96 results on '"Yajun Bai"'
Search Results
2. Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPARγ-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats
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Yuhang Ge, Fei Zhen, Ziqi Liu, Zhaowei Feng, Gui Wang, Chu Zhang, Xingqi Wang, Ying Sun, Xiaohui Zheng, Yajun Bai, and Ruiqin Yao
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α-asaronol ,glutamic acid ,PPARγ ,white matter injury ,oligodendrocyte precursor cells ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Preterm white matter injury (PWMI) is the most common form of brain damage in premature infants caused by hypoxia-ischemia (HI), inflammation, or excitotoxicity. It is characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination. Our previous study confirmed that alpha-asarone (α-asaronol), a major compound isolated from the Chinese medicinal herb Acorus gramineus by our lab, could alleviate neuronal overexcitation and improve the cognitive function of aged rats. In the present study, we investigated the effect and mechanism of α-asaronol on myelination in a rat model of PWMI induced by HI. Notably, α-asaronol promoted OPC differentiation and myelination in the corpus callosum of PWMI rats. Meanwhile, the concentration of glutamate was significantly decreased, and the levels of PPARγ and glutamate transporter 1 (GLT-1) were increased by α-asaronol treatment. In vitro, it was also confirmed that α-asaronol increased GLT-1 expression and recruitment of the PPARγ coactivator PCG-1a in astrocytes under oxygen and glucose deprivation (OGD) conditions. The PPARγ inhibitor GW9662 significantly reversed the effect of α-asaronol on GLT-1 expression and PCG-1a recruitment. Interestingly, the conditioned medium from α-asaronol-treated astrocytes decreased the number of OPCs and increased the number of mature oligodendrocytes. These results suggest that α-asaronol can promote OPC differentiation and relieve dysmyelination by regulating glutamate levels via astrocyte PPARγ-GLT-1 signaling. Although whether α-asaronol binds to PPARγ directly or indirectly is not investigated here, this study still indicates that α-asaronol may be a promising small molecular drug for the treatment of myelin-related diseases.
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- 2022
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3. A Novel Compound, Tanshinol Borneol Ester, Ameliorates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Oxidative Stress via the mTOR/β-TrCP/NRF2 Pathway
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Dongjian Han, Fuhang Wang, Bo Wang, Zhentao Qiao, Xinyue Cui, Yi Zhang, Qingjiao Jiang, Miaomiao Liu, Jiahong Shangguan, Xiaohui Zheng, Yajun Bai, Chunyan Du, and Deliang Shen
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cardiac hypertrophy ,antioxidant ,er stress ,Nrf2 ,mTOR ,autophagy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Tanshinol borneol ester (DBZ) exerts anti-atherosclerotic and anti-inflammatory effects. However, its effects on cardiac hypertrophy are not well understood. In this work, we investigated the treatment effects and potential mechanisms of DBZ on the hypertrophic heart under oxidative stress and endoplasmic reticulum (ER) stress. A hypertrophic model was established in rats using transverse-aortic constriction (TAC) surgery and in neonatal rat cardiomyocytes (NRCMs) using angiotensin II (Ang II). Our results revealed that DBZ remarkably inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis in vivo and in vitro through nuclear NRF2 accumulation, and enhanced NRF2 stability via regulating the mTOR/β-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.
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- 2022
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4. A novel compound DBZ ameliorates neuroinflammation in LPS-stimulated microglia and ischemic stroke rats: Role of Akt(Ser473)/GSK3β(Ser9)-mediated Nrf2 activation
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Sha Liao, Jingni Wu, Ruimin Liu, Shixiang Wang, Jing Luo, Yang Yang, Yannan Qin, Tao Li, Xiaopu Zheng, Jing Song, Xinfeng Zhao, Chaoni Xiao, Yajun Zhang, Liujiao Bian, Pu Jia, Yajun Bai, and Xiaohui Zheng
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Stroke ,Neuroinflammation ,Microglia polarization ,Nrf2 ,Antioxidant ,Functional recovery ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Microglia-mediated neuroinflammation plays a crucial role in the pathophysiological process of multiple neurological disorders such as ischemic stroke, yet lacks effective therapeutic agents. Previously, we discovered one novel synthetic compound, tanshinol borneol ester (DBZ), possesses anti-inflammatory and anti-atherosclerotic activities, whereas little is known about its effects in CNS. Therefore, the present study aims to explore the effects and potential mechanism of DBZ on neuroinflammation and microglial function. Our studies revealed that DBZ significantly inhibited NF-κB activity, suppressed the production of pro-inflammatory mediators meanwhile promoted M2 mediators expression in LPS-stimulated BV2 cells and mouse primary microglia cells. DBZ also exhibited antioxidant activity by enhancing Nrf2 nuclear accumulation and transcriptional activity, increasing HO-1 and NQO1 expression, and inhibiting LPS-induced ROS generation in BV2 cells. Importantly, the anti-neuroinflammatory and antioxidant effects of DBZ above were reversed by Nrf2 knockdown. Additionally, DBZ ameliorated sickness behaviors of neuroinflammatory mice induced by systemic LPS administration, and significantly reduced infract volume, improved sensorimotor and cognitive function in rats subjected to transient middle cerebral artery occlusion (tMCAO); besides, DBZ restored microglia morphological alterations and shifted the M1/M2 polarization in both murine models. Mechanistically, DBZ-induced Nrf2 nuclear accumulation and antioxidant enzymes expression were accompanied by increased level of p-Akt(Ser473) (activation) and p-GSK3β(Ser9) (inactivation), and decreased nuclear level of Fyn both in vitro and in vivo. Pharmacologically inhibiting PI3K or activating GSK3β markedly increased nuclear density of Fyn in microglia cells, which blocked the promoting effect of DBZ on Nrf2 nuclear accumulation and its antioxidant and anti-neuroinflammatory activities. Collectively, these results indicated the effects of DBZ on microglia-mediated neuroinflammation were strongly associated with the nuclear accumulation and stabilization of Nrf2 via the Akt(Ser473)/GSK3β(Ser9)/Fyn pathway. With anti-neuroinflammatory and antioxidant properties, DBZ could be a promising new drug candidate for prevention and/or treatment of cerebral ischemia and other neuroinflammatory disorders.
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- 2020
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5. Correction: Sun, Y.; et al. Design, Synthesis, and Evaluation of Novel 2-Hydroxypyrrolobenzodiazepine-5,11-dione Analogues as Potent Angiotensin Converting Enzyme (ACE) Inhibitors. Molecules 2017, 22, 1739
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Ying Sun, Yujun Bai, Xirui He, Yajun Bai, Pei Liu, Zefeng Zhao, Xufei Chen, and Xiaohui Zheng
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n/a ,Organic chemistry ,QD241-441 - Abstract
The author wishes to make the following corrections to this paper [...]
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- 2018
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6. Anticonvulsant Activity of Halogen-Substituted Cinnamic Acid Derivatives and Their Effects on Glycosylation of PTZ-Induced Chronic Epilepsy in Mice
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Ye Cuan, Xirui He, Yuhui Zhao, Jiajun Yang, Yajun Bai, Yin Sun, Qiang Zhang, Zefeng Zhao, Xiaoyang Wei, and Xiaohui Zheng
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epilepsy ,cinnamic acid ,anticonvulsant activities ,glycosylation ,neurotoxicity ,Organic chemistry ,QD241-441 - Abstract
Epilepsy is a common chronic neurological disorder disease, and there is an urgent need for the development of novel anticonvulsant drugs. In this study, the anticonvulsant activities and neurotoxicity of 12 cinnamic acid derivatives substituted by fluorine, chlorine, bromine, and trifluoromethyl groups were screened by the maximal electroshock seizure (MES) and rotarod tests (Tox). Three of the tested compounds (compounds 3, 6 and 12) showed better anticonvulsant effects and lower neurotoxicity. They showed respective median effective dose (ED50) of 47.36, 75.72 and 70.65 mg/kg, and median toxic dose (TD50) of them was greater than 500 mg/kg, providing better protective indices. Meanwhile, they showed a pentylenetetrazol (PTZ) ED50 value of 245.2, >300 and 285.2 mg/kg in mice, respectively. Especially, the most active compound 3 displayed a prominent anticonvulsant profile and had lower toxicity. Therefore, the antiepileptic mechanism of 3 on glycosylation changes in chronic epilepsy in mice was further investigated by using glycomics techniques. Lectin microarrays results showed that epilepsy was closely related to abnormal glycosylation, and 3 could reverse the abnormal glycosylation in scPTZ-induced epilepsy in mice. This work can provide new ideas for future discovery of potential biomarkers for evaluation of antiepileptic drugs based on the precise alterations of glycopatterns in epilepsy.
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- 2017
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7. Design, Synthesis, and Evaluation of Novel Phenolic Acid/Dipeptide/Borneol Hybrids as Potent Angiotensin Converting Enzyme (ACE) Inhibitors with Anti-hypertension Activity
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Ying Sun, Yujun Bai, Xirui He, Yajun Bai, Pei Liu, Zefeng Zhao, Xufei Chen, and Xiaohui Zheng
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phenolic acid/dipeptide/borneol hybrid ,ACE inhibitor ,hypertension ,combination of traditional Chinese medicine chemistry ,Organic chemistry ,QD241-441 - Abstract
Under the guidance of combination of traditional Chinese medicine chemistry (CTCMC), this study describes the preparation of a phenolic acid/dipeptide/borneol hybrid consisting of phenolic acid and a bornyl moiety connected to the dipeptide N-terminal and C-terminal respectively. It also evaluates their angiotensin converting enzyme (ACE) inhibitory and synergistic antihypertensive activities. Briefly, a series of novel phenolic acid/dipeptide/borneol hybrids were prepared and investigated for their ability to inhibit ACE. The influence of the phenolic acid and bornyl moiety on subsite selectivity is also demonstrated. Among all the new compounds, two compounds—7a and 7g—reveal good inhibition potency in in vitro ACE-inhibitory tests. Interestingly, favorable binding results in molecular docking studies also supported the in vitro results. Additionally, the bioassay showed that oral administration of the two compounds displayed high and long-lasting antihypertensive activity both in acute antihypertensive tests and in therapeutic antihypertensive tests by non-invasive blood pressure measurements in spontaneously hypertensive rats.
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- 2017
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8. Phytochemistry, Pharmacology and Traditional Uses of Plants from the Genus Trachelospermum L.
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Zefeng Zhao, Xirui He, Yuhui Zhao, Ying Sun, Xufei Chen, Ye Cun, Linhong Huang, Yajun Bai, and Xiaohui Zheng
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Trachelospermum ,lignans ,anti-inflammatory ,analgesic ,antitumor ,review ,Organic chemistry ,QD241-441 - Abstract
This paper is intended to review advances in the botanical, phytochemical, traditional uses and pharmacological studies of the genus Trachelospermum. Until now, 138 chemical constituents have been isolated and characterized from these plants, particularly from T. asiaticum and T. jasminoides. Among these compounds, lignans, triterpenoids, and flavonoids are the major bioactive constituents. Studies have shown that plants from the genus Trachelospermum exhibit an extensive range of pharmacological properties both in vivo and in vitro, including anti-inflammatory, analgesic, antitumor, antiviral and antibacterial activities. In Traditional Chinese Medicine (TCM) culture, drugs that include T. jasminoides stems have been used to cure rheumatism, gonarthritis, backache and pharyngitis, although there are few reports concerning the clinical use and toxicity of these plants. Further attention should be paid to gathering information about their toxicology data, quality-control measures, and the clinical value of the active compounds from genus Trachelospermum.
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- 2017
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9. Simultaneous Determination of Volatile Constituents from Acorus tatarinowii Schott in Rat Plasma by Gas Chromatography-Mass Spectrometry with Selective Ion Monitoring and Application in Pharmacokinetic Study
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Xue Meng, Xinfeng Zhao, Shixiang Wang, Pu Jia, Yajun Bai, Sha Liao, and Xiaohui Zheng
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Analytical chemistry ,QD71-142 - Abstract
A sensitive and specific gas chromatographic-mass spectrometry with selected ion monitoring (GC-MS/SIM) method has been developed for simultaneous identification and quantification of α-asarone, β-asarone, and methyl eugenol of Acorus tatarinowii Schott in rat plasma. Chromatographic separation was performed on a Restek Rxi-5MS capillary column (30 m × 0.32 mm × 0.25 μm), using 1-naphthol as internal standard (IS). MS detection of these compounds and IS was performed at m/z 178, 208, 208, and 144. Intra- and interday precisions of all compounds of interest were less than 10%. The recoveries are situated in the range of 92.4–105.2%. Pharmacokinetics of methyl eugenol confirmed to be one-compartment open model, α-asarone and β-asarone was two-compartment open model, respectively. The method will probably be an alternative to simultaneous determination and pharmacokinetic study of volatile ingredients in Acorus tatarinowii Schott.
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- 2013
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10. Hydroxytyrosol production from l-DOPA by engineered Escherichia coli co-expressing l-amino acid deaminase, α-keto acid decarboxylase, aldehyde reductase and glucose dehydrogenase with NADH regeneration
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Jingjing Huo, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, and Yujie Cai
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Bioengineering ,Applied Microbiology and Biotechnology ,Biochemistry - Published
- 2022
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11. Characterisation of aldo-keto reductases from Lactobacillus reuteri DSM20016
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Wenhao Qu, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, and Yujie Cai
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Bioengineering ,Applied Microbiology and Biotechnology ,Biochemistry - Published
- 2022
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12. Microspore‐expressed <scp>SCULP1</scp> is required for p ‐coumaroylation of sporopollenin, exine integrity, and pollen development in wheat
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Lei Xu, Yimiao Tang, Yanzhi Yang, Dezhou Wang, Haijun Wang, Jianmei Du, Yajun Bai, Shichao Su, Changping Zhao, and Lei Li
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Physiology ,Plant Science - Published
- 2023
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13. Characterization of a novel type homoserine dehydrogenase with high oxidation activity from Arthrobacter nicotinovorans
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Xinxin Liang, Huaxiang Deng, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, and Yujie Cai
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Bioengineering ,Applied Microbiology and Biotechnology ,Biochemistry - Published
- 2022
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14. Biosynthesis of phenylpyruvic acid from <scp>l</scp> ‐phenylalanine using chromosomally engineered Escherichia coli
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Xiaohui Zheng, Tai-Ping Fan, Yujie Cai, Xiong Tianzhen, and Yajun Bai
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Phenylpyruvic Acids ,Phenylalanine ,Biomedical Engineering ,lac operon ,Bioengineering ,medicine.disease_cause ,Applied Microbiology and Biotechnology ,chemistry.chemical_compound ,Plasmid ,Biotransformation ,Drug Discovery ,Escherichia coli ,Proteus myxofaciens ,medicine ,Strain (chemistry) ,Process Chemistry and Technology ,Phenylpyruvic acid ,General Medicine ,respiratory system ,Molecular biology ,Metabolic Engineering ,chemistry ,bacteria ,Molecular Medicine ,Plasmids ,Biotechnology - Abstract
The efficiency of whole-cell biotransformation is often affected by genetic instability of plasmid-based expression systems, which require selective pressure to maintain the stability of the plasmids. To circumvent this shortcoming, we constructed a chromosome engineering strain for synthesis of phenylpyruvic acid (PPA) from L-phenylalanine. Firstly, L-amino acid deaminase (pmLAAD) from Proteus myxofaciens was incorporated into E. coli BL21 (DE3) chromosome and the copy-numbers of pmLAAD were increased by chemically induced chromosomal evolution (CIChE). 59 copies of pmLAAD was obtained in E. coli BL8. The PPA titer of E. coli BL8 reached 2.22 g/L at 6 h. Furthermore, the deletion of lacI improved PPA production. In the absence of Isopropyl-β-D-thiogalactopyranoside (IPTG), the resulting strain, E. coli BL8△recA△lacI, produced 2.65 g/L PPA at 6 h and yielded a 19.37 % increase in PPA production compared to E. coli BL8△recA. Finally, the engineered E. coli BL8△recA△lacI strain achieved 19.14 g/L PPA at 24 h in 5 L bioreactor. The culture of the strain does not require the addition of antibiotics and inducers. The production level of CIChE strains can catch up with plasmid expression strains. This work extends production methods for whole-cell biotransformation. This article is protected by copyright. All rights reserved.
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- 2021
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15. Human lactate dehydrogenase and malate dehydrogenase possess the catalytic properties to produce aromatic α-hydroxy acid
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Litong Wang, Tai-Ping Fan, Mei Wang, Yajun Bai, Xiaohui Zheng, and Yujie Cai
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Microbiology ,Applied Microbiology and Biotechnology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Food Science - Published
- 2022
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16. 221S-1a inhibits endothelial proliferation in pathological angiogenesis through ERK/c-Myc signaling
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Xinye Yao, Yanbo Xue, Qiang Ma, Yajun Bai, Pu Jia, Yiman Zhang, Baochang Lai, Shuting He, Qiong Ma, Junbo Zhang, Hongyan Tian, Qian Yin, Xiaohui Zheng, and Xiaopu Zheng
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Pharmacology - Published
- 2023
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17. Applications of chromatography in giant complex drug-organism system
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Xue Meng, Xiaohui Zheng, Yangyang Bian, Yujie Cai, Shuomo Gao, Yajun Bai, Pu Jia, and Ye Zhao
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Chromatography ,Chemistry ,Process (engineering) ,Mechanism (biology) ,General Chemical Engineering ,Causal relations ,Organic Chemistry ,Traditional Chinese medicine ,Biochemistry ,Analytical Chemistry ,Electrochemistry ,Humans ,In patient ,Identification (biology) ,Medicine, Chinese Traditional ,Guanxi ,Organism - Abstract
Chromatography is an important branch of analytical chemistry that focuses on the separation and analysis of complex structures. Following more than 100 years of development and improvement, chromatography theory and technology have gradually become sophisticated. It has become a coalition of science, technology, and art. Recently, chromatography has been successfully used in combination with mass spectrometry, nuclear magnetic resonance spectroscopy, and atomic emission spectroscopy. Chromatography and the combination with other techniques has significantly improved the analysis of complex systems, such as the environment, food, petrochemicals, biological specimens, and medicine. As one of the oldest healing systems, Traditional Chinese Medicine (TCM) has served to maintain the health of people in China and worldwide for thousands of years. Therefore, it has become a core representative of traditional Chinese culture. In the past two years, TCM has been widely used to treat COVID-19, especially in patients with mild symptoms. Recently, Chinese government emphasized the inheritance and innovation of TCM and stepped up efforts to promote its modernization. TCM includes herbal medicine, acupuncture, moxibustion, massage, food therapy, and physical exercise, such as Tai Chi. In most cases, the patients are administered a mixture of TCM formulas containing more than two herbal medicines, resulting in a highly complicated compound mixture. There is no doubt that long-term clinical practices have demonstrated the safety and therapeutic effect of TCM. However, the compound mixture must be simplified to identify the active compounds. This is mainly because of the existence of carcinogenic compounds, pesticides, and heavy metal residues introduced through plantation and production processes. Moreover, enzymes within the human system generate further new compounds in response to the entry of the TCM containing thousands of components. Consequently, the complex TCM and organism systems interact with each other, constituting a giant complex drug-organism system. The analysis of this giant complex system is acknowledged as a key aspect in the modernization process of TCM. In the last 20 years, many studies have been conducted to screen and identify effective compounds in TCM. These effective compounds can be either the original compounds or new metabolic components generated in vivo. All these efforts are aimed at simplifying the components of TCM and elucidating the therapeutic mechanism. It is well known that chromatography can provide technical support for complex systems owing to its unique advantage of outstanding separation and analysis capabilities. Therefore, chromatography and its combination with other technologies have become mainstream technologies for promoting the compilation of molecular structure, information, digitalization, and modernization of TCM. This paper reviews the research and application of chromatography and combination technologies in a giant complex TCM formula-organism system. Furthermore, the authors briefly introduce and summarize the understanding, research ideas, and activities of the authors' team on the modernization of TCM. "Liang Guanxi" and "He strategy" are proposed as novel strategies for studying the giant complex drug-organism system. A distinguished technology integrated with mathematical model of causal relation, combined receptor chromatography, identification of chemical molecular structure and evaluating of pharmacological activities was established. It was successfully employed to determine the core effector-response substances of "Liang Guanxi" herb pairs in a giant complex drug-organism system. Subsequently, utilizing the proposed technology of Combination of Traditional Chinese Medicine Molecular Chemistry, the author's team designed and developed four series of innovative drugs. Inspired by the hundred years of chromatography history and thousands of years of TCM culture, the future development of chromatographic technology is expected. Furthermore, the mechanisms of TCM in medical healthcare, prevention, and treatment of diseases are likely be explained through chromatography, leading to a new strategy to realize the molecularization and digitalization of TCM, which is beneficial to the development of original new drugs.
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- 2021
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18. Constitutive expression of tyrosine phenol-lyase from Erwinia herbicola in Escherichia coli for l-DOPA production
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Yujie Cai, Yajun Bai, Mengqing Tang, Tai-Ping Fan, and Xiaohui Zheng
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food and beverages ,Tyrosine phenol-lyase ,medicine.disease_cause ,law.invention ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Cell culture ,Tryptone ,law ,Glycerol ,medicine ,Recombinant DNA ,Yeast extract ,Tyrosine ,Escherichia coli - Abstract
l-DOPA is a major drug for the treatment of Parkinson’s disease, and microbial enzymatic synthesis is an essential way for its industrial production. The expression of tyrosine phenol-lyase (TPL) derived from Erwinia herbicola under six different constitutive promoters in Escherichia coli was studied. The recombinant strain 5 can express TPL well with growth. The optimal medium composition of this strain was as follows: tryptone 18 g/L, yeast extract 28 g/L, glycerol 10 g/L. After the cell culture is completed, the collected cells were used to catalyze the production of l-DOPA, and the concentration can reach 67.9 g/L.
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- 2021
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19. Characterization of acid-resistant aldo–keto reductases capable of asymmetric synthesis of (R)-CHBE from Lactobacillus plantarum DSM20174
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Jiufeng Zhu, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, and Yujie Cai
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- 2022
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20. Primary analysis of four salt tolerant plants growing in Hai-He Plain, China
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Yajun, Bai, Xiaojing, Liu, Weiqiang, Li, Kratochwil, A., editor, Lieth, Helmut, editor, and Mochtchenko, Marina, editor
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- 2003
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21. Highly efficient biosynthesis of spermidine from L-homoserine and putrescine using an engineered Escherichia coli with NADPH self-sufficient system
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Xinxin Liang, Huaxiang Deng, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, and Yujie Cai
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Carboxy-Lyases ,Spermidine ,Escherichia coli ,Homoserine ,Putrescine ,General Medicine ,Applied Microbiology and Biotechnology ,NADP ,Biotechnology - Abstract
Spermidine is an important polyamine that can be used for the synthesis of various bioactive compounds in the food and pharmaceutical fields. In this study, a novel efficient whole-cell biocatalytic method with an NADPH self-sufficient cycle for spermidine biosynthesis was designed and constructed by co-expressing homoserine dehydrogenase (HSD), carboxyspermidine dehydrogenase (CASDH), and carboxyspermidine decarboxylase (CASDC). First, the enzyme-substrate coupled cofactor regeneration system from co-expression of NADP
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- 2022
22. A novel feruloyl esterase with high rosmarinic acid hydrolysis activity from Bacillus pumilus W3
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Weiyue Liang, Xiaohui Zheng, Xiong Tianzhen, Huaxiang Deng, Xiaomei Wang, Yujie Cai, Tai-Ping Fan, and Yajun Bai
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medicine.disease_cause ,Depsides ,Biochemistry ,Substrate Specificity ,chemistry.chemical_compound ,Hydrolysis ,Caffeic Acids ,Chlorogenic acid ,Structural Biology ,Feruloyl esterase ,Escherichia coli ,medicine ,Caffeic acid ,Molecular Biology ,Bacillus pumilus ,Chromatography ,biology ,Chemistry ,Rosmarinic acid ,Temperature ,Substrate (chemistry) ,General Medicine ,Hydrogen-Ion Concentration ,biology.organism_classification ,Molecular Weight ,Cinnamates ,Chlorogenic Acid ,Carboxylic Ester Hydrolases - Abstract
A novel feruloyl esterase (BpFae12) with rosmarinic acid (RA) hydrolysis activity was isolated from Bacillus pumilus W3 and expressed in Escherichia coli BL21 (DE3). With RA as a substrate, the optimal pH and temperature of BpFae12 were pH 8.0 and 50 °C, respectively. The specific enzyme activity was 12.8 U·mg−1. BpFae12 showed the highest activity and substrate affinity toward RA (Vmax of 13.13 U·mg−1, Km of 0.41 mM). Moreover, it also presented strong hydrolysis performance against chlorogenic acid (190.17 U·mg−1). RA was effectively Hydrolyzed into more bioactive caffeic acid and 3,4-dihydroxyphenyllactic acid by BpFae12, which have potential applications in the food industry.
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- 2020
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23. Unveiling the Multipath Biosynthesis Mechanism of 2-Phenylethanol in Proteus mirabilis
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Tai-Ping Fan, Yajun Bai, Xiaohui Zheng, Liu Jinbin, and Yujie Cai
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0106 biological sciences ,chemistry.chemical_classification ,Aromatic L-amino acid decarboxylase ,biology ,010401 analytical chemistry ,General Chemistry ,Metabolism ,biology.organism_classification ,01 natural sciences ,Proteus mirabilis ,0104 chemical sciences ,Amino acid ,chemistry.chemical_compound ,Enzyme ,chemistry ,Biochemistry ,Biosynthesis ,Transferase ,General Agricultural and Biological Sciences ,Gene ,010606 plant biology & botany - Abstract
Proteus mirabilis could convert l-phenylalanine into 2-phenylethanol (2-PE) via the Ehrlich pathway, the amino acid deaminase pathway, and the aromatic amino acid decarboxylase pathway. The aromatic amino acid decarboxylase pathway was proved for the first time in P. mirabilis. In this pathway, l-aromatic amino acid transferase demonstrated a unique catalytic property, transforming 2-penylethylamine into phenylacetaldehyde. Eleven enzymes were supposed to involve in 2-phenylethanol synthesis. The mRNA expression levels of 11 genes were assessed over time by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in vivo. As a result, the expression of 11 genes was significantly increased, suggesting that P. mirabilis could transform l-phenylalanine into 2-phenylethanol via three pathways under aerobic conditions; nine genes were significantly overexpressed, suggesting that P. mirabilis could synthesize 2-phenylethanol via the Ehrlich pathway under anaerobic conditions. This study reveals the multipath synthetic metabolism for 2-phenylethanol in P. mirabilis and will enrich the new ideas for natural (2-PE) synthesis.
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- 2020
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24. Immunomodulatory role of recombinant human erythropoietin in acute kidney injury induced by crush syndromeviainhibition of the TLR4/NF-κB signaling pathway in macrophages
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Ping Fu, Rongshuang Huang, Padamata Tarun, Yajun Bai, Jiaojiao Zhou, Yuying Feng, and Yong Jiang
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0301 basic medicine ,Immunology ,Toxicology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,medicine ,Immunology and Allergy ,Macrophage ,Crush syndrome ,Pharmacology ,business.industry ,Acute kidney injury ,General Medicine ,medicine.disease ,030104 developmental biology ,Erythropoietin ,030220 oncology & carcinogenesis ,TLR4 ,Cancer research ,Recombinant DNA ,Signal transduction ,business ,Function (biology) ,medicine.drug - Abstract
Objective: The present study aimed to investigate whether recombinant human erythropoietin (rHuEPO) plays an immunomodulatory function by regulating the TLR4/NF-κB signaling pathway.Materials and m...
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- 2020
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25. Structure-Based Engineering of Substrate Specificity for Blastochloris Viridis Homospermidine Synthase
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Wenjing Liu, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, and Yujie Cai
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- 2022
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26. A Novel Compound, Tanshinol Borneol Ester, Ameliorates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Oxidative Stress via the mTOR/β-TrCP/NRF2 Pathway
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Dongjian Han, Fuhang Wang, Bo Wang, Zhentao Qiao, Xinyue Cui, Yi Zhang, Qingjiao Jiang, Miaomiao Liu, Jiahong Shangguan, Xiaohui Zheng, Yajun Bai, Chunyan Du, and Deliang Shen
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Pharmacology ,autophagy ,antioxidant ,cardiac hypertrophy ,mTOR ,Pharmacology (medical) ,Therapeutics. Pharmacology ,RM1-950 ,er stress ,Nrf2 - Abstract
Tanshinol borneol ester (DBZ) exerts anti-atherosclerotic and anti-inflammatory effects. However, its effects on cardiac hypertrophy are not well understood. In this work, we investigated the treatment effects and potential mechanisms of DBZ on the hypertrophic heart under oxidative stress and endoplasmic reticulum (ER) stress. A hypertrophic model was established in rats using transverse-aortic constriction (TAC) surgery and in neonatal rat cardiomyocytes (NRCMs) using angiotensin II (Ang II). Our results revealed that DBZ remarkably inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis in vivo and in vitro through nuclear NRF2 accumulation, and enhanced NRF2 stability via regulating the mTOR/β-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.
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- 2021
27. Revealing the Antiepileptic Effect of α-Asaronol on Pentylenetetrazole-Induced Seizure Rats Using NMR-Based Metabolomics
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Xue Zhao, Lihong Liang, Ru Xu, Peixuan Cheng, Pu Jia, Yajun Bai, Yajun Zhang, Xinfeng Zhao, Xiaohui Zheng, and Chaoni Xiao
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General Chemical Engineering ,General Chemistry - Abstract
α-Asaronol from
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- 2021
28. Overexpression and biochemical characterization of a carboxyspermidine dehydrogenase from Agrobacterium fabrum str. C58 and its application to carboxyspermidine production
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Xinxin Liang, Huaxiang Deng, Tianzhen Xiong, Yajun Bai, Tai‐Ping Fan, Xiaohui Zheng, and Yujie Cai
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Nutrition and Dietetics ,Spermidine ,Polyamines ,Agrobacterium ,Oxidoreductases ,Agronomy and Crop Science ,NADP ,Food Science ,Biotechnology - Abstract
Carboxyspermidine (C-Spd) is a potentially valuable polyamine carboxylate compound and an excellent building block for spermidine synthesis, which is a critical polyamine with significant implications for human health and longevity. C-Spd can also be used to prepare multivalent cationic lipids and modify nucleoside probes. Because of these positive effects on human health, C-Spd is of considerable interest as a food additive and pharmaceutical target.A putative gene afcasdh from Agrobacterium fabrum str. C58, encoding carboxyspermidine dehydrogenase with C-Spd biosynthesis activity, was synthesized and transformed into Escherichia coli BL21 (DE3) for overexpression. The recombinant AfCASDH was purified and fully characterized. The optimum temperature and pH for the recombinant enzyme were 30 °C and 7.5, respectively. The coupled catalytic strategy of AfCASDH and various NADPH regeneration systems were developed to enhance the efficient production of C-Spd compound. Finally, the maximum titer of C-Spd production successfully achieved 1.82 mmol LA novel AfCASDH from A. fabrum str. C58 was characterized that could catalyze the formation of C-Spd from putrescine and l-aspartate-β-semialdehyde (L-Asa). A whole-cell catalytic strategy coupled with NADPH regeneration was established successfully for C-Spd biosynthesis for the first time. The coupled system indicated that AfCASDH might provide a feasible method for the industrial production of C-Spd. © 2021 Society of Chemical Industry.
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- 2021
29. Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia
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Yajun, Bai, Pu, Jia, Ye, Zhao, Lingjian, Yang, Xiaoxiao, Wang, Xue, Wang, Jing, Wang, Ni'er, Zhong, Huaxiang, Deng, Linxiang, Du, Jiacheng, Fang, Yanbo, Xue, Yongyong, Chen, Shuomo, Gao, Ying, Feng, Yi, Yan, Tianzheng, Xiong, Jinbin, Liu, Ying, Sun, Jing, Xie, Xirui, He, Xuexia, An, Pei, Liu, Jinjin, Xu, Fanggang, Qin, Xue, Meng, Qian, Yin, Qiuxiang, Yang, Rong, Gao, Xiaokang, Gao, Kai, Luo, Qiannan, Li, Xing, Wang, Jing, Liang, Puye, Yang, Yajun, Zhang, Sha, Liao, Shixiang, Wang, Xinfeng, Zhao, Chaoni, Xiao, Jie, Yu, Qinshe, Liu, Rui, Wang, Ning, Peng, Xiaowen, Wang, Jianbo, Guo, Xia, Li, Haijing, Liu, Yan, Bai, Zijian, Li, Youyi, Zhang, Yefei, Nan, Qunzheng, Zhang, Xunli, Zhang, Jin'e, Lei, Erna, Alberts, Angélique, de Man, Hye Kyong, Kim, Su-Jung, Hsu, Yu Sheng, Jia, Joerg, Riener, Jianbin, Zheng, Wanbin, Zhang, Xiaopu, Zheng, Yujie, Cai, Mei, Wang, Tai-Ping, Fan, and Xiaohui, Zheng
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Inflammation ,Pharmacology ,Heart Diseases ,Swine ,Humans ,Animals ,Hypoxia ,Dihydroxyphenylalanine - Abstract
Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×10
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- 2022
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30. Synthesis, crystal structure and bioactivities of α-asaronol
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Qun-Zheng Zhang, Zhen-Hua Zhong, Ding Hao, Ming-Nan Feng, Si-Chang Wang, Qi-Long Han, Yajun Bai, Danni Xu, Sha Liao, Chaoni Xiao, Xun-Li Zhang, and Xiaohui Zheng
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Inorganic Chemistry ,Mice ,Spectroscopy, Fourier Transform Infrared ,Materials Chemistry ,Animals ,Hydrogen Bonding ,Physical and Theoretical Chemistry ,Anisoles ,Condensed Matter Physics ,Crystallography, X-Ray - Abstract
α-Asaronol [or (E)-3′-hydroxyasarone; systematic name: (E)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-ol; C12H16O4] was synthesized towards the development of a potential antiepileptic drug. Following purification by recrystallization, single crystals of α-asaronol were obtained by a liquid interface diffusion method at room temperature. The product was characterized by 1H and 13C NMR, and FT–IR spectroscopic analysis. X-ray crystallography revealed the title crystal to belong to the orthorhombic space group P212121. Preliminary bioassays with mouse neuroblastoma N2a cells demonstrated the neuroprotective activities of the synthesized α-asaronol.
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- 2021
31. Modified Catalytic Performance of Lactobacillus Fermentum L-lactate Dehydrogenase by Rational Design
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Tai-Ping Fan, Xiaohui Zheng, Aiai Wu, Yajun Bai, and Yujie Cai
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Active center ,chemistry.chemical_classification ,Enzyme ,Biochemistry ,biology ,Chemistry ,Lactobacillus fermentum ,Glyoxylate cycle ,Substrate (chemistry) ,Dehydrogenase ,Enzyme kinetics ,biology.organism_classification ,Amino acid - Abstract
L-lactate dehydrogenases can reduce alpha-keto carboxylic acids asymmetrically and generally have a broad substrate spectrum. L-lactate dehydrogenase gene (LF-L-LDH0845) with reducing activity towards 3,4-dihydroxyphenylpyruvate and phenylpyruvate was obtained from Lactobacillus fermentum JN248. To change the substrate specificity of LDH0845 and improve its catalytic activity towards large substrates, site-directed mutation of Tyr221 was performed by analyzing the amino acids in active center. Kinetic parameters show that the k cat values of Y221F mutant on 3,4-dihydroxyphenylpyruvate, 4-methyl-2-oxopentanoate, and glyoxylate are 1.21 s -1 , 1.35 s -1 , and 0.72 s -1 , respectively, which are 420%, 150% and 130% of the wild-type LDH0845. This study shows that the mutations of Y221 can significantly change the substrate specificity of LDH0845, making it become a potential tool enzyme for the reduction of alpha-keto carboxylic acids with large functional groups.
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- 2021
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32. Characterization of a putative tropinone reductase from Tarenaya hassleriana with a broad substrate specificity
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Yixiang Li, Yajun Bai, Tai‐Ping Fan, Xiaohui Zheng, and Yujie Cai
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Process Chemistry and Technology ,Drug Discovery ,Biomedical Engineering ,Molecular Medicine ,Bioengineering ,General Medicine ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
A novel short-chain alcohol dehydrogenase from Tarenaya hassleriana labeled as putative tropinone reductase was heterologously expressed in Escherichia coli. Purified recombinant protein had molecular weight of approximately 30 kDa on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. T. hassleriana tropinone reductase-like enzyme (ThTRL) had not detected oxidative activity. The optimum pH for enzyme activity of ThTRL was weakly acidic (pH 5.0). 50°C was the optimum temperature for ThTRL. The highest catalytic efficiency and substrate affinity for recombinant ThTRL were observed with (+)-camphorquinone (k
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- 2021
33. Characterisation of five alcohol dehydrogenases from Lactobacillus reuteri DSM20016
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Tai-Ping Fan, Xiaohui Zheng, Zhenghong Hu, Yujie Cai, Yajun Bai, and Pu Jia
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chemistry.chemical_classification ,biology ,Substrate (chemistry) ,Bioengineering ,Propionaldehyde ,Cheese ripening ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Biochemistry ,Hexanal ,Enzyme assay ,Lactobacillus reuteri ,chemistry.chemical_compound ,Enzyme ,chemistry ,biology.protein ,Food science ,Enzyme kinetics - Abstract
Alcohol dehydrogenases convert aldehydes causing volatile aromas in cheese into corresponding alcohols. In this study, we cloned and recombinantly produced five novel ADHs from Lactobacillus reuteri DSM20016 in Escherichia coli BL21 (DE3). The resulting proteins have molecular weights between 35 and 39 kDa. The optimum pH for enzyme activity of ADH-1, ADH-2 and ADH-3 was weakly acidic (pH 5, 6 and 5, respectively), compared with pH 7 for ADH-4 and ADH-5. The optimum temperature range for ADH-1, ADH-3, ADH-4 and ADH-5 was 40 °C ―55 °C, compared with 35 °C for ADH-2. These enzymes reduced a broad range of substrates; the highest catalytic efficiency and substrate affinity for ADH-1 was observed with heptaldehyde (Kcat/Km = 39.4 s−1·mM−1, Km = 0.459 mM), while 3-methylbutanal was the best substrate for ADH-5 (Kcat/Km = 24.0 s−1·mM−1, Km = 1.35 × 10−2 mM). ADH-2, ADH-3 and ADH-4 exhibited the highest substrate affinity for valeraldehyde, propionaldehyde, and hexanal, respectively (Km = 1.19 × 10−2 mM, 2.81 × 10−2 mM, 1.35 × 10−2 mM). The enzymatic properties indicated that these enzymes effectively converted fragrant compounds during cheese ripening.
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- 2019
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34. Expression and characterisation of feruloyl esterases from Lactobacillus fermentum JN248 and release of ferulic acid from wheat bran
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Yujie Cai, Tai-Ping Fan, Jiang Jing, Yajun Bai, Pu Jia, Huaxiang Deng, and Xiaohui Zheng
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Dietary Fiber ,Limosilactobacillus fermentum ,Coumaric Acids ,Lactobacillus fermentum ,Gene Expression ,02 engineering and technology ,Biochemistry ,Esterase ,Substrate Specificity ,Ferulic acid ,03 medical and health sciences ,chemistry.chemical_compound ,Structural Biology ,Food science ,Cloning, Molecular ,Molecular Biology ,030304 developmental biology ,Thermostability ,chemistry.chemical_classification ,0303 health sciences ,biology ,Bran ,Hydrolysis ,General Medicine ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Enzyme assay ,Biomechanical Phenomena ,Kinetics ,Enzyme ,chemistry ,Xylanase ,biology.protein ,0210 nano-technology ,Carboxylic Ester Hydrolases - Abstract
Genes encoding six feruloyl esterases (FAEs; lbff0997, lbff0272, lbff1432, lbff1695, lbff1849, lbff0153) from Lactobacillus fermentum JN248 were cloned, overexpressed and characterised. Maximum enzyme activity was observed at 35 °C for recombinant FAEs LFFae0997, LFFae0272 and LFFae0153, at 30 °C for LFFae1695, and at 40 °C for LFFae1432and LFFae1849. For five of the enzymes, optimal activity was observed at pH 7.0 or pH 8.0, and high thermostability was measured up to 55 °C. By contrast, LFFae1432 lost less than 10.0% activity after incubation at 40 °C for 2 h, and pH stability was highest between pH 7.0 and pH 9.0. In addition, LFFae1432 was the most robust esterase, with a higher affinity and hydrolytic activity against synthetic esters. The enzymes released ferulic acids (FAs) from de-starched wheat bran (DSWB), and 60.7% of the total alkali-extractable FAs were released when LFFae1432 was added alone, compared with less than 10% for the other enzymes. The amount of FAs released by FAEs increased when combined with xylanase. These FAEs could serve as promising biocatalysts for biodegradation, and LFFae1432 may hold promise for potential industrial applications.
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- 2019
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35. Synthesis of Imatinib by C–N Coupling Reaction of Primary Amide and Bromo-Substituted Pyrimidine Amine
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Yun Ai, Rui Wang, Yajun Bai, Xiao Bai, Yifeng Liu, Huan Chen, Cuiling Wang, Xiumei Ma, and Xudong Zheng
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Primary (chemistry) ,Pyrimidine ,010405 organic chemistry ,Organic Chemistry ,Imatinib ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Coupling reaction ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Amide ,medicine ,Amine gas treating ,Physical and Theoretical Chemistry ,Benzamide ,medicine.drug - Abstract
A new method for imatinib synthesis is described by using the C–N coupling reaction of 4-(4-methylpiperazine-1-methyl)benzamide with N-(5-bromo-2-tolyl)-4-(3-pyridyl)pyrimidin-2-amine to form imati...
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- 2019
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36. A simple risk score for prediction of sepsis associated-acute kidney injury in critically ill patients
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Lichuan Yang, Xin Wang, Jia Yang, Ping Fu, Dingming Cai, Jiaojiao Zhou, and Yajun Bai
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Male ,Nephrology ,medicine.medical_specialty ,Critical Illness ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Kidney Function Tests ,urologic and male genital diseases ,Risk Assessment ,law.invention ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,law ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Framingham Risk Score ,business.industry ,Acute kidney injury ,Disease Management ,Retrospective cohort study ,Acute Kidney Injury ,Middle Aged ,Prognosis ,medicine.disease ,Intensive care unit ,Primary Prevention ,Heart failure ,Female ,business ,Follow-Up Studies ,Kidney disease - Abstract
Sepsis is common and frequently fatal condition in critically ill patients and is a major cause of acute kidney injury (AKI). In this retrospective study, we sought to develop a comprehensive risk score model of sepsis associated-AKI (SA-AKI). A total of 2617 patients were randomly assigned to a development (1554 patients) and a validation group (777 patients). The risk score model for SA-AKI was developed with multivariate regression analysis in development group and the model was further evaluated on validation group. We identified 16 independent predictors of SA-AKI in development group (age ≥ 60 years, hypertension/coronary heart disease, diabetes, chronic kidney disease, heart failure, chronic obstructive pulmonary disease, acute severe pancreatitis, hypotension, hypoproteinemia, lactic acidosis, the length of stay in intensive care unit(ICU), 60 g/L
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- 2019
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37. Biosynthesis of D-danshensu from L-DOPA using engineered Escherichia coli whole cells
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Jiang Jing, Xiaohui Zheng, Ye Zhao, Yajun Bai, Tai-Ping Fan, Yujie Cai, and Xiong Tianzhen
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Gene Expression ,Dehydrogenase ,medicine.disease_cause ,Applied Microbiology and Biotechnology ,Levodopa ,03 medical and health sciences ,chemistry.chemical_compound ,Plasmid ,Biotransformation ,Biosynthesis ,Glucose dehydrogenase ,Escherichia coli ,medicine ,Gene ,030304 developmental biology ,0303 health sciences ,Strain (chemistry) ,030306 microbiology ,Chemistry ,Temperature ,Cardiovascular Agents ,General Medicine ,Hydrogen-Ion Concentration ,Recombinant Proteins ,digestive system diseases ,Enzymes ,stomatognathic diseases ,Metabolic Engineering ,Biochemistry ,Lactates ,Biotechnology - Abstract
D-Danshensu (D-DSS), a traditional Chinese medicine, is used to treat cardiovascular and cerebrovascular diseases. However, current isolation protocols for D-DSS both natural and synthetic are not ideal; therefore, in this study, we have developed a whole-cell biotransformation method to produce D-DSS from L-DOPA. This was done by co-expressing L-amino acid deaminase (aadL), D-lactate dehydrogenase (ldhD), and glucose dehydrogenase (gdh). To begin to optimize the production of D-DSS, varying copy number plasmids were used to express each of the required genes. The resulting strain, Escherichia coli ALG7, which strongly overexpressed aadL, ldhD, and weakly overexpressed gdh, yielded a 378% increase in D-DSS production compared to E. coli ALG1. Furthermore, the optimal reaction conditions for the production of D-DSS were found to be a pH of 7.5, temperature at 35 °C, and 50 g/L wet cells for 12 h. Under these optimized conditions, the D-DSS amount achieved 119.1 mM with an excellent ee (> 99.9%) and a productivity of 9.9 mM/h.
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- 2019
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38. The interaction mechanism between alkaloids and pepsin based on lum-AuNPs in the chemiluminescence analysis
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Yajun Bai, Xiaohui Zheng, Pu Jia, Sha Liao, Meimei Zhao, Shixiang Wang, Jingni Wu, Ruimin Liu, Kai Luo, and Jing Luo
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Jatrorrhizine ,biology ,Stereochemistry ,General Chemical Engineering ,Active site ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Binding constant ,0104 chemical sciences ,law.invention ,Luminol ,chemistry.chemical_compound ,Berberine ,Matrine ,chemistry ,law ,biology.protein ,Binding site ,0210 nano-technology ,Chemiluminescence - Abstract
Herein, novel luminol functional gold nanoparticles (lum-AuNPs) were quickly prepared in an alkaline luminol solution with HAuCl4, which had the unique characteristics of uniform size and excellent luminescence properties. A self-made flow injection-chemiluminescence (FI-CL) system was established to study the interaction between pepsin (Pep) and five alkaloids (anisodamine, berberine, reserpine, jatrorrhizine and matrine) using lum-AuNPs as the CL probe. Based on the abovementioned home-made CL system, the possible interaction mechanisms of Pep with five alkaloids have been comprehensively discussed by molecular docking simulation, chemical thermodynamics and kinetic studies. The results indicated that there were obvious CL enhancement and inhibition effects on the lum-AuNPs CL system for the Pep and the complex of Pep/alkaloids, respectively. The possible mechanism for the interaction of Pep–five alkaloids was mainly mediated by the hydrophobic force. The binding constant K and binding site n for the Pep–alkaloid interaction are consistent with the list of Ber > Res > Ani, Jat > Mat, which is relative to the potential of groups of alkaloids interacting with the active site of Pep.
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- 2019
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39. Heterologous expression and characterization of a borneol dehydrogenase from Arabidopsis lyrate and its application for the enzymatic resolution of rac-camphor
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Xiaoxiang Hu, Huaxiang Deng, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, and Yujie Cai
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Process Chemistry and Technology ,Physical and Theoretical Chemistry ,Catalysis - Published
- 2022
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40. Simultaneous and rapid analysis of chiral Danshensu and its ester derivatives by supercritical fluid chromatography
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Ying, Sun, Pu, Jia, Jingdong, Wei, Yujun, Bai, Lingjian, Yang, Yajun, Bai, and Xiaohui, Zheng
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Clinical Biochemistry ,Drug Discovery ,Lactates ,Pharmaceutical Science ,Chromatography, Supercritical Fluid ,Esters ,Stereoisomerism ,Spectroscopy ,Analytical Chemistry - Abstract
The analysis and separation of chiral compounds with wide polar range by supercritical fluid chromatography is of major importance in the process of drug development and quality control. In this work, a fast and reliable enantioselective method for the simultaneous quantitative determination of 8 DBZ-related enantiomers has been successfully developed by supercritical fluid chromatography using an amylose-based reversed-chiral stationary phase. Within less than seven minutes all target compounds could be baseline resolved, using a mobile phase comprising supercritical carbon dioxide and methanol with 0.05 % H
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- 2022
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41. Converting the 3-quinuclidinone reductase from Agrobacterium tumefaciens into the ethyl 4-chloroacetoacetate reductase by site-directed mutagenesis
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Tai-Ping Fan, Yajun Bai, Xiaohui Zheng, Di Liu, Yujie Cai, and Linbo Gou
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Quinuclidines ,Stereochemistry ,Biomedical Engineering ,Bioengineering ,Reductase ,Applied Microbiology and Biotechnology ,Acetoacetates ,Substrate Specificity ,Drug Discovery ,Enzyme kinetics ,Site-directed mutagenesis ,chemistry.chemical_classification ,biology ,Process Chemistry and Technology ,Mutagenesis ,General Medicine ,Agrobacterium tumefaciens ,biology.organism_classification ,Directed evolution ,Enzyme assay ,Kinetics ,Enzyme ,chemistry ,biology.protein ,Mutagenesis, Site-Directed ,Molecular Medicine ,Oxidoreductases ,Biotechnology - Abstract
In this study, the 3-quinuclidinone reductase from Agrobacterium tumefaciens (AtQR) was modified by site-directed mutagenesis. And we further obtained a saturation mutant library in which the residue 197 was mutated. A single-point mutation converted the wild enzyme that originally had no catalytic activity in reduction of ethyl 4-chloroacetoacetate (COBE) into an enzyme with catalytic activity. The results of enzyme activity assays showed that the 7 variants could asymmetrically reduce COBE to ethyl (S)-4-chloro-3-hydroxybutyrate ((S)-CHBE) with NADH as coenzyme. In the library, the variant E197N showed higher catalytic efficiency than others. The E197N was optimally active at pH 6.0 and 40°C, and the catalytic efficiency (kcat /Km ) for COBE was 51.36 s-1 ·mM-1 . This study showed that the substrate specificity of AtQR could be changed through site-directed mutagenesis at the residue 197. This article is protected by copyright. All rights reserved.
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- 2021
42. Unveiling the Multipath Biosynthesis Mechanism of 2-Phenylethanol in
- Author
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Jinbin, Liu, Yajun, Bai, Tai-Ping, Fan, Xiaohui, Zheng, and Yujie, Cai
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Bacterial Proteins ,Phenylalanine ,Phenylethyl Alcohol ,Proteus mirabilis ,Biosynthetic Pathways - Published
- 2020
43. A novel type alanine dehydrogenase from Helicobacter aurati: Molecular characterization and application
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Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, Xiaoxiang Hu, and Yujie Cai
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Alanine dehydrogenase ,02 engineering and technology ,medicine.disease_cause ,Biochemistry ,Substrate Specificity ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,Structural Biology ,Oxaloacetic acid ,Helicobacter ,medicine ,Escherichia coli ,Enzyme kinetics ,Molecular Biology ,Glyoxylic acid ,030304 developmental biology ,Alanine ,0303 health sciences ,Substrate (chemistry) ,General Medicine ,021001 nanoscience & nanotechnology ,Recombinant Proteins ,chemistry ,Alanine Dehydrogenase ,Specific activity ,0210 nano-technology - Abstract
A novel alanine dehydrogenase (ADH; EC.1.4.1.1) with high pyruvate reduced activity was isolated from Helicobacter aurati and expressed in Escherichia coli BL21 (DE3). The optimum pH of the reduction and oxidation reaction were 8.0 and 9.0, respectively, and the optimum temperature was 55 °C. With pyruvate and alanine as substrates, the specific activity of HAADH1 were 268 U·mg−1 and 26 U·mg−1, respectively. HAADH1 had a prominent substrate specificity for alanine (Km = 2.23 mM, kcat/Km = 8.1 s−1·mM−1). In the reduction reaction, HAADH1 showed the highest substrate affinity for pyruvate (Km = 0.56 mM, kcat/Km = 364 s−1·mM−1). Compared to pyruvate, oxaloacetic acid, 2-ketobutyric acid, 3-fluoropyruvate, α-ketoglutaric acids, glyoxylic acid showed a residual activity of 93.30%, 8.93%, 5.62%, 2.57%, 2.51%, respectively. Phylogenetic tree analysis showed that this is a new type of ADH which have a low sequence similarity to available ADH reported in references. 3-Fluoropyruvate was effectively reduced to 3-fluoro-L-alanine by whole-cell catalysis.
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- 2020
44. Immunomodulatory role of recombinant human erythropoietin in acute kidney injury induced by crush syndrome
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Jiaojiao, Zhou, Yajun, Bai, Yong, Jiang, Padamata, Tarun, Yuying, Feng, Rongshuang, Huang, and Ping, Fu
- Subjects
Toll-Like Receptor 4 ,Mice ,RAW 264.7 Cells ,Macrophages ,NF-kappa B ,Animals ,Immunologic Factors ,Crush Syndrome ,Acute Kidney Injury ,Erythropoietin ,Recombinant Proteins ,Signal Transduction - Published
- 2020
45. Advanced strategy for metabolite exploration in filamentous fungi
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Huaxiang Deng, Tai-Ping Fan, Yajun Bai, Xiaohui Zheng, and Yujie Cai
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0106 biological sciences ,Metabolite ,Mutagenesis (molecular biology technique) ,Computational biology ,Biology ,ENCODE ,01 natural sciences ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,chemistry.chemical_compound ,Metabolic balance ,010608 biotechnology ,Drug Discovery ,Gene ,030304 developmental biology ,Gene Editing ,0303 health sciences ,Cellular metabolism ,Drug discovery ,Fungi ,General Medicine ,Biosynthetic Pathways ,chemistry ,Multigene Family ,Genetic Engineering ,Biotechnology - Abstract
Filamentous fungi comprise an abundance of gene clusters that encode high-value metabolites, whereas affluent gene clusters remain silent during laboratory conditions. Complex cellular metabolism further limits these metabolite yields. Therefore, diverse strategies such as genetic engineering and chemical mutagenesis have been developed to activate these cryptic pathways and improve metabolite productivity. However, lower efficiencies of gene modifications and screen tools delayed the above processes. To address the above issues, this review describes an alternative design-construction evaluation optimization (DCEO) approach. The DCEO tool provides theoretical and practical principles to identify potential pathways, modify endogenous pathways, integrate exogenous pathways, and exploit novel pathways for their diverse metabolites and desirable productivities. This DCEO method also offers different tactics to balance the cellular metabolisms, facilitate the genetic engineering, and exploit the scalable metabolites in filamentous fungi.
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- 2020
46. Reducing 3,4-dihydroxyphenylpyruvic acid to<scp>d</scp>-3,4-dihydroxyphenyllactic acid via a coenzyme nonspecific<scp>d</scp>-lactate dehydrogenase fromLactobacillus reuteri
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Y.H. Wang, Yujie Cai, Xiaohui Zheng, Yajun Bai, and Tai-Ping Fan
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0301 basic medicine ,chemistry.chemical_classification ,biology ,fungi ,030106 microbiology ,Dehydrogenase ,General Medicine ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Cofactor ,Lactic acid ,Lactobacillus reuteri ,Turnover number ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Enzyme ,chemistry ,Biochemistry ,Glucose dehydrogenase ,D-lactate dehydrogenase ,biology.protein ,Biotechnology - Abstract
AIMS The purpose of this work was to find an efficient enzyme to synthesize d-3,4-dihydroxyphenyllactic acid (d-DSS). METHODS AND RESULTS Nineteen lactic acid bacteria strains were screened for production of d-DSS using 3,4-dihydroxyphenylpyruvic acid (DPA) as a substrate. Lactobacillus reuteri JN516 exhibited the highest d-DSS yield. A nonspecific coenzyme, d-lactate dehydrogenase (d-LDH82319), from L. reuteri JN516 with high DPA reducing activity was identified. This enzyme reduced DPA to form d-DSS with excellent optical purity (enantioselectivity >99%). Its molecular weight was 35 kDa based on SDS-PAGE migration. The Michaelis-Menten constant (Km ), turnover number (kcat ), and catalytic efficiency (kcat /Km ) of d-LDH82319 for DPA were 0·09 mmol l-1 , 2·17 s-1 and 24·07 (mmol l-1 )-1 s-1 , respectively, with NADH as the coenzyme. The (Km ), (kcat ) and (kcat /Km ) of d-LDH82319 for DPA were 0·10 mmol l-1 , 0·13 s-1 and 1·30 (mmol l-1 )-1 s-1 , respectively, with NADPH as the coenzyme. The optimum temperature and pH of d-LDH82319 were 25°C and pH 8 respectively. Additionally, d-LDH82319 had a broad substrate range for alpha-keto acids, among which the activity of reducing pyruvate was the strongest; therefore, it belongs to the group of d-lactate dehydrogenases. d-LDH82319 and glucose dehydrogenase (GDH) were coexpressed to produce d-DSS from DPA. CONCLUSIONS d-LDH82319 from L. reuteri JN516 with high DPA reducing activity has the characteristics of a nonspecific coenzyme. SIGNIFICANCE AND IMPACT OF THE STUDY d-LDH82319 is the first reported coenzyme nonspecific d-lactate dehydrogenase with DPA-reducing activity. The coexpression system provided an effective method to produce d-DSS.
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- 2018
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47. Design, synthesis and biological evaluation of (E)-3-(3,4,5-trimethoxyphenyl) acrylic acid (TMCA) amide derivatives as anticonvulsant and sedative agents
- Author
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Shaoping Wu, Yajun Bai, Zefeng Zhao, Xiaohui Zheng, Xirui He, Xufei Chen, Ying Sun, and Yujun Bai
- Subjects
Pentobarbital ,Molecular model ,010405 organic chemistry ,Hydrochloride ,medicine.drug_class ,medicine.medical_treatment ,Organic Chemistry ,Neurotoxicity ,medicine.disease ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Anticonvulsant ,chemistry ,Amide ,Sedative ,medicine ,General Pharmacology, Toxicology and Pharmaceutics ,medicine.drug ,Acrylic acid - Abstract
In this article, a novel series of (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (TMCA) amide derivatives 1-18 were designed and synthesized by a facile and one-pot step, which were achieved with good yields using 1-hydroxybenzotriazole (HOBT) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as activation system. All the synthesized derivatives were biologically evaluated for their anticonvulsant, sedative activity and neurotoxicity using the maximal electroshock (MES) model, sc-pentylenetetrazol (PTZ) model, pentobarbital sodium-induced sleeping model, and locomotor activity tests, respectively. Among them, compounds 4, 9 and 16 exhibited good anticonvulsant activity in primary evaluation. Furthermore, compound 4 is the most effective anticonvulsant and sedative agent in subsequent tests, while the low threshold of toxicity of compound 4 is vigilant. Compounds 9 and 16 also performed significantly anticonvulsant activity in subsequent tests with weak toxicity. The molecular modeling experiments also predicted good binding interactions of the obtained active molecules with the GABA transferas. Therefore, it could be concluded that the synthesized derivatives 4, 9 and 16 would represent useful lead compounds for further investigation in the development of anticonvulsant and sedative agents.
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- 2018
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48. Identification of a l-Lactate dehydrogenase with 3,4-dihydroxyphenylpyruvic reduction activity for l-Danshensu production
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Tai-Ping Fan, Ye Zhao, Xiaohui Zheng, Yajun Bai, Huan Lu, and Yujie Cai
- Subjects
0301 basic medicine ,biology ,Lactobacillus fermentum ,030106 microbiology ,Substrate (chemistry) ,Bioengineering ,Dehydrogenase ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Biochemistry ,Cofactor ,Enzyme assay ,Lactic acid ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Glucose dehydrogenase ,Lactate dehydrogenase ,biology.protein - Abstract
Danshensu (DSS), also known as 3,4-dihydroxyphenyllactate, is an herbal preparation with prominent pharmacological activities. It has lactic acid structure and may be obtained by reducing 3,4-dihydroxyphenylpyruvate with lactate dehydrogenase. We screened a coenzyme-aspecific L-lactate dehydrogenase (LF-L-LDH0845) from lactobacillus fermentum for the bioconversion of 3,4-dihydroxyphenylpyruvate to optically pure (ee ≥ 99.99%) L-DSS. LF-L-LDH0845 has an approximate molecular weight of 33.65 kDa, exhibits wide substrate scope for 2-keto-carboxylic acids. Values of Km, Kcat, and Kcat/Km for LF-L-LDH0845 with 3,4-dihydroxy-phenylpyruvate substrate were 11.37 mM, 0.2931 s−1, and 0.0258 mM−1 s−1, respectively. LF-L-LDH0845 was most active and stable at pH 6.0, the optimum temperature was 25 °C, stability decreased with increasing temperature, and activity was lost completely at 50 °C. K+ stimulated while Fe2+ and Cu2+ inhibited the enzyme activity significantly. Glucose dehydrogenase gene was coexpressed with lf-l-ldh0845 in E. coli to regenerate cofactors by oxidising glucose, which efficiently reduced 3,4-dihydroxyphenylpyruvate to L-DSS with 95.45% isolation yield.
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- 2018
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49. Mimicking a New 2-Phenylethanol Production Pathway from Proteus mirabilis JN458 in Escherichia coli
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Ye Zhao, Tai-Ping Fan, Liu Jinbin, Yajun Bai, Xiaohui Zheng, Yujie Cai, and Jiang Jing
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0106 biological sciences ,0301 basic medicine ,Phenylalanine ,Gene Expression ,medicine.disease_cause ,01 natural sciences ,Cofactor ,03 medical and health sciences ,Bacterial Proteins ,Biotransformation ,Glucose dehydrogenase ,010608 biotechnology ,Escherichia coli ,medicine ,Proteus mirabilis ,Alcohol dehydrogenase ,chemistry.chemical_classification ,biology ,Chemistry ,Alcohol Dehydrogenase ,General Chemistry ,Phenylethyl Alcohol ,biology.organism_classification ,Recombinant Proteins ,030104 developmental biology ,Enzyme ,Biochemistry ,biology.protein ,General Agricultural and Biological Sciences ,Bacteria - Abstract
Bacteria rarely produce natural 2-phenylethanol. We verified a new pathway from Proteus mirabilis JN458 to produce 2-phenylethanol using Escherichia coli to coexpress l-amino acid deaminase, α-keto acid decarboxylase, and alcohol dehydrogenase from P. mirabilis. Based on this pathway, a glucose dehydrogenase coenzyme regeneration system was constructed. The optimal conditions of biotransformation by the recombinant strain E-pAEAKaG were at 40 °C and pH 7.0. Finally, the recombinant strain E-pAEAKaG produced 3.21 ± 0.10 g/L 2-phenylethanol in M9 medium containing 10 g/L l-phenylalanine after a 16 h transformation. Furthermore, when the concentration of l-phenylalanine was 4 g/L (24 mM), the production of 2-phenylethanol reached 2.88 ± 0.18 g/L and displayed a higher conversion rate of 97.38 mol %.
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- 2018
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50. Anticonvulsant activities of α-asaronol (( E )-3′-hydroxyasarone), an active constituent derived from α-asarone
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Tai-Ping Fan, Qiang Zhang, Ni Wu, Xiaohui Zheng, Zehua Li, Zefeng Zhao, Min Zeng, Yajun Bai, Fanggang Qin, Xirui He, Xiaoyang Wei, Meimei Zhao, Yajun Zhang, and Ning Xu
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Male ,0301 basic medicine ,medicine.medical_treatment ,Population ,Allylbenzene Derivatives ,Anisoles ,Motor Activity ,Pharmacology ,Lethal Dose 50 ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Epilepsy ,0302 clinical medicine ,Seizures ,Stiripentol ,Animals ,Medicine ,Asarone ,education ,3-Mercaptopropionic Acid ,Electroshock ,education.field_of_study ,Dose-Response Relationship, Drug ,business.industry ,Neurotoxicity ,Brain ,Dioxolanes ,General Medicine ,Carbamazepine ,medicine.disease ,Acute toxicity ,Disease Models, Animal ,030104 developmental biology ,Anticonvulsant ,chemistry ,Rotarod Performance Test ,Pentylenetetrazole ,Anticonvulsants ,Neurotoxicity Syndromes ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Epilepsy is one of chronic neurological disorders that affects 0.5–1.0% of the world’s population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. Methods α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety evaluation, acute neurotoxicity was assessed with minimal motor impairment screening determined in the rotarod test, and acute toxicity was also detected in mice. Results In our results, α-asaronol displayed a broad spectrum of anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in MES, PI = 8.68 in PTZ) and lower acute toxicity (LD50 = 2940 mg/kg) than its metabolic parent compound (α-asarone). Additionally, α-asaronol displayed a prominent anticonvulsant profile with ED50 values of 62.02 mg/kg in the MES and 79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED50 of 240 mg/kg and 115 mg/kg in the relevant test, respectively. Conclusion The results of the present study revealed α-asaronol can be developed as a novel molecular in the search for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity. Meanwhile, the results also suggested that α-asaronol has great potential to develop into another new aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet’s syndrome.
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- 2018
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