation is one of the important mechanisms of trimethyltin chloride (TMT) central neurotoxicity . Artemisinin (ARS) is a well-known antimalarial drug that also has significant anti-inflammatory effects. Prokineticin 2 (PK2) is a small molecule secreted protein that is widely expressed in the nervous system and plays a key role in the development of neuroinflammation. However, it remains unclear whether ARS can ameliorate neuroinflammation caused by TMT and whether PK2/PKRs signaling pathway plays a part in it. In this research, male Balb/c mice were administered TMT (2.8 mg/kg, i.p.) followed by immunohistochemistry to assess the expression of PK2, PKR1, and PKR2 proteins in the hippocampus. Network pharmacology was used to predict the intersection targets of ARS, central nervous system(CNS) injury and TMT. The neurobehavior of mice was evaluated by behavioral scores. Histopathological damage of the hippocampus was evaluated by HE, Nissl and Electron microscopy . Western blotting was used to identify the expression of synapse-related proteins (PSD95, SYN1, Synaptophysin), PK system-related proteins (PK2, PKR1, PKR2), and inflammation-related proteins (TNF-α, NF-κB p65). Immunohistochemistry showed that TMT resulted in elevated PK2 and PKR2 protein expression in the CA2 and CA3 regions of the hippocampus in mice, while PKR1 protein was not significantly altered. Network pharmacology showed that PK2 could interact with the intersectional targets of ARS, CNS injury, and TMT. ARS remarkably attenuated TMT-induced seizures and hippocampal histological damage. Further studies demonstrated that ARS treatment attenuated TMT-induced hippocampal ultrastructural damage, possibly by increasing the number of rough endoplasmic reticulum and mitochondria as well as upregulating the levels of synapse-associated proteins (PSD95, SYN1, Synaptophysin). Western blotting results revealed that ARS downregulated TMT-induced TNF-α and NF-κB p65 protein levels. In addition, ARS also decreased TMT-induced protein expression of PK2 and PKR2 in the mouse hippocampus, but had no significant effect on PKR1 protein expression. Our results suggested that ARS ameliorated TMT-induced abnormal neural behavior and hippocampal injury, which may be achieved by regulating PK2/PKRs inflammatory pathway and ameliorating synaptic injury. Therefore, we suggest that PK2/PKRs pathway may be involved in TMT neurotoxicity and ARS may be a promising drug that can relieve TMT neurotoxicity.
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BIOMACROMOLECULES
·
2022
·
IF 6.978
Hanning Zhang,Shuangyu Tian,Mu Li,Jinhai Xie,HongLian Dai,Liuyong Hu,Lesan Yan
In this study, a novel donor–acceptor conjugated polymer PDPPDTP was designed and synthesized by D–A polymerization using 2,6-di(trimethyltin)-N-dithieno[3,2-b:20,30-d]pyrrole as the electron-donating (D) unit and 3,6-bis(5-bromothiophen-2-yl)-2,5-dihexadecylpyrrolo[3,4-c]pyrrole-1,4-dione as the electron-accepting (A) unit. The prepared polymer has strong absorption in the near-infrared (NIR) range of 700–900 nm. Moreover, it shows excellent photothermal performance under irradiation at 808 nm. Next, the biodegradable amphiphilic polymer polyethylene glycol–polycaprolactone was used to encapsulate the new conjugated polymer into nanomicelles by the microemulsion method. The obtained PDPPDTP-loaded micelles exhibited a regular spherical structure, and their hydrodynamic diameter was about 78 nm, characterized by transmission electron microscopy and dynamic light scattering. Notably, the micelles exhibited good stability, and the encapsulation efficiency of the conjugated polymer in the micelles was ∼80%. In vitro cell experiments demonstrated that the nanomicelles not only showed good biocompatibility and low toxicity but also could effectively inhibit the proliferation of breast cancer cells 4T1 under the NIR light irradiation of 808 nm. Furthermore, in vivo studies of photothermal therapy (PTT) efficacy showed that the PDPPDTP-loaded micelles exhibited a remarkable tumor growth inhibition in a syngeneic murine tumor model, indicating that the nanomicelles loaded with this novel conjugated polymer could be further explored as a new type of theranostic agent and applied in the PTT of tumors.
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RSC Advances
·
2021
·Vol. 11
·期 62
·39291-39305
·
IF 3.361
Rui Li,Haoran Xu,Yuhang Zhang,Lijing Chang,Yang Ma,Yanjun Hou,Shoulei Miao,Cheng Wang
Pyrene is composed of four benzene rings and has a unique planar melting ring structure. Pyrene is the smallest condensed polycyclic aromatic hydrocarbon, and its unique structural properties have been extensively studied. Pyrene has excellent properties such as thermal stability, high fluorescence quantum efficiency and high carrier mobility. This paper mainly used thiophene, EDOT and triphenylamine groups to enhance the pyrene based π-conjugated system and control the molecular accumulation of organic semiconductors, and improve their charge transport performances. Five kinds of polymer were synthesized and correspondingly characterized. The five kinds of pyrene conductive polymer had outstanding properties in terms of solubility, fluorescence intensity and thermal stability, good film-forming properties, stable electrochromic properties and high coloring efficiency. The coloration efficiency (CE) of PPYTP was as high as 277 cm2 C−1, and the switching response time was short. The coloring time of PPYEDOT was 1.3 s and the bleaching time was 3.2 s. The lower impedance will also provide the possibility of such polymers being incorporated into electrochromic devices in the future. In short, the synthesized new pyrene conductive polymers will have wide application prospects in the field of electrochromic materials.
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RSC Advances
·
2017
·Vol. 7
·期 6
·3117-3124
·
IF 3.108
Zhen Liu,Le Wang,Weiwei Bian,Min Zhang,Jinhua Zhan
Preclinical research reveals the risk of organotin compounds (OTCs) as potent endocrine disruptors, immunotoxicants and environmental obesogens for mammals. OTCs are commercial antifungal agents which are found extensively in clothing, female hygiene products and childcare articles. OTCs have been listed as restricted chemicals by REACH Regulation (Annex XVII). Here, a hyphenated method combining surface enhanced Raman spectroscopy (SERS) with solid phase microextraction (SPME) is proposed for rapid screening of OTCs. A porous Ag layer was synthesized in situ and served as the SERS-active SPME coating for adsorption. The SERS spectra of trimethyltin chloride, tributyltin chloride and triphenyltin chloride were investigated, the bands at 554 cm−1, 1410 cm−1 and 999 cm−1, respectively, being selected as the characteristic peaks for quantitative determination. The extraction conditions were optimized. The good stability and uniformity of porous Ag fibers insure a high enhancement factor of 9.1 × 105 and low LOD of 0.2 ppb for triphenyltin chloride. The proposed method was successfully applied to identify a mixture of OTCs in a textile matrix with satisfactory results.
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2024
·
IF 3.8
Songlin Wang,Chi Chen,Peng Yang,Yu Guo,Bingxing Wang,Hongying Niu,Qiying Zhang,Jianji Wang
Dimethyl carbonate (DMC) is an important synthetic intermediate with widespread applications in the chemical industry. In recent years, the one-step conversion of CO2 into DMC has gained significant attention, but the development of an efficient catalytic system remains a considerable challenge to realize this process. Herein, a series of organotin-oxometalate coordination polymers were developed for DMC synthesis from CO2 and methanol without any solvent/dehydrating agent, and it was found that the metal complexes displayed excellent catalytic performances, especially (nBu3Sn)2MoO4 with the n-butyl group (Bu) was very active, and a high DMC yield (15.7 mmol gcat–1) and high TON value (3.90) were achieved under mild conditions, which was remarkably higher than the recently reported catalytic systems. Moreover, the polymer was highly stable and easy to be recycled with no significant activity loss. Experimental and in situ FT-IR studies revealed that the synergetic catalysis of [Bu3Sn]+ and [MoO4]2– to active CO2 and methanol was the key reason for improved catalytic activity. This study offers a promising strategy for the efficient synthesis of organic carbonates catalyzed by metal complexes to realize better CO2 utilization.
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ENVIRONMENTAL TOXICOLOGY
·
2024
·
IF 4.4
Xiaotong Ni,Haozheng Hong,Haotian Xu,Meng Qi,Shiwen Xu
Trimethyltin chloride (TMT) is a highly toxic organotin pollutant frequently found in aquatic environments, posing a significant threat to the ecological system. The kidney plays a vital role in the body's detoxification processes, and TMT present in the environment tends to accumulate in the kidneys. However, it remained unclear whether exposure to different doses of TMT could induce pyroptosis and immune dysfunction in grass carp kidney cells (CIK cells). For this purpose, after assessing the half-maximal inhibitory concentration (IC50) of TMT on CIK cells, we established a model for exposure of CIK cells at varying concentrations of TMT. CIK cells were treated with various doses of TMT (2.5, 5, 10 μM) for 24 h. Oxidative stress levels were measured using kits and fluorescence methods, whereas the expression of related genes was verified through western blot and quantitative real-time PCR (qRT-PCR). The results indicated that TMT exposure led to oxidative stress, with increased levels of ROS, H 2 O 2 , MDA, and GSH, and inhibited activities of T-AOC, SOD, and CAT. It activated the NF-κB pathway, leading to the upregulation of NF-κB p65, NF-κB p50, GSDMD, NLRP3, ASC, and Caspase-1. Furthermore, TMT exposure also resulted in increased expression of cytokines (IL-18, IL-6, IL-2, IL-1β, and TNF-α) and decreased expression of antimicrobial peptides (LEAP2, HEPC, and β-defensin). In summary, exposure to TMT induces dose-dependent oxidative stress that activates the NF-κB pathway, leading to pyroptosis and immune dysfunction in grass carp CIK cells.
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ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Jun Li,Meixin Hu,Yingying Liu,Rongrong Lu,Weijun Feng
Heavy metals, such as Lead (Pb), are ubiquitous environmental pollutants that is a considerable problem worldwide. Increasing evidences suggest that Pb exposure negatively impact central nervous system. However, the exact toxic mechanism of Pb on early human brain development remain unclear due to the limitations of animal models and 2D cell models. In this study, we used human cortical organoids to reveal that Pb had specific early neurodevelopmental toxicity during the neural differentiation stage. We observed that short-term Pb exposure (10 days) is sufficient to induce premature neuronal differentiation. Mechanistically, Pb exposure downregulates the Wnt signaling in cortical organoids, and the activation of Wnt signaling reverses the neurodevelopmental phenotype. In support, Pb exposure during pregnancy lead to premature neuronal differentiation and reduced neurogenesis in mice. In conclusion, our study reveals the neuropathogenesis of Pb exposure and uncovers the potential intervention role of Wnt activation.
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MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Jiamiao Wang,Jurong Lv,Zheyu Shen,Yan Liu,Xia Gao,Qiang Chen,Pei Liang
Organotin compounds (OTCs) are a hazardous substance that threatens the environment and human health. This study aims to detect organotin effectively. The first step was to compute the Raman spectra of organotin substances using density functional theory (DFT). This was followed by the collection of experimental data for the corresponding spectra. Finally, the gold and silver nanoparticles were prepared as substrates for surface-enhanced Raman scattering (SERS) detection. The SERS spectra were used to extract Raman characteristics that exclusively belong to the same type of metabolites. Additionally, a correspondence was established between these Raman characteristics and their respective vibration modes. The database contains the original SERS spectra and mapping data of the mentioned OTCs, along with the detailed characteristics of their Raman peaks, particularly their unique ones. The results indicate that silver nanoparticles are an effective substrate for SERS detection, providing a sensitive technique for trace detection of organotin compounds.
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POULTRY SCIENCE
·
2024
·
IF 3.8
Xinzhang Chen,Xu Lin
Trimethyl tin (TMT) is a good stabilizer for plastic products but is also a toxic environmental pollutant. Selenium has good antioxidant and anti-inflammatory properties and has been widely used in the poultry industry. However, it has not been reported whether selenium enrichment can antagonize TMT-induced viral hepatitis in poultry. To fill this gap, AA broiler models exposed to TMT for 42 d were established and fed a Se-enriched diet at the same time. H&E staining showed that selenium could significantly alleviate TMT-induced liver inflammation. Further analysis of the underlying mechanism revealed that TMT induced nitrosation stress (RNS), increased NO content and iNOS expression, which in turn activated the NF-κB/NLRP3 pathway and induced pyroptosis. However, selenium enrichment can reverse this situation, that is, reduce the occurrence of RNS, reduce the degree of pyroptosis, and thus alleviate the occurrence of inflammation. In our study, we demonstrated for the first time that TMT could induce hepatotoxicity other than neurotoxicity in poultry and that selenium could antagonize TMT-induced hepatotoxic hepatitis in chickens through the RNS/NF-κB/NLRP3 pathway.
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