Aquaculture Reports
·
2025
·
IF 3.7
Jia Xu,Fajun Jiang,Yichao Li,Ermeng Yu,Shiwei Xie,Junxiang Lai,Fan Wang
Present study investigated the effects and underlying mechanisms of different primary bile acids (BAs) on liver health in pearl gentian grouper ( Epinephelus fuscoguttatus ♂ × Epinephelus lanceolatus ♀) fed a high-lipid (HL) diet. A total of 375 healthy grouper (15.21 ± 0.05 g) was assigned randomly to 15 tanks, ensuring three replicates per group: control (C), HL, HL with glycocholic acid (GCA), HL with taurocholic acid (TCA), and HL with cholic acid (CA), for 8 weeks. The HL and all BAs treatment did not affect the FBW and WG ( P > 0.05). Compared to C, the HL increased the lipid deposition and the il1β and tnfα expression, decreased the SOD and catalase activities ( P < 0.05). Compared to HL, the GCA increased the lipid deposition, il1β and tnfα expression, malondialdehyde level, and pentanoic acid concentration ( P < 0.05). Compared to HL, the TCA decreased the lipid deposition, il1β and tnfα expression, malondialdehyde level, hexanoic acid and pentanoic acid concentration, increased the SOD and catalase activities ( P < 0.05). Compared to HL, the CA increased the lipid deposition and decreased pentanoic acid concentration ( P < 0.05). Furthermore, all BA treatment groups were found to increase the size of the BA pool. The GCA, TCA, and CA treatments did not induce substantial changes in the structure and composition of the gut microbiota. The composition of SCFAs and BAs is influenced by the dietary intake of different BAs, resulting in distinct microbial-metabolite correlation. In summary, TCA protected grouper form liver impairment induced by a HL diet via improving lipid metabolism and inflammatory responses, and increasing antioxidant capacity.
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CHROMATOGRAPHIA
·
2026
·
IF 1.6
Wang Meng,Zhang Renjun,Shang Lulu,Zhang Jingzhen,Wang Liwei,Zhang Mo
Comprehensive profiling of carboxyl metabolites (CMs) is critical for biomarker discovery in disease pathogenesis but remains challenging due to matrix interference and poor ionization in mass spectrometry (MS). To overcome these limitations, we developed APH (amino-terminated polyuria–magnetic hexamethylenediamine composite), an integrated chemoselective probe for superior separation and detection. APH combines a magnetic Fe₃O₄@SiO₂ core for rapid isolation, a functionalized polyurea shell with high-density binding sites, a chemoselective moiety for covalent CMs capture, and a cleavable linker incorporating an MS signal-enhancing tag. This design enables specific enrichment of CMs directly from complex biosamples and efficient matrix removal via magnetic separation and gentle analyte release. Applied to mouse cecum samples, APH demonstrated deep carboxyl sub-metabolome profiling capabilities. By effectively reducing matrix suppression and enhancing sensitivity, APH facilitates the annotation of low-abundance CM biomarkers previously obscured in conventional analyses. This platform advances separation science for targeted metabolomics in biomarker research.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Chenhui Gu,Xuewen Hu,Baixi Shan,Xiaojing Wu,Jun Chen
Er-Miao-Wan formula (EMW), composed of Phellodendri Chinensis Cortex and Atractylodis Rhizoma, is widely used in the treatment of hyperuricemia (HUA), gout, and related complications as a classic compound formula. However, its mechanisms for the treatment of HUA still need to be further systematically investigated. The study aimed to perform modern analytical techniques to elucidate the mechanisms of EMW in improving the symptoms of HUA from the perspective of metabolomics. We used a high-fructose diet to establish a rat model of HUA to evaluate the effects of EMW on improving HUA. Next, we established a targeted metabolomics analysis method to quantitatively analyze purine metabolites in plasma by using ultra-high-performance liquid chromatography with ultraviolet and triple quadrupole mass spectrometry (UHPLC-UV-QQQ MS), and combined with plasma non-targeted metabolomics analysis by using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF MS) to clarify the potential mechanisms of EMW to improve HUA. Oral administration of EMW could significantly increase the urinary uric acid and decrease the serum uric acid, and exhibited a remarkable effect on improving HUA. Plasma targeted metabolomics analysis showed that six purine metabolites related to HUA, including uric acid, hypoxanthine , xanthine , deoxyadenosine , deoxyguanosine , and deoxyinosine , were changed in the EMW-treated group. Further, principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) showed that the mechanism of EMW interfering with purine metabolic pathway in the rats with HUA could be different from that of allopurinol . On the basis of plasma non-targeted metabolomics, PCA and orthogonal partial least squares discriminant analysis (OPLA-DA) screened and identified 23 potential biomarkers in the rats with HUA, and 11 biomarkers showed a trend of reversion after the intervention of EMW. The pathway analysis suggested that EMW might have therapeutic effects on the rats with HUA via the metabolic pathways including phenylalanine metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In this study, a plasma targeted metabolomics method that can simultaneously quantify nine purine metabolites in rats with HUA was established for the first time, which can be used to study diseases closely related to HUA. In addition, we further explored the overall effect of EMW on HUA in combination with the metabonomic method established by non-targeted metabolomics, which was helpful to solve the defect that the pharmacological mechanism caused by multi-components and multi-targets of traditional Chinese medicine was difficult to explain scientifically and comprehensively. In summary, EMW could effectively alleviate the symptoms of high-fructose-induced HUA, and the study provided a reference for the potential therapeutic mechanism of EMW.
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Drug Design Development and Therapy
·
2023
·
IF 4.8
Qin Guo,Jie Cai,Pengyu Li,Dongling Xu,Xiaomin Ni,Hui Wen,Dan Liu,Suizhen Lin,Haiyan Hu
Androst-3β,5α,6β-triol (Triol) is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC) after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of drug-loaded mixed micelles.
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2022
·Vol. 103
·期 3
·1283-1293
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IF 4.125
Wei Xu,Yingying Kong,Tuo Zhang,Zhihua Gong,Wenjun Xiao
BACKGROUND l -Theanine (LTA) is a biologically active ingredient in tea that shows great potential for regulating lipid metabolism. Bile acids (BA), an important end-product of cholesterol catabolism, participate in the regulation of lipid metabolism and gut microbiota. Here, we investigated the effect of LTA on lipid metabolism and the mechanism by which it regulates BA metabolism and gut microbiota. Male BALB/c mice were treated with LTA for 28 days. RESULTS Daily LTA doses of 100 and 300 mg kg −1 d −1 altered the gut microbiota in mice, predominantly by decreasing Lactobacillus , Streptococcus, Bacteroides , Clostridium and Enterorhabdus microbes associated with bile-salt hydrolase (BSH) activity, thereby decreasing the activity of BSH and increasing the levels of ileum conjugated BA (such as glycocholic acid (GCA) and lithocholic acid), thereby inhibiting the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway. Inhibition of FXR-FGF15 signaling was accompanied by upregulation of cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and increased hepatic production of cholic acid, deoxycholic acid, GCA, glycine cholic acid and glycine ursodeoxycholic acid. Meanwhile, increasing hepatic unconjugated BA upregulated the mRNA and protein expression of liver 3-hydroxy-3-methylglutaryl-CoA reductase and downregulated the mRNA and protein expression of stearoyl-CoA desaturase-1, liver low-density lipoprotein receptor and type B scavenger receptor. Therefore, the serum levels of cholesterol and triglycerides decreased. CONCLUSION Our findings indicate that LTA regulates lipid metabolism by modulating the gut microbiota and BA metabolism via the FXR-FGF15-CYP7A1 pathway. © 2022 Society of Chemical Industry.
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JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Jiating Zheng,Xiaoru Peng,Taifeng Zhu,Shuyao Huang,Chao Chen,Guosheng Chen,Shuqin Liu,Gangfeng Ouyang
In recent years, bile acids (BAs), the important component of bile, were found closely related to the occurrence and development of diseases, therefore, determination of BAs in bile samples is of great significance. However, biological matrix complexity and low concentrations of BAs were still challenging for BA detection in small amount of bile samples. In this work, a core-shell NH 2 -MIL101@mSiO 2 was designed to improve the capture ability of BAs in biological samples, as well as possess good biocompatibility. Subsequently, solid-phase microextraction (SPME) probe of the NH 2 -MIL101@mSiO 2 was coupled with HPLC-MS/MS to establish the analysis method for detecting eight BAs in bile samples. The established method received extraction efficiencies of (30–2143)-fold higher than those of the commercial probes and low limit of detection (LOD ≤ 0.21 ng mL −1 ). The miniaturization of SPME sampling devices, as well as the low LOD of this work, endowed this method advantage of low consumption of bile samples (30 μL). Based on the proposed method, eight BAs in bile samples of pancreatic cancer patients and cholelithiasis patients were detected successfully. A distinct difference was found in the concentrations of four targeted BAs in bile samples from pancreatic cancer patients and cholelithiasis patients. This work provided a method for quantification of eight BAs in small volume human bile samples, and it could open up a perspective regarding the relationship between BA metabolism and the occurrence of diseases.
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CELLULAR SIGNALLING
·
2022
·
IF 4.85
Zihang Yuan,Jie Wang,Haoran Zhang,Yuanyuan Chai,Yunxia Xu,Yingying Miao,Ziqiao Yuan,Luyong Zhang,Zhenzhou Jiang,Qinwei Yu
Aims The precise role of bile acid in the progression of liver fibrosis has yet to be elucidated. In this study, common bile duct ligation was used as an in vivo mouse model for the evaluation of bile acids that promote liver connective tissue growth factor expression. Main methods Primary rat and mice hepatocytes, as well as primary rat hepatic stellate and HepaRG cells were evaluated as in vitro models for promoting the expression of connective tissue growth factor by bile acids. Key findings Compared with taurochenodeoxycholic acid , glycochenodeoxycholic acid, and taurocholic acid , glycocholic acid (GCA) most strongly promoted the secretion of connective tissue growth factor in mouse primary hepatocytes, rat primary hepatocytes and HepaRGs. GCA did not directly promote the activation of hepatic stellate cells . The administration of GCA in mice with ligated bile ducts promotes the progression of liver fibrosis, which may promote the yes-associated protein of hepatocytes into the nucleus, resulting in the hepatocytes secreting more connective tissue growth factor for hepatic stellate cell activation. In conclusion, our data showed that GCA can induce the expression of connective tissue growth factor in hepatocytes by promoting the nuclear translocation of yes-associated protein, thereby activating hepatic stellate cells. Significance Our findings help to elucidate the contribution of GCA to the progression of hepatic fibrosis in cholestatic disease and aid the clinical monitoring of cholestatic liver fibrosis development.
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MICROCHIMICA ACTA
·
2022
·Vol. 189
·期 7
·1-8
·
IF 6.408
Ma Wen,Yang Bingxin,Li Jun,Liu Mingxia,Li Xianjiang,Liu Huwei
A series of functional metal–organic frameworks (MOFs) were facilely prepared through an one-pot procedure or post-synthetic modification strategy and used as matrices in laser desorption ionization mass spectrometry (LDI-MS). Compared with traditional organic matrices and other MOFs, maltose-functional MOF MIL-101-maltose demonstrated ultrahigh ionization efficiency, free matrix background, uniform crystallization, and good dispersibility. A simple, general, and efficient LDI-MS platform was developed for rapid detection of various small biomolecules using MIL-101-maltose as matrix, providing several advantages including low sample consumption of 500 nL, short analysis time of few seconds, strong salt tolerance (500 mM NaCl), and satisfactory reproducibility. The MIL-101-maltose matrix was used for serum glucose determination and successfully distinguished the diabetic patients from the healthy controls. This work provides a generic LDI-MS platform for fast determination of small biomolecules with high potential in clinical diagnosis and disease monitoring. Graphical abstract
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2022
·
IF 3.318
Xiaoxu Cheng,Zifeng Pi,Zhong Zheng,Shu Liu,Fengrui Song,Zhiqiang Liu
Wu-tou decoction (WTD) is a traditional Chinese medicine (TCM) formula which has been used for treating rheumatoid arthritis (RA) for a thousand years. However, the underlying mechanism of WTD in treating RA is still unclear. In recent years, more and more attention has been paid to the role of gut microbiota and microbiota-derived metabolites in the treatment of RA. Hence, this study aims to investigate the roles of microbiota and microbial metabolites in the treatment of RA with WTD. Firstly, the therapeutic effects of WTD on adjuvant-induced arthritis (AIA) rats were evaluated. Then, the 16S rRNA sequencing analysis was used to clarify the changes of the intestinal microbiota and obtain the key microbiota affected by WTD. The important microbial metabolites were quantitated to explore the metabolic characteristics of WTD against RA by targeted metabolomics method. Finally, correlation analysis was performed to investigate the functional correlation among the gut microbiota, metabolites and RA-related serum indexes. The results indicated that WTD could relieve arthritis and reverse gut microbiota dysbiosis. The variation of short-chain fatty acids, bile acids, tryptophan metabolites and amino acids, which are important microbial metabolites, were reversed by WTD intervention. The correlation studies proved that WTD could regulate inflammation and intestinal barrier function partially by modulating Bacteroides, Prevotella, Akkermansia and their associated acetic acid, butyric acid, cholic acid and indole propionic acid. The anti-RA effects of WTD were partially mediated by gut microbiota and microbial metabolites. This study provides a new insight for treating RA and highlights the importance of gut microbiota in the treatment of diseases.
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高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 7
·3799-3811
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IF 5.882
Min Wen,Yubei Liu,Ruiying Chen,Ping He,Feihua Wu,Rui Li,Yining Lin
Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti-inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro-inflammatory (IL-6, VCAM-1, MCP-1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF-β, and α-SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC-fed mice, suggesting that GE could ameliorate DDC-induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR-FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC-fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.
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AQUACULTURE RESEARCH
·
2021
·Vol. 52
·期 7
·2963-2979
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IF 2.082
Qin Ni,Chunfang Cai,Shengjie Ren,Junbiao Zhang,Yijun Zhao,Xinyi Wei,Yiyang Ge,Chengrui Wang,Wenjian Li,Ping Wu,Yuantu Ye,Xiamin Cao
This study aimed to reveal the impact of excessive dietary fibre (DF) intake on inflammatory responses and bile acid (BA) homeostasis in largemouth bass ( Micropterus salmoides ) and the potential mechanism. In vitro BA binding capacity was compared, and the results showed that the BA binding capacity to chenodeoxycholic acid and glycocholic acid by pectin and soybean meal was higher than cellulose and cottonseed meal respectively. An in vivo trial was conducted using a diet without DF as a control (CON diet), while test diets contained 150 g/kg cellulose (CEL diet) or pectin (PEC diet), 500 g/kg soybean meal (SBM diet) or cottonseed meal (CSM diet). Fish were overfed and ate ad libitum . Compared to fish fed the CON diet, fish fed the PEC and SBM diets showed high expression of inflammatory factor genes and BA synthesis factor genes and obvious histopathological damage in the gut and liver, while the responses of fish fed the CEL and CSM diets were mild. Whole-body BA contents in fish fed all test diets were lower than those in fish fed the CON diet ( p < 0.05). These results support the hypothesis that excessive DF intake induces inflammatory responses and dysregulation of BA homeostasis, which might be attributed to their binding capacity to BAs.
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ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Dandan Jiang,Tong Gao,Shuang Liang,Weiwei Mu,Shunli Fu,Yang Liu,Rui Yang,Zipeng Zhang,Yongjun Liu,Na Zhang
Lymph nodes are the main sites for immune activation and surveillance. Effective delivery of immunomodulators into lymph nodes to trigger antitumor immunity is essential for cancer treatment. Here, we propose a lymph node delivery strategy to modulate the immune response by activating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells simultaneously. Novel pH/redox dual-sensitive micelles were prepared using poly(l-histidine)-poly(ethylene glycol) (PLH-PEG) as a skeleton, which can effectively deliver immunomodulators to the lymph nodes due to their suitable particle size. At 48 h after subcutaneous injection, the accumulation efficiency in lymph nodes increased 8.12-fold compared with the control group. Subsequently, Trp2/CpG-coloaded pH/redox dual-sensitive micelles (Trp2/CpG-NPs) acted on antigen-presenting cells, fully promoting CTL activation through dendritic cell antigen cross-presentation and macrophage repolarization. IL-15-loaded pH/redox dual-sensitive micelles (IL-15-NPs) were developed to activate the killing effect of NK cells by interacting with IL-15 receptors. In the tumor-bearing mice model, this lymph node delivery strategy showed significant antitumor efficiency and the tumor inhibition rate reached 93.76%. Meanwhile, the infiltration of CTLs and NK cells in tumor tissues increased, and the immunosuppressive microenvironment was relieved by the repolarization of macrophages from M2-type to M1-type. Overall, this study highlighted the potential of the lymph node delivery strategy for cancer immunotherapy.
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