FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Dongsheng Jia,Xi Tian,Yuting Chen,Jie Liu,Man Wang,Zhangsen Hao,Changshun Wang,Ding Zhao
Introduction The incidence of inflammatory bowel disease (IBD) has been increasing year by year in recent years. Flavonoids are the main components of mulberry leaves exerting anti-inflammatory effects and have potential applications in drug screening for IBD treatment. Enzymatic hydrolysis can enhance the bioavailability and activity of flavonoid glycosides. No relevant reports on the potentiation of mulberry leaf flavonoids (MLF) after deglycosylation have been retrieved. Methods An enzymatic method was used to prepare enzymatic hydrolysates of MLF (EMLF). The protective effect of EMLF on zebrafish with IBD was evaluated by observing zebrafish intestinal length and width, intestinal histopathological morphology, as well as neutrophil and goblet expression. Network pharmacology and metabolomics were performed to explore the mechanism of action of EMLF against IBD. Finally, the mechanism of EMLF against IBD was validated using Western Blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results The EMLF was successfully prepared by hydrolyzing MLF with snailase for the first time, and the anti-inflammatory effect of EMLF was clarified to be superior to that of MLF in IBD zebrafish. The network pharmacology and metabolomics studies showed that the mechanism of EMLF for IBD may be related to regulation of purine metabolic pathway. The expression levels of adenosine deaminase (ADA), critical targets in purine metabolism, were significantly down-regulated, while the expression of adenine phosphoribosyltransferase (APRT) and xanthine dehydrogenase (XDH) was significantly increased when compared with the TNBS group. Conclusion The results suggested that enzymatic deglycosylation is an effective measure to enhance the anti-inflammatory activity of MLF, which provides referable ideas and methods for the deep processing and utilization of natural drug resources.
研究领域:
药理学
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分子生物学
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生物化学
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斑马鱼研究
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DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yaoyu Hu,Pengfei Zhu,Junwei Deng,Yi Yu,Qian Chen,Haitao Wu,Zhengbao Zha,Hua Wang,Yan Ma
Individuals diagnosed with inflammatory bowel disease (IBD) frequently encounter dysbiosis of the intestinal microbiota and are predisposed to psychiatric comorbidities, such as depression and anxiety. The development of oral therapeutics that concurrently attenuate intestinal inflammation, modulate gut microbiota, and ameliorate psychiatric symptoms is imperative for effective IBD management. This study introduced an orally administered Inulin gel incorporating magnesium diboride nanosheets (MgB2@Inulin gel). The hydrolysis of MgB2 nanosheets could generate reductive hydrogen gas (H2), which is critical for scavenging excess reactive oxygen/nitrogen species (RONS), and boron ions that neutralize harmful lipopolysaccharides (LPS). Prebiotic Inulin could effectively protect MgB2 nanosheets from gastric acid degradation, ensuring their persistence in the intestinal tract, where it modulated the gut microbiota and preserved intestinal barrier integrity. Notably, MgB2@Inulin gel markedly alleviated anxiety and depressive behaviors in the model of colitis by regulating the gut–brain axis. Thus, this work underscores the pivotal role of the gut–brain axis in the therapeutic approach to IBD and its associated psychiatric manifestations, proposing a straightforward, safe, and efficacious oral hydrogen treatment strategy for IBD and concurrent mental health disorders.
研究领域:
纳米医学
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胃肠病学
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神经科学
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微生物学
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药理学
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材料科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Min Nie,Danqing Huang,Guopu Chen,Yuanjin Zhao,Lingyun Sun
Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin-27 (IL-27) MSC-derived extracellular vesicles (MSC IL-27 EVs) is developed to treat IBD. The MSC IL-27 EVs prepared through lentivirus-mediated gene transfection technology show ideal anti-inflammatory and damage repair function. By encapsulating MSC IL-27 EVs into dopamine methacrylamide-modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSC IL-27 EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSC IL-27 EVs-loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSC IL-27 EVs-loaded microcarriers provide a promising strategy for the biomedical application of MSC-derived EVs, and broaden the clinical potential of MSC therapy.
研究领域:
药学
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生物医学工程
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干细胞治疗
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炎症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Huai Manxiu,Pei Mingliang,Chen Jie,Duan Xiaoyan,Zhu Yun,Yang Fan,Ge Wensong
The damnification of mitochondrion is often considered to be an important culprit of inflammatory bowel disease (IBD), however, there are fewer reports of mechanisms of mitochondria-mediated IBD treatment. Therefore, we first proposed to reboot mitochondrial energy metabolism to treat IBD by capturing the double-sided factor of ROS and creatine (Cr)-assisted energy adjustment. Herein, an oral Cr-modified selenium-based hyaluronic acid (HA) nanogel (HASe-Cr nanogel) was fabricated for treatment of IBD, through ROS elimination and energy metabolism upgradation. More concretely, due to IBD lesion-specific positive charge and the high expression of CD44, HASe-Cr nanogel exhibited dual targeted inflammatory bio-functions, and ROS-driven degradation properties in high-yield ROS levels in inflammation areas. As expected, multifunctional HASe-Cr nanogel could effectively ameliorate IBD-related symptoms, such as mitochondrial biological function restoration, inhibition of M1-like macrophage polarization, gut mucosal reconstruction, microbial ecological repair, etc., thus excellently treating IBD. Overall, the proposed strategy underlined that the great potentiality of HASe-Cr nanogel by restarting mitochondrial metabolic energy in colitis lesions, providing new a pavement of mitochondrion-mediated colitis treatment in clinical applications.
研究领域:
药学
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纳米技术
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胃肠病学
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线粒体生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Chenlan Xu,Shuting Chen,Cuiping Chen,Yangcan Ming,Jiahao Du,Jinyi Mu,Fang Luo,Da Huang,Na Wang,Zhenyu Lin,Zuquan Weng
Co-delivery of anti-inflammatory drugs and reactive oxygen species (ROS) scavengers by stimuli-responsive oral nanoparticles is deemed to be a favorable strategy for inflammatory bowel disease (IBD) therapy. In this study, using micelles formed by CUR conjugated hydroxyethyl starch (HES) as vehicles, dexamethasone (DEX)-loaded HES-CUR nanoparticles (DHC NPs) with desirable size, negative surface charge, good stability in the harsh gastric environment, and excellent ROS scavenging activity are developed as a colon-targeted oral formulation for treating IBD. Due to the degradation of HES in response to α-amylase overexpressed in the inflamed colon, the DHC NPs release drugs in an α-amylase-responsive manner. Meanwhile, the DHC NPs can be effectively internalized by macrophages and show excellent cytocompatibility with macrophages since they are composed of food-derived compounds. Importantly, in vivo studies reveal that the DHC NPs are capable of targeting the inflamed colon induced by dextran sulfate sodium (DSS), and the targeted and combination therapy enhances the efficacy of free DEX and significantly relieves the impairment caused by DSS-induced ulcerative colitis. Incorporating the merits of targeted drug delivery and combined therapy with an anti-inflammatory drug and ROS scavenger, the DHC NPs are promising for developing novel oral formulations for IBD therapy.
研究领域:
药学
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纳米技术
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药物递送系统
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炎症
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yue Li,Yayue Zhang,Xuran Ding,Taotao Zou,Hu Li,Ke Xu,Cheng Su,Yuting Wang,Ziming Zhao,Yuan He
Effective delivery of drugs to the inflamed colon is an attractive strategy for treating inflammatory bowel disease (IBD). Here we designed a drug delivery platform for IBD treatment by hybridizing platelet membrane (PM) with phosphatidylserine (PS)-containing liposomes (PM-Lipo). Introducing PM into hybrid nanovesicles enhanced their adhesion to the inflammatory endothelium in vitro , and increased their recruitment to the inflamed colon in a mouse IBD model. Meanwhile, adding PS into PM-Lipo improved macrophage targeting and uptake in vitro and in vivo . Rosiglitazone (ROSI) loading PM-Lipo (PM-Lipo-ROSI) effectively reprogrammed the pro-inflammatory macrophages towards an anti-inflammatory status in the inflamed colon, reducing pro-inflammatory cytokine secretion and immune cell infiltration. Moreover, PM-Lipo-ROSI also promoted the epithelial barrier regeneration of the damaged colon. The present study not only provides a novel paradigm for the precision treatment of IBD, but also lays a theoretical foundation for developing nanomedicines for other inflammatory diseases.
研究领域:
纳米医学
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药物递送系统
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炎症性疾病
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生物医学工程
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免疫治疗
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胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
Clinical and Translational Medicine
·
2023
·Vol. 13
·期 4
·e1227
·
IF 10.6
Peijie Zhong,Hang Wu,Yuanqiao Ma,Xiaoxiao Xu,Yizhuo Jiang,Chaolei Jin,Qiaozhen Zhu,Xinlei Liu,Zhimin Suo,Junpeng Wang
Background Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms. Methods Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild-type mice. Clinical and histopathological parameters were monitored throughout the disease progression. Results Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS-induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor-positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild-type C57BL/6 mice. Further antibiotic-treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4 . Conclusions Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Fang Shi,Yong-Sheng Gao,Shu-Mei Han,Huan Shi,Qing-Sheng Hou,Yang Gao,Xiao-Wen Wen,Zhen-Yu Zhu,Kai Liu,Wei-Peng Gong,Ben-Shi Wang,Xin Liu,Lei Zou
There is a growing amount of research that highlights the significant connection between the development of colitis and both metabolic imbalance and the inflammatory response. Tagatose, an inherent sweetening agent and alternative to sugar, plays a crucial role in the biosynthesis of several chemicals and metabolic pathways in living organisms. However, the specific biochemical mechanism via which tagatose hinders colitis is still not understood. According to recent study, tagatose plays a crucial role in safeguarding the integrity of tight junctions inside the intestinal mucosal barrier. Furthermore, it is crucial to acknowledge the presence of a correlation between the severity of inflammatory bowel disease (IBD) and the occurrence of colorectal cancer (CRC), chemically-induced colitis in rodents, and reduced blood levels of tagatose. The treatment of tagatose resulted in a decrease in intestinal mucosal injury in mice with colitis, regardless of whether it was caused by dextran sodium sulfate (DSS) or spontaneous colitis in IL-10 -/- mice and C3H/HeJBir mice. The introduction of tagatose in a colitis model triggers a cascade of events, wherein it hinders the expulsion of cathepsin B and enhances lysosomal cohesiveness. The aforementioned method successfully inhibits the activity of myosin light chain kinase (MLCK) in the context of intestinal epithelial damage, hence impeding the deterioration of tight junction integrity and the initiation of mitochondrial dysfunction. In summary, the outcomes of the study have provided empirical evidence that substantiates the beneficial effects of tagatose in mitigating the progression of colitis. The ability to prevent the disruption of the intestinal barrier is responsible for this achievement. Hence, tagatose has promise as a therapeutic adjunct for the management of colitis.
研究领域:
胃肠病学
·
药理学
·
免疫学
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2023
·
IF 13.3
Jingang Liu,He Ren,Chen Zhang,Jiexin Li,Qian Qiu,Nan Zhang,Ning Jiang,Jonathan F. Lovell,Yumiao Zhang
The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal-IL10-EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal-IL10-EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal-IL10-EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal-IL10-EVs (C/A) features biocompatibility, pH-responsive drug release, and macrophage-targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.
研究领域:
药学
·
生物技术
·
胃肠病学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2023
·Vol. 8
·期 1
·1-17
·
IF 39.3
Liu Yi,Ji Yanhong,Jiang Ruiyi,Fang Chao,Shi Gang,Cheng Lin,Zuo Yinan,Ye Yixin,Su Xiaolan,Li Junshu,Wang Huiling,Wang Yuan,Lin Yi,Dai Lei,Zhang Shuang,Deng Hongxin
Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population. Given the increased incidence of cancer and the population ageing trend globally, it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer. In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer (CAC), we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation, although ageing does not affect the incidence of AOM-induced, sporadic non-inflammatory CRC. Mechanistically, reduced fibroblasts were observed in the colitis microenvironment of ageing mice. Through conditional lineage tracing, an important source of fibroblasts potentially derived from intestinal smooth muscle cells (ISMCs) was identified orchestrating intestinal wound healing and CAC initiation in young mice. However, the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice, accompanied by decreased intestinal wound healing and decreased CAC initiation. ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments. We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts. Meanwhile, the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice. Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment, decreased intestinal wound healing and decreased CAC initiation, similar to the phenotype of ageing mice. In addition, the data from intestine samples derived from inflammatory bowel disease (IBD) patients show that activation of YAP/TAZ also occurs in ISMCs from these patients. Collectively, our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation. Furthermore, our work also identified a potential source of fibroblasts involved in colitis and CAC.
研究领域:
胃肠病学
·
肿瘤学
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老年医学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jiahu Yao,Yang Yang,Hu Zhao,Chuanming Wang,Liang Jin,Tengyun Long,Wei Huang,Xiang Zhan,Xin Li,Xin Chen,Jinhu Xie,Bin Wu,Chuansi Wang,Liling Huang,Hongnian Pan,Xuan Nie,Changjun Yu,Wei Chen
The accumulation of reactive oxygen species (ROS) within colonic tissue represents a critical factor in the pathogenesis of inflammatory bowel disease (IBD). The application of antioxidant therapy utilizing artificial nanozymes has emerged as an effective strategy for the management of IBD. Nevertheless, current nanozymes exhibit limitations in stability, tissue compatibility, and systemic toxicity, which constrain their applicability within the biomedical domain. Herein, we designed a biocompatible colon-targeted integrated therapeutic system (BiOSe-RA@FP), the core of which is Bi 2 O 2 Se (BiOSe) nanosheets encapsulating natural plant rosmarinic acid (RA), enclosed within pH-responsive enteric hydrogel microspheres (FP). This system ensures targeted delivery of BiOSe-RA to the inflamed colon and prolongs its local retention time. BiOSe-RA fully exerts the activities of superoxide dismutase (SOD) and catalase (CAT) in the colon, effectively removing ROS (·OH, ·O 2 − , and H 2 O 2 ). Concurrently, BiOSe-RA exerts excellent anti-inflammatory activities in the colon, which could inhibit the secretion of inflammatory factors, and induce macrophages to polarize the M2 type. The ultimate effect is to preserve the integrity of the intestinal epithelial mucosal barrier and restore microbial homeostasis in the colon by mitigating intestinal oxidative stress and ameliorating the inflammatory microenvironment. The constructed BiOSe-RA@FP could regulate intestinal microbial community disorders, providing a safe and effective new solution for the treatment of IBD.
研究领域:
纳米技术
·
药学
·
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Minxuan Xu,Fang Shi,Yongshen Gao,Shumei Han,Chensuo Huang,Qinsheng Hou,Xiaoweng Wen,Bengshi Wang,Zhenyu Zhu,Lei Zou,Mingxin Xiong,Wei Dong,Jun Tan
There is a growing amount of research that highlights the significant involvement of metabolic imbalance and the inflammatory response in the advancement of colitis. Arabinose is a naturally occurring bioactive monosaccharide that plays a crucial role in the metabolic processes and synthesis of many compounds in living organisms. However, the more detailed molecular mechanism by which the administration of arabinose alleviates the progression of colitis and its associated carcinogenesis is still not fully understood. In the present study, arabinose is recognized as a significant and inherent protector of the intestinal mucosal barrier through its role in preserving the integrity of tight junctions within the intestines. Also, it is important to note that there is a positive correlation between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), as well as chemically-induced colitis in mice, and lower levels of arabinose in the bloodstream. In two mouse models of colitis, caused by dextran sodium sulfate (DSS) or by spontaneous colitis in IL-10 -/- mice, damage to the intestinal mucosa was reduced by giving the mice arabinose. When arabinose is administrated to model with colitis, it sets off a chain of events that help keep the lysosomes together and stop cathepsin B from being released. During the progression of intestinal epithelial injury, this process blocks myosin light chain kinase (MLCK) from damaging tight junctions and causing mitochondrial dysfunction. In summary, the results of the study have provided evidence supporting the beneficial effects of arabinose in mitigating the progression of colitis. This is achieved through its ability to avoid dysregulation of the intestinal barrier. Consequently, arabinose may hold promise as a therapeutic supplementation for the management of colitis.
研究领域:
胃肠病学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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