References (6)

Title : Gene signatures of SARS-CoV\/SARS-CoV-2-infected ferret lungs in short- and long-term models - Liu_2020_Infect.Genet.Evol_85_104438
Author(s) : Liu HL , Yeh IJ , Phan NN , Wu YH , Yen MC , Hung JH , Chiao CC , Chen CF , Sun Z , Jiang JZ , Hsu HP , Wang CY , Lai MD
Ref : Infect Genet Evol , 85 :104438 , 2020
Abstract : Coronaviruses (CoVs) consist of six strains, and the severe acute respiratory syndrome coronavirus (SARS-CoV), newly found coronavirus (SARS-CoV-2) has rapidly spread leading to a global outbreak. The ferret (Mustela putorius furo) serves as a useful animal model for studying SARS-CoV/SARS-CoV-2 infection and developing therapeutic strategies. A holistic approach for distinguishing differences in gene signatures during disease progression is lacking. The present study discovered gene expression profiles of short-term (3 days) and long-term (14 days) ferret models after SARS-CoV/SARS-CoV-2 infection using a bioinformatics approach. Through Gene Ontology (GO) and MetaCore analyses, we found that the development of stemness signaling was related to short-term SARS-CoV/SARS-CoV-2 infection. In contrast, pathways involving extracellular matrix and immune responses were associated with long-term SARS-CoV/SARS-CoV-2 infection. Some highly expressed genes in both short- and long-term models played a crucial role in the progression of SARS-CoV/SARS-CoV-2 infection, including DPP4, BMP2, NFIA, AXIN2, DAAM1, ZNF608, ME1, MGLL, LGR4, ABHD6, and ACADM. Meanwhile, we revealed that metabolic, glucocorticoid, and reactive oxygen species-associated networks were enriched in both short- and long-term infection models. The present study showed alterations in gene expressions from short-term to long-term SARS-CoV/SARS-CoV-2 infection. The current result provides an explanation of the pathophysiology for post-infectious sequelae and potential targets for treatment.
ESTHER : Liu_2020_Infect.Genet.Evol_85_104438
PubMedSearch : Liu_2020_Infect.Genet.Evol_85_104438
PubMedID: 32615317

Title : Design, synthesis and evaluation of diosgenin carbamate derivatives as multitarget anti-Alzheimer's disease agents - Yang_2020_Eur.J.Med.Chem_187_111913
Author(s) : Yang GX , Huang Y , Zheng LL , Zhang L , Su L , Wu YH , Li J , Zhou LC , Huang J , Tang Y , Wang R , Ma L
Ref : Eur Journal of Medicinal Chemistry , 187 :111913 , 2020
Abstract : In order to produce an effective and multi-targeted clinical drug that could prevent progressive neurodegeneration, a series of diosgenin carbamate derivatives were designed, synthesized and tested for their anti-inflammatory, antioxidant and anti-Abeta activities. The results demonstrated that compound M15 was the most promising derivative against inflammatory (NO inhibition 22.7 +/- 2.2%,10 muM) and cellular damage induced by H2O2 (SH-SY5Y cell protection = 75.3 +/- 3.4%, 10 muM) or Abeta (astrocytes protection = 70.2 +/- 6.5%, 10 muM). Molecular docking studies revealed the strong binding affinity of M15 to the active site of nNOS, Abeta42 and pro-inflammatory proteins. Western blot demonstrated that M15 decreased IL-1beta, IL-6 and TNF-alpha level, which may contribute to its anti-inflammatory effects. In addition, M15 maintained mitochondrial function as well as cell viability through reducing H2O2-induced ROS production. The results indicated that oral administration of M15 attenuated memory deficits and played a neuroprotective effect on subcutaneous (s.c.) D-gal aging mice. In summary, M15 could be considered as a potential multifunctional neuroprotective agent due to the effects of anti-inflammatory, antioxidant and anti-Abeta activities.
ESTHER : Yang_2020_Eur.J.Med.Chem_187_111913
PubMedSearch : Yang_2020_Eur.J.Med.Chem_187_111913
PubMedID: 31837501

Title : Characterization of a novel alkaline esterase from Altererythrobacter epoxidivorans CGMCC 1.7731(T) - Rong_2018_Prep.Biochem.Biotechnol_48_113
Author(s) : Rong Z , Huo YY , Jian SL , Wu YH , Xu XW
Ref : Preparative Biochemistry & Biotechnology , 48 :113 , 2018
Abstract : A novel esterase gene (e25) was identified from Altererythrobacter epoxidivorans CGMCC 1.7731(T) by genome sequence screening. The e25 gene is 948 nucleotides in length and encodes a 315 amino acid protein (E25) with a predicted molecular mass of 33,683 Da. A phylogenetic tree revealed that E25 belongs to the hormone-sensitive lipase (HSL) family of lipolytic enzymes. An activity assay of E25 showed that it exhibited the highest catalytic efficiency when using p-nitrophenyl caproate (C6) as a substrate. The optimum pH and temperature were determined to be approximately pH 9 and 45 degrees C, and the Km and Vmax values were 0.12 mM and 1,772 micromol/min/mg, respectively. After an incubation at 40 degrees C for 80 min, E25 retained 75% of its basal activity. The enzyme exhibited good tolerance to metal cations, such as Ba(2+), Ca(2+), and Cu(2+) (10 mM), but its activity was strongly inhibited by Co(2+), Ni(2+), Mn(2+), and Zn(2+). The E25 enzyme was stimulated by glycerol and retained over 60% of its basal activity in the presence of 1% Tween-80 and Triton X-100. Overall, the activity of E25 under alkaline conditions and its organic solvent and detergent tolerance indicate that E25 could be useful as a novel industrial catalyst in biotechnological applications.
ESTHER : Rong_2018_Prep.Biochem.Biotechnol_48_113
PubMedSearch : Rong_2018_Prep.Biochem.Biotechnol_48_113
PubMedID: 29099313
Gene_locus related to this paper: 9sphn-a0a0m3ta89

Title : Higher levels of thyroxine may predict a favorable response to donepezil treatment in patients with Alzheimer disease: a prospective, case-control study - Chang_2018_BMC.Neurosci_19_36
Author(s) : Chang YS , Wu YH , Wang CJ , Tang SH , Chen HL
Ref : BMC Neurosci , 19 :36 , 2018
Abstract : BACKGROUND: Cholinergic hypothesis has been advanced as an etiology of Alzheimer disease (AD) on the basis of the presynaptic deficit found in the diseased brains, and cholinesterase inhibitors (ChEIs) are the treatment of choice for these patients. However, only about half of treatment efficacy was found. Because increasing evidence supports an extensive interrelationship between thyroid hormones (THs), cortisol level and the cholinergic system, the aim of the present study was to evaluate thyroid function and cortisol level in patients with mild to moderate AD before and after ChEIs treatment, and to identify possible variations in response. This was a prospective, case-control, follow-up study. Levels of cortisol and THs were evaluated in 21 outpatients with mild to moderate AD and 20 normal controls. All patients were treated with 5 mg/day of donepezil (DPZ) and were reevaluated after 24-26 weeks of treatment. RESULTS: The patients had worse cognitive function, higher cortisol level, and lower levels of triiodothyronine (T3) and its free fraction than the controls. There were no significant differences in global cognitive function or cortisol level after treatment, however, significant reductions in T3 and thyroxin (T4) levels were observed. Responders had higher levels of T4 than non-responders, followed by a significant reduction after treatment. CONCLUSIONS: These results suggest that relatively higher levels of T4 may predict a favorable response to DPZ treatment. Further studies are warranted to confirm the relationship between THs and ChEIs therapy in AD and to explore new therapeutic strategies. On the other hand, cortisol levels are more likely to respond to interventions for stress-related neuropsychiatric symptoms in patients with AD rather than ChEIs treatment. Further studies are warranted to investigate the association between cortisol level and the severity of stress-related neuropsychiatric symptoms in patients with AD.
ESTHER : Chang_2018_BMC.Neurosci_19_36
PubMedSearch : Chang_2018_BMC.Neurosci_19_36
PubMedID: 29929471

Title : Effect of Tributyltin, Cadmium, and Their Combination on Physiological Responses in Juvenile Grass Carp - Mu_2016_J.Aquat.Anim.Health_28_181
Author(s) : Mu WN , Li ZH , Zhong LQ , Wu YH
Ref : J Aquat Anim Health , 28 :181 , 2016
Abstract : Tributyltin (TBT) and cadmium (Cd) are two common pollutants in aquatic environments. This study was designed to examine the physiological responses of juvenile Grass Carp Ctenopharyngodon idella to TBT, Cd, and their combination. Fish were apportioned into a control group, a TBT group (7.5 mug/L), a Cd group (2.97 mg/L), and a TBT-Cd group (7.5 mug/L TBT, 2.97 mg/L Cd(2+)) for 7 d. The following activities were measured: Na(+),K(+)-ATPase in gill tissues; nitric oxide synthase (NOS), acetylcholinesterase (AChE), and monoamine oxidase (MAO) in brain tissues; and lipid peroxidation (LPO), malondialdehyde (MDA), total antioxidative capacity (T-AOC), and glutathione (GSH) in liver tissues. Cadmium-induced stress was suggested by alterations in antioxidant responses (MDA, LPO, and T-AOC) and neurological parameters (AChE, MAO, and NOS). Cadmium also induced Na(+),K(+)-ATPase and GSH activity. Compared with the responses among the Cd group, the combination of TBT and Cd not only decreased the level of GSH and Na(+),K(+)-ATPase but also increased the levels of MDA, LPO, AChE, MAO, and NOS. These results suggest that a combination of TBT and Cd could reduce the adverse effects of Cd on Grass Carp. However, the exact mechanisms for the combined effects TBT and Cd on these biomarkers require further investigation. Received September 28, 2015; accepted April 17, 2016.
ESTHER : Mu_2016_J.Aquat.Anim.Health_28_181
PubMedSearch : Mu_2016_J.Aquat.Anim.Health_28_181
PubMedID: 27484920

Title : Quantitative structure-activity relationships for the pre-steady state acetylcholinesterase inhibition by carbamates - Lin_2004_J.Biochem.Mol.Toxicol_18_353
Author(s) : Lin G , Liao WC , Chan CH , Wu YH , Tsai HJ , Hsieh CW
Ref : J Biochem Mol Toxicol , 18 :353 , 2004
Abstract : 4-Nitrophenyl-N-substituted carbamates (1) are characterized as pseudosubstrate inhibitors of acetylcholinesterase. The first step is formation of the enzyme-inhibitor tetrahedral intermediate with the inhibition constant (Ki), the second step is formation of the carbamyl enzyme with the carbamylation constant (kc), and the third step is hydrolysis of the carbamyl enzyme with decarbamylation constant (kd). According to pre-steady state kinetics the Ki step is divided further into two steps: (1) formation of the enzyme-inhibitor complex with the dissociation constant (KS) and (2) formation of the enzyme-inhibitor tetrahedral intermediate from the complex with the equilibrium constant (k2/k-2). Since the inhibitors are protonated in pH 7.0 buffer solution, the virtual dissociation constant (KS') of the enzyme-protonated inhibitor complex can be calculated from the equation, -log KS'=-log KS-pKa + 14. The -logKS, -log KS', log k2, and log k-2 values are multiply linearly correlated with the Jave equation (log(k/k0)=rho*sigma* + deltaEs + psi pi). For -log KS'-sigma*-Es)pi-correlation, the rho* value of -0.4 indicates that the enzyme-protonated inhibitor complexes have more positive charges than the protonated inhibitors, the delta value of 0.44 suggests that the bulkily substituted inhibitors lessen the reaction due to the difficulty of the inhibitors to enter the narrow enzyme active site gorge, and the psi value of 0.27 implies that the inhibitors with hydrophobic substituents accelerate the inhibitors entering the active site gorge of the enzyme. For log k2/k-2,-sigma*-Es-pi-correlation, the rho* value of 1.1 indicates that the enzyme-protonated inhibitor tetrahedral intermediates have more negative charges than the enzyme-protonated inhibitor complexes, the delta value of 0.15 suggests that the bulkily substituted inhibitors are difficult to bind into a small acyl binding site of the enzyme, and the psi value of -0.3 implies that the inhibitors with hydrophobic substituents resist binding to the hydrophilic acyl binding site of the enzyme.
ESTHER : Lin_2004_J.Biochem.Mol.Toxicol_18_353
PubMedSearch : Lin_2004_J.Biochem.Mol.Toxicol_18_353
PubMedID: 15674842