Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: Structural formula of AVCRI104P4.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: X-ray diffraction patterns of ( A ) dimyristoylphosphatidylcholine (DMPC) and ( B ) dimyristoylphosphatidylethanolamine (DMPE) in water and incubated with aqueous solutions of AVCRI104P4; (SA) small-angle and (WA) wide-angle reflections.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Incubation

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: Decrease in the area under the curve (%) in the (SA) small-angle and (WA) wide-angle reflections of DMPC and DMPE by the effect of AVCRIP104P4. Percentages obtained from the analysis of microdensitograms from X-ray diffraction patterns of DMPC and DMPE in water and incubated with AVCRI104P4 solutions.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: X-ray Diffraction, Incubation, Concentration Assay

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: X-ray diffraction patterns of ( A ) dimyristoylphosphatidylcholine (DMPC) and ( B ) dimyristoylphosphatidylethanolamine (DMPE) in water and incubated with Aβ(1-42); ( C ) DMPC in water, and incubated with AVCRI104P4 and Aβ(1-42); (SA) small-angle and (WA) wide-angle reflections.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Incubation

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: Decrease in the area under the curve (%) in the (SA) small-angle and (WA) wide-angle reflections of DMPC and DMPE by the effect of 20 µM Aβ(1-42) and AVCRI104P4 solutions. Percentages obtained from the analysis of microdensitograms from X-ray diffraction patterns of DMPC and DMPE in water and incubated with 20 µM Aβ(1-42) and AVCRI104P4 solutions.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: X-ray Diffraction, Incubation, Concentration Assay

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: ( A ) Representative DSC curves obtained for multilamellar DMPC liposomes containing different AVCRI104P4 concentrations. Scans were recorded at a heating rate of 1 °C min −1 ; ( B ) a plot of phase transition temperature of DMPC multilamellar liposomes determined for cooling and heating scans as a function of AVCRI104P4 concentration.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Liposomes, Sublimation, Concentration Assay

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: Thermodynamic parameters of pre-transition and main phase transition of pure, fully hydrated, multilamellar liposomes and mixtures of DMPC/AVCRI104P4 obtained from heating and cooling; scans collected at a rate of 1 °C min −1 for both processes. The accuracy of the main phase transition temperature and enthalpy was ±0.01 °C and ±0.8 kJ/mol, respectively.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Sublimation, Liposomes, Concentration Assay

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: ( A ) Representative DSC curves obtained for multilamellar DMPE liposomes containing different AVCRI104P4 concentrations. Scans were recorded at a heating rate of 1 °C min −1 ; ( B ) a plot of phase transition temperature of DMPE multilamellar liposomes determined for cooling and heating scans as a function of AVCRI104P4 concentration.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Liposomes, Sublimation, Concentration Assay

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: Thermodynamic parameters of pre-transition and main phase transition of pure, fully hydrated, multilamellar liposomes and mixtures of DMPE/AVCRI104P4 obtained from heating and cooling scans collected at a rate of 1 °C min −1 for both processes. The accuracy of the main phase transition temperature and enthalpy was ±0.01 °C and ±0.8 kJ/mol, respectively.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Sublimation, Liposomes, Concentration Assay

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: AVCRI104P4 effects on the morphology of human erythrocytes. Images obtained by scanning electron microscopy (SEM) of ( A ) Control, ( B ) 10 μM, ( C ) 30 μM, and ( D ) 50 μM AVCRI104P4. Arrows in B,D highlight an echinocyte and a stomatocyte, respectively.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Electron Microscopy, Control

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: AVCRI104P4 protective effect on human erythrocytes. SEM images of ( A ) untreated erythrocytes; incubated with ( B ) 20 μM Aβ(1-42); ( C ) 10 μM AVCRI104P4 and 20 μM Aβ(1-42); ( D ) 20 μM AVCRI104P4 and 20 μM Aβ(1-42).

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Incubation

Journal: International Journal of Molecular Sciences

Article Title: Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

doi: 10.3390/ijms22179563

Figure Lengend Snippet: Representative schematic of the possible routes of action of AVCRI104P4. ( A ) AVCRI104P4 is able to interact with both monolayers of the cell membrane, so it can probably have a protective role at this position against the toxic effect of peptide Aβ (1-42) (represented by pathway ( B ). Pathway ( C ) illustrates the binding capacity of AVCRI104P4 to the enzyme AChE, which has a demonstrated Aβ (1-42)-aggregatory capacity. Finally, pathway ( D ) outlines the binding of AVCRI104P4 to Aβ (1-42), which would prevent its binding to the lipid membrane.

Article Snippet: In order to elucidate the molecular mechanisms of the interaction of the multitarget hybrid compound AVCRI104P4 and cell membranes and to determine the possible protective effect of the hybrid against the toxic effect of Aβ(1-42) peptide, human erythrocytes and molecular models of its membrane were used.

Techniques: Membrane, Binding Assay

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Effects of AVCRI104P3 on pAKt (Ser473) and Akt in the hippocampus and cortex of 12-month-old 129/Sv × C57BL/6 male mice. ( A ) Representative Western blot images of pAKt (Ser473) and Akt β-actin were used as internal control. ( B ) Photodensitometric quantification of WB experiments was used to evaluate changes in pAkt (Ser473) and Akt expression. The results are the mean ± SEM of 3–4 experiments (5 mice/treatment group). The statistical analysis used was one-way ANOVA followed by Dunnett’s test ** p < 0.01 vs. CNT.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques: Western Blot, Control, Expressing

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Effect of AVCRI104P3 on Bcl2 in the hippocampus and cortex of 12-month-old 129/Sv × C57BL/6 male mice. ( A ) Representative Western blot images of Bcl2. β-actin was used as internal control. ( B ) Representation of the photodensitometric analysis of the Bcl2 levels. The results are the mean ± SEM of 3–4 experiments (5 mice/treatment group). The statistical analysis used was one-way ANOVA followed by Dunnett’s test, ** p < 0.01 vs. CNT, *** p < 0.001 vs. CNT.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques: Western Blot, Control

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Effect of AVCRI104P3 on pGSK3β (Ser9) and GSK3β in the hippocampus and cortex of 12-month-old 129/Sv × C57BL/6 male mice. ( A ) Representative Western blot images of pGSK3β (Ser9) and GSK3β. β-actin were used as internal control. ( B ) Photodensitometric quantification of WB experiments was used to evaluate changes in pGSK3β and GSK3β expression. The results are the mean ± SEM of 3–4 experiments (5 mice/treatment group). The statistical analysis used was one-way ANOVA followed by Dunnett’s test, * p < 0.05 vs. CNT.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques: Western Blot, Control, Expressing

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Effect of AVCRI104P3 on p25/p35 ratio in the hippocampus and cortex of 12-month-old 129/Sv × C57BL/6 male mice. ( A ) Representative Western blot images of p25/p35 ratio. β-actin were used as internal control. ( B ) Photodensitometric quantification of WB experiments was used to evaluate changes in the p25/p35 ratio. The results are the mean ± SEM of 3–4 experiments (5 mice/treatment group). The statistical analysis used was one-way ANOVA followed by Dunnett’s test.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques: Western Blot, Control

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Effect of AVCRI104P3 on synaptophysin in the hippocampus and cortex of 12-month-old 129/Sv × C57BL/6 male mice. ( A ) Representative Western blot images of synaptophysin. β-actin were used as internal control. ( B ) Photodensitometric quantification of WB experiments was used to evaluate changes in synaptophysin expression. The results are the mean ± SEM of 3–4 experiments (5 mice/treatment group). The statistical analysis used was one-way ANOVA followed by Dunnett’s test, * p < 0.05, ** p < 0.01 vs. CNT.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques: Western Blot, Control, Expressing

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Effect of AVCRI104P3 on GFAP, Iba1 and DCX in the hippocampus (dentate gyrus, DG) of 12-month-old 129/Sv × C57BL/6 male mice. ( A ) Representative images of immunohistochemical studies for GFAP, Iba1 and DXC. Scale bar: 50 µm. ( B ) Semi-quantitative analysis of optical density using the free Image J 1.49 programme. Each point is the mean ± S.E.M. (% of arbitrary fluorescent units) of 3–4 animals and each experiment ( n = 3) was carried out at least in triplicate. The statistical analysis used was the Student t test for each antibody; ** p < 0.01 vs. CNT.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques: Immunohistochemical staining

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Effects of AVCRI104P3 on mRNA AChE-S and AChE-R expression in the pre-frontal cortex. (left) mRNA control levels (mRNA-S expression was considered 100%), (right) mRNA-S and mRNA-R expression in the pre-frontal cortex after AVCRI104P3 treatment. The mRNA expression levels were normalised to those of β-actin and considered to be 100% for control mice. Each point is the mean ± S.E.M. of 3–5 animals, and each experiment was carried out in triplicate. The statistical analysis used was one-way ANOVA followed by Dunnett’s test.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques: Expressing, Control

Journal: International Journal of Molecular Sciences

Article Title: Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

doi: 10.3390/ijms19092615

Figure Lengend Snippet: Chemical structure of AVCRI104P3.

Article Snippet: Differences among the pharmacological profiles of the multitarget hybrid compound AVCRI104P3 and the parent compounds huprine and donepezil or among the animal models used in the different studies might account for these conflicting results.

Techniques:

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Chemical structure of PQM130.

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques:

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Experimental protocol and treatment schedule. The mice received i.p. injections of DON (1 mg/kg) or PQM130 (0.5 or 1.0 mg/kg) or VH solution for 10 days. The animals were sacrificed 20 days after Aβ 1-42 oligomer injection.

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Injection

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on the performance in the training (A) and probe trials (B–D) of the MWM test in the Aβ 1-42 O-injected mice. The training trials were carried out for 5 days (four per day); the probe trial was performed on day 6. The escape latency (B) , the frequency in the platform zone (C) , and the time spent in the opposite quadrant to the platform zone (D) were recorded in the probe test. The values are expressed as mean ± SEM ( n = 10) ( A : * p < 0.05 vs. Aβ/VH group; D : * p < 0.05 and ** p < 0.01 vs. Aβ/VH; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Injection

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on the performance in the Y-maze test in the Aβ 1-42 O-injected mice. The spontaneous alternation percentage was recorded in a 5 min trial. The values are expressed as mean ± SEM ( n = 10) ( # p < 0.05 vs. Sham/VH, * p < 0.05 and *** p < 0.001 vs. Aβ/VH; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Injection

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on neuronal cell death in the Aβ 1-42 O-injected mice. Representative H&E staining of coronal sections containing the hippocampus. Magnification, 20× and 40×; scale bar, 100 µm (A) . Quantitative analysis of H&E staining (B) . The values are expressed as mean of % of increment ± SEM ( n = 10) of the density of each experimental group compared to the Sham/VH group ( B : ** p < 0.01 vs. Aβ/VH; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Injection, Staining

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on tp53 mRNA relative expression (A) and caspase-9 (B) and caspase-3 (C) activations in the Aβ 1-42 O-injected mice. The tp53 mRNA relative expression was determined in hippocampal samples through the 2 −ΔΔCt method and represented as percentage vs. the Sham/VH group. ACTB was used as control housekeeping gene. Caspase-9 and -3 activations were determined using a specific chromogenic substrate in the hippocampal samples. The values are expressed as mean ± SEM ( n = 10) of optical density (OD) of each experimental group ( A : * p < 0.05 vs. Aβ/VH, §§ p < 0.01 vs. Aβ/DON; B : # p < 0.05 vs. Sham/VH, * p < 0.05 vs. Aβ/VH; C : # p < 0.05 vs. Sham/VH, * p < 0.05 and ** p < 0.01 vs. Aβ/VH; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Expressing, Injection, Control

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on cellular redox status in the Aβ 1-42 O-injected mice. Redox status was evaluated in the hippocampal samples based on DCF’s fluorescence emission at 535 nm after excitation at 485 nm. The values are expressed as mean ± SEM ( n = 10) of fluorescence intensity arbitrary units (UF) of each experimental group (A) . GSH content was measured using a colorimetric assay in the hippocampal samples. The values are calculated using a standard calibration curve and expressed as mean ± SEM ( n = 10) of mmol GSH/mg protein (B) . GR and Nrf2 mRNA relative expressions (C and D) were determined through the 2 −ΔΔCt method and presented as percentage vs. the Sham/VH group. ACTB was used as control housekeeping gene. ( A : ### p < 0.001 vs. Sham/VH, ** p < 0.01 and *** p < 0.001 vs. Aβ/VH; B : ** p < 0.01 vs. Aβ/VH group; C : * p < 0.05 and ** p < 0.01 vs. Aβ/VH group; D : ### p < 0.001 vs. Sham/VH group, *** p < 0.001 vs. Aβ/VH group, §§ p < 0.01 vs. Aβ/DON group; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Injection, Fluorescence, Colorimetric Assay, Control

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on GSK3 (A) and ERK1/2 (B) phosphorylations (pGSK3β Ser21/9 residue and pERK1/2) in the Aβ 1-42 O-injected mice. pGSK3β and pERK1/2 were determined by Western blotting in the hippocampal samples at 46 and 42/44 kDa, respectively, and using total GSK3, total ERK1/2, and β-actin (42 kDa) as loading control. Top: representative images of pGSK3β, GSK3, and β-actin (A) and pERK1/2, ERK1/2, and β-actin (B) expressions in hippocampus. Bottom: quantitative analysis of the Western blotting results for the pGSK3β (A) and pERK1/2 (B) levels. The graphs show densitometry analysis of the bands appertaining to the protein of interest. The values are expressed as mean ± SEM ( n = 10) of each group. ( A : * p < 0.05 vs. Aβ/VH group; B : ### p < 0.001 vs. Sham/VH, * p < 0.05 vs. Aβ/VH group; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Residue, Injection, Western Blot, Control

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on astrocyte activation in the Aβ 1-42 O-injected mice. Representative photomicrographs (A) of immunostaining for GFAP in brain coronal sections containing hippocampal structure of each experimental group. Magnification, 10× and 40×; scale bar, 100 µm. Quantitative analysis of GFAP immunostaining (B) . The values are expressed as mean of % of increment ± SEM ( n = 10) of the fluorescent intensity of each experimental group compared to the Sham/VH group ( B : ## p < 0.01 vs. Sham/VH, ** p < 0.01 vs. Aβ/VH; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Activation Assay, Injection, Immunostaining

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on the total BDNF (A) , long 3′UTR BDNF (B) , BDNF exon IV (C) , and BDNF exon VI (D) mRNA relative expressions in the Aβ 1-42 O-injected mice. The mRNA relative expressions were determined in the hippocampal samples through the 2 −ΔΔCt method and represented as percentage vs. the Sham/VH group. ACTB was used as control housekeeping gene. ( B : § p < 0.05 vs. Aβ/DON; C : * p < 0.05 vs. Aβ/VH; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Injection, Control

Journal: Frontiers in Pharmacology

Article Title: PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease

doi: 10.3389/fphar.2019.00658

Figure Lengend Snippet: Effects of donepezil and PQM130 treatments (0.5 or 1.0 mg/kg) on sinaptophysin levels in the Aβ 1-42 O-injected mice. Synaptophysin mRNA relative expressions in the hippocampal samples (A) . The mRNA relative expressions were determined through the 2 −ΔΔCt method and represented as percentage vs. the Sham/VH group. ACTB was used as control housekeeping gene. Synaptophysin activation was determined by Western Blotting in hippocampal samples at 33 kDa using β-actin (42 kDa) as loading control (B) . Top: representative images of synaptophysin and β-actin expressions in hippocampus. Bottom: quantitative analysis of the Western blotting results for the synaptophysin levels. The values are expressed as mean ± SEM ( n = 10) of each experimental group. ( B : * p < 0.05 vs. Aβ/VH; ANOVA, post hoc test Bonferroni).

Article Snippet: In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ 1-42 oligomer (AβO) injection in mice.

Techniques: Injection, Control, Activation Assay, Western Blot

Journal: International Journal of Molecular Medicine

Article Title: Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (Review)

doi: 10.3892/ijmm.2019.4112

Figure Lengend Snippet: Bioinformatics programs for the design of gRNA and search of off-target cuts.

Article Snippet: Identification of the optimal gRNA among various candidates for a given target site, and the localization of potential off-target sites can be supported by different bioinformatics tools ( ); for example: CRISPRdirect , E-CRISPR , WU-CRISPR , CRISPR gRNA design tool ( https://www.atum.bio/eCom-merce/cas9/input ), sgRNA Designer , sgRNA Scorer 2.0 ( , ), CRISPRscan , CRISPR-ERA , CCtop , CRISPOR , Breaking-Cas , CHOPCHOP , CRISP MultiTarget , GT-Scan , ge-CRISPR , CRISPR Design , Cas-Designer , Cas-OFFinder , COSMID , DESKGEN Guide Picker , and CRISPR Genome Analyzer ( ) ( ).

Techniques: CRISPR, Activation Assay, Selection, Biomarker Discovery, Sequencing