MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Yulu Wang,Minghao Yuan,Sihui Li,Jiamei Tang,Yan Wan,Xue Liang,Yiping Guo,Li Guo
Alcohol liver disease (ALD) is a chronic liver disorder resulting from long-term heavy alcohol consumption. The pathogenesis of ALD is multifactorial, and existing therapeutic agents primarily target specific aspects of the disease while presenting significant side effects, including drug-induced liver injury and hepatobiliary disease. Silibinin (SLB) has attracted widespread attention for its hepatoprotective effects and favorable safety profile. However, inherent limitations associated with SLB, such as poor solubility and bioavailability, have significantly limited its clinical application. Drug delivery systems, including liposomes, offer promising potential for the delivery of hydrophobic drugs. However, the selection of an appropriate delivery vehicle requires optimization. Ursodeoxycholic acid sodium (UAS) serves as a promising alternative to cholesterol in liposomal formulations, offering a potential strategy to mitigate the health risks associated with cholesterol. In this study, UAS was employed as the liposomal membrane material to prepare a UAS liposome loaded with SLB (SUL), and its efficacy and mechanism of action in alcoholic-induced liver injury were subsequently evaluated. The experimental results demonstrated that SUL exhibited a uniform particle size distribution, good stability, and an effective release profile in vitro. Following oral administration, SUL effectively inhibited alcohol-induced liver damage, oxidative stress, and fat accumulation. In addition, SUL regulated the expression of the kelch-1ike ECH- associated protein l (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) proteins, thereby exerting antioxidative stress effects. Furthermore, it also modulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and cleaved caspase-3, to mitigate hepatocyte apoptosis. In summary, SUL demonstrates enhanced therapeutic efficacy against ALD, offering a novel approach for the clinical application of SLB in the prevention and treatment of ALD.
研究领域:
药理学
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肝病学
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药物递送系统
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分子生物学
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DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
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2025
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IF 2.8
Cheng Cheng,Yanfan Cui,Yujie Wang,Jingfeng Huang,Jiale Ma,Tao Luo,Wen Chen
Microplastics and nanoplastics (MNPs) are widespread in the environment and have male reproductive toxicity. However, toxic interventions involving MNPs have not been extensively examined. In this investigation, we explored the elimination capacity of magnetic nano-Fe 3 O 4 on polystyrene microplastics and nanoplastics (PS-MNPs) of different sizes. This study also investigated whether magnetic nano-Fe 3 O 4 could alleviate the toxicity of PS-MNPs in spermatogonial GC-1 cells. After coprecipitation by magnetic nano-Fe 3 O 4 in ddH 2 O, the removal rates of polystyrene microplastics (PS-MPs, 4 and 10 μm) are much higher than those of PS-NPs (25 nm, 100 nm, and 500 nm). The removal rate of the PS-NPs dramatically enhanced in the salt ion solutions. In addition, 25-nm, 100-nm, 500-nm, and 4-µm PS-MNPs penetrated GC-1 cells. Nevertheless, exclusively 25-nm PS-NPs decreased cell viability, elevated reactive oxygen species, disrupted the mitochondrial membrane potential, and induced apoptosis and inflammation through the P38/MAPK and Nrf2/HO-1 signaling pathways in GC-1 cells. Interestingly, magnetic nano-Fe 3 O 4 alleviated these harmful impacts of the 25-nm PS-NPs on the GC-1 cells. In conclusion, we demonstrated the toxicity of PS-NPs in GC-1 cells and provided a viable way to alleviate their toxicity.
研究领域:
环境毒理学
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纳米技术
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生殖生物学
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材料科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Xinyu Zhao,Huirong Huang,Xinyu Jiang,Shimin Zheng,Chenyu Qiu,Yingfeng Cheng,Yinhao Lin,Yunzhi Wang,Yuqi Yan,Xinyu Di,Miyun Hu,Wanling Zhu,Fugen Wu,Xianbao Shi,Ruijie Chen,Longfa Kou
Osteoarthritis (OA) is a chronic inflammation that gradually leads to cartilage degradation. Prolonged chondrocyte oxidative stress contributes to the development of diseases, including chondrocyte apoptosis, cartilage matrix degradation, and aggravation of articular cartilage damage. Bilirubin (BR) possesses strong antioxidant properties by scavenging reactive oxygen species (ROS) and potent protection effects against inflammation. However, its insolubility and short half-life limit its clinical use. Therefore, we developed a supramolecular system of ε-polylysine (EPL) conjugated by β-cyclodextrin (β-CD) on the side chain, and bilirubin was loaded via host-guest interactions, which resulted in the self-assemble of this system into bilirubin-loaded polylysine-β-cyclodextrin nanoparticle (PB) with improving solubility while reducing toxicity and prolonging medication action time. To explore PB's potential pharmacological mechanisms on OA, we established in vitro and in vivo OA models. PB exerted ROS-scavenging proficiency and anti-apoptotic effects on rat chondrocytes by activating the Nrf2-HO-1/GPX4 signaling pathway. Additionally, PB reprogrammed the cartilage microenvironment by regulating the NF-κB signaling pathway to maintain chondrocyte function. Animal experiments further confirmed that PB had excellent scavenging ability for ROS and inflammatory factors related to charge adsorption with cartilage as well as long retention ability. Together, this work suggests that PB has superior protective abilities with beneficial effects on OA, indicating its great potential for intervention therapy targeting chondrocytes.
研究领域:
药理学
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纳米技术
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骨科
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炎症
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氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Chenxin Xu,Yinghua Chen,Zhuoen Zhou,Ying Yan,Wenying Fu,Peng Zou,Daoyong Ni
Lung cancer is one of the leading causes of death. Celastrol is a natural product that has shown anticancer activity but has not yet been applied in clinical settings due to its narrow therapeutic window. In this study, we discovered that celastrol stimulates an abnormal rise in the reactive oxygen species (ROS) level in lung cancer cells and that the ROS scavenger N-acetylcysteine (NAC) could counteract the cell death caused by celastrol. At the same time, celastrol upregulated the expression of cytoprotective transcription factor Nrf2 and its downstream proteins, which are effective in preventing the oxidative damage caused by ROS accumulation. Notably, we found that the overexpression of Nrf2 enhances the tolerance of lung cancer cells to celastrol and that lung cancer cells H460 with a Keap1 mutation are insensitive to celastrol. This indicates that the increase in Nrf2 contributes to the survival of lung cancer cells. Thus, we brought in an Nrf2 inhibitor ML385 to suppress the activation of Nrf2. We found that when ML385 and celastrol were added together the survival rates of lung cancer cells decreased more and the detected ROS level became much higher compared to treatment with celastrol alone. We also discovered that ML385 suppressed the expression of HO-1 and GCLC, which amplified celastrol-induced ATF4/CHOP-dependent endoplasmic reticulum stress (ER stress). Above all, our study found that ML385 enhanced celastrol-induced increases in ROS and ER stress, leading to lung cancer cell death. This research provides a potential strategy for the preclinical investigation of celastrol.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
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2020
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IF 5.186
Chen Xiao,Liang Huaibin,Xi Zhiyu,Yang Yong,Shan Huimin,Wang Baofeng,Zhong Zhihong,Xu Canxin,Yang Guo-Yuan,Sun Qingfang,Sun Yuhao,Bian Liuguan
Intracerebral hemorrhage (ICH) is a particularly severe form of stroke, and reactive astrogliosis is a common response following injury to the central nervous system (CNS). Mesenchymal stem cells (MSCs) are reported to promote neurogenesis and alleviate the late side effects in injured brain regions. Gap junctions (Gjs) are abundant in the brain, where the richest connexin (Cx) is Cx43, most prominently expressed in astrocytes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor regulating antioxidant reactions. Here, we aimed to explore whether bone marrow MSCs (BM-MSCs) could alleviate brain injury and protect astrocytes from apoptosis, by regulating Cx43 and Nrf2. We validated the effect of BM-MSC transplantation in an ICH model in vivo and in vitro and detected changes using immunofluorescence, as well as protein and mRNA expression of glial fibrillary acidic protein (GFAP), vimentin (VIM), Cx43, Nrf2, and heme oxygenase-1 (HO-1). Our results showed that BM-MSC transplantation attenuated brain injury after ICH and upregulated VIM expression in vivo and in vitro. Additionally, Cx43 upregulation and Nrf2 nuclear translocation were observed in astrocytes cocultured with BM-MSC. Knockdown of Cx43 by siRNA restrained Nrf2 nuclear translocation. Cx43 and Nrf2 had a connection as determined by immunofluorescence and coimmunoprecipitation. We demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and have anti-apoptotic abilities after BM-MSC transplantation, where Cx43 upregulation triggers Nrf2 nuclear translocation and promotes its phase II enzyme expression. The Cx43/Nrf2 interaction of astrocytes after BM-MSC transplantation may provide an important therapeutic target in the management of ICH.
研究领域:
神经科学
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干细胞研究
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神经病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Cleaner Production
·
2026
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IF 10.7
Rui Hu,Hao-Tong Zheng,Boxi Tang,Jialing Tu,Yu-Hong Cui,Xuedong Zhai,Gang Wen,Zheng-Qian Liu
Effluent organic matter (EfOM) from municipal wastewater treatment plants is an emerging concern because of its refractory and potential risk to ecological environment. Herein, this investigation comprehensively evaluated the effects of HO • and O 3 exposures on EfOM transformation and micropollutant degradation under different pre-coagulation operating conditions during ozonation. Compared to coagulation and ozonation alone, coupling two processes could effectively reduce total organic carbon, color and UV 254 of effluent. Fe-based coagulant was easier to combine with OH − to generate floc in bulk than Al-based coagulant for EfOM capture, which could decrease total scavenging capacities of effluents as well as increase the exposures of O 3 and HO • during ozonation, enhancing ozonation efficiency for EfOM degradation. EfOM from membrane bioreactor treatment was more difficult to capture during pre-coagulation but more easily degraded during ozonation than that from conventional activated sludge treatment due to its lower molecular weight distribution and higher contents of humic-like and tryptophan-like substances. Parallel factor analysis shows that coagulation combined with ozonation breaks the fluorescent groups of humic-like and tryptophan-like substances effectively. Molecular weight distribution determination indicates that coupling two processes could more effectively remove humic-like substances, organic colloids and polysaccharides compared to coagulation or ozonation alone. Furthermore, micropollutants with higher energy of highest occupied molecular orbital were degraded more efficiently during ozonation. The investigation reveals that O 3 utilization efficiency for micropollutant degradation can be significantly improved by pre-coagulation, offering new ideas for reducing energy consumption during advanced ozonation treatment and ensuring the safety of effluent and sustainable water reuse.
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2025
·
IF 3.8
Yu Luyao,Liu Meichen,Niu Ziyi,Zhang Jiarui,Deng Yue,Zhou Xinyue,You Jiansong,Xue Hongyu,Yin Lei,Shi Meiyun
Monodisperse polyethylene glycol (PEG) derivatives offer significant advantages over conventional polydisperse PEGs for biomedical applications due to their precisely defined molecular structures. This study establishes an eco-efficient, selective, and sensitive analytical assay integrating microscale solid-phase extraction (μ-SPE) with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to investigate the cellular uptake of HO-PEG 8 -OH polymers in MCF-7 cells. The method achieved greater than 91% recovery from 20 μL lysates using M-PEG 6 -OH as the internal standard, with validated linearity (10–1000 ng/mL, R > 0.997), accuracy (relative error < ± 7.49%), and precision (RSD < 7.50%). The novelty of the assay is the harmonization of analytical performance with green analytical chemistry principles. The validated method provides a robust platform for studying monodisperse PEG derivatives while addressing growing demands for sustainable analytical technologies. Green analytical chemistry metric assessments confirmed the environmental sustainability of the method. Cellular pharmacokinetic analysis revealed time-/concentration-dependent uptake kinetics of HO-PEG 8 -OH polymers in MCF-7 cells, showing 3.2-fold accumulation between 0.5 and 48 h exposure. These findings offer important insights for PEG-based drug delivery system optimization and establish a new standard for environmentally conscious bioanalytical method development. Graphical
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产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2025
·
IF 6.4
Zhen-Cheng Wu,Fang-Xu Tian,Rui Xiao,Mao-Yin Ran,Wenlong Liu,Wen-Tong Chen,Sheng-Ping Guo
The study of infrared nonlinear optical (NLO) materials with wide band gaps and high laser induced damage thresholds (LIDTs) is an urgent and challenging topic. Here, we report the NLO properties of CsRESiS4 (RE = Sm, Gd–Ho), which were synthesized by the reactive flux CsCl assisted RExOy–B–S routine. The structure of CsRESiS4, [CsS7] pentagonal bipyramids are orderly arranged to populate the interlayer space created by [RES7] monocapped triangular prisms consolidated [SiS4] tetrahedra. They all exhibit wide band gaps of 3.51–3.95 eV, high LIDTs of 3.6–5.5 × AGS, and NLO activity, with CsHoSiS4 possessing the largest band gap among rare-earth chalcogenides. The theoretical calculation results indicate that [RES7] monocapped triangular prisms are the main source of NLO activity and have a wide band gap. This work provides an effective case for exploring wide band gap infrared NLO materials.
研究领域:
材料科学
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凝聚态物理
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无机化学
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光学材料
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功能晶体
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产品关联
DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Yan-Ting Lv,Tian-Bin Liu,Yue Li,Zhen-Yong Wang,Cai-Yu Lian,Lin Wang
Cadmium (Cd), a prevalent environmental contaminant, has attracted widespread attention due to its serious health hazards. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to the development of various kidney diseases. However, the mechanisms underlying the occurrence of ferroptosis in Cd-induced renal tubular epithelial cells (TECs) have not been fully elucidated. Hereby, both in-vitro and in-vivo experiments were established to elucidate this issue. In this study, we found that Cd elicited accumulation of lipid peroxides due to intracellular ferrous ion (Fe 2+ ) overload and glutathione depletion, contributing to ferroptosis. Inhibition of ferroptosis via chelation of Fe 2+ or reduction of lipid peroxidation can significantly mitigate Cd-induced cytotoxicity. Renal transcriptome analysis revealed that the activation of heme oxygenase 1 (HO-1) was closely related to ferroptosis in Cd-induced TECs injury . Cd-induced ferroptosis and resultant TECs injury are significantly alleviated due to HO-1 inhibition, demonstrating the crucial role of HO-1 in Cd-triggered ferroptosis. Further studies showed that accumulation of lipid peroxides due to iron overload and mitochondrial ROS (mtROS) generation was responsible for HO-1-triggered ferroptosis in Cd-induced cytotoxicity. In conclusion, the current study demonstrates that excessively upregulating HO-1 promotes iron overload and mtROS overproduction to trigger ferroptosis in Cd-induced TECs injury, highlighting that targeting HO-1-mediated ferroptosis may provide new ideas for preventing Cd-induced nephrotoxicity .
研究领域:
毒理学
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细胞生物学
·
肾脏生理学
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产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2023
·
IF 5.2
Hang Liu,Ziyi Zhang,Jian Liu,Kailin Wang,Yuhong Zhang
In this paper, the upconversion(UC) and downshifting(DS) luminescence and thermal sensing performances of the CaIn 2 O 4: RE 3+ /Tm 3+ /Yb 3+ (RE=Er, Ho) phosphors are investigated in detail. The bright UC emission bands from 450 to 900 nm and the DS luminescence bands from 1000 to 1700 nm are obtained under 980 nm excitation. The typical near infrared(NIR) emisson band(∼1550 nm) of Er 3+ ions and the NIR emission band(∼1200 nm) of Ho 3+ ions are gained. The temperature sensing features of CaIn 2 O 4: RE 3+ /Tm 3+ /Yb 3+ (RE=Er, Ho) phosphors are investigated with the luminescence intensity ratio (LIR) technique. The results indicate that the maximum relative sensitivity (S Rmax ) of CaIn 2 O 4: Er 3+ /Tm 3+ /Yb 3+ sample reaches 1.576% K -1 at 313 K, and the S Rmax of CaIn 2 O 4: Ho 3+ /Tm 3+ /Yb 3+ sample reaches 0.797% K -1 at 353 K in UC range. In addition, the higher temperature measuring sensitivities have been obtained in NIR-II region with the DS luminescence of CaIn 2 O 4: RE 3+ /Tm 3+ /Yb 3+ phosphors. The above results indicate that the CaIn 2 O 4: RE 3+ /Tm 3+ /Yb 3+ phosphors show bright emission bands in visible and NIR-II, and higher sensitivity for temperature measurement. The CaIn 2 O 4: RE 3+ /Tm 3+ /Yb 3+ phosphors present great application in optical temperature measurement.
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产品关联
DOI
高影响因子
Iranian Journal of Basic Medical Sciences
·
2023
·
IF 2.2
Junyuan Li,Gang Wang,Yehao Zhang,Xiaodi Fan,Mingjiang Yao
Objective(s): To explore the ability and underlying molecular mechanisms involved in the protective effects of Baicalin (BA) against L-Glutamate-induced mouse hippocampal neuron cell line HT-22. Materials and Methods: The cell injury model of HT-22 cells was induced by L-glutamate, and cell viability and damage were detected by CCK-8 and LDH assays. Generation of intracellular reactive oxygen species (ROS) was measured by DCFH-DA in situ fluorescence method. The SOD activity and MDA concentration in the supernatants were determined by WST-8 and colorimetric method, respectively. Furthermore, Western blot and real-time qPCR analysis were utilized to detect the expression levels of the Nrf2/HO-1 signaling pathway and NLRP3 inflammasome proteins and genes. Results: L-Glutamate exposure induced cell injuries in HT-22 cells, and the concentration of 5 mM L-Glutamate was chosen to be the modeling condition. Co-treatment with BA significantly promoted cell viability and reduced LDH release in a dose-dependent manner. In addition, BA attenuated the L-Glutamate-induced injuries by decreasing the ROS production and MDA concentration, while increasing the SOD activity. Moreover, we also found that BA treatment up-regulated the gene and protein expression of Nrf2 and HO-1, and then inhibited the expression of NLRP3. Conclusion: Our study found that BA could relieve oxidative stress damage of HT-22 cells induced by L-Glutamate, and the mechanism might be related to the activation of Nrf2/HO-1 and inhibition of NLRP3 inflammasome.
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Runhong Zhou,Jianan Hu,Jingnan Qiu,Shengsheng Lu,Haixing Lin,Ruifeng Huang,Shaofen Zhou,Guoqing Huang,Jian He
Influenza A virus (IAV) is one of the leading causes of respiratory illness and continues to cause pandemics around the world. Against this backdrop, drug resistance poses a challenge to existing antiviral drugs, and hence, there is an urgent need for developing new antiviral drugs. In this study, we obtained a phenolic compound SG -7, a derivative of natural compound 2-hydroxymethyl-1,4-hydroquinone, which exhibits inhibitory activity toward a panel of influenza viruses and has low cellular toxicity. Mechanistic studies have shown that SG -7 exerts its anti-IAV properties by acting on the virus itself and modulating host signaling pathways. Namely, SG -7 targets the HA2 subunit of hemagglutinin (HA) to block the fusion of viral-cellular membranes and inhibits IAV-induced oxidative stress and overexpression of pro-inflammatory factors by activating the Nrf2/HO-1 pathway and reducing NF-κB activation. In addition, SG -7 can enhance type I IFN antiviral response by inducing Nrf2 expression. Importantly, SG-7 showed the ability to inhibit viral replication in the lungs of IAV-infected mice and reduce their mortality. Therefore, SG-7 may be a promising lead compound for anti-influenza drug development .
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）