JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2024
·Vol. 28
·期 13
·e18527
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IF 4.3
Maomao Miao,Mengying Li,Yunjie Sheng,Peijian Tong,Yang Zhang,Dan Shou
Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-β signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-β/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.
研究领域:
骨科
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药理学
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分子生物学
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信号转导
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2017
·
IF 2.956
Yi Zhou,Jing Wang,Weidong Yang,Xiaowen Qi,Lei Lan,Lan Luo,Zhimin Yin
Bergapten (BG) is a cumarine-derivate compound in many medicinal plants . Here, in vitro and in vivo experimental results indicated that BG possesses anti-inflammatory properties, Based on this, we further investigated the precise molecular mechanisms of BG in LPS-stimulated inflammation response . Studies revealed that BG inhibited LPS-stimulated productions of TNF-α, IL-1β, IL-6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time, it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264.7 cells. Mechanistically, BG suppressed the activations of JAK/STAT, but not that of MAPKs and NF-κB. In addition, BG, as an antioxidant, prevented the accumulation of ROS , which further exerted its anti-inflammatory function. In vivo researches revealed that BG decreased LPS-induced mortality in mice. In conclusions, BG may be a potential candidate for inflammation therapy via inhibiting JAK/STAT activation and ROS production in RAW264.7 cells.
研究领域:
药理学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 5
·914
·
IF 7.675
Tianle Xu,Run Liu,Hao Zhu,Yu Zhou,Tianxu Pei,Zhangping Yang
This study aimed to evaluate whether (-)-epigallocatechin-3-gallate (EGCG) alleviates hepatic responses to lipopolysaccharide (LPS)-induced inflammation and oxidation. Isolated bovine hepatocytes and BALB/c mice were used for LPS challenge and EGCG pretreatment experiments in vitro and in vivo. LPS-challenged (6 μg/mL) hepatocytes exhibited increased levels of NF-κB (p65 and IκBα) and MAPK (p38, ERK, JNK) phosphorylation as well as increased binding activity of p65 to target pro-inflammatory gene promoters, and these effects were suppressed by pretreatment with 50 μM EGCG. Moreover, the reduction in Nrf2 signaling and antioxidant enzyme activities induced by LPS stimulation were reversed upon EGCG treatment. In vivo experiments demonstrated the protective role of EGCG in response to GalN/LPS-induced mortality and oxidative damage. Together, our results suggest that EGCG is hepatoprotective via inhibition of MAPK/NF-κB signaling and activation of the Nrf2 cascade. This information might help design strategies for counteracting hepatitis in ruminants and monogastric animals.Keywords:EGCG;bovine hepatocytes;hepatoprotective;MAPK/NF-κB signaling;antioxidant activity
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PubMed
高影响因子
RESEARCH IN VETERINARY SCIENCE
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2022
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IF 2.554
Mohammad Reza Tabandeh,Sadegh Jozaie,Zohre Ghotbedin,Saad Gorani
The stimulation of pro-inflammatory pathways by lipopolysaccharide (LPS) endotoxins is a key player in the pathological mechanisms involved in the development of ovarian dysfunctions in dairy cows. Dimethyl itaconate acid (DMIA) is a novel immunometabolite that has recently emerged as a regulator of inflammatory responses in mammals. The present study was undertaken to determine the anti-inflammatory effects of DMIA on bovine granulosa cells (GCs) and to explore its possible molecular mechanisms. The ovarian GCs were obtained from small follicles of dairy cows. The GCs were stimulated with 1 μg/mL LPS for 4 h and then treated with 250 μM DMIA for 12 h. The viability, production of pro-inflammatory cytokines, activation of inflammatory signaling pathways and synthesis of steroid hormones were evaluated in treated GCs. Our results showed that DMIA reduced the inflammatory responses in LPS stimulated GCs by down-regulating the expression of nod-like receptor family pyrin domain containing 3 inflammasome , and toll-like receptor 4 and by suppressing the phosphorylation of nuclear factor kappa B and c-Jun N-terminal kinase proteins . DMIA also attenuated the increased production of pro inflammatory cytokines (interleukin 6, tumor necrosis factor α and interleukin 1 beta ( p < 0.01) in LPS stimulated GCs. Exposure of LPS stimulated GCs to DMIA improved the impaired steroidogenesis by up-regulation of steroid synthesis genes including 3-beta-hydroxysteroid dehydrogenase, follicle stimulating hormone receptor and cytochrome P450 aromatase . The results of the present study highlight the potential role of itaconic acid for the improvement of GCs inflammation in dairy cows with ovarian dysfunctions.
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PubMed
高影响因子
Food & Function
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2024
·
IF 5.1
Bufan Xu,Luyao Zhang,Di Wu,Zihe Qi,Juanjuan Cao,Wenrui Li,Lihua Fan,Yiheng Shi,Yongning Wu,Guoliang Li
Copper II oxide nanoparticles (CuO NPs), a kind of widely used nanomaterial, have been detected in food and the environment, which has aroused widespread public concern. Recently, increasing data have suggested that intestinal microecology is closely related to immune homeostasis. However, the intestinal immunotoxicity induced by CuO NPs through intestinal microbiota is still unknown. Therefore, in this study, zebrafish were exposed to CuO NPs to explore intestinal immunotoxicity by evaluating physiological indicators, intestinal tissue injury, antioxidant enzyme activities, gene expression of immune factors, and changes in intestinal microbiota and its metabolites (short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS)). The results revealed that the intestinal immunotoxicity of CuO NPs was mediated by the impact on intestinal microbiota and its metabolite levels. Specifically, changes were observed in the abundance of microbes that participated in the metabolism of SCFAs and LPS. The reduction in acetic acid, propionic acid and valeric acid upregulated GPR84 expression, and the decline in LPS levels further resulted in the suppression of the key immune regulatory pathways TLR4/MyD88/NF-κB, ultimately leading to intestinal immunotoxicity. This study would provide a scientific basis for the risk assessment of CuO NPs and a new perspective for research on the immunotoxicity of nanoparticles.
研究领域:
环境科学
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毒理学
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微生物学
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免疫学
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水生生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Yuxin Zhang,Lixuan Yang,Yonghui Gan,Chenchen Zhao,Chao Zhou,Jian Chen,Yanping Yin,Shengnan Xia,Haiyan Yang,Xinyu Bao,Meijuan Zhang,Yun Xu,Jingwei Li
Microglia, the primary immune cells of the central nervous system, play a crucial role in the neuroinflammatory processes following ischemic stroke. Targeting neuroinflammation is a promising strategy to enhance the outcomes of ischemic stroke. Benzydamine (BA), a well-known non-steroidal anti-inflammatory drug, has demonstrated potential in inhibiting pro-inflammatory cytokines across various disease models. However, the potential role of BA in microglial activation and post-stroke neuroinflammation remains unclear. Our study reveals that BA effectively suppresses the lipopolysaccharide (LPS)-stimulated pro-inflammatory responses of primary microglia, with high-dose BA (10 μM) suppressing LPS-induced inflammatory markers by up to 59.1 % in the mRNA levels of IL-1β. Furthermore, BA mitigated ischemic brain injury in experimental stroke mice. BA treatment also significantly attenuated neuroinflammatory responses and attenuates ischemic brain injury in experimental stroke mice. Further investigation revealed that BA reduces the release of the LPS-stimulated pro-inflammatory factors and activation of primary microglia by directly binding to and inhibiting the activity of cathepsin S (CTSS). In conclusion, our study identifies BA as a promising CTSS inhibitor with potential to suppress neuroinflammation following ischemic stroke. Our findings provide a theoretical basis for developing new neuroprotective strategies.
研究领域:
神经科学
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药理学
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免疫学
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神经病学
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DOI
PubMed
高影响因子
JOURNAL OF GENE MEDICINE
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2024
·Vol. 26
·期 10
·e3742
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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
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DOI
PubMed
高影响因子
TALANTA
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2024
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IF 5.6
Hong He,Xiaoli Wang,Haolan Tan,Songtao Xiang,Yi Xu
A multifunctional microfluidic chip integrated with perfusion cell culture and in situ SERS detection of cell secretion was designed and developed for the detection of IL-6 secretion from LPS-stimulation of A549 cells in this paper. Researching works were focused on A549 cell activity and secretion in the constructed LPS-stimulated A549 cells model. On the designed microchip, a bubble trap chamber was designed to remove the bubbles in the culture medium which could also be simultaneously preheated by a split hot plate. Then, a long-time perfusion culture process of 549 cells could be realized. Under the optimized conditions the A549 cells could be cultured and kept in good activity for more than 36 h. Subsequently, the model of interaction between LPS and A549 cells was established on the designed microchip. When LPS-stimulated A549 cells, the IL-6 which was one of the secretions formed in this process was detected quantitatively by SERS spectral technique. The silver-coated gold nano-stars were prepared and taken as a sensitive enhancing probe for the SERS detection of IL-6 secreted from LPS-stimulated A549 cells. The immunomagnetic beads, IL-6 antigen, and SERS probes were mixed and incubated in the microchip and form a sandwich structure which was captured by the permanent magnet in the detection zone for SERS detection. The reference material of IL-6 was used to establish the calibration curve, and the linear range and detection limit were 1–10000 pg/mL and 0.75 pg/mL, respectively. Then, the IL-6 secretion from LPS-stimulated A549 cells was detected hourly for 7 h by this established method. The process of LPS stimulation of A594 cells did not lead to a sustained increase in the SERS spectral signature of IL-6. Instead, IL6 secretion initially increased sharply, then decreased and eventually stabilized. It could be due to a potential mechanism that the cells self-regulated to mitigate the inflammatory effects in response to sustained stimulation. The proposed multifunctional microfluidic chip, characterized by high sensitivity and the ability to perform continuous hourly detection, exhibited significant application prospects in the study of external stimulation on cells.
研究领域:
生物医学工程
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细胞生物学
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分析化学
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微流控技术
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Xinhui Fan,Ke Li,Xuemei Qin,Zhenyu Li,Yuguang Du
Astragali Radix polysaccharides (APSs) exhibit a broad spectrum of biological activity, which is mainly related to immune regulation. At present, most available studies focus on total APSs or a certain component of APSs. However, structural structure study and screening for the anti-inflammatory activity of polysaccharides with different molecular weights (MW) have yet to be conducted. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of APSs and its fractions. The results revealed that fraction APS-I had better anti-inflammatory effects than APS-II. After APS-Ⅰ was hydrolyzed by trifluoroacetic acid (TFA), the resulting degradation products oligosaccharides were fully methylated. These derivatized oligosaccharides were further analyzed by MALDI-TOF-MS and UPLC-Q-Exactive-MS/MS. The results showed that APS-Ⅰ was a hetero-polysaccharide with a molecular weight of about 2.0 × 106 Da, mainly consisting of glucose (46.8%) and galactose (34.4%). The degree of polymerization of Astragali Radix oligosaccharides (APOS) was 2-16. APOS were identified as 1,4-glucooligosaccharides and 1,4-galactooligosaccharides. The findings of this study lay the foundation for further elucidation of structure-function relationships of APSs and provide guidance for the development of anti-inflammatory drugs.
研究领域:
药理学
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生物化学
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免疫学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
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2024
·
IF 3.8
Linglian Kong,Peng Sun,Xue Pan,Chuanpi Xiao,Bochen Song,Zhigang Song
ABSTRACT Macrophages play a crucial role in both innate and adaptive immunity. However, their abnormal activation can lead to undesirable inflammatory reactions. This study aimed to investigate the effects of glycerol monolaurate (GML), a natural monoester known for its anti-inflammatory and immunoregulatory properties, on avian macrophages using the HD11 cell line. The results indicated that a concentration of 10 μg/mL of GML enhanced the phagocytic activity of HD11 cells ( P < 0.05) without affecting cell viability ( P > 0.05). GML decreased the expression of M1 macrophage polarization markers, such as CD86 and TNF-α genes ( P < 0.05), while increasing the expression of M2 macrophage polarization markers, such as TGF-β1 and IL-10 genes ( P < 0.05). GML suppressed ROS production, apoptosis, and the expression of proinflammatory genes (IL-1β and IL-6) induced by LPS ( P < 0.05). GML also promoted the expression of TGF-β1 and IL-10 ( P < 0.05), both in the presence and absence of LPS exposure. Moreover, GML suppressed the gene expression of TLR4 and NF-κB p65 induced by LPS ( P < 0.05), as well as the phosphorylation of NF-κB p65 ( P < 0.05). In conclusion, GML exhibited regulatory effects on the polarized state of avian macrophages and demonstrated significant anti-apoptotic and anti-inflammatory properties by suppressing intracellular ROS and the NF-κB signaling pathway.
研究领域:
免疫学
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细胞生物学
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兽医学
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DOI
PubMed
高影响因子
Journal of Ocean University of China
·
2024
·Vol. 23
·期 6
·1615-1629
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IF 1.4
Wang Wenwen,Wei Shu,Chen Yadong,Tan Suxu,Shi Kunpeng,Zang Shaoqing,Wang Minmin,Yang Teng,Yang Yingming,Cui Zhongkai,Sha Zhenxia
As an efficient immunostimulant, chitosan oligosaccharide (COS) can enhance the immunity of teleosts; however, the underlying molecular mechanisms still require elucidation. Competing endogenous RNAs (ceRNAs) are vital regulators in the immune response, but their roles in half-smooth tongue sole ( Cynoglossus semilaevis ) remain unclear. In this study, for the first time, we studied whole-transcriptome expression profiles and analyzed ceRNA networks in peripheral blood leukocytes of half-smooth tongue sole treated with COS. A total of 19 circRNAs (DE-circRNAs), 18 miRNAs (DE-miRNAs) and 50 previously identified lncRNAs (DE-lncRNAs) were differentially expressed after COS stimulation. The DE-lncRNAs and DE-miRNAs targeted numerous immunity-related genes, and were enriched in important pathways, including MAPK and Toll-like receptor signaling pathways, suggesting the immunoregulatory roles of COS. Furthermore, we constructed circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA regulatory networks using DE-circRNAs, DE-miRNAs, DE-lncRNAs, and DE-mRNAs. Additionally, a ceRNA network with immunity-related DE-mRNAs was constructed, showing that 3 DE-circRNAs, 12 DE-lncRNAs, and 29 DEGs exhibited crosstalk through 9 DE-miRNAs. Intriguingly, a DE-miRNA in the ceRNA network, miR-144-3p, was targeted by DE-lncRNA tnrc6a , and negatively regulated the genes of inhibitor of nuclear factor kappa B kinases (IKKs) ( ikbkg , ikbkb , and ikbip ) and c3ar1 . Ikbkg , ikbkb , and c3ar1 were significantly up-regulated in macrophages stimulated by LPS. It could be inferred that ncRNAs participated in the immune and inflammatory response by acting as ceRNAs after COS stimulation in teleosts. These findings indicate that COS could enhance the immunity of teleosts by regulating ncRNAs, and lay the foundation for further practical application of COS in aquaculture.
研究领域:
免疫学
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分子生物学
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水产养殖
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转录组学
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DOI
高影响因子
Journal of Biomedical Nanotechnology
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2024
·Vol. 20
·期 8
·1307-1314
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IF 2.9
Zhu Yunhan,Chen Renshou
Sepsis-induced Acute kidney injury (SA-AKI), a common complication in sepsis, significantly impacts patients’ health and quality of life. M1 macrophages have been demonstrated to release inflammatory mediators that exacerbate kidney injury. MiR-155 has been implicated in promoting
inflammation and damage during sepsis while reducing miR-155 levels alleviates SA-AKI. However, the relationship between miR-155 and M1 macrophage-derived exosomes in regulating autophagy during SA-AKI remains unclear. In this study, we aim to investigate the relationship between M1 macrophage-derived
exosomes and miR-155 in regulating autophagy during SA-AKI. A mouse model of SA-AKI was established by performing cecal ligation and puncture (CLP) surgery. Additionally, the HK-2 cell line was utilized to establish a sepsis cell model by inducing lipopolysaccharide (LPS). We demonstrated
that the mice model of SA-AKI exhibited renal injury along with enhanced autophagy, inflammation response, and macrophage polarization after CLP surgery. M1 macrophages attenuated cell viability and enhanced autophagy in LPS-treated HK-2 cells. Additionally, M1 macrophage-derived exosomes
were observed to enhance autophagy in LPS-treated HK-2 cells. Furthermore, we confirmed an increased expression of miR-155 in M1 macrophage-derived exosomes. Furthermore, exosome-mediated miR-155 enhanced autophagy in LPS-treated HK-2 cells. In conclusion, this study provides the first evidence
that exosomal miR-155 derived from M1 macrophages enhances autophagy in SA-AKI. These findings suggest that targeting exosomal miR-155 could be a promising therapeutic strategy for SA-AKI.
研究领域:
免疫学
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肾病学
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分子生物学
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重症医学
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DOI
高影响因子
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