Frontiers in Pharmacology
·
2021
·
IF 5.811
Zou Meina,Chen Yanrong,Zheng Zongji,Sheng Shuyue,Jia Yijie,Wang Xiangyu,Ren Shijing,Yang Yanling,Li Xiaomin,Dong Wenhui,Guan Meiping,Zhang Qian,Xue Yaoming
High-salt intake leads to kidney damage and even limits the effectiveness of drugs. However, it is unclear whether excessive intake of salt affects renal tubular energy metabolism and the efficacy of dapagliflozin on renal function in diabetic kidney disease (DKD). In this study, we enrolled 350 DKD patients and examined the correlation between sodium level and renal function, and analyzed influencing factors. The results demonstrated that patients with macroalbuminuria have higher 24 h urinary sodium levels. After establishment of type 2 diabetes mellitus model, the animals received a high-salt diet or normal-salt diet. In the presence of high-salt diet, the renal fibrosis was aggravated with fatty acid metabolism dysregulation. Furthermore, Na+/K+-ATPase expression was up-regulated in the renal tubules of diabetic mice, while the fatty acid metabolism was improved by inhibiting Na+/K+-ATPase of renal tubular epithelial cells. Of note, the administration with dapagliflozin improved renal fibrosis and enhanced fatty acid metabolism. But high salt weakened the above-mentioned renal protective effects of dapagliflozin in DKD. Similar results were recapitulated in vitro after incubating proximal tubular epithelial cells in high-glucose and high-salt medium. In conclusion, our results indicate that high salt can lead to fatty acid metabolism disorders by increasing Na+/K+-ATPase expression in the renal tubules of DKD. High salt intake diminishes the reno-protective effect of dapagliflozin in DKD.
研究领域:
肾病学
·
内分泌学
·
药理学
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代谢学
✓ 已验证
DOI
PubMed
高影响因子
Water
·
2024
·Vol. 16
·期 7
·921
·
IF 3
Teng-Zhou Li,Cheng-Zhuang Chen,Shao-Ying Xing,Ling Liu,Ping Li,Zhi-Hua Li
Triphenyltin (TPT) is an organotin pollutant widely found in the aquatic environment. It has endocrine-disrupting and osmotic pressure toxicity. In this study, the physiological and biochemical effects of TPT and various salinities were investigated in different tissues (gut, gill, and brain) of marine medaka. The exposure experiments were conducted for 42 days in different salinities (0, 15, and 30 ppt) without TPT exposure and in different salinity groups with TPT exposure concentrations of 100 ng/L, respectively. The results showed that the Na+-K+-ATPase (NKA) and Ca2+ATPase activity had significant tissue-specific differences, with the highest activity observed in the gills, indicating their major contribution to osmoregulation. Changes in salinity also resulted in significant alterations in the ion concentrations of the gut and gill tissues in the 0-C and 15-C groups. While the changes in Na+and Cl−were relatively stable, the presence of TPT disrupted the regulation of Ca2+and K+. In conclusion, substantial variations were observed in the osmoregulatory capacity of marine medaka tissues. Environmental concentrations of TPT had little effect on osmotic enzyme activity but interfered with the regulation of Ca2+and K+concentrations in the tissues. This study provides valuable insights into the osmotic toxicity of TPT in aquatic environments with different salinities.
研究领域:
环境科学
·
水生毒理学
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海洋生物学
·
生理学
✓ 已验证
产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Xiaolong Yu,Xu Jin,Hang Liu,Yuanyuan Yu,Jin Tang,Rujin Zhou,Aiguo Yin,Jianteng Sun,Lizhong Zhu
Atrazine residue in the environment continues to threaten aquatic ecosystem and human health owing to its adverse effect. However, limited researches focused on degradation mechanism of atrazine by UV/bisulfite, especially risk of intermediates at cellular and molecular level has not been seriously elaborated. In current work, transformation patterns and residual toxicity of intermediates of atrazine by UV/bisulfite were systematically investigated. The atrazine degradation was described by a pseudo first-order kinetic model ( K obs = 0.1053 min −1 ). The presence of H 2 PO 4 − , HCO 3 − and HA had a powerful inhibition. Scavenging test of radicals illustrated that SO 4 •− , •OH and O 2 •− existed in UV/bisulfite system, SO 4 •− and •OH were mainly responsible for atrazine degradation. Eight degradation intermediates were identified, which were involved in dealkylation, alkyl oxidation, dechlorination-hydroxylation, and alkylic-hydroxylation. E. coli as a model microorganism was selected to assess the risk of degradation intermediates. The levels of reactive oxygen species , MDA and Na + /K + -ATPase were declined, suggesting that oxidative damage induced by these intermediates was weakened. According to differential metabolites expression analysis, several key metabolites including aspartate , L-tryptophan, L-asparagine, cytidine, cytosin, stearic acid , behenic acid, were up-regulated, and glutathione , cadaverin, L-2-hydroxyglutaric acid and phytosphingosine were downregulated, clarifying that effective detoxification of atrazine can be performed by UV/bisulfite.
研究领域:
环境科学
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毒理学
·
化学工程
·
微生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Ruizeng Luo,Yijie Fan,Yilin Qi,Yuan Bai,Meng Xiao,Yujia Lv,Jinrui Liang,Mingcheng Tang,Jiaping Zhang,Zhou Li,Dan Luo
Endogenous electric field (EF) originating from differences in ionic gradients plays a decisive role in the wound healing process. Based on this understanding, a self-manipulating sodium ion gradient-based endogenic electrical stimulation dressing (smig-EESD) is developed to achieve passive, non-invasive, endogenic electrical stimulation of wounds, which avoids the side effects of electrode occupancy, electrochemical reactions, and thermal effects present in traditional exogenous electrical stimulation. smig-EESD reduced the potential at the center of the wound by specifically absorbing Na+ in the exudate, ultimately strengthening the wound endogenous EF. Importantly, smig-EESD converted the active transport dependent on Na + /K + -ATPase into passive diffusion by adsorbing extracellular matrix Na+, and the saved ATP consumption promoted tissue repair process. smig-EESD regulated innate and adaptive immune responses by upregulating the secretion of multiple cytokines, thereby suppressing injury-associated inflammatory responses and reducing scar formation. smig-EESD reveals an endogenic electrical stimulation strategy that is independent of electrodes and circuits, and provides new insights into the future development of electronic medicine.
研究领域:
生物医学工程
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伤口愈合
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组织工程
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电疗法
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aquaculture Reports
·
2021
·
IF 3.216
Dongyong Fu,Yadong Hu,Peng Chu,Tao Wang,Mingxu Chu,Yonghai Shi,Shaowu Yin,Yongxiang Zhu,Yaohui Wang,Zhenglong Guo
Copper nanoparticles (Cu-NPs) are water pollutants, which has significant toxic environmental effects. However, the effects of Cu-NPs on Takifugu fasciatus are still relatively unknown. Compared with the control (no add CuSO 4 and Cu-NPs). This study aims to describe the pathological changes in the gill and liver of pufferfish exposed to CuSO 4 (Cu 2+ for short) and Cu-NPs dissolved at a concentration of either 20 or 100 μg/L, in a semi-static waterborne exposure regime for 28 days. All Cu treatments resulted in organ injuries, and the pathologies observed following exposure to Cu-NPs were broadly of the same type as those observed following exposure to Cu 2+ . In the gill, these included lamellar fusion, clubbed tips, and mucocytes swollen, and in the liver included oedema, aggregation of blood cells, and necrosis. Furthermore, enzyme activity assays revealed that Ca 2+ -ATP activity significantly increased under the influence of Cu, whilst Na + -K + -ATPase activity was significantly inhibited. In this study, the CRT in T. fasciatus (referred to as Tf CRT) was identified and full-length cDNA sequences were characterized. Subsequently, RT-PCR and western blot analysis were carried out to assess the expressions of Tf CRT in the gill and liver at both the mRNA and protein levels. Under both the Cu-NPs and Cu 2+ treatments, both the mRNA and protein expressions of Tf CRT were considerably higher in the gill and liver compared to that of the control treatment. Furthermore, there were no significant differences between Cu-NPs and Cu 2+ treatment (at the same treatment concentration) in the expressions of Tf CRT at the mRNA or protein levels. Overall, both Cu 2+ and Cu-NPs had negative effects on T. fasciatus , and Cu-NPs had the toxic effects similar to dissolved Cu. Our results provide the ecological safety data service of Cu-NPs in water, and provide a reference for the health T. fasciatus aquaculture.
研究领域:
环境毒理学
·
水生毒理学
·
分子生物学
·
鱼类生理学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2017
·
IF 2.896
Cheng-yuan Li,Mei Su,Yun-yi Yan,Lin Zhou,Lu-yao Ao,Wei-rong Fang,Yun-man Li
1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine (KFP-H008)，a novel and potent potassium-competitive acid blocker for the treatment of acid secretion related diseases, has not been reported previously. In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 2-deoxy- D -glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and reversed acid output in isolated gastric perfusion under histamine stimulation. In all the animal experiments, KFP-H008 exerted a more effective, potent and longer-lasting inhibitory action in comparison with lansoprazole , a proton pump inhibitor (PPI) commonly used in clinic. KFP-H008 inhibited H + -K + -ATPase activity both at pH 6.5 and pH 7.5, and was unaffected by pH. The inhibitory action was reversible and was achieved in a K + -competitive manner. Furthermore, KFP-H008 did not affect Na + -K + -ATPase activity, thus exhibiting high selectivity, which is different from PPIs. In all, KFP-H008, a novel potassium-competitive acid blocker, may provide new option for the patients with acid-related diseases and provide longer-lasting inhibitory action than drugs commonly used in clinical treatment.
研究领域:
药理学
·
胃肠病学
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药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MARINE ENVIRONMENTAL RESEARCH
·
2022
·
IF 3.737
Shaoying Xing,Ping Li,Shuwen He,Zhihan Cao,Xu Wang,Xuqian Cao,Bin Liu,Chengzhuang Chen,Hong You,Zhi-Hua Li
Triphenyltin (TPT) has attracted considerable attention owing to its vitality, bioaccumulation , and lurking damage. TPT widely exists in complex salinity areas such as estuaries and coastal regions. However, there are few studies on the toxicological behavior of TPT under different salinity. In the study, juvenile Nile tilapia ( Oreochromis niloticus ) were utilized as model animals to investigate the effects of environmental relevant TPT exposure on the osmoregulation and energy metabolism in gill under different salinity. The results showed that salinity and TPT single or combined exposure affected the morphology of the gill tissue. After TPT exposure, Na + -K + -ATPase (NKA) activity significantly decreased at 0 ppt, while NKA and Ca 2+ -Mg 2+ -ATPase (CMA) activities significantly increased at 15 ppt. In addition, significantly higher succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) activities were found in the control fish compared to the TPT-exposed ones at 15 ppt. Quantitative real-time PCR results showed that TPT exposure affected the expression of osmoregulation and energy metabolism-related genes under different salinity. Overall, TPT exposure interfered with osmoregulation and energy metabolism under different salinity. The study will provide reference data for assessing the toxicity of organotin compounds in complex-salinity areas.
研究领域:
水生毒理学
·
环境科学
·
鱼类生理学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 11
·2207228
·
IF 15.1
Wei Zhang,Jing-Jing Hu,Rui Liu,Jun Dai,Lizhen Yuan,Yiheng Liu,Bochao Chen,Mingxing Gong,Fan Xia,Xiaoding Lou
Despite the promising advancements of in situ forming nanoassembly for the inhibition of tumor growth and metastasis, the lack of sufficient triggering sites and hardly controlling the forming position restrict their further developments. Herein, a smart transformable peptide-conjugated probe (DMFA) with enzyme cleavage-induced morphological change is designed for treatment on the tumor cell membrane. Specifically, after self-assembling into nanoparticles and anchoring on the cell membrane with sufficient interaction sites rapidly and stably, DMFA will be efficiently cleaved into α -helix forming part (DP) and β -sheet forming part (LFA) by overexpressed matrix metalloproteinase-2. Thus, the promoted Ca 2+ influx by DP-induced cell membrane breakage and decreased Na + /K + -ATPase activity by LFA-assembled nanofibers wrapping the cells can inhibit PI3K-Akt signaling pathway, leading to the inhibition of tumor cell growth and metastasis. This peptide-conjugated probe undergoes in situ morphological transformation on the cell membrane, exhibiting great potential in tumor therapy.
研究领域:
生物技术
·
纳米技术
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癌症治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Wang Yang-Yang,Sun Yan-Ping,Yang Bing-You,Wang Qiu-Hong,Kuang Hai-Xue
Herbs with a “hot” properties are frequently used to treat cold symptoms in TCM. However, the underlying mechanisms of the herbs with “hot” properties on hypothyroidism have not been investigated. This study aimed to explore four typical “hot” and “cold” property herb on hypothyroidism. Firstly, the difference efficacy between the four typical “hot” property herbs and the four typical “cold” property herbs was assessed by physical signs, thyroid function, and the metabolic profile using multivariate statistical analysis. The influence of the four typical “hot” property herbs on hypothyroidism was validated pathologically. The impact mechanism of the four typical “hot” property herbs on hypothyroidism was investigated through a metabolomics method combined with network analysis. Na+/K+-ATP, ACC1 enzyme, UCP-1, and the PI3K-Akt pathway were used to confirm the metabolite pathways and target-associated metabolites. The results showed that the four typical “hot” property herbs could significantly improve physical signs, thyroid function, and the metabolic profile in hypothyroidism rats, the four typical “cold” property herbs did not show any benefit. Moreover, the four typical “hot” property herbs could improve lipid metabolism, energy metabolism, and thyroid hormone levels by the PI3K-Akt signaling pathway, Ca2+- AMPK signaling pathways, purine metabolism, and tryptophan metabolism. Additionally, the levels of UCP-1, Na+/K + -ATP enzyme, and ACC1 were ameliorated by the four typical “hot” property herbs in hypothyroidism rats. Therefore, a metabolomics strategy combined with network analysis was successfully performed and interpreted the mechanism of the four typical “hot” property herbs on hypothyroidism based on the theory of “cold and hot” properties of TCM well.
研究领域:
中医中药
·
药理学
·
代谢组学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2022
·
IF 8.943
Bohan Yuan,Jiachao Yao,Zeyu Wang,Luyao Dai,Min Zhao,Dzmitry Hrynsphan,Savitskaya Tatsiana,Jun Chen
In this work, Rhodococcus ruber HJM-8 and Paracoccus communis YBH-X were isolated and used to enhance N , N -dimethylacetamide (DMAC) degradation and mineralization efficiencies. The monoculture and co-culture of the two strains for DMAC degradation were compared; results indicated that, a degradation efficiency of 97.62% was obtained in co-culture, which was much higher than that of monocultures of HJM-8 (57.34%) and YBH-X (34.02%). The degradation mechanism showed that co-culture could efficiently improve extracellular polymeric substances production, electron transfer , and microbial activity . Meanwhile, the mineralization mechanism suggested that acetate was the dominant intermediate which had an inhibitory effect on HJM-8, and co-culture was conducive to mineralization due to the high performance of acetate conversion and Na + K + -ATPase vitality. Besides, a pathway of DMAC biodegradation was proposed for co-culture: DMAC was degraded into acetate by HJM-8, then the accumulated acetate was mineralized by YBH-X. Additionally, the co-culture system was further optimized by Box-Behnken design.
研究领域:
环境微生物学
·
生物修复
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2015
·Vol. 171
·期 1
·116-123
·
IF 1.748
Zhang Qiuyue,Cao Zheng,Sun Xudong,Zuang Cuicui,Huang Wanyue,Li Yanfei
Aluminum (Al) is the most abundant metal in the earth’s crust. Al accumulates in erythrocyte and causes toxicity on erythrocyte membrane. The dysfunction of erythrocyte membrane is a potential risk to hypertension. The high Al content in plasma was associated with hypertension. To investigate the effect of AlCl 3 on blood pressure and the function of erythrocyte membrane, the rats were intragastrically exposed to 0, 64(1/20 LD 50 ), 128(1/10 LD 50 ), and 256(1/5 LD 50 ) mg/kg body weight AlCl 3 in double distilled water for 120 days, respectively. Then, we determined the systolic and mean arterial blood pressures of rats, the osmotic fragility, the percentage of membrane proteins, the activities of Na + /K + -ATPase, Mg 2+ -ATPase, Ca 2+ -ATPase, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-pX), and malondialdehyde (MDA) content of the erythrocyte membrane in this experiment. The results showed that AlCl 3 elevated the systolic and mean arterial blood pressure of rats, increased the osmotic fragility, decreased the percentage of membrane protein, inhibited the activities of Na + /K + -ATPase, Mg 2+ -ATPase, Ca 2+ -ATPase, CAT, SOD and GSH-pX, and increased the MDA content of erythrocyte membrane. These results indicate that AlCl 3 may induce hypertension by disturbing the function of erythrocyte membrane.
研究领域:
药理学
·
毒理学
·
心血管研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Yangyang Wang,Yanping Sun,Bingyou Yang,Qiuhong Wang,Haixue Kuang
Ethnopharmacological relevance The ‘cold’ property herbs are commonly applied in heat syndrome. Unfortunately, the underlying mechanisms of the ‘cold’ property herbs on heat syndrome has not been investigated. Aim of the study The study aimed to probe the activities of the four typical ‘cold’ property herbs on hyperthyroidism . Materials and methods Firstly, the four typical ‘heat’ property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical ‘cod’ property herbs and the four typical ‘heat’ property herbs. H&E staining were used to confirmed the influence of the typical ‘cold’ property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical ‘cold’ property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na + /K + -ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-γ, which detected by commercial kits and Western blot . Results It is proved that the four typical ‘cold’ property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical ‘heat’ property herbs showed no benefit. Moreover, the four typical ‘cold’ property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca 2+ and MAPK signaling pathway. And the levels of UCP-1, Na + /K + -ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-γ were ameliorated by the four typical ‘cold’ property herbs. Conclusion The four typical ‘cold’ property herbs could alleviate hyperthyroidism by ameliorate thyroid hormone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca 2+ /MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism.
研究领域:
民族药理学
·
代谢组学
·
药理学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）