INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2016
·Vol. 39
·期 2
·307-316
·
IF 2.348
Yongsheng Yang,Qiumei Dong,Rongheng Li
The induction of apoptosis-resistant rheumatoid synovial tissue cells has been related to constitutively active Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling in rheumatoid arthritis (RA). The excessive proliferation and inherent resistance to apoptosis of fibroblast-like synoviocytes (FLS) is an important mechanism by which RA originates. However, the effects of matrine on FLS in RA is unclear. The present study aimed to investigate the mechanism of action of matrine in a rat model of collagen‑induced arthritis (CIA). The CIA model was established using bovine type II collagen. FLS were isolated from control and CIA rats, cultured in vitro, and confirmed to harbor fibroblast‑like characteristics. After treatment of FLS with varying concentrations of matrine, the JAK2 inhibitor AG490, or a combination of both drugs, cell proliferation, apoptosis rate, expression of apoptotic markers and the activation of the JAK/STAT pathway were assessed. Additionally, CIA rats were administered either matrine or methotrexate by oral gavage to examine the effects of therapeutic intervention on arthritis pathogenesis. The arthritis index (AI) was measured and ankle joint structure was analyzed histologically to determine the severity of CIA. Furthermore, expression levels of apoptotic markers and members of the JAK/STAT family were also examined in vivo. Compared with the CIA group, matrine reduced AI and improved ankle pathology. Matrine also inhibited FLS proliferation, induced G0/G1 cell cycle arrest, and increased the rate of apoptosis in vitro. The effects of matrine on apoptosis induction were further confirmed by observations that Bcl-2 levels were decreased, whereas Bax and caspase-3 levels were increased in the matrine-treated synovial tissues and FLS. Finally, matrine treatment also diminished the phosphorylation, and hence activation of JAK2, STAT1 and STAT3. Our results suggest that matrine induces the apoptosis of FLS from rats with CIA by inhibiting activation of the JAK/STAT signaling pathway.
研究领域:
药理学
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免疫学
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风湿病学
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细胞生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 17
·8678
·
IF 4.9
Yamin Zhang,Jiajia Lin,Xiaomei Xu,Xuehua Lu,Lisha Li,Yuezhen Yang,Wenjin Lin
This study aimed to compare the therapeutic effects of fresh (CMF) and dried (CMD) Centipeda minima against allergic rhinitis (AR), elucidate their underlying molecular mechanisms, and identify the bioactive compounds responsible for their immunomodulatory actions. An ovalbumin-induced AR mouse model was treated with CMF or CMD extracts, followed by evaluation of nasal symptoms, serum biomarkers (IgE, histamine, cytokines), and nasal mucosa histopathology. Transcriptomics and widely targeted metabolomics were integrated with network pharmacology to identify differentially expressed genes and bioactive components, which were further validated in RAW264.7 and RBL-2H3 cells. CMF and CMD exhibited distinct anti-AR mechanisms: CMF predominantly suppressed Th2 responses (reducing IgE, IL-6, and histamine while elevating IL-10), whereas CMD enhanced Th1 activity (increasing IFN-γ). Metabolomic analysis revealed CMF was rich in amino acids while CMD contained higher flavonoids, with neocnidilide and 6-gingerol identified as key bioactive compounds that modulated TNF-α, IL-6, and IL-10 via NF-κB and JAK-STAT pathways. These findings demonstrate that CMF and CMD exert complementary anti-inflammatory effects through Th2 inhibition and Th1 activation, respectively, providing a molecular basis for the traditional use of Centipeda minima and highlighting its bioactive compounds as potential therapeutics for inflammatory diseases.
研究领域:
药理学
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免疫学
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民族药理学
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分子生物学
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植物学
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生物医学
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DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2025
·
IF 4.4
Niu Lingdi,Li Hai,Guo Junjie,Jia Zheng,Chang Qingru,Liu Ning,Zhang Shuhe,Ge Junwei
The gut microbiota plays a complex role in immune system maturation and function. The induction of memory in innate immune cells appears to be part of a co-adaptation between the host and microbiome. As important gut commensals, certain Lactobacillus have been shown to induce innate immune memory. However, the universality, phenotypic characteristics, mechanisms of Lactobacillus -induced innate immune memory, and its potential applications in vaccine immunology remain poorly understood. Here, we discovered that specific strains of the gut commensal Lactobacillus can induce innate immune memory, resulting in a more balanced trained immunity phenotype through SOCS activation. Upon secondary stimulation, macrophages exhibited increased expression of IL-6 , IL-1β , IL-10 , IL-12 , IFN-β , and TGF-β . Peptidoglycan and components in the secretome sensitive to pancreatic enzymes were identified as key elements in inducing trained immunity. Furthermore, mice that underwent training demonstrated rapid resistance to S. aureus infection. Additionally, Lactobacillus -induced trained immunity significantly enhanced the protective efficacy of vaccines against MRSA. Our findings demonstrate that certain Lactobacillus strains can activate non-classical trained immunity, offering potential for enhancing vaccine efficacy. Our study provides new insights into the role of some gut commensals in immune modulation and suggests a novel approach to vaccine enhancement through trained immunity induced by specific gut commensals.
研究领域:
免疫学
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微生物组研究
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疫苗学
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固有免疫
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分子生物学
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宿主-微生物相互作用
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DOI
PubMed
高影响因子
Food Science & Nutrition
·
2025
·Vol. 13
·期 11
·e71234
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IF 3.8
Liang Xue,Chun Cao
Inflammatory bowel disease (IBD) is a complex chronic intestinal inflammatory disease involving immune, genetic and environmental interactions. A disrupted balance in the polarization of intestinal macrophages is a key pathogenic link. This study explored whether octanoic acid (OA)‐rich enteral nutrition (EN) regulated intestinal M1/M2 macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway to alleviate IBD. First, to assess the effects of OA‐rich EN on IBD, four groups were established: the sham, IBD, IBD + EN, and IBD + OA‐rich EN. Second, to verify the regulatory role of intestinal M1/M2 macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway, six groups were established: the sham, IBD, IBD + OA‐rich EN, IBD + OA‐rich EN with intraperitoneal injections of IFNγ, AS1517499, or SR202. RAW264.7 cells were also used to observe how OA influences LPS/IFNγ‐induced M1 polarization. OA‐rich EN notably alleviated IBD symptoms, activated the PPARγ/STAT‐1/STAT‐6 pathway and remodeled the M1/M2 polarization balance of intestinal macrophages. These effects were greater than those in the IBD + EN group. Blocking the activation of PPARγ, activating STAT‐1 or inhibiting STAT‐6 reversed the protective effect of OA‐rich EN on remodeling the M1/M2 polarization balance of intestinal macrophages and IBD symptoms. In vitro experiments further confirmed that OA regulated macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway. This is the first confirmation that OA‐rich EN alleviates IBD by activating PPARγ/STAT‐1/STAT‐6 to regulate macrophage polarization, highlighting its potential as a nutritional therapy for IBD. Octanoic acid‐rich enteral nutrition could regulate the M1/M2 polarization of intestinal macrophages and simultaneously repair the intestinal mucosal barrier by activating the PPARγ/STAT‐1/STAT‐6 pathway, thereby significantly alleviating inflammatory bowel disease‐induced intestinal injury.
研究领域:
免疫学
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胃肠病学
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营养科学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2016
·
IF 2.74
Wenzhe Ji,Dingqiang Lu,Shaoning Yang,Tongqi Liu,Xinxian Wang,Xiuquan Ling
This study aimed to explore the solubility and solution thermodynamics of cetilistat. Data on solid–liquid equilibrium of cetilistat are essential for a preliminary study of industrial applications. The solubility of cetilistat in binary solvent mixtures consisting of (water + acetone), (water + isopropyl alcohol), and (water + acetonitrile) was measured in the temperature range of 278.15 K–323.15 K. The modified Apelblat equation, general cosolvency model and Jouyban-Acree model were used to correlate with the solubility of cetilistat. The modified Apelblat equation provided a more accurate mathematical representation of the experimental data by comparing the models. The thermodynamic properties of the solution process, including the Gibbs free energy , enthalpy, and entropy, were calculated by the van't Hoff analysis.
研究领域:
药学
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物理化学
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产品关联
DOI
高影响因子
Journal of Cardiovascular Translational Research
·
2025
·
IF 2.5
Zhou Qiaofeng,Jiang Na,Li Shihuan,Li Suqin,Liu Jie,Yu Liangzhu,Liu Guoli,Xia Hongli,Li Mincai
Myocardial fibrosis (MF) severely impairs the heart structure and function post-myocardial infarction. The study investigated the effectiveness and mechanism of diammonium glycyrrhizinate (DG) on ISO-induced MF. ISO-stimulated mouse cardiac fibroblasts (CFs) were treated with DG to assess the proliferation, inflammation, and fibrosis markers (α-SMA, collagen, TGF-β1, Smad3). The MF model was induced in mice by administering ISO, followed by a 4-week treatment with DG (60 mg/kg/day). Cardiac function was measured using echocardiography, and histology and molecular analyses were performed. DG significantly suppressed the CF proliferation and reduced the expression of fibrotic markers. In ISO-treated mice, DG improved the cardiac function and attenuated the upregulated fibrosis markers. Molecular analysis revealed DG suppressed the TGF-β1/Smad3 pathway activation. The antifibrotic effect was enhanced when combined with STAT3 inhibition. DG effectively alleviates ISO-induced myocardial fibrosis dysfunction by inhibiting the STAT3/Smad3 signaling pathway, demonstrating its potential as a treatment for cardiac fibrosis. Graphical abstract
研究领域:
心脏病学
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药理学
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分子生物学
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细胞生物学
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病理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 4
·2018
·
IF 6.208
Yan Zhang,Pei Ma,Zhiguang Duan,Yannan Liu,Yu Mi,Daidi Fan
Lung adenocarcinoma (LAC) is a common lung cancer with a high malignancy that urgently needs to be treated with effective drugs. Ginsenoside Rh4 exhibits outstanding antitumor activities. However, few studies reported its effects on growth, metastasis and molecular mechanisms in LAC. Here, Rh4 is certified to show a strong anti-LAC efficiency in vitro and in vivo. Results of flow cytometry and Western blot are obtained to exhibited that Rh4 markedly restrained cellular proliferation and colony formation by arresting the cell cycle in the G1 phase. Results from a wound healing assay and transwell assays demonstrated that Rh4 is active in the antimigration and anti-invasion of LAC. The analysis of Western blot, immunofluorescence and RT-qPCR confirmed that Rh4 reverses the epithelial–mesenchymal transition (EMT) through upregulating the gene expression of E-cadherin and downregulating that of snail, N-cadherin and vimentin. In vivo results from immunohistochemistry show consistent trends with cellular studies. Furthermore, Rh4 suppresses the Janus kinases2/signal transducer and activator of the transcription3 (JAK2/STAT3) signaling pathway stimulated by TGF-β1. Silencing the STAT3 signal or co-treating with AG490 both enhanced the EMT attenuation caused by Rh4, which revealed that Rh4 suppressed EMT via inhibiting the JAK2/STAT3 signaling pathway. These findings explore the capacity and mechanism of Rh4 on the antimetastasis of LAC, providing evidence for Rh4 to LAC therapy.Keywords:ginsenoside Rh4;lung adenocarcinoma;metastasis;cell cycle;JAK/STAT signaling
研究领域:
肿瘤学
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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
Antioxidants
·
2022
·Vol. 11
·期 2
·426
·
IF 7.675
Tian Wei,Lei Wu,Xiaowen Ji,Yan Gao,Guiran Xiao
Ursolic acid (UA) is a bioactive molecule widely distributed in various fruits and vegetables, which was reported to play a therapeutic role in ulcerative colitis (UC) induced by toxic chemicals. However, the underlying mechanism has not been well clarified in vivo. Here, using aDrosophilaUC model induced by sodium dodecyl sulfate (SDS), we investigated the defensive effect of UA on intestinal damage. The results showed that UA could significantly protectDrosophilafrom the damage caused by SDS exposure. Further, UA alleviated the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) induced by SDS and upregulated the activities of total superoxide dismutase (T-SOD) and catalase (CAT). Moreover, the proliferation and differentiation of intestine stem cells (ISCs) as well as the excessive activation of the c-Jun N-terminal kinase (JNK)-dependent JAK/STAT signaling pathway induced by SDS were restored by UA. In conclusion, UA prevents intestine injury from toxic compounds by reducing the JNK/JAK/STAT signaling pathway. UA may provide a theoretical basis for functional food or natural medicine development.Keywords:ursolic acid;ulcerative colitis;JNK;JAK/STAT;Drosophila
研究领域:
药理学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Fangfei Zhou,Qingge Lu,Lingyu Kong,Sitong Wang,Haixia Zhang,Meng Zhao,Yue Hu,Fanwu Wu,Chenxi Wu
Background: Cancer is a global public health crisis and the leading cause of death among middle-aged and older individuals, with its incidence increasingly shifting toward younger populations. Approximately 90% of the patients succumb to advanced metastasis, and effective treatments remain elusive. The specific molecular mechanisms underlying cancer cell invasion and migration remain poorly understood, hindering the development of effective targeted therapies. Therefore, inhibiting or reversing cancer cell invasion and migration may be crucial for reducing mortality. Our previous research revealed that the five drugs (FD), derived from Xuefu Zhuyu Decoction (XFZYD), play a significant role in inhibiting cell migration.Hypothesis/purpose: This study aims to explore the main drug components of FD and investigate the underlying mechanism in inhibiting cell migration.Methods: We used the Drosophila ptc>scrib-IR cell migration model to investigate the effects of FD. FD was disassembled and analyzed using an orthogonal design. Drug extracts were prepared and administered to Drosophila larvae. We assessed the effects of FD on cell migration, reactive oxygen species (ROS) levels, and gene expression.Results: In FD disassembled recipes and orthogonal test design, a significant difference was observed in the intervention with or without Glycyrrhiza uralensis Fisch. (GUF) in migrating cell number (P < 0.01), which emerged as a more potent inhibitor of FD from XFZYD in cell migration. High-performance liquid chromatography revealed that GUF and its extract contained effective medicinal components, namely glycyrrhizic acid, liquiritin, liquiritigenin, and glycyrrhetinic acid. Moreover, GUF at 4.0 mg/mL displayed strong inhibitory effect in migrating cell number and distance when compared with model, XFZYD or FD. Excessive ROS can activate the JAK/STAT signaling pathway and promote the EMT process. GUF inhibited ptc>scrib-IR-induced cell migration by reducing ROS levels, JAK/STAT signalling, and the transcription of upd2, upd3, hop and socs36E. Finally, GUF rescued the altered expressions of the epithelial-mesenchymal transition (EMT)-related proteins, including matrix metalloproteinase 1 (MMP1), β-integrin and E-cadherin, triggered by cell migration.Conclusion: Our findings demonstrate that GUF may serve as a promising candidate for targeting advanced metastatic tumors by suppressing ROS-mediated JAK/STAT signaling and EMT.
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高影响因子
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
INFLAMMATION RESEARCH
·
2014
·Vol. 63
·期 7
·597-608
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IF 2.143
Pan Xiaolong,Cao Xiang,Li Na,Xu Yimiao,Wu Qiuyue,Bai Jing,Yin Zhimin,Luo Lan,Lan Lei
Objective Forsythin (FOR) is an active ingredient extracted from the fruit of the medicinal plant Forsythia suspensa (Thunb.) Vahl. Here, we investigated the effect of FOR on LPS-induced inflammatory response and the underlying molecular mechanisms in RAW264.7 macrophages. Materials and methods RAW264.7 cells were pre-treated with or without FOR and then stimulated with or without LPS. The productions of TNF-α, IL-1β, IL-6, PGE 2 and NO were determined by ELISA and nitrite analysis, respectively. The expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blotting and RT-PCR analysis. The activations of signaling molecules were detected by Western blotting using phosphorylation specific antibodies. Reactive oxygen species (ROS) production was determined by ROS assay. Results LPS-induced productions of IL-1β, IL-6, TNF-α, NO and PGE 2 were inhibited by FOR in a dose-dependent manner. FOR also suppressed the LPS-elevated expressions of iNOS and COX-2. Further investigations revealed that FOR significantly inhibited the LPS-induced activations of JAK-STATs and p38 MAPKs, but not of IKKα/β in LPS-stimulated RAW264.7 cells. Additionally, FOR interfered with both JAK-STATs and p38 MAPKs signaling pathways to modulate the expressions of IL-1β, IL-6, TNF-α, iNOS and COX-2. Furthermore, FOR reduced the LPS-induced ROS accumulation, validating that FOR serves as an antioxidant. Conclusions Our data suggested that FOR exerts anti-inflammatory action, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signalings and production of ROS in macrophage 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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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Jia-Wei Wu,Wei Gao,Li-Ping Shen,Yong-Lin Chen,Shi-Qing Du,Zhi-Yong Du,Xu-Dong Zhao,Xiao-Jie Lu
ABSTRACT Ethnopharmacological relevance Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. Aims of the study This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. Materials and methods The study employed network pharmacology, UPLC-Q-TOF-MS technique,molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. Results Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. Conclusion Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.
研究领域:
药理学
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神经科学
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传统中药
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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）