CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Pengchao Xie,Yan Peng,Liyan Qiu
To explore effective therapeutic strategy on nonalcoholic fatty liver disease (NAFLD), the amphiphilic oligochitosan derivative containing ursodeoxycholic acid (UDCA) was synthesized and named as UBC, which could self-assemble and encapsulate exenatide (Exe) to obtain Exe-UBC nano-vesicle. Exe-UBC could be uptaken by fatty-acid cultured cells and release UDCA and Exe responsive to the high esterase concentration. In vitro experiments demonstrated that Exe-UBC activated the expression level of SIRT1 with inhibited expression of PGC-1β and PPAR-γ and consequently exerted synergistic bioaction immediately on reducing lipidosis. After a month of Exe-UBC treated through intravenous injection, the body weight of high-fat diet feeding C57BL/6 mice recovered to ordinary level, and their lipid contents in the liver declined significantly. The recovery in hepatic function indexes like TG , AST , and ALT further revealed the superiority of Exe-UBC vesicles. These results suggested that the co-delivery of UDCA and Exe via Exe-UBC could be a potent platform for NAFLD treatment.
研究领域:
药学
·
生物技术
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2022
·
IF 4.336
Hong-shuang Liu,Man-yu Zhou,Xi Zhang,Ya-lan Li,Jing-wei Kong,Xin Gao,Dong-yu Ge,Jia-jing Liu,Pei-guang Ma,Gui-ying Peng,Yan Liao
The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD( P )H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.
研究领域:
药理学
·
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 8
·期 9
·3259-3270
·
IF 3.247
Xiaozhou Zhou,Shiguo Chen,Xingqian Ye
The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.
研究领域:
药理学
·
营养学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2014
·
IF 3.63
Demei Xu,Lihua Hu,Chuanyang Su,Xiaomin Xia,Pu Zhang,Juanli Fu,Wenchao Wang,Duo Xu,Hong Du,Qiuling Hu,Erqun Song,Yang Song
This study investigated the protective effects of curcumin on tetrachloro- p -benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS , COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling.
研究领域:
药理学
·
毒理学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
IF 3.973
Mingyu Zhang,Yaodong Hu,Wei Li,Chen Sun,Chunjing Guan,Ying Peng,Jiang Zheng
2,6-Dimethylphenol (2,6-DMP) is an environmental pollutant found in industrial wastewater. Exposure to 2,6-DMP is of increasing concern as it endangered reportedly some aquatic animals. In this study, we investigated the metabolic activation and hepatotoxicity of 2,6-DMP. 2,6-DMP was metabolized to an o-quinone methide intermediate in vitro and in vivo. The electrophilic metabolite was reactive to the sulfhydryl groups of glutathione, N-acetyl cysteine, and cysteine. NADPH was required for the formation of the reactive metabolite. The quinone methide intermediate reacted with cysteine residues to form hepatic protein adduction. A single dose of 2,6-DMP induced marked elevation of serum ALT and AST in mice. Both the protein adduction and hepatotoxicity of 2,6-DMP showed dose dependency.
研究领域:
毒理学
·
环境科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Tingting Yan,Yuying Zhang,Hengyu Lu,Jun Zhao,Chengrong Wen,Shuang Song,Chunqing Ai,Jingfeng Yang
An alcohol-induced liver injury model was induced in C57BL/6 mice to assess the protective efficacy of Enteromorpha prolifera polysaccharides (EP) against liver damage. Histological alterations in the liver were examined following hematoxylin-eosin (H&E) staining. Biochemical assay kits and ELISA kits were employed to analyze serum and liver biochemical parameters, as well as the activity of antioxidant enzymes and alcohol metabolism-related enzymes. The presence of oxidative stress-related proteins in the liver was detected using western blotting. Liquid chromatography and mass spectrometry were used to profile serum metabolites in mice. The findings demonstrated that EP-H (100 mg/Kg) reduced serum ALT and AST activity by 2.31-fold and 2.32-fold, respectively, when compared to the alcohol-induced liver injury group. H&E staining revealed a significant attenuation of microvesicular steatosis and ballooning pathology in the EP-H group compared to the model group. EP administration was found to enhance alcohol metabolism by regulating metabolite-related enzymes (ADH and ALDH) and decreasing CYP2E1 expression. EP also modulated the Nrf2/HO-1 signaling pathway to bolster hepatic antioxidant capacity. Furthermore, EP restored the levels of lipid metabolites (Glycine, Butanoyl-CoA, and Acetyl-CoA) to normalcy. In summary, EP confers protection to the liver through the regulation of antioxidant activity and lipid metabolites in the murine liver.
研究领域:
药理学
·
毒理学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2025
·
IF 3.6
Duan Yunping,Liu Hui,Zhang Weichuan,Pei Zhuo,Huang Yong
In this study, 360 healthy juvenile largemouth bass, averaging body weights of 11.26 ± 0.49 g, were randomly assigned to four experimental groups. These groups were exposed to water environments containing different concentrations of cadmium (Cd): 0 mg/L for the control (Con) group, 0.9804 mg/L for the low-cadmium (LCd) group, 1.9608 mg/L for the medium-cadmium (MCd) group, and 9.804 mg/L for the high-cadmium (HCd) group, over a duration of 21 days, to study how different levels of Cd impact the liver. Ultrastructural changes manifest as nuclear deformation, blurred cell membrane boundaries, mitochondrial swelling, matrix dissolution, cristae rupture, and disappearance. TUNEL analysis indicates that the apoptotic rate of hepatocytes increases with increasing Cd concentration. Compared with the Con group, serum biochemical results showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glucose (GLU), and urea (UREA) were significantly elevated in the HCd group. With increasing Cd concentration, the activities of hepatic catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) were significantly altered, accompanied by a reduction in ATP content and an increase in the malondialdehyde (MDA) levels. Analysis of inflammatory gene expression showed upregulation of pro-inflammatory genes (IL-1β, TNF-α, and IL-6) and downregulation of the anti-inflammatory gene IL-10. In addition, significant changes in the mRNA levels of apoptosis-related genes were observed in these Cd-exposed groups. Collectively, these findings consistently indicate that Cd exposure can lead to liver injury in largemouth bass by inducing oxidative stress, inflammatory responses, and apoptosis. Graphical
研究领域:
环境毒理学
·
水生毒理学
·
生物化学
·
分子生物学
·
生态毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
IF 3.973
Si-wei Rao,Yuan-yuan Duan,Dong-sheng Zhao,Cheng-jun Liu,Shao-hua Xu,Dong Liang,Feng-xiang Zhang,Wei Shi
Matrine (MT) is a major bioactive compound extracted from Sophorae tonkinensis. However, the clinical application of MT is relatively restricted due to its potentially toxic effects, especially hepatotoxicity. Although MT-induced liver injury has been reported, little is known about the underlying molecular mechanisms. In this study, transcriptomics and metabolomics were applied to investigate the hepatotoxicity of MT in mice. The results indicated that liver injury occurred when the administration of MT (30 or 60 mg/kg, i.g) lasted for 2 weeks, including dramatically increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc. The metabolomic results revealed that steroid biosynthesis, purine metabolism, glutathione metabolism, and pyruvate metabolism were involved in the occurrence and development of MT-induced hepatotoxicity. Further, the transcriptomic data indicated that the downregulation of NSDHL with CYP51, FDFT1, and DHCR7, involved in steroid biosynthesis, resulted in a lower level of cholic acid. Besides, Gstps and Nat8f1 were related to the disorder of glutathione metabolism, and HMGCS1 could be treated as the marker gene of the development of MT-induced hepatotoxicity. In addition, other metabolites, such as taurine, flavin mononucleotide (FMN), and inosine monophosphate (IMP), also made a contribution to the boosting of MT-induced hepatotoxicity. In this work, our results provide clues for the mechanism investigation of MT-induced hepatotoxicity, and several biomarkers (metabolites and genes) closely related to the liver injury caused by MT are also provided. Meanwhile, new insights into the understanding of the development of MT-induced hepatotoxicity or other monomer-induced hepatotoxicity were also provided.
研究领域:
药理学
·
毒理学
·
分子生物学
·
系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Dan Zhao,Yan Jiao,Changpeng Zhang,Xincai Xiao
The sensitive detection of foodborne pathogenic and rapid antibiotic susceptibility testing (AST) is of great significance. This paper reports the enzyme-triggered in situ synthesis of yellow emitting silicon nanoparticles (SiNPs) and the detection of Escherichia coli ( E. coli ) O157:H7 in food samples and the rapid AST. The rapid counting of E. coli O157:H7 has been achieved through direct visual observation, equipment detection, and smartphone digitalization. A simple detection platform based on smartphone senses and cotton swabs has been established. Meanwhile, rapid AST based on enzyme-catalyzed SiNPs can intuitively obtain colorimetric samples. This paper established a system for bacterial enzyme-triggered in situ synthesis of SiNPs, with high responsiveness, luminescence ratio, and specificity. The detection limit for E. coli O157:H7 can reach 100 CFU/mL during 5 h, and the recovery efficiency ranges from 90.14% to 110.16%, which makes it a promising strategy for the rapid detection of E. coli O157:H7 and AST.
研究领域:
生物技术
·
纳米技术
·
食品安全
·
微生物学
·
分析化学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LAB ON A CHIP
·
2016
·Vol. 17
·期 1
·120-127
·
IF 5.586
Jin-Wen Shangguan,Yu Liu,Jian-Bin Pan,Bi-Yi Xu,Jing-Juan Xu,Hong-Yuan Chen
In this paper, we propose a generalized concept of microfluidic polydimethylsiloxane (PDMS) on paper (POP) devices, which combines well the merits of paper chips and PDMS chips. First, we optimized the conditions for accurate PDMS spatial patterning on paper, based on screen printing and a high temperature enabled superfast curing technique, which enables PDMS patterning to an accuracy of tens of microns in less than ten seconds. This, in turn, makes it available for seamless, reversible and reliable integration of the resulting paper layer with other PDMS channel structures. The integrated POP devices allow for both porous paper and smooth channels to be spatially defined on the devices, greatly extending the flexibility for designers to be able to construct powerful functional structures. To demonstrate the versatility of this design, a prototype POP device for the colorimetric analysis of liver function markers, serum protein, alkaline phosphatase (ALP) and aspartate aminotransferase (AST), was constructed. On this POP device, quantitative sample loading, mixing and multiplex analysis have all been realized.
研究领域:
微流控技术
·
生物医学工程
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2020
·
IF 3.723
Yu Miao,Yanling Wu,Yingjin Jin,Mengze Lei,Jixing Nan,Xue Wu
Liver fibrosis is a common pathological consequence of liver injury, which increases liver failure-related morbidity and mortality. Hence, anti-fibrotic treatment is urgently needed. Oxidative stress plays a pivotal role in the progression of liver fibrosis. Thus, targeting ROS may be an effective strategy for liver fibrosis treatment. In this study, we investigated four benzoquinones derivatives, including 5-isopropyl-2-methyl-1,4-benzoquinone (TQ), 2-tert-butyl-1,4-benzoquinone ( t Bu-Q) 2,5-dimethyl-p-benzoquinone (Dime-Q) and p-benzoquinone (Ph-Q), as well as the evaluation of their antioxidant activity and anti-fibrotic effects on activated hepatic stellate cells and TAA-induced mice. Electrochemical analysis showed that all compounds possessed antioxidant property. The result was first confirmed by in vitro experiments, which revealed potential anti-fibrotic activity of all four compounds at the cellular level. Benzoquinone derivatives act as ROS-scavenging molecules, which modulated the TLR4-CD14 signaling pathway to inhibit the expression of procaspase-1 and IL-1β in cells, induced apoptosis via a mitochondrial pathway by upregulating the ratio of Bax/Bcl-2 and by activating caspase-3, as well as inhibited the expression of the anti-apoptotic proteins FLIP and XIAP in activated LX-2 cells. In addition, a TAA (Thioacetamide)-induced mouse model was used to further validate the results. Treatment with benzoquinone derivatives significantly decreased the levels of liver injury markers and lipid peroxidation caused by excessive ROS, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). Moreover, treatment with benzoquinone derivatives significantly inhibited extracellular matrix (ECM) deposition and downregulated the mRNA and protein expression of liver fibrosis markers, such as collagen I, alpha-smooth muscle actin (α-SMA), and TIMP-1. In summary, these results indicate that benzoquinone derivatives may act as potential therapeutic drugs against liver fibrosis.
研究领域:
药理学
·
肝病学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
·
IF 4.679
Di Wu,Shuangqiu Li,Peixuan Li,Aimin Jiang,Ziyi Liu,Yong Zhang,Jingjing Wang,Zhengtao Yang,Zhengkai Wei
Diacetoxyscirpenol (DAS) is one kind of type A trichothecene mycotoxin which produced by Fusarium species which contaminates agricultural crops and food . DAS attracts particular attention because of the strong toxicity. Heterophil extracellular traps (HETs) is a defense mechanism in the chicken innate immune. In this study, we firstly examine the effects and molecular mechanisms of DAS on HETs release, and then investigate the immune toxicity of DAS-induced HETs on chicken liver. HETs structures were observed by immunofluorescence staining and mechanisms were investigated by fluorescence microplate and Western blot . The results showed DAS triggered HETs formation which consists of chromatin decorated with citrullinated histone 3 (citH3) and elastase . Glycolysis was confirmed to be involved in this process and the inhibitors of NADPH oxidase , ERK 1/2 , p38 MAPK-signaling pathways and glycolysis significantly decreased HETs formation. Moreover, investigation in vivo showed DAS significantly increased HETs formation in serum and DNase I (a standard degradative agent of HETs) significantly decreased the ALT and AST levels and ameliorated DAS-caused inflammatory cell infiltration of liver. In conclusion, this study proves that DAS-induced HETs formation plays an immune toxicity role in chicken liver injury and these results provide a new therapeutic target for DAS-induced liver injury in chickens.
研究领域:
兽医学
·
免疫学
·
毒理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）