ACS Nano
·
2022
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IF 18.027
Ruoyao Li,Yuanyuan Fan,Lulu Liu,Hongna Ma,Deyan Gong,Zhaohua Miao,Hua Wang,Zhengbao Zha
The exciting success of NBTXR3 in the clinic has triggered a tumult of activities in the design and development of hafnium-based nanoparticles. However, due to the concerns of nondegradation and limited functions, the biomedical applications of Hf-based nanoparticles mainly focus on tumors. Herein, tannic acid capped hafnium disulfide (HfS2@TA) nanosheets, a 2D atomic crystal of hafnium-based materials prepared by liquid-phase exfoliation, were explored as high-performance anti-inflammatory nanoagents for the targeted therapy of inflammatory bowel disease (IBD). Benefiting from the transformation of the S2–/S6+ valence state and huge specific surface area, the obtained HfS2@TA nanosheets were not only capable of effectively eliminating reactive oxygen species/reactive nitrogen species and downregulating pro-inflammatory factors but also could be excreted via kidney and hepatointestinal systems. Unexpectedly, HfS2@TA maintained excellent targeting capability to an inflamed colon even in the harsh digestive tract environment, mainly attributed to the electrostatic interactions between negatively charged tannic acid and positively charged inflamed epithelium. Encouragingly, upon oral or intravenous administration, HfS2@TA quickly inhibited inflammation and repaired the intestinal mucosa barrier in both dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid induced IBD models. This work demonstrated that ultrathin HfS2@TA atomic crystals with enhanced colon accumulation were promising for the targeted therapy of IBD.
研究领域:
纳米技术
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材料科学
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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 Crohns & Colitis
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2023
·Vol. 17
·期 8
·1278-1290
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IF 8
Hu Xiaoming,Jiao Fuxin,Deng Jiali,Zhou Ziheng,Chen Shanghai,Liu Changqin,Liu Zhanju,Guo Feifan
Background and AimsThe incidence of inflammatory bowel disease [IBD] in the elderly has increased in recent years. However, the mechanisms underlying the ageing-related IBD susceptibility remain elusive. Cytokine-inducible SH2-containing protein [CISH] is involved in regulating metabolism, the expansion of intestinal tuft cells and type-2 innate lymphoid cells, and ageing-related airway inflammation. Here, we investigated the role of CISH in ageing-related colitis susceptibility.MethodsCISH and phosphorylated signal transducer and activator of transcription-3 [p-STAT3] levels were evaluated in the colons of ageing mice and older ulcerative colitis [UC] patients. Mice with intestinal epithelial cell-specific knockout of Cish [CishΔIEC] and Cish-floxed mice were administered dextran sodium sulphate [DSS] or trinitrobenzene sulphonic acid [TNBS] to induce colitis. Colonic tissues were analysed in quantitative real-time polymerase chain reaction, immunoblotting, immunohistochemical, and histological staining experiments. Differentially expressed genes from colonic epithelia were analysed by RNA sequencing.ResultsAgeing increased the severity of DSS-induced colitis and the expression of colonic epithelial CISH in mice. CishΔIEC prevented DSS- or TNBS-induced colitis in middle-aged mice but not in young mice. RNA-sequencing analysis revealed that CishΔIEC significantly suppressed DSS-induced oxidative stress and proinflammatory responses. During ageing in the CCD841 cell model, knockdown of CISH decreased ageing-induced oxidative stress and proinflammatory responses, whereas these effects were compromised by knocking down or inhibiting STAT3. The increase in CISH expression was higher in the colonic mucosa of older patients with UC than in that of healthy controls.ConclusionsCISH might be a proinflammatory regulator in ageing; therefore, targeted therapy against CISH may provide a novel strategy for treating ageing-related IBD.
研究领域:
免疫学
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胃肠病学
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分子生物学
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衰老研究
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产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2025
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IF 8.2
Bowen Jiao,Nanting Zhu,Decheng Bi,Lijun Yao,Yan Wu,Beiwei Zhu,Xu Xu
Fucoxanthin (FUC), a lipid-soluble carotenoid with various bioactivities, demonstrates promise as a preventive agent against inflammatory bowel disease (IBD). Nevertheless, the inherent instability and low aqueous solubility of FUC limit its application in functional food formulations and pharmaceutical applications. In this study, a FUC-loaded pickering emulsion (G-SPI-COS/FUC emulsion) with high encapsulation efficiency and small particle size was developed by using genipin-crosslinked soy protein isolate (SPI)-chitooligosaccharide (COS) nanoparticles as stabilizers. G-SPI-COS/FUC emulsion exhibited excellent stability under varying pH values, ionic strengths, and storage conditions. In vitro digestion experiments showed that G-SPI-COS/FUC emulsion controlled FUC release and enhanced its intestinal absorption and bioavailability. Furthermore, G-SPI-COS/FUC emulsion was more effective in preventing dextran sulfate sodium (DSS)-induced colitis than free FUC and FUC-loaded pickering emulsion stabilized by native SPI. These findings indicated that G-SPI-COS/FUC emulsion could serve as a promising delivery system for FUC, providing a novel approach to the prevention of IBD.
研究领域:
食品科学
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药学
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纳米技术
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生物技术
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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 Functional Foods
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2023
·
IF 5.6
Chongwei Yu,Jingtianyi Liu,Zonghao Liu,Qinchao Ding,Qinchao Zhu,Nan Chen,Jinfeng Fu,Teresa G. Valencak,Daxi Ren
Probiotics have been shown to inhibit the development of IBD but the specific mechanism remains unclear. In this study, the mitigating effect and underlying mechanisms induced by Lactobacillus plantarum ZJUIDS04 ( L. plantarum ZJUIDS04) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice were investigated. After L. plantarum ZJUIDS04 feeding, symptoms of DSS-induced colitis were remarkably reduced, including weight loss, colon shortening, colonic tissue damage, decreased tight junction protein, and pro-inflammatory cytokines. Furthermore, L. plantarum ZJUIDS04 significantly altered the structure of the intestinal microbiota, including decreasing the abundance of Romboutsia , Escherichia − Shigella , and Parabacteroides, as well as increasing the abundance of Akkermansia and Ruminococcus _1. More importantly, the genera of butyric acid-producing bacteria as well as short-chain fatty acids (SCFAs) were increased after L. plantarum ZJUIDS04 intervention, indicating regulation of gut microbiota and its metabolism might be an important factor for L. plantarum ZJUIDS04 alleviation against colitis.
研究领域:
胃肠病学
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微生物学
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免疫学
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产品关联
DOI
高影响因子
BMC IMMUNOLOGY
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2023
·Vol. 24
·期 1
·1-12
·
IF 3
Cai Jing,Wu Hao,Wang Chenxing,Chen Yujiao,Zhang Dingli,Guan Shiwei,Fu Beilei,Jin Yingli,Qian Cao
Inflammatory bowel disease (IBD) is a common immune-mediated condition with its molecular pathogenesis remaining to be fully elucidated. This study aimed to deepen our understanding of the role of FUT2 in human IBD, by studying a new surrogate gene Sec1, a neighboring gene of Fut2 and Fut1 that co-encodes the α 1,2 fucosyltransferase in mice. CRISPR/Cas9 was used to prepare Sec1 knockout (Sec1−/−) mice. IBD was induced in mice using 3% w/v dextran sulphate sodium. Small interfering RNA (siRNA) was employed to silence Sec1 in murine colon cancer cell lines CT26.WT and CMT93. IBD-related symptoms, colonic immune responses, proliferation and apoptosis of colon epithelial cells were assessed respectively to determine the role of Sec1 in mouse IBD. Impact of Sec1 on the expression of death receptor 5 (DR5) and other apoptosis-associated proteins were determined. Sec1 knockout was found to be associated with deterioration of IBD in mice and elevated immune responses in the colonic mucosa. Silencing Sec1 in CT26.WT and CMT93 cells led to greater secretion of inflammatory cytokines IL-1β, IL-6 and TNF-α. Cell counting kit 8 (CCK8) assay, flow cytometry and TUNEL detection suggested that Sec1 expression promoted the proliferation of colon epithelial cells, inhibited cell apoptosis, reduced cell arrest in G0/G1 phase and facilitated repair of inflammatory injury. Over-expression of DR5 and several apoptosis-related effector proteins was noticed in Sec1−/− mice and Sec1-silenced CT26.WT and CMT93 cells, supporting a suppressive role of Sec1 in cell apoptosis. Our results depicted important regulatory roles of Sec1 in mouse IBD, further reflecting the importance of FUT2 in the pathogenesis of human IBD.
研究领域:
免疫学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Biomedical Journal
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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
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胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Nannan Peng,Jingmin Wang,Haimei Zhu,Ziyue Liu,Jiayi Ren,Wenjing Li,Yongzhong Wang
Inflammatory bowel disease (IBD) is a recurrent chronic colitis disease with increasing incidence and prevalence year by year. The single efficacy and significant side effects of traditional IBD treatment drugs have promoted the flourishing development of new drugs. Inspired by many health benefits of carbon dots (CDs) based nanomedicine in biomedical applications, a metal-free carbon dots (CP-CDs) was synthesized from citric acid and polyethylene polyamine to treat colitis. Oxidative stress tests at the cellular and nematode levels demonstrated CP-CDs have good antioxidant effects, while the toxicity of CP-CDs to cells and nematodes is low. CP-CDs were further applied to dextran sodium sulfate (DSS)-induced colitis in mice models, and it was found that CP-CDs can reduce the disease activity index (DAI) score of colon tissue and restore the intestinal barrier. Further, the anti-colitis mechanisms of CP-CDs were explored, one of which is to regulate intestinal oxidative stress in inflammatory mice, further reducing the expression of inflammatory cytokines, and thus alleviating colitis. Notably, 16S rRNA sequence analysis showed that the abundance of beneficial bacteria ( Ligilactobacillus and Enterorhabdus ) in the intestinal tract increased, while that of harmful bacteria ( unclassified_Clostridia_UCG_014 ) decreased after CP-CDs treatment, indicating that CP-CDs rebalancing the gut microbiota destroyed by DSS is another important mechanism. In short, these non-toxic carbon dots not only have the potential for multi-factor combined relief of colitis but also offer an alternative therapy medicine for patients suffering from IBD.
研究领域:
药理学
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胃肠病学
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纳米医学
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微生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
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2023
·
IF 5.5
Chang Yongliang,Wu Xiawei,Lu Shengwei,Du Jiahao,Long Yixiu,Zhu Yefei,Qin Huanlong
Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.
研究领域:
纳米技术
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药学
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胃肠病学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Fang Dong,Liangwen Hao,Lin Wang,Ying Huang
Convincing evidence suggests that aberrant gut microbiota changes play a critical role in the progression and pathogenesis of inflammatory bowel disease (IBD). Probiotic therapeutic interventions targeting the microbiota may provide alternative avenues to treat IBD, but currently available probiotics often suffer from low intestinal colonization and limited targeting capability. Here, we developed azido (N 3 )-modified Prussian blue nanozyme (PB@N 3 ) spatio-temporal guidance enhances the targeted colonization of probiotics to alleviate intestinal inflammation. First, clickable PB@N 3 targets intestinal inflammation, simultaneously, it scavenges reactive oxygen species (ROS). Subsequently, utilizing “click” chemistry to spatio-temporally guide targeted colonization of dibenzocyclooctyne (DBCO)-modified Lactobacillus reuteri DSM 17938 (LR@DBCO). The “click” reaction between PB@N 3 and LR@DBCO has excellent specificity and efficacy both in vivo and in vitro. Despite the complex physiological environment of IBD, “click” reaction can prolong the retention time of probiotics in the intestine. Dextran sulfate sodium (DSS)-induced colitis mice model, demonstrates that the combination of PB@N 3 and LR@DBCO effectively mitigates levels of ROS, enhances the colonization of probiotics, modulates intestinal flora composition and function, regulates immune profiles, restores intestinal barrier function, and alleviates intestinal inflammation. Hence, PB@N 3 spatio-temporal guidance enhances targeted colonization of LR@DBCO provides a promising medical treatment strategy for IBD.
研究领域:
生物医学工程
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微生物学
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胃肠病学
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药理学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2023
·
IF 10.7
Hui Wang,Xiaojun Huang,Shengkun Xia,Chunhua Chen,Xiaomin Chen,Yanli Zhang,Mohamed A. Farag,Jianbo Xiao,Shaoping Nie
Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). However, it is unclear the interaction between dietary fiber and flavonoids in gut health. Objective The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF + CF and CIDF + CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. Methods 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. Results Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. However, CSDF + CF showed weaker improvement than CF or SDF in most physical and biochemical signs. Furthermore, CSDF and CF decreased intestinal g_Escherichia-Shihella and g_Clostridium_sensu_stricto_1 induced by DSS administration. Interestingly, celery flavonoid promoted g_Akkermansia proliferation both in vivo and in vitro , and which can be inhibited by CSDF. Conclusions This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia , and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect.
研究领域:
胃肠病学
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营养科学
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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 Nanomedicine
·
2023
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IF 8
Bingqing Zhang,Qiang Li,Qinglin Xu,Baochao Li,Heng Dong,Yongbin Mou
Background Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy.Methods CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model.Results Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury.Conclusion The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.
研究领域:
纳米技术
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药理学
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免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
mBio
·
2023
·
IF 6.4
Jie Peng,Tong Liu,Pengfei Meng,Yue Luo,Siyue Zhu,Yanxin Wang,Mingxia Ma,Jiaojiao Han,Jun Zhou,Xiurong Su,Shiming Li,Chi-Tang Ho,Chenyang Lu
Gut microbiota dysbiosis is causally related to inflammatory bowel disease (IBD), and increased levels of the gut metabolite ammonia have been proposed to contribute to IBD development. In this study, we aimed to clarify the anti-colitis mechanism of gallic acid (GA) based on its ability to trap the deleterious metabolite ammonia and improve gut microbiota. Aminated product was detected in the fecal samples of mice after oral gavage of gallic acid (GA) and identified as 4-amino-substituted gallic acid (4-NH2-GA), thus confirming the ability of GA to trap ammonia in vivo. Then, we compared the beneficial effects of GA and 4-NH2-GA on dextran sulfate sodium (DSS)-induced colitis mouse and found that both compounds managed to alleviate colitis phenotypes, indicating ammonia trapping had no adverse effect on the original anti-colitis activity of GA. In addition, both GA and 4-NH2-GA improved the gut microbiota dysbiosis induced by DSS, and fecal microbiota transplantation was subsequently performed, which further revealed that the gut microbiota mediated the anti-colitis activity of both GA and 4-NH2-GA. In summary, this study clarified that GA alleviated colitis by targeting both the symptoms and root causes: it directly reduced the deleterious metabolite ammonia by forming aminated metabolites without compromising the original anti-colitis activity, and it also improved gut microbiota dysbiosis, which in turn contributed to the alleviation of colitis. Since the GA structure is presented in various polyphenols as a common building block, the novel anti-colitis mechanism obtained from GA may also apply to other complex polyphenols.
研究领域:
药理学
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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）