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LIFE SCIENCES · 2023 · IF 6.1

7-hydroxycoumarin-β-D-glucuronide protects against cisplatin-induced acute kidney injury via inhibiting p38 MAPK-mediated apoptosis in mice

Haijie Wu,Xiaohu Shi,Yingda Zang,Xiaodi Zhao,Xikun Liu,Weida Wang,Wenying Shi,Clarence T.T. Wong,Li Sheng,Xiaoguang Chen,Sen Zhang

Aims Cisplatin is a widely-used drug in the clinical treatment of tumors, but kidney nephrotoxicity is one of the reasons that limits its widespread use. We previously found that 7-hydroxycoumarin-β-D-glucuronide (7-HCG) was one of metabolites of skimmin and highly enriched in the kidneys and maintained a high blood concentration in skimmin-treated rats. Therefore, we investigated whether 7-HCG has a protective effect on cisplatin-induced acute kidney injury. Materials and methods Male C57BL/6 mice were continuously administered 7-HCG for five days, and on the third day, an intraperitoneal injection of cisplatin was given to induce acute kidney injury. After 72 h, the mice were sacrificed for analysis. Serum and renal tissue were collected for renal function evaluation. RNA sequencing was used to explore mechanism, and further validated by western blot and immunohistochemistry. In addition, pharmacokinetic study of oral 7-HCG administration was performed to examine how much 7-hydroxycoumarin (7-HC) was metabolized and 7-HC possible effect on renal protection. Key findings 7-HCG significantly reduced serum BUN and SCR levels, and alleviated pathological damage in renal tissue, and reduced the renal index. RNA sequencing revealed that 7-HCG could reverse p38 MAPK regulation and apoptosis. By western blotting, it was found that 7-HCG could reduce renal injury by reducing p-p38, p-ERK, p-JNK, cleaved-caspase3 and Bax. The immunohistochemical results of cleaved-caspase3 were consistent with western blotting. 7-HCG also significantly reduced the production of ROS in kidney tissue. Pharmacokinetic experiments have shown that 7-HCG in the blood increased rapidly and was eliminated slowly, with an average t 1/2β of 18.3 h. And the concentration of 7-HCG in the target organ kidney was about 4 times higher than that in blood. Significance Our findings indicate that 7-HCG could exert its protective effect against cisplatin-induced acute kidney injury by inhibiting apoptosis via p38 MAPK regulation and elucidates its pharmacokinetics.

CAS / MDL: 20537-88-6
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REGULATORY TOXICOLOGY AND PHARMACOLOGY · 2023 · IF 3.4

Subchronic toxicity study of ferric oxide nanoparticles through intragastric administration: A 94-d, repeated dose study in Sprague Dawley rats

Lang Yan,Jingjing Mao,Wenjing Shi,Lijun Ren,Jinfeng Li,Bijiang Geng,Haoneng Wang,Jiqianzhu Zhang,Yijun Tian,Bin Zhang,Fangyuan Gao,Xiaofang Zhang,Jikuai Chen,Jiangbo Zhu

In this study, the toxicity of ferric oxide nanoparticles (Fe 2 O 3 NPs) administered through gavage to Sprague Dawley (SD) rats for 94 d, consecutively and the recovery after Fe 2 O 3 NPs withdrawal for 30 d were evaluated. The vehicle control group, low-, medium-, and high-dose groups were administered with the vehicle (0.5% sodium carboxymethyl cellulose [CMC-Na]), 125, 250, and 500 mg/kg of Fe 2 O 3 NPs, respectively, administered every morning for 94 d. There was no significant difference in the body weight, food intake, hematological, blood biochemical, and urine indices of SD rats in each administration group and the control group (P > 0.05). There was no significant difference in organ weight, organ indices, and the coefficient of the visceral brain between the SD rats in the different dosage groups and the SD rats in the vehicle control group (P > 0.05). Histopathological observations showed that there was no correlation between the pathological lesions of the organs observed in this study and the dose of Fe 2 O 3 NPs (P > 0.05). The no-observed-adverse-effect level (NOAEL) dose of Fe 2 O 3 NPs was initially determined to be 500 mg/kg administered to SD rats through oral gavage for 94 d, consecutively, followed by recovery after Fe 2 O 3 NPs withdrawal for 30 d.

CAS / MDL: 1317-60-8
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Frontiers in Microbiology · 2023 · IF 5.2

Microbial metabolites indole derivatives sensitize mice to D-GalN/LPS induced-acute liver failure via the Tlr2/NF-κB pathway

Zhou Ziyuan,Wang Baohong,Pan Xiaxia,Lv Jiawen,Lou Zhuoqi,Han Yuqiu,Yao Yuanyuan,Chen Jun,Wang Qiangqiang,Li Lanjuan

Introduction: Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge.Methods: To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites.Results: Contrary to their typical role as anti-inflammatory agents in the host, indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indolepropionic acid (IPA) gavage sensitize mice to D-GalN/LPS-induced-ALF with a rapid rise in serum transaminases and histologic lesion. For a clearer picture, we performed comprehensive analysis for the IAA therapy. IAA markedly amplified inflammatory response and cellular damage. The transcriptome analysis indicated the participation of the TNF-α/NF-κB signaling pathway. The structure of gut microbiota in ileum and the expression of Toll-like receptor 2 (Tlr2) in the liver were also significantly changed.Discussion: In conclusion, IAA pretreatment can exacerbate D-GalN/LPS-induced ALF via probable Tlr2/NF-κB pathway involvement and ileac dysbiosis characterized by enriched gram-positive genus with potential pathogenesis. Microbial metabolites IAA may aggravate individual susceptibility to D-GalN/LPS-induced ALF. Further investigation of the underlying mechanism is needed, and intervention with indole derivatives and related commensal species should be undertaken with caution.

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Journal of Zhejiang University-SCIENCE B · 2019 · IF 1.879

Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine

Su-fang Gu,Li-ying Wang,Ying-jie Tian,Zhu-xian Zhou,Jian-bin Tang,Xiang-rui Liu,Hai-ping Jiang,You-qing Shen

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS ( D -α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations’ physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5-and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2-and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration ( C max ) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2-and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations’ potential applications in drugs and healthcare products.

CAS / MDL: 9002-96-4
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FITOTERAPIA · 2019 · IF 2.431

Semi-synthesis and structural elucidation of brevicanines A–D, four new C19-diterpenoid alkaloids with rotameric phenomenon from Aconitum brevicalcaratum

Zhong-Sheng Wang,Wei Chen,Hai-Yue Jiang,Feng Gao,Xian-Li Zhou

Four new C 19 -diterpenoid alkaloids brevicanines A–D ( 1–4 ) with rotameric phenomenon were isolated from Aconitum brevicalcaratum . They all possessed an unusual axial chiral phenyl-quinazoline side chain and their structures were elucidated by extensive spectroscopic analysis and chemical methods. Meanwhile, brevicanines A and B were semi-synthesized from their parent compound scaconine to further confirm their structures. Variable-temperature NMR spectroscopy was also used to investigate the atropisomers of brevicanine A, in which two sets of signals in 1 H NMR spectra were observed at room temperature and coalesced over 140 °C. It's the first time to determine the atropisomeric preference of diterpenoid alkaloids.

CAS / MDL: 14913-33-8
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BRITISH JOURNAL OF PHARMACOLOGY · 2019 ·Vol. 176 ·期 17 ·3336-3349 · IF 6.583

Involvement of d-amino acid oxidase in cerebral ischaemia induced by transient occlusion of the middle cerebral artery in mice

Hao Liu,Meng-Jing Zhao,Zi-Ying Wang,Qiao-Qiao Han,Hai-Yun Wu,Xiao-fang Mao,Yong-Xiang Wang

Background and Purpose d -Amino acid oxidase (DAAO) is a flavine adenine dinucleotide-containing flavoenzyme and specifically catalyses oxidative deamination of d -amino acids. This study aimed to explore the association between increased cerebral DAAO expression or enzymic activity and the development of cerebral ischaemia. Experimental Approach A mouse model of transient (90 min) middle cerebral artery occlusion (MCAO) was established, and western blotting, enzymic activity assay, and fluorescent immunostaining techniques were used. Key Results The expression and enzymic activity of DAAO increased over time in the cortical peri-infarct area of the mice subjected to transient MCAO. The DAAO was specifically expressed in astrocytes, and its double immunostaining with the astrocytic intracellular marker, glial fibrillary acidic protein, in the cortical peri-infarct area was up-regulated following ischaemic insult, with peak increase on Day 5 after MCAO. Single intravenous injection of the specific and potent DAAO inhibitor Compound SUN reduced the cerebral DAAO enzymic activity and attenuated neuronal infarction and neurobehavioural deficits with optimal improvement apparent immediately after the MCAO procedure. The neuroprotective effect was dose dependent, with ED 50 values of 3.9–4.5 mg·kg −1 . Intracerebroventricular injection of the DAAO gene silencer siRNA/DAAO significantly reduced cerebral DAAO expression and attenuated MCAO-induced neuronal infarction and behavioural deficits. Conclusions and Implications Our results, for the first time, demonstrated that increased cerebral astrocytic DAAO expression and enzymic activity were causally associated with the development of neuronal destruction following ischaemic insults, suggesting that targeting cerebral DAAO could be a potential approach for treatment of neurological conditions following cerebral ischaemia.

CAS / MDL: 492-27-3 146-14-5
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JOURNAL OF APPLIED POLYMER SCIENCE · 2019 ·Vol. 136 ·期 44 ·48177 · IF 2.188

3D printing of shape memory poly(d,l-lactide-co-trimethylene carbonate) by direct ink writing for shape-changing structures

Xue Wan,Hongqiu Wei,Fenghua Zhang,Yanju Liu,Jinsong Leng

Four-dimensional (4D) printing of shape memory materials has attracted increasing interests for personalized structures. In this study, a biocompatible poly( d , l -lactide- co -trimethylene carbonate) (PLMC) is utilized to fabricate 4D shape-changing structures with customized geometries through direct ink writing. The printed objects show shape transformations at different dimensions under thermal programming. The influence of the printing parameters on the properties including rheological, solvent evaporation, and static mechanical behavior are systematically investigated. A printing map is further depicted to achieve high-quality printing with high viscous ink flowed from micronozzle to construct various structures. The printed structures in one-dimensional, two-dimensional, and three-dimensional (3D) exhibit shape-changing behavior with fast response around body temperature. The fast responsive time shows potential in the field of surgical suture (4 s), nonwoven fabric (3 s), and self-expandable stent (35 s). The feasibility of 3D printing of PLMC opens the way for applications in shape-changing devices with small diameter. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136 , 48177.

CAS / MDL: 75-09-2
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2018 · IF 2.88

A stimuli-responsive fluorescence platform for simultaneous determination of d-isoascorbic acid and Tartaric acid based on Maillard reaction product

Yanmei Zhao,Haiyan Yuan,Xinling Zhang,Jidong Yang

An activatable fluorescence monitoring platform based on a novel Maillard reaction product from d -glucose and L-arginine was prepared through a facile one-pot approach and applied for simultaneous detection of d -isoascorbic acid and tartaric acid . In this work, the new Maillard reaction product GLA was first obtained, and its fluorescence intensity can be effectively quenched by KMnO 4 , resulting from a new complex (GLA-KMnO 4 ) formation between GLA and KMnO 4 . Upon addition of d -isoascorbic acid or tartaric acid, an enhanced fluorescence was observed under the optimumed experimental conditions, indicating a stimuli-responsive fluorescence turn on platform for d -isoascorbic acid or tartaric acid can be developed. The corresponding experimental results showed that this turn on fluorescence sensing platform has a high sensitivity for d -isoascorbic acid or tartaric acid, because the detection limits were 5.9   μM and 21.5   μM, respectively. Additionally, this proposed sensing platform was applied to simultaneously detection of d -isoascorbic acid and tartaric acid in real tap water samples with satisfactory results.

CAS / MDL: 74-79-3 89-65-6
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Scientific Reports · 2018 ·Vol. 8 ·期 1 ·1-10 · IF 4.122

Antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid in liver and brain of rats treated by D-galactose

Chen Peng,Chen Fuchao,Zhou Benhong

Accumulating evidence has suggested that oxidative stress and apoptosis are involved in the ageing process. D-galactose (gal) has been reported to cause symptoms of ageing in rats, accompanied by liver and brain injuries. Our study aimed to investigate the potential antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid and to explore how these effects act on rats in a D-gal-induced ageing model. Ageing was induced by subcutaneous injection of D-gal (100 mg/kg/d for 8 weeks). Ellagic acid was simultaneously administered to the D-gal-induced ageing rats once daily by intragastric gavage. Finally, the mental condition, body weight, organ index, levels of inflammatory cytokines, antioxidative enzymes, and liver function, as well as the expression of pro- and anti-apoptotic proteins, were monitored. Our results showed that ellagic acid could improve the mental condition, body weight, organ index and significantly decrease the levels of inflammatory cytokines, normalize the activities of antioxidative enzymes, and modulate the expression of apoptotic protein in ageing rats. In conclusion, the results of this study illustrate that ellagic acid was suitable for the treatment of some ageing-associated problems, such as oxidative stress, and had beneficial effects for age-associated diseases.

CAS / MDL: 476-66-4
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SEPARATION AND PURIFICATION TECHNOLOGY · 2018 · IF 3.927

Ultrahigh permeability of graphene-based membranes by adjusting D-spacing with poly (ethylene imine) for the separation of dye wastewater

Jia-Jie Lu,Yi-Hang Gu,Yan Chen,Xi Yan,Ya-Jun Guo,Wan-Zhong Lang

Graphene oxide (GO) as a unique 2D material attracts much attention. It can be employed to prepare graphene-based membranes by vacuum filtration on microporous substrates. However, the permeability of graphene-based membranes is mainly limited by its interlamellar spacing. In this work, the interlamellar spacing of graphene-based membranes is expanded by grafting poly (ethylene imine) (PEI) on GO sheets. The novel graphene-based membranes present ultrahigh permeability without sacrificing the rejection for the filtration of dye wastewater. The original GO membrane (GOM) only has a pure water permeation flux (PWP) value of 27.0 L·m −2 ·h −1  bar −1 . However, the novel graphene-based membranes prepared with the modified GO by PEI-600 and PEI-10000 (recorded as PGOM-600 and PGOM-10000) markedly increase to 208.1 and 450.2 L·m −2 ·h −1 ·bar −1 respectively. In the separation of dye wastewater, GOM, PGOM-600 and PGOM-10000 exhibit much higher rejections for direct red and methyl blue. However, the modified graphene-based membranes (PGOM-600 and PGOM-10000) present more than 7–20 times higher permeation flux than that of original GOM without sacrificing dye rejection. Thus, this work provides graphene-based membranes with ultrahigh permeation flux for dye removal from wastewater.

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FOOD AND CHEMICAL TOXICOLOGY · 2018 · IF 3.977

Diallyl sulfide protects against lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in mice

Ming Li,Shuo Wang,Xianjie Li,Lulu Jiang,Xujing Wang,Ruirui Kou,Qiong Wang,Lin Xu,Ning Zhao,Keqin Xie

The effects of diallyl sulfide (DAS) and the potential mechanisms were investigated on lipopolysaccharide (LPS)/ d -galactosamine (D-GalN)-induced acute liver injury in mice. DAS (50, 100, 200 μmol/kg) were orally given 1 h prior to LPS (10 μg/kg)/D-GalN (500 mg/kg) intraperitoneal injection . Serum and liver were collected at 8 h after LPS/D-GalN treatment. DAS Pretreatment reduced the activities of serum aminotransferase and attenuated histopathological damage in LPS/D-GalN-induced liver injury. Additionally, LPS/D-GalN-induced liver oxidative stress was ameliorated by DAS pretreatment, as evidenced by the decreased content of MDA and increased level of GSH, SOD , CAT in liver. Moreover, LPS/D-GalN-induced the excessive levels of TNF-α, IL-1β and MCP-1 in serum and liver was decreased by DAS pretreatment. Furthermore, DAS pretreatment attenuated LPS/D-GalN-induced hepatocyte apoptosis , as evidenced by TUNEL staining and protein expression of cleaved caspase3, Bax and Bcl-2 in liver. DAS also up-regulated the expression of p-PI3K p85 and p-Akt in a dose-dependent manner, and Akt inhibitor MK-2206 weakened the inhibitory effect of DAS on hepatocyte apoptosis induced by LPS/D-GalN. In conclusion, the results suggest that DAS exerts the protective effect on LPS/GalN-induced acute liver injury, and this effects possibly by suppressing oxidative stress, inflammation and regulating hepatocyte apoptosis via the PI3K/Akt pathway.

CAS / MDL: 1772-03-8
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ADVANCES IN POLYMER TECHNOLOGY · 2018 ·Vol. 37 ·期 8 ·3038-3044 · IF 2.073

Comparison of supercapacitive behaviors of polyaniline doped with two low-molecular-weight organic acids: D-tartaric acid and citric acid

Wensheng Tan,Renjun Fu,Hong Ji,Datong Wu,Yueguo Xu,Yong Kong

Polyaniline (PANI) is chemically synthesized using two low-molecular-weight organic acids (D-tartaric acid and citric acid) as the dopants, respectively. The doped PANI is characterized by field emission scanning electron microscopy, FT-IR spectra, and X-ray diffraction. The two doped PANIs exhibit different electrochemical properties, especially in the supercapacitive behaviors. Compared with citric acid-doped PANI, D-tartaric acid-doped PANI shows higher specific capacitance (525 F/g at 1 A/g) and cyclic stability. The good electrochemical behaviors of D-tartaric acid-doped PANI might be attributed to the two carboxyl groups of D-tartaric acid, which are beneficial to the oriented growth of PANI chains. The results demonstrate that compared with citric acid, D-tartaric acid is a promising dopant for PANI used in supercapacitors.

CAS / MDL: 62-53-3 147-71-7
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