FOOD AND CHEMICAL TOXICOLOGY
·
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
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2024
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
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
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呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2021
·
IF 3.636
Wei Liu,Ling Zhang,Shuo Sun,Long-sheng Tang,Shi-min He,An-qi Chen,Li-na Yao,Da-Long Ren
As a natural extract, cordycepin has been shown to play important regulatory roles in many life activities. In the study, the effects of cordycepin on inflammatory responses and the underlying mechanisms was explored using a zebrafish model. In the model of LPS-induced inflammation, cordycepin was found to significantly inhibited the expression of pro-inflammatory cytokines such as tnf-α, il-1β, il-6, and il-8 . Using in vivo imaging model, cordycepin significantly inhibited fluorescent-labeled neutrophils migrating towards injury sites. Furthermore, results showed that the phosphorylation level of ERK protein dramatically decreased after cordycepin treatment. Meanwhile, the ERK inhibitor, PD0325901, significantly inhibited the expression of pro-inflammatory cytokines in LPS-induced inflammatory model and neutrophils migration in the caudal fin injury model. This study indicated the important roles of cordycepin in inhibiting LPS and injury-induced inflammation and preliminarily explained the role of ERK protein in this process.
研究领域:
免疫学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
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IF 3.4
Fanzhuo Zeng,Anqi Chen,Wei Chen,Shuai Cheng,Sen Lin,Rongcheng Mei,Xifan Mei
Background Spinal cord injury (SCI) is a serious and difficult to treat traumatic disease of the central nervous system. Spinal cord injury causes a variety of detrimental effects, including neuroinflammation and ferroptosis, leading to chronic functional impairment and death. Recent studies have shown that microglia/macrophages (M/Ms) at the injury site remain primarily in the pro-inflammatory state, which is detrimental to recovery. However, information on the factors behind pro-inflammatory polarization skew in the injured spinal cord remains unclear. In this study, we found that Tumor Necrosis Factor-α(TNF-α) ablation protected after SCI by suppressing neuroinflammation and ferroptosis. Though using TNF-α knock out mice (TNF−/−), we induced downregulation of TNF-α in M/Ms and further investigated its effect on SCI outcome. In TNF−/− mice, significant behavioral improvements were observed as early as 7 days after injury. We showed that TNF-α inhibition promote injury-mediated M/Ms polarization from pro-inflammatory to anti-inflammatory phenotype in vivo. Furthermore, accumulated iron in M/Ms after SCI increased the expression of TNF-α and the population of M/Ms to pro-inflammatory phenotype. Moreover, zinc supplement reduced the secondary damage caused by iron overload. In conclusion, we found that knock out of TNF-α promotes recovery of motor function after spinal cord injury in mice by inhibiting ferroptosis and promoting the shift of macrophages to an anti-inflammatory phenotype, indicating that there is great potential for this therapy to SCI.
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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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 36
·5478-5489
·
IF 5.047
Yiyuan Duan,Xuguang Li,Xingang Zuo,Tao Shen,Shan Yu,Linhong Deng,Changyou Gao
The design of hyaluronic acid (HA)-based and stimuli-responsive hydrogels to elicit highly controlled and tunable cell response and behaviors is a major field of interest in tissue engineering and regenerative medicine. The pH-responsive hydrogel can respond to pH variation during wound healing, which may in turn regulate the tissue regeneration process. In this study, a double-network hydrogel cross-linked with vinyl double bonds and Schiff base was prepared, whose properties were further adjusted by incubation in pH 7.4 and pH 5 buffers. The endothelial cells (ECs) migrated much deeper into the softer HA hydrogel pre-treated with pH 5 buffer than the stiffer hydrogel. By contrast, the mesenchymal stem cells (MSCs) migrated easily into the stiffer hydrogel. The ECs highly expressed RhoA and non-muscle myosin (NM) II genes in the softer hydrogel, which may facilitate amoeboid migration. Meanwhile, the MSCs were stiffer than the ECs, and highly expressed Rac1, RhoA, vinculin, NM II, hyaluronidase (HYAL) 2 and CD44 genes in the stiffer hydrogel, which facilitate mesenchymal migration. These results provide important clues for revealing the different migration strategies of the ECs and MSCs in HA hydrogels with different stiffness, and suggest that the mechanical properties and the network structure of hydrogels play an important role in regulating the three-dimensional migration process of these cells.
研究领域:
组织工程
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再生医学
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 16
·12583
·
IF 5.6
Chen Yan,Huiru Qu,Xinli Li,Bin Feng
Some biologically active compounds isolated from sea cucumbers stimulate the body’s immune response by activating immune cells. Immune function is closely related to the integrity intestinal barrier and balanced gut microbiota. However, it is unknown whether the daily administration of holothurian wall hydrolysate (HWH) ameliorated intestinal dysbiosis and barrier injury induced by immunodeficiency. This study aimed to investigate the immunomodulatory effect and the underlying mechanism of HWH in cyclophosphamide (CTX)-induced immunocompromised mice. BALB/c mice received CTX (80 mg/kg, intraperitoneally) once a day for 3 days to induce immunodeficiency, and then they received the oral administration of HWH (80 or 240 mg/kg) or levamisole hydrochloride (LH, 40 mg/kg, positive control), respectively, once a day for 7 days. We utilized 16S rRNA sequencing for microbial composition alterations, histopathological analysis for splenic and colonic morphology, Western blotting for expressions of tight junction proteins (TJs), and quantitative real-time (qRT)-PCR for measurements of pro-inflammatory cytokines. HWH attenuated the immune organ damage induced by CTX, increased the secretions of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, and promoted the recovery of goblet cells and the production of TJs (claudin-1, occludin, and ZO-1) in the colon of the immunocompromised mice. Moreover, HWH promoted the growth of beneficial microorganisms such asLactobacillus,Lachnospiraceae,Christensenellaceae, andBifidobacterium, while it suppressed the populations ofRuminococcus,Staphylococcus, andStreptococcus. These results demonstrate that HWH elicits intestinal mucosal immunity, repairs the damage to intestinal mucosal integrity, and normalizes the imbalanced intestinal microbial profiles in immunocompromised mice. It may be helpful to identify the biological activities of HWH to support its potential use in new prebiotics, immunomodulatory agents, and medical additives for intestinal repair.Keywords:holothurian wall hydrolysate;immunodeficiency;tight junction proteins;pro-inflammatory cytokines;microbial composition
研究领域:
免疫学
·
微生物学
·
营养学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Peng She,Shuai Bian,Yuanqiang Cheng,Shujun Dong,Jianguo Liu,Wanguo Liu,Chunsheng Xiao
Osteoarthritis (OA) is a synovial inflammatory condition characterized by cartilage destruction and osteophyte formation. Macrophages play a central role in OA pathogenesis by producing proinflammatory cytokines. Intra-articular corticosteroid administration can relieve refractory pain and inflamed effusion of knee joints. However, limitations, such as rapid clearance from the joint space, potential damage to articular cartilage, and accelerated joint degeneration, may hamper the clinical application of corticosteroids. In this study, we reported the design and preparation of dextran sulfate-triamcinolone acetonide conjugate (DS-TA) nanoparticles (NPs) for treating OA by specifically targeting scavenger receptor class A (SR-A) on activated macrophages. We verified the excellent targeting specificity of DS-TA NPs to SR-A by flow cytometry and confocal laser scanning microscopy. DS-TA NPs were found to effectively reduce the viability of activated macrophages (RAW 264.7 cells) and the expression of proinflammatory cytokines. Intra-articular injection of DS-TA NPs effectively alleviated the structural damages to the joint cartilage, as confirmed in histopathological analysis. Additionally, DS-TA NPs decreased the expression of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, in the cartilage tissue. Thus, DS-TA NPs are a potential therapeutic nanomedicine for the targeted treatment of OA.
研究领域:
药理学
·
纳米医学
·
风湿病学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Jianbo Li,Ertai Ye,Jingwen Huang,Meng Xu,Jieke Zhang,Junrong Zhang,Huijie Cai,Jinjie Zhang
The timely suppression of inflammatory mediator production and mitigation of their effects on pancreatic acinar cells are crucial for the successful management of acute pancreatitis . To achieve effective treatment, we present a novel approach utilizing cysteine modified PEG nanoparticles for both precise accumulation at the site of pancreatitis and specific targeting of acinar cells. Methylprednisolone , a nonsteroidal anti-inflammatory drug, was tailored to enhance its circulation time in the bloodstream, preferentially accumulate in the pancreas and enhance cell uptake efficiency by acinar cells through specifically targeting L-Type amino acid transporter 1. The nanosystem significantly downregulated pro-inflammatory cytokines in plasma, resulting in the effective suppression of inflammation in acinar cells within an acute pancreatitis rat model. The utilization of the dual targeted therapy strategy holds considerable potential for the clinical management of pancreatitis.
研究领域:
药学
·
纳米技术
·
炎症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Sixin Xu,Lingkai Meng,Qian Hu,Fang Li,Jieying Zhang,Na Kong,Zhenyu Xing,Guosong Hong,Xingjun Zhu
Macrophage engineering has emerged as a promising approach for modulating the anti-tumor immune response in cancer therapy. However, the spatiotemporal control and real-time feedback of macrophage regulatory process is still challenging, leading to off-targeting effect and delayed efficacy monitoring therefore raising risk of immune overactivation and serious side effects. Herein, a focused ultrasound responsive immunomodulator-loaded optical nanoplatform (FUSION) is designed to achieve spatiotemporal control and status reporting of macrophage engineering in vivo. Under the stimulation of focused ultrasound (FUS), the immune agonist encapsulated in FUSION can be released to induce selective macrophage M1 phenotype differentiation at tumor site and the near-infrared mechanoluminescence of FUSION is generated simultaneously to indicate the initiation of immune activation. Meanwhile, the persistent luminescence of FUSION is enhanced due to hydroxyl radical generation in the pro-inflammatory M1 macrophages, which can report the effectiveness of macrophage regulation. Then, macrophages labeled with FUSION as a living immunotherapeutic agent (FUSION-M) are utilized for tumor targeting and focused ultrasound activated, immune cell-based cancer therapy. By combining the on-demand activation and feedback to form a closed loop, the nanoplatform in this work holds promise in advancing the controllability of macrophage engineering and cancer immunotherapy for precision medicine.
研究领域:
生物医学工程
·
纳米技术
·
癌症研究
·
免疫学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Fan Su,Chong Zhang,Qianyun Zhang,Yi Shen,Saiqi Li,Jianlin Shi,Ya-Xuan Zhu,Han Lin,Bin He
The sepsis-induced acute lung injury (ALI) still represents one of the leading causes of death in critically ill patients, underscoring the need for novel therapies. Excessive activation of immune cells and damage of reactive oxygen species (ROS) are the main factors that exacerbate lung injury. Here, the multifaceted immunomodulatory nanocomplexes targeting the proinflammatory neutrophilic activation and ROS damage are established. The S100A8/9 inhibitor, ABR2575, is loaded in the nanocomplexes, which effectively blocks the neutrophils-S100A8/A9- toll-like receptors (TLRS)-Inflammasome signaling in ALI. Synergically, the SiH nanosheets are encapsulated together with ABR2575 into the core of poly(lactic- co -glycolic acid) (PLGA) nanosponges, to achieve sustainable hydrogen release for the alleviation of ROS-induced lung tissue injury, and also promote the M2 polarization of macrophages. This novel combination strategy is proven to significantly suppress the infiltration of neutrophils and pro-inflammatory macrophages into the lungs, decrease the activation of neutrophils and pro-inflammatory monocytes in the blood, facilitate the anti-inflammatory polarization of macrophages and monocytes, and reduce the expression of pro-inflammatory cytokines in both the lung and blood circulation, all of which alleviate the lung injuries in preclinical murine ALI models. The current investigations offer a novel nanomedicine for the treatment of ALI with great potential in clinical invention.
研究领域:
纳米医学
·
免疫学
·
肺科学
·
药理学
·
重症医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFECTION GENETICS AND EVOLUTION
·
2021
·
IF 3.342
M.A. Abo-Kadoum,Mohammed Assad,Moure UAE,Stech A.E. Nzaou,Zhen Gong,Asmaa Moaaz,Samson Teweldebrhan,Adel Eltoukhy,Ai Xuefeng,Yu Chen,Jianping Xie
Mycobacterium tuberculosis (Mtb) survival and virulence largely reside on its ability to manipulate the host immune response . We have previously shown that M. tuberculosis Raf kinase inhibitor protein (RKIP) Rv2140c regulates diverse phosphorylation events in M. smegmatis . However, its role during infection is unknown. In this report, we show that Rv2140c can mimic the mammalian RKIP function. Rv2140c inhibit the activation of extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) via decreasing the phosphorylation capacity of upstream mediators MEK1, ERK1/2, and IKKα/β, thus leading to a reduction in pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. This effect can be reversed by RKIP inhibitor locostatin. Furthermore Rv2140c mediates apoptosis associated with activation of caspases cascades. This modulation enhances the intracellular survival of M. smegmatis within macrophage. We propose that Rv2140c is a multifunctional virulence factor and a promising novel anti-Tuberculosis drug target.
研究领域:
微生物学
·
免疫学
·
传染病学
✓ 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）