INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 24
·9576
·
IF 4.556
Bin Zhang,Xueying Li,Xiuhong Li,Zhigang Lu,Xiaona Cai,Qing Ou Yang,Pengda Ma,Juane Dong
Tanshinones, the major bioactive components inSalvia miltiorrhizaBunge (Danshen), are synthesized via the mevalonic acid (MVA) pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway and the downstream biosynthesis pathway. In this study, the bacterial component lipopolysaccharide (LPS) was utilized as a novel elicitor to induce the wild type hairy roots ofS. miltiorrhiza.HPLC analysis revealed that LPS treatment resulted in a significant accumulation of cryptotanshinone (CT) and dihydrotanshinone I (DTI). qRT-PCR analysis confirmed that biosynthesis genes such asSmAACTandSmHMGSfrom the MVA pathway,SmDXSandSmHDRfrom the MEP pathway, andSmCPS,SmKSLandSmCYP76AH1from the downstream pathway were markedly upregulated by LPS in a time-dependent manner. Furthermore, transcription factorsSmWRKY1 andSmWRKY2, which can activate the expression ofSmDXR,SmDXSandSmCPS, were also increased by LPS. Since Ca2+signaling is essential for the LPS-triggered immune response, Ca2+channel blocker LaCl3and CaM antagonist W-7 were used to investigate the role of Ca2+signaling in tanshinone biosynthesis. HPLC analysis demonstrated that both LaCl3and W-7 diminished LPS-induced tanshinone accumulation. The downstream biosynthesis genes includingSmCPSandSmCYP76AH1were especially regulated by Ca2+signaling. To summarize, LPS enhances tanshinone biosynthesis throughSmWRKY1- andSmWRKY2-regulated pathways relying on Ca2+signaling. Ca2+signal transduction plays a key role in regulating tanshinone biosynthesis inS. miltiorrhiza.Keywords:lipopolysaccharide;tanshinones;Ca2+signaling;SmWRKY
研究领域:
植物学
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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
Bioactive Materials
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2022
·
IF 16.874
Liping Ouyang,Baohui Chen,Xingdan Liu,Donghui Wang,Yang Li,Yun Liao,Kelvin W.K. Yeung,Xuanyong Liu
It is important to eliminate lipopolysaccharide (LPS) along with killing bacteria in periprosthetic joint infection (PJI) therapy for promoting bone repair due to its effect to regulate macrophages response. Although natural antimicrobial peptides (AMPs) offer a good solution, the unknown toxicity, high cost and exogenetic immune response hamper their applications in clinic. In this work, we fabricated a nanowire-like composite material, named [email protected] , by combining chitosan and puerarin via solid-phase reaction, which can finely mimic the bio-functions of AMPs. Chitosan, serving as the bacteria membrane puncture agent, and puerarin, serving as the LPS target agent, synergistically destroy the bacterial membrane structure and inhibit its recovery, thus endowing [email protected] with good antibacterial property. In addition, [email protected] possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation modulation. The in vivo results show that [email protected] can inhibit the LPS induced bone destruction in the Escherichia coli infected rat. [email protected] exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property, and its ability of LPS elimination and immunomodulation. [email protected] can well mimic the functions of AMPs, which provides a novel and effective method for treating the PJI in clinic.
研究领域:
医学
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生物材料学
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DOI
PubMed
高影响因子
MOLECULES
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2020
·Vol. 25
·期 20
·4815
·
IF 3.267
Minmin Sun,Yaoting Ji,Zhen Li,Rourong Chen,Shuhui Zhou,Chang Liu,Minquan Du
Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 onPorphyromonas gingivalisLPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 amelioratedPorphyromonas gingivalisLPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.Keywords:anti-inflammatory agents;chronic periodontitis;ginsenoside;lipopolysaccharides
研究领域:
药理学
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牙科
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2025
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IF 4
Ziwei Yang,Zhiwei Zhang,Ying Zhang,Xiaoqiang Chen
As the first step of resource utilization, the extraction and separation of active ingredients play an important role in the evaluation and application of their activity. In this study, a macroporous resin purification process was optimized to obtain high-purity sea buckthorn flavonoids (SBF). The AB-8 resin exhibited optimal adsorption and desorption properties, with adsorption and desorption rates of 75.25% and 84.78%, respectively. Under optimal purification conditions, the purity of the flavonoid extract was enhanced from 17.17 ± 0.19% to 63.2 ± 0.16%. Kinetic and thermodynamic analyses demonstrated that the purification of SBF on AB-8 resin conformed to the pseudo-secondary kinetic model and the Langmuir adsorption isotherm model. The major components of the SBF were taxifolin, isoquercitrin, narcissoside, and quercetin. The SBF not only inhibited lipopolysaccharide-induced nitric oxide production but also exerted significant anti-inflammatory effects, suppressing the expression of proteins such as nitric oxide synthase, tumor necrosis factor, interleukin 6, and interleukin 1β and inhibiting apoptosis. Therefore, the purified SBF demonstrated improved anti-inflammatory activity, which can be applied in the development of drugs and functional foods.
研究领域:
植物化学
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药理学
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生物技术
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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
TALANTA
·
2024
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IF 5.6
Jiayue Shi,Sijia Li,Rongguang Shao,Yang Jiang,Yanxia Qiao,Jin Liu,Yaqian Zhou,Yan Li
In this study, an ultrasensitive electrochemiluminescence (ECL) aptasensing method was developed for lipopolysaccharide (LPS) determination based on CRISPR-Cas12a accessory cleavage activity. Tris (2,2'-bipyridine) dichlororuthenium (II) (Ru(bpy) 3 2+ ) was adsorbed on the surface of a glassy carbon electrode (GCE) coated with a mixture of gold nanoparticles (AuNPs) and Nafion film via electrostatic interaction. The obtained ECL platform (Ru(bpy) 3 2+ /AuNP/Nafion/GCE) exhibited strong ECL emission. Thiol-functionalized single-stranded DNA (ssDNA) was modified with a ferrocenyl (Fc) group and autonomously assembled on the ECL platform of Ru(bpy) 3 2+ /AuNP/Nafion/GCE via thiol-gold bonding, resulting in the quenching of ECL emission. After hybridization of the LPS aptamer strand (AS) with its partial complementary strand (CS), the formed double-stranded DNA (dsDNA) could activate CRISPR-Cas12a to indiscriminately cleave ssDNA-Fc on the surface of Ru(bpy) 3 2+ /AuNP/Nafion/GCE, resulting in recovery of the ECL intensity of Ru(bpy) 3 2+ due to the increasing distance between Fc and the electrode surface. The combination of LPS and AS suppressed the formation of dsDNA, inhibited the activation of CRISPR-Cas12a, and prevented further cleavage of ssDNA-Fc. This mechanism aided in upholding the integrity of ssDNA-Fc on the surface of the electrode and was combined with ECL quenching induced by the target. The ECL intensity decreased linearly as the concentration of LPS increased from 1 to 50,000 pg/mL and followed a logarithmic relationship. This method exhibited a remarkably low detection limit of 0.24 pg/mL, which meets the requirement for low-concentration detection of LPS in the human body. The proposed method demonstrates the capacity of CRISPR-Cas12a to perform non-specific cutting of single-stranded DNA and transform the resultant cutting substances into changes in the ECL signal. By amalgamating this approach with the distinct identification abilities of LPS and its aptamers, a simple, responsive, and discriminatory LPS assay was established that holds immense significance for clinical diagnosis.
研究领域:
生物传感
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分子诊断
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临床医学
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DOI
PubMed
高影响因子
PLoS One
·
2014
·Vol. 9
·期 9
·e108314
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IF 3.534
Xiang Hou,Jingfei Zhang,Hussain Ahmad,Hao Zhang,Ziwei Xu,Tian Wang
The aim of this study was to investigate the antioxidant potential of ampelopsin (APS) by using various methods in vitro , as well as to determine effects of APS on LPS-induced oxidative stress in piglets. The results showed that APS exhibited excellent free radical scavenging by DPPH, ABTS, O 2 • − , H 2 O 2 and ferric reducing antioxidant power. Ampelopsin also protected pig erythrocytes against AAPH-induced apoptosis and hemolysis, decreased total superoxide dismutase activity, and increased lipid peroxidation. Furthermore the results demonstrated that APS enhanced the total antioxidant capacity and decreased the malondialdehyde and protein carbonyl contents in LPS-treated piglets. The results of the present investigation suggest that APS possesses a strong antioxidant activity and alleviates LPS-induced oxidative stress, possibly due to its ability to prevent reactive oxygen species.
研究领域:
动物医学
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生物化学
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DOI
PubMed
高影响因子
LANGMUIR
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2019
·
IF 3.683
Zhenxin Han,Xi Ren,Qiang Huang,Ting Shi,Yuping Lai,Yi-Lei Zhao
Aggregation behavior of proteins on the surface of gold nanoparticles (AuNPs) has been extensively studied for its promising applications in biosensing, bioimaging, photodynamic therapy, drug delivery, etc. In this work, we studied adsorption kinetics of an antimicrobial protein, regenerating islet-derived protein 3-alpha (REG3A), on the surface of as-synthesized citrate-capped AuNPs under the influence of lipopolysaccharides (LPSs), with a combined method of UV–vis spectroscopy, multivariate analysis, and molecular dockings. In the AuNPs–REG3A binary system, a component with an “up-and-down” signal was detected by the in-depth data analysis on time-resolved spectroscopic data, corresponding to the protein agglomeration and exfoliation observed in transmission electron microscopy and atomic force microscopy experiments. Intriguingly, LPSs can rescue the spectral oddity—the adsorption pattern in the AuNPs–REG3A–LPS ternary system becomes normal and similar to a typical single-layer mode as in our previous study of the serum albumin–AuNP system (Ren, X.; et al., Spectrosc. Lett., 2016, 49, 434−443). The following molecular modeling suggests that LPS molecules mainly interact with three segments of REG3A amino acid sequences, i.e., P109–T110–Q111–G112, P115–N116, and P137–S138–T139. The latter two protein–ligand interactions impair the REG3A–REG3A protein–protein interaction between the two subunits (E114–P115–N116–G117–E118 and N136–P137–S138–T139–I140). Thus, our results elucidate the LPS inhibitory effect on fibrous protein self-aggregation at the AuNP surface, and molecular dockings give a plausible mechanism to rationalize the competition among protein–protein and protein–ligand interactions.
研究领域:
生物化学
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纳米生物学
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分子建模
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DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2017
·
IF 1.667
Xiao-Xiao LU,Yi-Fan JIANG,Hong LI,Ying-Ye OU,Zhi-De ZHANG,Hong-Ye DI,Dao-Feng CHEN,Yun-Yi ZHANG
Lipopolysaccharides (LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate (PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages (MPMs). The nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in cell culture supernatant, as the indications of cell response, were assayed. Bupleurum chinensis polysaccharides (BCPs) with trace amount contamination of LPS was treated with PB. 30 μg·mL −1 of PB, treating LPS (10 and 1 000 ng·mL −1 in stimulating RAW264.7 and MPMs respectively) at 37 °C for 24 h, successfully abolished the stimulating effect of LPS on the cells. When the cells were stimulated with LPS, BCPs further promoted NO production. However, pretreated with PB, BCPs showed a suppression of NO production in MPMs and no change in RAW264.7. In the in vitro experiments, LPS contamination in polysaccharide might bring a great interference in assessing the activity of drug. Pretreatment with PB (30 μg·mL −1 ) at 37 °C for 24 h was sufficient to abolish the effects of LPS contamination (10 and 1 000 ng·mL −1 ).
研究领域:
免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE RESEARCH
·
2016
·Vol. 48
·期 5
·2278-2290
·
IF 1.606
Jing Qian,Chunhua Ren,Ting Chen,Jianjun Xia,Zonghe Yu,Yan Gao,Chaoqun Hu
The broad-spectrum protease inhibitor alpha-2-macroglobulin (α 2 M) is widely found in vertebrates and invertebrates. However, no research regarding α 2 M has been described in sea cucumbers to date. In this study, the first sea cucumber α 2 M named Stm α 2 M was identified from Stichopus monotuberculatus , a tropical species with high edible and economic values in Southern China. The Stm α 2 M cDNA is 5276 bp in length, containing a 5′-untranslated region (UTR) of 279 bp, a 3′-UTR of 344 bp and an open reading frame of 4653 bp that encodes a protein of 1550 amino acids. The Stmα 2 M possesses all the three characteristics of known α 2 M proteins, including the bait region domain, thioester domain and receptor-binding domain. Higher levels of mRNA expression were noticed in intestine, respiratory tree, coelomocytes and tentacle of S. monotuberculatus . Transcriptional expression of Stm α 2 M showed the strongest response to lipopolysaccharides (LPS, 8.19-fold up-regulation) after 6 h post-challenge in coelomocytes. In addition, the α 2 M activity was detected in S. monotuberculatus and protein activity of α 2 M increased remarkably at 6 h after LPS stimulation. As a whole, this study indicated that Stmα 2 M is an important immune-related molecule, and the study on functions of Stmα 2 M may provide some new and valuable ideas for preventing and controlling diseases of cultured sea cucumbers.
研究领域:
免疫学
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分子生物学
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海洋生物学
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DOI
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 9
·1662
·
IF 7.675
Yibin Xu,Xiaoqing Ding,Yuanyuan Wang,Danlei Li,Lingyu Xie,Shuang Liang,Yunfeng Zhang,Weifen Li,Aikun Fu,Xiuan Zhan
Reuterin is well-known for its broad-spectrum antimicrobial ability, while the other potential bioactivity is not yet clear. The present study aims to investigate the immunomodulatory activity of reuterin on chicken macrophage HD11 cells for the first time and evaluate whether reuterin is able to regulate the lipopolysaccharide-stimulated inflammatory response. The results showed that the safe medication range of reuterin was less than 250 μM. Reuterin treatment for 6 h decreased the transcriptional ofCD86,IL-1βandiNOSand increased the expression ofCD206in a dose-dependent way, but reuterin treatment for 12 h contrary increased the expression ofIL-1β,IL-6andIL-10. However, it was noticed that reuterin treatment for 12 h significantly decreased the production of reactive oxygen species (ROS) and suppressed the phagocytosis activity of HD11 macrophages against bacteria. Further, the results showed that preincubation or coincubation with reuterin significantly attenuated the promotive effects of lipopolysaccharide (LPS) on transcription of proinflammatory cytokines (includingIL-1β,IL-6andTNF-α) and obviously inhibited nitric oxide (NO) production as well as the protein expression of inducible nitric oxide synthase (iNOS). Meanwhile, Mechanism studies implied that reuterin might exert an anti-inflammatory effect on LPS-stimulated cells by downregulating the expression ofTLR4/MyD88/TRAF6and blocking the activation of NF-κB as well as MAPKs signaling pathways. Additionally, it was found that both pretreatment and cotreatment with reuterin remarkably inhibited the oxidative stress induced by LPS stimulation by activating the Nrf2/HO-1 signaling pathway and enhancing the activities of antioxidative enzymes. These findings suggested the immunoregulatory function of reuterin and indicated this bacterial metabolite was able to inhibit the inflammation and oxidative stress of HD11 macrophages once exposed to LPS stimulation.Keywords:reuterin;HD11 cell line;lipopolysaccharide (LPS);inflammation response;oxidative stress
研究领域:
免疫学
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细胞生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
RENAL FAILURE
·
2024
·
IF 3
Weike Hu
Sepsis represents an organ dysfunction resulting from the host’s maladjusted response to infection, and can give rise to acute kidney injury (AKI), which significantly increase the morbidity and mortality of septic patients. This study strived for identifying a novel therapeutic strategy for patients with sepsis-induced AKI (SI-AKI). Rat tubular epithelial NRK-52E cells were subjected to lipopolysaccharide (LPS) exposure for induction of in-vitro SI-AKI. The expressions of E1A binding protein p300 (EP300) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in NRK-52E cells were assessed by western blot and qRT-PCR, and their interaction was explored by chromatin immunoprecipitation performed with antibody for H3K27 acetylation (H3K27ac). The effect of them on SI-AKI-associated mitochondrial dysfunction of tubular epithelial cells was investigated using transfection, MTT assay, TUNEL staining, 2′,7′-Dichlorodihydrofluorescein diacetate probe assay, Mitosox assay, and JC-1 staining. MTHFD2 and EP300 were upregulated by LPS exposure in NRK-52E cells. LPS increased the acetylation of H3 histone in the MTHFD2 promoter region, and EP300 suppressed the effect of LPS. EP300 ablation inhibited the expression of MTHFD2. MTHFD2 overexpression antagonized LPS-induced viability reduction, apoptosis promotion, reactive oxygen species overproduction, and mitochondrial membrane potential collapse of NRK-52E cells. By contrast, MTHFD2 knockdown and EP300 ablation brought about opposite consequences. Furthermore, MTHFD2 overexpress and EP300 ablation counteracted each other’s effect in LPS-exposed NRK-52E cells. EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction of tubular epithelial cells in SI-AKI.
研究领域:
分子生物学
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医学
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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）