31 results on '"Luan, Zhi-Lin"'
Search Results
2. Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/β-catenin signaling
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Ming, Wen-hua, Luan, Zhi-lin, Yao, Yao, Liu, Hang-chi, Hu, Shu-yuan, Du, Chun-xiu, Zhang, Cong, Zhao, Yi-hang, Huang, Ying-zhi, Sun, Xiao-wan, Qiao, Rong-fang, Xu, Hu, Guan, You-fei, and Zhang, Xiao-yan
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- 2023
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3. Association between MAP3K4 gene polymorphisms and the risk of schizophrenia susceptibility in a Northeast Chinese Han population
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Sun, Yang, Lv, Ye, Ren, Hui-Wen, Wang, Guan-Yu, Xuan, Li-Na, Luo, Yi-Yang, and Luan, Zhi-Lin
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- 2022
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4. Effects of movement direction and limb dominance on ankle muscular force in sidestep cutting
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Wu, Chen-Xiao, Liu, Hai-Bin, Zhao, Zhi-Nan, Wang, Yu-Bin, and Luan, Zhi-Lin
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- 2022
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5. Metabolites isolated from the human intestinal fungus Penicillium oxalicum SL2 and their agonistic effects on PXR and FXR
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Zhao, Wen-Yu, Luan, Zhi-Lin, Sun, Cheng-Peng, Zhang, Bao-Jing, Jin, Ling-Ling, Deng, Sa, Zhang, Hou-Li, Yu, Zhen-Long, Wang, Chao, and Ma, Xiao-Chi
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- 2022
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6. Highly potent non-steroidal FXR agonists protostane-type triterpenoids: Structure-activity relationship and mechanism
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Luan, Zhi-Lin, Huo, Xiao-Kui, Dong, Pei-Pei, Tian, Xiang-Ge, Sun, Cheng-Peng, Lv, Xia, Feng, Lei, Ning, Jing, Wang, Chao, Zhang, Bao-Jing, and Ma, Xiao-Chi
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- 2019
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7. Positive association between PTN polymorphisms and schizophrenia in Northeast Chinese Han population
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Lv, Ye, Sun, Yang, Dai, Di, Luan, Zhi-Lin, Lu, He-Yuan, Li, Cheng-Jie, and Luo, Yi-Yang
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- 2020
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8. Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO‐1 pathway.
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Xuan, Li‐Na, Hu, Zhen‐Xin, Jiang, Zhen‐Fu, Zhang, Cong, Sun, Xiao‐Wan, Ming, Wen‐Hua, Liu, Hui‐Tao, Qiao, Rong‐Fang, Shen, Lin‐Jie, Liu, Shao‐Bo, Wang, Guan‐Yu, Wen, Lin, Luan, Zhi‐Lin, and Yin, Jian
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PREGNANE X receptor ,SPINAL cord injuries ,CENTRAL nervous system ,NEUROLOGICAL disorders ,SEQUENCE analysis ,XENOBIOTICS - Abstract
Introduction: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand‐activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI. Methods: The clip‐compressive SCI model was performed in male wild‐type C57BL/6 (PXR+/+) and PXR‐knockout (PXR−/−) mice. The N2a H2O2‐induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α‐carbonitrile (PCN), a mouse‐specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO‐1 pathway in the SCI process. Results: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase‐1 (HO‐1) after SCI. We further verified that PXR deficiency activated the NRF2/HO‐1 pathway and PXR activation inhibited this pathway in vitro. Conclusion: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO‐1 pathway. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Association of MSI2 Gene Polymorphism with Age-at-Onset of Schizophrenia in a Chinese Population
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Luan, Zhi-Lin, Cui, Xiao-Hui, Xu, Hu, Lu, He-Yuan, Li, Yu-Yuan, Lu, Tian-Lan, and Zhang, Dai
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- 2017
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10. Association of SOX11 Polymorphisms in distal 3'UTR with Susceptibility for Schizophrenia.
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Sun, Cheng‐Peng, Sun, Dong, Luan, Zhi‐Lin, Dai, Xin, Bie, Xu, Ming, Wen‐Hua, Sun, Xiao‐Wan, Huo, Xiao-Xiao, Lu, Tian‐Lan, Zhang, Dai, Sun, Cheng-Peng, Luan, Zhi-Lin, Ming, Wen-Hua, Sun, Xiao-Wan, and Lu, Tian-Lan
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- 2020
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11. Inhibition of microRNA‐129–2‐3p protects against refractory temporal lobe epilepsy by regulating GABRA1.
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Wang, Guan‐Yu, Luan, Zhi‐Lin, Che, Ning‐Wei, Yan, De‐Bin, Sun, Xiao‐Wan, Zhang, Cong, and Yin, Jian
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TEMPORAL lobe epilepsy , *KAINIC acid , *GABA receptors , *RATS , *EPILEPSY - Abstract
Background: Accumulating evidence demonstrates that certain microRNAs play critical roles in epileptogenesis. Our previous studies found microRNA (miR)‐129–2‐3p was induced in patients with refractory temporal lobe epilepsy (TLE). In this study, we aimed to explore the role of miR‐129–2‐3p in TLE pathogenesis. Method: By bioinformatics, we predicted miR‐129–2‐3p may target the gene GABRA1 encoding the GABA type A receptor subunit alpha 1. Luciferase assay was used to investigate the regulation of miR‐129–2‐3p on GABRA1 3'UTR. The dynamic expression of miR‐129–2‐3p and GABRA1 mRNA and protein levels were measured in primary hippocampal neurons and a rat kainic acid (KA)‐induced seizure model by quantitative reverse transcription‐polymerase chain reaction (qPCR), Western blotting, and immunostaining. MiR‐129–2‐3p agomir and antagomir were utilized to explore their role in determining GABRA1 expression. The effects of targeting miR‐129–2‐3p and GABRA1 on epilepsy were assessed by electroencephalography (EEG) and immunostaining. Results: Luciferase assay, qPCR, and Western blot results suggested GABRA1 as a direct target of miR‐129–2‐3p. MiR‐129–2‐3p level was significantly upregulated, whereas GABRA1 expression downregulated in KA‐treated rat primary hippocampal neurons and KA‐induced seizure model. In vivo knockdown of miR‐129–2‐3p by antagomir alleviated the seizure‐like EEG findings in accordance with the upregulation of GABRA1. Furthermore, the seizure‐suppressing effect of the antagomir was partly GABRA1 dependent. Conclusions: The results suggested GABRA1 as a target of miR‐129–2‐3p in rat primary hippocampal neurons and a rat kainic acid (KA) seizure model. Silencing of miR‐129–2‐3p exerted a seizure‐suppressing effect in rats. MiR‐129–2‐3p/GABRA1 pathway may represent a potential target for the prevention and treatment of refractory epilepsy. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Application of Physical Examination Data on Health Analysis and Intelligent Diagnosis.
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Wang, Xiao-Ling, Liu, Jun, Li, Zi-Qi, and Luan, Zhi-Lin
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PHYSICAL diagnosis ,STATISTICS ,HEALTH status indicators ,MACHINE learning ,ARTIFICIAL intelligence ,UNIVERSITIES & colleges ,DESCRIPTIVE statistics ,DATA analysis ,STATISTICAL models ,COMPUTER-aided diagnosis - Abstract
Analysis and diagnosis according to the collected physical data are an important part in the physical examination. Through the data analysis of the physical examination results and expert diagnoses, the physical condition of a specific physical examination unit can be achieved which may guide individual health development. However, in general, the application of physical examination data is insufficient in most of the current physical examination organizations. Therefore, in the present study, statistical analysis and intelligent diagnosis were applied to maximize the utilization of physical examination data. The physical examination data collected from different departments of Dalian University of Technology were statistically analyzed and then synthesized for stimulating the thinking mode and knowledge framework of medical experts by a learning model on machine, resulting in the construction of an intelligent physical examination diagnosis method with 93.4% accuracy confirmed by experts. In conclusion, a potential artificial intelligence model of psychical examination data on health analysis and intelligent diagnosis was established, which may become more and more accurate with data accumulation in the near future. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Discovery of New Iridoids as Farnesoid X Receptor Agonists from Morinda officinalis: Agonistic Potentials and Molecular Stimulation.
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Luan, Zhi‐Lin Please confirm that given names (blue) and surnames/family names (vermilion) have been identified correctly. -->, Qiao, Fei, Zhao, Wen‐Yu, Ming, Wen‐Hua, Yu, Zhen‐Long, Liu, Jie, Dai, Sheng‐Yun, Jiang, Shuang‐Hui, Lian, Chao‐Jie, Sun, Cheng‐Peng, Zhang, Bao‐Jing, Zheng, Jian, Ma, Shuang‐Cheng, and Ma, Xiao‐Chi
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FARNESOID X receptor , *IRIDOIDS , *AMINO acid residues , *MOLECULAR docking , *MOLECULAR dynamics , *GLYCOSIDES , *QUANTUM wells - Abstract
Main observation and conclusion: The investigation of Morinda officinalis led to the isolation of twelve compounds (1—12), including three new iridoid glycosides morindalins A—C (1—3) and nine known compounds (4—12). Their structural identifications were conducted using HRMS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectra as well as quantum chemical computations. Compound 6 displayed the most significantly agonistic activity against farnesoid X receptor (FXR) with an EC50 value of 7.18 μM, and its agonistic effect was verified through the investigation of FXR downstream target genes including small heterodimer partner 1 (SHP1), bile salt export pump (BSEP), and organic solute transporter subunit alpha and beta (OSTα and OSTβ). The potential interaction of compound 6 with FXR was analyzed by molecular docking and molecular dynamics stimulation, revealing that amino acid residues Leu287, Thr288, and Ser332 played a crucial role in the activation of compound 6 towards FXR. These findings suggested that compound 6 could be regarded as a potential candidate for the development of FXR agonists. [ABSTRACT FROM AUTHOR]
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- 2021
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14. Uncarialins J—M from Uncaria rhynchophylla and Their Anti‐depression Mechanism in Unpredictable Chronic Mild Stress‐Induced Mice via Activating 5‐HT1A Receptor.
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Yu, Zhen‐Long Please verify that the linked ORCID identifiers are correct for each author., Bai, Rong, Zhou, Jun‐Jun, Huang, Hui‐Lian, Zhao, Wen‐Yu, Huo, Xiao‐Kui, Yang, Ya‐Hui, Luan, Zhi‐Lin, Zhang, Bao‐Jing, Sun, Cheng‐Peng, and Ma, Xiao‐Chi
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MONOTERPENES ,INDOLE alkaloids ,CENTRAL nervous system diseases ,AMINO acid residues ,QUANTUM computing ,PSYCHOLOGICAL stress - Abstract
Main observation and conclusion: Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history. After investigation of U. rhynchophylla, eleven monoterpene indole alkaloids, including four new compounds uncarialins J—M (1—4) and seven known analogues (5—11), were isolated and identified. Their structural characterization was conducted using HRESIMS, 1D and 2D NMR, electronic circular dichroism (ECD) spectra, and quantum chemical computations. Compounds 1, 2, 7, and 9—11 displayed significant agonistic effects towards 5‐HT1A receptor, and their EC50 values were 7.86, 7.32, 2.24, 1.18, 1.52, and 3.75 μmol/L, respectively. Furthermore, in vivo experimental results fully revealed that hirsuteine (7) displayed a significant antidepression effect in unpredictable chronic mild stress (UCMS)‐induced depression mice mainly via regulating 5‐HT1A signaling pathway. Molecular docking and site‐directed amino acid mutation verified that amino acid residues Asp116 and Asn386 were the binding sites of hirsuteine (7) with 5‐HT1A receptor. In addition, pre‐treatment of mice with WAY 100635 also blocked the anti‐depression effect of hirsuteine (7), which further demonstrated that 5‐HT1A receptor was a potential target of hirsuteine (7) to effectively treat depression. These findings indicated the therapeutic material basis of U. rhynchophylla and the anti‐depression underlying mechanism of hirsuteine (7), and further provided the useful guidance for the development of hirsuteine (7) as a potential antidepressant candidate. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Uncarialins A-I, Monoterpenoid Indole Alkaloids from as Natural Agonists of the 5-HT1A Receptor.
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Liang, Jia-Hao, Luan, Zhi-Lin, Tian, Xiang-Ge, Zhao, Wen-Yu, Wang, Ya-Li, Sun, Cheng-Peng, Huo, Xiao-Kui, Deng, Sa, Zhang, Bao-Jing, Zhang, Zhan-Jun, and Ma, Xiao-Chi
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- 2019
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16. Drechmerin H, a novel 1(2), 2(18)-diseco indole diterpenoid from the fungus Drechmeria sp. as a natural agonist of human pregnane X receptor.
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Zhao, Jian-Chao, Luan, Zhi-Lin, Liang, Jia-Hao, Cheng, Zhong-Bin, Sun, Cheng-Peng, Wang, Ya-Li, Zhang, Meng-Yue, Zhang, Tian-Yuan, Wang, Yong, Yang, Tian-Mei, Wu, Ying-Ying, Zhang, Yi-Xuan, Zhao, Xin-Yu, and Ma, Xiao-Chi
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DITERPENES , *INDOLE derivatives , *PREGNANE X receptor , *SINGLE crystals , *NUCLEAR magnetic resonance spectroscopy - Abstract
A novel 1(2), 2(18)-di seco indole diterpenoid , drechmerin H ( 1 ), was isolated from the fermentation broth of Drechmeria sp. together with a new indole diterpenoid, 2′- epi terpendole A ( 3 ), and a known analogue, terpendole A ( 2 ). Their structures were determined by HRESIMS, 1D and 2D NMR, ECD, and X-ray single crystal diffraction analyses as well as quantum chemical calculation. The abosulte configuration of terpendole A ( 2 ) was determined for the first time. Compound 1 displayed the significant agonistic effect on pregnane X receptor (PXR) with EC 50 value of 134.91 ± 2.01 nM, and its interaction with PXR was investigated by molecular docking. Meantime, a plausible biosynthetic pathway for compounds 1–3 is also discussed in the present work. [ABSTRACT FROM AUTHOR]
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- 2018
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17. Uncaria rhynchophylla ameliorates unpredictable chronic mild stress-induced depression in mice via activating 5-HT1A receptor: Insights from transcriptomics.
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Qiao, Yan-Ling, Zhou, Jun-Jun, Liang, Jia-Hao, Deng, Xiao-Peng, Zhang, Zhan-Jun, Huang, Hui-Lian, Li, Song, Dai, Shu-Fang, Liu, Chun-Qing, Luan, Zhi-Lin, Yu, Zhen-Long, Sun, Cheng-Peng, and Ma, Xiao-Chi
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Background: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain.Purpose: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE).Study Design and Methods: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system.Results: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 μg/ml.Conclusion: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor. [ABSTRACT FROM AUTHOR]- Published
- 2021
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18. Inula japonica ameliorated bleomycin-induced pulmonary fibrosis via inhibiting soluble epoxide hydrolase.
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Zhao, Wen-Yu, Luan, Zhi-Lin, Liu, Tian-Tian, Ming, Wen-Hua, Huo, Xiao-Kui, Huang, Hui-Lian, Sun, Cheng-Peng, Zhang, Bao-Jing, and Ma, Xiao-Chi
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PULMONARY fibrosis , *EPOXIDE hydrolase , *CHINESE medicine , *LUNG diseases - Abstract
• I. japonica extract (IJE) ameliorated BLM-induced pulmonary fibrosis in mice. • IJE could regulate GSK3β signaling pathway. • IJE displayed the inhibition of sEH activity with an IC 50 value of 0.98 μg/mL. • I. japonica could be regarded as a candidate resource for the treatment of pulmonary fibrosis. Pulmonary fibrosis is a progressive, irreversible, and fatal fibrotic lung disease with a high mortality and morbidity, and commonly nonresponsive to conventional therapy. Inula japonica Thunb. is a traditional Chinese medicine, known as " Xuan Fu Hua " in Chinese, and has been widely applied to relieve cough and dyspnea and eliminate retained phlegm with a long history. In this study, we aimed to evaluate the anti-fibrosis effect and action mechanism of I. japonica extract (IJE) for the treatment of bleomycin (BLM)-induced pulmonary fibrosis in mice. IJE treatment significantly restored BLM-induced alterations in body weight loss and lung function decline, decreased the collagen deposition induced by BLM in lung tissues, and inhibited fibrotic and inflammatory factors, such as α-SMA, TGF-β1, TNF-α, IL-6, COX-2, NF-κB, and GSK3β, in a dose-dependent manner. We found that IJE could enhance the concentration of 8,9-epoxyeicosatrienoic acid (8,9-EET) and decrease concentrations of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET), 11,12-DHET, and 14,15-DHET in BLM-induced mice. Meanwhile, IJE suppressed protein and mRNA expression levels of soluble epoxide hydrolase (sEH), and significantly displayed the inhibition of sEH activity with an IC 50 value of 0.98 μg/mL. Our results indicated that IJE exerted remarkable anti-fibrosis effect on BLM-induced pulmonary fibrosis in mice via inhibiting sEH activity, resulting in the regulation of GSK3β signaling pathway. Our findings revealed the underlying action mechanism of I. japonica , and suggested that I. japonica could be regarded as a candidate resource for the treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]
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- 2020
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19. Correction to Uncarialins A-I, Monoterpenoid Indole Alkaloids from as Natural Agonists of the 5-HT1A Receptor.
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Liang, Jia-Hao, Luan, Zhi-Lin, Tian, Xiang-Ge, Zhao, Wen-Yu, Wang, Ya-Li, Sun, Cheng-Peng, Huo, Xiao-Kui, Deng, Sa, Zhang, Bao-Jing, Zhang, Zhan-Jun, and Ma, Xiao-Chi
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- 2020
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20. Mangrove Tirucallane- and Apotirucallane-Type Triterpenoids: Structure Diversity of the C-17 Side-Chain and Natural Agonists of Human Farnesoid/Pregnane–X–Receptor.
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Jiang, Zhong-Ping, Liu, Ruo-Xi, Zhang, Qun, Shen, Li, Luan, Zhi-Lin, Ma, Xiao-Chi, and Wu, Jun
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Ten new triterpenoid compounds with structure diversity of the C-17 side-chain, including nine tirucallanes, named xylocarpols A–E (1–5) and agallochols A–D (6–9), and an apotirucallane, named 25-dehydroxy protoxylogranatin B (10), were isolated from the mangrove plants Xylocarpus granatum, Xylocarpus moluccensis, and Excoecaria agallocha. The structures of these compounds were established by HR-ESIMS and extensive one-dimensional (1D) and two-dimensional (2D) NMR investigations. The absolute configurations of 1 and 2 were unequivocally determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation; whereas those of 4, 6–8 were assigned by a modified Mosher's method and the comparison of experimental electronic circular dichroism (ECD) spectra. Most notably, 5, 6, 7, and 9 displayed potent activation effects on farnesoid–X–receptor (FXR) at the concentration of 10.0 μM; 10 exhibited very significant agonistic effects on pregnane–X–receptor (PXR) at the concentration of 10.0 nM. [ABSTRACT FROM AUTHOR]
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- 2018
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21. Positive Association of TEAD1 With Schizophrenia in a Northeast Chinese Han Population.
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Sun Y, Wen L, Luo YY, Hu WJ, Ren HW, Lv Y, Zhang C, Gao P, Xuan LN, Wang GY, Li CJ, Xiang ZX, and Luan ZL
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Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case-control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia., Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped., Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls., Conclusion: The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.
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- 2023
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22. Direct targeting of sEH with alisol B alleviated the apoptosis, inflammation, and oxidative stress in cisplatin-induced acute kidney injury.
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Zhang J, Luan ZL, Huo XK, Zhang M, Morisseau C, Sun CP, Hammock BD, and Ma XC
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- Humans, NF-kappa B metabolism, NF-E2-Related Factor 2 metabolism, Tumor Suppressor Protein p53 metabolism, Apoptosis, Kidney metabolism, Oxidative Stress, Inflammation drug therapy, Inflammation metabolism, Cisplatin toxicity, Acute Kidney Injury chemically induced, Acute Kidney Injury drug therapy, Acute Kidney Injury metabolism
- Abstract
Acute kidney injury (AKI) is a pathological condition characterized by a rapid decrease in glomerular filtration rate and nitrogenous waste accumulation during hemodynamic regulation. Alisol B, from Alisma orientale, displays anti-tumor, anti-complement, and anti-inflammatory effects. However, its effect and action mechanism on AKI is still unclear. Herein, alisol B significantly attenuated cisplatin (Cis)-induced renal tubular apoptosis through decreasing expressions levels of cleaved-caspase 3 and cleaved-PARP and the ratio of Bax/Bcl-2 depended on the p53 pathway. Alisol B also alleviated Cis-induced inflammatory response (e.g. the increase of ICAM-1, MCP-1, COX-2, iNOS, IL-6, and TNF-α) and oxidative stress (e.g. the decrease of SOD and GSH, the decrease of HO-1, GCLC, GCLM, and NQO-1) through the NF-κB and Nrf2 pathways. In a target fishing experiment, alisol B bound to soluble epoxide hydrolase (sEH) as a direct cellular target through the hydrogen bond with Gln384, which was further supported by inhibition kinetics and surface plasmon resonance (equilibrium dissociation constant, K
D = 1.32 μM). Notably, alisol B enhanced levels of epoxyeicosatrienoic acids and decreased levels of dihydroxyeicosatrienoic acids, indicating that alisol B reduced the sEH activity in vivo . In addition, sEH genetic deletion alleviated Cis-induced AKI and abolished the protective effect of alisol B in Cis-induced AKI as well. These findings indicated that alisol B targeted sEH to alleviate Cis-induced AKI via GSK3β-mediated p53, NF-κB, and Nrf2 signaling pathways and could be used as a potential therapeutic agent in the treatment of AKI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)- Published
- 2023
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23. The role of pregnane X receptor (PXR) in substance metabolism.
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Lv Y, Luo YY, Ren HW, Li CJ, Xiang ZX, and Luan ZL
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- Animals, Bile Acids and Salts, Glucose, Ligands, Lipids, Mammals metabolism, Receptors, Cytoplasmic and Nuclear, Vitamins, Pregnane X Receptor metabolism, Receptors, Steroid physiology, Xenobiotics metabolism
- Abstract
As a member of the nuclear receptor (NR) superfamily, pregnane X receptor (PXR; NR1I2) is a ligand-activated transcription factor that plays a crucial role in the metabolism of xenobiotics and endobiotics in mammals. The tissue distribution of PXR is parallel to its function with high expression in the liver and small intestine and moderate expression in the kidney, stomach, skin, and blood-brain barrier, which are organs and tissues in frequent contact with xenobiotics. PXR was first recognized as an exogenous substance receptor regulating metabolizing enzymes and transporters and functioning in detoxification and drug metabolism in the liver. However, further research revealed that PXR acts as an equally important endogenous substance receptor in the metabolism and homeostasis of endogenous substances. In this review, we summarized the functions of PXR in metabolism of different substances such as glucose, lipid, bile acid, vitamin, minerals, and endocrines, and also included insights of the application of PXR ligands (drugs) in specific diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Luo, Ren, Li, Xiang and Luan.)
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- 2022
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24. Nuclear receptors in renal health and disease.
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Luan ZL, Zhang C, Ming WH, Huang YZ, Guan YF, and Zhang XY
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- Fibrosis, Humans, Kidney pathology, Kidney physiology, Receptors, Cytoplasmic and Nuclear genetics, Acute Kidney Injury etiology, Acute Kidney Injury pathology, Diabetic Nephropathies pathology, Reperfusion Injury pathology
- Abstract
As a major social and economic burden for the healthcare system, kidney diseases contribute to the constant increase of worldwide deaths. A deeper understanding of the underlying mechanisms governing the etiology, development and progression of kidney diseases may help to identify potential therapeutic targets. As a superfamily of ligand-dependent transcription factors, nuclear receptors (NRs) are critical for the maintenance of normal renal function and their dysfunction is associated with a variety of kidney diseases. Increasing evidence suggests that ligands for NRs protect patients from renal ischemia/reperfusion (I/R) injury, drug-induced acute kidney injury (AKI), diabetic nephropathy (DN), renal fibrosis and kidney cancers. In the past decade, some breakthroughs have been made for the translation of NR ligands into clinical use. This review summarizes the current understanding of several important NRs in renal physiology and pathophysiology and discusses recent findings and applications of NR ligands in the management of kidney diseases., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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25. A naturally occurring FXR agonist, alisol B 23-acetate, protects against renal ischemia-reperfusion injury.
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Luan ZL, Ming WH, Sun XW, Zhang C, Zhou Y, Zheng F, Yang YL, Guan YF, and Zhang XY
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- Acute Kidney Injury metabolism, Acute Kidney Injury pathology, Animals, Apoptosis drug effects, Disease Models, Animal, HEK293 Cells, Hep G2 Cells, Humans, Inflammation Mediators metabolism, Kidney metabolism, Kidney pathology, Ligands, Male, Mice, Inbred C57BL, Mice, Knockout, Oxidative Stress drug effects, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Cytoplasmic and Nuclear metabolism, Reperfusion Injury metabolism, Reperfusion Injury pathology, Signal Transduction, Mice, Acute Kidney Injury prevention & control, Cholestenones pharmacology, Drugs, Chinese Herbal pharmacology, Kidney drug effects, Receptors, Cytoplasmic and Nuclear agonists, Reperfusion Injury prevention & control
- Abstract
The ligand-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating renal function. Activation of FXR by its specific agonists exerts renoprotective action in animals with acute kidney injury (AKI). In the present study, we aimed to identify naturally occurring agonists of FXR with potential as therapeutic agents in renal ischemia-reperfusion injury. In vitro and in vivo FXR activation was determined by a dual-luciferase assay, docking analysis, site-directed mutagenesis, and whole kidney transcriptome analysis. Wild-type (WT) and FXR knockout ( FXR
-/- ) mice were used to determine the effect of potential FXR agonist on renal ischemia-reperfusion injury (IRI). We found that alisol B 23-acetate (ABA), a major active triterpenoid extracted from Alismatis rhizoma , a well-known traditional Chinese medicine, can activate renal FXR and induce FXR downstream gene expression in mouse kidney. ABA treatment significantly attenuated renal ischemia-reperfusion-induced AKI in WT mice but not in FXR-/- mice. Our results demonstrate that ABA can activate renal FXR to exert renoprotection against ischemia-reperfusion injury-induced AKI. Therefore, ABA may represent a potential therapeutic agent in the treatment of ischemic AKI. NEW & NOTEWORTHY In the present study, we found that alisol B 23-acetate (ABA), an identified natural farnesoid X receptor (FXR) agonist from the well-known traditional Chinese medicine Alismatis rhizoma , protects against ischemic acute kidney injury (AKI) in an FXR-dependent manner, as reflected by improved renal function, reduced renal tubular apoptosis, ameliorated oxidative stress, and suppressed inflammatory factor expression. Therefore, ABA may have great potential as a novel therapeutic agent in the treatment of AKI in the future.- Published
- 2021
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26. Farnesoid X receptor (FXR) inhibits coagulation process via inducing hepatic antithrombin III expression in mice.
- Author
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Luan ZL, Wei YY, Wang YC, Ming WH, Zhang HB, Wang B, Cui XH, Li YY, Guan YF, and Zhang XY
- Subjects
- Animals, Blood Coagulation, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Antithrombin III, Hepatocytes, Receptors, Cytoplasmic and Nuclear genetics
- Abstract
Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.
- Published
- 2021
27. Uncaria rhynchophylla ameliorates unpredictable chronic mild stress-induced depression in mice via activating 5-HT 1A receptor: Insights from transcriptomics.
- Author
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Qiao YL, Zhou JJ, Liang JH, Deng XP, Zhang ZJ, Huang HL, Li S, Dai SF, Liu CQ, Luan ZL, Yu ZL, Sun CP, and Ma XC
- Subjects
- Adrenocorticotropic Hormone blood, Animals, Antidepressive Agents chemistry, Computational Biology, Corticosterone blood, Corticotropin-Releasing Hormone blood, Depression genetics, Disease Models, Animal, Gene Expression Regulation drug effects, Male, Mice, Inbred C57BL, Plant Extracts pharmacology, Receptor, Serotonin, 5-HT1A, Serotonin metabolism, Stress, Psychological, Mice, Antidepressive Agents pharmacology, Depression drug therapy, Serotonin 5-HT1 Receptor Agonists pharmacology, Uncaria chemistry
- Abstract
Background: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain., Purpose: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE)., Study Design and Methods: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT
1A receptor was assayed by dual-luciferase reporter system., Results: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A , CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 μg/ml., Conclusion: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor., (Copyright © 2020. Published by Elsevier GmbH.)- Published
- 2021
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28. Positive Association of Human SHC3 Gene with Schizophrenia in a Northeast Chinese Han Population.
- Author
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Lv Y, Sun Y, Wang GY, Yin J, Li CJ, Luo YY, and Luan ZL
- Abstract
Objective: Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (SHC3) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of SHC3 and schizophrenia., Methods: An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population., Results: The allelic and genotypic association analyses showed that four SNPs in SHC3 significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia., Conclusion: Our present results suggest SHC3 as a susceptibility gene for schizophrenia.
- Published
- 2020
- Full Text
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29. Correction to Uncarialins A-I, Monoterpenoid Indole Alkaloids from Uncaria rhynchophylla as Natural Agonists of the 5-HT 1A Receptor.
- Author
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Liang JH, Luan ZL, Tian XG, Zhao WY, Wang YL, Sun CP, Huo XK, Deng S, Zhang BJ, Zhang ZJ, and Ma XC
- Published
- 2020
- Full Text
- View/download PDF
30. Uncarialins A-I, Monoterpenoid Indole Alkaloids from Uncaria rhynchophylla as Natural Agonists of the 5-HT 1A Receptor.
- Author
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Liang JH, Luan ZL, Tian XG, Zhao WY, Wang YL, Sun CP, Huo XK, Deng S, Zhang BJ, Zhang ZJ, and Ma XC
- Subjects
- Animals, CHO Cells, Cricetulus, Molecular Docking Simulation, Molecular Structure, Secologanin Tryptamine Alkaloids chemistry, Secologanin Tryptamine Alkaloids isolation & purification, Serotonin Receptor Agonists chemistry, Serotonin Receptor Agonists isolation & purification, Spectrum Analysis methods, Receptor, Serotonin, 5-HT1A drug effects, Secologanin Tryptamine Alkaloids pharmacology, Serotonin Receptor Agonists pharmacology, Uncaria chemistry
- Abstract
Nine new monoterpenoid indole alkaloids, uncarialins A-I ( 1 - 9 ), were isolated from Uncaria rhynchophylla as well as 14 known analogues ( 10 - 23 ). Their structures were determined by HRESIMS, 1D and 2D NMR, and experimental and calculated electronic circular dichroism data. Compounds 5 , 7 , 15 , and 22 displayed significant agonistic effects against the 5-HT
1A receptor with EC50 values of 2.2 ± 0.1, 0.1 ± 0.1, 1.6 ± 0.3, and 2.0 ± 0.5 μM, respectively. The mechanisms of action of these four compounds with the 5-HT1A receptor were investigated by molecular docking, and the results suggested that amino acid residues Asp116, Thr196, Asn386, and Tyr390 played critical roles in the observed activity of the above-mentioned compounds.- Published
- 2019
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31. Alismanin A, a Triterpenoid with a C 34 Skeleton from Alisma orientale as a Natural Agonist of Human Pregnane X Receptor.
- Author
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Wang C, Huo XK, Luan ZL, Cao F, Tian XG, Zhao XY, Sun CP, Feng L, Ning J, Zhang BJ, and Ma XC
- Subjects
- Humans, Molecular Structure, Pregnane X Receptor, Triterpenes, Alisma, Receptors, Steroid agonists
- Abstract
Alismanin A (1), a novel aromatic triterpenoid with a C
34 skeleton, was isolated from Alisma orientale together with a rearranged nor-triterpenoid (2) and a 13,17-seco triterpenoid (3). Their structures were determined by a combination of HRESIMS, 2D NMR spectra, electronic circular dichroism (ECD), theoretical calculations, and X-ray diffraction analysis. Compounds 1 and 2 displayed significant activation effects on pregnane X receptor (PXR) at 10 nM. A plausible biosynthetic pathway for 1-3 is also discussed.- Published
- 2017
- Full Text
- View/download PDF
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