Annals of Translational Medicine
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2022
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IF 3.616
Huili Huang,Ying Tong,Tong Fu,Danmei Lin,Hansheng Li,Li Xu,Senyue Zhang,Yanzhe Yin,Yiran Gao
Background To use network pharmacology and gut microbiota sequencing to investigate the probable mechanism of Bining decoction (BN) in the treatment of gouty nephropathy (GN). Methods Firstly, the mechanism of therapeutic effects of BN on GN were collected by integrating network pharmacology. Secondly, the treatment effects of BN against GN in 30 Institute of Cancer Research (ICR) mice were evaluated by performing biochemical tests [uric acid, blood urea nitrogen, and creatinine (UA, BUN, and Cr)] and evaluating the renal weight index. Finally, 16S rRNA sequencing was utilized for elucidating the therapeutical effect of BN in GN. Results The results of gut microbiota sequencing analysis showed the abundance of Faecalibaculum , Romboutsia , Bifidobacterium , Bacteroides , Odoribacter , Lachnospiraceae NK4A136 group, unclassified_f__ Lachnospiraceae , Roseburia , norank_f__ Lachnospiraceae , Lactobacillus , Dubosiella , norank_f__ Muribaculaceae , and Turicibacter in the BN group had a significant changed between-group comparisons. Using a network pharmacology-related database, 413 active components of BN were identified, as well as 1,085 GN-associated targets. The 118 targets of disease targets and component targets were mapped, of which the top 10 genes were selected. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that 157 pathways were enriched, which was partially consistent with the metabolic pathways of gut microbiota sequencing analysis. Conclusions Combining 16S rRNA gene sequencing and network pharmacology analysis, similar signaling pathways were followed: “Pathways in cancer” and “Adipocytokine signaling pathway”. The results reveal that BN increases the abundance of Turicibacter , regulates the expression of JAK2 in the JAK/STAT pathway, increases the beneficial bacteria Turicibacter associated with intestinal butyric acid, which could enhance the intestinal barrier, and exert anti-inflammatory effects.
研究领域:
药理学
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微生物学
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分子生物学
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肾病学
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PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
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2026
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IF 3.7
Wen Qiang,Yuan Yi,Liu Zhihua,Wang Lei,Pan Chunguo
Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. While the chemokine CCL25 is implicated in the tumor microenvironment, its specific role in LC is not fully understood. Here, we identify CCL25 as a key promoter of tumor progression through a novel macrophage-mediated signaling axis. Bioinformatics and clinical analyses revealed that CCL25 is highly expressed in LC and correlates with M2 macrophage infiltration and poorer patient survival. In vitro, tumor-derived CCL25 drove M2 polarization of macrophages by upregulating its receptor CCR9. Functionally, these CCL25-CCR9-induced M2 macrophages secreted TGF-β1 and significantly enhanced the proliferation, migration, and invasion of LC cells. Mechanistically, this effect was mediated through the activation of the JAK/STAT signaling pathway and the subsequent upregulation of the downstream oncogene PIM2 in tumor cells. Both pharmacological inhibition of JAK/STAT and genetic knockdown of PIM2 reversed the tumor-promoting crosstalk. Single-cell transcriptomics confirmed the presence of a TGF-β1-expressing CCR9 + M2 macrophage subset in human tumors and revealed co-expression of CCR9 and PIM2 in tumor cells. In vivo, CCL25 overexpression accelerated tumor growth and M2 macrophage infiltration. Collectively, our findings define a complete CCL25-CCR9-TGF-β1-JAK/STAT-PIM2 signaling circuit wherein tumor cells educate macrophages to, in turn, fuel their own malignant progression, highlighting this axis as a potential therapeutic target in lung cancer.
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PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
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2022
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IF 5.546
Xianqiang Zeng,Liguo Wang,Yan Cao,Chen Liu,Ziqiang Han,Peng He,Huiquan Li
Aliphatic polyethers are synthesized byring-opening polymerization (ROP) of the most common epoxide monomers, such as ethylene oxide (EO) and propylene oxide (PO). 1,2-Butylene oxide (BO) and tetrahydrofuran (THF) are potentially extended ROP monomers, which can give polyether unique properties. In this work, a series of poly(1,2-butylene oxide- stat -tetrahydrofuran)s (PBO- stat -PTHFs) with M n of 900–3700 g·mol −1 were synthesized by cationic ring-opening polymerization (CROP) of BO with THF using strong Lewis acid Rare Earth triflates (RE(OTf) 3 ) as catalysts and diols as an initiator at room temperature. PBO- stat -PTHFs product with yield up to 90 %, narrow polydispersity of Đ <1.30, and molar ratio of PBO to PTHF 1:1 were obtained. The copolymerization process was studied by in-situ IR and 1 H NMR spectroscopy analysis, and the results showed that PBO- stat -PTHF is a statistical copolymer. The early stage of the polymerization reaction was dominated by the activated chain end mechanism (ACEM), which incorporates a large amount of THF into the polymer chains. However, the late stage of the polymerization reaction was dominated by the activated monomer mechanism (AMM), which incorporates a large amount of BO into the polymer chains. Most PBO- stat -PTHFs have a suitable M n range, super high viscosity index (≥198) and low pour point (≤-53 °C), which can be used as a lubricant base oil and additives. In addition, PBO- stat -PTHFs have excellent miscibility with polyalphaolefin (PAO), which could significantly improve the PAO viscosity index. This study provides a mild route to construct high-performance copolyether materials through cationic ring-opening controllable polymerization.
研究领域:
材料科学
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化学工程
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高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Sun Jingjun,Zhu Shuangjiu,Xu Weixuan,Jiang Guoqin
The combination of chemo-photothermal therapy has a wide application prospect in the intensive treatment of cancer. In this study, we developed a complex nanoparticle consist of polypyrrole, cystine dihydrochloride and hyaluronan. The polypyrrole nanoparticles loaded with paclitaxel exhibited good photothermal effects, and the drug release can be triggered by combined response of temperature and redox. In vitro biological studies indicated the nanoparticles could effectively induced apoptosis of MDA-MB-231 breast cancer cells involved in the potential mechanism of inhibition of biological expression of heat shock proteins and JAK-STAT signaling pathway. In addition, the nanoparticles have a significant inhibitory effect on cancer growth in breast tumor-bearing mice model, indicating that they have great potential for synergistic chemo-photothermal therapy.
研究领域:
纳米技术
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癌症治疗
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药学
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生物医学工程
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DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
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2021
·Vol. 193
·期 7
·2029-2042
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IF 2.926
Xu Jian-Miao,Cao Hui-Ting,Wang Ming,Ma Bao-Jian,Wang Liu-Yu,Zhang Kai,Cheng Feng,Xue Ya-Ping,Zheng Yu-Guo
d -amino acid oxidase (DAAO) is widely used in the industrial preparation of l -amino acids, and cultivating Escherichia coli ( E. coli ) expressing DAAO for the biosynthesis of l -phosphinothricin ( l -PPT) is very attractive. At present, the biomass production of DAAO by fermentation is still limited in large-scale industrial applications because the expression of DAAO during the fermentation process inhibits the growth of host cells, which limits higher cell density. In this study, the factors that inhibit the growth of bacterial cells during a 5-L fed-batch fermentation process were explored, and the fermentation process was optimized by co-expressing catalase (CAT), by balancing the biomass and the enzyme activity, and by adding exogenous d -alanine ( d -Ala) to relieve the limitation of DAAO on the cells and optimize fermentation. Under optimal conditions, the DO-STAT feeding mode with DO controlled at 30% ± 5% and the addition of 27.5 g/L lactose mixed with 2 g/L d -Ala during induction at 28 °C resulted in the production of 26.03 g dry cell weight (DCW)/L biomass and 390.0 U/g DCW specific activity of DAAO; an increase of 78% and 84%, respectively, compared with the initial fermentation conditions. The fermentation strategy was successfully scale-up to a 5000-L fermenter.
研究领域:
生物技术
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微生物学
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酶学
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工业发酵
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PubMed
高影响因子
BMC CANCER
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2019
·Vol. 19
·期 1
·1-9
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IF 2.933
Xiao Hui,He Mudan,Xie Guogang,Liu Yanan,Zhao Yuxia,Ye Xiong,Li Xingjing,Zhang Min
Background Cancer cells release exosomes and can be taken up by mast cells (MCs), but the potential functional effects of MCs on tumor metastasis remain unknown.MethodExosomes were isolated from the lung adenocarcinoma cell line A549, and the uptake of PKH26-labeled exosomes by bone marrow MCs was examined via flow cytometry and fluorescence microscopy. Cytokines and tryptase in MC supernatant were analyzed using an ELISA kit, and the presence of tryptase was evaluated by Western blotting. Cell proliferation and migration were determined through CCK-8 and transwell assays. Proteins in the tryptase-JAK-STAT signaling pathway were detected by Western blotting.Results In this study, we show that exosomes from A549 cells can be taken up by MCs. Moreover, A549 exosomes contain stem cell factor (SCF) to MCs and subsequently induce the activation of MCs through SCF-KIT signal transduction, which leads to MC degranulation and the release of tryptase. Tryptase accelerates the proliferation and migration of human umbilical vein endothelial cells (HUVECs) through the JAK-STAT signaling pathway.Conclusion sOur results reveal a mechanism for metastasis in which exosomes can transfer SCF to and activate MCs, which can affect the release of tryptase and the angiogenesis of HUVECs.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2017
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IF 2.956
Yi Zhou,Jing Wang,Weidong Yang,Xiaowen Qi,Lei Lan,Lan Luo,Zhimin Yin
Bergapten (BG) is a cumarine-derivate compound in many medicinal plants . Here, in vitro and in vivo experimental results indicated that BG possesses anti-inflammatory properties, Based on this, we further investigated the precise molecular mechanisms of BG in LPS-stimulated inflammation response . Studies revealed that BG inhibited LPS-stimulated productions of TNF-α, IL-1β, IL-6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time, it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264.7 cells. Mechanistically, BG suppressed the activations of JAK/STAT, but not that of MAPKs and NF-κB. In addition, BG, as an antioxidant, prevented the accumulation of ROS , which further exerted its anti-inflammatory function. In vivo researches revealed that BG decreased LPS-induced mortality in mice. In conclusions, BG may be a potential candidate for inflammation therapy via inhibiting JAK/STAT activation and ROS production in RAW264.7 cells.
研究领域:
药理学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Hongqiao Hou,Bowen Jiang,Aiqing Zhu,Junjun Hou,Zhe Qu,Ruping Liu,Aiqun Li
This study was designed to investigate the protective effect and mechanism of Sufentanil on acute lung injury in septic mice based on network pharmacology and animal experiments, and to provide new ideas for clinical treatment. To this end, a protein-protein interaction (PPI) network for common targets was first constructed with Swiss Target Prediction Database, GeneCards Database, Draw Venn Diagram Software, STRING 11.5 Database, Cytoscape 3.10.0 Software and Metascape Database, and then key targets were subject to enrichment analysis by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to obtain the key targets of Sufentanil for the treatment of pulmonary sepsis, and then verified by animal experiments. A sepsis model was constructed by cecal ligation and puncture (CLP) in this study, and lung tissues and bronchoalveolar lavage fluid (BALF) were taken from each group of mice. The morphological changes of lung tissues and apoptosis were observed by HE and TUNEL staining, the content of inflammatory factors in the lung tissues was detected by ELISA, and the expression of proteins, such as p-JAK2 and p-STAT3, was detected in the lung tissues by Western blotting. According to the results of network pharmacology, a total of 40 common targets of were screened out for Sufentanil and pulmonary sepsis, and GO enrichment analysis involved 1,483 biological processes (BPs), 84 cellular components (CCs) and 125 molecular functions (MFs); KEGG enrichment analysis identified 137 signaling pathways with p < 0.05 such as JAK-STAT. According to the results of animal experiments, compared with the control group, mice in the model group had severe lung tissue injury and elevated expression of relevant inflammatory factors in lung tissue. Compared with the model group, CLP + Sufentanil group showed reduced pathomorphologic lesions, lower expression of inflammatory factors and apoptosis level, as well as lower expression of p-JAK2 and p-STAT3 proteins in lung tissue. The results of animal experiments were consistent with network pharmacology. In summary, Sufentanil may improve lung injury in septic mice by inhibiting the JAK2-STAT3 signaling pathway, which provides a basis for research on the mechanism of Sufentanil on pulmonary sepsis and clinical treatment.
研究领域:
药理学
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免疫学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
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2018
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IF 2.776
Min Xu,Huaqiao Tang,XueRong Zhou,Helin Chen,Qi Dong,Yuanli Zhang,Gang Ye,Fei Shi,Cheng Lv,Bo Jing,Changliang He,Ling Zhao,Yinglun Li
Copper nanoparticles (Cu NPs) have widespread application because of their special physicochemical characteristics, however we need to more clearly study the toxicity mechanism of Cu NPs to ensure its safe use in pharmaceutical and animal feed. Thus, the aim of this study was to evaluate the effects and mechanisms of sub-chronic exposure to Cu NPs on renal CYP450 s of rats. In this study, we investigated the effects of Cu NPs on renal oxidative stress, cytokines and histopathology of rats. We found that Cu NPs (200 mg/kg) significantly disordered the function and structure of the kidney and caused a dose-dependent increase in oxidative stress and cytokines, which significantly decreased the levels of mRNA, protein, and activity of CYP450 s. Micro-coppers (Cu MPs) and Cu ions have similar effects, but their effects on CYP450 s were weaker than Cu NPs. The expression of nuclear receptors were inhibited and the expression of Akt, STAT3/5, CREB, p70S6K, NF-κB, P38 and ERK1/2 were activated when the inhibition effects of CYP450 s activity were observed in renal of rats. Therefore, we believe that Cu NPs can activate the STAT, NF-κB and MAPK signaling pathways to down-regulate the expression and activity of CYP450 s by inducing oxidative stress and inflammatory response in rat kidney.
研究领域:
毒理学
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药理学
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分子生物学
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PubMed
高影响因子
Journal of Advanced Research
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2023
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IF 10.7
Xin Zong,Hao Zhang,Luoyi Zhu,Edward C. Deehan,Jie Fu,Yizhen Wang,Mingliang Jin
Introduction Auricularia auricula is a well-known traditional edible and medical fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. Nondigestible fermentable polysaccharides are identified as primary bioactive constituents of Auricularia auricula extracts. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood. Methods The effects of AAP on obesity were assessed within high-fat diet (HFD)-based mice through obesity trait analysis and metabolomic profiling. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo-germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling. Results High-fat diet (HFD) murine exposure to AAP thwarted weight gains, reduced fat depositing and enhanced glucose tolerance, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. Serum metabolome indicated these effects were associated with changes in fatty acid metabolism. Intestine-dwelling microbial population assessments discovered that AAP selectively enhanced Papillibacter cinnamivorans , a commensal bacterium with reduced presence in HFD mice. Notably, HFD mice treated with oral formulations of P. cinnamivorans attenuated obesity, which was linked to decreased intestinal lipid transportation and hepatic thermogenesis. Mechanistically, it was demonstrated that P. cinnamivorans regulated intestinal lipids metabolism and liver thermogenesis by reducing the proinflammatory response and gut permeability in a JAK-STAT signaling-related manner. Conclusion Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders by regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal P. cinnamivorans. These results indicated AAP and P. cinnamivorans as newly identified pre- and probiotics that could serve as novel therapeutics against obesity.
研究领域:
营养学
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药理学
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微生物学
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代谢学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2026
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IF 8.7
Chen Jingdi,Hao Xiaotian,Xian Chunxing,He Xiang,Wang Taoran,Gao Jiakai,Liu Tao,Wu Wei,Yang Zhao,Bi Long
Repairing segmental bone defects remains difficult because conventional bone substitutes rarely integrate immunomodulation with efficient tissue regeneration. To address this limitation, zinc-silicate-collagen-hydroxyapatite (ZCH) composites were developed wherein the incorporation of zinc allows controlled material degradation and imparts immunoreactive properties. The addition of moderate concentrations of zinc silicate (<0.337 M) maintained good biocompatibility while enabling tuneable degradation rates and bioactivity. Among the composites, the composite containing 0.224 M zinc silicate (10ZCH) exhibited the most favourable balance between material degradation and bone regeneration and promoted accelerated angiogenesis and osteogenesis. Mechanistic studies revealed that 10ZCH transiently activated M1 macrophages and promoted their polarization towards the proregenerative M2 phenotype by activating the JAK/STAT pathway. These findings demonstrate that rational zinc incorporation can orchestrate immune responses, improve material resorption, and promote rapid tissue repair. This work provides an innovative design concept for fabricating immune-responsive and resorbable bone graft substitutes that couple degradation dynamics with regenerative efficacy.
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DOI
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Zhang Jinju,Lin Danlin,Wu Yuting,Chen Lixia,Ma Zhiguo,Wu Menghua,Liu Xindan,Zhang Ying,Cao Hui
Background: Equus asinus L. [Equidae; Asini Corri Colla] (donkey-hide gelatin, E-Jiao) is a traditional Chinese medicine renowned for its exceptional blood-supplementing effect. However, the specific components that contribute to its efficacy remain elusive. This study aimed to demonstrate that peptides are responsible for E-Jiao’s blood-supplementing effect and to explore the specific peptides contributing to its efficacy.Methods: The low molecular weight peptides of E-Jiao (LMEJ) were obtained using an in vitro digestion method. LMEJ and peptides in the rat bloodstream were characterized by peptidomics analysis. The blood-supplementing effect of LMEJ was assessed using blood-deficient zebrafish and mouse models. The effect of the peptides detected in rat blood was evaluated using the same zebrafish model, and network pharmacology analysis was performed to investigate the underlying mechanisms.Results: A total of 660 unique peptides were identified within LMEJ. Both E-Jiao and LMEJ significantly alleviated myelosuppression in mice but only LMEJ attenuated myelosuppression in zebrafish. After the administration of E-Jiao to rats, 67 E-Jiao-derived peptides were detected in the bloodstream, 41 of which were identical to those identified in LMEJ. Out of these 41 peptides, five were synthesized. Subsequent verification of their effects revealed that two of them were able to alleviate myelosuppression in zebrafish. Network pharmacology study suggested that E-Jiao may exert a blood-supplementing effect by regulating signaling pathways such as JAK-STAT, IL-17 and others. These results indicated that peptides are at least partially responsible for E-Jiao’s efficacy.Conclusion: This study provides a crucial foundation for further exploration of the bioactive components of E-Jiao.
研究领域:
药理学
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传统中药
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肽组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）