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      • Inhibition of α-glucosidase by 2-thiobarbituric acid: Molecular dynamics simulation integrating parabolic noncompetitive inhibition kinetics

        Qin, Xiu-Yuan,Lee, Jinhyuk,Zheng, Li,Yang, Jun-Mo,Gong, Yan,Park, Yong-Doo Elsevier 2018 Process biochemistry Vol.65 No.-

        <P><B>Abstract</B></P> <P>The phenomenon of α-glucosidase inhibition has attracted the attention of researchers due to its association with type 2 diabetes treatment in humans. In this study, we found that 2-thiobarbituric acid (TBA) induces complex inhibition of α-glucosidase using kinetics tests and molecular dynamics (MD) simulations. Computational MD and docking simulations demonstrate that TBA interacts with three residues on active sites of α-glucosidase such as Met69, Arg212, and His348. These biochemical tests indicate that TBA reversibly inhibits α-glucosidase in a parabolic noncompetitive manner (<I>IC</I> <SUB>50</SUB> =17.13±1.14mM; <I>K</I> <SUB>i</SUB> =13.25±0.56mM) and that this inhibition is accompanied by a biphasic kinetic process. The tertiary conformational changes were not synchronized with TBA inhibition but we observed hydrophobic disruption after inactivation at higher concentrations of TBA. Our results provide insight into the functional roles of residues located at the active sites of α-glucosidase, and we suggest that compounds similar to TBA (heterocyclic compounds) targeting the key residues of active sites are potential α-glucosidase inhibitors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 2-Thiobarbituric acid (TBA) induces complex inhibition of α-glucosidase. </LI> <LI> Computational MD simulations demonstrate that TBA interacts with Met69, Arg212, and His348. </LI> <LI> TBA reversibly inhibits α-glucosidase in a parabolic noncompetitive manner (<I>IC</I> <SUB>50</SUB> =17.13±1.14mM; <I>K</I> <SUB>i</SUB> =13.25±0.56mM). </LI> <LI> The high dose of TBA induces hydrophobic disruption after inactivation. </LI> <LI> Heterocyclic compounds targeting the key residues of active sites are potential α-glucosidase inhibitors. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCOPUSKCI등재

        Urinary Biomarkers for the Noninvasive Detection of Gastric Cancer

        Li, Dehong,Yan, Li,Lin, Fugui,Yuan, Xiumei,Yang, Xingwen,Yang, Xiaoyan,Wei, Lianhua,Yang, Yang,Lu, Yan The Korean Gastric Cancer Association 2022 Journal of gastric cancer Vol.22 No.-

        Gastric cancer (GC) is associated with high morbidity and mortality rates. Thus, early diagnosis is important to improve disease prognosis. Endoscopic assessment represents the most reliable imaging method for GC diagnosis; however, it is semi-invasive and costly and heavily depends on the skills of the endoscopist, which limit its clinical applicability. Therefore, the search for new sensitive biomarkers for the early detection of GC using noninvasive sampling collection methods has attracted much attention among scientists. Urine is considered an ideal biofluid, as it is readily accessible, less complex, and relatively stable than plasma and serum. Over the years, substantial progress has been made in screening for potential urinary biomarkers for GC. This review explores the possible applications and limitations of urinary biomarkers in GC detection and diagnosis.

      • KCI등재

        Transcriptome Analysis Reveals Molecular Mechanisms Underlying Methyl Jasmonate-mediated Biosynthesis of Protopanaxadiol-type Saponins in Panax notoginseng Leaves

        Li Ying,Lin Yuan,Jia Bing,Chen Geng,Shi Huineng,Xu Rui,Li Xuejiao,Tang Junrong,Tang Qingyan,Zhang Guanghui,Yang Jianli,Fan Wei,Yang Shengchao 한국식물학회 2022 Journal of Plant Biology Vol.65 No.1

        Methyl jasmonate (MeJA) has been widely used to improve the biosynthesis of secondary metabolites such as triterpenoid saponins in medicinal plants. However, the underlying molecular mechanisms remain poorly understood. Differing from roots that accumulate protopanaxatriol-type saponins, Panax notoginseng leaves with a lower biomass mainly contain protopanaxadiol (PPD)-type saponins. Therefore, it is interesting to explore whether MeJA can activate the biosynthesis of PPD-type saponins in P. notoginseng leaves. In this study, we found MeJA could effectively induce the accumulation of PPD-type saponins, including ginsenoside Rb1, Rc, Rb2, Rb3 and notoginsenoside Fa, Fe in P. notoginseng leaves based on a newly established high-performance liquid chromatography method. Transcriptome analysis showed that differentially expressed genes (DEGs) induced by MeJA were mainly enriched in “terpenoid backbone biosynthesis”, “biosynthesis of unsaturated fatty acids”, “sesquiterpenoid and triterpenoid biosynthesis”, “fatty acid metabolism”, and “phenylpropanoid biosynthesis”. Furthermore, the expression profile and quantitative real-time PCR analysis of DEGs showed that MeJA could positively induce the molecular response of endogenous jasmonic acid (JA) signaling pathway, and increased PPD-type saponins mediated by MeJA in P. notoginseng leaves may be related to the high expression of FPS, SS, SE, DS and UGTs, and the low expression of CYP716A53v2 and β-AS. The results provide a molecular understanding for MeJA-elicited biosynthesis of triterpenoid saponins and facilitate the further characterization of the genes responsible for biosynthesis of PPD-type saponins in P. notoginseng leaves.

      • SCIESCOPUSKCI등재

        An Interleaved Converter for 12-pulse Rectifier Harmonic Suppression

        Li, Yuan,Yang, Wei,Cang, Sheng,Yang, Shiyan The Korean Institute of Power Electronics 2017 JOURNAL OF POWER ELECTRONICS Vol.17 No.5

        In order to further improve the harmonic suppression capability of conventional 12-pulse rectifiers, this paper proposes a low harmonic 12-pulse rectifier using an Active Inter-Phase Reactor (AIPR). Through a detailed analysis of the relationship between the input current, output current and circulating current of the DC side, the mechanism where the AC grid side current harmonics can be suppressed by the DC side circulating current is revealed. On this basis, an interleaved APFC controlled by a DSP is designed and used as an AIPR along with an interphase reactor. A simulation is carried out with MATLAB/Simulink and an experiment is performed on a 9-kVA prototype. The obtained results verify the feasibility and validity of the proposed approach. Compared with a traditional 12-pulse rectifier, the THD can be reduced to 1/5 of the original value, and the capacity of the AIPR is only 2% of the load power. Thus, it is suitable for high-power applications.

      • SCIESCOPUSKCI등재

        Effect of Glutamate on the Vestibulo-Solitary Projection after Sodium Nitroprusside-Induced Hypotension in Conscious Rats

        Li, Li-Wei,Ji, Guang-Shi,Yang, Yan-Zhao,Ameer, Abdul Nasir,Kim, Min Sun,Park, Byung Rim,Jin, Yuan-Zhe The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.3

        Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.

      • KCI등재

        An Interleaved Converter for 12-pulse Rectifier Harmonic Suppression

        Yuan Li,Wei Yang,Sheng Cang,Shiyan Yang 전력전자학회 2017 JOURNAL OF POWER ELECTRONICS Vol.17 No.5

        In order to further improve the harmonic suppression capability of conventional 12-pulse rectifiers, this paper proposes a low harmonic 12-pulse rectifier using an Active Inter-Phase Reactor (AIPR). Through a detailed analysis of the relationship between the input current, output current and circulating current of the DC side, the mechanism where the AC grid side current harmonics can be suppressed by the DC side circulating current is revealed. On this basis, an interleaved APFC controlled by a DSP is designed and used as an AIPR along with an interphase reactor. A simulation is carried out with MATLAB/Simulink and an experiment is performed on a 9-kVA prototype. The obtained results verify the feasibility and validity of the proposed approach. Compared with a traditional 12-pulse rectifier, the THD can be reduced to 1/5 of the original value, and the capacity of the AIPR is only 2% of the load power. Thus, it is suitable for high-power applications.

      • Liposome-mediated Induction of Apoptosis of Human Hepatoma Cells by C-Myc Antisense Phosphorothioate Oligodeoxynucleotide and 5-Fluorouracil

        Yuan, Yuan,Cai, Hui,Yang, Xiao-Jun,Li, Wei,He, Jin,Guo, Tian-Kang,Chen, Yi-Rong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

        Background: The aim of this study was to investigate the effect of a c-myc antisense oligodeoxynucleotide and 5-fluorouracil on the expression of c-myc, invasion and proliferation of HEPG-2 liver cancer cells. Materials and Methods: HEPG-2 cells were treated with lipiosome-mediated c-myc ADSON and 5-fluorouracil. The proliferation inhibition rate and invasion were measured by MTT and invasion assay, respectively. Cell apoptosis was detected by flow cytometry and expression of c-myc by RT-PCR and immunohistochemistry. Results: The proliferation inhibition rate was significantly higher in the antisense oligodeoxynucleotide added-5-fluorouracil group than single antisense oligodeoxynucleotide or 5-fluorouracil group (p<0.05). G0/G1 cells in the antisense oligodeoxynucleotide group and S cells in the 5-fluorouracil groups were significantly increased than that in the control group, respectively (P<0.01). The amplification strips of PCR products in 5-FU, ASODN and combination groups were significantly weaker than that in the control group (P<0.01). The percentage of c-myc-protein-positive cells were significantly lower in antisense oligodeoxynucleotide, 5-fluorouracil and combination groups than that in the control group (P<0.01). Conclusions: A liposome-mediated c-myc antisense oligodeoxynucleotide and 5-fluorouracil can inhibit the proliferation and invasion of liver cancer cells by reducing the expression of c-myc. A c-myc antisense oligodeoxynucleotide can increase the sensitivity of liver cancer cells to 5-fluorouracil and decrease the dosage of the agent necessary for efficacy, providing an experimental basis for the clinical therapy of liver cancer.

      • KCI등재

        Effect of Glutamate on the Vestibulo-Solitary Projection after Sodium Nitroprusside-Induced Hypotension in Conscious Rats

        Li-Wei Li,Guang-Shi Jin,Yan-Zhao Yang,Abdul Nasir Ameer,김민선,박병림,Yuan-Zhe Jin 대한약리학회 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.3

        Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.

      • KCI등재

        Urinary Biomarkers for the Noninvasive Detection of Gastric Cancer

        Li Dehong,Yan Li,Lin Fugui,Yuan Xiumei,Yang Xingwen,Yang Xiaoyan,Wei Lianhua,Yang Yang,Lu Yan 대한위암학회 2022 Journal of gastric cancer Vol.22 No.4

        Gastric cancer (GC) is associated with high morbidity and mortality rates. Thus, early diagnosis is important to improve disease prognosis. Endoscopic assessment represents the most reliable imaging method for GC diagnosis; however, it is semi-invasive and costly and heavily depends on the skills of the endoscopist, which limit its clinical applicability. Therefore, the search for new sensitive biomarkers for the early detection of GC using noninvasive sampling collection methods has attracted much attention among scientists. Urine is considered an ideal biofluid, as it is readily accessible, less complex, and relatively stable than plasma and serum. Over the years, substantial progress has been made in screening for potential urinary biomarkers for GC. This review explores the possible applications and limitations of urinary biomarkers in GC detection and diagnosis.

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