Sharif Digital Repository

Background: Focal segmental glomerulosclerosis (FSGS) is considered one of the most severe glomerular diseases and around 80% of cases are resistant to steroid treatment. Since a large proportion of steroid-resistant (SR) FSGS patients progress to end-stage renal disease, other therapeutic strategies may benefit this population. However, identification of non-invasive biomarkers to predict this high-risk population is needed. Objective: We aimed to identify the biomarker candidates to distinguish SR from steroid-sensitive (SS) patients using metabolomics approach and to identify the possible molecular mechanism of resistance. Methods: Urine was collected from biopsy-proven FSGS patients... 

Structure and conformational properties of valsartan were studied by advanced NMR techniques and quantum calculation methods. Potential energy scanning using B3LYP/6-311++g** and B3LYP-D3/6-311++g** methods were performed and four conformers (V1-V4) at minimum points of PES diagram were observed. According to the NMR spectra in acetone-d6, there are two conformers (M and m) with mM = 0.52 ratio simultaneously and energy barriers of the two conformers were predicted from chemical shifts and multiplicities. While, intramolecular hydrogen bond at tetrazole ring and carboxylic groups prevent the free rotation on N6[sbnd]C11 bond in M-conformer, this bond rotates freely in m-conformer. On the... 

Experimental and theoretical conformational study of repaglinide in chloroform and dimethyl sulfoxide was investigated. By applying potential energy scanning (PES) at B3LYP/6-311++g** and B3LYP-D3/6-311++g** level of theory on rotatable single bonds, four stable conformers (R1-R4) were identified. Spin-spin coupling constant values were obtained from a set of 2D NMR spectra (H[sbnd]H COSY, H[sbnd]C HMQC and H[sbnd]C HMBC) and compared to its calculated values. Interestingly, from 1HNMR and 2D-NOESY NMR, it has been found that repaglinide structure is folded in CDCl3 and cause all single bonds to rotate at an extremely slow rate. On the other hand, in DMSO-d6, with strong solvent-solute... 

The structural and conformational behavior of gemcitabine (20; 20-diuoro cytidine) was investigated by advanced NMR experiments and a computational quantum mechanical method (DFT) using Potential Energy Scanning (PES) in gas and solution phases in the Polarizable Continuum Model (PCM). Three stable conformers (G1, G2, and G3) were predicted from minimum points in a potential energy diagram. In order to measure coupling constant values, a set of 2D spectra (H-H COSY, H-C HMQC, and H-C HMBC) was analyzed. Optimized structures and spin-spin coupling constant calculations in gas and solution phases were performed by B3LYP/6-311++G(d,p) method. Both energy and NMR parameters showed that G1-form... 

Background/Objectives: Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. Subjects/Methods: Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects... 

Objective(s): Hepatitis B virus infection causes chronic disease such as cirrhosis and hepatocellular carcinoma. The metabolomics investigations have been demonstrated to be related to pathophysiologic mechanisms in many disorders such as hepatitis B infection. The aim of this study was to investigate the saliva metabolic profile of patients with chronic hepatitis B infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Materials and Methods: Saliva from 16 healthy subjects and 20 patients with chronic hepatitis B virus were analyzed by nuclear magnetic resonance (NMR). Then, multivariate statistical analysis was performed to identify... 

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The 13C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible... 

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The 13C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible... 

Background: Nonalcoholic fatty liver disease (NAFLD) is the most abundant chronic liver disorder, because racial and ethnic differences may influence prevalence and severity of NAFLD. Objectives: This metabolomic study was conducted to identify the metabolic biomarkers and determine the mechanism of progress of NAFLD in Iranian patients. Methods: Serum samples were collected from 75 participants (37 healthy controls and 38 patients with NAFLD) after an overnight fast. The metabolome of all samples were determined by nuclear magnetic resonance (NMR) and were compared by multivariate statistical analysis. Results: Totally, 19 metabolomic biomarkers were identified by NMR. Compared to healthy... 

Calcineurin is an essential calcium-activated serine/threonine phosphatase. The six NMR-observable methionine methyl groups in the catalytic domain of human calcineurin Aα (CNA) were assigned and used as reporters of the presence of potential cis-trans isomers in solution. Proline 84 is found in the cis conformation in most calcineurin X-ray structures, and proline 309, which is part of a highly conserved motif in phosphoprotein phosphatases, was modeled with a cis peptide bond in one of the two molecules present in the asymmetric unit of CNA. We mutated each of the two prolines to alanine to force the trans conformation. Solution NMR shows that the P84A CNA mutant exists in two forms,... 

Objective(s): The molecular basis of “metabolically healthy obese” and “metabolically unhealthy non-obese” phenotypes is not fully understood. Our objective was to identify metabolite patterns differing in obese (metabolically healthy vs unhealthy (MHO vs MUHO)) and non-obese (metabolically healthy vs unhealthy (MHNO vs MUHNO)) individuals. Materials and Methods: This case-control study was performed on 86 subjects stratified into four groups using anthropometric and clinical measurements: MHO (21), MUHO (21), MHNO (22), and MUHNO (22). Serum metabolites were profiled using nuclear magnetic resonance (NMR). Multivariate analysis was applied to uncover discriminant metabolites, and enrichment... 

Learning a foreign language encompasses a process of trial and error that can lead to the progression of the learner's interlanguage, meaning that the learners make use of their language knowledge that receives feedback and brings about progress through diagnosis of the problems and being corrected by the teacher. Therefore, there exists a need to analyze the underlying reasons causing the students to remain taciturn with a low willingness to communicate (WTC) during a language class. There has been much work done investigating the role of the learner's stable personal characteristics (traits) along with their situational changes at a specific time (states) that influence the student's... 

Using 3-D scanned data to analyze and extract pore network plays a vital role in investigation of porous media's characteristics. In this paper, a new simple method is developed to detect pores and throats for analyzing the connectivity and permeability of the network. This automated method utilizes some of the common and well-known image processing functions which are widely accessible by researchers and this has led to an easy algorithm implementation. In this method, after polishing and quality control of images, using city-block distance function and watershed segmentation algorithm, pores and throats are detected and 3-D network is produced. This method can also be applied on 2-D images... 

In this paper, we try to recognize and distinguish different groups of arrhythmia using novel features which have been obtained from the heart rate's phase space in recent years. For this purpose, we used Triangular Phase Space Mapping (TPSM) and Parabolic Phase Space Mapping (PPSM). For recognition, we used three groups of 15 subjects using the Physionet database (Arrhythmia, Congestive Heart Failure (CHF), and Atrial Fibrillation (AF)) with Normal Sinus Rhythm (NSR). The obtained features discriminate arrhythmia from NSR by p