Frontiers in Pharmacology
·
2025
·
IF 4.8
Qian Feng,Cai-Zhi Li,Yi-Hua Zou,Xue-Yu Wang,Xia Yang,Rong Zhang*,Zhong-Qiu Liu*,Rong-Rong Zhang
Introduction: Brain metastasis (BM) is the most common and serious complication of breast cancer (BC). There is significant interest in investigating the crosstalk between BC cells and immune cells. β-elemene is the main pharmacodynamic component of Curcumae Rhizoma, a traditional Chinese medicine that is commonly used for the clinical treatment and prevention of various tumors. However, the specific underlying mechanism of β-elemene in BC-BM is still unclear.Methods: An intracardiac (ICT) injection model was used to establish specific BC-BM cells, then an intracarotid (ICD) injection model was used to verify the inhibitory effect of β-elemene in BC-BM. Tumor-cell-conditioned media, a primary microglia co-culture model, and an in vitro recruitment experiment were used to explore crosstalk between BC cells and immune cells. TMT-based quantitative proteomic, ELISA, IF, and other molecular biotechnologies were used to investigate the mechanisms.Results: The BC-BM cells established in our study not only increased BM rates but also exhibit mesenchymal phenotype and activated the JAK–STAT signaling pathway. Microglia, particularly M2 microglia, were enriched in BM lesions and secreted high levels of both IL6 and CCL2. Hypersecretory IL6 reversed the MET process of BC cells by regulating the JAK2/STAT3 signaling pathway to promote colonization in the brain. Increased levels of CCL2 significantly recruited monocytic myeloid-derived suppressor cells (M-MDSCs) to induce an immunosuppressive brain microenvironment. β-elemene could significantly inhibit BC-BM in mice by regulating the IL6/STAT3 signaling pathway and suppressing the M-MDSC recruitment.Conclusion: Our work first demonstrated that β-elemene regulated the IL6/STAT3 axis and M-MDSC recruitment to reconstruct immunosuppressive brain microenvironment to suppress BC-BM.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Yi Wu,Yilin Ling,Yuqi Yang,Haoxing Long,Linghao Kong,Peiyang Song,Yujie Lu,Wanqiu Zhao,Wei Wang,Jingrong Zhu,Nan Wang
Obesity is a growing global health concern associated with severe metabolic disorders, necessitating the development of safer and more effective therapeutic strategies. Soybean sprout peptides (SSPs), derived from germinated soybeans, are bioactive compounds with potential antiobesity effects. This study aimed to investigate the molecular mechanisms of SSPs through an integrated approach combining network pharmacology, molecular docking, and in vivo experiments. SSP sequences were identified using UPLC-Orbitrap-MS/MS, and their bioactivity was predicted using PeptideRanker. Network pharmacology identified key SSP targets, including AKT1, SRC, STAT3, ESR1, FOS, and NFKB1, which are implicated in the PI3K-Akt and JAK-STAT pathways. Molecular docking validated strong interactions between SSPs and these targets. In vivo, SSP administration significantly reduced body weight gain, abdominal fat accumulation, and serum lipid abnormalities in high-fat-diet-induced obese mice while modulating gut microbiota composition by restoring the Firmicutes-to-Bacteroidetes ratio and reducing pathogenic taxa. Fecal metabolomics revealed that SSP alleviated oxidative stress and improved amino acid metabolism, contributing to its antiobesity effects. These findings suggest that SSP holds promise as a functional food ingredient or nutraceutical for obesity prevention and management.
研究领域:
营养学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
International Journal of Environmental Research and Public Health
·
2016
·Vol. 13
·期 11
·1085
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IF 2.035
Yiyang Jia,Te Liu,Liting Zhou,Jian Zhu,Juan Wu,Di Sun,Jin Xu,Qi Wang,Huaiji Chen,Feng Xu,Yuezhu Zhang,Tianrong Zhang,Hongbo Liu,Lin Ye
The most widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP), is known to affect lipid metabolism and adipogenesis. We studied the effects of dietary DEHP exposure on metabolism in rats as well as the role of the JAK/STAT pathway in this process. Eighty rats were exposed to DEHP (0, 5, 50 and 500 mg/kg/d) through dietary intake for 4 weeks. We then collected blood samples, liver, and adipose tissues to detect modifications in the levels of serum lipids, leptin, adiponectin and insulin. JAK3, STAT5a and PPARγ expression were detected at both the gene and protein levels. The activation of JAK3 and STAT5a was also detected. The DEHP-exposed rats had increased body weight, serum lipid, insulin, and leptin levels. Moreover, the JAK3/STAT5a pathway was activated in the adipose tissue; however, this pathway was not activated in the liver. The mRNA of SREBP-1c in the liver was increased significantly among each of the groups, in contrast to the levels found in the mature SREBP-1c protein form. Furthermore, the expression ofFABP4,AcoxandFASnwas decreased in the liver, but increased in adipose tissue. Thus, we conclude that exposure to DEHP reduces the hydrolysis of lipid and promotes triglyceride accumulation by oppositely regulating the activation state of JAK/STAT pathway in the liver and adipose tissue, resulting in the disorder of body lipid metabolism and obesity.Keywords:di-(2-ethylhexyl) phthalate;JAK/STAT;lipid metabolism;adipose tissue
研究领域:
毒理学
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代谢研究
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分子生物学
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DOI
PubMed
高影响因子
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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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Li Jin,Xinyu Zheng,Chenxi Yu,Ping Li,Guiran Xiao
Metastasis is one of the most important factors related to malignant tumor development and therapeutic failure. Phytic acid (PA), a poly-phosphorylated inositol derivative in plant seeds and grains, has been shown to have antitumoral activity. However, the effect of PA on tumor metastasis and the underlying mechanisms remain uncharacterized. In the current study, we aimed to identify the effect of PA on tumor metastasis by employing a Drosophila model of malignant tumor Raf GOF Scrib −/− . We observed that PA supplementation in food inhibited the invasion and migration of tumors. Further studies indicated that PA drives Yki phosphorylation and inactivation through Lats kinase, which subsequently results in decreased expression of the JAK/STAT pathway ligands unpaired cytokines (Upds). Moreover, the reduced JAK/STAT pathway inhibits the recruitment and proliferation of hemocytes. To summarize, these findings provide valuable pathological and mechanistic insights into the potential application of PA for functional food or natural medicine development.
研究领域:
肿瘤学
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分子生物学
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遗传学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Xianbin Wang,Wenjun Cao,Chuanfen Sun,Yutie Wang,Mingyu Wang,Jiarong Wu
Rheumatoid arthritis (RA) is a chronic and symmetrical autoimmune disease that primarily characterized with articular synovial hyperplasia, joint swelling, cartilage and bone destruction. The in-depth understanding of the role of immune signaling pathway inhibitors provides inspiration for the construction of new and more effective strategy for RA therapy. In this study, by loading methotrexate (MTX) into an acetalated dextran biopolymer, AcDEX, we developed a pH-sensitive, MTX-loaded and molecularly targeted nanodrug [email protected] NPs) to decrease the toxicity of MTX and simultaneously enhance its therapeutic effect. The resultant [email protected] NPs showed the spherical morphology and notable pH-responsiveness with high drug loading of 88.32%. As demonstrated in vitro and in vivo , the reduced cytotoxicity of both RAW264.7 cells and LPS-activated RAW264.7 cells treated with [email protected] NPs was found compared to free MTX. Upon intravenous administration into adjuvant-induced arthritis (AIA) rat model, the nanodrug had potent pharmacokinetic and pharmacodynamic profiles, which can accumulate in RA lesions and release MTX inhibitors for regulating the JAK-STAT pathways. As a result, the [email protected] NPs achieved the cartilage and bone protective and a better anti-inflammatory effect with negligible systemic toxicity, suggesting the strong potential of safe and effective nanodrug for RA therapy as well as other autoimmune diseases.
研究领域:
药学
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纳米技术
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
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2020
·Vol. 12
·期 45
·23013-23027
·
IF 6.895
Ziqian Wang,Chenyue Zhan,Fang Zeng,Shuizhu Wu
Rheumatoid arthritis (RA) is a common chronic autoimmune disease associated with progressive disability, systemic complications, and poor prognosis. The improved understanding of the roles of immune signaling pathway inhibitors has shed light on designing new and more effective approaches for RA treatment. In this work, an inflammation-responsive and molecularly targeted drug system has been developed for RA therapy. The drug carrier was synthesized by covalently grafting hydrophobic cholesterol (Chol) molecules onto a hydrophilic chondroitin sulfate (CS) chain via the inflammation-responsive diselenide bonds (SeSe). The resultant amphiphilic polymer CSSeSeChol readily forms nanoparticles (NPs) and encapsulates two kinase inhibitors tofacitinib and SP600125 in aqueous media. Upon administration into the RA mouse model, the nanodrug accumulates in RA lesions and releases the inhibitors for regulating the JAK-STAT and JNK pathways. As a result, the nanodrug exhibits satisfactory efficacy in RA treatment by suppressing the expression of relevant pro-inflammatory cytokines, blocking the activation of osteoclasts and providing protection for cartilage and joints.
研究领域:
药理学
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纳米技术
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2024
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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
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DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2024
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IF 3.8
Yali Zhang,Xiaoxue Wang,Jianjun Zhang
Rheumatoid arthritis (RA), an autoimmune disease, is related to environmental factors, sex hormones, genetics, and other factors, affecting 0.5–1% of the global population. The JAK-STAT pathway plays an important role in the signal transduction of inflammatory cytokines and chemokines in the pathogenesis of RA. Tofacitinib (TF), the first approved JAK inhibitor for treating RA, can reduce inflammatory reactions, improve RA conditions, prevent irreversible joint injury, and improve the quality of life of patients. However, the traditional oral administration of TF causes poor compliance and severe side effects owing to the long-term and high-frequency treatment. Therefore, highly efficient pharmaceutical formulations for TF are necessitated. Here, a novel TF-loaded poly(lactic-co-glycolic acid) (PLGA) sustained release nanoparticle (NanoTF-PLGA) was prepared using a high-gravity nanoprecipitation technique (HGNPT), and its therapeutic effect on RA was verified in vitro and in vivo. The influence of the different operation parameters of HGNPT on the particle size of PLGA, including the rotating speed of the rotating bed, the volume ratio of solvent to antisolvent, and the concentration of the surfactant, was investigated using an orthogonal design. The optimum reaction conditions for preparing PLGA nanoparticles were selected by optimizing the formula, and TF was then added to the reaction mixture to prepare NanoTF-PLGA. The results demonstrated that NanoTF-PLGA had a smaller size (603.8 nm), a more uniform shape, a higher drug loading efficiency, and long-term sustained release properties (over 14 days). Furthermore, in vitro experiments proved that NanoTF-PLGA could enter RAW264.7 cells by cell uptake, demonstrated good biocompatibility, inhibited the migration of RAW264.7 cells, and simultaneously inhibited the expression of IL-6, IL-1β, and TNF-α in a dose-dependent manner. In vivo experiments showed that subcutaneous administration of NanoTF-PLGA significantly alleviated articular cartilage injury and reduced the level of inflammatory cell infiltration into the joint cavity. This study presents a promising technique for preparing sustained drug formulations that can be extended to numerous therapeutic drugs.
研究领域:
药学
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纳米技术
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风湿病学
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药物递送系统
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Qibin Li,Yameng Wang,Qing Guo,Jie Cao,Yangjun Feng,Xue Ke
Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8 + NKG2D + T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.
研究领域:
药剂学
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皮肤科
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
VETERINARNI MEDICINA
·
2023
·
IF 0.7
Weifeng Zhang,Hualong Deng,Yanfen Liu,Shaohong Chen,You Liu,Yuntao Zhao
Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small ruminants and has been rapidly spreading over various regions in Africa, the Middle East, and Asia. Although vaccination is thought to be an effective management strategy against PPR infections, the heat sensitivity of PPRV vaccines severely restricts their use in regions with hot climates. In this research, we studied the antiviral activities of ribavirin and aimed to understand the potential mechanisms of action of ribavirin in the African green monkey kidney cells (Vero cells). In brief, the adsorption, intrusion, replication, and release of PPRV, as well as the mRNA expression level of RNA-dependent RNA polymerase ( RdRp ), were significantly inhibited in the ribavirin-treated Vero cells compared to those in the PPRV-infected cells that were not treated with ribavirin. Additionally, ribavirin has potential as an antiviral drug against PPRV, and its antiviral activity is mediated by the Janus kinase signal transducer and activator of transcription (JAK/STAT) and PI3K/AKT pathways.
研究领域:
兽医学
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病毒学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2021
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IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
研究领域:
免疫学
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药理学
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分子生物学
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生物化学
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DOI
高影响因子
危险品化学品经营许可证（带存储）