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1.
RSC Adv ; 14(28): 20056-20060, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38911828

ABSTRACT

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

2.
RSC Adv ; 13(44): 31047-31058, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37881754

ABSTRACT

Dehydroabietane-type bifunctional organocatalysts derived from rosane-type diterpenes of dehydroabietic acid (DHAA) and dehydroabietylamine (DA) have been utilized in a wide variety of highly enantioselective reactions. Since one well-documented review exclusively reported on the development of terpene-derived bifunctional thioureas in asymmetric organocatalysis in 2013, fragmentary progress on the dehydroabietane-type bifunctional thioureas and squaramides has been mentioned in other reviews. In this mini-review, we systematically analyze and reorganize the published literature on dehydroabietane-type bifunctional organocatalysts in the recent decade according to the type of catalysts. Our aim is for this review to provide helpful research information and serve as a foundation for further design and application of rosin-based organocatalysts.

3.
Gels ; 7(4)2021 Dec 16.
Article in English | MEDLINE | ID: mdl-34940331

ABSTRACT

Gelatin hydrogels are widely used materials that may require surfactants to adjust their solution's surface tension for cell attachment, surface adsorption enhancement, or foaming. However, gelatin is a highly surface-active polymer, and its concentrated solutions usually do not require surfactants to achieve low surface tension. However, anionic surfactants, such as sodium dodecyl sulfate (SDS), interact strongly with gelatin to form complexes that impact its hydrogels' rheological properties, influencing processability and functionality. Nevertheless, there is a lack of systematic research on the impact of these complexes on high gelatin content (i.e., high strength) hydrogels' rheological properties. In this work, the SDS/gelatin ratio-dependent viscoelastic properties (e.g., gel strength, gelation kinetics, and melting/gelling temperature) of high-strength gelatin hydrogels were investigated using rheology and correlated to surface tension, viscometry, FTIR, and UV-Vis spectrophotometry. SDS-gelatin ratio was proved to be an important factor in tailoring the rheological properties of gelatin hydrogels. The gel strength, gelation kinetics, and melting/gelling temperature of the gelatin hydrogels linearly increased with SDS incorporation up to a maximum value, from which they started to decline. The findings of this work have wide applicability in tailoring the properties of gelatin-SDS solutions and hydrogels during their processing.

4.
J Biochem Mol Toxicol ; 34(2): e22430, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31833155

ABSTRACT

The aim of this study was to investigate the effect of melatonin (MT) and its metabolite N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) on Alzheimer-like learning and memory impairment in rats intracerebroventricularly injected with streptozotocin (STZ). The results showed that the escape latency of the STZ group was longer than that of the control (CON), MT, and AFMK groups. Increased levels of hyperphosphorylated tau, neurofilament proteins, and malondialdehyde and decreased superoxide dismutase levels were observed in the brains of the rats from the STZ group compared with the brains of the rats from the CON, MT, AFMK high and low group. These results suggest that exogenous MT and AFMK can improve memory impairment and downregulate AD-like hyperphosphorylation induced by STZ, most likely through their antioxidation function. Meanwhile, we found that an equal dose of AFMK had a stronger effect than that of MT. Our results indicate that MT and its metabolite AFMK represent novel treatment strategies for Alzheimer's disease.


Subject(s)
Alzheimer Disease/drug therapy , Antioxidants/therapeutic use , Kynuramine/analogs & derivatives , Melatonin/therapeutic use , Spatial Memory/drug effects , Alzheimer Disease/chemically induced , Animals , Antioxidants/pharmacology , Behavior, Animal/drug effects , Brain/drug effects , Brain/metabolism , Glutathione Peroxidase/metabolism , Kynuramine/pharmacology , Kynuramine/therapeutic use , Male , Malondialdehyde/metabolism , Maze Learning/drug effects , Melatonin/pharmacology , Neurofilament Proteins/metabolism , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Streptozocin/adverse effects , Streptozocin/pharmacology , Superoxide Dismutase/metabolism , tau Proteins/metabolism
5.
Neuropharmacology ; 157: 107668, 2019 10.
Article in English | MEDLINE | ID: mdl-31199957

ABSTRACT

Glucagon-like peptide-1 (GLP-1) signaling in the brain plays an important role in the regulation of glucose metabolism, which is impaired in Alzheimer's disease (AD). Here, we detected the GLP-1 and GLP-1 receptor (GLP-1R) in AD human brain and APP/PS1/Tau transgenic (3xTg) mice brain, finding that they were both decreased in AD human and mice brain. Enhanced GLP-1 exerts its protective effects on AD, however, this is rapidly degraded into inactivated metabolites by dipeptidyl peptidase-4 (DPP-4), resulting in its extremely short half-time. DPP-4 inhibitors, thus, was applied to improve the level of GLP-1 and GLP-1R expression in the hippocampus and cortex of AD mice brains. It is also protected learning and memory and synaptic proteins, increased the O-Glycosylation and decreased abnormal phosphorylation of tau and neurofilaments (NFs), degraded intercellular ß-amyloid (Aß) accumulation and alleviated neurodegeneration related to GLP-1 signaling pathway.


Subject(s)
Adamantane/analogs & derivatives , Dipeptides/pharmacology , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Learning/drug effects , Memory Disorders/prevention & control , Nerve Degeneration/prevention & control , Sitagliptin Phosphate/pharmacology , Adamantane/pharmacology , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Animals , Brain/metabolism , Brain/pathology , Cerebral Cortex/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glycosylation/drug effects , Hippocampus/metabolism , Humans , Intermediate Filaments/metabolism , Mice , Mice, Transgenic , Nerve Degeneration/pathology , Phosphorylation/drug effects , Signal Transduction/drug effects , tau Proteins/metabolism
6.
Chem Biol Interact ; 310: 108688, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31173752

ABSTRACT

Glucagon-like peptide 1 (GLP-1) has neuroprotective properties in Alzheimer's disease (AD). In this study, our aim is to explore the neuroprotective effects of liraglutide, a GLP-1 analogue, on AD-like neurodegeneration induced by H2O2 in human neuroblastoma SH-SY5Y cells. Cytotoxicity was determined by MTT assay and lactate dehydrogenase level was monitored by LDH assay. The level of lipid peroxidation and cell apoptosis rate were measured by malondialdehyde (MDA) assay and Annexin V-FITC/propidium iodide (PI) staining. Western blotting was used to assess the expression of Bcl-2, Bax, caspase-3, tau and the Akt/GSK-3ß. Liraglutide pre-treatment enhanced cell viability with reduced cytotoxicity, lipid peroxidationand and apoptosis. In addition, pre-treatment of liraglutide displayed that increased the expression of the pro-survival Bcl-2 and reduced pro-apoptotic Bax with ameliorated the hyperphosphorylation of tau and Akt/GSK-3ß signaling pathway in H2O2 stressed SH-SY5Y cells. These finding provided evidences that liraglutide protected the H2O2 induced AD-like neurodegeneration through improving Akt/GSK-3ß signaling pathway. These results suggest that liraglutide may have potential values for the treatment for AD.


Subject(s)
Alzheimer Disease/drug therapy , Liraglutide/therapeutic use , Neuroblastoma/metabolism , Neurodegenerative Diseases/drug therapy , Oxidative Stress , Cell Line, Tumor , Glucagon-Like Peptide 1/analogs & derivatives , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Hydrogen Peroxide/pharmacology , Neuroblastoma/pathology , Neurodegenerative Diseases/chemically induced , Neurodegenerative Diseases/etiology , Neuroprotective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
7.
Biochem Biophys Res Commun ; 511(1): 154-160, 2019 03 26.
Article in English | MEDLINE | ID: mdl-30773255

ABSTRACT

Dulaglutide, a novel long-acting glucagon-like peptide 1 (GLP-1) receptor agonist, is an incretin mimetic approved for type 2 diabetes mellitus (T2DM) treatment. Alzheimer's disease (AD) is called type 3 diabetes. The aim of this study is to explore the effects of dulaglutide on the learning and memory impairment in AD mice induced by injection of streptozocin (STZ) via intracerebroventricularly (i.c.v.). 32 male C57/BL6 mice were randomly divided into four groups: control group (CON); AD model group (STZ); dulaglutide treated (Dul); dulaglutide and exendin(9-39) (Ex). Western blotting was used to detect the levels of phosphorylated tau, neurofilament (NFs) proteins and phosphorylated PI3K/AKT/GSK3ß signaling pathway. Morris water maze (MWM) test was used to assess the spatial learning and memory ability. The results displayed that the hyperphosphorylation of tau and NFs were increased in the STZ and Ex groups compared to the control and Dul groups. Dulaglutide also significantly shortened the escape latency and increased the number of hidden platform crossings in MWM test. The effects of dulaglutide on decreasing the hyperphosphorylation of tau and NFs proteins through improving the PI3K/AKT/GSK3ß signaling pathway may be related to its protective effects on impairment of AD-like learning and memory.


Subject(s)
Alzheimer Disease/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptides/analogs & derivatives , Glycogen Synthase Kinase 3 beta/metabolism , Immunoglobulin Fc Fragments/therapeutic use , Memory Disorders/drug therapy , Recombinant Fusion Proteins/therapeutic use , tau Proteins/metabolism , Alzheimer Disease/chemically induced , Alzheimer Disease/complications , Alzheimer Disease/metabolism , Animals , Glucagon-Like Peptide-1 Receptor/metabolism , Glucagon-Like Peptides/therapeutic use , Hypoglycemic Agents/therapeutic use , Intermediate Filaments/metabolism , Male , Maze Learning/drug effects , Memory/drug effects , Memory Disorders/etiology , Memory Disorders/metabolism , Mice, Inbred C57BL , Phosphorylation/drug effects , Signal Transduction/drug effects , Streptozocin
8.
Neurosci Lett ; 698: 97-104, 2019 04 17.
Article in English | MEDLINE | ID: mdl-30395884

ABSTRACT

Neurofilaments (NFs), the most abundant cytoskeletal components in the mature neuron, are hyperphosphorylated and accumulated in the neuronal cell body of AD brain, and the abnormalities of NFs appear to contribute to neurodegeneration. Although previous studies have showed that O-GlcNAcylation and phosphorylation of NFs regulate each other reciprocally, the NFs O-GlcNAcylation and its effects on assembly and axonal transport are poorly explored. Here, we focus on the role of dysregulation of O-GlcNAcylation on structure and function of neurofilaments by corresponding phosphorylation. In the study, we found that decreased O-GlcNAcylation by intracerebroventricular administration of Alloxan, 6-diazo-5-oxonorleucine (Don) and okadaic acid (OA) in the rats resulted in increased phosphorylation with assembly of lower and shorter NFs. In contrast, in the sample of NAG-thiazoline (NAG-Ae) causing increased O-GlcNAcylation, NFs showed elongated filaments fibers and higher proportion of assembly. Furthermore, alloxan treatment induced abnormal accumulation of NFs bodies and delayed time of Fluorescence Recovery After Photobleaching (FRAP) in SK-N-SH cells, but the NAG-Ae treatment speeded up the axonal transport. Our experiments suggest that increased O-GlcNAcylation plays a key role in protecting the structure and function of NFs including filament assembly and axonal transport via decreased phosphorylation. These results expanded the function of O-GlcNAcylation in AD pathogenesis.


Subject(s)
Acetylglucosamine/metabolism , Intermediate Filaments/metabolism , Alloxan/pharmacology , Animals , Axonal Transport , Azo Compounds/pharmacology , Intermediate Filaments/ultrastructure , Male , Norleucine/analogs & derivatives , Norleucine/pharmacology , Okadaic Acid/pharmacology , Phosphorylation , Rats, Sprague-Dawley
9.
Article in English | MEDLINE | ID: mdl-30181664

ABSTRACT

BACKGROUND: O-GlcNAcylation is a highly dynamic post-translational modification that plays a key role in regulating phosphorylation of protein and cell survival. The proteins O-GlcNAcylation level is regulated dynamically by O-GlcNAc transferase (OGT) and ß-N-acetylglucosaminidase (O-GlcNAcase, OGA). Although previous studies have suggested the role of O-GlcNAcylation in neurodegenerative diseases, the mechanism of O-GlcNAcylation in Alzheimer's disease (AD) remains unclear. METHODS: The decrease of O-GlcNAcylation by alloxan, an OGT inhibitor, and increase by NAG-thiazolines (NAG-Ae), an O-GlcNAcase inhibitor were tested to investigate the effects of O-GlcNAc alteration on AD like neurodegeneration in SK-N-SH cells. RESULTS: The level of O-GlcNAcylation was decreased in alloxan treated cells and increased in NAG-Ae treated cells. Meanwhile, it was observed that both abnormal phosphorylation of NFs in cell bodies and apoptosis induced by alloxan treatment can be resisted by pretreatment or simultaneous treatment with appropriate NAG-Ae. CONCLUSION: These results demonstrated that increasing O-GlcNAc with NAG-Ae protected AD like neurodegeneration from NFs hyperphosphorylation and the cell loss, suggesting the role of O-GlcNAc in the pathogenesis and therapy of AD.


Subject(s)
Alzheimer Disease/enzymology , N-Acetylglucosaminyltransferases/metabolism , Acetylation , Alloxan/pharmacology , Alzheimer Disease/etiology , Apoptosis/physiology , Cell Death/physiology , Cell Line, Tumor , Enzyme Inhibitors/pharmacology , Humans , N-Acetylglucosaminyltransferases/antagonists & inhibitors , Phosphorylation/physiology , beta-N-Acetylhexosaminidases/antagonists & inhibitors
10.
Int J Mol Med ; 39(6): 1381-1392, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28440471

ABSTRACT

Long non-coding RNAs (lncRNAs) are widely accepted as key players in various biological processes. However, the roles of lncRNA in peripheral nerve regeneration remain completely unknown. Thus, in this study, we performed microarray analysis to measure lncRNA expression in the distal segment of the sciatic nerve at 0, 3, 7 and 14 days following injury. We identified 5,354 lncRNAs that were differentially expressed: 3,788 lncRNAs were differentially expressed between days 0 and 3; 3,314 lncRNAs were differentially expressed between days 0 and 7; and 2,400 lncRNAs were differentially expressed between days 0 and 14. The results of RT-qPCR of two dysregulated lncRNAs were consistent with those of microarray analysis. Bioinformatics approaches, including lncRNA classification, gene ontology (GO) analysis and target prediction, were utilized to investigate the functions of these dysregulated lncRNAs in peripheral nerve damage. Importantly, we predicted that several lncRNA-mRNA pairs may participate in biological processes related to peripheral nerve injury. RT-qPCR was performed for the preliminary verification of three lncRNA­mRNA pairs. The overexpression of NONMMUG014387 promoted the proliferation of mouse Schwann cells. Thus, the findings of our study may enhance our knowledge of the role of lncRNAs in nerve injury.


Subject(s)
Gene Expression Profiling , Peripheral Nerve Injuries/genetics , RNA, Long Noncoding/genetics , Animals , Cell Proliferation , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , Genomics , Mice, Inbred C57BL , RNA, Messenger/genetics , Sciatic Nerve/injuries , Sciatic Nerve/metabolism
11.
Neurochem Res ; 42(8): 2326-2335, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28382596

ABSTRACT

The purpose of this study was to explore how liraglutide affects AD-like pathology and cognitive function in APP/PS1/Tau triple transgenic (3 × Tg) Alzheimer disease (AD) model mice. Male 3 × Tg mice and C57BL/6 J mice were treated for 8 weeks with liraglutide (300 µg/kg/day, subcutaneous injection) or saline. Levels of phosphorylated tau, neurofilaments (NFs), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in brain tissues were assessed with western blots. Fluoro-Jade-B labeling were applied to detect pathological changes. The Morris water maze (MWM) was used to assess the spatial learning and memory. Liraglutide decreased levels of hyperphosphorylated tau and NFs in 3 × Tg liraglutide-treated (Tg + LIR) mice, increased ERK phosphorylation, and decreased JNK phosphorylation. Liraglutide also decreased the number of degenerative neurons in the hippocampus and cortex of Tg + LIR mice, and shortened their escape latencies and increased their hidden platform crossings in the MWM task. Liraglutide did not significantly affect the animals' body weight (BW) or fasting blood glucose. Liraglutide can reduce hyperphosphorylation of tau and NFs and reduce neuronal degeneration, apparently through alterations in JNK and ERK signaling, which may be related to its positive effects on AD-like learning and memory impairment.


Subject(s)
Intermediate Filaments/metabolism , Liraglutide/pharmacology , Maze Learning/physiology , Memory/physiology , tau Proteins/metabolism , Amyloid beta-Protein Precursor/genetics , Animals , Hypoglycemic Agents/pharmacology , Intermediate Filaments/drug effects , Male , Maze Learning/drug effects , Memory/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Phosphorylation/drug effects , Phosphorylation/physiology , Presenilin-1/genetics , Random Allocation , tau Proteins/antagonists & inhibitors
12.
Yao Xue Xue Bao ; 49(6): 807-12, 2014 Jun.
Article in Chinese | MEDLINE | ID: mdl-25212024

ABSTRACT

This study is to investigate the protective effect of rosiglitazone (RSG) against learning and memory impairment of APP/PS1/tau transgenic mice. AD mice model was replicated by using 6-month APP/PS1/tau transgenic mice. The learning and memory ability of mice was evaluated by Morris water maze and Western blotting assays was applied to measure the phosphorylation and O-glycosylation of Tau and neurofilaments (NFs) protein. The results demonstrated that RSG could reverse the learning and memory deficits of 3 x Tg mice significantly. It was also found that RSG could suppress the hyperphosphorylation of Tau and NFs protein levels and increase the glycosylation expression of Tau and NFs proteins in 3 x Tg mice brain. Together, RSG ameliorates cognitive impairments of 3 x Tg mice via the alleviation of the hyperphosphorylated Tau and NFs proteins burden in the brain.


Subject(s)
Learning/drug effects , Memory/drug effects , Thiazolidinediones/pharmacology , Alzheimer Disease , Amyloid beta-Peptides , Animals , Brain/drug effects , Disease Models, Animal , Glycosylation , Memory Disorders/drug therapy , Mice , Mice, Transgenic , Neurofilament Proteins/metabolism , Phosphorylation , Rosiglitazone , tau Proteins/metabolism
13.
Eur J Med Chem ; 78: 65-71, 2014 May 06.
Article in English | MEDLINE | ID: mdl-24681066

ABSTRACT

The design and synthesis of a new series of N-trisubstituted (at C2, C4 and C6 respectively) pyrimidine derivatives were reported, their in vitro structure-activity relationships vs. aurora A kinase were also discussed. Our results demonstrated that the introduction of characteristic N-substituted side chain at C2 of pyrimidines possessed a potent aurora A inhibitory activity, the position and the nature of the substituents on the phenyl ring of aniline side chain played key roles in cellular kinase inhibitory potency. Most tested compounds exhibited good inhibitory activities against aurora A kinase and various human tumor cell lines. Compounds 7j, 7m-n and 7p showed strong growth-inhibitory activities in the solid CNE-2 tumor cell and selectively blocked cell-cycle progression at the G2/M phase.


Subject(s)
Antineoplastic Agents/pharmacology , Aurora Kinase A/antagonists & inhibitors , Drug Design , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Aurora Kinase A/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , K562 Cells , MCF-7 Cells , Models, Molecular , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , U937 Cells
14.
Neurosci Bull ; 30(2): 282-94, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24652456

ABSTRACT

Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid ß precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.


Subject(s)
Alzheimer Disease/metabolism , Brain/metabolism , Insulin/metabolism , Signal Transduction/physiology , Amyloid beta-Protein Precursor/metabolism , Animals , Glucose/metabolism , Humans , Memory/physiology
15.
J Alzheimers Dis ; 37(3): 623-35, 2013.
Article in English | MEDLINE | ID: mdl-24008687

ABSTRACT

The aim of this study was to investigate the effect of liraglutide on Alzheimer-like learning and memory impairment in mice, which were intracerebroventricularly (i.c.v.) injected with streptozotocin (STZ). Twenty-four mice were randomly divided into three groups: control (CON), AD model (STZ), and liraglutide-treated (LIR). The results show that both hyperphosphorylated tau and neurofilament proteins had deceased protein glycosylation and the tau bound to microtubules was lower in the STZ group compared to the CON group. The expression of JNK phosphorylation was higher and the number of Fluoro-Jade-B-positive degenerative neurons was increased in the STZ group as compared to both the CON and liraglutide groups. Escape latency in the STZ group was longer than that in both the CON and LIR groups, while the number of hidden platform crossings in path length was less than that in the other two groups. Liraglutide decreased the hyperphosphorylation levels of tau and neurofilament proteins, increased protein O-glycosylation, increased tau bound to microtubules, and also significantly improved the learning and memory ability of the mice. These results suggest that the effects of liraglutide on decreasing the hyperphosphorylation of tau and neurofilament proteins by enhancing O-glycosylation of neuronal cytoskeleton protein, improving the JNK and ERK signaling pathway, and reducing neural degeneration may be related to its protective effects on AD-like learning and memory impairment induced by i.c.v. injection of STZ. Our results indicate that GLP-1 analogs represent a novel treatment strategy for Alzheimer's disease.


Subject(s)
Alzheimer Disease/metabolism , Glucagon-Like Peptide 1/analogs & derivatives , Insulin/metabolism , Memory Disorders/prevention & control , Neurofilament Proteins/metabolism , tau Proteins/metabolism , Alzheimer Disease/prevention & control , Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Glucagon-Like Peptide 1/administration & dosage , Hypoglycemic Agents/administration & dosage , Injections, Intraventricular , Liraglutide , Male , Maze Learning/drug effects , Maze Learning/physiology , Memory Disorders/metabolism , Mice , Neuroprotective Agents/administration & dosage , Phosphorylation/drug effects , Phosphorylation/physiology , Random Allocation , Signal Transduction/drug effects , Signal Transduction/physiology
16.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 6): o1515, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21754880

ABSTRACT

The five-membered ring in the the title mol-ecule, C(24)H(25)NO, fused with the phenyl-ene ring, is almost planar (r.m.s. deviation = 0.023 Å), with the methyl-ene C atom deviating most from this mean plane [0.031 (1) Å]. The tertiary N atom shows a flattened pyramidal configuration [Σ(angles at N) = 350.3 (6)°].

17.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 6): o1344, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21754739

ABSTRACT

The mol-ecule of the title compound, C(35)H(27)N(3)O(2), lies on a twofold rotation axis passing through the pyridine ring. The five-membered ring is approximately flat (r.m.s. deviation = 0.065 Å) and is essentially coplanar [dihedral angle = 4.2 (2)°] with the pyridine ring.

18.
Zhonghua Zhong Liu Za Zhi ; 33(1): 18-22, 2011 Jan.
Article in Chinese | MEDLINE | ID: mdl-21575458

ABSTRACT

OBJECTIVE: To explore the effect of Chlamydia pneumoniae (C.pn) infection on human laryngeal carcinoma cell line HEp-2 cell adhesion and migration, to further clarify the role and mechanism of C.pn infection in tumor metastasis. METHODS: HEp-2 cells were infected with C.pn after the culture and propagation of C.pn. The cytopathic effect was observed by microscopy. Morphological characteristics of C.pn inclusions in HEp-2 cells were examined by fluorescence microscopy and acridine orange staining. The ultrastructural changes of C.pn inclusions in the HEp-2 cells were examined by transmission electron microscopy (TEM). Cell adhesion assay was performed to investigate the effect of C.pn infection on the adhesion of HEp-2 cells to collagen I. Wound-healing assay and transwell assay were performed to explore the effect of C.pn infection on HEp-2 cell migration. RESULTS: At 72 h post-infection, C.pn infected-HEp-2 cells were swollen and partially desquamated. Numerous vacuoles (inclusions) were observed and C.pn inclusions occupied almost the whole cytoplasm of the HEp-2 cells. Grape-like C.pn inclusions were observed in the HEp-2 cells stained with acridine orange under a fluorescence microscope at 72 h after infection. Under TEM, there were more mature pear-shaped elementary bodies, but less larger and round reticulate bodies in the HEp-2 cells infected with C.pn for 72 h. In the cell adhesion assay, the A value in C.pn infection group was 0.669 ± 0.011, significantly higher than that in the control group (0.558 ± 0.005) at 2 h after infection (P < 0.001). The cell adhesion ratio in the C.pn infection group was 119.89%. The migration distance of C.pn infected-HEp-2 cells in the wound-healing assay was significantly longer than that of control cells at 24 h after infection (P < 0.05). HEp-2 cells infected with C.pn for 12 h migrated more than the control cells in the transwell assay (23.40 ± 2.41 vs 10.40 ± 1.67) (P < 0.001). CONCLUSIONS: C.pn infection can significantly promote HEp-2 cell adhesion to collagen I and migration of HEp-2 cells, indicating that C.pn infection may play an important role in promoting the metastasis of laryngeal cancer.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cell Adhesion , Cell Movement , Chlamydophila Infections , Laryngeal Neoplasms/pathology , Carcinoma, Squamous Cell/microbiology , Cell Line, Tumor , Chlamydophila Infections/microbiology , Chlamydophila Infections/physiopathology , Chlamydophila pneumoniae , Humans , Laryngeal Neoplasms/microbiology
19.
Biochem Biophys Res Commun ; 408(1): 154-9, 2011 Apr 29.
Article in English | MEDLINE | ID: mdl-21463610

ABSTRACT

N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, migration and invasion activities without affecting cell proliferation. cDNA microarray analysis revealed 96 deregulated genes with more than 2-fold changes in both cell lines after NDRG1 knockdown. Ten common upregulated genes (LPXN, DDR2, COL6A1, IL6, IL8, FYN, PTP4A3, PAPPA, ETV5 and CYGB) and one common downregulated gene (CLCA2) were considered to enhance tumor cell invasive activity. BisoGenet network analysis indicated that NDRG1 regulated these invasion effector genes/proteins in an indirect manner. Moreover, NDRG1 knockdown also reduced pro-invasion genes expression such as MMP7, TMPRSS4 and CTSK. These results suggest that regulation of invasion and metastasis by NDRG1 is a highly complicated process.


Subject(s)
Cell Cycle Proteins/metabolism , Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins/metabolism , Neoplasm Proteins/genetics , Ovarian Neoplasms/pathology , Uterine Cervical Neoplasms/pathology , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cell Proliferation , Female , Gene Knockdown Techniques , Humans , Intracellular Signaling Peptides and Proteins/genetics , Neoplasm Invasiveness , Neoplasm Metastasis , Ovarian Neoplasms/genetics , Uterine Cervical Neoplasms/genetics
20.
Am J Pathol ; 175(5): 2089-98, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19815707

ABSTRACT

Recent studies have suggested a possible role of insulin dysfunction in the pathogenesis of sporadic Alzheimer's disease (AD). In AD, brain glucose metabolism is impaired, and this impairment appears to precede the pathology and clinical symptoms of the disease. However, the exact contribution of impaired insulin signaling to AD is not known. In this study, by using a nontransgenic rat model of sporadic AD generated by intracerebroventricular administration of streptozotocin, we investigated insulin signaling, glucose transporters, protein O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain. We found impaired insulin signaling, overactivation of glycogen synthase kinase-3beta, decreased levels of major brain glucose transporters, down- regulated protein O-GlcNAcylation, increased phosphorylation of tau and neurofilaments, and decreased microtubule-binding activity of tau in the brains of streptozotocin-treated rats. These results suggest that impaired brain insulin signaling may lead to overactivation of glycogen synthase kinase-3beta and down-regulation of O-GlcNAcylation, which, in turn, facilitate abnormal hyperphosphorylation of tau and neurofilaments and, consequently, neurofibrillary degeneration.


Subject(s)
Alzheimer Disease , Glucose Transport Proteins, Facilitative/metabolism , Insulin/metabolism , N-Acetylglucosaminyltransferases/metabolism , Neurofilament Proteins/metabolism , Signal Transduction/physiology , tau Proteins/metabolism , Acetylglucosamine/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/physiopathology , Animals , Glucose/metabolism , Glucose Transport Proteins, Facilitative/genetics , Humans , Male , Microtubules/metabolism , N-Acetylglucosaminyltransferases/genetics , Neurofilament Proteins/genetics , Phosphorylation , Rats , Rats, Wistar , Streptozocin/metabolism , tau Proteins/genetics
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