JOURNAL OF APPLIED MICROBIOLOGY
·
2019
·Vol. 127
·期 6
·1716-1726
·
IF 2.683
Cheng R.,Wang L.,Li J.,Fu R.,Wang S.,Zhang J.
AimsTo purify and characterize an exopolysaccharide (EPS) from an Agrobacterium strain ZCC3656 with high EPS‐secreting performance and investigate its anti‐inflammatory activity using lipopolysaccharide (LPS)‐induced macrophage cells in an acute liver injury mouse model.Methods and ResultsTwelve rhizobial strains were compared for EPS fermentation production in modified M9 salts supplemented with mannitol or sucrose as the sole carbon source. Agrobacterium sp. ZCC3656 exhibited the highest EPS yield (21·1 g l−1) and was characterized for EPS production by carbon source utilization, time course fermentation and serial subcultivation assays. The EPS, designated Riclin, was purified by deproteinization using the Sevag method. The combined results of gel permeation chromatography, monosaccharide composition, methylation analysis and nuclear magnetic resonance analyses indicated that Riclin is a succinoglycan‐like polysaccharide comprised of glucose, galactose, succinate and pyruvate at a ratio of 7·8. : 1·0 : 0·9 : 1·1 and has an molecular weight of approximately 2·5 × 106 Da. Riclin inhibited TNF‐α, IL‐1β and IL‐6 expression in LPS‐stimulated RAW 264.7 macrophage cells in a dose‐dependent manner. In addition, Riclin pretreatment increased the survival rate of D‐Gal/LPS treated mice, inhibited serum ALT and AST activities and reduced the production of the inflammatory mediators TNF‐α, IL‐1β and IL‐6.ConclusionsAgrobacterium sp. ZCC3656 is a highly stable EPS‐producing strain. The EPS Riclin from ZCC3656 is a succinoglycan‐type polysaccharide that is noncytotoxic and exhibits remarkable anti‐inflammatory effects in vivo and in vitro.Significance and Impact of the StudySuccinoglycans are well known for good rheological properties and their physiological interactions with plants. However, their potential activity towards mammals has received little attention. Our study revealed that the succinoglycan Riclin exhibited excellent anti‐inflammatory activities and could be considered as a promising reagent in anti‐inflammatory treatment.
研究领域:
微生物学
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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
BIODRUGS
·
2024
·
IF 5.4
Liu Yujie,Xie Jianhua,Li Zhuxiang,Mei Xiong,Cao Di,Li Shengfeng,Engle Linda,Liu Suli,Ebbers Hans C.,Liu Cuihua
Background and Objective Tocilizumab is an immunoglobulin G1 monoclonal antibody targeting the interleukin-6 receptor (IL-6R). BAT1806/BIIB800 (tocilizumab-bavi) has been developed as a biosimilar to the reference product tocilizumab (TCZ). The objective of this study was to demonstrate physicochemical and functional similarity between BAT1806/BIIB800 and TCZ in a comprehensive comparability exercise. Methods A comprehensive panel of over 20 methods was used to generate datasets comparing critical and non-critical product quality attributes for 10 BAT1806/BIIB800 lots and 44 TCZ lots (16 sourced from China, 16 from the EU, and 12 from the US). Primary structure, higher-order structure, and physicochemical properties were assessed using liquid chromatography, mass spectrometry, various spectroscopy techniques/methods, capillary electrophoresis, and thermoanalytical techniques. Fragment antigen-binding (Fab)- and fragment crystallizable (Fc)-mediated biological properties were assessed using cell-based assays, immunoassays, flow cytometry, and kinetic binding assays. Results BAT1806/BIIB800 and TCZ (irrespective of source) were shown to be similar in terms of structural and functional properties. No differences were observed in terms of the most critical quality attributes, that is, soluble-IL-6R binding and inhibition of IL-6-mediated cell proliferation. BAT1806/BIIB800 and TCZ demonstrated similarity in terms of Fab- and Fc-mediated binding and biological activity. Minor differences were observed in glycosylation (afucosylation and sialylation), glycation, aggregation, and charge variants, which were demonstrated to be not clinically relevant. Conclusion BAT1806/BIIB800 and TCZ were highly similar for all critical quality attributes. Where differences were observed in less critical quality attributes, additional analytical assessments and clinical study results determined these to be not clinically meaningful.
研究领域:
药学
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免疫学
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生物技术
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临床研究
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DOI
PubMed
高影响因子
Tissue Engineering and Regenerative Medicine
·
2021
·Vol. 18
·期 1
·113-125
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IF 4.169
Mou Donggang,Yu Qunying,Zhang Jimei,Zhou Jianping,Li Xinmin,Zhuang Weiyi,Yang Xuming
Background: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy. Methods: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N -carboxyethyl chitosan ( N -chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). Results: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. Conclusion: This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.
研究领域:
骨科
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生物材料
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药理学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Ying Lu,Dan Xu,Jingyao Liu,Lina Gu
Sophocarpine (SOP) is a tetracyclic quinolizidine alkaloid isolated from Sophora alopecuroides L. A number of studies have shown that SOP has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The purpose of this study was to investigate the protective effects of SOP on LPS-induced acute lung injury (ALI) in mice. Lung histological alterations, edema, and MPO activity were measured in this study. Furthermore, the production of inflammatory cytokines and the expression of NF-κB and MAPKs signaling pathways were measured. The results showed that the LPS-induced lung histological alterations, edema, protein concentration, inflammatory cell level in BALF, MDA content, and MPO activity were significantly attenuated by SOP. The LPS-induced inflammatory cytokine TNF-α, IL-1β, and IL-6 were also inhibited by SOP. SOP also inhibited the LPS-induced IL-6 and IL-8 production in A549 cells. Western blot analysis demonstrated that SOP remarkably inhibited the phosphorylation of IκBα and NF-κB. LPS-induced MAPKs activation and TLR4 expression were also suppressed by treatment with SOP. In conclusion, the results indicate that SOP protects against LPS-induced ALI by inhibiting TLR4 signaling pathway.
研究领域:
药理学
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免疫学
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肺病学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2021
·
IF 3.269
Haibo Xie,Hanfei Chai,Xiaohong Du,Rongna Cui,Yinan Dong
Sepsis, resulting from infections, is a systemic inflammatory response syndrome with a high fatality rate. The present study revolves around probing into the function and molecular mechanism of long non-coding RNA OIP5 antisense RNA 1 (lncRNA OIP5-AS1) in modulating acute lung injury (ALI) mediated by sepsis. Here, a sepsis model was constructed using cecal ligation and puncture (CLP) surgery in vivo. The alveolar macrophage cell line NR8383 and the alveolar type II cell line RLE-6TN were dealt with lipopolysaccharide (LPS) for in-vitro experiments. We discovered that OIP5-AS1 and Sirtuin1 (SIRT1) were markedly down-regulated in sepsis models elicited by CLP or LPS, while miR-128-3p experienced a dramatic up-regulation. OIP5-AS1 overexpression attenuated NR8383 and RLE-6TN cell apoptosis triggered by LPS and suppressed the expressions of nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in NR8383 and RLE-6TN cells, whereas miR-128-3p overexpression resulted in the opposite phenomenon. Moreover, OIP5-AS1 overexpression relieved lung edema, lung epithelial cell apoptosis, infiltration of myeloperoxidase (MPO)-labeled polymorphonuclear neutrophils (PMN), inflammatory responses triggered by CLP in vivo. Mechanistically, miR-128-3p, which targeted SIRT1, was hobbled by OIP5-AS1. All in all, OIP5-AS1 overexpression enhanced sepsis-induced ALI by modulating the miR-128-3p/SIRT1 pathway, which helps create new insights into sepsis treatment.
研究领域:
分子生物学
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传染病学
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呼吸病学
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重症医学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL LUNG RESEARCH
·
2023
·
IF 1.7
Ting Yang,Chang Xu,Niu Ding,Shujuan Luo,Bichen Wu,Shijie Jin,Yanping Chen
Background To investigate the protective effect of p14ARF in a nitric acid (NA) aerosol inhalation-induced bronchiolitis obliterans (BO) mouse model and its potential regulatory mechanism.Methods A BO mouse model was established by NA aerosol inhalation. The expressions of p14ARF, phosphatidylinositol-3-kinase (PI3K), and protein kinase B (AKT) were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot (WB). Hematoxylin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining observed pulmonary histological changes. TdT-mediated dUTP nick end labeling (TUNEL) staining detected pulmonary cell apoptosis, and enzyme-linked immunosorbent assay (ELISA) measured matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukon-6 (IL-6), and transforminh growth factor-β (TGF-β) levels in lung tissue and bronchoalveolar lavage fluid (BALF).Results The expressions of p14ARF, PI3K, and AKT showed a time gradient change, with a decrease trend (*P < 0.05 and **P < 0.01). Severe inflammatory infiltration and tracheal fibrosis were found in lung tissue in the modeling group (BO group) compared with the control group (Con group). The pH, PaO2, and PaO2/FiO2 values significantly reduced, while the PaCO2 value and the number of TUNEL-positive cells increased in BO group (P < 0.05). In addition, MMP-2, MMP-9, IL-6, and TGF-β levels remarkably increased, with an increase in the number of white blood cells, neutrophils, and lymphocytes in BO group (P < 0.05). Furthermore, p14ARF up-regulation reversed the trend of the aforementioned indexes in BO mice.Conclusions p14ARF ameliorated the inflammatory response and airway remodeling in a BO mouse model via the PI3K/AKT pathway.
研究领域:
呼吸医学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2023
·
IF 3.3
Lu-Lu Lin,Gui-Jun Song,Hui Zhang,Yan Yin,Shi-Meng Xin,Li Ding,Yu Li
Alzheimer's disease (AD) is a serious neurodegenerative disease characterized by amyloid-β (Aβ) aggregation and neuroinflammation. G-protein-coupled receptor 34 (Gpr34) was found highly expressed in the hippocampus of APP/PS1 mice. However, its role in AD remains unclear. Herein, the role of Gpr34 as well as its molecular mechanism was explored. Data in GSE85162 were analyzed and the differently expressed genes in the hippocampus tissues of APP/PS1 mouse model of AD were subjected to GO, KEGG and GSEA enrichment analyses. APP/PS1 mice were used as an animal model of AD and the cognitive impairment was evaluated by a water maze test. The level of Gpr34 in hippocampus and BV-2 cells as well as the activation of ERK/NF-κB signal was determined by quantitative real-time PCR, western blot or immunofluorescence. Our results showed that, in BV-2 cells exposed to Aβ 1-42 , Gpr34 knockdown decreased the levels of TNF-α, IL-1β, IL-6 and iNOS and suppressed the activation of ERK/NF-κB signal. Moreover, the Gpr34-overexpression-induced activation of ERK/NF-κB signal and up-regulated levels of TNF-α, IL-1β, IL-6 and iNOS were abolished by FR180204, an ERK inhibitor. On the other hand, the in vivo study showed that Gpr34 knockdown ameliorated the cognitive impairment in APP/PS1 mice, decreased the levels of TNF-α, IL-1β and IL-6, the activation of microglia and ERK/NF-κB signal. In conclusion, Gpr34 knockdown relieved cognitive deficits in APP/PS1 mice and suppressed neuroinflammation and microglial activation, maybe via the ERK/NF-κB signal. It is indicated that the high level of Grp34 in hippocampus may contribute to the pathogenesis of AD.
研究领域:
神经科学
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分子生物学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AFFECTIVE DISORDERS
·
2024
·
IF 4.9
Aoqi Song,Ru Cheng,Jingjing Jiang,Han Qu,Zhenghua Wu,Feng Qian,Shuyu Shen,Liwen Zhang,Zhiyu Wang,Wenjuan Zhao,Yuefen Lou
Background The antidepressant effect of hyperoside (HYP), which is the main component of Hypericum perforatum , is not established. This study aimed to determine the effects of HYP on depression. Methods The antidepressant-like effect of HYP was studied in mice induced by chronic restraint stress (CRS). The effects of HYP on behavior, inflammation, neurotransmitters, gut microbiota, and short-chain fatty acids (SCFAs) were studied in CRS mice. Results HYP improved depressive-like behavior in mice induced by CRS. Nissl staining analysis showed that HYP improved neuronal damage in CRS mice. Western blot (WB) analysis showed that HYP increased the expression levels of BDNF and PSD95 in the hippocampus of CRS mice. The results of ELISA showed that HYP down-regulated the expression levels of IL-6, IL-1β, TNF-α, and CORT in the hippocampus, blood, and intestinal tissues of mice and up-regulated the expression levels of 5-HT and BDNF. Hematoxylin and eosin (HE) staining results indicate that HYP can improve the intestinal histopathological injury of CRS mice. The results of 16S rRNA demonstrated that HYP attenuated the dysbiosis of the gut microbiota of depressed mice, along with altering the concentration of SCFAs. Limitations In the present study, direct evidence that HYP improves depressive behaviors via gut microbiota and SCFAs is lacking, and only female mice were evaluated, which limits the understanding of the effects of HYP on both sexes. Conclusions HYP can improve CRS-induced depressive-like behaviors in mice, which is associated with regulating the gut microbiota and SCFAs concentration.
研究领域:
药理学
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神经科学
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微生物学
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行为科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF GENE MEDICINE
·
2024
·Vol. 26
·期 10
·e3742
·
IF 3.2
Fuyun Zhu,Dezeng Zou,Ping Shi,Lianhua Tang,Dan Wu,Xiaoxue Hu,Fei Yin,Jianhui Liu
Background With its rapidly increasing incidence and prevalence, ulcerative colitis (UC) has become a major global health challenge. Recent evidence suggests that ferroptosis plays a significant role in the development of UC. However, the relationship between ferroptosis and the progression of UC needs to be extensively studied. Methods The differentially expressed genes in UC patients were screened from the GEO database. The ferroptosis-related genes were obtained from FErrDB and GeneCards. The UC subtypes were identified with the R package “CancerSubtype” and evaluated with consensus clustering (CC) to identify gene expression patterns in patients with UC. The key genes were detected with qRT-PCR, Western blot, and immunohistochemistry in vitro and in vivo models. Ferroptosis was identified with western blotting on ferrotic-associated proteins and staining on Fe 2+ with commercial FerroOrange kits. Results Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a potential biomarker for ferroptosis in UC patients. Transcriptome sequencing data showed a positive correlation between decreased DPP4 expression and proinflammatory cytokines such as TNF-α, IL-6, and IL-β, as well as immune cell infiltration in the colon tissues of UC patients. Furthermore, DPP4 was strongly associated with ferroptosis biomarkers, particularly in Subtype 2 of UC. Interestingly, our study also found that DPP4 expression was significantly reduced in RSL3-treated ferroptotic intestinal epithelial cells, more so than in LPS-treated cell models. Inhibition of DPP4 had a significant impact on the expression of ferroptotic biomarkers. Additionally, DPP4 expression was decreased in the colon tissues of DSS-treated mice, and the ferroptosis inhibitor Ferritin-1 effectively counteracted the effects of DSS on immune cell infiltration, colon length, and DPP4 expression. Conclusions DPP4 can serve as a biomarker for ferroptosis in the diagnosis and management of UC. Highlights DPP4-mediated ferroptosis is involved in ulcerative colitis DPP4 is a novel diagnostic biomarker of ulcerative colitis Ferroptosis involves intestinal epithelial cell death in ulcerative colitis
研究领域:
胃肠病学
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分子生物学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Qiulu Li,Kaixin Ping,Yannan Xiang,Ying Sun,Zunhan Hu,Shujuan Liu,Xinying Guan,Mian Fu
Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 μg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-β1 and il-10 , while significantly down-regulated the gene expression levels of tnf-α , il-6 and il-1β . These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.
研究领域:
水生毒理学
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药理学
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生物化学
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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 CONTROLLED RELEASE
·
2022
·
IF 11.467
Long Xi,Yunfeng Han,Chang Liu,Yihan Liu,Zhenping Wang,Ruibing Wang,Ying Zheng
The cross-talk between hyperproliferative keratinocytes and activated immune cells is responsible for the progression of psoriasis . The strategy to alleviate psoriasis through inhibiting the abnormal proliferation of keratinocytes remains challenging due to limited therapeutic effects and low skin penetration of drugs. Herein we designed an ultrasound-triggered phase-transition nanodroplet that could produce cavitation to enhance skin penetration and effectively generate reactive oxygen species (ROS) to induce keratinocyte apoptosis for psoriasis treatment. After ultrasound stimulation, the perfluoro-n-pentane (PFP) liquid core of the nanodroplets vaporized, and the Haematoporphyrin monomethyl ether (HMME) encapsulated in the nanodroplets generated plenty of intracellular ROS which caused the apoptosis of HaCat cells through inducing mitochondrial dysfunction. In addition, the blank nanodroplets successfully inhibited the secretion of IL-6 and TNF-α from macrophages and dendritic cells in vitro due to the anti-inflammatory effect of POPG. For the skin penetration test, the phase-transition nanodroplets could effectively accumulate in the epidermis of the skin and generate intracellular ROS. The in-vivo anti-psoriasis experiment demonstrated that the phase-transition nanodroplets relieved the symptoms of psoriasis lesion and inhibited epidermal hyperplasia through induction of cell apoptosis under ultrasound irritation. Meanwhile, the inflammatory cytokines in the skin lesion almost decreased to the normal baseline level after SDT. Collectively, this study demonstrated a new strategy to inhibit keratinocyte hyperproliferation for psoriasis management based on sonodynamic responded nanodroplets.
研究领域:
皮肤科
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纳米技术
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治疗学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Xue-Yan Dai,Shi-Yong Zhu,Jian Chen,Mu-Zi Li,Milton Talukder,Jin-Long Li
Lycopene (Lyc) has anti-inflammatory and antioxidant biological functions. Di-2-ethylhexyl phthalate (DEHP) is an extremely harmful and persistent environmental pollutant and is a threat to animal health. The toll-like receptor (TLR)/MyD88 pathway is an important pathway in the inflammatory response. To illustrate the potential antagonistic action of Lyc against DEHP by the TLR/MyD88 pathway, 140 ICR mice were randomly assigned groups and continuously gavaged with corn oil, distilled water, different DEHP concentrations (500 or 1000 mg/kg BW/day), and/or Lyc (5 mg/kg BW/day) for 28 days. The data show that Lyc effectively attenuates the DEHP-induced activation of the TLR/MyD88 pathway, the upregulation of JNK expression, the content of IL-6 and TNF-α, and the downregulation of the IL-10 content, which eventually inhibit the inflammatory response and mitochondrial injuries. These findings underline the TLR/MyD88 pathway as a potential therapeutic target in DEHP and Lyc as a new therapeutic method to inhibit DEHP toxicity.
研究领域:
毒理学
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免疫学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
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