Redox Biology
·
2021
·
IF 11.799
Chen Jin,Pengfei Wu,Yushun Yang,Zhenxiang He,Hailiang Zhu,Zhen Li
Realizing the early diagnosis of acute liver injury has become a hotspot in recent years. Since the current indexes are not specific, developing novel probes with new recognition group remains a necessity. In this work, we developed a novel fluorescent probe, NNP , for the detection of ONOO − in acute liver injury (ALI). The in vitr o evaluation of NNP indicated the advantages including high sensitivity (LOD = 0.13 μ M), rapid response (<25 s), naked-eye (red to yellow), and stability under various pH (4–10) and time (>48 h) conditions. Accordingly, NNP achieved the dose-dependent detection of ONOO − in human hepatic stellate LX-2 cells. Further, in the ALI model mice, NNP could monitor the ONOO − level in the occurrence of ALI in situ (in the liver region) with a steady performance. Subsequent immunohistochemical and imaging studies confirmed that NNP could achieve the detection of endogenous ONOO − in ALI liver tissues. This work introduced a practical implement for the ONOO − detection in ALI as well as a referable example for the establishment of molecular indexes in pre-clinical diagnosis.
研究领域:
生物化学
·
分子生物学
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医学诊断
·
药理学
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DOI
PubMed
高影响因子
Nanoscale
·
2023
·
IF 6.7
Yu Ran,Shanmei Yin,Pei Xie,Yaxue Liu,ying wang,Zongning Yin
Acute Lung Injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target to the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). In vitro, Dex/PSB-γ3 NPs had rapid H2O2 responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.
研究领域:
药理学
·
纳米技术
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炎症
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yinan Qiu,Jia Gao,Wenhui Chu,Shanshan Xia,Chen Huang,Huayue Zhu,Xiaolong Sun,Yongqian Fu
Acute lung injury (ALI) is a critical respiratory syndrome significantly impacting patient health. Tetrastigma hemsleyanum Diels et Gilg (Sanyeqing, SYQ) is a traditional Chinese medicine and its polysaccharides (SYQP) have demonstrated efficacy in counteracting lipopolysaccharide-induced ALI. This study characterized the structure of SYQP and synthesized the SYQP@ZIF-8 composite using biomimetic mineralization, evaluating encapsulation and release efficiency. The biocompatibility of SYQP@ZIF-8 in vitro was assessed by the CCK-8 colorimetric assay and hemolytic activity. Inflammatory cytokine was measured to evaluate the therapeutic effect. The efficacy of SYQP@ZIF-8 in lung injury was assessed using a mice ALI model. Characterization showed SYQP as a homogeneous α-type polysaccharide, comprising galactose, mannose, glucuronide, glucose, galacturonide, and arabinose, with a molecular weight of 516.94 kDa. SYQP@ZIF-8 exhibited high encapsulation rate (> 90 %), rapid pH-responsive release (within 60 min up to ~100 %), low toxicity and favorable hemolytic characteristics. Furthermore, it demonstrated reduced inflammatory cytokine secretion compared to SYQP, along with a superior inhibitory effect. The outcomes of in vivo experiments, including a decrease in the W/D ratio and LDH activity, further confirmed the efficacy of SYQP@ZIF-8 in treating LPS-induced ALI. In conclusion, SYQP@ZIF-8 released SYQP in acidic inflammatory conditions, outperforming SYQP alone in treating ALI.
研究领域:
药理学
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药物化学
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生物医学工程
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
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IF 3.6
Zhu Xiaona,Bai Bin,Ge Xiangting,Zheng Bin,Xiao Zhongxiang,Tang Yue,Fang Letong,Tang Yelin,Dai Yuanrong,Zhang Bing,Zhang Yali
Inflammation is an important pathological process of many acute and chronic diseases, such as sepsis, arthritis, and cancer. Many factors can lead to an inflammatory state of the body, among which bacterial infection plays an important role. Bacterial infection often leads to sepsis, acute lung injury (ALI), or its more serious form of acute respiratory distress syndrome, which are the main fatal diseases in intensive care units. Costunolide has been reported to possess excellent anti-inflammatory activity; however, whether it can affect inflammation induced by gram-negative bacterial is still unclear. Lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages (MPMs) to release proinflammatory cytokines was used as the cell model. The mouse model of sepsis and ALI was built through injecting intravenously and intratracheally of LPS. In the present study, costunolide inhibited LPS-induced inflammatory response through IKK/NF-κB signaling pathway in macrophages. In vivo, costunolide attenuated LPS-induced septic death in mice. Meanwhile, costunolide treatment alleviated LPS-induced lung injury and inflammation via inhibiting the infiltration of inflammatory cells and the expression of inflammatory cytokines. Taken together, these results demonstrated that costunolide could attenuate gram-negative bacterial induced inflammation and diseases and might be a potential candidate for the treatment of inflammatory diseases.
研究领域:
免疫学
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药理学
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炎症研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
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IF 13.2
Beiduo Wang,Yanping Xu,Qigu Yao,Liang Song,Min Liang,Hongcui Cao,Changyou Gao
Selective modulation of the types of reactive oxygen species (ROS) for the treatment of acute lung injury (ALI) has not been tackled, whereas the usually applied hydrophobic nanoparticles (NPs) are easily excreted and metabolized. Herein, a zwitterionic-segment containing polyurethane was synthesized to formulate into Pazopanib (Pazo)-loaded NPs (PUSB@Pazo NPs), which had the ability to selectively enhance the expression of H 2 O 2 but suppress other types of ROS, and achieved long retention in lung and thereby improved treatment efficacy. The zwitterionic group of PUSB effectively decreased the clearance rate of PUSB@Pazo NPs in vivo , and prolonged their resident time in lung post inhalation up to 48 h. The increase of local H 2 O 2 concentration decreased the permeability of lung epithelial cells, accompanied by the significantly reduced tissue edema and inflammatory cell recruitment. The system also reduced the expression of various inflammatory factors, revealing its effective and promising treatment for ALI.
研究领域:
药学
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材料科学
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肺病学
✓ 已验证
产品关联
DOI
高影响因子
BMC Complementary Medicine and Therapies
·
2024
·Vol. 24
·期 1
·1-13
·
IF 3.3
Li Jiao,Zhang Qi-Yun,Lu Qing-Yu,Liu Qiao-Zhou,Guo Li,Li Min,Sun Qian-Yun
IntroductionAcute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation.Methods Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue.Results Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue.Conclusion Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.
研究领域:
药理学
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免疫学
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肺医学
✓ 已验证
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Yu Xu,Wen Jiang,Xin-Chuang Wang,Feng-Xian Luo,Jiang-Ning Hu
As a global public health issue, the treatment of acute liver injury (ALI) is facing serious challenges due to the lack of specific drugs. Selenium nanoparticles (Se NPs), due to their robust antioxidant attributes, have shown considerable potential in ALI prevention. However, the application of Se NPs is impeded by their instability, propensity to aggregate, and tendencies towards precipitation. In this study, we modified the surface of Se NPs with phlorotannin (PT) to synthesize PT-Se NPs. Our initial results suggested that PT-Se NPs, having a reduced particle size of 107.10 ± 4.04 nm, exhibited superior stability, enhanced cellular absorption, and sustained liver accumulation in comparison to Se NPs. In concordance with our expectations, PT-Se NPs demonstrated enhanced therapeutic performance in mitigating CCl 4 -induced ALI, as demonstrated by the preservation of liver functionality, decrease in oxidative stress markers, reduction of inflammatory factor levels, and improvement in histological damage. This research contributes a promising strategy for effectively improving the stability of Se NPs and preventing ALI, broadening the horizon for effective liver protection and potential clinical translation.
研究领域:
纳米技术
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药理学
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肝病学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-11
·
IF 4.122
Li Lili,Zhang Sheng,Xin Yanfei,Sun Junying,Xie Feng,Yang Lin,Chen Zhiqin,Chen Hao,Liu Fang,Xuan Yaoxian,You Zhenqiang
Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro . In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.
研究领域:
药理学
·
免疫学
·
呼吸医学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Immunology Research
·
2023
·
IF 4.1
Hui Du,Shiwen Tong,Ge Kuang,Xia Gong,Ningman Jiang,Xian Yang,Hao Liu,Nana Li,Yao Xie,Yang Xiang,Jiashi Guo,Zhenhan Li,Yinglin Yuan,Shengwang Wu,Jingyuan Wan
Acetaminophen (APAP) overdose would lead to liver toxicity and even acute liver failure in severe cases by triggering an inflammatory response and oxidative stress. Sesamin has been reported to possess anti-inflammatory and antioxidant actions in several animal disease models. In the present study, the effects and mechanisms of sesamin on APAP-induced acute liver injury (ALI) were explored. The results showed that pretreatment with sesamin significantly alleviated APAP-induced ALI, as indicated by decreased serum aminotransferase activities, hepatic pathological damages, and hepatic cellular apoptosis. But sesamin has no significant effects on the expression of cytochrome P450 2E1 (CYP2E1), APAP-cysteine adducts (APAP-CYS) production, and glutathione content in the liver of APAP-administered mice. Moreover, APAP-induced liver oxidative stress and inflammatory response also were remarkedly attenuated by sesamin, including reducing hepatic reactive oxygen species levels, promoting antioxidant generation, and inhibiting the expression of TNF-α and IL-1β, as well as decreasing inflammatory cell recruitment. Notably, sesamin inhibited serum high-mobility group box 1 (HMGB1) releases and blocked hepatic activation of Toll-like receptor 4 (TLR4)-interleukin 1 receptor-associated kinase 3-nuclear factor kappa B (NF-κB) signaling pathway in APAP-administered mice. These findings indicated that sesamin could mitigate APAP-induced ALI through suppression of oxidative stress and inflammatory response, which might be mediated by the deactivation of HMGB1/TLR4/NF-κB signaling in mice.
研究领域:
肝病学
·
药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Hua Fang,Xiumei Wang,Mengyu Li,Mengxian Huang,Yiping Zhang,Taige Zhao,Cuiling Sun,Min Xu,Wenhui Jin,Weizhu Chen,Meijuan Fang
In this study, twenty-five novel carboxylic acid DHA-alkanolamine derivatives were synthesized by the reaction of cis -docosa-4,7,10,13,16,19-hexaenoic acid-alkanolamine (DHA-AA) with various carboxylic acids, including Naproxen (S1), Ibuprofen (S2), Ferulic acid (S3), Mefenamic acid (S4), and Aspirin (S5). Their molecular structures were characterized using 1 H/ 13 C NMR and HRMS techniques. To evaluate the anti-inflammatory activities of synthesized compounds, RAW264.7 macrophage cells pretreated with or without these compounds, were stimulated by LPS, and the levels of pro-inflammatory cytokines (NO, TNF-α, IL-1β, and IL-6) were then measured by ELISA, qPCR, and Western Blot. The cell-based assays showed that compound 11 had marked anti-inflammatory activity. In addition, the molecular docking study and SPR assay demonstrated that compound 11 exhibited good Nur77-binding affinity (K D = 3.61 × 10 −6 M). Moreover, compound 11 was found to inhibit NF-κB activation in a Nur77-dependent manner. Notably, compound 11 could attenuate LPS-induced inflammation in the mouse acute lung injury (ALI) model. In conclusion, these derivatives are potential Nur77-targeting anti-inflammatory agents against versatile inflammatory and autoimmune disorders.
研究领域:
药理学
·
炎症研究
·
药物化学
✓ 已验证
DOI
高影响因子
FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
·
2022
·Vol. 61
·期 1
·34-46
·
IF 1.49
Lili Ji Xiaojing Shi Gaopin Wang Huiping Wu Zhansheng Hu
Introduction. Acute lung injury (ALI) is a major cause of death in sepsis patients. The Six-transmembrane protein of prostate 2 (STAMP2) is a key regulator of inflammation, while its role in septic ALI remains unclear. Material and methods. Male C57BL/6 mice were subjected to cecal ligation puncture (CLP) to induce experimental sepsis whereas lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used as the models of septic ALI in vivo and in vitro , respectively. Overexpression of STAMP2 in mouse lungs and RAW264.7 cells was performed with an adenoviral vector. We measured histological lung injury, lung wet/dry weight (W/D) ratio, and pulmonary myeloperoxidase (MPO) activity to assess lung injury extent. Cell counts in bronchoalveolar lavage fluid (BALF) were measured using Giemsa staining. The concentration of inflammatory factors was detected by enzyme-linked immunosorbent assay. The polarization of macrophages was evaluated by inducible nitric oxide synthase (iNOS) and F4/80 staining. The activation of cell apoptosis and NF-κB pathway was evaluated using Western blot, TUNEL staining, immunofluorescence, and immunohistochemistry. Results. Overexpression of STAMP2 alleviated CLP-induced lung injury of mice with decreased W/D ratio of the lung, and MPO activity in lung tissue. STAMP2 overexpression reduced the lung infiltration of inflammatory cells, and the levels of TNF-a, IL-6, and macrophage chemoattractant protein-1 (MCP-1) in BALF. Overexpressed STAMP2 inhibited macrophage M1 polarization in lung tissues as indicated by F4/80 and iNOS stainings in lung tissue. STAMP2 overexpression inhibited RAW 264.7 cell apoptosis by increasing Bcl-2 and decreasing Bax and cleaved-caspase 3 expression. Besides, STAMP2 overexpression suppressed nuclear factor κB (NF-κB) p65 pathway activation, as evidenced by reduced phosphorylation of IκBα, and phosphorylation and translocation of NF-κB p65. In vitro study further proved that STAMP2 overexpression suppressed the NF-κB pathway (IκBα/p65) in macrophages and decreased macrophage M1 polarization and M1-associated inflammatory factor production (TNF-a, IL-6, and MCP-1). Conclusions. Our study for the first time demonstrated that STAMP2 might be able to reduce inflammation in sepsis-induced ALI by inhibiting macrophage M1 polarization through repressing NF-κB signaling activation.
研究领域:
免疫学
·
病理生理学
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分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
XingXing Zhang,Demin Lv,Bingxia Li,Yuting Ding
Sepsis-associated acute lung injury (ALI) poses a significant threat, characterized by inflammation and oxidative damage. Effective drugs targeting these aspects with reliable drug delivery systems are vital for ALI management. This study aimed to evaluate the influence of algal polysaccharides (APs) with aerosolized drug delivery in ALI mice and clarify the underlying mechanism. To induce the sepsis-associated acute lung injury (ALI) model, mice were administered intraperitoneal injections of 10 mg/kg LPS for 48 h in vivo . ALI mice received APs via atomization to arrive at different sites within the lungs. Lung tissue samples and bronchoalveolar lavage fluid (BALF) were collected to access lung injury parameters. Concurrently, western blotting, H&E staining, and immunofluorescence (IF) were applied to investigate the specific impact of APs on ALI. The results showed that APs protect lung tissue against ALI by inhibiting inflammation and mitigating oxidative stress-induced damage. This study highlights promising avenues for ALI intervention using natural compounds with anti-inflammatory and antioxidant properties.
研究领域:
药理学
·
肺病学
·
免疫学
·
生物化学
·
分子生物学
✓ 已验证
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）