ANNALS OF MEDICINE
·
2025
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IF 4.3
Yun Yang,Lengqiu Guo,Jinghua Yu,Wei Peng,Qi Wang,Lan Wei,Xihua Chen,Chunyan Min,Xiaogang Jiang,Song Zhu,Haixin Zhao,Zhenyu Xuan,Jianzhong Yu,Jian Zhang
Background Da-Yuan-Yin Decoction (DYY), used since the early Qing Dynasty in China for damp-heat syndrome, was evaluated for its comprehensive protective effects.Materials and methods Rats received a high-fat/high-sugar diet for 14 days, then daily exposure to high temperature/humidity (31.0 ± 0.5°C, 85%-95%) for 10 hours over 14 days. Damp-heat syndrome was induced on day 29 via intraperitoneal lipopolysaccharide (LPS) injections (1 mg/kg and 0.5 mg/kg after 4 hours). Two hours post-modeling, rats received DYY (400 or 800 mg/kg/day) orally for 5 days. Symptoms were scored. On day 33, kidney, spleen, tongue, lung, liver, stomach, and colon tissues underwent histopathological and immunochemical/immunofluorescence analysis. Serum levels of inflammation factors, C-reactive protein (CRP), cell-free DNA (cfDNA), myeloperoxidase (MPO), and superoxide dismutase (SOD) were quantified. Complete blood count (CBC), blood biochemistry, short-chain fatty acids (SCFAs), gut microbiota composition in the colon, and metabolites in the cecum were analyzed.Results DYY significantly reduced symptom scores and decreased CRP level, while also regulating parameters in CBC and biochemical profiles. The treatment ameliorated tissue damage in the kidney, spleen, tongue, lung, liver, stomach, and colon. DYY downregulated citrullinated histone H3 (Cit H3), polyclonal peptidylarginine deiminase 4 (PADI4), and MPO expressions in the lung, stomach, and colon. Furthermore, it modulated inflammatory responses, suppressed the interleukin-23 (IL-23)/janus kinase-2 (JAK2)/signal transduction and transcription activator-3 (STAT3) signaling pathway and enhanced antioxidant activity. DYY administration significantly increased total SCFA content. The intervention restored gut microbiota diversity and abundance, while ameliorating metabolic dysregulation.Conclusion Systemic pathophysiological alterations were observed in rats with damp-heat syndrome. The comprehensive protective effects of DYY involved suppression of neutrophil extracellular traps (NETs) formation through downregulation of PADI4 expression, modulation of inflammatory responses, inhibition of the IL-23/JAK2/STAT3 signaling pathway, restoration of intestinal microecological balance and metabolic homeostasis, and enhancement of antioxidant.
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PubMed
高影响因子
Cell Host & Microbe
·
2024
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IF 20.6
Zhen He,Jing Yu,Junli Gong,Jinjie Wu,Xuan Zong,Zhanhao Luo,Xiaowen He,Wai Ming Cheng,Yugeng Liu,Chen Liu,Qiang Zhang,Lei Dai,Tao Ding,Beile Gao,Raad Z. Gharaibeh,Jinlin Huang,Christian Jobin,Ping Lan
Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni -derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni -infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB ( ΔcdtB ) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni’s pro-metastatic property. In C.-jejuni -colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.
研究领域:
肿瘤学
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微生物学
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分子生物学
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PubMed
高影响因子
Molecular Medicine Reports
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2024
·Vol. 30
·期 2
·1-15
·
IF 3.4
Jingxia Du,Yibo Dong,Jingjing Song,Hanqi Shui,Chengyao Xiao,Yue Hu,Shiyao Zhou,Shanshan Wang
Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophage‑mediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSC‑Exo) harboring miR‑25‑3p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An in vivo MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSC‑Exo carrying miR‑25‑3p (BMSC‑Exo‑25‑3p) were administered through tail vein injection. A hypoxia‑reoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSC‑Exo‑25‑3p in vitro. The results of the present study demonstrated that BMSC‑Exo or BMSC‑Exo‑25‑3p could be taken up by cardiomyocytes in vivo and H9C2 cells in vitro. BMSC‑Exo‑25‑3p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1‑like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RT‑qPCR, such as interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6). As hypothesized, BMSC‑Exo‑25‑3p inhibited M1‑like macrophage polarization and proinflammatory cytokine expression while promoting M2‑like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R in vivo and in LPS‑stimulated macrophages in vitro, and BMSC‑Exo‑25‑3p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSC‑Exo‑25‑3p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1‑like macrophage polarization.
研究领域:
心脏病学
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分子生物学
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干细胞研究
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炎症
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外泌体治疗
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高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2024
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IF 3.3
Miao Yang,Kanmin Mao,Xin Cao,Hongjuan Liu,Weifeng Mao,Liping Hao
Benzo[ a ]pyrene (BaP) is a ubiquitous environmental pollutant posing various toxicity effects on organisms. Previous studies demonstrated that BaP could induce hepatotoxicity, while the underlying mechanism remains incompletely elucidated. In this study, a comprehensive strategy including network toxicology, transcriptomics and gut microbiomics was applied to investigate the hepatotoxicity and the associated mechanism of BaP exposure in mice. The results showed that BaP induced liver damage, liver oxidative stress and hepatic lipid metabolism disorder. Mechanistically, BaP may disrupt hepatic lipid metabolism through increasing the uptake of free fatty acid (FFA), promoting the synthesis of FA and triglyceride (TG) in the liver and suppressing lipid synthesis in white adipose tissue. Moreover, integrated network toxicology and hepatic transcriptomics revealed that BaP induced hepatotoxicity by acting on several core targets, such as signal transducer and activator of transcription 1 (STAT1), C-X-C motif chemokine ligand 10 (CXCL10) and toll-like receptor 2 (TLR2). Further analysis suggested that BaP inhibited JAK2-STAT3 signaling pathway, as supported by molecular docking and western blot. The 16S rRNA sequencing showed that BaP changed the composition of gut microbiota which may link to the hepatotoxicity based on the correlation analysis. Taken together, this study demonstrated that BaP caused liver injury, hepatic lipid metabolism disorder and gut microbiota dysbiosis, providing novel insights into the hepatotoxic mechanism induced by BaP exposure.
研究领域:
毒理学
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分子生物学
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基因组学
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微生物组学
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高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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2025
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IF 1.3
Jing Gao,Xiaohui Dong,Hang Li,Qing Yang,Wenting Ji,Xianying Lu,Xinyu Chen,Fei Wang,Chaoming Hou
Objective Fujin Shengji (FJSJ) Powder has a positive effect on healing Diabetic Ulcers (DU), but the specific compounds at work have not been identified. Methods Network pharmacology was employed to investigate the primary constituents, potential therapeutic targets, and pharmacological mechanisms of FJSJ Powder treating DU. In vitro experiments were further performed to validate these findings: an LPS-induced RAW264.7 cell model was established to assess the anti-inflammatory effects of FJSJ Powder active constituents treating DU, while a high glucose-induced HUVEC model was cultured to verify the pro angiogenic effect of FJSJ Powder active constituents treating DU. Additionally, the mechanisms by which the optimal active monomers suppress inflammation and enhance angiogenesis in DU were investigated, focusing on the JAK2/STAT3 and PI3K/AKT signaling pathways. Results Network pharmacology identified quercetin (Que), kaempferol (Kae), abietic acid (Aba) and acetyl-11-keto-β-boswellic acid (AKBA) as the primary active constituents of FJSJ Powder treating DU; IL6, TNF, AKT1, and VEGFA were the core targets; and anti-inflammatory effect was mainly enriched in the JAK2/STAT3 signaling pathway, while angiogenesis promotion was mainly enriched in the PI3K/AKT signaling pathway. The vitro experiments have confirmed Que, Kae, Aba, and AKBA could play important roles in anti-inflammatory and angiogenic effects, with AKBA and Aba playing important roles in anti-inflammatory and pro-angiogenic effects, respectively. AKBA can upregulate P-JAK2, P-STAT3, IL-4, and downregulate INOS protein levels to exert anti-inflammatory. Aba can upregulate the P-AKT, P-PI3K, HIF-1α, and VEGFA proteins levels to promote angiogenesis. Conclusion FJSJ Powder promotes DU healing through dual-pathway regulation in anti-inflammatory and pro-angiogenic effects, with AKBA mediating the best anti-inflammatory activity through the JAK2/STAT3 pathway and Aba driving the strongest pro-angiogenic effects via the PI3K/AKT/HIF-1α/VEGFA axis, providing a basis for formula optimization.
研究领域:
药理学
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网络药理学
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中医药
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分子生物学
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创面愈合
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糖尿病并发症
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-21
·
IF 10.2
Liu Fan,Xiang Qinyanqiu,Luo Yuanli,Luo Ying,Luo Wenpei,Xie Qirong,Fan Jingdong,Ran Haitao,Wang Zhigang,Sun Yang
Background Oxidative stress (OS) induced by an imbalance of oxidants and antioxidants is an important aspect in anticancer therapy, however, as an adaptive response, excessive glutathione (GSH) in the tumor microenvironment (TME) acts as an antioxidant against high reactive oxygen species (ROS) levels and prevents OS damage to maintain redox homoeostasis, suppressing the clinical efficacy of OS-induced anticancer therapies.Results A naturally occurring ROS-activating drug, galangin (GAL), is introduced into a Fenton-like catalyst (SiO2@MnO2) to form a TME stimulus-responsive hybrid nanopharmaceutical (SiO2-GAL@MnO2, denoted SG@M) for enhancing oxidative stress. Once exposed to TME, as MnO2 responds and consumes GSH, the released Mn2+ converts endogenous hydrogen peroxide (H2O2) into hydroxyl radicals (·OH), which together with the subsequent release of GAL from SiO2 increases ROS. The “overwhelming” ROS cause OS-mediated mitochondrial malfunction with a decrease in mitochondrial membrane potential (MMP), which releases cytochrome c from mitochondria, activates the Caspase 9/Caspase 3 apoptotic cascade pathway. Downregulation of JAK2 and STAT3 phosphorylation levels blocks the JAK2/STAT3 cell proliferation pathway, whereas downregulation of Cyclin B1 protein levels arrest the cell cycle in the G2/M phase. During 18 days of in vivo treatment observation, tumor growth inhibition was found to be 62.7%, inhibiting the progression of pancreatic cancer. Additionally, the O2 and Mn2+ released during this cascade catalytic effect improve ultrasound imaging (USI) and magnetic resonance imaging (MRI), respectively.Conclusion This hybrid nanopharmaceutical based on oxidative stress amplification provides a strategy for multifunctional integrated therapy of malignant tumors and image-visualized pharmaceutical delivery.Graphical Abstract
研究领域:
药理学
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肿瘤学
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纳米技术
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生物医学工程
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成像技术
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Xiao-Lu Jie,Zi-Rui Luo,Jin Yu,Zhe-Ren Tong,Qiao-Qiao Li,Jia-Hui Wu,Yi Tao,Pei-Shi Feng,Ji-Ping Lan,Ping Wang
Ethnopharmacological relevance Pi-Pa-Run-Fei-Tang (PPRFT) is an empirical TCM prescription for treating asthma. However, the underlying mechanisms of PPRFT in asthma treatment have yet to be elucidated. Recent advances have revealed that some natural components could ameliorate asthma injury by affecting host metabolism. Untargeted metabolomics can be used to better understand the biological mechanisms underlying asthma development and identify early biomarkers that can help advance treatment. Aim of the study The aim of this study was to verification the efficacy of PPRFT in the treatment of asthma and to preliminarily explore its mechanism. Materials and methods A mouse asthma model was built by OVA induction. Inflammatory cell in BALF was counted. The level of IL-6, IL-1β, and TNF-α in BALF were measured. The levels of IgE in the serum and EPO , NO , SOD , GSH-Px, and MDA in the lung tissue were measured. Furthermore, pathological damage to the lung tissues was detected to evaluate the protective effects of PPRFT. The serum metabolomic profiles of PPRFT in asthmatic mice were determined by GC-MS. The regulatory effects on mechanism pathways of PPRFT in asthmatic mice were explored via immunohistochemical staining and western blotting analysis. Results PPRFT displayed lung-protective effects through decreasing oxidative stress, airway inflammation , and lung tissue damage in OVA-induced mice, which was demonstrated by decreasing inflammatory cell levels, IL-6, IL-1β, and TNF-α levels in BALF, and IgE levels in serum, decreasing EPO, NO, and MDA levels in lung tissue, elevating SOD and GSH-Px levels in lung tissue and lung histopathological changes. In addition, PPRFT could regulate the imbalance in Th17/Treg cell ratios, suppress RORγt, and increase the expression of IL-10 and Foxp3 in the lung. Moreover, PPRFT treatment led to decreased expression of IL-6, p-JAK2/Jak2, p-STAT3/STAT3, IL-17, NF-κB, p-AKT/AKT, and p-PI3K/PI3K. Serum metabolomics analysis revealed that 35 metabolites were significantly different among different groups. Pathway enrichment analysis indicated that 31 pathways were involved. Moreover, correlation analysis and metabolic pathway analysis identified three key metabolic pathways: galactose metabolism; tricarboxylic acid cycle; and glycine, serine , and threonine metabolism. Conclusion This research indicated that PPRFT treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating serum metabolism. The anti-asthmatic activity of PPRFT may be associated with the regulatory effects of IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB mechanistic pathways.
研究领域:
药理学
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免疫学
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代谢组学
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中医
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PubMed
高影响因子
ACS Nano
·
2024
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IF 15.8
Hao Wu,Changcheng Chen,Jiangfeng Li,Dongmei Yu,Xun Wu,Hai Huang,Zhen Tang,Qi Wu,Shichao Yan,Ning Wang,Mo Wang,Feilong Wei,Yunlong Yu,Duan Wang,Mengting Shi,Xusong Yue,Pengfei Cao,Zenghui Zheng,Xiaokang Li,Baolin Guo,Lei Shi,Zheng Guo
Infectious bone defects pose significant clinical challenges due to persistent infection and impaired bone healing. Icam1+ macrophages were identified as crucial and previously unrecognized regulators in the repair of bone defects, where impaired oxidative phosphorylation within this macrophage subset represents a significant barrier to effective bone regeneration. To address this challenge, dual-responsive iron-doped barium titanate (BFTO) nanoparticles were synthesized with magnetic and ultrasonic properties. These nanoparticles were further loaded with the anti-inflammatory agent curcumin and coated with engineered mesenchymal stem cell membranes (EMM) modified with γ3 peptide, creating BFTO-Cur@EMM nanoparticles specifically designed to target Icam1+ macrophages. These nanoparticles were shown to disrupt bacterial biofilms under alternating magnetic fields (AMF) and to activate oxidative phosphorylation and osteogenic immune responses in Icam1+ macrophages via low-intensity pulsed ultrasound (LIPUS). Transcriptomic sequencing and validation experiments demonstrated that this approach activates oxidative phosphorylation (OXPHOS) by stimulating the JAK2-STAT3 pathway and inhibiting the MAPK-JNK pathway, thereby promoting the polarization of Icam1+ macrophages toward a pro-reparative phenotype and enhancing the secretion of pro-angiogenic and osteogenic cytokines. These nanoparticles were subsequently integrated into quaternized chitosan (QCS) and tricalcium phosphate (TCP) to create a bioink for three-dimensional (3D) printing anti-infection QT/BFTO-Cur@EMM bone repair scaffolds. In vivo studies indicated that these scaffolds significantly improved the healing of infectious bone defects without causing thermal damage to surrounding tissues. This work highlights the potential of this material and the targeting of Icam1+ macrophages as an effective strategy for simultaneously controlling infection and promoting bone regeneration.
研究领域:
生物材料
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纳米技术
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骨科
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免疫学
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再生医学
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DOI
PubMed
高影响因子
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