Journal of Functional Foods
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2025
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IF 4
Xiaoxiang Chen,Yan Chen,Zhichao Chen,Jiayao He,Xiahao Sun,Zuisu Yang
This study explored the beneficial effects of canthaxanthin (CX) on dextran sulfate sodium (DSS)-induced chronic colitis in mice and its underlying mechanisms. Oral administration of CX alleviated colitis severity, as demonstrated by reduced weight loss, diarrhea, hematochezia, colon shortening, and pathological colon injury. Improvements in intestinal permeability and inflammation were indicated by significantly decreased levels of permeability markers and pro-inflammatory cytokines. Moreover, CX mitigated mucus barrier dysfunction by enhancing goblet cell proliferation and mucin-2 secretion. CX reinforced the epithelial barrier by preserving tight junction function and preventing excessive apoptosis of colonic epithelial cells. Furthermore, CX modulated DSS-induced gut microbiota dysbiosis by reshaping the diversity and structure of both bacterial and fungal communities, increasing the abundance of beneficial microbes while reducing the prevalence of harmful microbes. To conclude, CX can effectively alleviate chronic colitis via modulating intestinal barrier function and maintaining microbiome homeostasis, providing a potential dietary therapy for UC.
研究领域:
免疫学
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营养学
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微生物学
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Zhong-Hao Ji,Hai-Xiang Guo,Bingbing Wang,Wen-Zhi Ren,Jin-Ping Hu,Chengzhen Chen,Bao Yuan
Ulcerative colitis (UC) significantly impairs quality of life and incurs substantial economic costs. Apigenin, a flavonoid abundant in fruits and vegetables, has demonstrated potential in UC management. Utilizing DSS-induced UC mouse models and LS 174 T goblet cell models, this study elucidates apigenin's protective mechanisms. Dietary supplementation with 40 mg/kg apigenin markedly alleviated UC symptoms. Antibiotic-mediated microbiota depletion confirmed that apigenin's efficacy is independent of gut microbiota. Mechanistically, apigenin enhances SERCA2 expression to maintain intracellular calcium homeostasis, thereby inhibiting excessive activation of the PERK-eIF2α-ATF4-CHOP pathway, reducing goblet cell apoptosis, and preserving mucosal barrier integrity. These findings provide a robust theoretical foundation for apigenin as a dietary supplement in the prevention and mitigation of colitis.
研究领域:
生物学
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医学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Gut Microbes
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2025
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IF 11
Yong Sun,Qiwen Wang,Yao Jiang,Jiamin He,Dingjiacheng Jia,Man Luo,Wentao Shen,Qingyi Wang,Yadong Qi,Yifeng Lin,Ying Zhang,Lan Wang,Liangjing Wang,Shujie Chen,Lina Fan
Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.
研究领域:
肿瘤学
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微生物学
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免疫学
✓ 已验证
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
Cancer Communications
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2023
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IF 16.2
Shujie Chen,Lina Fan,Yifeng Lin,Yadong Qi,Chaochao Xu,Qiwei Ge,Ying Zhang,Qiwen Wang,Dingjiacheng Jia,Lan Wang,Jianmin Si,Liangjing Wang
Background The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is not well explored. Here, we elucidated the functional role of Bifidobacterium adolescentis ( B.a ) on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts (CAFs) in CRC. Methods Different CRC animal models and various cell line models were established to explore the function of B.a on CRC. The single-cell RNA sequencing (scRNA-seq) or flow cytometry was used to detect the cell subsets in the TME of CRC. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1 (GAS1) on CD143 + CAFs. Chromatin immunoprecipitation quantitative real-time PCR (CHIP-qPCR) was performed to investigate the regulation of transcription factor 4 (TCF4) on GAS1. Multi-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue microarray. Results We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of GMrepo. Supplementation with B.a suppressed Apc Min/+ spontaneous or AOM/DSS-induced tumorigenesis in mice. scRNA-seq revealed that B.a facilitated a subset of CD143 + CAFs by inhibiting the infiltration of Th2 cells, while promoting the TNF-alpha + B cells in TME. CD143 + CAFs highly expressed GAS1 and exhibited tumor suppressive effect. Mechanistically, GAS1 was activated by the Wnt/β-catenin signaling in CD143 + CAFs. B.a abundance was correlated with the expression level of CD143 and GAS1. The level of CD143 + CAFs predicted the better survival outcome in CRC patients. Conclusions These results highlighted that B.a induced a new subset of CD143 + CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.
研究领域:
癌症生物学
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微生物学
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分子生物学
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细胞生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
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2024
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IF 11.4
Xue Bai,Zhiguang Duan,Jianjun Deng,Zhuo Zhang,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Introduction Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored. Objectives We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota. Methods We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC. Results Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila ( A. muciniphila ), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila -mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC. Conclusion Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.
研究领域:
癌症生物学
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微生物学
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药理学
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分子生物学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2022
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IF 9.273
Huijuan Zhang,Yaping Wang,Mengting Li,Kexuan Cao,Zijun Qi,Ling Zhu,Zhenzhong Zhang,Lin Hou
Colorectal cancer is often accompanied by multiple organ metastasis. Anaerobic Bifidobacterium Infantis (BI) bacterial can selectively grow in hypoxic colorectal tumor microenvironment (TME), to own the natural advantage of preferentially colorectal tumor targeting. Herein, a self-guidance biological hybrid drug delivery system (BI-ES-FeAlg/DOX) based on BI was constructed to inhibit the proliferation and metastasis of colon cancer. Results demonstrated that BI-ES-FeAlg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues. Then DOX was released to kill tumor cells along with the phase transition (solid to liquid) of FeAlg hydrogel, due to Fe 3+ was reduced to Fe 2+ by intracellular GSH. Meanwhile, BI-ES selectively colonized into tumors and expressed endostatin (ES) protein to down-regulate VEGF and bFGF expression, exerting anti-angiogenic effect. Moreover, FeAlg catalyzed H 2 O 2 in the local tumor to generate cytotoxic ·OH, further enhancing the antitumor effect. The pharmacodynamic result in AOM/DSS model proved that BI-ES-FeAlg/DOX had the best therapeutic effect, with the final V/V 0 of 2.19 ± 0.57, which was significantly lower than the other groups. Meanwhile, on CT-26 tumor-bearing model, it also showed an outstanding anti-tumor effect with inhibition rate of 82.12% ± 3.08%. In addition, lung metastases decreased significantly in tumor metastasis model after BI-ES-FeAlg/DOX treatment.
研究领域:
肿瘤学
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药学
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生物技术
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分子生物学
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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