ABSTRACT
Alzheimer's disease (AD) is the most prevalent and age-related dementia accompanied by neurodegenerative disorder, memory loss, and abnormal behaviors. Recent studies have shown an increasing interest in studying the role of microRNAs (miRNAs) and their potential values in the early diagnostics of AD. MiR-425-5p has extensively expression within various tissues and organs, acting as an important regulator in many pathological procedures. The functions of miR-425-5p involved in AD were investigated in the present study. The results showed that miR-425-5p was upregulated in patients with AD and HEK293/tau cells. Transfections with miR-425-5p overexpression vector significantly enhanced cell apoptosis, activated glycogen synthase kinase-3ß (GSK-3ß), and increased tau phosphorylation in HEK293/tau cells. Heat shock protein B8 (HSPB8) was directly targeted by miR-425-5p. Upregulation of miR-425-5p induced cell apoptosis and promoted tau phosphorylation partially via targeting HSPB8 in AD. Therefore, miR-425-5p might act as a new therapeutic target for AD treatment.
Subject(s)
Alzheimer Disease/metabolism , Apoptosis/physiology , Brain/metabolism , Cognitive Dysfunction/metabolism , Heat-Shock Proteins/metabolism , MicroRNAs/metabolism , Molecular Chaperones/metabolism , tau Proteins/metabolism , Cells, Cultured , Glycogen Synthase Kinase 3 beta/metabolism , HEK293 Cells , Humans , Phosphorylation/physiology , Up-RegulationABSTRACT
Alzheimer's disease (AD) is a public health issue worldwide. Berberine (Ber) acts as the neuroprotective role in an animal experiment of AD. MicroRNA-188 (miRNA-188) was reported to be decreased in primary hippocampal neurons of mice. However, the roles and molecular basis of Ber and miRNA-188 in the treatment of AD need to be further explored. In this study, 5 µM Ber treatment has little effect on cell viability. Ber treatment or miR-188 overexpression expedited proliferation and inhibited caspase-3 activity and apoptotic rate in amyloid-beta (Aß)-treated BV2 and N2a cells. MiR-188 was downregulated, and nitric oxide synthase 1 (NOS1) was upregulated in Aß-induced BV2 and N2a cells. NOS1 worked as the target of miR-188. NOS1 overturned miR-188-induced effects on cell viability, caspase-3 activity, and apoptotic rate in Aß-induced BV2 and N2a cells. Ber mitigated neuronal damage in Aß-induced BV2 and N2a cells by miR-188/NOS1 axis. These results suggested that Ber accelerated cell viability and suppressed caspase-3 activity and apoptotic rate possible by miR-188/NOS1 pathway, implying the treatment of Ber as an underlying effective drug for AD patients.
Subject(s)
Amyloid beta-Peptides/toxicity , Berberine/pharmacology , MicroRNAs/genetics , Microglia/drug effects , Neurons/drug effects , Neuroprotective Agents/pharmacology , Nitric Oxide Synthase Type I/metabolism , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/prevention & control , Animals , Cells, Cultured , Gene Expression Regulation , Humans , Mice , Microglia/metabolism , Microglia/pathology , Neurons/metabolism , Neurons/pathology , Nitric Oxide Synthase Type I/genetics , Signal TransductionABSTRACT
A practical synthetic strategy to a chiral azabicycclooctanyl derivative (1), a potent DPP-4 inhibitor, starting from a commercially available nortropine is described. The stereogenic center of 1 was established employing a modified protocol of Ellman's diastereoselective addition of a benzylic nucleophile to tert-butanesulfinimine. Other key steps include Corey-Chaykovsky reaction, Meinwald rearrangement, and CDMT-promoted amide bond formation involving a sterically hindered amine 2.
Subject(s)
Azabicyclo Compounds/chemical synthesis , Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis , Aldehydes/chemistry , Azabicyclo Compounds/chemistry , Azabicyclo Compounds/pharmacology , Butanes/chemistry , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Imines/chemistry , Stereoisomerism , Sulfonium Compounds/chemistryABSTRACT
Acetophenone and its derivatives reacted on thionyl chloride to form an intermediate, which can react on the secondary aminnes to form alpha-carbonylthioformamides (1a-1f), followed by sulfurization with lawesson reagent to give target compounds alpha-thiocarbonylthioformamides (2a-2f). Compounds 2a-2f are the deep-red or deep-green crystals because there are two thiocarbonyl groups in the molecule, and they can be used as far-infraed adsorbent dyes, laser-Q switch and organic conductors. Moreover, they are very important intermediates, can react on reagents with amino or diamino groups to produce a variety of acyclic or heterocyclic compounds, which can be used as pesticides and medicines. Therefore, it is necessary to develop a new method for the analysis of alpha-thiocarbonylthioformamides (2a-2f). OA-TOF high resolution mass spectrometer is suitable to do this because of its small volume, high speed and giving elemental composition of ions. In this paper, the mass fragmentation pattern of alpha-thiocarbonylthioformamides was studied in detail using OA-TOF high resolution mass spectrometer of Micromass. The results showed that the molecular ions appeared, then, a neutral molecule S2 was lost easily from the molecular ion of alpha-thiocarbonylthioformamides, forming a particular ion M-S2 (base peak). This provides an effective method for the analysis of these compounds.
ABSTRACT
BACKGROUND: The current study explored the main symptom dimensions and clinical characteristics of obsessive-compulsive disorder (OCD) in Chinese patients. METHODS: Obsessive-compulsive (OC) symptoms of participants (N=512) were assessed through the Yale-Brown Obsessive Compulsive Scale Checklist (YBOCS-CL). Exploratory category-level and item-level factor analyses were performed. Regression analysis was carried out to study the relationships between clinical characteristics in our sample and the symptom dimensions obtained. Relationships among the clinical characteristics were explored using the chi-square test. RESULTS: We found five symptom dimensions in the category-level analysis and six similar symptom dimensions in the item-level analysis. Moreover, the factors identified in our study overlapped with the results of prior studies. Association between gender and the symptom dimension of 'contamination/cleaning' was observed, with females showing more significant association with this dimension than males. Age of onset was associated with the symptom dimension of 'symmetry/arranging/repeating/counting', with the early-onset group more actively associated with this dimension than the late-onset group. Early-onset patients with OCD were more likely to be male and show tic comorbidity. LIMITATIONS: Data from only one site do not represent the full range of Chinese OCD patients. Furthermore, past symptoms may show memory bias. Inherent problems in the YBOCS-CL have also been identified. CONCLUSION: Symptoms in Chinese OCD patients are multidimensional. The main components of symptom dimensions of OCD patients show similarity or consistency among different regions and sociocultural backgrounds. The pathogenic mechanism of OCD may show potential distinctions.