ANALYTICAL BIOCHEMISTRY
·
2021
·
IF 3.365
Haiyan Zhou,Guorui Zhong,Jing Bai,Xiaolei Li,Wen Peng,Lei Zhang,Jing Li
The urate transporter 1 (URAT1) inhibitors were considered a very promising class of uricosuric agents for the treatment of hyperuricemia and gout. In vitro activity testing of these compounds has been conducted by radio-labeling uric acid for a long time. However, relatively few offer the convenience and speed of fluorescence-based assays. Herein, we report the development of a non-radioactive cell-based method for the screening of URAT1 inhibitors using the human embryonic kidney 293T cells stably expressing human URAT1, and 6-carboxyfluorescein (6-CFL) as a substrate. The URAT1-mediated transport of 6-CFL was time dependent and saturable (Km = 239.5 μM, Vmax = 6.2 pmol/well/min, respectively). Molecules known to interact with organic anion transporters, including benzbromarone , probenecid , and lesinurad, demonstrated concentration-dependent inhibition of 6-CFL transport by URAT1. Moreover, we screened a small subset of compounds, and identified compound 4 as a promising URAT1 inhibitor. This in vitro assay may be employed to screen for novel URAT1 inhibitors, which are effective against hyperuricemia.
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PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Chen Haiyan,Li Rongji,Zhao Feng,Luan Li,Han Tiantian,Li Zhong
Numerous studies reported that betulinic acid (BA), a natural product extracted from birch bark, exhibited various beneficial effects in vitro. However, its pharmacological activities in aging are rarely understood. In this study, Caenorhabditis elegans was deployed as a whole animal model to investigate the impacts of BA on lifespan and stress resistance. Wild-type C. elegans were fed in the presence or absence of BA and tested for a series of phenotypes, including longevity, mobility, reproductive capacity, pharyngeal pumping, heat stress, and oxidative stress. BA at the optimal dose (50 μg/mL) extended the lifespan, improved the healthspan, and significantly evoked the increased oxidative stress resistance in C. elegans. Incorporating the genetic analysis with different types of longevity mutants, DAF-16, the downstream effector of the Insulin/IGF-1 receptor signaling, was revealed to mediate the protective effects of BA on lifespan and antioxidant activity. Together, these data showcased the potential of BA in promoting healthy aging, which shall facilitate its further development in the food and pharmaceutical industries.
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ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 41
·期 11
·1465-1475
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IF 5.064
Liang Li-min,Zhou Jun-jie,Xu Feng,Liu Pei-hua,Qin Lan,Liu Li,Liu Xiao-dong
Peptide transporter 1 (PepT1), highly expressed on the apical membrane of enterocytes, is involved in energy balance and mediates intestinal absorption of peptidomimetic drugs. In this study, we investigated whether and how diabetes affected the function and expression of intestinal PepT1. Diabetes was induced in rats by combination of high-fat diet and low dose streptozocin injection. Pharmacokinetics study demonstrated that diabetes significantly decreased plasma exposures of cephalexin and acyclovir following oral administration of cephalexin and valacyclovir, respectively. Single-pass intestinal perfusion analysis showed that diabetes remarkably decreased cephalexin absorption, which was associated with decreased expression of intestinal PepT1 protein. We assessed the levels of bile acids in intestine of diabetic rats, and found that diabetic rats exhibited significantly higher levels of chenodeoxycholic acid (CDCA), cholic acid (CA) and glycocholic acid (GCA), and lower levels of lithocholic acid (LCA) and hyodeoxycholic acid (HDCA) than control rats; intestinal deoxycholic acid (DCA) levels were unaltered. In Caco-2 cells, the 6 bile acids remarkably decreased expression of PepT1 protein with CDCA causing the strongest inhibition, whereas TNF-α, LPS and insulin little affected expression of PepT1 protein; short-chain fatty acids induced rather than decreased expression of PepT1 protein. Farnesoid X receptor (FXR) inhibitor glycine-β-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). In diabetic rats, the expression of intestinal FXR protein was markedly increased. Oral administration of CDCA (90, 180 mg·kg −1 ·d −1 , for 3 weeks) dose-dependently decreased the expression and function of intestinal PepT1 in rats. In conclusion, diabetes impairs the expression and function of intestinal PepT1 partly via CDCA-mediated FXR activation.
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CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Junwei Yao,Jingxia Liu,Heng Zhi,Hongbing Tao,Xiaobao Xie,Qingshan Shi
The primary purpose of this study was to develop an innovative chitosan (CS) modified polylactic acid (PLA) nanospheres for enhancing the bioavailability of 1, 2-benzisothiazolin-3-one (BIT). The cellular uptake efficiency was corresponded positively to the quantity of CS coated on BIT-PLA nanospheres against E. coli and S. aureus . The membrane potentials of E.coli and S. aureus treated with BIT-PLA, BIT-PLA-0.1%CS and BIT-PLA-0.5%CS were reduced with the extension of incubation time and the ratio of coated CS. The enhancement of CS modified on BIT-PLA nanospheres was reduced antioxidase activities and generated excessive reactive oxygen species . The lowest EC 50 value of the modified BIT-PLA-0.5%CS suggested that its toxicity index was around 2.95-fold and 2.11-fold that of non-modified BIT-PLA against E. coli and S. aureus , respectively. These results revealed that the CS modified BIT-PLA nanospheres had a bright prospect in antibacterial formulation delivery system and improving the bioavailability.
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JCI Insight
·
2021
·
IF 8.315
Tonghui Xu,Jialin Guo,Maozeng Wei,Jiali Wang,Kehui Yang,Chang Pan,Jiaojiao Pang,Li Xue,Qiuhuan Yuan,Mengyang Xue,Jian Zhang,Wentao Sang,Tangxing Jiang,Yuguo Chen,Feng Xu
The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of acetaldehyde and endogenous lipid aldehydes. Approximately 40% of East Asians, accounting for 8% of the human population, carry the E504K mutation in ALDH2 that leads to accumulation of toxic reactive aldehydes and increases the risk for cardiovascular disease, cancer, and Alzheimer disease, among others. However, the role of ALDH2 in acute kidney injury (AKI) remains poorly defined and is therefore the subject of the present study using various cellular and organismal sources. In murine models, in which AKI was induced by either the contrast agent iohexol or renal ischemia/reperfusion, KO, activation/overexpression of ALDH2 were associated with increased and decreased renal injury, respectively. In murine renal tubular epithelial cells (RTECs), ALDH2 upregulated Beclin-1 expression, promoted autophagy activation, and eliminated ROS. In vivo and in vitro, both 3-MA and Beclin-1 siRNAs inhibited autophagy and abolished ALDH2-mediated renoprotection. In mice with iohexol-induced AKI, ALDH2 knockdown in RTECs using AAV-shRNA impaired autophagy activation and aggravated renal injury. In human renal proximal tubular epithelial HK-2 cells exposed to iohexol, ALDH2 activation potentiated autophagy and attenuated apoptosis. In mice with AKI induced by renal ischemia/reperfusion, ALDH2 overexpression or pretreatment regulated autophagy mitigating apoptosis of RTECs and renal injury. In summary, our data collectively substantiate a critical role of ALDH2 in AKI via autophagy activation involving the Beclin-1 pathway.
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MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Shishan Xiao,Hongqian Zhu
Background Leukemia cells have strong proliferation and anti-apoptosis capabilities. The purpose of this study was to investigate the effect of silencing the leucine-rich alpha-2-glycoprotein1 (LRG1) gene, which was found to regulate tumor proliferation and apoptosis in acute myeloid leukemia (AML) cell lines. Material/Methods Plasmid interference technique was used to silence the LRG1 gene in the KASUMI-1 cell line. The cell counting kit-8 (CCK-8) assay was used to test the effect of transduction on cell viability. Cell cycle and apoptosis were detected by flow cytometry. Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) were applied to detect the expression levels of proteins and mRNA, respectively. Results KASUMI-1 cells with the CD34 + CD38 − phenotype were sorted by flow cytometry. After transfection of the siLRG1 plasmid, the level of LRG1 expression was downregulated and cell viability was reduced. Silencing of LRG1 gene blocked KASUMI-1 cells in G0/G1 phase and promoted apoptosis. Further experiments found that LRG1 gene silencing significantly downregulated cell cycle-associated proteins and anti-apoptotic proteins, while upregulating pro-apoptotic proteins. Downregulation of LRG1 gene expression also inhibits signal transduction of the JAK-STAT pathway. Conclusions LRG1 gene silencing regulates the expression of cyclin and apoptosis-related proteins to reduce cell viability and promote apoptosis, probably through inhibition of the JAK-STAT pathway.
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CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Qingling Meng,Mingjiang Mao,Chenhuan Shentu,Shijie Dai,Hao Qian,Jie Hao,Buyang Chen,Bin Ding,Zhiqiang Zhang,Xiaofeng Yuan
Atractylodes macrocephala is a traditional Chinese medicinal (TCM) herb widely used for treating gastrointestinal disorders, yet the structural features and mechanisms of its polysaccharides remain insufficiently understood. In this study, we isolated and characterized a neutral glucan ( A. macrocephala polysaccharide 1, AMP1) from the rhizome of A. macrocephala , with an average molecular weight of 7.98 kDa and a monosaccharide composition of glucose (Glc) and arabinose (Ara) in a molar ratio of approximately 129: 1. Structural analyses revealed that AMP1 is a glucan with a backbone composed of →4)-α-Glc p -(1→ residues and three types of branching units, namely →4)-α-Glc p -(1→, →6)-α-Glc p -(1→, and →6)-β-Glc p -(1→. Notably, the →6)-β-Glc p -(1→ branches appear to carry an additional substitution at the C-4 position. Functional assays demonstrated that AMP1 suppressed the release of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in LPS-stimulated macrophages. In vivo, AMP1 markedly ameliorated DSS-induced colitis in mice, as evidenced by a lower disease activity index (DAI), restoration of epithelial barrier integrity, and modulation of gut microbiota composition. Metabolomic profiling further revealed enrichment of beneficial microbial metabolites, implicating coordinated regulation of host–microbe metabolic pathways. Collectively, these findings establish AMP1 as a structurally defined polysaccharide with multifaceted protective effects, highlighting its therapeutic potential against ulcerative colitis (UC).
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
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2018
·Vol. 29
·期 21
·18634-18639
·
IF 2.324
Li Yu-nan,Yuan Shifeng,An Shaobo,Niu Shuting,Jiang Juan,Gan Lin,Zhang Tianjin
The x(Ca 0.8 Na 0.1 Sm 0.1 )TiO 3 –(1 − x)(Sm 0.5 Nd 0.5 )AlO 3 (CNST–SNA, 0.60 ≤ x ≤ 0.75) ceramic materials were prepared by a conventional two-step solid-state reaction route. The effects of the sintering temperature and composition on the phases, microstructures, and microwave dielectric properties were investigated. The optimal sintering temperature of the CNST–SNA ceramics was found at 1475 °C. The optimal microwave dielectric properties were achieved at x = 0.69 with ε r = 43.8, Q × f = 34303 GHz (at 5.968 GHz), and τ f = − 1.64 ppm/°C.
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Journal of Functional Foods
·
2024
·
IF 3.8
Shuwei Ke,Siyu Zhang,Dongsheng Liu,Tengjiao Zhao,Xiayan Lou,Sunying Cheng,Tingheng Zhu,Hanbing Li
Ectopic olfactory receptors, such as OR1A1, are involved in the regulation of lipid metabolism homeostasis. In this study, we investigated the effects of three monoterpenes, (+)-limonene, (−)-carvone and thymol, upon hepatic lipid deposition. Oral administration of (+)-limonene, (−)-carvone and thymol for 8 weeks in high-fat-diet (HFD)-fed mice significantly lowered the levels of fasting blood glucose, improved glucose intolerance, serum lipid parameters, adiposity, and hepatic steatosis. In LO2 cells, (+)-limonene, (−)-carvone and thymol increased the cyclic adenosine monophosphate (cAMP), induced protein kinase A (PKA) activity and phosphorylation of AMPK, downregulated the expression of SREBP-1 and FASN, and eventually led to a reduction in hepatic lipid deposition. Meanwhile, these beneficial effects in cultured LO2 cells were negated by OR1A1 knockdown and the adenylyl cyclase inhibitor SQ22536, respectively, indicating that they can ameliorate disorders of lipid metabolism through activating OR1A1 and subsequent AMPK/SREBP-1/FASN pathway, indicating OR1A1 as a potential target for counteracting hepatic steatosis.
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JOURNAL OF MATERIALS CHEMISTRY
·
2012
·Vol. 22
·期 42
·22619-22623
·
IF 5.968
Yuhan Lin,Fang Zhang,Daocheng Pan
A series of (ZnS)x(CuInS2)1−x hierarchical micro/nano-structured solid solutions with precisely controlled chemical composition were synthesized via a facile one-pot solvothermal method. ZnO, Cu2O, and In(OH)3 are used as the starting materials and dissolved in ethanol dithiocarbamic acid which is formed from CS2 and ethanolamine in situ. The ethanol dithiocarbamic acid not only serves as a thermally-degradable ligand, but also acts as sulfur source during synthesis, and can be completely removed by a simple calcination process. As-prepared (ZnS)x(CuInS2)1−x microspheres have a hierarchical micro/nano structure composed of around 7 nm nanoparticles. These samples show excellent photocatalytic H2 evolution activity under visible-light irradiation without any noble metal loading owing to their high surface area (as high as 101.6 m2 g−1) and unique hierarchical structure.
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JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2018
·Vol. 315
·期 3
·581-593
·
IF 1.181
Jie Fengping,Bai Zhishan,Yang Xiaoyong
A microemulsion consisting of sodium laurate, n -pentanol, n -heptane and NaCl solution was investigated for Co(II) extraction. The dilution method and conductivity method were used for the determination of structural parameters of sodium laurate/pentan-1-ol/heptane/NaCl microemulsion system. Co(II) was found to be extracted into the microemulsion phase due to the compound formation of [CoCl] + [R 11 COO] − , which was confirmed by the continuous variation of R 11 COONa concentration. Moreover, the effects of cosurfactant, the contact time, the phase ratios, PH and the NaCl concentration in feed solutions on the cobalt extraction yield were investigated. Under the optimum conditions, the extraction percentage of Co(II) could reach 98.9%.
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Cancer Nanotechnology
·
2024
·Vol. 15
·期 1
·1-16
·
IF 4.5
Jiang Qiping,Yao Fengjiao,An Yacong,Lai Xialian,Li Xundou,Yu Zhen,Yang Xian-Da
Background PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherapeutics can accumulate in tumor tissues due to enhanced permeability and retention (EPR) effects. In this study, a novel nanotherapeutic for cancer immunotherapy was implemented with albumin nanoparticles functionalized by both PD-1 and PD-L1 aptamers.Results Albumin nanoparticles (NP) were functionalized with either PD-1 aptamers (PD1-NP), PD-L1 aptamers (PDL1-NP), or both types of aptamers (PD1-NP-PDL1). Average sizes of PD1-NP, PDL1-NP, and PD1-NP-PDL1 were 141.8 nm, 141.8 nm, and 164.2 nm, respectively. PD1-NP had good affinity for activated T cells that expresses PD-1. Similarly, PDL1-NP could bind with MDA-MB-231 or CT26 tumor cells that express PD-L1. Moreover, the bispecific PD1-NP-PDL1 could bind with both the activated T cells and the PD-L1-expressing tumor cells, and tether the two type of cells together. Functionally, aptamer-modified nanoparticles exhibited stronger immune-stimulating effects vs. free aptamers. Specifically, PD1-NP or PDL1-NP induced stronger lymphocyte-mediated cytotoxicity against PD-L1-expressing tumor cells in vitro vs. free PD-1 or PD-L1 aptamers. Animal studies also showed that PD1-NP or PDL1-NP significantly improved antitumor efficacy against CT26 colon cancer in vivo vs. free PD-1 or PD-L1 aptamers. Importantly, the bispecific PD1-NP-PDL1 further boosted the in vivo antitumor efficacy compared with PD1-NP or PDL1-NP, without raising systemic toxicity.Conclusion The results suggest that the bispecific PD1-NP-PDL1 is a promising nanotherapeutic to improve the efficacy of PD-1/PD-L1 blockade, and may have application potential in colon cancer treatment.
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