Frontiers in Physiology
·
2023
·
IF 4
Senyue Liu,Lin Luo,Fengyuan Zuo,Xiaoli Huang,Liang Zhong,Sha Liu,Yi Geng,Yangping Ou,Defang Chen,Wenlong Cai,Yongqiang Deng
Nitrogen from ammonia is one of the most common pollutants toxics to aquatic species in aquatic environment. The intestinal mucosa is one of the key mucosal defenses of aquatic species, and the accumulation of ammonia nitrogen in water environment will cause irreversible damage to intestinal function. In this study, histology, immunohistochemistry, ultrastructural pathology, enzyme activity analysis and qRT-PCR were performed to reveal the toxic effect of ammonia nitrogen stress on the intestine of Pelteobagrus fulvidraco . According to histological findings, ammonia nitrogen stress caused structural damage to the intestine and reduced the number of mucous cells. Enzyme activity analysis revealed that the activity of bactericidal substances (Lysozyme, alkaline phosphatase, and ACP) had decreased. The ultrastructure revealed sparse and shortened microvilli as well as badly degraded tight junctions. Immunohistochemistry for ZO-1 demonstrated an impaired intestinal mucosal barrier. Furthermore, qRT-PCR revealed that tight junction related genes ( ZO-1, Occludin, Claudin-1 ) were downregulated, while the pore-forming protein Claudin-2 was upregulated. Furthermore, as ammonia nitrogen concentration grew, so did the positive signal of Zap-70 (T/NK cell) and the expression of inflammation-related genes ( TNF , IL-1β , IL-8, IL-10) . In light of the above findings, we conclude that ammonia nitrogen stress damages intestinal mucosal barrier of Pelteobagrus fulvidraco and induces intestinal inflammation.
研究领域:
水生毒理学
·
环境科学
·
鱼类生理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Aili Suo,Weijun Xu,Yaping Wang,Tiantian Sun,Lijie Ji,Junmin Qian
In tumor biology, it is widely recognized that 3D rather than 2D cell culture can recapitulate key features of solid tumors, including cell-extracellular matrix (ECM) interactions. In this study, to mimick the ECM of breast cancer, hyaluronic acid (HA) hydrogels were synthesized from two polyvalent HA derivatives through a hydrazone and photo dual crosslinking process. HA hydrogels could be formed within 120 s. The hydrogels had similar topography and mechanical properties to breast tumor and displayed glutathione and hyaluronidase dual-responsive degradation behavior. Biological studies demonstrated that HA hydrogel could support the proliferation and clustering of breast cancer MCF-7 cells. The expression levels of VEGF, IL-8 and bFGF in hydrogel-cultured cells were significantly greater than those in 2D culture. Moreover, cells from hydrogel culture exhibited greater migration/invasion abilities and tumorigenicity than 2D-cultured cells. Therefore, the HA hydrogels are a promising ECM-mimicking matrix for in vitro construction of breast cancer.
研究领域:
生物材料
·
癌症生物学
·
组织工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xi Chen,Di Wang,Xuejun Guo,Xiaoming Li,Wenjing Ye,Yang Qi,Wen Gu
The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin's effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.
研究领域:
药理学
·
纳米技术
·
呼吸医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Zekun Li,Jun Guo,Kun Jia,Zhiguo Zheng,Xiaomei Chen,Zhonghui Bai,Yuhao Yang,Bo Chen,Wei Yuan,Weihua Chen,Jian Yang
Oxyfluorfen (OXY) is widely used in agriculture as a herbicide, resulting in its continuous accumulation in the environment. The presence of OXY can be detected in soil and rivers. However, until now, the potential toxicity of OXY to aquatic organisms has not been evaluated. In this study, zebrafish was used as a model animal to evaluate OXY-induced liver toxicity. The study found that 0.25, 0.5, and 1 mg/L of OXY affected the early development of zebrafish and severely damaged the lipid and sugar metabolism in the liver of zebrafish larvae. Furthermore, a metabolic function disorder caused liver damage. OXY also caused inflammation by upregulating the inflammatory factors IL-6 , IL-8 , and TNF-α , and activated the apoptotic pathway to inhibit hepatocyte proliferation, resulting in zebrafish liver toxicity. Our research showed that OXY had certain toxic effects on zebrafish development and liver and could cause potential harm to other aquatic organisms and humans.
研究领域:
环境毒理学
·
水生生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yuling Tong,Ruilin Wang,Xia Liu,Miao Tian,Yanling Wang,Yanfei Cui,Wenjun Zou,Yanling Zhao
Ethnopharmacological relevance Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases . Aim of this study The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG . Materials and methods The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot . Results The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. Conclusion ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.
研究领域:
药理学
·
民族药理学
·
胃肠病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2020
·Vol. 20
·期 1
·1-9
·
IF 0
Li Jiashun,Jie Xiang,Liang Xiaoli,Chen Ziyu,Xie Peifang,Pan Xiping,Zhou Beixian,Li Jing
Background Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the anti-inflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations. Methods The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virus-triggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. Results Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E 2 (PGE 2 ) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings. Conclusion Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.
研究领域:
药理学
·
免疫学
·
病毒学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
Frontiers in Pharmacology
·
2019
·
IF 3.845
Linghu Ke-Gang,Wu Guo-Ping,Fu Ling-Yun,Yang Hong,Li Hai-Zhi,Chen Yan,Yu Hua,Tao Ling,Shen Xiang-Chun
1,8-Cineole (eucalyptol), a monoterpene, has been widely reported for the anti-inflammatory effects. Our previous data confirmed that 1,8-cineole ameliorated the inflammatory phenotype of human umbilical vein endothelial cells (HUVECs) by mediating NF-κB expression in vitro. At present, we investigated the protection effects of 1,8-cineole on vascular endothelium in lipopolysaccharide (LPS)-induced acute inflammatory injury mice and the potential mechanisms involved in the protection in HUVECs. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed the secretion of interleukin (IL)-6 and IL-8 and increased the expression of IL-10 in the serum of LPS-induced mice. 1,8-Cineole reduced the inflammatory infiltration and the expression of vascular cell adhesion molecular 1 (VCAM-1) in the sections of thoracic aorta in LPS-induced acute inflammatory mice. Western blotting indicated that 1,8-cineole significantly decreased the phosphorylation of NF-κB p65 and increased the expression of PPAR-γ in the thoracic aorta tissue. 1,8-Cineole increased the expression of PPAR-γ in LPS-induced HUVECs. 1,8-Cineole and rosiglitazone reduced the protein and mRNA levels of VCAM-1, E-selectin, IL-6, and IL-8 in LPS-induced HUVECs, which could be reversed by the action of GW9662 (inhibitor of PPAR-γ). 1,8-Cineole and rosiglitazone blocked the LPS-induced IκBα degradation and NF-κB p65 nucleus translocation, which could be reversed by the pretreatment of GW9662 or silence of PPAR-γ gene. In conclusion, 1,8-cineole attenuated LPS-induced vascular endothelial cells injury via PPAR-γ dependent modulation of NF-κB.
研究领域:
药理学
·
免疫学
·
分子生物学
·
心血管科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Ping Guan,Zhaoxu Meng,Xinran Liu,Jiaxiang Mu,Zichun Gao,Xinrong Yu,He Lian
The complex, invasive, and metastatic nature of malignant tumors make the current treatment of patients challenging in advanced stages. The present study proposes a multi-effect synergistic biomimetic mineralization nanosystem ( [email protected] 4 ) to regulate tumor cell metabolism and relevant biological behaviors through glycolysis-oxidative stress-autophagy process. Bovine serum albumin complexed with lonidamine served as a template to induce the formation of iron phosphate mineralization in situ . After intratumoral administration, the released lonidamine inhibited hexokinase II and down-regulated the level of glycolysis, cutting off the energy and biosynthesis supply source for tumor growth. Ferric ions dissociated from biomineralization in acidic microenvironment converted reduced glutathione to oxidized glutathione, elevated oxidative stress and induced ferroptosis through chemokinetic reactions. The dissociated phosphate ions function as an autophagy inhibitor to block the protective autophagy cased by energy deprivation for efficacy enhancement. The up-regulation of Nrf2 and LC3 proteins, the down-regulation of HK2 and GPX4 proteins, and the increase of ROS level in tumors all confirmed this conclusion. Notably, the nanosystem also down-regulated the release of inflammatory factors (IL-6, IL-8) and metastasis-related proteins (N-Cadherine, Vimentin) simultaneously, effectively preventing distant lung metastasis of tumor. In summary, this biomineralization-based nanosystem exhibited powerful antitumor effects both in vitro and in vivo and provides a new perspective for addressing the dilemma of malignant tumor treatment.
研究领域:
癌症生物学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Lingling Wang,Yan Yin,Gang Hou,Jian Kang,Qiuyue Wang
Background Cigarette smoking is a well-known risk factor in multiple chronic pulmonary diseases. This study aims to investigate the role of peroxisome proliferator-activated receptor (PPAR) γ in cigarette smoking-induced inflammation. Material/Methods Cigarette smoking extract (CSE) was employed to induce inflammation in bronchial epithelial cells (BECs). After CSE administration, several autophagy-related proteins (Beclin1, autophagy-related gene (ATG)5, ATG7, p62, and LC3) and PPARγ levels were examined by western blot. Subsequently, PPARγ agonists and antagonist were used to treat CSE-induced BECs, several inflammatory factors (interleukin (IL)-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2) and autophagy-related proteins were detected to measure the inflammatory and autophagy levels. Then LC3 knockdown was performed to verify the role of autophagy in CSE-induced inflammation. Finally, the AMP-activated protein kinase (AMPK) and its downstream S6 kinase (S6K) were detected in CSE-stimulated BECs. Results CSE administration caused insufficient autophagy and the decrease of PPARγ in BECs. The PPARγ agonists ameliorate the CSE-induced inflammation and promote the autophagy development, evidenced by the changes of inflammatory factors and autophagy-related proteins. Loss-of-function experiments demonstrated that the PPARg played an anti-inflammatory role in an autophagy-dependent manner. In addition, CSE administration inactivated the AMPK signaling, which was restored by PPARγ agonists. The effects of PPARγ agonists on inflammation and autophagy could be abolished by AMPK inhibitor. Conclusions We demonstrated that PPARγ played a protective role in CSE-induced inflammation and autophagy by activating AMPK signaling in BECs, which may provide investigation basis for clinical therapy of chronic pulmonary diseases.
研究领域:
肺部疾病
·
分子生物学
·
细胞信号传导
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Andrology and Urology
·
2024
·Vol. 13
·期 9
·1971
·
IF 1.9
Jiahao Jiang,Fei Xiao,Lanxin Yang,Yan Zeng,Jing Chen,Hengcheng Zhu,Lingqi Liu
Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain and various discomforts. Astaxanthin (AST) has multiple functions, including anti-inflammatory property, but it is unclear whether AST plays a key role in CP/CPPS and how it works. This study aimed to investigate the protective effect of AST on CP/CPPS in rats and the underlying mechanism. Methods A CP/CPPS rat model was induced by intraprostatic injection of carrageenan and the blood specimens and prostates were harvested for further research after oral administration of AST for 4 weeks. Results Tactile allodynia test showed that AST ameliorated chronic pelvic pain in a dose-depended manner. In addition, histological evaluation indicated that AST alleviated CP/CPPS rat prostate histological inflammation. Meanwhile, AST suppressed the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Besides, AST inhibited the activities of prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2). Furthermore, AST decreased the activation of the nuclear factor-κB (NF-κB) signaling pathway. Conclusions Our study has shown that AST exerts an anti-inflammatory and protective effect against CP/CPPS and the function is mediated at least through the suppression of NF-κB signaling pathway. These results provide evidence of AST as the potential agents for the treatment of CP/CPPS.
研究领域:
泌尿科
·
药理学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 22
·11676-11689
·
IF 6.317
Abel Wend-Soo Zongo,Daniel Zogona,Mahmoud Youssef,Shuxin Ye,Fuchao Zhan,Jing Li,Bin Li
The intestinal barrier dysfunction associated with chronic inflammation is a major health concern. This work aimed to investigate the protective effect and molecular mechanism of Senegalia macrostachya seed polysaccharide fraction (SMSP2) on inflammation-induced barrier dysfunction using Caco-2 cells and RAW264.7 macrophage co-culture model. The results showed that LPS stimulation of the basolateral RAW264.7 compromised the integrity of the apical differentiated Caco-2 cells monolayer, resulting in decreased transepithelial electrical resistance (TER) and increased inflammatory markers. SMSP2 apical treatment maintained a higher TER value and reduced the epithelial permeability to lucifer yellow (LY) dye. In addition, the SMSP2 group showed a significant decrease in the mRNA level of inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) in the Caco-2 monolayer compared to the LPS group. Moreover, SMSP2 increased the expression of the tight junctions (TJ) zonula occludens (ZO-1), occludin, and claudin-1 at the mRNA and protein levels. Furthermore, the immunofluorescence assay showed that SMSP2 ameliorated the overall distribution of the TJ proteins in the Caco-2 monolayer. SMSP2 application also resulted in the downregulation of the nuclear factor kappa-B (NF-κB) phosphorylation and the myosin light chain kinase (MLCK) expression, which implies that SMSP2 preserved the monolayer integrity from the inflammation-induced barrier disruption through the inhibition of the NF-kB-mediated MLCK signaling pathway activation. Senegalia macrostachya seeds could therefore be a promising functional food that could be used to improve intestinal barrier function.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
分子生物学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Pan Chen,Hongliang Yao,Weiwei Su,Yudong He,Keling Cheng,Yonggang Wang,Wei Peng,Peibo Li
Aims Sleep deficiency has been reported to be associated with some oral health problems. Oral ulcers are very common lesions of the oral mucosa, which severely impact patients' quality of life. However, the association between sleep deficiency and the oral ulcer remains unknown. The present study aims to explore the effects of sleep deficiency on oral ulcers. Main methods Rats were divided into normal control group (n = 30) and oral ulcer group (OU group, n = 50). Model rats with phenol-induced oral ulcers were deprived of sleep for 72 h by using the modified multiple platform technique. Key findings Sleep deprivation worsened oral ulcers and delayed healing process in rats. In addition, sleep deprivation increased the γ-aminobutyric acid (GABA, P < 0.01) and 5-hydroxytryptamine (5-HT, P < 0.05) levels in serum and brain, the corticotrophin (ACTH, P < 0.05), corticosterone (CORT, P < 0.01), immunoglobulin (Ig)M ( P < 0.01), tumor necrosis factor-alpha (TNF-α) ( P < 0.01), interleukin (IL)-1β ( P < 0.01), IL-6 ( P < 0.01), IL-8 ( P < 0.01), monocyte chemoattractant protein-1 (MCP-1) ( P < 0.01), and 8-hydroxy-deoxyguanosine (8-OHdG, P < 0.01) levels in serum. Sleep deprivation also up-regulated malonaldehyde (MDA) ( P < 0.05), TNF-α ( P < 0.05), and IL-1β ( P < 0.01) levels in oral mucosa tissue and delayed superoxide dismutase (SOD, P < 0.05) activity recovery. Significance These data suggest that sleep deprivation impaired the oral ulcer healing in rat oral mucosa, and the mechanisms of this effect are probably related to neuro-immuno-endocrine system and oxidative stress.
研究领域:
神经科学
·
免疫学
·
内分泌学
·
口腔健康
✓ 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）