Advances in proteomics analytical techniques

   Proteins are fundamental components of cells which mediate many essential biological processes. Proteomics is a rapidly growing field for the study of proteome, the protein complement expressed by the genome of an organism or cell type. The large-scale analysis of proteins leads to a more comprehensive view of molecular and cellular pathways that improves the overall understanding of the complex processes supporting the living systems. The analysis of proteome is significantly challenging due to high dynamic range and difficulties in assessment of low abundance proteins and the absence of efficient purification and identification techniques. A variety of methods have been utilized for protein studies including gel-based techniques, protein microarrays, mass spectrometry-based approaches such as MALDI and SELDI, high and ultra-performance liquid chromatography and fourier transform ion cyclotron resonance mass spectrometry. NMR spectroscopy and X-Ray crystallography methods are also used for structural study of proteins. This review aims to give a brief overview of some of the above techniques and their most recent advances. We also introduce Proteominer, a recent protein enrichment technology for the exploration of the entire proteome conten

Investigating the Mechanism of Arsenic-induced Ferroptosis in the Skin

Background: Ferroptosis, an oxidative and iron-dependent cell death, is a new type of regulated cell death. There are few studies on the mechanisms of ferroptosis in the skin and related diseases. Arsenic is shown to induce ferroptosis cell death. This study aimed to decipher the relationship between arsenic exposure and ferroptosis cell death in the skin. Methods: Arsenic-gene interactions were obtained. Then, skin-specific arsenic-gene interactions were screened. Ferroptosis-related genes were identified. Analysis of functional and biological interactions was performed to identify possible mechanisms. Results: The arsenic-gene interactions and the ferroptosis-related genes showed an overlap of 59 genes. Functional enrichment, protein-protein interaction, and transcription factor (TF)/miRNA target gene interaction analyses were used to look into the mechanism of arsenic-induced ferroptosis in the skin. ACTB, CTNNB1, HSPA8, SRC, RACK1, CD44, and SQSTM1 were identified as key proteins. Gene ontology analysis of these proteins indicated the mitochondrial morphology and functionality changes following arsenic-induced ferroptosis in the skin. HIF1A and SP1 TFs regulate a large number of genes compared to other TFs. Ten miRNAs with high interaction with ferroptosis-associated genes were identified. Conclusion: This work investigated the mechanism of arsenic-induced ferroptosis in the skin and identified key genes and regulators, and functional analysis highlighted the role of mitochondria in this skin exposure

Investigating the Mechanism of Arsenic-induced Ferroptosis in the Skin

Background: Ferroptosis, an oxidative and iron-dependent cell death, is a new type of regulated cell death. There are few studies on the mechanisms of ferroptosis in the skin and related diseases. Arsenic is shown to induce ferroptosis cell death. This study aimed to decipher the relationship between arsenic exposure and ferroptosis cell death in the skin. Methods: Arsenic-gene interactions were obtained. Then, skin-specific arsenic-gene interactions were screened. Ferroptosis-related genes were identified. Analysis of functional and biological interactions was performed to identify possible mechanisms. Results: The arsenic-gene interactions and the ferroptosis-related genes showed an overlap of 59 genes. Functional enrichment, protein-protein interaction, and transcription factor (TF)/miRNA target gene interaction analyses were used to look into the mechanism of arsenic-induced ferroptosis in the skin. ACTB, CTNNB1, HSPA8, SRC, RACK1, CD44, and SQSTM1 were identified as key proteins. Gene ontology analysis of these proteins indicated the mitochondrial morphology and functionality changes following arsenic-induced ferroptosis in the skin. HIF1A and SP1 TFs regulate a large number of genes compared to other TFs. Ten miRNAs with high interaction with ferroptosis-associated genes were identified. Conclusion: This work investigated the mechanism of arsenic-induced ferroptosis in the skin and identified key genes and regulators, and functional analysis highlighted the role of mitochondria in this skin exposure

Potential Molecular Mechanisms of Bisphenol A in Obesity Development

Bisphenol A (BPA), an endocrine disruptor, is associated with metabolic disorders. However, several studies have suggested that exposure to BPA can cause obesity. It has recently got more attention from scientists as a risk factor for obesity due to its ability to mimic natural estrogens and bind to their receptors. Nonetheless, the molecular mechanism underpinning the environmental etiology of metabolic disorders has not been not fully clarified. In this regard, BPA exposure directly disrupts endocrine regulation, neuroimmune and signaling pathways, and gut microbes, resulting in obesity. In addition, epidemiological studies have revealed a significant relationship between BPA exposure and the development of obesity, although conflicting results have been reported. Therefore, this review summarized the possible role and molecular mechanisms associated with BPA exposure that may lead to obesity based on in vivo and in vivo studies

Identification of Agents with Potential Leishmania Malate Dehydrogenase Inhibitor Activity: A Proteomic and Molecular Docking Approach

Background and purpose: Leishmaniasis is one of the most important infectious diseases caused by different species of the Leishmania, which is a public health problem worldwide. So far, no effective vaccine is introduced for this disease and drug therapy is associated with many side effects. Therefore, this study was designed to identify novel FDA-approved compounds with anti-leishmanial activity. Materials and methods: In this experimental study, proteomics, protein network analysis, and molecular docking were used. Protein profile was identified by LC-MS/MS and protein network analysis was performed using Cytoscape. Processing of the compound structure and molecular docking was performed by HyperChem and AutoDock Vina, respectively. Finally, docking results were interpreted by LigPlot+. Results: Based on proteomics and protein network analysis, glycosomal malate dehydrogenase was suggested as a potential drug target. Among the compounds, the best docking results were associated with Conivaptan and Avodart with a binding energy level of -10.5 and -10.2, respectively. Also, molecular docking studies showed that the most important bonds involved in drug-receptor binding were hydrogen and hydrophobic bonds. Conclusion: The current study demonstrated the importance of integrated proteomics, protein network and docking to identify novel compounds with anti-Leishmania properties. According to this study, Conivaptan and Avodart, also approved by the Food and Drug Administration, are effective inhibitors of glycosomal malate dehydrogenase in Leishmania major and Leishmania tropica which meanwhile require further in-vitro and in-vivo experiments

Resveratrol: A miraculous natural compound for diseases treatment

Resveratrol (3, 5, 4′‐trihydroxystilbene) is a nonflavonoid polyphenol that naturally occurs as phytoalexin. It is produced by plant sources such as grapes, apples, blueberries, plums, and peanut. This compound has critical roles in human health and is well known for its diverse biological activities such as antioxidant and anti‐inflammatory properties. Nowadays, due to rising incidence of different diseases such as cancer and diabetes, efforts to find novel and effective disease‐protective agents have led to the identification of plant‐derived compounds such as resveratrol. Furthermore, several in vitro and in vivo studies have revealed the effectiveness of resveratrol in various diseases such as diabetes mellitus, cardiovascular disease, metabolic syndrome, obesity, inflammatory, neurodegenerative, and age‐related diseases. This review presents an overview of currently available studies on preventive properties and essential molecular mechanisms involved in various diseases

Potential Molecular Mechanisms of Bisphenol A in Obesity Development: Bisphenol A and obesity

Bisphenol A (BPA), an endocrine disruptor, is associated with metabolic disorders. However, several studies have suggested that exposure to BPA can cause obesity. It has recently got more attention from scientists as a risk factor for obesity due to its ability to mimic natural estrogens and bind to their receptors. Nonetheless, the molecular mechanism underpinning the environmental etiology of metabolic disorders has not been not fully clarified. In this regard, BPA exposure directly disrupts endocrine regulation, neuroimmune and signaling pathways, and gut microbes, resulting in obesity. In addition, epidemiological studies have revealed a significant relationship between BPA exposure and the development of obesity, although conflicting results have been reported. Therefore, this review summarized the possible role and molecular mechanisms associated with BPA exposure that may lead to obesity based on in vivo and in vivo studies

Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic β-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated