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Shahrzad Ghafary Roshanak Ghobadian Mohammad Mahdavi Hamid Nadri Alireza Moradi Tahmineh Akbarzadeh Zahra Najafi Mohammad Sharifzadeh Najmeh Edraki Farshad Homayouni Moghadam Mohsen Amini 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2020,28(2):463
BackgroundAcetylcholine deficiencies in hippocampus and cortex, aggregation of β-amyloid, and β-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer’s disease.MethodsColorimetric Ellman’s method was used for determination of IC50 value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and β-secretase inhibitory activities, evaluation of inhibitory potency on β-amyloid (Aβ) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action.Result and discussionA new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC50 = 11.51 μM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC50 = 1.95 μM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak β-secretase inhibitory activities. This compound also inhibited aggregation of β-amyloid (Aβ) in self-induced peptide aggregation test at concentration of 10 μM.ConclusionIt is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. Graphical abstractOpen in a separate windowA new series of cinnamic-derived acids-tryptamine hybrid derivatives were designed, synthesized and evaluated as butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) inhibitors and neuroprotective agents. Compound 5b and 5q, as the more potent compounds, interacted with both the peripheral site and the choline binding site having mixed type inhibition. Results suggested that derivatives have a therapeutic potential for the treatment of AD.Electronic supplementary materialThe online version of this article (10.1007/s40199-020-00346-9) contains supplementary material, which is available to authorized users. 相似文献
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Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM–Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2?h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM–Glu20 represented much higher (p?<?0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM–Glu20 in MDA-MB231 cells, 173.56?±?1.37%, was significantly higher than that of MCF7 cells, 65.00?±?1.73% (p?<?0.05). The results indicated that hPAMAM–Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM–glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method. 相似文献
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Jerry R. Paugh Alba Alfonso-Garcia Andrew Loc Nguyen Jeffrey L. Suhalim Marjan Farid Sumit Garg Jeremiah Tao Donald J. Brown Eric O. Potma James V. Jester 《The ocular surface》2019,17(1):151-159
Purpose
This study examined whether hyperspectral stimulated Raman scattering (hsSRS) microscopy can detect differences in meibum lipid to protein composition of normal and evaporative dry eye subjects with meibomian gland dysfunction.Methods
Subjects were evaluated for tear breakup time (TBUT), staining, meibum expression and gland dropout. Expressed meibum was analyzed using SRS vibrational signatures in the CH stretching region (2800–3050?cm?1). Vertex component analysis and K-means clustering were used to group the spectral signatures into four fractions containing high lipid (G1) to high protein (G4).Results
Thirty-three subjects could be statistically analyzed using pooled meibum (13 with stable tear films (TBUTs?>?10?s) and 20 with unstable tear films (TBUTs?≤?10?s). Significant differences in meibum from subjects with unstable vs. stable TBUTs were found for the G1 fraction (medians 0.164 and 0.020, respectively; p?=?0.012) and the G2 fraction (medians 0.244 and 0.272, respectively; p?=?0.045). No differences were observed for the G3 and G4 fractions. Single orifice samples were not significantly different vs. pooled samples from the fellow eye, and eyelid sector samples (nasal, central and temporal) G2:G3 fractional components were not significantly different (p?=?0.449). Spearman analysis suggested a significant inverse correlation between G1 fraction and TBUT (R?=??0.351; p?=?0.045).Conclusions
hsSRS microscopy allows compositional analysis of expressed meibum from humans which correlated to changes in TBUT. These findings support the hypothesis that hsSRS may be useful in classifying meibum quality and evaluating the effects of therapy. 相似文献6.
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Farid Saad 《Asian journal of andrology》2015,17(1):58-60
It is no exaggeration to say that our conceptualization of the (patho-) physiological functions of testosterone has undergone a revolutionary development over the last three decades. The traditional thinking was that the biological functions of testosterone were restricted mainly to the area of reproduction and male sexuality. However, scientific research has clearly demonstrated that testosterone is a multi-system hormone serving a wide range of hitherto unsuspected biological functions.In line with this, it will be argued in this contribution that the physiological role of testosterone has been underestimated, while the risks of testosterone administration have been overstated. Space does not permit to elaborate extensively on all new insights of the role of testosterone in the biology of the male. Three areas will be addressed: (1) the role that testosterone can play in body weight management of hypogonadal men; (2) the role of testosterone in inflammatory processes; (3) the strategy required to let patients benefit from the recent insights that testosterone is a multi-system hormone whose use should not be limited to reproductive/sexual medicine. 相似文献
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Tahereh Fathi Najafi Sareh Dashti Nasibeh Bolghanabadi Malihe Rezvanifard Nafise Andaroon Dina Abadibavil Fahimeh Tahoonian Golkhatmy Narjes Bahri 《Archives of Psychiatric Nursing》2021,35(3):255-260
Non-medical approaches including cognitive behavioral therapy (CBT) have been proposed for the management of tocophobia. A new method of performing CBT is through internet. The aim of this systematic review and meta-analysis was to evaluate the effect of internet-based and traditional CBT on tocophobia. A literature search was conducted on qualitative and quantitative articles from 2000 to 2019 in Pubmed, Scopus, Web of Science and Cochrane databases using search terms referring to tocophobia and CBT. Identified articles were screened in two steps; 1) title and abstract and 2) full text screening. The quality of the quantitative and qualitative studies was assessed using the quality criteria proposed by the Cochrane Collaboration and Jonna Briggs Institute (JBI) checklist respectively. Out of the 382 relevant studies, 9 studies were eligible for the review. A high level of heterogeneity was observed in the studies (I2 = 94%, P < 0.001). The meta-analysis showed that both internet-based, and traditional CBT were effective in reducing tocophobia. CBT was more effective in interventions in the Middle Eastern compared to European countries. More than five CBT sessions could significantly reduce tocophobia. Healthcare providers and midwives should have basic knowledge on physiological interventions to reduce tocophobia. 相似文献