JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yan Liu,Meiling Zhou,Maochang Xu,Xueqin Wang,Yingying Zhang,Yiping Deng,Zongquan Zhang,Jun Jiang,Xiangyu Zhou,Chunhong Li
Delivering therapeutic agents efficiently to inflamed regions remains an intractable challenge following myocardial ischemia-reperfusion injury (MI/RI) due to the transient nature of the enhanced permeability and retention effect, which disappears after 24 h. Leveraging the inflammation-homing and plasticity properties of circulating monocytes (MN) as hitchhiking carriers and further inducing their polarization into anti-inflammatory phenotype macrophages upon reaching the inflamed sites is beneficial for MI/RI therapy. Herein, DSS/PB@BSP nanoparticles capable of clearing reactive oxygen species and inhibiting inflammation were developed by employing hollow Prussian blue nanoparticles (PB) as carriers to encapsulate betamethasone sodium phosphate (BSP) and further modified with dextran sulfate sodium (DSS), a targeting ligand for the scavenger receptor on MN. This formulation was internalized into MN as living cell drug depots, reprogramming them into anti-inflammation type macrophages to inhibit inflammation. In vitro assessments revealed the successful construction of the nanoparticle. In a murine MI/RI model, circulating MN laden with these nanoparticles significantly enhanced drug delivery and accumulation at the cardiac injury site, exhibiting favorable therapeutic ability and promoting M2-biased differentiation. Our study provides an effective approach with minimally invasion and biosecurity that makes this nanoplatform as a promising candidate for immunotherapy and clinical translation in the treatment of MI/RI.
研究领域:
心脏病学
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纳米技术
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免疫疗法
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xinyu Wang,Haoyu Qiu,Chengnan Chu,Kai Wang,Bitao Lu,Chao Yang,Baochen Liu,Guangqian Lan,Weiwei Ding
Noninvasive treatment of inflammatory bowel disease with lower gastrointestinal bleeding is a major clinical challenge. In this study, we designed an orally targeted microsphere based on sunflower pollen microcapsules to localize the site of inflammatory injury and promote hemostasis and tissue repair. Due to the Eudragit and ascorbate palmitate coatings, EL/AP@PS(t+Dex) demonstrates pH- and enzyme-responsive release of loaded drugs and helps to resist the harsh environment of the gastrointestinal tract. Both in vitro and in vivo experiments show the characteristics of inflammation targeting and mucosal adhesion, which reduce the systematic exposure and increase the local drug concentration. In the DSS model, orally administered EL/AP@PS(t+Dex) significantly alleviates hematochezia, inhabits intestinal inflammation, and remarkably promotes the recovery of the intestinal epithelial barrier to reduce the exposure of intestinal microvessels. Furthermore, EL/AP@PS(t+Dex) optimized the composition of intestinal microbiota, which benefits intestinal homeostasis. This finding provides a fundamental solution for the treatment of intestinal bleeding caused by inflammatory bowel disease (IBD).
研究领域:
药学
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生物医学工程
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF GENE MEDICINE
·
2024
·Vol. 26
·期 10
·e3742
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IF 3.2
Fuyun Zhu,Dezeng Zou,Ping Shi,Lianhua Tang,Dan Wu,Xiaoxue Hu,Fei Yin,Jianhui Liu
Background With its rapidly increasing incidence and prevalence, ulcerative colitis (UC) has become a major global health challenge. Recent evidence suggests that ferroptosis plays a significant role in the development of UC. However, the relationship between ferroptosis and the progression of UC needs to be extensively studied. Methods The differentially expressed genes in UC patients were screened from the GEO database. The ferroptosis-related genes were obtained from FErrDB and GeneCards. The UC subtypes were identified with the R package “CancerSubtype” and evaluated with consensus clustering (CC) to identify gene expression patterns in patients with UC. The key genes were detected with qRT-PCR, Western blot, and immunohistochemistry in vitro and in vivo models. Ferroptosis was identified with western blotting on ferrotic-associated proteins and staining on Fe 2+ with commercial FerroOrange kits. Results Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a potential biomarker for ferroptosis in UC patients. Transcriptome sequencing data showed a positive correlation between decreased DPP4 expression and proinflammatory cytokines such as TNF-α, IL-6, and IL-β, as well as immune cell infiltration in the colon tissues of UC patients. Furthermore, DPP4 was strongly associated with ferroptosis biomarkers, particularly in Subtype 2 of UC. Interestingly, our study also found that DPP4 expression was significantly reduced in RSL3-treated ferroptotic intestinal epithelial cells, more so than in LPS-treated cell models. Inhibition of DPP4 had a significant impact on the expression of ferroptotic biomarkers. Additionally, DPP4 expression was decreased in the colon tissues of DSS-treated mice, and the ferroptosis inhibitor Ferritin-1 effectively counteracted the effects of DSS on immune cell infiltration, colon length, and DPP4 expression. Conclusions DPP4 can serve as a biomarker for ferroptosis in the diagnosis and management of UC. Highlights DPP4-mediated ferroptosis is involved in ulcerative colitis DPP4 is a novel diagnostic biomarker of ulcerative colitis Ferroptosis involves intestinal epithelial cell death in ulcerative colitis
研究领域:
胃肠病学
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分子生物学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Yajuan Li,David Julian McClements,Fei Pan,Longjiang Tian,Shanglin Li,Xin Zhang,Jingbo Liu,Ting Zhang,Zhiyang Du
Multicomponent peptides, composed of numerous peptides with various binding sites and functionalities, are increasingly exploited in nanotechnology, biomedicine and functional food applications. This article reported that nucleation and growth of Zein (Z) during solvent exchange could form a confined space to drive spontaneous self-assembly of multicomponent peptides. The self-assembly process began with a concentration gradient generated by the exchange of water and ethanol driving the nucleation of Z to form small aggregates, while multicomponent peptides selectively or anisotropically adsorbed on the Z surface via electrostatic interactions and hydrophobic interactions, participating in and controlling the assembly kinetics, ultimately leading to the formation of well-defined nanoparticles (NPs). The multicomponent peptides-based assemblies could effectively encapsulate the hydrophobic functional agent quercetin (Que), presenting good biocompatibility, antioxidant activity, and preventing DSS-induced colitis. This study elucidated the self-assembly mechanism of multicomponent peptides and demonstrated their synergistic effects with hydrophobic compounds for disease prevention, offering valuable insights into the development of novel functional materials to regulate human health.
研究领域:
纳米技术
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生物医学
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功能食品
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产品关联
DOI
高影响因子
Chinese Medicine
·
2022
·Vol. 17
·期 1
·1-12
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IF 4.546
Wang Li,Shao Li,Chen Man-Yun,Wang Lin,Zhang Wei,Tan Feng-Bo,Huang Wei-Hua
Background Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota. Methods DSS was used to establish a chronic colitis mouse model. Body weight analysis, colon length measurement, HE staining, and inflammatory factors levels were processed in animal experiments. Flow cytometry was employed to analyze Th17/Treg cells in the mouse spleen and blood. 16S rRNA sequencing was utilized to analyze gut microbiota. Fecal microbiota transplantation (FMT) experiment was employed to verify the anti-colitis efficacy of GC-K by reshaping gut microbiota. Results GC-K significantly relieved colitis-related symptoms due to decreased disease activity index (DAI) scores, spleen weight, and increased colon length. Additionally, the tight junction proteins were increased, and the pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β and IL-17, were decreased after GC-K treatment. Furthermore, Bacteroides spp. significantly increased after modeling. Moreover, FMT experiments confirmed that GC-K-driven gut microbiota greatly relieved DSS-induced colitis. Conclusion GC-K alleviated colitis via the modulation of gut microbiota. Graphical Abstract
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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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2022
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IF 0
Meng Yan,Li Zhu,Shuai Wu,Yu Cao,Nianlian Mou,Qingjia Chi,Guixue Wang,Yuan Zhong,Wei Wu
Oxidative stress is a key factor in the development of inflammatory diseases. Elimination of reactive oxygen species (ROS) in the inflamed colon has been confirmed as an effective strategy to alleviate inflammatory bowel disease (IBD). The conventional approaches will cause systemic absorption and potential side effects. To address these issues, we develop a nanomedicine ( [email protected] NPs) that is capable of delivering to target inflammatory lesions by electrostatic adsorption, subsequently effectively scavenging the excess ROS and alleviating inflammation to ameliorate ulcerative colitis (UC). In the DSS induced acute colitis mice model, [email protected] NPs can significantly reduce the production of pro-inflammatory cytokines, alleviate oxidative stress, and promote the favorable recovery of the damaged colonic tissue. These results indicate that [email protected] NPs are able to effectively alleviate intestinal inflammation and provide strong theoretical support for the treatment of other inflammatory diseases.
研究领域:
纳米技术
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药理学
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炎症性肠病
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纳米药物
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产品关联
DOI
PubMed
Foods
·
2025
·Vol. 14
·期 4
·619
·
IF 5.1
Kaijie Shang,Zhiheng Zhao,Hua Chen,Xiaonan Bian,Xianquan Zhong,Xiaoping Hu,Xue Lin,Lu Wang
The consumption of wampee has traditionally been utilized to alleviate gastrointestinal inflammation and associated disorders; however, its exact mechanism has remained unknown. The aim of this study was to elucidate the therapeutic efficacy and underlying mechanism of wampee polyphenol extract (WPE) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). The findings revealed that WPE alleviated diverse symptoms of UC, regulated various inflammatory cytokines, and effectively protected the colon tissue structure and barrier integrity, thereby inhibiting LPS translocation. Moreover, WPE restored the richness and diversity of gut microbiota and optimized its structure at the phylum and genus levels, causing a notable improvement in short- chain fatty acid (SCFA) metabolism, particularly acetic acid, propionic acid, and butyric acid. Consequently, WPE was demonstrated to effectively suppress the LPS-induced TLR4-p38 MAPK/NF-κB signaling pathway by modulating gut microbiota and SCFA metabolism. These findings provided a theoretical basis for the use of wampee as a potential functional natural food for UC.
研究领域:
营养学
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胃肠病学
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免疫学
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微生物学
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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
·
2024
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IF 7.7
Minghui Wang,Xiaoxuan Xu,Mingxuan Sheng,Ming Zhang,Fang Wu,Zhi Zhao,Meng Guo,Bing Fang,Jianmin Wu
Tannic acid, a bioactive polyphenol found in various phytogenic foods and medicinal plants, has potential prevention effects on colitis, though more evidence and mechanistic studies are required to substantiate this. In this study, we investigated the effects of different doses from 0 to 3 mg/mL of tannic acid on mice, ultimately selecting a dose of 3 mg/mL for the anti-colitis trial based on growth and intestinal morphology assessments. Using the DSS-induced colitis model, we found that tannic acid may alleviate colitis by inhibiting the IL-17 - NF-κB p65 signaling pathway and modulating epigenetic pathways, particularly methylation modifications. Additionally, tannic acid altered the gut microbiota, increasing the abundances of Prevotella , Eubacterium_siraeum_group , and Enterorhabdus in the colon. Supplementation with Eubacterium siraeum via gavage also inhibited colitis, accompanied by increased folate and methylation regulators in the colon. These findings suggest that tannic acid may inhibit colitis through the suppression of the IL-17 - NF-κB pathway and the enhancement of microbiota-mediated methylation pathways.
研究领域:
免疫学
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胃肠病学
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微生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-18
·
IF 52.7
Xiao Xina,Hu Meng,Gao Li,Yuan Huan,Chong Baochen,Liu Yu,Zhang Rou,Gong Yanqiu,Du Dan,Zhang Yong,Yang Hao,Liu Xiaohui,Zhang Yan,Zhang Huiyuan,Xu Heng,Zhao Yi,Meng Wenbo,Xie Dan,Lei Peng,Qi Shiqian,Peng Yong,Tan Tao,Yu Yang,Hu Hongbo,Dong Biao,Dai Lunzhi
Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largely unknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine. By developing a low-input and user-friendly pipeline for the simultaneous profiling of five distinct cysteine (Cys) states, including free SH, total Cys oxidation (Sto), sulfenic acid (SOH), S -nitrosylation (SNO), and S -glutathionylation (SSG), we shed light on Cys redox modification stoichiometries and signaling with regional resolution in the aging gut of monkeys. Notably, the proteins modified by SOH and SSG were associated primarily with cell adhesion. In contrast, SNO-modified proteins were involved in immunity. Interestingly, we observed that the Sto levels ranged from 0.97% to 99.88%, exhibiting two distinct peaks and increasing with age. Crosstalk analysis revealed numerous age-related metabolites potentially involved in modulating oxidative stress and Cys modifications. Notably, we elucidated the role of fumarate in alleviating intestinal oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed that fumarate treatment promotes the recovery of several cell types, signaling pathways, and genes involved in oxidative stress regulation. Calorie restriction (CR) is a known strategy for alleviating oxidative stress. Two-month CR intervention led to the recovery of many antioxidative metabolites and reshaped the Cys redoxome. This work decodes the complexities of redoxomics during the gut aging of non-human primates and identifies key metabolic regulators of oxidative stress and redox signaling.
研究领域:
还原生物学
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胃肠科学
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衰老研究
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代谢组学
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蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS Neglected Tropical Diseases
·
2024
·Vol. 18
·期 12
·e0012714
·
IF 3.4
Xuanyin Cui,Yi Cheng,Hongyan Wang,Xiaomao Li,Jinfu Li,Ke Zhang,Rong Mou
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with an unknown etiology and is difficult to treat. Studies have shown that some helminths and their associated products have therapeutic potential in controlling or preventing inflammatory diseases. This study is to investigate the mitigation effects of Hymenolepis nana antigens (HnAg) on the UC model. HnAg significantly improved the disease activity index, colon length, and colonic pathological damage in mice with dextran sulfate sodium (DSS)-induced colitis. HnAg intervention could protect the number of goblet cells and enhance the expression of tight junction proteins and mucins, thereby improving intestinal barrier integrity. HnAg attenuated small intestinal organoid damage and stimulated intestinal stem cells proliferation in a DSS-induced mouse organoid inflammation model. The protective mechanism of HnAg might be related to the activation of the aryl hydrocarbon receptor (AhR)/IL-22 signaling pathway, which regulates intestinal barrier function and promotes the proliferation and differentiation of intestinal stem cells. In conclusion, HnAg has a therapeutic effect on UC mice. Our study provides a new approach for alleviating UC by Hymenolepis nana and its associated products.
Ulcerative colitis (UC) is an immune-mediated chronic inflammatory disease. Currently, commonly used drugs such as aminosalicylates and glucocorticosteroids are difficult to treat and have many adverse effects. In recent years, there has been a growing interest in utilizing the immunomodulatory abilities of worms to develop new therapies for the treatment of inflammatory and allergic diseases. Hymenolepis nana is a zoonotic parasitic worm that parasitizes the small intestines of humans and rodents and generally does not cause serious pathologic damage to their hosts, making it a potential class of intestinal parasites in helminthic therapy. In this study, we investigated the mitigating effect of Hymenolepis nana antigens (HnAg) on UC in mice from the perspective of maintaining intestinal mucosal barrier integrity. The results showed that HnAg alleviated UC in mice by activating the aryl hydrocarbon receptor (AhR)/IL-22 signaling pathway, promoting the proliferation and differentiation of intestinal stem cells, and modulating the integrity of the intestinal mucosal barrier. Meanwhile, HnAg attenuated DSS-induced inflammatory damage in mouse small intestinal organoid tissues and promoted intestinal stem cells proliferation. Suggesting that Hymenolepis nana and its related products may become a new option for alleviating UC.
研究领域:
免疫学
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胃肠病学
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药理学
·
炎症性肠病
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Yuanfang Kong,Yulong Hu,Jieming Li,Juntao Cai,Yuanhao Qiu,Chunhong Dong
Rubus chingii Hu has been used as a functional food for a long time. A novel pectin polysaccharide named RCHP-S from R. chingii Hu was structurally identified and explored its anti-inflammatory effect on colitis mice. RCHP-S was composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. NMR spectroscopy and methylation analysis showed that RCHP-S was mainly composed of HG-type pectin domains but also contains a small amount of RG-I. The anti-inflammatory tests indicated that the mouse macrophage RAW 264.7 cells pretreated with RCHP-S could show a significant inhibitory effect on the mRNA level of iNOS, IL-1β, IL-6, and TNF-α in vitro . Polysaccharide RCHP-S reduced the enteritis symptoms in dextran sulfate sodium (DSS)-induced colitis mice by inhibiting released inflammatory factors. These results indicated that the R. chingii Hu polysaccharide can be used as food additives for the treatment of intestinal inflammation.
研究领域:
食品科学
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药理学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Journal
·
2023
·
IF 5.5
Shi-Le Wang,Man-Man Zhang,Han Zhou,Guo-Qiang Su,Yi Ding,Guang-Hui Xu,Xu Wang,Cheng-Fu Li,Wei-Feng Huang,Li-Tao Yi
Background Inflammatory bowel disease (IBD) is a chronic, life-threatening inflammatory disease of gastrointestinal tissue characterized by inflammation of the gut. Recent studies have shown that gut microbiota is involved in the pathophysiology of IBD. However, it is unknown whether direct inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome regulates IBD and alters gut microbiota. Methods Here, the NLRP3 expression was evaluated in the colon of IBD subjects. Then, we investigated the effects of NLRP3 inhibition by MCC950 on the gut microbiota and IBD-like symptoms induced by dextran sulfate sodium (DSS). Results Firstly, NLRP3 and IL-1β levels were increased in patients with IBD as compared with healthy individuals. Then, the animal experiment showed that NLRP3 inhibition by MCC950 significantly attenuated IBD-like symptoms such as diarrhea and colonic inflammation in DSS-induced mice. In addition, NLRP3 inhibition inhibited NLRP3/ASC/caspase-1/IL-1β signaling pathway in the colon, which was over-activated by DSS. Furthermore, MCC950 increased the abundance of phylum Firmicutes, decreased the abundance of phylum Bacteroidetes, and increased the Firmicutes/Bacteroidetes ratio, indicating that the inhibition of NLRP3 inflammasome could regulate the abundance of intestinal flora. According to correlation analysis, NLRP3 might produce its functional role in the regulation of oxidation indicators by changing the gut microbiota composition, especially the phylum Bacteroidota, genus Lactobacillus and species Lactobacillus reuteri . Conclusions This study suggests that NLRP3 inflammasome inhibition attenuates IBD-like symptoms by regulating gut microbiota, and provides a basis for the clinical application of NLRP3 as a target for the treatment of IBD.
研究领域:
免疫学
·
胃肠病学
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微生物学
✓ 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）