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
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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PubMed
高影响因子
BMC CANCER
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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
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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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PubMed
高影响因子
Frontiers in Pharmacology
·
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
Journal of Advanced Research
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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
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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
·
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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DOI
PubMed
高影响因子
Frontiers in Immunology
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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
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DOI
高影响因子
FITOTERAPIA
·
2025
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IF 2.6
Wenjing Ren,Yue Zhou,Jiahui Zhao,Xiutong Ge,Shiru Jiang,Yang Chen,Gui Xu,Shuo Zhang,Li Li,Ji Shi,Fan Zhang
Songaria Cynomorium Herb (SCH), a traditional Chinese medicinal herb, is recognized for its dual role as both a dietary supplement and a therapeutic agent. It is traditionally reputed to have kidney-tonifying and Yang-strengthening effects, which have made it a common ingredient in nutritious food supplements and health products. This study investigates the underlying mechanisms by which wine-steamed SCH, enhances kidney aphrodisiac qualities, focusing on the tyrosine kinase/signal transduction and transcriptional activation factor (JAK/STAT) signaling pathway. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to qualitatively analyze the chemical constituents of SCH both before and after the wine-steaming process, and the significant differential components were screened out. A kidney-Yang deficiency model was induced by intragastric administration of hydrocortisone. Subsequently, the rats were treated with either raw SCH (RSCH) or wine-steamed SCH (WSCH) medicinal solutions. Urine output, organ indices, target gland axis-related indices, and renal tissue lesions were recorded and statistically compared between the treatment and control groups. RT-qPCR and Western blot analysis were utilized to assess the mRNA and protein expression levels of the JAK/STAT pathway and HIF-1α in the renal tissues of the animals. The results indicated that the chemical composition of the SCH underwent changes before and after the steaming process. The tonifying effects observed were more pronounced with WSCH than with RSCH, suggesting that the mechanism involves the inhibition of the JAK/STAT pathway and the downregulation of HIF-1α expression.
研究领域:
中药学
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分子生物学
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药理学
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
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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DOI
PubMed
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2024
·
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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高影响因子
危险品化学品经营许可证（带存储）