EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Congna Zi,Xian Ma,Maodong Zheng,Ying Zhu
Myocardial injury triggers intense inflammatory reactions and oxidative stress responses. S100 calcium-binding protein A16 (S100A16), a multi-functional calcium (Ca 2+ )-binding protein, participates in inflammatory responses and contributes to ischemia/reperfusion (I/R) injury. Nevertheless, the precise mechanism by which S100A16 operates in myocardial I/R injury remains uncertain. Cardiac I/R injury was produced by ligation/release of the left anterior descending artery, and mouse cardiac cells were subjected to hypoxia/reoxygenation (H/R) to determine the biological effects in vitro . We demonstrated that S100A16 was upregulated in the ischemic hearts and cardiac cells after I/R and H/R injury. Adenovirus-mediated S100A16 inhibition led to a considerable improvement in cardiac function with a reduced infarct size, accompanied by a reduction in cardiomyocyte apoptosis. Similar effects of S100A16 inhibition on inflammation and reactive oxygen species (ROS) production were observed in cultured cardiomyocytes. Importantly, we showed that I/R and H/R treatment upregulated the expression of voltage-dependent anion channel 1 (VDAC1), which subsequently activated NF-κB/p65 to facilitate the binding of NF-κB/p65 to the S100A16 promoter, thereby activating the transcription and expression of S100A16. Mechanically, S100A16 responded to increasing Ca 2+ and interacted with calmodulin (CaM) to regulate the activation of calcium/calmodulin-dependent protein kinase 2 (CAMKK2)/AMPK pathway. In conclusion, VDAC1 sustained the NF-κB p65 pathway activation to elicit increased S100A16 expression, contributing to myocardial damage and heart failure post-I/R via the CaM/CaMKK2/AMPK pathway. This study revealed a crucial role of the VDAC1-S100A16 axis in the process of myocardial I/R injury, providing novel molecular targets for the treatment of cardiac conditions associated with I/R injury.
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高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
IF 3.973
Xiaoying He,Jiali Wang,Qian Wang,Jing Liu,Xi Yang,Lingjuan He,Haihong Hu,Su Zeng,Lushan Yu,Yunqing Qiu,Yan Lou
Hand-foot syndrome (HFS) is a major adverse reaction to capecitabine (CAP). The exact pathogenesis of this disease remains unclear. In this study, metabolomics combined with cell RNA sequencing was used to study the mechanisms of CAP-induced HFS. The murine model of HFS was constructed by intragastric administration of CAP or its metabolites. Quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to verify the mechanisms. Metabolomics showed the phosphatidylinositol signaling pathway and amino acid and fatty acid metabolism to be the major metabolic alterations related to the occurrence of HFS. Transcriptomics profiles further revealed that the cytokine–cytokine receptor interaction, IL17 signaling pathway, Toll-like receptor signaling pathway, arachidonic acid metabolism, MAPK signaling pathway, and JAK-STAT3 signaling pathway were the vital steps in skin toxicity induced by CAP or its metabolites. We also verified that the inflammation mechanisms were primarily mediated by the abnormal expression of interleukin (IL) 6 or IL8 and not exclusively by COX-2 overexpression. Finally, the P38 MAPK, NF-κB, and JAK-STAT3 signaling pathways, which mediate high levels of expression of IL6 or IL8, were identified as potential pathways underlying CAP-induced HFS.
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高影响因子
Antioxidants
·
2021
·Vol. 10
·期 6
·976
·
IF 6.313
Chongshan Dai,Hui Li,Yang Wang,Shusheng Tang,Tony Velkov,Jianzhong Shen
This study investigates the protective effect of baicalein on carbon tetrachloride (CCl4)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl4injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl4exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl4-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl4. In vitro, baicalein treatment improved CCl4-induced decreases of cell viabilities and knockdown ofNrf2and arachidonate 12-lipoxygenase (ALOX12) genes partly abolished the protective effect of baicalein on CCl4-induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl4-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways.Keywords:baicalein;oxidative stress;ferroptosis;acute liver injury;ALOX12 pathway;Nrf2 pathway
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2017
·
IF 2.956
Zhixin Peng,Xiaobao Gong,You Yang,Ligua Huang,Qingyan Zhang,Peng Zhang,Rongzhen Wan,Baoshun Zhang
Quercetin is regarded as a potential hepatoprotective agent in the treatment of acute liver injury. However, the underlying mechanism of how quercetin to protect against lipopolysaccharides/ d -galactosamine (LPS/ d -GalN) induced acute liver injury remains unclear. To investigate the mechanism, the antioxidative, anti-inflammatory and antiapoptotic responses were performed. The results showed that quercetin pretreatment improved the survival rate and substantially reduced the liver histopathological changes in mice. It also alleviated the hepatic damage and reduced the productions of oxidative markers induced by LPS/ d -GalN. In addition, quercetin pretreatment significantly diminished the production of inflammatory cytokines, including TNF-α, IL-6 and IL-1β, and inhibited the activation of the NF-κB and MAPK signaling pathways as well as the expression of apoptotic-related proteins induced by LPS/ d -GalN. We found that the potential mechanism of this quercetin-induced protection is mainly mediated through its powerful antioxidative capacity, inhibition of hepatocyte apoptosis and suppression of inflammatory cytokines through the IKK/NF-κB and MAPK signaling pathways. Thus, quercetin shows a promising therapeutic effect on acute liver injury in mice.
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JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2020
·
IF 4.873
Liu Tang,Xiao-Lei Li,Zi-Xin Deng,Yao Xiao,Ya-Hong Cheng,Jing Li,Hong Ding
Conjugated linoleic acid (CLA), commonly found in beef, lamb and dairy products, has been reported to exhibit anti-inflammatory and antipruritus effects and to inhibit the release of chemical mediators such as histamine and eicosanoid in laboratory rodents. The chief objective of the study is to assess the efficacy of CLA on atopic dermatitis (AD) in mice and to explore possible mechanisms with CLA treatments . To develop a new therapy for AD, the anti-AD potential of CLA was investigated by inducing AD-like skin lesions in mice using 2,4-dinitrofluorobenzene. We evaluated dermatitis severity; histopathological changes; serum levels of T helper (Th) cytokines (interferon-γ, interleukin-4); changes in protein expression by western blotting and immunohistochemistry staining for cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), toll like receptor 4 (TLR-4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB) and tumor necrosis factor α (TNF-α); and production of the proinflammatory lipid mediators, such as prostaglandin E 2 and leukotriene B4 , in the skin lesions. Treatment with CLA ameliorated the development of AD-like clinical symptoms and effectively inhibited epidermal hyperplasia and infiltration of mast cells and CD4 + T cells in the AD mouse skin. Total serum immunoglobulin E levels and the expression levels of Th1/Th2 cytokines and lipid mediators in dorsal skin were dramatically suppressed by CLA. Furthermore, CLA down-regulated the expressions of COX-2, 5-LOX, TLR4, MyD88, NF-κB and TNF-α. Taken together, our findings demonstrate the potential usefulness of CLA as an anti-inflammatory dietary supplement or drug for the prevention and management of AD skin diseases by modulating the COX-2/5-LOX and TLR4/MyD88/NF-κB signaling pathways .
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Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Rui Yang,Yurong Yan,Zheng Wu,Yong Wei,Hao Song,Lian Zhu,Chenchen Zhao,Na Xu,Jijiang Fu,Kaifu Huo
Although titanium and its alloys are widely used in bone surgeries, the implantation failures caused by sterile inflammation still occur. The excessive reactive oxygen species (ROS) in the peri-implant region are considered to cause inflammation and impede the osseointegration of titanium implants. In this study, a coating of resveratrol-loaded titania nanotube (TNT-Res) for eliminating ROS was fabricated on titanium surface through electrochemical anodization and following surface adsorption of resveratrol. The resveratrol concentration of released from TNT-Res coating was controlled by modulating the loading amount. The ROS production in macrophage cell lineage RAW 264.7 and bone mesenchymal stem cells (BMSCs) were significantly decreased when cultured on TNT-Res coatings. The pro-inflammatory factors, including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), and NO produced by RAW 264.7 cells were reduced when cells were cultured on TNT-Res coatings. These results proved that the TNT-Res coating can effectively eliminate ROS and inhibit inflammation. Moreover, the osteogenic indicators, including alkaline phosphatase (ALP) production, extracellular calcium deposition, and osteogenesis-related gene expression, including collagen І (Col-І), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2), were significantly promoted for TNT-Res groups, which demonstrated that the TNT-Res coating can enhance the osteogenic differentiation of BMSCs. Additionally, the phosphorylation of nuclear factor κ-B (NF-κB) were down-regulated both in RAW 264.7 cells and BMSCs, which indicated that the TNT-Res coating could inhibit inflammation and promote osteogenesis by inhibiting the activation of NF-κB signaling pathway. The TNT-Res coating could be an effective implant surface for improving osseointegration ability of titanium implants.
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高影响因子
EXPERIMENTAL ANIMALS
·
2022
·
IF 1.798
Zhanchun SONG,Xiaozeng WANG,Lianqi HE,Liang CHEN,Zhichao REN,Siyu SONG
Myocardial infarction (MI) as the remarkable presentation of coronary artery disease is still a reason for morbidity and mortality in worldwide. Lysosomal-associated protein transmembrane 5 (LAPTM5) is a lysosomal-related protein found in hematopoietic tissues and has been confirmed as a positive regulator of pro-inflammatory pathways in macrophages. However, the role of LAPTM5 in MI remains unknown. In this study, we found that both mRNA and protein expression levels of LAPTM5 were significantly elevated in MI mice. Suppression of LAPTM5 in myocardial tissues decreased cardiac fibrosis and improved cardiac function after MI. At the molecular level, downregulated LAPTM5 dramatically suppressed the macrophage activation and inflammatory response via inhibiting the activation of the NF-κB pathway. Collectively, suppression of LAPTM5 in myocardial tissues inhibits the pro-inflammatory response and the cardiac dysfunction caused by MI. This study indicated that LAPTM5 as a pro-inflammatory factor plays a crucial role in MI disease.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Hongyan Li,Yiying Fu,Wangbao Gong,Guangjun Wang,Zhifei Li,Jingjing Tian,Kai Zhang,Ermeng Yu,Yun Xia,Wenping Xie,Jun Xie
The pregnane X receptor (PXR) / nuclear factor-kB (NF-kB) signaling pathway plays a critical role in regulating toxin-induced inflammation and apoptosis in mammals. Whether dietary curcumin (CUR) can prevent copper (Cu)-induced liver injury via this signaling pathway remains to be established in aquatic animals. Juvenile largemouth bass ( Micropterus salmoides ) were exposed to dietary Cu and CUR treatments for 8 weeks. The results showed that chronic Cu exposure induced oxidative stress, causing liver function damage and liver injury. Cu exposure stimulated inflammation by regulating nf-kb and pro-inflammatory genes such as tnfα and il-1β and promoted apoptotic signals in the liver by modulating bcl2 and casp3 mRNA levels. In addition, Pearson correlation analysis verified that inflammatory and apoptotic responses were important indicators of Cu-induced liver injury. CUR attenuated stress responses by enhancing the antioxidant system. Importantly, CUR significantly stimulated PXR mRNA and protein levels in the Cu + CUR group and suppressed NF-κB activation to inhibit the inflammatory and apoptotic signaling cascade. These results suggest that CUR may be an effective activator of PXR in teleost fishes, exerting cytoprotective effects on Cu-induced liver injury via a PXR-mediated NF-κB repression mechanism. In conclusion, this study is the first to demonstrate that CUR may act as a potent PXR ligand that exerts hepatoprotective effects against Cu-induced liver injury. The findings shed light on the specific regulatory role of the PXR/NF-κB signaling pathway in liver pathogenesis and its potential as a therapeutic target in teleost fishes.
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高影响因子
NEUROREPORT
·
2024
·
IF 1.6
Bian Jing,Liu Chunxu,Li Xiang,Qin Xiaoye,Wang Feng,Xuan Lina,Zhang Weimin
This study aims to investigate how electroacupuncture regulates the learning and memory abilities of poststroke cognitive impairment (PSCI) rats through the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia. Thirty male rats were randomly divided into three groups: sham surgery group, PSCI model group, and electroacupuncture group, with 10 rats in each group. Middle cerebral artery occlusion was used to establish the PSCI model. The Zea Longa method was used to score the rats’ neurological function. Electroacupuncture was utilized for 21 days to improve PSCI. The learning and memory abilities of rats were tested using the Morris water maze. Hematoxylin–eosin staining and immunofluorescence were used to find the hippocampus’ pathological changes. The concentration of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-18 were detected by ELISA. The mRNA expression levels of associated inflammatory corpuscles were measured by quantitative real-time PCR. The protein expression levels of TLR4, MyD88, NF-κB, and NLRP3 were measured using western blotting. Electroacupuncture improved not only the learning and memory abilities of PSCI rats but also hippocampal morphology. Electroacupuncture inhibited the activation of microglia and the TLR4/NF-κB/NLRP3 signaling pathway. Electroacupuncture also reduced proinflammatory factors and restrained the mRNA levels of NLRP3-associated inflammatory cytokines. Its mechanism was related to inhibiting the expression of the TLR4/NF-κB/NLRP3 signaling pathway, attenuating the release of inflammatory factors, and regulating the activation of hippocampal microglia in the brain.
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高影响因子
Foods
·
2025
·Vol. 14
·期 7
·1270
·
IF 5.1
Jiali Tang,Mengyao Zhang,Jiaying Wang,Haijing Zhang,Zhong Wang,Ziteng Lei,Chengtao Wang,Wei Chen
Inflammatory bowel disease (IBD) is a chronic disease influenced by a complex interplay of factors, including genetics, environmental, and gut microbiota. This study aimed to explore the therapeutic potential of the natural polyphenolic compound hydroxytyrosol (HT) in modulating dextran sodium sulfate (DSS)-induced colitis in mice. The findings demonstrate that oral administration of HT significantly alleviated colitis symptoms, as evidenced by a reduction in the disease activity index and improvements in colonic pathology. HT was found to inhibit the release of pro-inflammatory cytokines, enhance antioxidant status, and mitigate oxidative stress. Furthermore, HT contributed to the restoration of the gut barrier by reinstating tight junction proteins, reducing the inflammatory marker lipopolysaccharide (LPS), and suppressing inflammation-related genes. This compound also modulated the NLRP3-Cas-1-GSDMD-IL-1β inflammatory pathway and inhibited the NF-κB (nuclear factor kappa B) pathway, thereby alleviating colitis. Gut microbial analysis revealed that HT enriched the abundance of Bacteroidota and altered the balance between Bacteroidota and Firmicutes in mice. Correlation analysis between bacterial microbiota and inflammatory factors suggested that HT may alleviate colitis by modulating the relative abundance of Alistipes , Bacteroides , and unclassified_f__ Muribaculaceae . These findings underscore the potential of HT as a therapeutic agent in the treatment of colitis.
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Aging-US
·
2021
·
IF 5.682
Qin Wu,Yuhua Wang,Qingfang Li
Brain injury is a familiar complication of severe sepsis, in which excessive inflammation and oxidative stress are the main mechanisms leading to acute brain injury. Here, we focus on probing the function and mechanism of Matairesinol (Mat) in sepsis-mediated brain injury. We established a rat sepsis model by cecal ligation and perforation (CLP) and constructed an in vitro sepsis model by treating neurons and microglia with lipopolysaccharide (LPS). Rats and cells were treated with varying concentrations of Mat, and the changes of neural function, neuronal apoptosis, microglial activation, neuroinflammation and the expression of oxidative stress factors in brain tissues were examined. Additionally, the activation of the MAPK, NF-κB and AMPK pathways in brain tissues and cells was evaluated by Western blot (WB) and/or immunohistochemistry (IHC). Our findings illustrated that Mat improved neuronal apoptosis and weakened microglial activation in CLP rats. Meanwhile, Mat hampered the expression of pro-inflammatory factors (TNF-α, IL-1β, IL-6, IFN-γ, IL-8, and MCP1) and facilitated the contents of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in brain tissues and microglia. Mechanistically, Mat concentration-dependently dampened the phosphorylation of MAPK, JNK and NF-κB in CLP rats and LPS-stimulated microglia and up-regulated Nrf2 and HO-1. Besides, Mat facilitated the AMPK expression. Meanwhile, Compound C, a specific inhibitor of the AMPK pathway, substantially reduced the neuronal protection and anti-inflammatory effects mediated by Mat. Overall, Mat exerts anti-inflammatory and anti-oxidative stress effects by up-regulating AMPK, thereby ameliorating sepsis-mediated brain injury.
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高影响因子
Journal of Biomedical Nanotechnology
·
2015
·Vol. 11
·期 3
·403-415
·
IF 5.338
Wang Jiao,Zhu Rongrong,Sun Dongmei,Sun Xiaoyu,Geng Zhengsong,Liu Hui,Wang Shi-Long
Curcumin (Cur) is a naturally derived, novel anti-inflammatory agent, but its poor solubility limits its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) to improve its anti-inflammatory activity. The Cur-loaded SLNs (Cur-SLNs)
were prepared using emulsification and low-temperature solidification methods. In contrast to free Cur, the particles were well dispersed in aqueous medium, showing a narrow size distribution with a range of 55 ± 1.2 nm, a zeta potential value of –26.2 ± 1.3 mV, and a high
drug loading efficiency of 37% ± 2.5%. The sustained release of Cur was observed for up to 6 days. The particles displayed enhanced stability in phosphate-buffered saline by protecting the encapsulated Cur against hydrolysis and biotransformation, as well as increasing biocompatibility.
Cur-SLNs were more effective than free Cur at reducing the expression levels of several proinflammatory mediators, including inflammatory cytokines (IL-6, TNF-α, and IL-1β) and nitric oxide (NO), under in vitro conditions. By Western blotting, we found that
Cur-SLNs were more active than free Cur in inhibiting the LPS-induced activation of the inflammatory transcription factor NF-κB through the suppression of IκB kinase activation. Compared to free Cur, Cur-SLNs had an increased intracellular uptake over time (observed
after 24 h) in RAW264.7 cells. Moreover, the Cur-SLNs (≥20 μM) significantly improved RAW264.7 cell viability by inhibiting apoptosis. Thus, these results demonstrated that SLNs could be used as potential anti-inflammatory drug carriers for the treatment of various chronic diseases.
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