PHYTOMEDICINE
·
2025
·
IF 8.3
Yixu Wang,Jin Zhang,Sihan Xu,Junjie Li,Wenjuan Liu,Min Jiang,Gang Bai
Background Acute lung injury (ALI) is a critical pathophysiological response in various respiratory diseases characterized by alveolar damage and excessive inflammation. It can progress to acute respiratory distress syndrome, with current treatments showing limited efficacy and considerable side effects. Psoralen (Pso), derived from Psoralea corylifolia L., has anti-inflammatory properties, but its role in ALI remains fully elucidated. Purpose This study aimed to investigate the therapeutic effects of Pso on ALI, and to explore its therapeutic targets and mechanisms. Methods The therapeutic potential of Pso was assessed using a model of ALI induced by lipopolysaccharide (LPS). The direct target was investigated using alkynyl-Psoralen (A-Pso) for chemical proteomic analysis, and a series of molecular biology methods were used to explore the underlying mechanism. Results Pso treatment significantly alleviated LPS-induced lung injury in mice, targeted macrophages, and inhibited the LPS-induced activation of macrophages. Target-fishing experiments identified high-mobility group box-1 (HMGB1) as a direct target of Pso in macrophages. FTS and CETSA confirmed Pso binding to HMGB1, and LC-MS/MS analysis indicated a covalent interaction between Pso and Cys106 of HMGB1. Furthermore, Pso covalently targeted Cys106, affecting HMGB1 binding to TLR4 and downregulating the phosphorylation of NF-κB, indicating the inhibition of the TLR4/NF-κB signaling pathway both in macrophages and in lung tissues of ALI mice. These findings suggest that Pso exerts its therapeutic effects by covalently targeting HMGB1 in macrophages and modulating the TLR4/NF-κB signaling pathway. Conclusion This study not only found that Pso improves LPS-induced ALI inflammation by targeting macrophages, but also verified that this mechanism of action is mainly caused by Pso covalently targeting Cys106 of HMGB1, inhibiting the HMGB1-TLR4 interaction, and thereby suppressing cytokine storm generation. As the first naturally derived HMGB1 covalent inhibitor with a clear binding site, Pso plays an important role in HMGB1 induced inflammatory diseases and is an active precursor for the development of new HMGB1 covalent inhibitors.
研究领域:
药理学
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免疫学
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呼吸病学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Guangzhe Xu,Chun Ma,Hongyan Chu,Wenxin Hu,Lihua Yang,Shuling Li
Purpose The pathological mechanisms underlying ischemic stroke are highly complex, with the neuroinflammatory response triggered by cerebral ischemia-reperfusion being a major contributor to secondary brain damage. This response significantly impedes neural tissue regeneration. Despite advancements in treatment, current anti-inflammatory strategies remain suboptimal in terms of safety and efficacy. This study aimed to develop an all-natural nanomedicine delivery system for the transnasal administration of puerarin, combined with the endogenous anti-inflammatory peptide Ac2-26, to enhance neuroprotection against ischemic stroke through a synergistic anti-inflammatory approach.Methods In this study, collagen nanoparticles (PueNps) loaded with puerarin were synthesized, followed by the preparation of a chitosan hydrogel. The PueNps and Ac2-26 were co-encapsulated within the hydrogel, resulting in the formation of the PueNps&Ac2-26 gel formulation. The physicochemical properties of this formulation, as well as its biodistribution and anti-ischemic efficacy in the MCAO rat brain, were evaluated.Results In this formulation system, the bioavailability of puerarin and Ac2-26 was enhanced, exhibiting sustained-release properties, which enabled efficient brain-targeted delivery. It effectively alleviated neurological impairment in MCAO rats, reduced the volume of cerebral infarction, and decreased brain water content. Additionally, the PueNps&Ac2-26 gel significantly inhibited neuroinflammation in rats and alleviated oxidative stress.Conclusion The PueNps&Ac2-26 gel is a purely natural and efficient formulation system, offering a promising approach for the clinical treatment of ischemic stroke in the future.
研究领域:
神经科学
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药学
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DOI
PubMed
高影响因子
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
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2025
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IF 1.4
Chanyu Wu,Xiaohan Wang,Xincan Li,Hexian Li,Qiuyue Peng,Xiaoxin Niu,Yutong Wu,Zhiying Wang,Zuoyong Zhou
Corynebacterium pseudotuberculosis , a zoonotic intracellular bacteria, is responsible for abscesses and pyogranuloma formation of the infected host, which is essentially a chronic inflammatory response. Tripartite motif-containing protein 21 (TRIM21) negatively regulates pro-inflammatory cytokines production during C . pseudotuberculosis infection, the mechanism of which remains unclear. This study found that C . pseudotuberculosis infection in macrophages induced phosphorylation of IκB and p65. TRIM21 interacted with IκBα by PRY/SPRY domain, stabilizes IκBα and negatively regulates IκBα phosphorylation in macrophages during C. pseudotuberculosis infection. In addition, TRIM21 positively regulates the ubiquitination of IκBα via K48 linkage rather than K63 linkage in C. pseudotuberculosis -infected macrophages. In brief, our research confirmed that TRIM21 negatively regulates canonical NF-κB activation by interacting with IκBα and decreasing IκBα phosphorylation in macrophages during C. pseudotuberculosis infection. Preventing inflammation induced by C. pseudotuberculosis infection through regulation of the NF-κB pathway is a potential way to control this pathogen.
研究领域:
免疫学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
ACS Omega
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2024
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IF 3.7
Hao Xu,Ning Ning Guo,Chen Ying Zhu,Lin Yan Ye,Xing Yi Yan,Yong Qin Liu,Ze Yan Zhang,Guangji Zhang,Liaqat Hussain
Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
研究领域:
肿瘤学
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药理学
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免疫学
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DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2022
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IF 4.52
Yipeng Gu,Kai Chen,Bingwen Xi,Jun Xie,Xuwen Bing
Paeonol (2′-hydroxy-4′-methoxyacetophenone) is a phenol that exhibits antioxidant and anti-inflammatory capabilities. In this study, the underlying mechanism of paeonol against LPS-induced oxidative stress and inflammatory responses in gibel carp was investigated. Three hundred healthy gibel carp were divided into five groups ( n = 9), intraperitoneally injected with LPS and thereafter treated with paeonol (16 mg/kg and 64 mg/kg). Fish were anesthetized with MS-222 (100 mg/L), and samples were collected at 72 h to investigate plasma biochemical indexes, liver histopathology , antioxidant enzymatic activity , and TLR receptor-related gene expression. Fish injected with LPS (20 mg/kg) exhibited significantly increased plasma aminotransferase (ALT), aminotransferase (AST), lactate dehydrogenase (LDH), glucose (GLU), diamine oxidase (DAO), and alkaline phosphatase (ALP) levels ( P < 0.05). In addition, LPS challenge significantly enhanced myeloperoxidase (MPO) and malondialdehyde (MDA) contents, whereas those of catalase (CAT) and glutathione peroxidase (GSH-Px) decreased ( P < 0.05). However, treatment with paeonol attenuated these LPS-induced changes ( P < 0.05). The mRNA expression of TLR4 , TIRAP , MyD88 , TRAF6 , NF-κB, TNF-α, IL-1β, and IL-8, which were activated by LPS challenge ( P < 0.05), were downregulated by paeonol. Additionally, histopathological examination demonstrated that paeonol alleviates LPS-induced hepatic tissue lesions in fish. Taken together, the results suggest that paeonol mitigates LPS-induced liver oxidative stress and inflammation in gibel carp.
研究领域:
水产养殖学
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免疫学
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药理学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2024
·Vol. 12
·期 17
·4184-4196
·
IF 6.1
Linsen Li,Yue Yu,Xiaoqing Sun,Xingyou Wang,Xiayan Yang,Qifeng Yu,Ke Kang,Yao Wu,Qiangying Yi
Stent implantation is one of the most effective methods for the treatment of atherosclerosis. Nitinol stent is a type of stent with good biocompatibility and relatively mature development; however, it cannot effectively achieve long-term anticoagulation and early endothelialization. In this study, nitinol surfaces with the programmed assembly of heparin, exosomes from endothelial cells, and endothelial affinity peptide (REDV) were fabricated through layer-by-layer assembly technology and click-chemistry, and then exosomes/REDV-modified nitinol interface (ACC-Exo-REDV) was prepared. ACC-Exo-REDV could promote the rapid proliferation and adhesion of endothelial cells and achieve anticoagulant function in the blood. Besides, ACC-Exo-REDV had excellent anti-inflammatory properties and played a positive role in the transformation of macrophage from the pro-inflammatory to anti-inflammatory phenotype. Ex vivo and in vivo experiments demonstrated the effectiveness of ACC-Exo-REDV in preventing thrombosis and hyperplasia formation. Hence, the programmed assembly of exosome interface could contribute to endothelialization and have potential application on the cardiovascular surface modification to prevent stent thrombosis and restenosis.
研究领域:
生物医学工程
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心血管疾病
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材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Yang Wang,Zhimin Chen,Fang You,Jing Sun,Hongyi Yang
Premature ovarian insufficiency (POI) is a female reproductive disorder characterized by impaired ovarian function. Protein tyrosine kinase 2 beta (PTK2B), a non-receptor tyrosine kinase, has been implicated in folliculogenesis, but its role in POI remains unknown. In this study, a rat POI model was established by intraperitoneal injection of cyclophosphamide (Cy) for 14 days. Electroacupuncture (EA) has been elicited to effectively improve ovarian function in POI. Here, mRNA sequencing (mRNA-seq) analysis found that PTK2B expression in ovarian tissues was upregulated by Cy treatment but downregulated by EA. To investigate PTK2B's role, primary rat ovarian granulosa cells (GCs) were co-treated with Cy (250 μM) and a PTK2B inhibitor PF-431396 (10 μM) for 48 h. PF-431396 inhibited Cy-induced inflammatory response and apoptosis in GCs. Further, PTK2B binds to AKT1 in GCs. PF-431396 facilitated AKT1 phosphorylation, and the inhibitory effects of PF-431396 on GC inflammatory response and apoptosis were reversed by an AKT1 inhibitor LY294002. In vivo , rats were given PF-431396 (10 mg/kg/d) by gavage for 7 days following Cy induction for 14 days. Treatment with PF-431396 increased ovarian weight, serum E2, and AMH levels, while decreased FSH and LH levels. Additionally, it could improve Cy-induced ovarian tissue injury, inhibit inflammation and apoptosis, and elevate p-AKT1 level in ovarian tissues. Together, our results unveil that PF-431396, a PTK2B inhibitor, ameliorates ovarian dysfunction in POI through promoting AKT1 phosphorylation, suggesting that PTK2B may be a therapeutic target for POI.
研究领域:
生殖生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Longwei Yang,Wenhao Ge,Xi Lin,Ning Yu,Xiaodong Xu,Jianfa Zhang
Allergic asthma is an inflammatory airway disease in which mast cells play a key role in its pathogenesis. Riclinoctaose (Rios), an octasaccharide composed of glucose and galactose, has been reported to modulate macrophage polarization in renal ischemia-reperfusion injury. This study investigates the effects of nebulized Rios in an ovalbumin (OVA)-induced allergic asthma model. Nebulized Rios significantly reduced airway hyperresponsiveness (AHR), inflammatory cell infiltration, pulmonary fibrosis, and mucus production in OVA-treated mice. Additionally, Rios suppressed lung inflammatory cytokine production and protected against OVA-induced oxidative injury. In bronchoalveolar lavage fluid (BALF), Rios decreased the number of neutrophils and macrophages, as well as serum immunoglobulin E (IgE) and interleukin-4 (IL-4) levels. Metabolomics analysis using 1 H NMR showed significant changes in the lung metabolic profile of OVA-induced asthma mice, which were partially reversed by Rios treatment. Confocal laser microscopy (CLM) revealed that fluorescently labeled Rios specifically binds to mast cell membranes. In vitro, Rios reduced degranulation and inflammatory responses in mast cells RBL-2H3 following anti-Dinitrophenyl-Immunoglobulin E (anti-DNP-IgE) sensitization and anti-Dinitrophenyl-Bovine Serum Albumin (anti-DNP-BSA) stimulation. These results suggest that Rios has therapeutic potential for allergic asthma, likely through the modulation of mast cell degranulation and mediator release.
研究领域:
免疫学
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呼吸病学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2025
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IF 8.4
Wang Hao,Xia Guo-qing,Ke Ting,Chen Xi-xi,Zhen Wen-jun,Tian Yuan-yuan,Chen Shi,Zhang Cheng,Li Jun,Zhang Lei,Wu De-jun,Wang Ye-tao,He Liang,Tian Wen-fang,Wu Bao-ming
Alcohol-related liver disease (ALD) refers to a spectrum of liver diseases caused by chronic or acute excessive alcohol consumption. Excess alcohol consumption and dysregulated immunometabolism are the major contributors to the disease progression. The pathogenesis of ALD remains unclear with macrophage activity playing a key role in disease development. Kv1.3 potassium channel is essential for the regulation of macrophage function. In this study, we investigated whether Kv1.3 channels influenced the progression of ALD by modulating macrophage function. A murine model of ALD was established in male mice. We showed that Kv1.3 knockdown significantly attenuated alcohol-induced liver injury, lipid deposition, and inflammatory responses in ALD mice. Metabolomic analysis revealed that Kv1.3 knockdown significantly increased the levels of tryptamine, a tryptophan metabolite, in the liver of ALD mice. During the last 5 days of the EtOH feeding period, injection of exogenous tryptamine (1, 10, 20 mg·kg −1 ·d −1 , i.p.) notably alleviated ethanol-induced liver steatosis and inflammation in ALD mice. In LPS-challenged RAW264.7 cells, tryptamine (62.5, 125, 250 μM) dose-dependently suppressed the secretion of pro-inflammatory cytokines IL-6, IL-1β and TNF-α. RNA-seq analysis of RAW264.7 cells revealed that tryptamine treatment significantly altered Toll-like receptor and NF-κB signaling pathways. We conclude that in the ALD mice, Kv1.3 negatively regulates tryptamine levels, which inhibits macrophage activation and reduces the inflammatory responses through the TLR4/NF-κB signaling pathway. Our results offer new targets and intervention strategies for the prevention and treatment of ALD.
研究领域:
医学
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免疫学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
CLINICAL SCIENCE
·
2025
·
IF 7.7
Renzi Zhang,Yuhua Zhong,Qiudie Liu,Mengqi Zhang,Daoxin Wang,Sheng Li,Di Qi
Acute respiratory distress syndrome (ARDS) is an acute and severe disease with a high mortality rate. The outbreak of immune inflammation in the lung is an important pathogenic mechanism of ARDS. Notably, an imbalance in macrophage polarization is an important link in the occurrence and development of this inflammatory response. Recently, neuropeptides have been shown to regulate inflammation, but the role of neuropeptides in ARDS remains unclear. The aim of this study was to investigate the regulatory effect of calcitonin gene-related peptide (CGRP) on the inflammatory response in ARDS. We found that CGRP expression was increased in the serum of ARDS patients and in both in vitro and in vivo models of ARDS. CGRP can regulate the polarization of macrophages by targeting its receptor (receptor activity-modifying protein 1); reduce the proportion of M1 macrophages; increase the proportion of M2 macrophages; and reduce pathological injury, inflammation, oxidative stress, and apoptosis in lung tissue in LPS-induced ARDS both in vitro and in vivo . Additionally, we performed transcriptome sequencing and found that hypoxia-inducible factor-1α (HIF-1α) is involved in the above process and that CGRP can alleviate ARDS-related pathological damage, inflammation, and oxidative stress by inhibiting the HIF-1α pathway to regulate macrophage polarization balance. These results indicate that CGRP has good potential for clinical translation in the treatment of pulmonary infection in ARDS. Furthermore, this study provides new ideas for the treatment of inflammatory bursts in ARDS.
研究领域:
免疫学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
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IF 9.4
Xingliang Dai,Dongdong Liu,Pengyu Pan,Guobiao Liang,Xianwen Wang,Weiwei Chen
Photothermal therapy (PTT) has gained widespread attention due to its significant advantages, such as noninvasiveness and ability to perform laser localization. However, PTT usually reaches temperatures exceeding 50 °C, which causes tumor coagulation necrosis and unfavorable inflammatory reactions, ultimately decreasing its efficacy. In this study, multifunctional two-dimensional Bi 2 Se 3 nanodisks were synthesized as noninflammatory photothermal agents for glioma therapy. The Bi 2 Se 3 nanodisks showed high photothermal stability and biocompatibility and no apparent toxicology. In addition, in vitro and in vivo studies revealed that the Bi 2 Se 3 nanodisks effectively ablated gliomas at relatively low concentrations and inhibited tumor proliferation and migration. Moreover, the multienzymatic activity of the Bi 2 Se 3 nanodisks inhibited the PTT-induced inflammatory response through their high ability to scavenge reactive oxygen species. Finally, the Bi 2 Se 3 nanodisks demonstrated computed tomography capabilities for integrating diagnosis and treatment. These findings suggest that multifunctional Bi 2 Se 3 nanodisk nanozymes can enable more effective cancer therapy and noninflammatory PTT.
研究领域:
生物医学工程
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肿瘤学
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材料科学
✓ 已验证
DOI
高影响因子
Brain Sciences
·
2023
·Vol. 13
·期 4
·541
·
IF 3.3
Min Zhou,Fang Pang,Dongmei Liao,Xinlu He,Yunhao Yang,Chenglin Tang
Background: Multiple studies have suggested that paralgesia (hyperalgesia and cutaneous allodynia) in migraine reflects the activation and sensitisation of the trigeminovascular system (TGVS). In particular, it reflects the second-order and higher nerve centre sensitisation, which is caused and maintained by neuroinflammation. Microglia activation leads to the release of proinflammatory cytokines involved in inflammatory responses. Accumulating evidence indicates that electroacupuncture (EA) is effective in ameliorating paralgesia, but the underlying mechanisms of EA in migraine attacks caused by microglia and microglia-mediated inflammatory responses are still unclear. The purpose of this study was to explore whether EA could ameliorate the dysregulation of pain sensation by suppressing microglial activation and the resulting neuroinflammatory response, and to evaluate whether this response was regulated by Toll-like receptor 4 (TLR4)/nuclear factor-kappa B(NF-κB) in the trigeminal nucleus caudalis (TNC) in a rat model of migraine. Methods: Repeated Inflammatory Soup (IS) was infused into the dura for seven sessions to establish a recurrent migraine-like rat model, and EA treatment was administered at Fengchi (GB20) and Yanglingquan (GB34) after daily IS infusion. Facial mechanical withdrawal thresholds were measured to evaluate the change in pain perception, and plasma samples and the TNC tissues of rats were collected to examine the changes in calcitonin gene-related peptide (CGRP), the Ibal-1-labelled microglial activation, and the resulting inflammatory response, including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and their regulatory molecules TLR4/NF-κB, via enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and Western blot analysis. Results: Repeated IS injections into the dura induced facial mechanical paralgesia, which is the manifestation of migraine attacks, and increased the expression of CGRP, Ibal-1, microglial mediated inflammatory cytokines (IL-1β, TNF-α, IL-6), and regulatory molecules TLR4/NF-κB. EA at GB20/34 significantly attenuated repetitive IS-induced pain hypersensitivity. This effect was consistent with decreased levels of CGRP and inflammatory cytokines in the plasma and the TNC via the inhibition of microglia activation, and this response may be regulated by TLR4/NF-κB. Conclusions: EA ameliorated paralgesia in repetitive IS-induced migraine-like rats, which was mainly mediated by a reduction in microglial activation and microglial-mediated inflammatory responses that could be regulated by TLR4/NF-κB.Keywords:migraine;electroacupuncture;paralgesia;microglia;inflammatory response
研究领域:
神经科学
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疼痛管理
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针灸
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炎症
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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）