Search

Expression of CREB-regulated transcription coactivator 1 (CRTC1) in the hippocampus is impaired in Alzheimer's disease (AD). However, CRTC1 related mechanisms associated with long-term synaptic plasticity impairment and cognitive decline in the onset of AD are unknown. In this study, electrophysiological recordings indicated that lentivirus-mediated CRTC1 overexpression effectively ameliorates suppression of late-phase long-term potentiation (L-LTP) in rat hippocampal slices treated with oligomeric amyloid β(1–42) peptides (oAβ42) (200 nM). In addition, application of oAβ42 and genetic knockdown of CRTC1 by lentivirus-mediated CRTC1-shRNA inhibit L-LTP, whereas their combination does not further impair L-LTP. Brain-derived neurotrophic factor (BDNF), an important downstream protein confers protection of CRTC1 overexpression against oAβ42-induced L-LTP impairment as shown by administration of K252a (200 nM) and TrkB-FC (20 μg/ml). Furthermore, behavioral and western blotting analyses showed that CRTC1 overexpression reverses oAβ42-induced hippocampal-dependent cognitive deficits, downregulation of CRTC1 and BDNF expression. Notably, CRTC1-shRNA directly elicits cognitive deficits. In summary, these findings show that hippocampal CRTC1 signaling is affected by soluble oAβ, and CRTC1-BDNF pathway is involved in hippocampal L-LTP impairment and memory deficits induced by oAβ42.

In this paper, the effects of hafnium (Hf) addition on the thermal stability of the microstructure and tensile properties of Al-containing 16Cr-ODS steels were investigated. High temperature aging tests of the ODS steels with and without Hf were conducted at 750 °C, 950 °C and 1150 °C for 100 h respectively. And the microstructure evolution after thermal aging was investigated using transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). The results indicated that Hf addition could improve the coarsening resistance of the oxide particles and the grains during aging treatment due to the formation of stable Y2Hf2O7 particles. Tensile tests on the aged-steels showed that the ultimate tensile strength and yield strength of 16Cr-Hf-ODS steel were higher than those of 16Cr-ODS steel. It was considered that the excellent thermal stability and tensile properties of 16Cr-Hf-ODS steel were related with the refined microstructure.

A high co-morbidity between Alzheimer’s disease (AD) and depression suggests there might be similar mechanisms underlying the course of these diseases. Previous studies have shown that p38MAPK plays a critical role in the pathophysiology of AD and depression. However, little is known about whether SB203580, a selective inhibitor of p38MAPK, may protect against AD-associated cognitive impairments and depression-like behavior, simultaneously. Herein, we have shown, for the first time, that SB203580 may reverse memory impairments and depression-like behavior induced by hippocampal infusion of β-amyloid 1–42 (Aβ1–42), as measured by novel object recognition, Morris water maze, tail-suspension and forced-swimming tests. In addition, phorbol 12-myristate 13-acetate (PMA), a PKC activator which also activates p38MAPK, significantly abolished the effects of SB203580. Moreover, Aβ1–42 causes increased phosphorylation of p38MAPK and decreased phosphorylation of Ser9-glycogen synthase kinase 3β (GSK3β) and cAMP-response element binding protein (CREB) in the hippocampus of mice, which could be significantly reversed by SB203580. Our results suggest that SB203580 reversed Aβ1–42-induced cognitive impairments and depression-like behavior via inhibiting p38MAPK signaling pathway, which not only supports p38MAPK as a therapeutic target for AD-associated cognitive dysfunction and depression-like behavior, but also provides experimental basis for the use of SB203580 in co-morbidity of AD and depression.

An effective and practical method has been developed for the diversity-oriented synthesis of 1-alkyl-3-aroylindolizines via the 1,3-dipolar cycloaddition of pyridinium ylides and aliphatic aldehydes in the presence of molecular iodine and a catalytic amount of MnO2. The synthesis proceeds by tandem reactions involving [3+2] cycloaddition, dehydration of the cycloadduct, and dehydroaromatization. Molecular iodine served both as a catalyst and a dehydroaromatization reagent in the reaction.

An iodine-promoted synthesis of acylindolizinecarboxylates via 1,3-dipolar cycloaddition of nitrogen ylides with acetylenecarboxylates and subsequent aromatization for the generation of a wide range of structurally interesting, pharmacologically and photoelectrically significant compounds is reported. Only readily available materials, mild conditions, and operationally trivial reaction protocols were required.

A one-pot reaction was developed to synthesise a variety of 1-iodoindolizines from substituted acetophenone, acetic acid, pyridine, and molecular iodine. The structure of 3-benzoyl-1-iodoindolizine (2a) and 1,3-dibenzoylindolizine (3a) was further confirmed by X-ray single crystal analysis.

A high co-morbidity between Alzheimer's disease (AD) and depression suggests there might be similar mechanisms underlying the course of these diseases. Previous studies have shown that p38MAPK plays a critical role in the pathophysiology of AD and depression. However, little is known about whether SB203580, a selective inhibitor of p38MAPK, may protect against AD-associated cognitive impairments and depression-like behavior, simultaneously. Herein, we have shown, for the first time, that SB203580 may reverse memory impairments and depression-like behavior induced by hippocampal infusion of β-amyloid 1-42 (Aβ

An effective and practical method has been developed for the diversity-oriented synthesis of trans-4,6-diaryl-5-nitro­piperidin-2-ones via four-component reaction from substituted nitro­styrenes, aromatic aldehydes, dimethyl malonate, and formamide for the generation of a wide range of structurally interesting and pharmacologically significant compounds. It is worth mentioning that in the course of this reaction, the formation of products was highly stereoselective.

A novel and efficient one-pot synthesis of 3,4-dihydronaphthalen-1(2H)-ones by employing 2-iodocyclohex-2-enones, 1-alkynes, and a Pd[(C6H5)3P]4/AgOAc catalytic system is described. The attractive features of this method, which enables the facile preparation of 3,4-dihydronaphthalen-1(2H)-one derivatives, are its very simple and straightforward procedure, mild reaction conditions, and good yields (65–87%).

An efficient preparation of hydroxysteroids by a one-pot, simultaneously rapid deprotection of 3-acyloxy groups and reduction of D-ring ketones (nitrile) of steroids using DIBAL-H in the presence of NiCl2 (10 mol %) is described. The attractive features of this procedure for the preparation of the hydroxysteroid derivatives are the mild reaction conditions, short reaction time, excellent yields, clean reaction profiles, and an inexpensive catalyst system.

An iodine-promoted synthesis of acylindolizinecarboxylates via 1,3-dipolar cycloaddition of nitrogen ylides with acetylenecarboxylates and subsequent aromatization for the generation of a wide range of structurally interesting, pharmacologically and photoelectrically significant compounds is reported. Only readily available materials, mild conditions, and operationally trivial reaction protocols were required.

Colorectal cancer (CRC) is the third leading cause of cancer mortality in the world. We report that one oncogene amplified on chromosome 3q26, LMO1, a master transcriptional regulator of stemness, operates to drive strong growth phenotype in CRC. The gene expression changes of LMO1 in human CRC tissues compared with noncancerous tissues were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of LMO1 in CRC. Moreover, we discovered that LMO1 promoted cancer cell proliferation in vitro/in vivo and LMO1 expression correlated with elevated AKT phosphorylation in CRC while the AKT phosphorylation was required for oncogenic effects of LMO1. Next, our data point to the usefulness of LMO1 overexpression, as a new predictive marker for responsiveness to cetuximab. All in all, LMO1 is a commonly activated tumor promoter that activates AKT signaling in CRC and a new predictive marker for targeted therapy.

A novel and efficient one-pot synthesis of 3,4-dihydronaphthalen-1(2H)-ones by employing 2-iodocyclohex-2-enones, 1-alkynes, and a Pd[(C6H5)3P]4/AgOAc catalytic system is described. The attractive features of this method, which enables the facile preparation of 3,4-dihydronaphthalen-1(2H)-one derivatives, are its very simple and straightforward procedure, mild reaction conditions, and good yields (65–87%).

An efficient and practical method has been developed for the diversity-oriented synthesis of polysubstituted 2-piperidinones via four-component reaction between substituted nitrostyrenes, aromatic aldehydes, ammonium acetate, and dialkyl malonates for the generation of a wide range of structurally interesting and pharmacologically significant compounds. It is worth mentioning that in the course of this reaction, the formation of products was highly stereoselective. Two differently stereochemical classes of polysubstituted 2-piperidinones depended on the substitutent position of aromatic aldehyde.

Various hydroxysteroids are efficiently obtained in a rapid one-pot reaction under mild reaction conditions.

The efficient synthesis of some 17E-(2-aryl-2-oxo-1-ethylidene)-5α-androstan-3β-ols was investigated. 17-Alkynyl-3,17-androstanediols were prepared through the nucleophilic addition of epiandrosterone using the corresponding 1-alkynes in the presence of a strong base n-BuLi firstly. The Meyer–Schuster rearrangement of 17-alkynyl-3,17-androstanediols was carried out efficiently catalyzed by 10% H2SO4 and HgSO4 in THF. This strategy offered a very straightforward and efficient method for access to conjugated α,β-unsaturated ketone 17E,5α-androstan-3β-ols from the 17-alkynyl-3,17-androstanediols in good overall yields, which are key intermediates for the preparation of some biologically important modified 17-side chain steroids. Evaluation of the synthesized compounds for cytotoxicity against A549, SKOV3, MKN-45 and MDA-MB-435 cell lines showed that 17E-(2-aryl-2-oxo-1-ethylidene)-5α-androstanes possessing a hydroxyl groups at C-3 and fluoro-substituted group of aromatic ring in the side chain have significant inhibition activity.