CELLULAR SIGNALLING
·
2024
·
IF 4.4
Zheng-Ming Cao,Su Fu,Chao Dong,Teng-Yue Yang,Xiao-Kang Liu,Chun-Lin Zhang,Dong-Zhe Li
The progression of osteoarthritis (OA) includes the initial inflammation, subsequent degradation of the extracellular matrix (ECM), and chondrocyte apoptosis. Down syndrome candidate region 1 (DSCR1) is a stress-responsive gene and expresses in varied types of cells, including chondrocytes. Bioinformatics analysis of GSE103416 and GSE104739 datasets showed higher DSCR1 expression in the inflamed cartilage tissues and chondrocytes of OA. DSCR1 had two major isoforms, isoform 1 (DSCR1–1) and isoform 4 (DSCR1–4). We found that DSCR1–1 had a faster ( in vitro ) and higher expression ( in vivo ) response to OA compared to DSCR1–4. IL-1β-induced apoptosis, inflammation, and ECM degradation in chondrocytes were attenuated by DSCR1–1 overexpression. DSCR1–1 triggered the phosphorylation of cAMP response element-binding 1 (CREB1) at 133 serine sites by decreasing calcineurin activity. Moreover, activated CREB1 moved into the cell nucleus and combined in the promoter regions of aldehyde dehydrogenase 2 (ALDH2), thus enhancing its gene transcription. ALDH2 could recover Wnt/β-catenin signaling transduction by enhancing phosphorylation of β-catenin at 33/37 serine sites and inhibiting the migration of β-catenin protein from the cellular matrix to the nucleus. In vivo , adenoviruses (1 × 10 8 PFU) overexpressing DSCR1–1 were injected into the articular cavity of C57BL/6 mice with medial meniscus surgery-induced OA, and it showed that DSCR1–1 overexpression ameliorated cartilage injury. Collectively, our study demonstrates that DSCR1–1 may be a potential therapeutic target of OA.
研究领域:
骨科
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2018
·
IF 3.234
Rongzong Qiu,Weifeng Yao,Haocong Ji,Dongdong Yuan,Xiaofeng Gao,Weiping Sha,Fei Wang,Pinjie Huang,Ziqing Hei
Background Acute kidney injury occurred after sepsis, resulting in high mortality. This research aims to elucidate the mechanistic effect of DEX on the renal inflammation resolution during sepsis in rats. Methods The rats were randomly divided into a sham group and the other three cecal ligation and puncture (CLP) model groups, based on different treatments: placebo, DEX and 2-adrenergic receptor (AR) inhibitor atipamezole (AT) treatment (DEX + AT) groups. The survival of septic rats within 24 h was recorded. Tissue pathology, plasma IL-1β, IL-6, TNF-α, lipoxygenase-5 and lipoxin A4 were evaluated. Western blotting and immunostaining was used to determine expression of TLR4 , IκB , IKK , NF-κB p65 and pp65 in kidney tissue. Then qPCR was used to analyze the mRNA expression of renal α 2A -AR, α 2B -AR and α 2C -AR. Results Rat mortality and kidney inflammation were significantly increased in septic rats. Specifically, IL-1β, IL-6 and TNF-α plasma levels, NF-κB activity, and TLR4 expression in rat kidney tissues were increased after CLP. In the DEX treatment group, mortality was reduced, histology changes were minor, and lipoxygenase-5, and lipoxin A4 expression were increased. The expression of IL-1β, IL-6 and TNF-α, NF-κB activity and TLR4 expression in rat kidney tissues were also decreased. These results indicated that DEX treatment alleviates acute kidney injury induced by CLP. However, the effects of DEX were apparently suppressed by atipamezole in the DEX + AT group. Conclusion The current study demonstrated the protective effect of DEX on CLP-induced kidney injury, which may be effective by attenuating NF-κB pathway activation with lipoxin A4.
研究领域:
药理学
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肾病学
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免疫学
·
重症医学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Hailin Liu,Xiuli Zhang,Xinglong Zhong,Zehua Li,Shaoai Cai,Pingzhen Yang,Caiwen Ou,Minsheng Chen
The risk of cardiovascular events in patients with chronic kidney disease is tremendously increased due to vascular calcification . Local vascular inflammation significantly promotes vascular calcification. A previous study has shown that puerarin inhibits calcification of mouse vascular smooth muscle cells (VSMCs) in vitro, but whether puerarin can inhibit vascular calcification in vivo and the underlying mechanisms remain unclear. In this study, we found that rat VSMCs treated with calcifying medium showed more mineral deposition, and this effect was inhibited by puerarin in a dose-dependent manner, as detected by alizarin red staining and calcium content assay. Puerarin also prevented the trans-differentiation of VSMCs into osteoblast-like cells, indicated by down-regulation of bone-related genes including Runx2 and BMP2 . In vivo study of uremic rats induced by renal nephrectomy further confirmed the inhibitory effect of puerarin on vascular calcification in uremic rats. Puerarin treatment significantly prevented mineral deposition in rat aortas and down-regulated the expression of Runx2 and BMP2. Furthermore, we detected the levels of pro-inflammatory cytokines including IL-1β, IL-6, IL-18 and TNFα in vitro and in vivo . The levels of IL-1β were remarkably increased in both calcified VSMCs and aortas of uremic rats, while puerarin treatment markedly decreased the expression of IL-1β. In addition, we found that puerarin reduced IL-1β possibly through targeting NLRP3/Caspase1/IL-1β and NF-κB signaling pathways and inhibiting the generation of reactive oxygen species . Taken together, we demonstrated that puerarin has the capability of inhibiting vascular calcification in uremic rats by inhibiting inflammation.
研究领域:
药理学
·
心血管疾病
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肾脏疾病
·
炎症
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2022
·Vol. 46
·期 12
·e14460
·
IF 3.654
Jing Guo,Jian-Kai Tang,Bai-Fang Wang,Wen-Rui Yan,Ting Li,Xue-Jian Guo,Lei Zhang,Tao Wang,Qian-Yun Sun,Li-Wei Zhang
Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1β, NO, and PGE 2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. Practical applications Phillygenin is one of the major active ingredients in Forsythia suspensa . But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.
研究领域:
药理学
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炎症
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疼痛管理
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天然产物
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传统中药
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2017
·Vol. 40
·期 6
·1709-1718
·
IF 2.341
Baochao Ji,Wentao Guo,Hairong Ma,Boyong Xu,Wenbo Mu,Zhendong Zhang,Abdusami Amat,Li Cao
Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been demonstrated to exert attenuation of the nuclear factor-κB (NF-κB) signaling pathway and anti-inflammatory activity in a wide variety of cells. In the present study, the authors first evaluated the effects of ISL on cartilage degeneration in interleukin-1β (IL-1β)-stimulated chondrocyte-like ATDC5 cells and in a mouse model of osteoarthritis (OA). The data of a cell counting kit-8 and flow cytometry assay indicated that ISL suppressed the inhibitory effect of IL-1β on cell viability. The mRNA and protein expression levels of cyclooxygenase-2 and matrix metalloproteinase-13 were significantly decreased, while the expression of collagen II was increased, as indicated by RT-qPCR and western blot analysis following the chondrocyte-like ATDC5 cells were co-intervened with IL-1β and ISL for 48 h. Also, ISL attenuated protein expressions level of pro-apoptotic Bax, cleaved-caspase-3 and cleaved-caspase-9 and promoted expression of anti-apoptotic Bcl-2. Moreover, ISL inhibited NF-κB p65 phosphorylation induced by IL-1β. In addition, ISL also increased improved the thickness of hyaline cartilage and the production of proteoglycans in the cartilage matrix in a mouse OA model. These results indicated that ISL exerted anti-inflammatory and anti-apoptotic effects on IL-1β-stimulated chondrocyte-like ATDC5 cells, which may be associated with the downregulation of the NF-κB signaling pathway. In this way, the data supported the conclusion that ISL may be a novel potential preventive agent suitable for use in OA therapy.
研究领域:
药理学
·
风湿病学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Haocong Zhang,Liangbi Xiang,Hong Yuan,Hailong Yu
Spinal cord injury (SCI) is a severe central nervous system injury and microglia are major participants in neuroinflammation after injury. ADP-ribosylation factor-like GTPase 11 (ARL11) is a GTP-binding protein. Whether ARL11 is involved in the SCI progression is unknown. In the impactor-induced moderate SCI mouse model, ARL11 protein and mRNA expression were significantly increased in the injury site. LPS (100 ng/mL) and IFN-γ (20 ng/mL) were incubated with BV2 cells (immortalized mouse microglial cell line) to drive them into an M1-like phenotype. ARL11 up-regulation was also observed in activated microglia in SCI mice and LPS and IFN-γ treated BV2 cells. Basso Mouse Scale scores and inclined plate test revealed that ARL11 deletion promoted motor function recovery in SCI mice. Pathological examination showed ARL11 knockdown reduced spinal cord tissue damage, increased neuron numbers, and inhibited neuronal apoptosis in SCI mice. ARL11 knockdown notably inhibited IL-1β and IL-6 production in vivo and in vitro. Furthermore, ARL11 deletion significantly inhibited iNOS protein and mRNA expression in vivo and in vitro, and COX-2 expression in vivo . Mechanism studies revealed that ARL11 silencing decreased phosphorylated ERK1/2 protein expression. Additionally, ELF1 knockdown significantly inhibited ARL11 protein and mRNA expression in vitro . ELF1 acted as a transcription activator in regulating ARL11 expression by binding to the promoter. In conclusion, ARL11 knockdown protects neurons by inhibiting M1 microglia-induced neuroinflammation, thereby promoting motor functional recovery in SCI mice. This may occur in part under the regulation of ELF1. Our study provides a new molecular target for SCI treatment.
研究领域:
神经科学
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炎症
·
分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Immunology Research
·
2020
·
IF 3.327
Yanan Shi,Jingming Xu,Bin Ding,Guiping Chen,Lu Jin,Liang Ke,Xiao Xu,JingXia Wang,Qiuhua Sun,Xiaohong Xu
Constipation, a gastrointestinal function disorder, is one of the side effects of paclitaxel (PTX) chemotherapy. Shenhuang plaster (SHP) application on the Shenque acupoint promotes gut motility in clinical settings. In this study, we elucidated the ingredients in SHP and evaluated its effects on PTX-induced constipation using a tumour-bearing mouse model. SHP was prepared using the traditional Chinese plaster preparation method. The ingredients were analysed using UPLC-MS/MS and identified via screening in a standard drug database. The gastrointestinal transit was evaluated by the movement of a fluorescein-labelled dextran in the gastrointestinal tract. A histological study of the mucosa was carried out after haematoxylin and eosin staining. mRNA expression was assessed using real-time RT-PCR, and the foetal microbiota composition was elucidated through 16 s rDNA sequencing and BLAST analysis. Our results indicate that the application of SHP attenuated weight gain inhibition by PTX; however, no inhibitory effect was observed on tumour growth. PTX-induced sluggish intestine, villus, and mucosal base layer damage were significantly improved following the application of SHP. Further, SHP enhanced the stimulation efficiency of PTX on TLR4 and its downstream cytokines, as well as on IL-1β in intestinal cells. SHP combined with PTX reshaped the microbiota, which showed beneficial effects on health. Hence, these results provide evidence that SHP alleviates PTX-induced constipation and intestinal morphological damage but augments the effects of PTX on the expression of cytokines in the TLR4 pathway and IL-1β. Therefore, we propose that SHP stimulates the host immune response to eradicate cancer cells.
研究领域:
药理学
·
肿瘤学
·
中医
·
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Yanke Lin,Shuai Wang,Zemin Yang,Lu Gao,Ziyue Zhou,Pei Yu,Baojian Wu
Bilirubin is an endogenous substance derived from heme catabolism. In this study, we aimed to assess the anti-inflammatory activity of bilirubin, and to determine the mechanism thereof. The anti-inflammatory activity of bilirubin was evaluated using lipopolysaccharide (LPS)-treated peritoneal macrophages (PMs) and Raw264.7 cells, and mice with alum-induced peritonitis. The mRNA and proteins of NOD-like receptor family pyrin domain containing 3 (Nlrp3) and inflammatory cytokines were determined using qPCR and Western blotting, respectively. Distribution of phosphorylated (p) p65 [a NF-κB (nuclear factor-κB) subunit] in the cytoplasm and nucleus were evaluated by immunofluorescence analysis and electrophoretic mobility shift assay. Bilirubin prior to LPS treatment decreased protein expressions of Nlrp3, pro-interleukin (IL)-1β and mature IL-1β in PMs, whereas bilirubin post LPS treatment showed no effects. Bilirubin prior to LPS treatment dose-dependently repressed expressions of Nlrp3 and IL-1β, and inhibited translocation of p-p65 to nucleus in Raw264.7 cells. Bilirubin treatment decreased myeloperoxidase activity and reduced the levels of inflammatory cytokines (i.e., IL-1β, TNFα and IL-6) in lavage fluid in mice with alum-induced peritonitis. This was accompanied by a lower mortality rate. In addition, the mRNAs of Nlr p3 and IL-1β in peritoneal exudates cells were decreased, and the levels of p-p65 and mature IL-1β proteins were reduced. In conclusion, bilirubin acted on inflammation and alleviated alum–induced peritonitis through inactivation of Nlrp3 inflammasome.
研究领域:
免疫学
·
炎症
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2017
·Vol. 12
·期 7
·e0181094
·
IF 2.806
Qi Sun,Jiajin Zhu,Feiwei Cao,Fengjia Chen
Chimonanthus nitens Oliv. (CN) is a species in the family Calycanthaceae. Its leaf is widely used to make traditional herbal tea in southern China and has a wide range of therapeutic effects. The profile of the ethanol extracts from CN leaves was identified by UPLC-QTOF-MS/MS. Forty seven compounds were determined including organic acids, phenolic acids and derivatives, flavonoids, coumarins, fatty acids and other compounds. The effect of the CN extracts on the inflammatory damage in zebrafish and in RAW 264.7 cells was investigated. The extracts demonstrated a strong ability to inhibit the recruitment of neutrophils in LPS-stimulated zebrafish, but macrophage migration was not significantly affected. Pro-inflammatory cytokines (i.e., TNF-α, IL-6 and IL-1β) were also determined by q-PCR. The extracts strongly reduced mRNA expression of TNF-α, IL-6 but not IL-1β in zebrafish model, while significantly inhibited the production of the factors in the RAW 264.7 cells. Therefore, our results suggest that the ethanol extracts of CN leaves may serve as a source of nutraceutical compounds with anti-inflammatory properties.
研究领域:
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Ji-Chun Ge,Xue-Qiang Zha,Chun-Yan Nie,Nian-Jun Yu,Qiang-Ming Li,Dai-Yin Peng,Jun Duan,Li-Hua Pan,Jian-Ping Luo
The present work investigated the inhibitory activity of the polysaccharide from cultivated Dendrobium huoshanense (cDHP) on lung inflammation in cigarette smoke (CS)-induced mouse model. cDHP was mainly composed of mannose and glucose in a molar ratio of 1.89: 1.00, and had a backbone with linkages of 1,4-Man p , 1,4-Glc p , 1,4,6-Man p and 1-Glc p . Hematoxylin and Eosin (HE) staining and immunohistochemistry analysis showed that cDHP can increase alveolar number, thicken alveolar wall, inhibit pulmonary bulla formation and decrease inflammatory cell infiltration as compared to the model group. ELISA determination revealed that cDHP can inhibit CS-induced enhancement in TNF-α and IL-1β secretion in serum and lung. These results suggested that cDHP can resist CS-induced lung inflammation. Further, the phosphorylation analysis of p65, IκB, p38 and JNK as well as the DNA binding activity analysis of NF-κB and AP-1 implied that the anti-inflammation function of cDHP is mediated via regulating NF-κB and MAPK signaling.
研究领域:
药理学
·
免疫学
·
呼吸病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Ruibang Wu,Leizhen Huang,Qinghong Xia,Zheng Liu,Yong Huang,Yulin Jiang,Juehan Wang,Hong Ding,Ce Zhu,Yueming Song,Limin Liu,Li Zhang,Ganjun Feng
Intervertebral disc degeneration (IDD) is a major contributing factor to both lower back and neck pain. As IDD progresses, the intervertebral disc (IVD) loses its ability to maintain its disc height when subjected to axial loading. This failure in the weight-bearing capacity of the IVD is a characteristic feature of degeneration. Natural polymer-based hydrogel, derived from biological polymers, possesses biocompatibility and is able to mimic the structure of extracellular matrix, enabling them to support cellular behavior. However, their mechanical performance is relatively poor, thus limiting their application in IVD regeneration. In this study, we developed an injectable composite hydrogel, namely, Mel-MBG/SA, which is similar to natural weight-bearing IVD. Mesoporous bioactive glasses not only enhance hydrogels, but also act as carriers for melatonin (Mel) to suppress inflammation during IDD. The Mel-MBG/SA hydrogel further provides a mixed system with sustained Mel release to alleviate IL-1β-induced oxidative stress and relieve inflammation associated with IDD pathology. Furthermore, our study shows that this delivery system can effectively suppress inflammation in the rat tail model, which is expected to further promote IVD regeneration. This approach presents a novel strategy for promoting tissue regeneration by effectively modulating the inflammatory environment while harnessing the mechanical properties of the material.
研究领域:
生物医学工程
·
组织工程
·
骨科
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 7
·2114
·
IF 4.927
Yi Li,Xia-Jin Liu,Shu-Lan Su,Hui Yan,Sheng Guo,Da-Wei Qian,Jin-Ao Duan
Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1β, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1β, IL-8 and MMP9.Keywords:Flos Chrysanthemi;chrysanthemum stem and leaf;inflammatory bowel disease (IBD);zebrafish;UPLC-TQ/MS
研究领域:
药理学
·
炎症研究
·
水生毒理学
·
分析化学
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DOI
PubMed
高影响因子
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