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>

Microporous Zn(II)-MOF for Selective C₂H₂ Adsorption and Anti-cancer Activity on Liver Cancer Combined with LL-37

Xiu-Qin Wei,Shuan-Yuan Yang,Xiao-Xia Li,Mei-Li Xu 한국고분자학회 2021 폴리머 Vol.45 No.6

By employment of a semi-rigid carboxylic acid ligand 5,5" -((5-carboxy-1,3-phenylene)bis(azanediyl))diiso- phthalic acid (H5L) with the -NH- joints, a new porous metal-organic framework (MOF) based on Zn(II) ions as nodes has been generated in success, and its chemical formula is {[Zn₃(μ₃-OH)(L)(H₂O₃)]·3DEF·H₂O}n (1). Owing to its Lewis basic -NH- joints and the π-electron-rich benzene rings on the skeleton, the activated complex 1 offers a favourable pore environment for binding C₂H₂ in preference to CO₂ and CH₄. The inhibitory activity of compound on the liver cancer viability was determined through exploiting the Cell Counting Kit-8 kit. Afterwards, the invasion and migration ability for the liver cancer cells was measured after indicated treatment. Multiple binding interactions are identified by performing the molecular docking simulation, indicating the stabilization effect of the Zn complex towards the target protein, and therefore, the proposed drug molecule exhibits good anticancer activities.

中国福州酒店宴会竞争力提升策略研究 - 基于宴会消费属性开发与IPA分析-

Xiu-bai Li(李秀白),JIan-en Qin(覃建恩),Jiong-lan Lu(卢,炯兰,) 융합관광콘텐츠학회 2018 융합관광콘텐츠학회지 Vol.4 No.2

The purpose of this study is to explore the hotel banquet satisfaction in Fuzhou City of China, and provides theoretical reference for hotel banquet quality management based on the research results. The results of the study shows that the banquet environment (temperature, hygiene, scale), banquet equipment (audio, stage, projection), menu (price, quality) can meet the expectations of consumers; menu design, decoration of banquet room and other aspects exceed the period of consumers. However, the banquet signs, service attitudes, service standards, service speed, humanized service, parking convenience and transportation convenience still lag behind the expectations of consumers and need to be improved.

Alu Tandem Sequences Inhibit GFP Gene Expression by Triggering Chromatin Wrapping

Xiu Fang Wang,Xiao Yan Wang,Jing Liu,Jing Jing Feng,Wen Li Mu,Xiao Juan Shi,Qin Qing Yang,Xiao Cui Duan,Ying Xie,Zhan Jun Lu 한국유전학회 2009 Genes & Genomics Vol.31 No.3

Alu elements belonging to the short interspersed nuclear elements (SINE) of repetitive elements are present in more than one million copies which altogether represent 10% of the whole human genome. In this study, the roles of Alu tandem sequences in the process of GFP gene (GFP) expression and packing into chromatin of its DNA were studied. To detect the effect of Alu repeats on gene expression, different copies of Alus were inserted GFP downstream respectively in pEGFP-C1 vector. We found that Alu sequences decreased the amount of GFP transcription, the percentage of GFP positive cells and the accessibility to DNase I in length-dependent manner. Inserting Alu caused the production of higher-molecular-mass RNA, indicating Alu sequence did not induce premature transcriptional termination. Tight packing chromatins keep silent and resist to DNase I digestion, which is a general phenomenon. We suggested that head and tail tandem Alu sequences suppressed GFP expression in length dependent manner by triggering chromatin packing.

Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling

Tao Jiang,Xiu-qin Wang,Chuan Ding,Xue-lian Du 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.

Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling

Tao Jiang,Xiu-qin Wang,Chuan Ding,Xue-lian Du 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.6

Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.

Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling

Jiang, Tao,Wang, Xiu-qin,Ding, Chuan,Du, Xue-lian The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.6

Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.

Diffusion-Weighted Imaging for the Left Hepatic Lobe has Higher Diagnostic Accuracy for Malignant Focal Liver Lesions

Han, Xue,Dong, Yin,Xiu, Jian-Jun,Zhang, Jie,Huang, Zhao-Qin,Cai, Shi-Feng,Yuan, Xian-Shun,Liu, Qing-Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: This study was conducted to investigate whether apparent diffusion coefficient (ADC) measurements by dividing the liver into left and right hepatic lobes may be utilized to improve the accuracy of differential diagnosis of benign and malignant focal liver lesions. Materials and Methods: A total of 269 consecutive patients with 429 focal liver lesions were examined by 3-T magnetic resonance imaging that included diffusion-weighted imaging. For 58 patients with focal liver lesions of the same etiology in left and right hepatic lobes, ADCs of normal liver parenchyma and focal liver lesions were calculated and compared using the paired t-test. For all 269 patients, ADC cutoffs for focal liver lesions and diagnostic accuracy in the left hepatic lobe, right hepatic lobe and whole liver were evaluated by receiver operating characteristic curve analysis. Results: For the group of 58 patients, mean ADCs of normal liver parenchyma and focal liver lesions in the left hepatic lobe were significantly higher than those in the right hepatic lobe. For differentiating malignant lesions from benign lesions in all patients, the sensitivity and specificity were 92.6% and 92.0% in the left hepatic lobe, 94.4% and 94.4% in the right hepatic lobe, and 90.4% and 94.7% in the whole liver, respectively. The area under the curve of the right hepatic lobe, but not the left hepatic lobe, was higher than that of the whole liver. Conclusions: ADCs of normal liver parenchyma and focal liver lesions in the left hepatic lobe were significantly higher than those in the right hepatic lobe. Optimal ADC cutoff for focal liver lesions in the right hepatic lobe, but not in the left hepatic lobe, had higher diagnostic accuracy compared with that in the whole liver.

Molecular Classification of Hepatocellular Carcinoma and Its Impact on Prognostic Prediction and Personized Therapy

Dhruba Kadel,Lun-Xiu Qin Korean Society of Gastrointestinal Cancer 2017 Journal of digestive cancer reports Vol.5 No.1

Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related death in the world. The aggressive but not always predictable pattern of HCC causes the limited treatment option and poorer outcome. Many researches had already proven the heterogeneity of HCC is one of the major challenges for treatment option and prognosis prediction. Molecular subtyping of HCC and selection of patient based on molecular profile can provide the optimization in the treatment and prognosis prediction. In this review, we have tried to summarize the molecular classification of HCC proposed by different valuable researches presented in the logistic way.

Salivary Pepsin as an Intrinsic Marker for Diagnosis of Sub-types of Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-related Disorders

( Yan-jun Wang ),( Xiu-qiong Lang ),( Dan Wu ),( Yu-qin He ),( Chun-hui Lan ),( Xiao-xiao ),( Bin Wang ),( Duo-wu Zou ),( Ji-min Wu ),( Yong-bin Zhao ),( Peter W Dettmar ),( Dong-feng Chen ),( Min Yan 대한소화기 기능성질환·운동학회 2020 Journal of Neurogastroenterology and Motility (JNM Vol.26 No.1

Background/Aims To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders. Methods Overall, 322 patients with different sub-types of GERD and 45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES). Results Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett’s esophagus had a higher prevalence of saliva and SPC (all P < 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both P < 0.001) and in EES (P = 0.001 and P = 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (P = 0.002). Conclusions Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.