International Journal of Nanomedicine
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2023
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IF 8
Ning-Ke Guo,Han She,Lei Tan,Yuan-Qun Zhou,Chun-Qiong Tang,Xiao-Yong Peng,Chun-Hua Ma,Tao Li,Liang-Ming Liu
Background Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured.Methods In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis.Results The encapsulation rate of Nano PTL was 95±1.5%, the drug loading rate was 11±0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL.Conclusion Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.
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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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RENAL FAILURE
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2024
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IF 3
Danyang Jing,Jingfeng Liu,Da Qin,Jin Lin,Tian Li,Yu Li,Meili Duan
Acute kidney injury (AKI), a common complication of sepsis, might be caused by overactivated inflammation, mitochondrial damage, and oxidative stress. However, the mechanisms underlying sepsis-induced AKI (SAKI) have not been fully elucidated, and there is a lack of effective therapies for AKI. To this end, this study aimed to investigate whether obeticholic acid (OCA) has a renoprotective effect on SAKI and to explore its mechanism of action. Through bioinformatics analysis, our study confirmed that the mitochondria might be a critical target for the treatment of SAKI. Thus, a septic rat model was established by cecal ligation puncture (CLP) surgery. Our results showed an evoked inflammatory response via the NF-κB signaling pathway and NLRP3 inflammasome activation in septic rats, which led to mitochondrial damage and oxidative stress. OCA, an Farnesoid X Receptor (FXR) agonist, has shown anti-inflammatory effects in numerous studies. However, the effects of OCA on SAKI remain unclear. In this study, we revealed that pretreatment with OCA can inhibit the inflammatory response by reducing the synthesis of proinflammatory factors (such as IL-1β and NLRP3) via blocking NF-κB and alleviating mitochondrial damage and oxidative stress in the septic rat model. Overall, this study provides insight into the excessive inflammation-induced SAKI caused by mitochondrial damage and evidence for the potential use of OCA in SAKI treatment.
研究领域:
药理学
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免疫学
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肾脏生理学
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分子生物学
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传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2022
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IF 9.417
Lingling Pan,Dawei Jiang,Luqi Pan,Zhizhen Meng,Yangyang Zhuang,Yueyue Huang,Fanrong Ye,Changcan Shi,Jie Chen,Jingye Pan
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and causes high ratios of morbidity and mortality worldwide. Although many potential therapeutic targets have been reported, the therapeutic effect needs to be further improved. Herein, we report a strategy to specifically target inflammation site via anti-ICAM-1 antibody bonded antibacterial peptides polymeric nanoparticle. Antibacterial peptide (KR-12) grafted amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 block copolymer and PCL- b -P(OEGMA- co -AMA)- g -biotin block copolymer were synthesized by ring-opening polymerization and click chemistry. Then, antibacterial peptides polymeric nanoparticles (AMPNP) were prepared by co-assembly of amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 and PCL- b -P(OEGMA- co -AMA)- g -biotin in aqueous solution. Intercellular adhesion molecule-1 (ICAM-1) is highly expressed on the surface of inflammatory endothelial cells, and the anti-ICAM-1 antibody can specifically bind to it. To obtain the anti-ICAM-1-AMPNP nanoparticles, biotinylated anti-ICAM-1 antibodies were bonded on the surface of AMPNP nanoparticles through the biotin-avidin system. The anti-ICAM-1-AMPNP nanoparticles had low systemic toxicity and exhibited ideal antibacterial property against drug-resistant bacteria, Gram-negative bacteria and Gram-positive bacteria. The anti-ICAM-1-AMPNP nanoparticles exhibited favorable targeting capabilities to inflammation endothelial cells in vitro and significantly reduced the inflammatory response of CLP mice in vivo . The present investigation might provide a specific strategy for targeting combating sepsis with anti-ICAM-1-AMPNP nanoparticles.
研究领域:
药学
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纳米技术
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感染病学
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免疫学
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高分子化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Baoshi Xu,Rongrong Yang,Jingchao Qiang,Xuhui Xu,Mengyuan Zhou,Xiaomeng Ji,Yingzhi Lu,Zibo Dong
Background To investigate the effect of Gypenoside XLIX (Gyp-XLIX) on acute splenic injury (ASI) induced by cecal ligation and puncture (CLP) in septic mice, a study was conducted. Methods Sixty healthy mice were randomly divided into six groups: the NC group, the Sham group, the Sham + Gyp-XLIX group, the CLP group, the CLP + Gyp-XLIX group, and the CLP + Dexamethasone (DEX) group. The NC group did not undergo any operation, while the rest of the groups underwent CLP to establish the sepsis model. The Sham group only underwent open-abdominal suture surgery without cecum puncture. After the operation, the groups were immediately administered the drug for a total of 5 days. Various methods such as hematoxylin and eosin (HE) staining, biochemical kits, qRT-PCR, and reactive oxygen species (ROS) were used for analysis. Results The results demonstrated that Gyp-XLIX effectively mitigated the splenic histopathological damage, while reducing the malondialdehyde (MDA) lipid peroxidation index and enhancing the antioxidant activities of catalase (CAT), glutathione (GSH) and total antioxidant capacity (T-AOC). The utilization of Dihydroethidium (DHE) fluorescent probe revealed that Gyp-XLIX inhibited the acute splenic accumulation of ROS induced by CLP in septic mice. Further investigations revealed that Gyp-XLIX exhibited a down-regulatory effect on the protein levels of inflammatory mediators iNOS and COX-2, consequently leading to the suppression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Additionally, it up-regulated the expression of anti-inflammatory factor IL-10. Conclusion In conclusion, Gyp-XLIX was significantly effective in attenuating CLP-induced acute splenic inflammation and oxidative stress in septic mice.
研究领域:
药理学
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免疫学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Zhihui Cai,Jinjin He,Jun Jiang,Zihan Zhao,Ye Shu
Background Sepsis is one of the major threats to human health with high mortality. Simiao Yong'an decoction (SMYAD) has the efficacy of anti-inflammation, improving coagulation and microcirculation, which is applicable for the clinical assistance treatment of sepsis . Yet, its material basis and relevant mechanisms are still vague. Purpose Explore the quality markers (Q-markers), biomarkers and potential mechanisms of SMYAD combined with imipenem/cilastatin sodium for anti-sepsis. Methods Linear-Trap-LC/MS n was employed to profile the compounds in the extract and medicated serum of SMYAD. Then, the components and targets obtained from databases were applied to network pharmacology. Q-markers’ range was narrowed via the affinity of three times docking and determined as per its screening criteria. Also, the content of them was detected by HPLC. Next, cecal ligation and puncture (CLP) model was reproduced to observe the effect of SMYAD united antibiotic by survival rate, histopathology score, ELISA, western blot and qPCR. Finally, metabolomics based upon GC–MS was exerted to discover the differential endogenous metabolites, metabolic pathway and joint pathway of SMYAD combined with antibiotic for sepsis. Results The 25 serum migrant ingredients derived from 113 chemical compounds of SMYAD were identified for the first time, and 6 components were determined as the Q-markers of SMYAD. The enrichment analysis indicated that the potential mechanism was mainly associated with the IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway. Then, SMYAD united antibiotic declined the mortality of septic rats, restored cytokine levels, ameliorated histopathological lesions and decreased the mRNA and protein expression of target proteins in a dose-dependent way. Furthermore, 8 differential metabolites were regarded as latent biomarkers related to the antiseptic effect of SMYAD united antibiotic, which were mainly involved in the Citrate cycle (TCA cycle) metabolic pathway. Conclusions Different skeletons of compounds, including iridoids, phenylpropanoids, organic acids, triterpenes and others, were the main compositions of SMYAD. Among them, 6 components were determined as the Q-markers, which provided a basis for the construction of quality standards for this ancient classic formula. The combination therapy of SMYAD and antibiotic obviously ameliorated inflammatory reaction, coagulation dysfunction and microcirculation abnormalities for sepsis by inhibiting IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway.
研究领域:
药理学
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中医药
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感染性疾病
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分子生物学
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代谢组学
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系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Kunmei Xie,Feibiao Wang,Yue Yang,Shoujie Pan,Junyao Wang,Nan Xiao,Xinyan Wang,Zhihao Ma,Xiaolong Xu,Zibo Dong
Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3β (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway.
研究领域:
药理学
·
免疫学
·
分子生物学
·
细胞生物学
·
病理学
✓ 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）