مقالات رزومه دکتر محمود میرزایی

By the importance of dealing with metabolic syndrome (MetS), this work was performed to systematically review available articles on effects of stevia on hypertension as a leading risk factor of metabolic syndrome. The stevia extracts are natural resource of non-caloric sweeteners and they attracted attentions of researchers especially in recent years for dealing with the issues of metabolic syndrome. To this aim, stevia effects on hypertension were reviewed based on the obtained results of original research publications of the following electronic databases: Web of Science, Scopus, and PubMed, from 2010 to June 2022. The following search strategy was used: (stevia OR stevia rebaudiana OR sweet leaf OR stevioside) AND (hypertension OR blood pressure). Six articles were eligible to be included in this review; three in vivo studies, one in vivo/in vitro study, and two clinical trials. Based on the results of in vivo studies, positive effects of stevia on lowering blood pressure were found besides observing an enzymatic inhibition activity through the in vitro results. The results of one of clinical trials reported a significant reduction in blood pressure after twelve weeks of stevia consumption, but the other one did not report any significant effect. Although the relatively low methodological rigor of these experiments limits the strength of these findings, further clinical trials and regulatory assessments are warranted.

Density functional theory (DFT) calculations were performed to investigate the features of vitamin B3 (Vit-B3) in oil and water environments. Two up and down structural conformations were found based on the orientation of hydrogen atom of attached carboxylic acid group to pyridine scaffold, in which the up-conformation was found more suitable than the down-conformation. The models were stabilized in gas phases and 1-octanol and water solvents environments to explore the partition coefficient (LogP) for each conformation. In addition, the electronic features were investigated based on frontier molecular orbital levels. The results of this work indicated a higher suitability of formation for the up-conformation in all three environments and the highest suitability of formation of both up and down conformations in water medium. Accordingly, the LogP value was found smaller than one indicating watery tendency for the models. As a final remark, the structural and electronic features of Vit-B3 indicated insights into its development for further applications.

In phytochemical analysis, Jacein derivatives: 5,7,4''-trihydroxy-3,6,3''-trimethoxyflavone-7(β)-D-glucopyranoside (1), and 3-demethyljacein: 3,5,7,4''-tetrahydroxy-6,3''-dimethoxyflavone-7(β)-D-glucopyranoside (2) were isolated from Campylopus schmidii (C. schmidii) for the first time. The structures were determined by interpretation of NMR, UV, and Mass spectra. To check the roles of ER stress and consequent apoptosis in MCF-7 cell by these compounds, UPR signaling pathway was further examined by analysis of expression of ER stress-related genes. In MTT assay, compounds 1-2 showed cytotoxicity activity against MCF-7 (A) and MDA-MB cells (B) with IC50 values (μM) of 1) 60.04 ± 7.98 (A), and > 200 (B); 2) 42.89 ± 1.91 (A), and 85.31 ± 2.68 (B). The Annexin/PI flow cytometry apoptosis of tested compounds 1-2 was increased significantly in a dose-dependent manner. For example, MCF-7 treatment at the concentration of 100 μM of compounds 1, 2 resulted in total apoptosis (early + late) of 42.04 (18.1 + 24.0), and 66.49 (2.7 + 63.8)%, respectively.  Fluorescence microscopy analysis detected an increased protein aggregation, indicating induced ER stress with a marked increase in XBP-1, sXBP-1, ATF-4, and CHoP compared to untreated cells. In-silico characterization, suggested that Adenosine diphosphate site (A-site) and quercetin site (Q-Site) in IRE1a enzyme are both available interacting sites of a target for the investigated ligands but with different strengths of interactions. The results indicated that the ligand∼A-Site complexes are stronger than the ligand∼Q-Site complexes, but the already available ADP ligand in cells does not allow other ligands to interact with the A-Site and cause them to bond in Q-Site.

Density functional theory (DFT) approach was employed to investigate relaxation processes of each of pyrimidine nucleobases (NBs); cytosine (C), thymine (T) and uracil (U), at the Cubane Cluster Surface (CCS). The main idea was about providing a material for recognition of NBs, in which a nanostructure form of cubane (CCS) was first generated by optimization process. In the next step, relaxation processes of each of NBs at the surface were investigated to examine the function of such system for NBs recognition. The results indicated that the electronic based molecular properties could work as proper parameters for recognizing such molecular system, in which energy gap (EG) could be referred for the purpose. Measuring EG could help to recognize the complexes of CCS-C, CCS-T and CCS-U from each other. Strength of such complex formations was investigated using values of binding energy (BE); CCS-U > CCS-C > CCS-T. Total results of EG, BE and additional atomic scale properties indicated that the investigated CCS could work very well to recognize U as the characteristic NB of RNA.

Natural products have been always using for several types of applications by humankind for so many years. Food and medical applications have been seen very much important for such products in their original forms or reproduction in new forms. As a main resource for generating so many other compounds, synthetic derivatives have been evaluated for the essential extractions of natural products for more specified applications especially for medical core with controlled dosage medication and compounds. Therefore, recognition of potency of natural products for such specified application have been always seen as a dominant factor for undergoing further improvements in this case. Besides the original extracted essentials, modifying chemical structures could help for lead optimization of such important compounds for possible efficient cares. Indeed, lead optimization could be provided very well by employing in silico approach for potent chemical compounds up to reaching them to specified medication.

It has been expected that AS1411 aptamer could work against the cancer cells. Although the general information is available, there is still lack of details for the purpose. Therefore, activity of AS1411 aptamer against the nucleolin (NCL) target of cancer cells has been investigated in current work at the molecular scale. In addition, the same features have been also investigated for examining the activity of AT11, one of AS1411 derivatives. 

This work has been done employing in silico Molecular Docking simulations. Ten starting 3D configurations have been considered for each aptamer to be docked against the NCL target. Conformational search processes of ligands against the target indicated that the starting configuration of ligand could play an important role in determining the final complex formation in both of quantitative and qualitative aspects. 

A04 and B01 are those starting configurations of AS1411 and AT11 making the strongest complexes with the NCL target among other ligands. The analyses indicated that the complexes of AT11 are slightly stronger than those of AS1411, in which the NCL target structure is more involved in the chelated complexes with the AT11 in comparison with the AS1411. 

AS1411 and AT11 are specified for targeting the NCL of cancer cells for the diagnosis and therapeutic purposes. They have reasonable binding affinity and could work as possible inhibitors of NCL.

In this work, phthalocyanine and its OCH3 derivatives were investigated to see their photosensitization characteristics for producing singlet molecular oxygen, which is important in photodynamic therapy type-II. All structures were first optimized to achieve the minimized energy 3D models Subsequently, they were prepared for the photosensitization investigations. All the experiments were conducted based on the density functional theory calculations. The energy absorption and emission observed between the occupied and unoccupied molecular orbitals based on the required energy for excitation and the corresponding energy of emission. The results indicated that the OCH3 models could be expected to be safer than the original phthalocyanin by their required energy at longer wavelengths. The ratio of singlet molecular oxygen generation was found to be 1:1 for each of the OCH3 derivatives.

Depression is a mood disorder which leads to sadness, emptiness, loss of interest and energy for the patient. Feeling, Thinking and behaving are all influenced by the effects of depression causing a variety of emotional and physical problems in considerable numbers of people all around the world. Herein, brain chemistry plays an important role in determination and also treatment of depression for individuals. During the last decade, so many researchers have dedicated their efforts to detect the most effective potent natural products with antidepressant activities, which reveal the importance of herbal natural products to be considered as psychoactive drugs.