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1.
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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Kai Yang Sara Fard Rudolf Furrer Michael C. Archer HoYin Lip 《Nutrition and cancer》2016,68(1):94-104
Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer, but the mechanisms responsible for these associations are not known. An animal model could facilitate such an understanding. Both genotoxic and nongenotoxic carcinogens induce aberrant crypt foci (ACF) in the colons of F344 rats. F344 rats were provided with diets that contained putative risk factors for CRC: low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure or a control diet for 14 wk. The rats were then assessed with biochemical measures and by topological examination for evidence of colon abnormalities. Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and ACF were increased from 0.7 to 13.6 lesions/colon (both P < 0.001). Rats exposed to the multiple environmental conditions associated with colon cancer, developed ACF similar to the heterogeneous or ill-defined ACF in the human colon. Heterogeneous ACF are the most frequently seen in humans and are also seen in rats shortly after exposure to the non-genotoxic colon carcinogen, dextransulfate sodium. The rodent model could be used to assess the pathways from diet and environment to colon cancer and to provide guidance for clinical studies. 相似文献
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Maryam Beheshtian Zohreh Fattahi Mahsa Fadaee Raheleh Vazehan Payman Jamali Elham Parsimehr Mahboubeh Kamgar Mehrshid Faraji Zonooz Shokouh Sadat Mahdavi Zahra Kalhor Sanaz Arzhangi Seyedeh Sedigheh Abedini Farahnaz Sabbagh Kermani Faezeh Mojahedi Vera M. Kalscheuer Hans-Hilger. Ropers Ariana Kariminejad Hossein Najmabadi Kimia Kahrizi 《Clinical genetics》2019,95(6):718-725
Neurodevelopmental delay and intellectual disability (ID) can arise from numerous genetic defects. To date, variants in the EXOSC gene family have been associated with such disorders. Using next-generation sequencing (NGS), known and novel variants in this gene family causing autosomal recessive ID (ARID) have been identified in five Iranian families. By collecting clinical information on these families and comparing their phenotypes with previously reported patients, we further describe the clinical variability of ARID resulting from alterations in the EXOSC gene family, and emphasize the role of RNA processing dysregulation in ARID. 相似文献
4.
Amir Ali Hamidieh Davood Beiki Pedram Paragomi Babak Fallahi Maryam Behfar Armaghan Fard‐Esfahani Ashraf Sadat Hosseini Ahmadreza Shamshiri Mohammad Eftekhari Ardeshir Ghavamzadeh 《Pediatric transplantation》2014,18(5):510-517
MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant 131I‐MIBG scintigraphy. Twenty high‐risk patients were enrolled. On day ?30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG‐avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m2), carboplatin (1500 mg/m2), and melphalan (210 mg/m2). Non‐MIBG‐avid subgroup received etoposide (600 mg/m2), carboplatin (1200 mg/m2), and melphalan (150 mg/m2). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17–65) in MIBG‐avid and 38.9 months (range, 18–65) in non‐MIBG‐avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG‐avid patients, the three‐yr OS was 66 ± 21%. In MIBG‐non‐avid subgroup, the three‐yr OS was 53 ± 20%. In MIBG‐avid and non‐MIBG‐avid subgroups, the three‐yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre‐ASCT MIBG scintigraphy in high‐risk neuroblastoma. MIBG‐avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy. 相似文献
5.
Fatemeh Shabani Alireza Farasat Majid Mahdavi Nematollah Gheibi 《Inflammation research》2018,67(10):801-812
Background
Calprotectin (S100A8/S100A9), a heterodimeric EF-hand Ca2+?binding protein, are abundant in cytosol of neutrophils and are involved in inflammatory processes and several cancerous pathogens.Objective
The purpose of the present systematic review is to evaluate the pro- and anti-tumorigenic functions of calprotectin and its relation to inflammation.Materials and methods
We conducted a review of studies published in the Medline (1966–2018), Scopus (2004–2018), ClinicalTrials.gov (2008–2018) and Google Scholar (2004–2018) databases, combined with studies found in the reference lists of the included studies.Results
Elevated levels of S100A8/S100A9 were detected in inflammation, neoplastic tumor cells and various human cancers. Recent data have explained that many cancers arise from sites of infection, chronic irritation, and inflammation. The inflammatory microenvironment which largely includes calprotectin, has an essential role on high producing of inflammatory factors and then on neoplastic process and metastasis.Conclusion
Scientists have shown different outcomes in inflammation, malignancy and apoptosis whether the source of the aforementioned protein is extracellular or intracellular. These findings are offering new insights that anti-inflammatory therapeutic agents and anti-tumorigenic functions of calprotectin can lead to control cancer development.6.
7.
Oxidative Stress Responses to Nigella sativa Oil Concurrent with a Low‐Calorie Diet in Obese Women: A Randomized,Double‐Blind Controlled Clinical Trial 下载免费PDF全文
Nazli Namazi Reza Mahdavi Mohammad Alizadeh Safar Farajnia 《Phytotherapy research : PTR》2015,29(11):1722-1728
The aim of the present study was to determine the effects of Nigella sativa (NS) oil concurrent with a low‐calorie diet on lipid peroxidation and oxidative status in obese women. In this double‐blind placebo‐controlled randomized clinical trial, 50 volunteer obese (body mass index = 30–35 kg/m2) women aged 25–50 years old were recruited. Participants were randomly divided into intervention (n = 25) and placebo (n = 25) groups. They received a low‐calorie diet with 3 g/day NS oil or low‐calorie diet with 3 g/day placebo for 8 weeks. Forty‐nine women (intervention group = 25; placebo group = 24) completed the trial. NS oil concurrent with a low‐calorie diet decreased weight in the NS group compared to the placebo group (?4.80 ± 1.50 vs. ?1.40 ± 1.90 kg; p < 0.01). Comparison of red blood cell superoxidase dismutase (SOD) indicated significant changes in the NS group compared to the placebo group at the end of the study (88.98 ± 87.46 vs. ?3.30 ± 109.80 U/gHb; p < 0.01). But no significant changes in lipid peroxidation, glutathione peroxidase, and total antioxidant capacity concentrations were observed. NS oil concurrent with a low‐calorie diet decreased weight and increased SOD levels in obese women. However, more studies are suggested to confirm the positive effects of NS in obesity and its complications. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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