Frontiers in Immunology
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2022
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IF 8.786
Wang Juan,Wang Furong,Yuan Lixia,Ruan Hongsheng,Zhu Zhibiao,Fan Xiaoling,Zhu Lingyan,Peng Xin
Polygonatum sibiricum Red. has been used as a medicinal herb and nutritional food in traditional Chinese medicine for a long time. It must be processed prior to clinical use for safe and effective applications. However, the present studies mainly focused on crude Polygonatum sibiricum (PS). This study aimed to investigate the chemical properties, blood-enriching effects and mechanism of polysaccharide from the steam-processed Polygonatum sibiricum (SPS), which is a common form of PS in clinical applications. Instrumentation analyses and chemistry analyses revealed the structure of SPS polysaccharide (SPSP). A mice model of blood deficiency syndrome (BDS) was induced by acetylphenylhydrazine (APH) and cyclophosphamide (CTX). Blood routine test, spleen histopathological changes, serum cytokines, etc. were measured. The spleen transcriptome changes of BDS mice were detected by RNA sequencing (RNA-seq). The results showed that SPSP consists predominantly of Gal and GalA together with fewer amounts of Man, Glc, Ara, Rha and GlcN. It could significantly increase peripheral blood cells, restore the splenic trabecular structure, and reverse hematopoietic cytokines to normal levels. RNA-seq analysis showed that 122 differentially expressed genes (DEGs) were obtained after SPSP treatment. GO and KEGG analysis revealed that SPSP-regulated DEGs were mainly involved in hematopoiesis, immune regulation signaling pathways. The reliability of transcriptome profiling was validated by quantitative real-time PCR and Western blot, and the results indicated that the potential molecular mechanisms of the blood-enriching effects of SPSP might be associated with the regulating of JAK1-STAT1 pathway, and elevated the hematopoietic cytokines (EPO, G-CSF, TNF-α and IL-6). This work provides important information on the potential mechanisms of SPSP against BDS.
研究领域:
药理学
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分子生物学
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中医药
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免疫学
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血液学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Meng Sun,Nan Hu,Yangyang Gao,Nan Lv,Xiaohong Fu,Yafeng Li,Shaodong Zhai,Ruiping Zhang
Ischemia-induced myocardial injury has become a serious threat to human health, and its treatment remains a challenge. The occurrence of ischemic events leads to a burst release of reactive oxygen species (ROS), which triggers extensive oxidative damage and leads to dysfunctional autophagy, making it difficult for cells to maintain homeostasis. Antioxidants and modulation of autophagy have thus become promising strategies for the treatment of ischemic myocardial injury. This study proposes an antioxidant-activated autophagy therapeutic regimen based on combining melanin (Mel), an excellent antioxidant with metformin mimetic ploymetformin via electrostatic interactions, to obtain a nanocomplex (Met-Mel). The nanocomplex is finally encapsulated with platelet membranes (PMN) to construct a biomimetic nanoparticle (PMN@Met-Mel) capable of targeting injured myocardium. The prepared PMN@Met-Mel has good Mel loading capacity and optimal biosafety. It exhibits excellent antioxidant activity and autophagy activation, rapidly restoring mitochondrial function. Moreover, RNA sequencing (RNA-seq) analysis reveals that PMN@Met-Mel operates mechanistically by triggering the activation of the autophagy pathway. Subsequent in vivo experiments showcase promising cardioprotective effects of these nanoparticles. These discoveries present a newly devised nanoplatform with promising potential for the effective treatment of myocardial infarction.
研究领域:
心血管疾病
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纳米医学
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2023
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IF 9.7
Xu Jin,Jie Shan,Jiemin Zhao,Tao Wang,Wei Zhang,Shijie Yang,Haisheng Qian,Liang Cheng,Xu-Lin Chen,Xianwen Wang
Infections and oxidative stress complicate wound healing. In recent years, nanomaterials with natural enzymatic activities have enabled the development of new antibacterial pathways. In this study, Cu-Fe 3 O 4 nanoclusters with multienzyme properties were synthesised. Interestingly, they exhibited activity similar to that of horseradish peroxidase (POD) in acidic environments but their functions resembled superoxide dismutase and catalase in neutral or weakly alkaline environments. In vitro studies have demonstrated the good free-radical scavenging activity of Cu-Fe 3 O 4 nanoclusters in a neutral environment. Under acidic conditions, Cu-Fe 3 O 4 nanoclusters combined with H 2 O 2 demonstrated good antibacterial activity against methicillin-resistant Staphylococcus aureus ( MRSA ) and Escherichia coli ( E. coli ). The combination of Cu-Fe 3 O 4 and H 2 O 2 was found to be effective in preventing MRSA infections and promoting wound healing in animal models. RNA sequencing (RNA-seq) technology revealed that chemodynamic therapy (CDT) using nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria, destroy the transport system on the surface of MRSA , and affect quorum sensing to hinder the formation of biofilms, thus achieving effective antibacterial efficacy. The use of Cu-Fe 3 O 4 nanoclusters as a novel class of multi-catalytically active nanozymes in the anti-infection of disease-causing pathogens and wound healing has significant potential. Statement of Significance Cu-Fe 3 O 4 nanoclusters with multienzyme properties were successfully prepared by a solvothermal method. Cu-Fe 3 O 4 nanoclusters exhibited horseradish peroxidase (POD)-like activity in acidic environments and also showed synergistic effects similar to superoxide dismutase peroxidase in neutral or weakly basic environments. More importantly, these Cu-Fe 3 O 4 nanoclusters showed high biosafety with no apparent in vivo toxicity. Chemodynamic therapy (CDT) using Cu-Fe 3 O 4 nanoclusters was revealed by RNA sequencing (RNA-Seq) technology to interfere with the metabolic processes of MRSA bacteria, such as galactose metabolism, disrupt the MRSA surface transport system, and impede biofilm formation, resulting in effective antibacterial efficacy. The use of Cu-Fe 3 O 4 nanoclusters for anti-infection and wound healing of pathogenic pathogens has significant potential as a novel class of multi-catalytic active nanoclusters.
研究领域:
纳米技术
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生物医学工程
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伤口愈合
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抗菌治疗
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酶模拟
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产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2025
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IF 8
Chuan Liang,Yang Chen,Yunzhe Ling,Peirun Li,Jiahao Liu,Xuantian Li,Yanhua Xu,Zhiying Liu
Non-steroidal anti-inflammatory drugs (NSAIDs), though designed to target specific molecular pathways, pose significant environmental risks to non-target organisms, particularly marine fish. This study investigated the toxicity mechanisms and adaptive responses to diclofenac (DCF) and meloxicam (MEX) during the early life stages (ELS) of Oryzias melastigma at environmentally relevant concentrations over a 31-day period. Mechanistic investigations of sub-lethal effects were conducted using Enzyme-Linked Immunosorbent Assay (ELISA), RNA sequencing (RNA-Seq) and quantitative PCR (qPCR). The results revealed that cyclooxygenase (COX) inhibition disrupted the renin-angiotensin system, leading to an accumulation of angiotensin II and cardiovascular developmental defects. Additionally, downregulation of the pla2 gene reduced substrates essential for COX enzyme activity, exacerbating the effects. Although NSAIDs are known to affect the digestive system, no significant effects on developmental factors were observed. RNA-Seq and qPCR analyses revealed an adaptive upregulation of key genes, including ace2 and cyp7a1 , involved in cardiovascular and metabolic regulation. Furthermore, 16S rRNA sequencing identified shifts in the microbial community, particularly in g_Rubritalea and g_Sphingomonas genera. Both the upregulated genes and the altered microbial taxa likely played a role in mitigating toxic effects and promoting homeostasis. Moreover, molecular docking suggested that MEX exhibited stronger sub-lethal effects than DCF, likely due to its higher binding affinity to COX. These findings provide valuable insights into NSAID toxicity mechanisms in marine fish, highlighting the importance of adaptive responses in countering environmental stress and underscoring the long-term ecological risks of chronic NSAID exposure.
研究领域:
海洋毒理学
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环境科学
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药理学
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分子生物学
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发育生物学
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生态毒理学
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微生物学
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生物信息学
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药物发现
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
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2021
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IF 4.418
Peng Wang,Xiaoxia Gao,Fang Zhao,Yao Gao,Kexin Wang,Jun-Sheng Tian,Zhenyu Li,Xue-Mei Qin
Depression has drawn increasing attention from the public around the world in recent years. Studies have shown that liver injury caused by chronic stress is relevant to depression and neurotransmitter changes. It is essential to clarify the relationship between neurotransmitter changes and hepatic gene expression in depression. In this study, we used the chronic unpredictable mild stress (CUMS) model combined with UHPLC–MS to explore the changes of neurotransmitters in serum and hippocampus and to decipher the differential gene expression in the liver by using the RNA-Seq combined with multivariate statistical analysis. Compared with the control group, the levels of neurotransmitters including 5-hydroxytryptamine (5-HT), acetylcholine, glutamate (Glu), and dopamine (DA) in the hippocampus and 5-HT, norepinephrine, γ-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid in serum were significantly changed in the CUMS rats. The results of liver transcriptomic analysis and correlation analysis showed that the Glu, DA, 5-HT, and GABA were impacted by 68 liver genes which were mainly enriched in three pathways including circadian rhythm, serotonergic synapse, and p53 signaling pathway. The expressive levels of clock genes and serotonergic synapse genes were validated by using q-PCR, and the diurnal rhythms of neurotransmitters were validated by in vivo hippocampus microdialysis. The CUMS stressors might cause phase advance of Glu and GABA by adjusting clock genes. The transcriptomic technique combined with correlation analysis and in vivo microdialysis could be used to discover comprehensive pathways of depression. It provides a new strategy for the rational assessment of the mechanism of disease.
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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转录组学
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行为科学
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DOI
PubMed
高影响因子