BIOCATALYSIS AND BIOTRANSFORMATION
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2020
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IF 1.863
Chou Li,Qingzhi Ji,Tongyao He,Yingying Liu,Yunqing Ma
Deconjugation of bile salts in vivo not only promotes the cholesterol metabolism of the host, but also provides cellular carbon, nitrogen and sulphur for some probiotics. In this study, the gene of BSH from Bifidobacterium bifidum (ATCC 29521) was amplified and expressed using glutathione S-transferase (GST) Gene Fusion System. The enzyme was purified in a mild conditions without denaturation and renaturation, and the molecular mass was estimated to be 35 kDa. The optimum pH for the enzyme catalysis was 5.5. The BSH enzyme was stable from 37 to 57 °C. In addition, this enzyme was completely inhibited by Cu2+, while many other metal ions only gave moderate inhibition. Hydrolysis efficiency of BSH was quantified in two ways: ninhydrin colouration method and high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD). The hydrolysis process was clearly observed through real-time picture monitoring. The activity of BSH on glycine-conjugated bile salts was better than on taurine-conjugated bile salts. The proportion of hydrolysis for both sodium glycochenodeoxycholate (GCDCA) and sodium glycoursodeoxycholate (GUDCA) were more than 90% in 60 min. However, the proportion of hydrolysis for sodium taurochenodeoxycholate (TCDCA) and sodium tauroursodeoxycholate (TUDCA) were only 68% and 43% at the same condition. The study of this paper provides a better choice for hydrolysis of glycine-conjugated bile salts.HighlightsThe specificity of BSH was high for glycine-conjugated bile salts.Hydrolysis process of bile acid was obtained through real-time picture monitoring.Hydrolysis efficiency of BSH was quantified in two ways: ninhydrin colouration method and HPLC-ELSD.
研究领域:
微生物学
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酶学
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益生菌研究
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代谢
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Zhouya Bai,Yunhui Zhang,Xiaojun Huang,Denglin Luo,Shaobin Gu,Kangyi Zhang,Shaoping Nie
The gut microbiota is vital in regulating glycolipid metabolism through bile acid pathways, while pectin maintains gut flora balance. Polysaccharides from red kidney beans (RKPs), particularly pectic types, lower blood sugar and lipids, although the mechanism is unclear. Our findings showed that RKP intervention significantly affects primary bile acid synthesis, especially conjugated bile acids, notably taurocholic acid (TCA). Correspondingly, FXR and TGR5 were identified as key receptors in glucolipid metabolism. Further, Akkermansia was proven to be a vital strain and to effectively improve glycolipid metabolism associated with regulating the activity of bile salt hydrolases (BSHs) and bile acid composition, especially for TCA in diabetic mice. Our results provide an antidiabetic mechanism of RKP and suggest that enriched Akkermansia via regulating the vitality of BSH is altered in response to the composition of bile acid, especially for TCA, thereby alleviating glycolipid metabolism through the TCA-FXR/TGR5 axis.
研究领域:
微生物组学
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代谢生物学
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内分泌学
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营养科学
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分子药理学
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胆汁酸代谢
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肠道菌群与宿主互作
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Jiejian Chen,Qiyao Yang,Minchen Liu,Mengting Lin,Tiantian Wang,Zhentao Zhang,Xincheng Zhong,Ningning Guo,Yiying Lu,Jing Xu,Changsheng Wang,Min Han,Qichun Wei
Purpose Boron neutron capture therapy (BNCT) is an emerging binary radiotherapy, which is limited for application due to the challenge of targeted delivery into tumor nowadays. Here, we propose the use of iRGD-modified polymeric nanoparticles for active targeted delivery of boron and doxorubicin (DOX) in BNCT.Methods 10B-enriched BSH was covalently grafted to PEG-PCCL to prepare 10B-polymer, then surface-modified with iRGD. And, DOX was physically incorporated into polymers afterwards. Characterization of prepared polymers and in vitro release profile of DOX from polymers were determined by several methods. Cellular uptake of DOX was observed by confocal microscope. Accumulation of boron in cells and tissues was analyzed by ICP-MS. Biodistribution of DOX was studied by ex vivo fluorescence imaging and quantitative measurement. Tumor vascular normalization of Endostar for promoting delivery efficiency of boron on refractory B16F10 tumor was also studied.Results The polymers were monodisperse and spheroidal in water with an average diameter of 24.97 nm, which were relatively stable at physiological pH and showed a sustained release of DOX, especially at endolysosomal pH. Enhanced cellular delivery of DOX was found in iRGD-modified polymer group. Cellular boron uptake of iRGD-modified polymers in A549 cells was remarkably raised fivefold (209.83 ng 10B/106 cells) compared with BSH. The polymers represented prolonged blood circulation, enhanced tumor accumulation of 10B against BSH, and favorable tumor:normal tissue boron concentration ratios (tumor:blood = 14.11, tumor:muscle = 19.49) in A549 tumor-bearing mice 24 hrs after injection. Both fluorescence imaging and quantitative measurement showed the highest tumor accumulation of DOX at 24 hrs after injecting of iRGD-modified polymers. Improvement of vascular integrity and reduction of vascular mimicries were found after Endostar injection, and raised tumor accumulation of boron as well.Conclusion The developed nanoparticle is an inspiring candidate for the safe clinical application for BNCT.
研究领域:
癌症治疗
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纳米技术
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药学
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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
Food Bioscience
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2024
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IF 4.8
Yu Shen,Baorong Jiang,Zejia Hao,Chenchen Zhang,Zhan Zhang,Qian Wu,Lei Li,Ping Jiang
Both chromium picolinate (Cr-pic) and chromium trichloride (CrCl 3 ) were used as dietary supplements in agricultural products and foodstuffs. We found either these two forms of Cr(III) could ameliorate inflammation and cholestasis in DDC-induced primary sclerosing cholangitis (PSC) mice via regulating bile acid metabolism. Although two Cr(III) are able to alleviate hepatic inflammation by reducing the aggregation of macrophage, Cr-pic exhibiting superior efficacy in decreasing M1 macrophages. Two Cr(III) show inconsistent in regulating intestinal Fxr , but Cr-pic could active intestinal Fxr , promoting intestinal barrier repair. Additionally, both Cr-pic and CrCl 3 enhanced functional abundance of BSH enzymes involved in bile acid transformation, with Cr-pic seems to perturb the abundance of genus more than CrCl 3. In conclusion, this study highlights the efficacy of Cr-pic and CrCl 3 in mitigating inflammation and cholestasis in PSC, Cr-pic is expected superior than CrCl 3 to be supplement ingredient used in PSC treatment via regulating bile acid metabolism.
研究领域:
营养学
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胃肠病学
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药理学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Xiaoxi Zhang,Shuai Zhao,Shengbao Cai,Junjie Yi,Tao Wang,Zhijia Liu,Yanfei Wang
Hypercholesterolemia is a cardiovascular condition resulting from elevated cholesterol levels. This study screened seven Lactiplantibacillus plantarum strains with efficient cholesterol (CHOL)-lowering abilities and investigated the mechanisms of CHOL degradation. HPLC analysis indicated that L. plantarum D5205 had high bile salt hydrolase (BSH) activity with a bile salt metabolism rate of 31.65% ± 0.43%, while L. plantarum C4507 excelled with a CHOL metabolism rate of 61.12% ± 0.32%. Microscopic analysis revealed that these strains reduced CHOL mainly through extracellular binding and intracellular metabolism. The genomic analysis indicated that the BSH and transporter protein genes were strongly associated with the CHOL metabolism capabilities of these strains. The molecular docking and molecular dynamics simulation analysis revealed the binding mechanism between sodium taurocholate and BSH. This study provides a method for screening CHOL-lowering lactic acid bacteria and uncovers their potential mechanisms for reducing CHOL levels.
研究领域:
微生物学
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基因组学
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生物信息学
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生物技术
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心血管医学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
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IF 4
Xiangxiang Zhao,Ke Xie,Yanghong Wang,Yao He,Hua Wei,Xueying Tao
Human breast milk is a recognized potential source of probiotics. In this study, sixteen lactic acid bacteria (LAB) were isolated from human breast milk. Among them, eleven strains, including seven strains of Limosilactobacillus fermentum ( L. fermentum ) and four strains of Lacticaseibacillus paracasei ( L. paracasei ), were systematically evaluated for their probiotic properties. Comprehensive assays, including survival in acidic and simulated intestinal fluid, antioxidant capacity, surface physicochemical properties, adherence to intestinal epithelial cells, antimicrobial properties, and in vitro anti-obesity potential (α-glucosidase inhibitory activity, cholesterol removal capacity, bile salt hydrolase activity (BSH) and lipase activity), as well as antibiotic resistance patterns and a principal component analysis, were conducted. The results showed that ELPA01 could effectively reduce cholesterol levels and inhibit Gram-negative pathogens, while ELFE07 exhibited strong α-glucosidase inhibitory activity and high BSH and antioxidant activities. These results demonstrate that both ELPA01 and ELFE07 may be promising candidates for the next generation of anti-obesity probiotics.
研究领域:
微生物学
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营养学
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生物技术
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药理学
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食品科学
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产品关联
DOI
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2024
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IF 2.6
Zhicheng Zhang,Xin Wang,Qi Dai,Yaxin Qin,Xiaoyan Sun,Minoru Suzuki,Xiaoying Ying,Min Han,Qichun Wei
Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 (10B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro, AuNPs-BSH&PEG-cRGD increased 10B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor αvβ3. In a subcutaneous glioma mouse model, 6 hours post-intratumoral administration, the 10B concentration in tumors was 17.98 μg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 μg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents.
研究领域:
肿瘤学
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纳米技术
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放射治疗
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
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2023
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IF 5.2
Li Guangquan,Wang Xianze,Liu Yi,Gong Shaoming,Yang Yunzhou,Wang Cui,Wang Huiying,He Daqian
Bile acids(BAs) are important components of bile and play a significant role in fat metabolism. However, there is currently no systematic evaluation of the use of BAs as feed additives for geese.This study aimed to investigate the effects of adding BAs to goose feed on growth performance, lipid metabolism, intestinal morphology, mucosal barrier function, and cecal microbiota. A total of 168 28-day-old geese were randomly assigned to four treatment groups and fed diets supplemented with 0, 75, 150, or 300 mg/kg of BAs for 28 days. The addition of 75 and 150 mg/kg of BAs significantly improved the feed/gain (F/G) (p < 0.05).The addition of BAs decreased abdominal fat percentage and serum total cholesterol (TC) levels, with 150 mg/kg of BAs significantly reducing serum triglyceride levels and increased expression of Farnesoid X Receptor (FXR) mRNA in the liver(p < 0.05), 300 mg/kg of BAs significantly increasing the expression level of liver peroxisome proliferator-activated receptor α (PPARα) (p < 0.05). In terms of intestinal morphology and mucosal barrier function, 150 mg/kg of BAs significantly increased villus height (VH) and VH/crypt depth (CD) in the jejunum (p < 0.05). The addition of 150 and 300 mg/kg of BAs significantly reduced the CD in the ileum, while increasing VH and VH/CD (p<0.05). Additionally, the addition of 150 and 300 mg/kg of BAs significantly increased the expression levels of zonula occludens-1 (ZO-1) and occludin in the jejunum. Simultaneously 150mg/kg and 300mg/kg BAs increased the total short-chain fatty acids (SCFA) concentrations in the jejunum and cecum(p < 0.05).Supplementation with BAs resulted in a significant increase in the ɑ-diversity of cecal microbiota and a decrease in the abundance of Proteobacteria in the cecum. The addition of 150 mg/kg of BAs significantly reduced the abundance of Bacteroidetes and increased the abundance of Firmicutes. Moreover,Linear discriminant analysis Effect Size analysis (LEfSe) showed that the abundances of bacteria producing SCFA and bile salt hydrolases (BSH) were increased in the BAs-treated group. Furthermore, Spearman’s analysis showed that the genus Balutia, which is negatively correlated with visceral fat area, was positively correlated with serum high-density lipoprotein cholesterol (HDL-C), while Clostridium was positively correlated with intestinal VH and VH/CD. In conclusion, BAs can be considered an effective feed additive for geese, as they increased SCFA concentration, improve lipid metabolism and intestinal health by enhancing the intestinal mucosal barrier, improving intestinal morphology, and altering the cecal microbiota structure.
研究领域:
动物科学
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营养学
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微生物学
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代谢学
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产品关联
DOI
PubMed
高影响因子
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