FOOD AND CHEMICAL TOXICOLOGY
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2023
·
IF 4.3
Xiaoyi He,Qianyi Zhong,Kai Yan,Guoying Li,Junhua Yang
This study aimed to investigate the effect of exposure to aspartame (ASP) at safe levels on proinflammatory cytokines in the cerebrospinal fluid (CSF) of rats. Sprague Dawley rats were sacrificed after 1, 2, 4 or 8 week(s) of continuous exposure to ASP (40 mg/kg body weight). Serum, CSF and brain tissue samples were prepared, and the levels of the IL-1β, IL-6 and TNF-α were analyzed by ELISA . In serum, the levels of all three cytokines showed a two-phase alteration, a decrease followed by an increase in the ASP group. In the brain, their levels increased from the second or fourth week compared with the control group. In CSF, the levels of these cytokines showed a similar change to that in brain tissue, but the increase appeared at a later time point. For each cytokine, there was a significant positive correlation between its levels in serum, brain tissue and CSF. This is the first discovery that ASP exposure increased the levels of proinflammatory cytokines in CSF in rats, which emerged later than in blood and brain tissue. This study suggests the necessity of conducting related clinical studies to evaluate potential neuroinflammatory effects induced by chronic ASP exposure through CSF analysis.
研究领域:
神经科学
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免疫学
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毒理学
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DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2019
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IF 3.559
Haihua Zhang,Haijun Gu,Qinghui Jia,Yanqing Zhao,Hongqiang Li,Shurui Shen,Xin Liu,Guisheng Wang,Qiumei Shi
Inflammatory bowel disease (IBD) is a chronic inflammatory condition with high incidence. Syringin exhibits multiple pharmacological properties, including anti-inflammatory effects. However, the effect of syringin on inflammation of IBD is still unclear. Here, the dextran sulfate sodium (DSS)-induced colitis model was established in vivo . Rat intestinal epithelium IEC6 cells were treated with lipopolysaccharide (LPS) in vitro . Syringin inhibited DSS or LPS-induced overproduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and proinflammatory substances (iNOS, COX-2). Moreover, syringin inactivated the proinflammatory NF-κB p65 pathway by decreasing IκBα phosphorylation at Ser 32. The activation of antioxidant Nrf2 signaling pathway was promoted by syringin. Additionally, LPS-induced inflammation in IEC6 cells was also suppressed by NF-κB inhibitor PDTC and Nrf2 activator RTA408. The anti-inflammatory effects of syringin were comparable to these two reagents. Taken together, our results suggest that syringin shows protective effects on intestinal inflammation through inhibiting NF-κB, while activating Nrf2 signaling pathway in colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2024
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IF 2.5
Jinyun Long,Xiukuan Li,Chunyan Yao,Xiaoling Liu,Na Li,Yumeng Zhou,Dawei Li,Shengquan Su,Liangmei Wang,Hao Liu,Ying Xiang,Long Yi,Yao Tan,Peng Luo,Tongjian Cai
Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 μg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.
研究领域:
神经科学
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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
Molecular Medicine Reports
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2024
·Vol. 29
·期 5
·1-11
·
IF 3.4
Jiayan Yang,Liangliang Dong,Yifan Wang,Lifen Gong,Hongwei Gao,Yicheng Xie
Acute lung injury (ALI) is an acute inflammatory lung disease associated with both innate and adaptive immune responses. Hexokinase 2 (HK2) is specifically highly expressed in numerous types of inflammation‑related diseases and models. In the present study in vitro and in vivo effects of targeted degradation of HK2 on ALI were explored. The degradation of HK2 by the targeting peptide TAT (transactivator of transcription protein of HIV‑1)‑ataxin 1 (ATXN1)‑chaperone‑mediated autophagy‑targeting motif (CTM) was demonstrated by ELISA and western blotting in vitro and in vivo. The inhibitory effects of TAT‑ATXN1‑CTM on lipopolysaccharide (LPS)‑induced inflammatory responses were examined using ELISAs. The therapeutic effects of TAT‑ATXN1‑CTM on LPS‑induced ALI were examined via histological examination and ELISAs in mice. 10 µM TAT‑ATXN1‑CTM administration decreased HK2 protein expression and the secretion of proinflammatory cytokines (TNF‑α and IL‑1β) without altering HK2 mRNA expression in LPS‑treated both in vitro and in vivo, while pathological lung tissue damage and the accumulation of leukocytes, neutrophils, macrophages and lymphocytes in ALI were also significantly suppressed by 10 µM TAT‑ATXN1‑CTM treatment. TAT‑ATXN1‑CTM exhibited anti‑inflammatory activity in vitro and decreased the severity of ALI in vivo. HK2 degradation may represent a novel therapeutic approach for ALI.
研究领域:
肺病学
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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
ENVIRONMENT INTERNATIONAL
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2016
·
IF 5.929
Ping Xiang,Rui-Wen He,Yong-He Han,Hong-Jie Sun,Xin-Yi Cui,Lena Q. Ma
Human cornea is highly susceptible to damage by dust. Continued daily exposure to housedust has been associated with increasing risks of corneal injury, however, the underlying mechanism has not been elucidated. In this study, a composite housedust sample was tested for its cytotoxicity on primary human corneal epithelial (PHCE) cells, which were exposed to dust at 5–320 μg/100 μL for 24 h. PHCE cell viability showed a concentration-dependent toxic effect, attributing to elevated intracellular ROS. Moreover, when exposed at > 20–80 μg/100 μL, dust-induced oxidative damage was evidenced by increased malondialdehyde and 8-hydroxy-2-deoxyguanosine (1.3–2.3-fold) and decreased antioxidative capacity (1.6–3.5-fold). Alteration of mRNA expression of antioxidant enzymes ( SOD1 , CAT , HO-1 , TRXR1 , GSTM1 , GSTP1 , and GPX1 ) and pro-inflammatory mediators ( IL-1β , IL-6 , IL-8 , TNF-α , and MCP-1 ) were also observed. Furthermore, the mitochondrial transmembrane potential was dissipated from 9.2 to 82%. Our results suggested that dust-induced oxidative stress probably played a vital role in the cytotoxicity in PHCE cells, which may have contributed to dust-induced impairment of human cornea.
研究领域:
眼科学
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毒理学
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细胞生物学
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Xiaomei Dai,Yu Li,Xiaojun Liu,Yongjie Zhang,Feng Gao
Intracellular bacteria are considered one of the mechanisms that result in the failed therapy of bacterial infection and increase of antibiotic resistance. Nanotechnology-based drug delivery carriers have been receiving increasing attention for improving the intracellular antibacterial activity of antibiotics, but are accompanied by disadvantages such as complex preparation procedures, lack of active targeting, and monotherapy, which need to be further designed. Herein, the bacteria-infected macrophage targeted nanoparticle is fabricated to eliminate intracellular bacterial infections by antibiotic release, intracellular reactive oxygen species (ROS) level and proinflammatory response up-regulation. These nanoparticles were formed through the reaction of the amino group on selenocystamine dihydrochloride and the aldehyde group on oxidized dextran (ox-Dex), that encapsulate vancomycin (Van) through hydrophobic interaction. These nanoparticles could targeted uptake by macrophages via endocytosis, and response to the bacteria infected intracellular microenvironment (ROS and glutathione (GSH)) to controlled release antibiotic. Furthermore, the nanoparticles could consume intracellular GSH and promote a significant rise in level of ROS in macrophage, subsequently up-regulating proinflammatory response to reinforce antibacterial activity. These nanoparticles could accelerate bacteria-infected wound healing. This work fabricated a nanoparticle with bacteria-infected macrophage targeted and microenvironment-responsive antibiotic delivery, cellular ROS generation, and proinflammatory up-regulation activity to eliminate intracellular bacteria, which open up a new possibility for developing multifunctional drug delivery against intracellular infection.
研究领域:
医学
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生物技术
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纳米医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2016
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IF 3.138
Li Zhang,Xinquan Liu,Yongjie Wang,Guangpu Liu,Zhen Zhang,Zhongxi Zhao,Huiling Cheng
Zizyphus jujuba has been used as a traditional Chinese medicinal herb since ancient time. Polysaccharides have been found to be important bioactive compounds in the jujube. This work was designed to investigate the physicochemical characteristics and bioactivities of polysaccharides purified from Zizyphus jujuba cv. Muzao . Water-soluble polysaccharides were extracted using an ultrasonically assisted extraction method. The purified polysaccharides (HJP) were obtained by deproteinization and decoloration. Three main fractions (HJP1, HJP2 and HJP3) were isolated using DEAE-Sepharose fast flow ion-exchange chromatography. The purified polysaccharides were found to consist of mannose, rhamnose, galactose, galacturonic acid, glucose and arabinose at various levels for different fractions. The HJP and its three main fractions displayed DPPH radical scavenging activities as well as relatively strong reducing power and HJP had stronger activities than homogeneous compositions. Moreover, the results from in vitro immunological activities studies indicated that HJP could improve the phagocytosis activity of THP-l cells and had effect on the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In conclusion, the polysaccharides from Zizyphus jujuba cv. Muzao were discovered to have antioxidative and immunological activities.
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
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
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2021
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IF 4.49
Da Cheng,Cichun Wu,Ying Li,Yao Liu,Juan Mo,Lei Fu,Shifang Peng
Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) is a clinical syndrome of severe liver damage. HBV infection is affected by N6-methyladenosine (m 6 A) RNA modification. Here, we investigated whether methyltransferase-like 3 (METTL3)-mediated m 6 A methylation can affect ACLF. Human hepatic cells (THLE-2) were treated with lipopolysaccharide (LPS) to induce cell damage. Proliferation, apoptosis and m 6 A modification were measured by MTT assay , flow cytometry and Dot blot assay. Our results showed that HBV infection significantly enhanced the levels of m 6 A modification and elevated the expression of METTL3 and mature-miR-146a-5p in THLE-2 cells, which was repressed by cycloleucine (m 6 A inhibitor). METTL3 overexpression enhanced m 6 A modification and promoted mature-miR-146a-5p expression. METTL3 overexpression promoted HBV replication and apoptosis, enhanced the levels of pro-inflammatory cytokines, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), and repressed cell proliferation in THLE-2 cells, which attributed to repress miR-146a-5p maturation. Moreover, a severe liver failure mouse model was established by HBV infection to verify the impact of METTL3 knockdown on liver damage in vivo . HBV-infection led to a severe liver damage and increase of apoptosis in hepatic tissues of mice, which was abolished by METTL3 knockdown. METTL3 knockdown reduced METTL3 expression and impeded miR-146a-5p maturation in HBV-infected mice. In conclusion, this work demonstrates that METTL3 inhibition ameliorates liver damage in mouse with HBV-associated ACLF, which contributes to repress miR-146a-5p maturation. Thus, this article suggests a novel therapeutic avenue to prevent and treat HBV-associated ACLF.
研究领域:
分子生物学
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肝病学
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病毒学
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药理学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
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IF 9.4
Liang Song,Zihe Zhai,Wei Ouyang,Jie Ding,Shuqin Wang,Shifen Li,Min Liang,Feng Xu,Changyou Gao
Hydrogel microparticles (HMPs) have many advantages for biomedical applications, particularly for minimally invasive therapy, for example, acute lung injury (ALI) that is characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators in the microenvironment. In this study, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were designed and prepared by using a membrane emulsification device. The HMPs were composed of double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal linkages and unsaturated double bonds. Surface-coating of inflammatory macrophage (M1) cell membranes was performed to obtain the membrane-coated HBPAK HMPs (mem HMPs) via electrostatic force. The mem HMPs exhibited strong ROS-scavenging and anti-inflammatory properties both in vitro and in vivo . After administered by inhalation in an ALI mouse model, the mem HMPs reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation. Our results suggest that the mem HMPs could serve as a potential therapeutic platform for treating inflammatory diseases with high efficiency. Statement of significance Hydrogel microparticles (HMPs) with minimally invasive delivery are advantageous for acute lung injury (ALI) characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators. Herein, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were prepared by copolymerizing double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal bonds and unsaturated double bonds in a membrane emulsification device. The HMPs covered with inflammatory macrophage (M1) cell membranes (mem HMPs) exhibited strong ROS-scavenging and anti-inflammation properties, reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation.
研究领域:
生物医学工程
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药理学
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材料科学
·
呼吸病学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Zhaoyan Zhao,Yuchen Xiao,Lingqing Xu,Ye Liu,Guanmin Jiang,Wei Wang,Bin Li,Tianchuan Zhu,Qingqin Tan,Lantian Tang,Haibo Zhou,Xi Huang,Hong Shan
COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.
研究领域:
药理学
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病毒学
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免疫学
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纳米技术
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肺病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 7
·3026-3037
·
IF 6.1
Chengxiao Yu,Yihao Chen,Shokouh Ahmadi,Dongmei Wu,Jiaxiong Wu,Tian Ding,Donghong Liu,Xingqian Ye,Shiguo Chen,Haibo Pan
Goji berry and mulberry are both popular berries with anti-colitis effects, but their leaves have received less attention. In this study, the anti-colitis effects of goji berry leaf and mulberry leaf were investigated in dextran-sulfate-sodium-induced colitis C57BL/6N mice compared with their fruits. Goji berry leaf and goji berry reduced colitic symptoms and ameliorated tissue damage, while mulberry leaf did not. ELISA and western blotting analysis suggested that goji berry showed the best performance in inhibiting the overproduction of pro-inflammatory cytokines (TNF-α, IL-6 and IL-10) and improving damaged colonic barrier (occludin and claudin-1). Besides, goji berry leaf and goji berry reversed the gut microbiota dysbiosis by increasing the abundance of beneficial bacteria like Bifidobacterium and Muribaculaceae, and decreasing the abundance of harmful bacteria like Bilophila and Lachnoclostridium. Goji berry, mulberry and goji berry leaf could restore acetate, propionate, butyrate and valerate to ameliorate inflammation, while mulberry leaf could not restore butyrate. To the best of our knowledge, this is the first report on the comparison of the anti-colitis effects of goji berry leaf, mulberry leaf and their fruits, which is meaningful for the rational utilization of goji berry leaf as a functional food.
研究领域:
药理学
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免疫学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Zhenming Gao,Jidong Sui,Rong Fan,Weikun Qu,Xuepeng Dong,Deguang Sun
Aim Lung injury is a common complication of acute pancreatitis (AP), which leads to the development of acute respiratory distress syndrome and causes high mortality. In the present study, we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved.Materials and Methods Thirty male Sprague-Dawley rats were randomly divided into AP (n=24) and normal (n=6) groups. Rats in the AP group received a retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct and then randomly assigned to untreated, emodin, combined emodin and ML385, and dexamethasone (DEX) groups. Pancreatic and pulmonary injury was assessed using H&E staining. In in vitro study, rat alveolar epithelial cell line L2 cells were exposed to lipopolysaccharide and treated with emodin. Nrf2 siRNA pool was applied for the knockdown of Nrf2. The contents of the pro-inflammatory cytokines in the bronchoalveolar lavage fluid and lung were determined using enzyme-linked immunosorbent assay. The expressions of related mRNAs and proteins in the lung or L2 cells were detected using real-time polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence.Key Findings Emodin administration alleviated pancreatic and pulmonary injury of rats with AP. Emodin administration suppressed the production of proinflammatory cytokines, downregulated NLRP3, ASC and caspase-1 expressions and inhibited NF-κB nuclear accumulation in the lung. In addition, Emodin increased Nrf2 nuclear translocation and upregulated HO-1 expression. Moreover, the anti-inflammatory effect of emodin was blocked by Nrf2 inhibitor ML385.Conclusion Emodin effectively protects rats against AP-associated lung injury by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling.
研究领域:
药理学
·
免疫学
·
病理生理学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）