Nanomaterials
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2020
·Vol. 10
·期 10
·2029
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IF 4.324
Runqing Geng,Yuanyuan Ren,Rong Rao,Xi Tan,Hong Zhou,Xiangliang Yang,Wei Liu,Qunwei Lu
Titanium dioxide nanoparticles (nano-TiO2), as a common nanomaterial, are widely used in water purification, paint, skincare and sunscreens. Its safety has always been a concern. Prior studies have shown that ultraviolet A (UVA) can exacerbate the toxicity of nano-TiO2, including inducing cell apoptosis, changing glycosylation levels, arresting cell cycle, inhibiting tumor cell and bacterial growth. However, whether the combination of UVA and nano-TiO2cause cell necrosis and its mechanism are still rarely reported. In this study, we investigated the cytotoxicity and phototoxicity of mixture crystalline nano-TiO2(25% rutile and 75% anatase, 21 nm) under UVA irradiation in HeLa cells. Our results showed that the abnormal membrane integrity and the ultrastructure of HeLa cells, together with the decreased viability induced by nano-TiO2under UVA irradiation, were due to cell necrosis rather than caspase-dependent apoptosis. Furthermore, nano-TiO2and UVA generated the reactive oxygen species (ROS) and caused the mitochondrial permeability transition pore (mPTP) of HeLa cells to abnormally open. Cell viability was significantly increased after adding vitamin C (VC) or cyclosporin A (CsA) individually to inhibit ROS and mPTP. Clearance of ROS could not only impede the opening of mPTP but also reduce the rate of cell necrosis. The results suggest the possible mechanism of HeLa cell necrosis caused by nano-TiO2under UVA irradiation through the ROS-mPTP pathway.Keywords:nano-TiO2;UVA;cell necrosis;reactive oxygen species;mitochondrial permeability transition pore
研究领域:
纳米技术
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细胞生物学
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毒理学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Zemin Ou,Yun You,Hong Yi,Xiaoqian Liu,Yan Tong,Dewen Liu,Jinyu Wang
Introduction Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.
研究领域:
神经科学
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药学
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生物技术
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2023
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IF 5.1
Hefei Wang,Dewei He,Zhe Li,Xiyu Gao,Shuo Yang,Mingchi Cui,Bojian Ye,Bingxu Huang,Shoupeng Fu,Dianfeng Liu
Neuronal apoptosis and neuroinflammation are key factors involved in the pathological changes of Parkinson's disease (PD). Sophoricoside (SOP) has shown anti-inflammatory and anti-apoptosis effects in various diseases. However, the role of SOP in PD has not been reported. In this experiment, we found that oral administration of SOP alleviated weight loss and motor symptoms in 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-injected mice. Further studies revealed that SOP inhibited inflammatory responses and neuronal apoptosis in the midbrain region of MPTP-injected mice. In vitro mechanistic study, we found that SOP exerts neuroprotective effects through a two-sided action. On the one hand, SOP inhibits Lipopolysaccharide (LPS)-induced inflammatory responses in microglia by inhibiting the Nuclear factor kappa-B(NF-κB) pathway. On the other hand, SOP inhibits 1-methyl-4-phenylpyridinium (MPP + )-induced neuronal apoptosis by regulating the Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Thus SOP is expected to be a potential therapeutic agent for PD by targeting neuroinflammation and neuronal apoptosis.
研究领域:
神经科学
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药理学
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神经退行性疾病
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DOI
PubMed
高影响因子
Neuropsychiatric Disease and Treatment
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2024
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IF 2.5
Yueyuan Wang,Bo Lv,Kai Fan,Cunjin Su,Delai Xu,Jie Pan
Purpose Parkinson’s disease (PD) is a common neurodegenerative disease that severely affects patients’ daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD.Methods We divided 78 mice into six equal groups, including five model PD groups (W1–W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group. Then, we used metabolomics technology to detect the serum small-molecule metabolites present in each group. Ultimately, we screened for potential biomarkers using the variable importance in the projection of the orthogonal partial least squares discriminant analysis and the coefficient value of LASSO ordinal logistic regression.Results We identified 12 potential biomarkers, including dehydroepiandrosterone sulfate, pipecolic acid, N-acetylleucine, 2-aminoadipic acid, L-tyrosine, uric acid, and 5-hydroxyindoleacetaldehyde. Pathway analysis revealed their involvement in amino acid metabolism, caffeine metabolism, steroid hormone biosynthesis, and purine metabolism. Additionally, the receiver operating characteristic curve indicated that a biomarker panel comprising the 12 biomarkers could differentiate between the different PD stages.Conclusion Different PD stages are characterized by different metabolites. The biomarkers identified in this study are helpful to understand the PD process.
研究领域:
神经科学
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代谢组学
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医学
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DOI
PubMed
高影响因子
Frontiers in Immunology
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2026
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IF 7
Jinli Ma,Luya Pu,Yundong Zhang,Baiao Wu,Rui Fei,Dongmei Han,Miao Hao,Jianshi Du
BackgroundSecondary lymphedema leads to progressive tissue remodeling and immune dysregulation. Dysregulation of macrophage polarization critically influences pathological progression. Oxidative stress and mitochondrial homeostasis are the critical components of secondary lymphedema.MethodsA secondary lymphedema model and an LPS-induced in vitro cell injury model were established. Mitochondrial dynamics were evaluated using the ROS assay, mitochondrial membrane potential analysis and mPTP opening assays. Mechanistic investigations included Nrf2 nuclear translocation analysis via immunofluorescence, western blotting, and pharmacological inhibition of exosome biogenesis using GW4869.ResultsSecondary lymphedema tissues exhibited a significant imbalance in M1/M2 macrophage infiltration (with an increase in M1 and decrease in M2), along with elevated IL-1β levels. M2-Exo significantly prevents the proliferation, migration, and tube formation of human lymphatic endothelial cells and alleviated the mitochondrial damage induced by LPS. This mechanism may involve activation of Keap1-Nrf2 signaling.ConclusionM2 macrophage exosomes activated the Nrf2 anti-oxidative stress pathway. This activation improves mitochondrial homeostasis and enhances the function of human lymphatic endothelial cells by delivering active ingredients, offering a new strategy for the treatment of secondary lymphedema.
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DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2025
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IF 5.4
Yu Sun,Li Cui,Wanqiu Peng,Rong Chen,Xueneng Guan,Jiangyun Liu
Parkinson’s disease (PD) is difficult to treat clinically and lacks an effective treatment. The aim of this study was to synthesize and characterize butyrate-modified hyaluronic acid (HA-But), validate its therapeutic efficacy, and elucidate its mechanisms of action in PD. Behavioral tests, including the open field test, Y-maze, and elevated plus maze test, demonstrated that HA-But significantly alleviated motor dysfunction in PD mice. ELISA results indicated a marked reduction in pro-inflammatory cytokine levels following the HA-But treatment. In addition, immunohistochemistry, immunofluorescence, and Western blot analyses revealed that HA-But improved dopaminergic neuron survival and reduced α-synuclein aggregation. Furthermore, HA-But activated PINK1/Parkin-mediated mitophagy, modulated gut microbiota composition, and increased short-chain fatty acid (SCFA) levels, especially butyric acid. Combining HA-But with gastrodin further improved the PD symptoms in mice. These findings suggested the potential of HA-But as a novel approach for PD treatment.
研究领域:
神经科学
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药学
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分子生物学
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肠脑轴
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2025
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IF 5.1
Yujun Chen,Yuhang Zhao,Qing Wang,Qiuchi Chen,Xiqun Chen,Kai Yang
Background Parkinson’s disease (PD) is a common neurodegenerative disorder. Emodin (EMD), which is derived from multiple Chinese medicinal herbs, has been reported to possess anti-inflammatory, anti-ferroptosis, and neuroprotective effects. However, the mechanisms underlying the regulation of PD-related ferroptosis remain unclear.Objective To investigate whether EMD protects dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced models of PD and to elucidate its underlying mechanisms.Methods Potential EMD targets were predicted using SEA and Swiss databases. The PD targets were identified using the OMIM and GeneCards databases. Overlapping genes were introduced to construct protein-protein interactions (PPI) and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was used to ascertain the possibility of the binding of EMD to p53 and TfR1. The stability of EMD-p53 complex was validated by using molecular dynamics simulations using the YASARA. To validate these mechanisms, we used an MPTP-induced mouse model to investigate the beneficial effects of EMD. Motor function was assessed using the open field and rotarod tests. Malondialdehyde (MDA) and iron contents in the midbrain were determined. SH-SY5Y cells were subjected with 1-methyl-4-phenyl-pyridinium (MPP+) or ferroptosis inducer. Ferroptosis signaling, iron metabolism, and mitochondrial superoxide levels were investigated using Western blotting, qPCR, immunofluorescence, and flow cytometry.Results Enrichment analysis revealed that the shared targets of the PD and EMD gene sets were involved in iron metabolism, with TP53 being the most connected protein in the PPI network. Molecular docking analysis suggested that EMD formed a stable complex with p53 or TfR1. Molecular Dynamics Simulation further confirmed that the interactions between EMD and p53 remained stable over time. In vivo studies demonstrated the beneficial effects of EMD in an MPTP mouse model of PD. This action was achieved by inhibiting p53 expression and mitigating ferroptosis signaling in the substantia nigra (SN). EMD similarly attenuated cell injury and ferroptosis in SH-SY5Y cells by inhibiting p53-ferroptosis signaling. In contrast, pharmacological enhancement of p53 nullified these effects in the MPP+-treated SH-SY5Y cells.Conclusion These preliminary results indicate that EMD could exert neuroprotective effects against MPTP-induced toxicity, possibly via modulating p53-ferroptosis signaling.
研究领域:
神经科学
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药理学
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分子生物学
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中医药学
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计算生物学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
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2024
·Vol. 22
·期 1
·1-16
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IF 6.1
Xiong Yi,Chen Jiawen,Liang Wei,Li Kun,Huang Yingqi,Song Jingwen,Zhang Baoyu,Qiu Xiusheng,Qiu Dongbo,Zhang Qi,Qin Yunfei
Background Liver surgery during the perioperative period often leads to a significant complication known as hepatic ischemia-reperfusion (I/R) injury. Hepatic I/R injury is linked to the innate immune response. The cGAS-STING pathway triggers the activation of innate immune through the detection of DNA within cells. Nevertheless, the precise mechanism and significance of the cGAS-STING pathway in hepatic I/R injury are yet to be investigated. Methods Mouse model of hepatic I/R injury was used in the C57BL/6 WT mice and the STING knockout (STING-KO) mice. In addition, purified primary hepatocytes were used to construct oxygen-glucose deprivation reperfusion (OGD-Rep) treatment models. Results Our research revealed a notable increase in mRNA and protein levels of cGAS and STING in liver during I/R injury. Interestingly, the lack of STING exhibited a safeguarding impact on hepatic I/R injury by suppressing the elevation of liver enzymes, liver cell death, and inflammation. Furthermore, pharmacological cGAS and STING inhibition recapitulated these phenomena. Macrophages play a crucial role in the activation of the cGAS-STING pathway during hepatic I/R injury. The cGAS-STING pathway experiences a significant decrease in activity and hepatic I/R injury is greatly diminished following the elimination of macrophages. Significantly, we demonstrate that the activation of the cGAS-STING pathway is primarily caused by the liberation of mitochondrial DNA (mtDNA) rather than nuclear DNA (nDNA). Moreover, the safeguarding of the liver against I/R injury is also attributed to the hindrance of mtDNA release through the utilization of inhibitors targeting mPTP and VDAC oligomerization. Conclusions The results of our study suggest that the release of mtDNA plays a significant role in causing damage to liver by activating the cGAS-STING pathway during I/R injury. Furthermore, inhibiting the release of mtDNA can provide effective protection against hepatic I/R injury.
研究领域:
免疫学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Qiang-Ming Li,Shu-Zhen Wu,Xue-Qiang Zha,Dan-Dan Zang,Feng-Yun Zhang,Jian-Ping Luo
Ethnopharmacological relevance Ganoderma lucidum , a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson’s disease (PD). Aim of the study To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. Materials and methods PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP + ), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. Results GAA significantly mitigated MPP + /MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss ( p ＜0.01 or p ＜0.05). In contrast to MPP + /MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models ( p ＜0.01 or p ＜0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 ( p ＜0.01). Conclusion GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.
研究领域:
神经药理学
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神经科学
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民族药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Shi Hongwei,Tang Heng,Ai Wen,Zeng Qingfu,Yang Hong,Zhu Fengqing,Wei Yunjie,Feng Rui,Wen Li,Pu Peng,He Quan
Objective: Pirarubicin (THP), one of the anthracycline anticancer drugs, is widely used in the treatment of various cancers, but its cardiotoxicity cannot be ignored. Schisandrin B (SchB) has the ability to upregulate cellular antioxidant defense mechanism and promote mitochondrial function and antioxidant status. However, it has not been reported whether it can resist THP-induced cardiotoxicity. The aim of this study was to investigate the effect of SchB on THP cardiotoxicity and its mechanism.Methods: The rat model of cardiotoxicity induced by THP was established, and SchB treatment was performed at the same time. The changes of ECG, cardiac coefficient, and echocardiogram were observed. The changes of myocardial tissue morphology were observed by H&E staining. Apoptosis was detected by TUNEL. The levels of LDH, BNP, CK-MB, cTnT, SOD, and MDA in serum were measured to observe the heart damage and oxidative stress state of rats. The expression of cleaved-caspase 9, pro/cleaved-caspase 3, Bcl-2/Bax, and cytosol and mitochondrial Cyt C and Bax was evaluated by western blot. H9c2 cardiomyocytes were cocultured with THP, SchB, and mPTP inhibitor CsA to detect the production of ROS and verify the above signaling pathways. The opening of mPTP and mitochondrial swelling were detected by mPTP kit and purified mitochondrial swelling kit.Results: After 8 weeks, a series of cardiotoxicity manifestations were observed in THP rats. These adverse effects can be effectively alleviated by SchB treatment. Further studies showed that SchB had strong antioxidant and antiapoptotic abilities in THP cardiotoxicity.Conclusion: SchB has an obvious protective effect on THP-induced cardiotoxicity. The mechanism may be closely related to the protection of mitochondrial function, inhibition of mPTP opening, and alleviation of oxidative stress and apoptosis of cardiomyocytes.
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Neuroscience
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2025
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IF 3.2
Shuai Shi,Xiaohan Bian,Mengyun Li,Xiaobing Zhang,Wenji Huang,Xian Shao,Tiantian Lu,Xuebin Yu
Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction and dopaminergic neuronal loss. Emerging evidence suggests that gut microbiota dysbiosis and systemic metabolic disturbances contribute to the pathogenesis of PD. This study aimed to investigate the neuroprotective effects of bavachalcone, a prenylated chalcone isolated from Psoralea corylifolia, in an MPTP-induced mouse model of PD, with a particular focus on its effects on motor function, inflammation, gut microbiota, and serum metabolism.Methods: Male C57BL/6 mice were divided into Control, MPTP, Bavac-L (low-dose bavachalcone), and Bavac-H (high-dose bavachalcone) groups. Bavachalcone was administered by gavage, followed by MPTP injection to induce PD. Behavioral assessments (open field test, pole test, and rotarod test), western blotting, immunohistochemistry, immunofluorescence, 16S rDNA sequencing of fecal microbiota, and untargeted metabolomics of serum were performed to evaluate the effects of bavachalcone.Results: Bavachalcone significantly alleviated MPTP-induced motor impairment, preserved dopaminergic neurons in the substantia nigra and striatum, and reduced systemic inflammation and glial activation. Gut microbiota analysis showed that bavachalcone improved microbial richness and diversity, enriched beneficial genera, such as Allobaculum, and suppressed harmful taxa, such as Ligilactobacillus and Helicobacter. Metabolomic profiling revealed that bavachalcone modulated pathways, including pyruvate metabolism, folate biosynthesis, and phenylalanine metabolism.Conclusion: Bavachalcone exerts neuroprotective effects in mice with PD by improving motor function, preserving dopaminergic neurons, reducing inflammation, modulating gut microbiota composition, and remodeling systemic metabolism. These findings highlight bavachalcone as a promising therapeutic candidate for PD.
研究领域:
神经生物学
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微生物组学
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代谢组学
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药理学
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神经退行性疾病
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免疫调节
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转化医学
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
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2024
·Vol. 22
·期 1
·1-21
·
IF 6.1
Guo Qinglong,Wang Yi,Yu Liangchen,Guan Liao,Ji Xuefei,Li Xiaohui,Pang Gang,Ren Zhenhua,Ye Lei,Cheng Hongwei
Background Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice.Methods MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines.Results Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis.Conclusion sThis study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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