INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yuan-Yuan Li,Jing-Wen Sun,Lei Chen,Yong-Ming Lu,Qing-Xi Wu,Chao Yan,Yan Chen,Mei Zhang,Wen-Na Zhang
A new polysaccharide fraction (ATP) was obtained from Armillariella tabescens mycelium. Structural analysis suggested that the backbone of ATP was →4)- α -D-Glc p (1 → 2)- α -D-Gal p (1 → 2)- α -D-Glc p (1 → 4)- α -D-Glc p (1→, which branched at O-3 of →2)- α -D-Glc p (1 → and terminated with T- α -D-Glc p or T- α -D-Man p . Besides, ATP significantly alleviated ulcerative colitis (UC) symptoms and inhibited the production of pro-inflammation cytokines (IL-1 β , IL-6). Meanwhile, ATP could improve colon tissue damage by elevating the expression of MUC2 and tight junction proteins (ZO-1, occludin and claudin-1) levels and enhance intestinal barrier function through inhibiting the activation of MMP12/MLCK/ p -MLC2 signaling pathway. Further studies exhibited that ATP could increase the relative abundance of beneficial bacteria such as f. Muribaculacese , g. Muribaculaceae , and g. Alistips , and decrease the relative abundance of g. Desulfovibrio , g. Colidextribacter , g. Ruminococcaceae and g .Oscillibacter , and regulate the level of short-chain fatty acids. Importantly, FMT intervention with ATP-derived microbiome certified that gut microbiota was involved in the protective effects of ATP on UC. The results indicated that ATP was potential to be further developed into promising therapeutic agent for UC.
研究领域:
药理学
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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
Food & Function
·
2022
·Vol. 14
·期 1
·122-132
·
IF 6.317
Ningbo Qin,Hongxu Liu,Yu Cao,Zhen Wang,Xiaomeng Ren,Xiaodong Xia
The seeds from Gleditsia sinensis Lam., a common ecologically and economically useful tree, have high economic and nutritional value. The protective effect of polysaccharides from Gleditsia sinensis Lam. seeds (ZJMP) against dextran sulfate sodium-induced colitis in mice was investigated in this study. ZJMP alleviated weight loss, reduced the disease activity index, prevented colon shortening, alleviated colonic tissue damage, and restored goblet cell secretion in colitic mice. Dietary ZJMP reduced proinflammatory cytokine overproduction in the colonic mucosa and serum, which was accompanied by suppression of NO levels and MPO and SOD activities. The addition of ZJMP increased the expression of Muc2 and tight junction proteins. Furthermore, dietary ZJMP partially reversed the alteration of gut microbiota in colitic mice by boosting the abundance of beneficial bacteria like Akkermansia, Lactobacillus, and Christensenella while lowering the abundance of harmful bacteria like Bacteroides, Prevotella, and Mucispirillum. Additionally, the decreased production of short-chain fatty acids in the colitic mice was recovered by ZJMP administration. The findings demonstrated the anti-inflammatory properties and mechanism of dietary ZJMP in the colon, which is essential for the sensible application of ZJMP in the prevention and amelioration of inflammation-related diseases as a nutritional supplement.
研究领域:
营养学
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免疫学
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微生物学
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药理学
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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 ETHNOPHARMACOLOGY
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2022
·
IF 5.195
Yajie Cai,Xiaojiaoyang Li,Qi Han,Jinzhao Bai,Qi Zheng,Rong Sun,Runping Liu
Ethnopharmacological relevance Ulcerative colitis (UC) is widely believed to be a leading risk factor of colorectal cancer . Gut microbiota is a known vital player in the progression of UC. Si–Ni-San (SNS) has been considered to effectively treat colitis in clinical practice during thousands of years, yet whether SNS ameliorated acute colitis mouse model by modulating intestinal flora has not been distinctly elucidated. Aim of the study Our study aimed to elucidate the effect of SNS against acute murine colitis and focused on the underlying mechanisms of SNS targeting gut microbiota . Materials and methods 16S RNA sequencing, molecular biological analysis, and fecal microbiota transplants (FMT) were conducted to reveal the mechanisms of SNS in regulating gut microbiota. Results In our study, SNS dramatically inhibited DSS-induced acute inflammatory responses by improving gut microbiota dysbiosis , as evidenced by decreased abundance proinflammatory species, upregulated abundance of anti-inflammatory species and potentially altered microbiota metabolite metabolism. Additionally, intestinal flora knockout and FMT experiments confirmed that the therapeutic effect of SNS on colitis was dependent on gut microbiota, and specifically on favoring the growth of potential probiotics , Akkermansia genus. Furthermore, we found that SNS alone and SNS combined with Akkermansia muciniphila ( A. muciniphila ) increased Mucin 2 (MUC2) production, thus enhancing the competitive edge of A. muciniphila among pathogenic gut microbiota. Conclusion Our study shed lights on the underlying mechanism of SNS in attenuating acute murine colitis from the perspective of intestinal flora and provides novel insights into the discovery of adjacent therapeutic strategy against colitis based on SNS and probiotics. Classification Gastro-intestinal system
研究领域:
消化系统
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药理学
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微生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
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IF 5.4
Qianru Li,Yuhe Zhu,Jiahui Ding,Weizhen Pan,Yuwei Hu,Jiao Lu,Sihai Gao,Hongyang Jiang,Zhongyuan Yin,Songwei Tan
Gene therapy is often limited by gene vectors. To reduce the impact of intracellular reactive oxygen species and improve transfection efficiency, thioether bonds were introduced in poly(β-amino ester) (PBAE), a well-known nonviral gene vector, to synthesize PBAE-poly(β-thioether ester) copolymer (PBAE-TE). By varying the monomer feeding ratio and reaction time, the optimized copolymer (PBAE-TE2–5) showed the highest transfection efficiency in SiHa and HeLa cells (75.00 and 78.70%) with a 75:1 copolymer/GFP ratio. PBAE-TE2–5 also demonstrated superior transfection performance compared to PBAE in multiple cell lines (HeLa, Me180, C666–1, and HEK 293T) and better penetration capability in 3D spheroid cell models (SiHa and HEK 293T). The PBAE-TE2–5-CRISPR/Cas9 plasmid polyplexes could effectively edit target genes in HEK 293T (MUC2) and SiHa (HPV16 E7) cells, and inhibit cancer cell proliferation both in vitro and in vivo. These findings highlight the promising potential of PBAE-TE as an effective gene delivery system.
研究领域:
生物材料
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基因治疗
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高分子化学
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生物医学工程
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分子生物学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
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IF 4.511
Ya Ma,Xiaoling Tong,Yamei Huang,Xin Zhou,Chunhua Yang,Jiucun Chen,Fangyin Dai,Bo Xiao
Silk sericin (SS) is abundant in silk industry wastewater, and it has emerged as a promising natural protein for biomedical research. However, its therapeutic potential against ulcerative colitis (UC) has not been exploited. The objective of this study is to investigate the therapeutic effects of SS in a dextran sulfate sodium-induced UC mouse model, and further discover its underlying mechanisms. The purified SS molecules showed negative cytotoxicity, and could be efficiently internalized by colonic epithelial cells and macrophages. In vitro experiments revealed that it could accelerate the mucosal healing, down-regulate the production of pro-inflammatory factors, increase the secretion of anti-inflammatory cytokines, and eliminate the intracellular reactive oxygen species. Finally, animal experiments confirmed that oral administration of hydrogel (chitosan/alginate)-embedding SS molecules attenuated UC-induced symptoms (e.g., body weight loss, colon shortening, increase of spleen weight, and histopathological appearance), which was supported by signs of mucosal healing, anti-inflammation, and elevation of the amounts of tight junction proteins (occludin and zonula occludens-1) and mucin protein (MUC2). Taken together, our results demonstrate that SS can be exploited as a promising oral natural therapeutic for UC treatment with the aid of hydrogel.
研究领域:
生物医学研究
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胃肠病学
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药理学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Liping Han,Ting Li,Yingying Wang,Weizi Lai,Hengpu Zhou,Zhuangwei Niu,Jie Su,Guiyuan Lv,Guangji Zhang,Jianli Gao,Jianbo Huang,Zhaohuan Lou
Ethnopharmacological relevance Weierning tablet (WEN) is a traditional Chinese patent medicine widely used in clinical for chronic atrophic gastritis (CAG) therapy for years. However, the underlying mechanisms of WEN on anti-CAG are still unveiled. Aim of the study The present study aimed to elucidate the characteristic function of WEN on anti-CAG and to illuminate its potential mechanism. Methods The CAG model was established by gavage rats with a modeling solution (consisting of 2% sodium salicylate and 30% alcohol) with irregular diets and free access to 0.1% ammonia solution for two months on end. An enzyme-linked immunosorbent assay was used to measure the serum levels of gastrin , pepsinogen , and inflammatory cytokines. qRT-PCR was applied to measure mRNA expressions of IL-6 , IL-18, IL-10, TNF-α, and γ-IFN in gastric tissue. Pathological changes and the ultrastructure of gastric mucosa were examined by hematoxylin and eosin staining and transmission electron microscopy , respectively. AB-PAS staining was applied to observe the intestinal metaplasia of gastric mucosa. Immunohistochemistry and Western blot were used to measure the expression levels of mitochondria apoptosis-related proteins and Hedgehog pathway-related proteins in gastric tissues. Expressions of Cdx2 and Muc2 protein were determined by immunofluorescent staining. Results WEN could dose-dependently lower the serum level of IL-1β and the mRNA expressions of IL-6, IL-8, IL-10, TNF-α, and γ-IFN in gastric tissue. Also, WEN significantly alleviated the collagen deposition in gastric submucosa, regulated the expressions of Bax, Cleaved-caspase9, Bcl2 , and Cytochrome c to reduce the apoptosis of gastric mucosa epithelial cells, and maintained the integrity of the gastric mucosal barrier. Moreover, WEN could reduce protein expressions of Cdx2, Muc2, Shh, Gli1, and Smo, and reverse intestinal metaplasia of gastric mucosa to block the progress of CAG. Conclusion This study demonstrated a positive effect of WEN on improving CAG and reverse intestinal metaplasia. These functions were related to the suppression of gastric mucosal cells' apoptosis and the inhibition of Hedgehog pathways’ activation.
研究领域:
药理学
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胃肠病学
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中医
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
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IF 4.8
Huanhuan Liu,Jiahui Li,Chunhong Yan,Jiaxiu Liu,Dongyun Zhao,Shugang Li,Xiaodong Xia
Inflammatory bowel disease is characterized by compromised epithelium barrier function and hyperactive intestinal inflammation. This study aims to investigate the effects of punicalagin, a bioactive ellagitannin in pomegranate, on dextran-sodium sulfate (DSS) - induced colitis in mice and to examine the underlying mechanisms involved. Oral administration of punicalagin (100 mg/kg/day) effectively mitigated the severity of experimental colitis in mice, evidenced by increased colon length, improved intestinal permeability, and decreased histological scores. Punicalagin up-regulated the mRNA expression level of Muc2 in and the protein expression of zonula occludens-1 (ZO-1) and Occludin in colitic mice. Moreover, punicalagin effectively decreased reactive oxygen species (ROS) levels in the colon, and in Caco-2 cells exposed to H 2 O 2 in vitro . Mechanistically, punicalagin attenuated inflammation by inhibiting the secretion of interleukin-6 (IL-6) and the phosphorylation of the NF-κB/STAT3 pathway. In addition, punicalagin increased adenosine monophosphate activated protein kinase (AMPK) phosphorylation in the colon of DSS-treated mice and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages. Knocking down AMPKα by siRNA diminished punicalagin's anti-inflammatory function in RAW 264.7 macrophages exposed to LPS. Furthermore , molecular docking analysis, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) analysis supported the direct interaction between punicalagin and AMPK. In conclusion, punicalagin could mitigate DSS-induced colitis through enhancing intestinal epithelial barrier, alleviating oxidative stress, and attenuating inflammation partly through modulation of AMPK–NF–κB-STAT3 pathway.
研究领域:
药理学
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免疫学
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胃肠病学
✓ 已验证
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2023
·
IF 4.3
Fangfang Min,Jielun Hu,Tao Huang,Yousheng Huang,Shaoping Nie,Tao Xiong,Mingyong Xie
Lactobacillus ( L. ) casei NCU011054 isolated from infant feces has been proven to be a potential probiotic in vitro . The present study aimed to investigate the effects of L. casei NCU011054 on the immune response and gut microbiota in cyclophosphamide (CP)-induced immunosuppression mice. Results indicated that L. casei NCU011054 could increase the levels of mucin (Muc2) and tight junction proteins (ZO-1, occludin and claudin-1). Moreover, L. casei NCU011054 was found to upregulate TLRs/NF-κB pathway (TLR-2, TLR-4, TLR-6, p65 and NF-κB) and two transcription factors (T-bet and GATA-3) mRNA levels, and enhance the number of CD4 + T cells. Th1-related cytokines (IL-12p70, IFN-γ and TNF-α) and Th2-related cytokines (IL-2, IL-4, IL-6 and IL-10) significantly increased after L. casei NCU011054 treatment. More importantly, L. casei NCU011054 increased the ratio of T-bet to GATA-3 and IFN-γ to IL-4. Apart from these, L. casei NCU011054 remodeled gut microbiota and modulated gut metabolites in CP-induced immunosuppressed mice. The correlation analysis showed that Lactobacillus upregulated by L. casei NCU011054 was positively correlated with TLRs/NF-κB pathway, and the ratio of T-bet to GATA-3 and IFN-γ to IL-4. All findings revealed that L. casei NCU011054 could improve intestinal immune dysfunction and modulate Th1/Th2 balance via TLRs/NF-κB pathway in CP-induced immunosuppressed mice.
研究领域:
免疫学
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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
Food & Function
·
2021
·Vol. 12
·期 16
·7343-7357
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IF 5.396
Songtao Fan,Zhihong Zhang,Yadong Zhong,Chang Li,Xiaojun Huang,Fang Geng,Shaoping Nie
Fructans such as fructo-oligosaccharides (FOS) and inulin have been reported to directly regulate ileal inflammatory responses in lipopolysaccharide (LPS)-induced endotoxemic mice, without alterations in the colonic microbiota. Firstly, we replicated this model and found that a single gavage of 10 mg g−1 of fructans directly promoted caecal acetate and propionate production. Thus, the previous understanding of microbiota-independent effects of prebiotic fructans in endotoxemic mice has been challenged. In parallel, we performed a daily gavage of 160 mg kg−1 of inulin, xylan, or Dendrobium officinale polysaccharides (DOP) for two weeks prior to LPS injection. The long-term intake of prebiotic fibres reduced the bacterial load in the spleen and mesenteric lymph nodes (MLNs), and in comparison, a single gavage of fructans increased that. However, the long-term intake was unable to improve the short-chain fatty acid (SCFA) synthesis and epithelial barrier function that were impaired by LPS. Notably, the three fibre types consistently reduced the expression of mucin 2 (MUC2) and variously modulated critical mediators (IL-18, IL-22, and HIF-1α) to regulate the host–commensal microbiota interactions in the ileum. In addition, the three fibre types consistently inhibited the inflammatory T helper (Th) cell response in the ileum, while they diversely modulated the peripheral and systemic Th cell responses. Overall, the prebiotic fibres displayed microbiota-related changes in endotoxemic mice, and the potential associations with the in vivo anti-inflammatory effects of prebiotic fibres need further investigation.
研究领域:
胃肠病学
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免疫学
·
微生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子