Proteomic study of advanced cirrhosis based on HCV to reveal potential biomarkers.

AIM: We aimed to carry out proteomic assessment of long-term effects of hepatitis C on liver. BACKGROUND: Cirrhosis is a condition where liver is damaged and loses its efficiency, and has the high rate of mortality in the world. Proteome profiling may help to identify important proteins and find the pathogenesis Cirrhosis is a condition where liver is damaged and loses its efficiency, and has the high rate of mortality in the world. Proteome profiling may help to identify important proteins and find the pathogenesis. METHODS: Here, by the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), combined with (MALDI-TOF-TOF MS), proteome profile of decompensated HCV cirrhosis is determined compared to healthy matched controls. Furthermore, Cytoscape has used network analysis. The proteome comparison between two groups identified proteins with significant expression changes (p<0.05 and fold change ≥ 1.5). RESULTS: We found upregulation of IGHA1, C3, A1BG, IGKC and one isoform of HP. Also, lower expression of APOA4 and the other spot of HP in advanced cirrhosis patients were revealed based on HCV compared to matched controls. According to network analysis, ALB has been introduced as a key protein, which may play an important role in pathogenesis. CONCLUSION: Integration of the proteomics with protein interaction data led to the identification of several novel key proteins related to the immune system that may reflect the long-term effects of hepatitis C virus on the liver, and can introduce as therapeutic targets for advanced HCV- cirrhosis.

Proteomic analysis of Lactobacillus casei in response to different pHs using two-dimensional electrophoresis and MALDI TOF mass spectroscopy.

BACKGROUND AND OBJECTIVES: Lactobacillus casei, an acid-resistant bacterium, has a protective role against the pathogens. So we aimed to determine the proteome of Lactobacillus casei ATCC39392 strain in response to different pHs of 5 and 7 using proteomic analysis. MATERIALS AND METHODS: Supernatant and bacterial extraction of Lactobacillus casei ATCC39392 adapts at pHs 5 and 7 were isolated using sodium dodecyl sulfate-polyacrylamide gel and two-dimensional gel electrophoresis. The comparison of results showed that 7 protein spots were seen in pH 5 but not in pH 7. Afterward, they were excised and sent for Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) to be identified. RESULTS: Seven different proteins (four secretory and three structural) with different roles in human body health were identified. Prescribed proteins include putative cell wall associated Hydrolase, Glycoside Hydrolase, beta-N-Acetyl hexosaminidase, Histidine Kinase, Chaperonin, metal dependent Hydrolase and Lysozyme. CONCLUSION: Seven isolated proteins with anti-cancer and digestive impresses are proper subjects in therapy or drug delivery approaches especially oral drug usage for protection against stomach acidic area.

Serum Proteomic Study of Women With Obsessive-Compulsive Disorder, Washing Subtype.

INTRODUCTION: Many genetic studies are conducted on Obsessive-Compulsive Disorder (OCD). however, a high-throughput examination of proteome profile of this severe disease has not been performed yet. METHODS: Here, the proteomic study of OCD patients' serum samples was conducted by the application of Two-Dimensional Electrophoresis (2DE) followed by Mass Spectrometry (MALDI-TOF-TOF). RESULTS: A total of 240 protein spots were detected and among them, five significant differentially expressed protein spots with the fold change of ≥1.5 were considered for further evaluations. These proteins include IGKC, GC, HPX, and two isoforms of HP. While IGKC and HP show down-regulation, GC and HPX indicate up-regulation. Moreover, a validation study of overall HP levels in patients' serum via nephelometric quantification confirmed the lower levels of this protein in the serum of OCD patients. Additionally, enrichment analysis and validation test revealed that inflammation is one of most dominant processes in OCD. CONCLUSION: It is suggested that these candidate proteins and their underlying processes (especially, inflammation) may be linked to OCD pathophysiology and can promise a clinical use after extensive validation studies.

Fluoxetine Regulates Ig Kappa Chain C Region Expression Levels in the Serum of Obsessive-Compulsive Disorder Patients: A proteomic Approach.

Obsessive-Compulsive Disorder (OCD) is one of the most common mental conditions. Proteome profiling may help identifying important proteins and finally shed lights to complexity of OCD underlying mechanisms. Here, by the application gel-based proteomic approach the proteome profile of patients with washing subtype of OCD before and after treatment with Fluoxetine (positive responders) are compared to healthy matched controls. However, only one of the differentially expressed proteins is examined and introduced in this paper. Proteomic analysis was done by the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), combined with (MALDI-TOF-TOF MS)-based. Furthermore, network analysis and biological annotation were handled by Cytoscape Plug-in and CluePedia. The proteome comparison between groups identified protein with the significant expression changes (p<0.05 and fold change ≥ 1.5). While the expression level of Ig Kappa Chain C Region is significantly decreased in OCD patients before any treatments, the trend is almost normalized after treatment with Fluoxetine in positive responders. In addition, interaction profile of IGKC shows that the interacting proteins may be affected as the expression pattern of IGKC changes in OCD patients. In conclusion, IGKC may be introduced as potential biomarker in our study; yet, investigation in bigger sample size and application of validation methods is a requirement.

Serum Proteomic Profiling of Obsessive-Compulsive Disorder, Washing Subtype: A Preliminary Study.

INTRODUCTION: Obsessive-Compulsive Disorder (OCD) is a disabling mental condition that its proteomic profiling is not yet investigated. Proteomics is a valuable tool to discover biomarker approaches. It can be helpful to detect protein expression changes in complex disorders such as OCD. METHODS: Here, by the application of 2D gel electrophoresis (2DE), a pilot study of serum proteome profile of females with washing subtype of OCD was performed. Serum samples were obtained from females with washing subtype of OCD. Following the protein extraction from the serum with acetone perception, the samples were subjected to 2DE for separation based on pI and molecular weight (MW) with triple replications. Finally, the protein spots were visualized using Coomassie blue staining method and analyzed by Progenesis SameSpots software. Furthermore, protein-protein interaction (PPI) network analysis was handled by the application of Cytoscape software. RESULTS: The results suggested that 41 matched spots demonstrated significant expression alterations among which 5 proteins including immunoglobulin heavy constant alpha-1 (IGHA1), apolipoprotein A-4 (APOA4), haptoglobin (HP), protein α-1-antitrypsin (SERPINA1), and component 3 (C3) were identified by database query. Additionally, PPI network analysis indicated the central role of SERPINA1 and C3 in the network integrity. However, albumin (ALB), amyloid precursor protein (APP), and protein α-1-antitrypsin (APOA1) proteins were important in OCD PPI network as well. The identified proteins were related to 3 processes: acute-phase response, hydrogen peroxide catabolic process, and regulation of triglyceride metabolic process. CONCLUSION: It was concluded that these proteins may have a fundamental role in OCD pathogenesis. Moreover, the dysregulation of inflammatory and antioxidant systems in OCD risk was suggested by the current study. However, evaluation of bigger sample sizes and application of mass spectrometry are essential requirements to confirm this preliminary evaluation.

Polyunsaturated fatty acids and modulation of cholesterol homeostasis in THP-1 macrophage-derived foam cells.

Transformation of macrophages to foam cells is determined by the rates of cholesterol uptake and efflux. This study uses a real time RT-PCR technique to investigate the role of conjugated linoleic acid (CLA), α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the regulation of the ATP-binding cassette A1 (ABCA1) and liver X receptor α (LXR) genes, which are involved in cholesterol homeostasis. Accordingly, these fatty acids significantly reduced the total, free and esterified cholesterols within the foam cells. While the expression of the ABCA1 and LXRα genes was increased in the presence of the pharmacological LXRα ligand, T0901317, their mRNA expression was not significantly affected by CLA, ALA and EPA. These results suggest that although polyunsaturated fatty acids have an effect on cholesterol homeostasis, they cannot change the expression of the ABCA1 and LXRα genes. Alternatively, several other genes and proteins may be involved.