Microbiology Spectrum
·
2024
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IF 3.7
Deyi Zhao,Miran Tang,Panjie Hu,Xiaowei Hu,Weijun Chen,Zhexiao Ma,Huanchang Chen,Haifeng Liu,Jianming Cao,Tieli Zhou
Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Escherichia coli (CREC) are frequently detected in clinical settings, restricting the use of carbapenems. Therefore, there is an urgent need for new antimicrobial strategies to address infections caused by CRKP and CREC. This study investigated the antibacterial, anti-biofilm, and anti-inflammatory effects of the cationic antimicrobial peptide Hs02, along with its potential antimicrobial mechanisms against CRKP and CREC. The results revealed that Hs02 had a low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against CRKP and CREC, effectively eliminating the bacteria within 30 min. Moreover, Hs02 significantly prevents biofilm formation and disrupts the established biofilms. Further mechanistic studies demonstrated that Hs02 specifically targeted and bound to bacterial outer membrane lipopolysaccharides (LPS), disrupted membrane permeability and integrity, which led to intracellular reactive oxygen species (ROS) accumulation. Furthermore, Hs02 neutralized LPS, thereby suppressing the production of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in murine macrophage RAW 264.7 cells. In vitro, hemolysis and cytotoxicity assays confirmed Hs02’s safety at the tested concentrations and proved that Hs02 improved the survival rate of Galleria mellonella larvae. In conclusion, the findings suggest that Hs02’s interaction with LPS and the resulting disruption of membrane integrity may be key factors driving its rapid bactericidal and anti-inflammatory effects.
研究领域:
微生物学
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药理学
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传染病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yuan Xu,Xin An,Lei Liu,Xinran Cao,Zhanfeng Wu,Wang Jia,Jiacheng Sun,Haoyu Wang,Jiawei Huo,Zihao Sun,Mingming Zhen,Chunru Wang,Chunli Bai
Endotoxemia is a life-threatening multiple organ failure disease caused by bacterial endotoxin infection. Unfortunately, current single-target therapy strategies have failed to prevent the progression of endotoxemia. Here, we reported that alanine fullerene redox modulator (AFRM) remodeled the intestinal microenvironment for multiple targets endotoxemia mitigation by suppressing inflammatory macrophages, inhibiting macrophage pyroptosis, and repairing epithelial cell barrier integrity. Specifically, AFRM exhibited broad-spectrum and self-cascade redox regulation properties with superoxide dismutase (SOD)-like enzyme, peroxidase (POD)-like enzyme activity, and hydroxyl radical (•OH) scavenging ability. Guided by proteomics, we demonstrated that AFRM regulated macrophage redox homeostasis and down-regulated LPS/TLR4/NF-κB and MAPK/ERK signaling pathways to suppress inflammatory hyperactivation. Of note, AFRM could attenuate inflammation-induced macrophage pyroptosis via inhibiting the activation of gasdermin D (GSDMD). In addition, our results revealed that AFRM could restore extracellular matrix and cell-tight junction proteins and protect the epithelial cell barrier integrity by regulating extracellular redox homeostasis. Consequently, AFRM inhibited systemic inflammation and potentiated intestinal epithelial barrier damage repair during endotoxemia in mice. Together, our work suggested that fullerene based self-cascade redox modulator has the potential in the management of endotoxemia through synergistically remodeling the inflammation and epithelial barriers in the intestinal microenvironment.
研究领域:
药理学
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免疫学
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病理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
·
2024
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IF 2.3
He Chengjian,Song Xiaojing,Zhu Zigui,Xiao Yan,Chen Jiacheng,Yao Hongyi,Xie Rongjun
Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment. Graphical Abstract We explored the effects of ghrelin on coagulopathy and vascular endothelial injury in vivo by establishing an ATC mouse model, and investigated the effects of ghrelin on LPS-induced HUVECs cell damage in vitro. The RhoA overexpression plasmid or adenovirus was used to examine the molecular mechanism. Abbreviations : ATC =acute traumatic coagulopathy; HUVECs =Human Umbilical Vein Endothelial Cells; LPS =lipopolysaccharide; RhoA =The Ras homolog family member A; aPTT =activated partial thromboplastin time; PT =prothrombin time; TEER =trans-endothelial electrical resistance
研究领域:
血液学
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血管生物学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Jinmiao Chen,Xihui Jia,Shuang Wang,Xueqin Wang,Ling Li,Guangting Han,Yuejie Dou,Jiwei Li
Although electrical stimulation (ES) and drugs are desirable for wound healing, dressings that combine ES and drugs are scarce. In this study, an electroactive drug-loaded nanofibrous dressing (PUE-Zn/AB@CA) was prepared by loading zinc/acetylene black nanoparticle particles (Zn/AB) in Puerarin/cellulose acetate (PUE/CA) nanofibres, respectively. Due to the different potentials, many galvanic couples can be formed between Zn and AB, generating electrical stimulation that promotes cell migration and proliferation. Benefiting from the synergistic effect of Zn/AB electrical stimulation and PUE, PUE-Zn/AB@CA exhibits excellent antioxidant, antibacterial, and anti-inflammatory properties. The whole-layer wound defect model experiment showed that PUE-Zn/AB@CA can significantly accelerate wound closure and promote granulation tissue formation, collagen deposition, and angiogenesis at the wound. Moreover, PUE-Zn/AB@CA could inhibit the inflammatory infiltration of M1-type macrophages in damaged wounds. In addition, flow cytometry and Western blot (WB) revealed that PUE-Zn/AB@CA could effectively down-regulate the lipopolysaccharide (LPS)-induced macrophage polarisation towards M1-type and reduce the protein level of pro-inflammatory cytokines (iNOS) in the cells. This work provided an effective wound healing strategy based on drug/electroactivity synergistic effects.
研究领域:
生物材料
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伤口愈合
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纳米技术
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电化学
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药学
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组织工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMISTRY & BIODIVERSITY
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2025
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IF 2.5
Tingli Qu,Shasha Suo,Liqiu Yan,Liwei Wang,Taigang Liang
Astragaloside IV (ATS) is an active component of Astragalus membranaceus, which has immune regulation and anti-inflammatory effects. However, owing to its large molecular weight and poor solubility in water, the therapeutic effects of ATS are limited. We aimed to prepare astragaloside IV-chitosan (ATS-CS) nanoparticles and determine their anti-inflammatory effect and mechanism of action on RAW264.7 cells using metabolomics. The size of the ATS-CS nanoparticles was 200.3 nm with a zeta potential of 30.5 mV, and the encapsulation rate and drug loading were 69% and 13%, respectively. ATS-CS nanoparticles not only significantly decreased the increase of NO, IL-6 and TNF-α levels induced by LPS, but also exerted an anti-inflammatory effect by acting on arginine and proline, glutathione, sphingolipid, glycerophospholipid, and glycine, serine, and threonine metabolism. Our findings confirmed that ATS-CS nanoparticles have good anti-inflammatory activity and showed that the activity of high molecular weight can be increased by producing nanoparticles. Our study paves the way for exploring the mechanism of nanoparticles through metabolomics.
研究领域:
药理学
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纳米技术
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免疫学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Anyi Zhao,Jiangmin Su,Qingxia Xu,Jun Zhang,Jinzhu Jiang,Sha Chen,Jintang Cheng,Chang Chen,Lianmei Wang,Jipeng Di,Xianju Liu,Liang Jiang,Li Liu,Yan Liu,An Liu,Cong Guo
Ethnopharmacological relevance Xiebai San (XBS), a classic Chinese prescription, has been used for the clinical treatment of pneumonia-related diseases for thousands of years. However, the anti-pneumonia pharmacodynamic material basis of XBS and its underlying mechanisms remain unclear. Aim of the study This study aimed to comprehensively investigate and verify the anti-pneumonia pharmacodynamic material basis and mechanisms of XBS. Materials and methods This study explored the anti-pneumonia activity and key pneumonia targets of XBS in lipopolysaccharide (LPS)-induced zebrafish and RAW264.7 cells in vivo and in vitro through transcriptomics, western blotting, and reverse transcription–quantitative polymerase chain reaction (RT–qPCR). The chemical fingerprint of XBS was established using high-performance liquid chromatography, and the similarities and areas of characteristic peaks of 15 batches of XBS were analyzed. Based on the spectrum–efficacy relationship, the potential anti-inflammatory components were screened according to their peak areas and efficacy using principal component analysis (PCA), bivariate correlation, and partial least squares regression analysis. Active components that bind to core targets were further screened based on surface plasmon resonance (SPR). The binding mode of proteins and components was simulated via molecular docking, which enabled the identification of the primary active components of XBS, thereby elucidating its anti-pneumonia properties. Finally, the anti-inflammatory activities of these components were verified in vitro . Results XBS decreased neutrophil aggregation in zebrafish and nitric oxide (NO) secretion in RAW264.7 cells as well as suppressed the release of downstream inflammatory cytokines such as iNOS, TNF-α, IL-1β, IL-18, and CXCL10 related to TNF and JAK–STAT signaling pathways. The phosphorylation of IκBα, Akt, and Stat3 was alleviated after XBS in cells. The fingerprint similarities of 15 batches of XBS ranged from 0.381 to 0.994, with a large difference. A total of 15 characteristic peaks were identified, and the relative standard deviation of their peak areas ranged from 24.1% to 70.7%. The results of in vitro anti-inflammatory activities of 15 batches of XBS showed that all samples inhibited the expression levels of NO and nine inflammatory markers. The anti-inflammatory index of 15 batches of XBS was determined to be 0.69–0.96 based on transformation of the anti-inflammatory rate and composite index method via PCA. The spectrum–efficacy relationship model of 15 characteristic peak areas and the anti-inflammatory index showed that 7 main potential active components were related to the anti-inflammatory activity of XBS. Moreover, four components (mulberroside A, isoquercitrin, liquiritigenin, and glycyrrhizic acid) screened based on SPR had different affinities toward TNFR1, Akt1, and Stat3 proteins, and the binding modes were elucidated via molecular docking. Finally, in LPS-induced RAW264.7 cells, all four active components (at a concentration of 60 μM) significantly inhibited the expression levels of NO and inflammatory markers. Conclusions Based on the comprehensive strategy of spectrum–efficacy relationship and SPR, mulberroside A, isoquercitrin, liquiritigenin, and glycyrrhizic acid were identified as the primary pharmacodynamic active components involved in the anti-pneumonia activity of XBS and were found to intervene in TNF and JAK–STAT signaling pathways.
研究领域:
药理学
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民族药理学
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转录组学
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生物化学
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分子生物学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
·
IF 4.8
Chengguang Zhao,Yali Zhang,Peng Zou,Jian Wang,Wenfei He,Dengjian Shi,Huameng Li,Guang Liang,Shulin Yang
A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs) were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 MAPK and suppressed IκBα degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-κB) and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure–activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases.
研究领域:
药理学
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药物化学
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免疫学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
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
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Yue Su,Zhengying Cui,Xinyan Yang,Yujun Jiang,Wei Zhang,Yu Zhang,Chaoxin Man
Ulcerative colitis (UC) is an immune-mediated intestinal disease without a comprehensive cure, and the alleviation of UC has become an urgent problem. The results showed that JY062 with its EPS group (JEC) alleviated the intestinal barrier damage caused by LPS. After JEC intervention on Caco-2 cells, resulted in upregulation of ZO-1, Claudin-1, Occludin and MUC2 transcript levels and decreased mRNA expression of Claudin-2 (p < 0.05). JEC effectively attenuated the inflammatory response in UC mice and restoration of immunoglobulin levels (IgG, IgM and IgA), which resulted in shortening and swelling of the colon, disappearance of goblet cells, infiltration of inflammatory cells and mucosal damage were alleviated in mice. Similarly, changes in the expression of MUC2 and tight junction proteins after JEC intervention also occurred in UC mice. Administration of JEC significantly inhibited the differentiation of pro-inflammatory Th17 cells in the thymus and peripheral blood, promoted the differentiation of CD4+ T cells to Treg cells, and effectively regulated DSS-induced macrophage imbalance, which was manifested by the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages. This study clearly demonstrates that JEC could significantly prevent intestinal barrier on DSS-induced experimental colitis and could be applied as a potential symbiotic strategy to assist in the alleviation of UC.
研究领域:
微生物学
·
免疫学
·
胃肠病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Fenfen Wei,Huibin Jiang,Chuang Zhu,Lingyue Zhong,Zihan Lin,Yan Wu,Lihua Song
A high-fat diet (HFD) is associated with various adverse health outcomes, including cognitive impairment and an elevated risk of neurodegenerative conditions. This relationship is partially attributed to the influence of an HFD on the gut microbiota. The objective of this research was to evaluate the neuroprotective benefits of co-fermented black barley and quinoa with Lactobacillus (FG) against cognitive impairments triggered by an HFD and to investigate the microbiota-gut–brain axis mechanisms involved. C57BL/6J mice were randomized into four groups: the normal control group (NC, n = 10), the high-fat diet group (HFD, n = 10), the high-fat diet group supplemented with FG (HFG, 10 mL per kg BW, n = 10), and the high-fat diet group supplemented with Lactobacillus (HFL, 10 mL per kg BW, n = 10). Our results showed that the FG intervention enhanced the behavioral and locomotor skills of the mice, elevated the levels of dopamine (DA) and norepinephrine (NPI) in brain tissues, and alleviated synaptic ultrastructural damage in the hippocampus. Furthermore, FG intervention was observed to exert a protective effect on both the blood–brain barrier and the colonic barrier, as evidenced by an increase in the mRNA levels of Zona occludens-1 (ZO-1), Claudin-4, and Occludin in the hippocampus and colon. These beneficial effects may be attributed to FG's regulation of gut microbiota dysbiosis, which involves the restoration of intestinal flora diversity, reduction of the Firmicutes/Bacteroidetes (F/B) ratio, and a decrease in the levels of pro-inflammatory bacteria such as s_Escherichia coli E and g_Escherichia; moreover, there was an increase in the abundances of anti-inflammatory bacteria, such as s_Bacteroides thetaiotaomicron and s_Parabacteroides goldsteinii. Metagenomic analysis revealed that the FG treatment downregulated the lipopolysaccharide (LPS) pathway and upregulated neurotransmitter biosynthetic pathways. These probiotic effects of FG resulted in reduced production and “leakage” of LPS and decreased mRNA expression of Toll-like receptor 4 (Tlr4), cluster of differentiation 14 (CD14), and myeloid differentiation factor 88 (Myd88) in hippocampal and colon tissues. Consequently, a reduction was observed in the levels of inflammatory cytokines in the serum, hippocampus, and colon, along with suppression of the immunoreactivity of microglia and astrocytes. Our results suggest that FG may serve as an intervention strategy for preventing cognitive impairments caused by an HFD.
研究领域:
营养神经科学
·
微生物组研究
·
神经免疫学
·
胃肠科学
·
宏基因组学
✓ 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）