CHEMICAL RESEARCH IN TOXICOLOGY
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2022
·
IF 3.973
Xiaoying He,Jiali Wang,Qian Wang,Jing Liu,Xi Yang,Lingjuan He,Haihong Hu,Su Zeng,Lushan Yu,Yunqing Qiu,Yan Lou
Hand-foot syndrome (HFS) is a major adverse reaction to capecitabine (CAP). The exact pathogenesis of this disease remains unclear. In this study, metabolomics combined with cell RNA sequencing was used to study the mechanisms of CAP-induced HFS. The murine model of HFS was constructed by intragastric administration of CAP or its metabolites. Quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to verify the mechanisms. Metabolomics showed the phosphatidylinositol signaling pathway and amino acid and fatty acid metabolism to be the major metabolic alterations related to the occurrence of HFS. Transcriptomics profiles further revealed that the cytokine–cytokine receptor interaction, IL17 signaling pathway, Toll-like receptor signaling pathway, arachidonic acid metabolism, MAPK signaling pathway, and JAK-STAT3 signaling pathway were the vital steps in skin toxicity induced by CAP or its metabolites. We also verified that the inflammation mechanisms were primarily mediated by the abnormal expression of interleukin (IL) 6 or IL8 and not exclusively by COX-2 overexpression. Finally, the P38 MAPK, NF-κB, and JAK-STAT3 signaling pathways, which mediate high levels of expression of IL6 or IL8, were identified as potential pathways underlying CAP-induced HFS.
研究领域:
药理学
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毒理学
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分子生物学
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免疫学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Li-Juan Zhao,Hai-Yu Zhao,Xiao-Lu Wei,Fei-Fei Guo,Jun-Ying Wei,Hong-Jie Wang,Jian Yang,Zhi-Gang Yang,Nan Si,Bao-Lin Bian
Ethnopharmacological relevance Arenobufagin (ArBu) is an important anti-tumor ingredient of Chan'su which has long been used as traditional Chinese medicine in clinic for tumor therapy in China. Aim of the study The purpose of our study is to investigate the lipid homeostasis regulation effects of ArBu on zebrafish model of liver cancer and hepatoma cells, and to provide a reference for further clarifying its active mechanisms. Materials and methods The zebrafish xenograft model was established by injecting HepG2 cells stained with CM-Dil red fluorescent dye . Both the xenograft model and HepG2 cells were used to evaluate the anti-hepatoma activity of ArBu. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was the main method to study lipidomics, proteomics and the semiquantification of endogenous metabolites. Bioinformatics was used as an assistant tool to further explore the antitumor mechanism of ArBu. Results The lipidomics analysis revealed that ArBu caused differential lipids changes in a dose-dependent manner, including PCs, PEs, TGs, SMs, DGs, Cer and PA . PCs, PEs, SMs and TGs were markedly altered in both two models. The influence of glycerophospholipid metabolism was the major and commonly affected pathway. Notably, DGs and Cer were significantly changed only in HepG2 cells. Furthermore, the proteomics research in HepG2 cells fished the target proteins related to lipid homeostasis abnormalities and tumor suppression. ArBu reduced the expression of 65 differential proteins associated with the lipid metabolism, apoptosis and autophagy, such as LCLAT1, STAT3, TSPO and RPS27. Meanwhile, 7 amino acids of 29 determined metabolites were significantly changed, including tyrosine, glutamate , glutamine, leucine , threonine , arginine and isoleucine . Conclusion ArBu has a significant anti-hepatoma effect in vitro and a therapeutic effect on zebrafish xenograft model. It regulated the lipid homeostasis. Activated SM synthase and arginine deiminase , inhibited sphingomyelinase , amino acid supply and JAK-STAT3 signaling pathway, and the affected glycerophospholipid metabolism might explain these results.
研究领域:
药理学
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肿瘤学
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生物化学
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分子生物学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
BMC CANCER
·
2019
·Vol. 19
·期 1
·1-9
·
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
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
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
EUROPEAN JOURNAL OF HISTOCHEMISTRY
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2020
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IF 2.172
Li Wu,Dan Han,Jie Jiang,Xiaojie Xie,Xunran Zhao,Tengfei Ke,Wen Zhao,Liu Liu,Wei Zhao
After the facial nerve axotomy (FNA), the distal end of the axon would gradually decay and disappear. Accumulated evidence shows that transplantation of bone marrow mesenchymal stem cells (BMSCs) reveals potential in the treatment of nervous system diseases or injuries. This study is aimed at investigating the therapeutic effects of co-transplantation of BMSCs and monocytes in FNA. We found that co-culture significantly elevated the CD4+/CD8+ ratio and CD4+ CD25+ T cell proportion compared with monocytes transplantation, and enhanced the differentiation of BMSCs into neurons. After the cell transplantation, the lowest apoptosis in the facial nerve nucleus was found in the co-transplantation group 2 (BMSCs:monocytes= 1:30). Moreover, the lowest expression levels of pro-inflammatory cytokines and the highest expression levels of anti-inflammatory cytokines were observed in the co-transplantation group 2 (BMSCs: monocytes= 1:30). The highest expression levels of protein in the JAK/STAT6 pathway and the SDF-1/CXCR4 axis were found in the co-transplantation group 2. BMSC/monocyte co-transplantation significantly improves the microenvironment in the facial nerve nucleus in FNA rats; therefore these findings suggest that it could promote the anti-/pro-inflammatory balance shift towards the anti-inflammatory microenvironment, alleviating survival conditions for BMSCs, regulating BMSC the chemotaxis homing, differentiation, and the section of BMSCs, and finally reducing the neuronal apoptosis. These findings might provide essential evidence for the in-hospital treatment of FNA with co-transplantation of BMSCs and monocytes.
研究领域:
神经科学
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干细胞生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2023
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
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.
✓ 已验证
DOI
高影响因子
CANCER RESEARCH
·
2025
·
IF 16.6
Zhang Jie,Chen Weiwu,Zhang Chen,He Qian,Wang Xudong,Han Jiayu,Gao Peng,Wang Kunyu,Xie Haoze,Gao Feng,Guo Yining,Guo Wenhao,Jiang Haofei,Le Jing,Zang Ruichen,Mo Sisi,Fan Haobo,Zhu Xiaoxiao,Jiang Xinrong,Gao Fengbin,Yu Yanlan,Ding Guoqing,Chen Yicheng
PD-1 restrains effective killing of cancer cells by the immune system and is predominantly located on the surface of T cells or other immune cells. However, cancer cells also express PD-1 to varying degrees, which is commonly associated with a poor prognosis. Here, we investigated the regulation and function of PD-1 expression in prostate cancer (PCa) and revealed the impact on the tumor microenvironment. PD-1 expression in cancer cells positively correlated with Gleason grade and metastasis but negatively correlated with CD8+ T cell infiltration in PCa patients. PCa cells secreted PD-1 in exosomes that enhanced the activity of myeloid-derived suppressor cells (MDSCs) by activating JAK/STAT3 signaling. The activated MDSCs in turn reduced the infiltration of CD8+ T cells within the tumor, promoting tumor immune evasion. The ubiquitin-specific protease USP7 induced deubiquitination and elevated the abundance of PD-1 in PCa, and USP7 inhibition sensitized PCa tumors to anti-PD-1 antibody treatment. Given the modest efficacy of current immunotherapeutic approaches for PCa, strategies to inhibit the secretion of PD-1-bearing exosomes or USP7 function may emerge as promising immunostimulatory interventions for treating PCa.
研究领域:
癌症生物学
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免疫学
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分子生物学
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细胞信号传导
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泌尿学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6065
·
IF 1.7
Yong Jiang,Wenjun Ji,Ying Lu,Qin Wang,Linwei Chen
The high mortality rate of chronic heart failure (CHF) makes it a primary battlefield in the field of cardiovascular diseases. Qiangxin Lishui Prescription (QLP) is a traditional Chinese medicine (TCM) prescription used clinically for treating CHF, but its underlying mechanism remains unclear. This study integrated plasma metabolomics, network pharmacology, and experimental validation to reveal the pharmacological effects of QLP and its potential mechanism of anti-CHF. Using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS/MS), 119 absorbed prototype compounds of QLP were identified from rat plasma. By applying network pharmacology and molecular docking techniques, a QLP absorption components–target–CHF network was constructed. The IL6/JAK/STAT3 signaling pathway is likely critical to QLP's therapeutic effect on CHF. A CHF mouse model was established using aortic ligation surgery to investigate the regulation of the IL6/JAK/STAT3 pathway by QLP in CHF mice. Network pharmacology analysis and in vivo experimental data indicate that QLP alleviates myocardial injury and inflammatory response in CHF mice by modulating the IL6/JAK/STAT3 pathway, significantly improving cardiac function. This presents a promising therapeutic strategy for CHF treatment.
研究领域:
中医药学
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心血管疾病
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药理学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
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
·
传统中药
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肽组学
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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 Immunology
·
2024
·
IF 5.7
Long Zhou,Yingxin Yang,Tingjie Li,Yafang Zhao,Jinye Yuan,Chenxin He,Yan Huang,Jinyu Ma,Yue Zhang,Fang Lu,Jiaze Wu,Zijian Li,Hui Kong,Yan Zhao,Huihua Qu
Background: Allergic rhinitis (AR) affects up to 40% of the population, leading to significant healthcare expenditures. Current mainstream treatments, while effective, can lead to side effects and do not address the underlying immunological imbalances. Zingiberis Rhizoma Carbonisatum (ZRC), the partially charred product of Zingiberis Rhizoma (ZR), has been widely used clinically in China since ancient times to treat respiratory disorders.Methods: Inspired by the similarity between high-temperature pyrolysis and carbonization processing of herbal medicine, ZRC derived CDs (ZRC-CDs) were extracted and purified through several procedures. Then, the physicochemical characteristics of CDs were delineated through a suite of characterization methods. Moreover, our investigation zeroed in on elucidating the ameliorative impacts of CDs on ovalbumin-induced rat models alongside their underlying mechanisms.Results: ZRC-CDs with particle sizes ranging from 1.0 to 3.5 nm and rich surface functional groups. Additionally, we observed that ZRC-CDs significantly attenuated nasal symptoms and pathological damage in ovalbumin-induced AR rats, and modulated lipid metabolism and type 2 inflammatory responses. They also inhibit PI3K/AKT and JAK/STAT pathways, which are associated with metabolism and inflammation. Importantly, ZRC-CDs demonstrated high biocompatibility, underscoring their potential as a novel therapeutic agent.Conclusion: ZRC-CDs offer a promising alternative for AR treatment and could help facilitate broader clinical use of the ZRC. In addition, the exploration of the inherent bioactivity of CDs can help to broaden their biological applications.
研究领域:
药理学
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免疫学
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纳米技术
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中医药
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）