ABSTRACT
A series of genistein derivatives were synthesized and evaluated as multifunctional anti-Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC50 value (0.034 µM) much lower than that of rivastigmine (6.53 µM). A Lineweaver-Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal-chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 µM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD.
Subject(s)
Cholinesterase Inhibitors/chemical synthesis , Genistein/chemistry , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amines/chemistry , Animals , Antioxidants/chemistry , Binding Sites , Catalytic Domain , Cell Survival/drug effects , Chelating Agents/chemistry , Cholinesterase Inhibitors/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Drug Design , Genistein/metabolism , Genistein/pharmacology , Genistein/therapeutic use , Hep G2 Cells , Humans , Kinetics , Molecular Docking Simulation , PC12 Cells , Rats , Structure-Activity RelationshipABSTRACT
This study aimed to characterize circular RNA (circRNA) expression profiles and biological functions in head and neck squamous cell carcinoma (HNSCC). Differentially expressed circRNAs were screened using an Arraystar Human CircRNA Array and verified by reverse transcription-quantitative polymerase chain reaction. Multiple bioinformatics methods and a hypergeometric test were employed to predict the interactions between RNAs and the functional circRNAmicroRNA (miRNA)-mRNA axes in HNSCC. As a result, 287 circRNAs and 1,053 mRNAs were determined to be differentially expressed in HNSCC compared with the adjacent tissue. In addition, the expression levels of circRNA_036186 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, ζ polypeptide (1433ζ) were identified to be significantly different. A competing endogenous RNA (ceRNA) network was constructed, consisting of 5 circRNAs, 385 miRNAs and 96 mRNAs. Furthermore, we predicted that miR193b3p exerts a significant effect on 1433ζ, and was significantly associated with the Hippo signaling pathway in HNSCC. On the whole, these findings suggest that circRNA_036186 likely regulates 1433ζ expression by functioning as a ceRNA in the development and progression of HNSCC.
Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , RNA, Messenger/metabolism , RNA/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics , 14-3-3 Proteins/genetics , 14-3-3 Proteins/metabolism , Adult , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Computational Biology , Female , Gene Expression Profiling , Gene Regulatory Networks/genetics , Humans , Male , MicroRNAs/genetics , Middle Aged , Oligonucleotide Array Sequence Analysis , RNA/genetics , RNA, Circular , RNA, Messenger/genetics , Signal Transduction/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Up-RegulationABSTRACT
Glutathione peroxidase 3 (GPX3) is an important member of antioxidant enzymes for reducing reactive oxygen species and maintaining the oxygen balance. Gpx3 mRNA is strongly expressed in decidual cells from days 5 to 8 of pregnancy. After pregnant mice are treated with GPX inhibitor for 3 days, pregnancy rate is significantly reduced. Progesterone stimulates Gpx3 expression through PR/HIF1α in mouse endometrial stromal cells. In the decidua, the high level of GPX3 expression is closely associated with the reduction of hydrogen peroxide (H2O2). Based on our data, GPX3 may play a major role in reducing H2O2 during decidualization.
Subject(s)
Decidua/enzymology , Gene Expression Regulation, Enzymologic , Glutathione Peroxidase/metabolism , Animals , Antioxidants/pharmacology , Cell Hypoxia , Corpus Luteum/drug effects , Decidua/physiology , Embryo Implantation , Female , Glutathione Peroxidase/antagonists & inhibitors , Glutathione Peroxidase/genetics , Humans , Hydrogen Peroxide/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mice , Oxidation-Reduction , Pregnancy , Progesterone/physiology , Selenic Acid/pharmacology , Thiomalates/pharmacology , Transcription, Genetic/drug effectsABSTRACT
OBJECTIVE: To evaluate the effect of electroacupuncture (EA) of Sanyinjiao (SP 6) on perimenopausal syndrome (PMS). METHODS: Multicentral randomized controlled trials and single blind test were adopted in the present study. A total of 157 PMS patients were randomly divided into EA group (n=81) and medication group (n=76) . EA (2/100 Hz, 8-10 mA) was applied to bilateral Sanyinjiao (SP 6), 3 times a week and for 3 months (mon). Patients of medication group were treated by oral administration of nylestriol, 2 mg/time, twice a mon for 3 mon. For PMS patients, medroxyprogesterone (6 mg/d, for 10 days) was added from the third mon on after the treatment. The therapeutic effect was evaluated by using "symptoms-signs score scale", and changes of serum estradiol (E2), follicle stimulating hormone (FSH) and luteotrophic hormone (LH) were detected by chemiluminescence immune assay. Kupperman index was determined before and after the treatment. RESULTS: In comparison with pre-treatment, Kupperman index of EA group decreased significantly (P < 0.01). After the treatment, contents of serum FSH and LH of EA group decreased significantly (P < 0.01), while serum E2 contents of EA and medication groups increased significantly (P < 0. 01). Serum LH and E2 levels of EA group were significantly lower than those of medication group (P < 0.05). No significant differences were found between two groups in Kupperman index, markedly-effective rates and total effective rates (P > 0.05). CONCLUSION: EA of Sanyinjiao (SP 6) is able to regulate serum E2, FSH and LH levels and effectively improve perimenopausal syndrome.
Subject(s)
Electroacupuncture , Meridians , Perimenopause/blood , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Middle AgedABSTRACT
OBJECTIVE: To objectively evaluate the effectiveness and safety of electroacupuncture (EA) at Sanyinjiao (SP 6) for treatment of peri-menopausal syndrome. METHODS: All the patients enrolled were randomly divided into a treatment group and a control group. The treatment group were treated with EA at Sanyinjiao (SP 6) for 3 therapeutic courses, thrice each week, 30 min each time, one month constituting one course. The control group were treated with oral administration of nylestriol for 3 months, 2 mg each time, twice each month. For the menopausal patient, medroxyprogesterone was added from the third month of the treatment for 7 days, 6 mg each day. Changes of vasomotorial symptoms, mental symptoms and scores of Kupperman indexes before and after treatment for 1 month, 2 months and 3 months were investigated. RESULTS: EA could significantly decrease the score of Kupperman indexes, improve vasomotorial symptoms and mental symptoms in the patient of peri-menopausal syndrome with no severe adverse effects. The control group in the score of Kupperman indexes was slightly higher than the treatment group with no significant difference between the two groups, but the treatment group in improvement of the vasomotorial symptoms was better than the control group and in improvement of mental symptoms was not as good as the control group. CONCLUSION: EA at Sanyinjiao (SP 6) is effective and safe for treatment of peri-menopausal syndrome.
