Dynamic changes in metabolites of the kynurenine pathway in Alzheimer's disease, Parkinson's disease, and Huntington's disease: A systematic Review and meta-analysis.

Background: Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD+), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases. Objectives: The purpose of this systematic review and meta-analysis is to assess the changes in KP metabolites such as TRP, kynurenine (KYN), kynurenic acid (KYNA), Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 5-Hydroxyindoleacetic acid (5-HIAA), and 3-Hydroxyanthranilic acid (3-HANA) in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) patients compared to the control group. Methods: We conducted a literature search using PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE electronic databases to find articles published up to 2022. Studies measuring TRP, KYN, KYNA, AA, 3-HK, 5-HIAA, 3-HANA in AD, PD, or HD patients and controls were identified. Standardized mean differences (SMDs) were used to determine the differences in the levels of the KP metabolites between the two groups. Results: A total of 30 studies compromising 689 patients and 774 controls were included in our meta-analysis. Our results showed that the blood levels of TRP was significantly lower in the AD (SMD=-0.68, 95% CI=-0.97 to -0.40, p=0.000, I2 = 41.8%, k=8, n=382), PD (SMD=-0.77, 95% CI=-1.24 to -0.30, p=0.001, I2 = 74.9%, k=4, n=352), and HD (SMD=-0.90, 95% CI=-1.71 to -0.10, p=0.028, I2 = 91.0%, k=5, n=369) patients compared to the controls. Moreover, the CSF levels of 3-HK in AD patients (p=0.020) and the blood levels of KYN in HD patients (p=0.020) were lower compared with controls. Conclusion: Overall, the findings of this meta-analysis support the hypothesis that the alterations in the KP may be involved in the pathogenesis of AD, PD, and HD. However, additional research is needed to show whether other KP metabolites also vary in AD, PD, and HD patients. So, the metabolites of KP can be used for better diagnosing these diseases.

Zebrafish Modeling of Autism Spectrum Disorders, Current Status and Future Prospective.

Autism spectrum disorder (ASD) refers to a complicated range of childhood neurodevelopmental disorders which can occur via genetic or non-genetic factors. Clinically, ASD is associated with problems in relationships, social interactions, and behaviors that pose many challenges for children with ASD and their families. Due to the complexity, heterogeneity, and association of symptoms with some neuropsychiatric disorders such as ADHD, anxiety, and sleep disorders, clinical trials have not yielded reliable results and there still remain challenges in drug discovery and development pipeline for ASD patients. One of the main steps in promoting lead compounds to the suitable drug for commercialization is preclinical animal testing, in which the efficacy and toxicity of candidate drugs are examined in vivo. In recent years, zebrafish have been able to attract the attention of many researchers in the field of neurological disorders such as ASD due to their outstanding features. The presence of orthologous genes for ASD modeling, the anatomical similarities of parts of the brain, and similar neurotransmitter systems between zebrafish and humans are some of the main reasons why scientists draw attention to zebrafish as a prominent animal model in preclinical studies to discover highly effective treatment approaches for the ASD through genetic and non-genetic modeling methods.

Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes.

Cancer stem cells (CSCs) are subpopulation of cells which have been demonstrated in a variety of cancer models and involved in cancer initiation, progression, and development. Indeed, CSCs which seem to form a small percentage of tumor cells, display resembling characteristics to natural stem cells such as self-renewal, survival, differentiation, proliferation, and quiescence. Moreover, they have some characteristics that eventually can demonstrate the heterogeneity of cancer cells and tumor progression. On the other hand, another aspect of CSCs that has been recognized as a central concern facing cancer patients is resistance to mainstays of cancer treatment such as chemotherapy and radiation. Owing to these details and the stated stemness capabilities, these immature progenitors of cancerous cells can constantly persist after different therapies and cause tumor regrowth or metastasis. Further, in both normal development and malignancy, cellular metabolism and stemness are intricately linked and CSCs dominant metabolic phenotype changes across tumor entities, patients, and tumor subclones. Hence, CSCs can be determined as one of the factors that correlate to the failure of common therapeutic approaches in cancer treatment. In this context, researchers are searching out new alternative or complementary therapies such as targeted methods to fight against cancer. Molecular docking is one of the computational modeling methods that has a new promise in cancer cell targeting through drug designing and discovering programs. In a simple definition, molecular docking methods are used to determine the metabolic interaction between two molecules and find the best orientation of a ligand to its molecular target with minimal free energy in the formation of a stable complex. As a comprehensive approach, this computational drug design method can be thought more cost-effective and time-saving compare to other conventional methods in cancer treatment. In addition, increasing productivity and quality in pharmaceutical research can be another advantage of this molecular modeling method. Therefore, in recent years, it can be concluded that molecular docking can be considered as one of the novel strategies at the forefront of the cancer battle via targeting cancer stem cell metabolic processes.

Anticancer properties of novel zinc oxide quantum dot nanoparticles against breast cancer stem-like cells.

Cancer stem cells (CSCs) play an essential role in cancer development, metastasis, relapse, and resistance to treatment. In this article, the effects of three synthesized ZnO nanofluids on proliferation, apoptosis, and stemness markers of breast cancer stem-like cells are reported. The antiproliferative and apoptotic properties of ZnO nanoparticles were evaluated on breast cancer stem-like cell-enriched mammospheres by MTS assay and flowcytometry, respectively. The expression of stemness markers, including WNT1, NOTCH1, ß-catenin, CXCR4, SOX2, and ALDH3A1 was assessed by real-time PCR. Western blotting was used to analyze the phosphorylation of Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3). Markers of stemness were significantly decreased by ZnO nanofluids, especially sample (c) with code ZnO-148 with a different order of addition of polyethylene glycol solution at the end of formulation, which considerably decreased all the markers compared to the controls. All the studied ZnO nanofluids considerably reduced viability and induced apoptosis of spheroidal and parental cells, with ZnO-148 presenting the most effective activity. Using CD95L as a death ligand and ZB4 as an extrinsic apoptotic pathway blocker, it was revealed that none of the nanoparticles induced apoptosis through the extrinsic pathway. Results also showed a marked inhibition of the JAK/STAT pathway by ZnO nanoparticles; confirmed by downregulation of Mcl-1 and Bcl-XL expression. The present data demonstrated that ZnO nanofluids could combat breast CSCs via decreasing stemness markers, stimulating apoptosis, and suppressing JAK/STAT activity.

Assessment of cancer prevention effect of exercise.

There are many documents about benefits of exercise on human health. However, evidences indicate to positive effect of exercise on disease prevention, understanding of many aspects of this mechanism need more investigations. Determination of critical genes which effect human health.GSE156249 including 12 gene expression profiles of healthy individual biopsy from vastus lateralis muscle before and after 12-week combined exercise training intervention were extracted from gene expression omnibus (GEO) database. The significant DEGs were included in interactome unit by Cytoscape software and STRING database. The network was analyzed to find the central nodes subnetwork clusters. The nodes of prominent cluster were assessed via gene ontology by using ClueGO. Number of 8 significant DEGs and 100 first neighbors analyzed via network analysis. The network includes 2 clusters and COL3A1, BGN, and LOX were determined as central DEGs. The critical DEGs were involved in cancer prevention process.

Expression of Hexokinase in the Proteome Profile of Leishmania major and Crithidia

Objective: The relationship between drug resistance and the expression of hexokinase (HK) has been indicated in leishmaniasis. According to the prolonged treatment period in cutaneous leishmaniasis (CL) patients co-infected with Crithidia in Iran, this study aims to investigate the expression of HK in the proteome of Leishmania major and Crithidia using a proteomic approach. Methods: A total of 205 samples were removed from the lesions of patients in Fars province, Iran, for the characterization of L. major and Crithidia using polymerase chain reaction (PCR). After protein extraction, two-dimensional gel electrophoresis was employed for protein separation. Several spots were isolated for HK determination in the proteomes of L. major and Crithidia using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF/TOF MS). Results: The PCR results showed 5 positive cases for Crithidia and 96 positive cases for L. major. MALDI TOF/TOF MS indicated HK as a common protein in the proteome of L. major and Crithidia. HK was up-regulated in the Crithidia proteome in comparison with the L. major proteome. Conclusion: Since a relationship between HK expression and drug resistance has been indicated in leishmaniasis, the overexpression of HK in Crithidia might be related to the increased duration of the treatment period in CL patients co-infected with Crithidia.

Prevalence of celiac disease in low and high risk population in Asia-Pacific region: a systematic review and meta-analysis.

This systematic review and meta-analysis study was conducted to estimate the pooled prevalence of CD in low and high risk groups in this region. Following keywords were searched in the Medline, PubMed, Scopus, Web of Science and Cochrane database according to the MeSH terms; celiac disease, prevalence, high risk population and Asian-Pacific region. Prevalence studies published from January 1991 to March 2018 were selected. Prevalence of CD with 95% confidence interval (CI) was calculated using STATA software, version 14. The pooled sero-prevalence of CD among low risk group in Asia-Pacific region was 1.2% (95% CI 0.8-1.7%) in 96,099 individuals based on positive anti-tissue transglutaminase (anti-t-TG Ab) and/or anti-endomysial antibodies (EMA). The pooled prevalence of biopsy proven CD in Asia-Pacific among high and low risk groups was 4.3% (95% CI 3.3-5.5%) and 0.61% (95% CI 0.4-0.8%) in 10,719 and 70,344 subjects, respectively. In addition, the pooled sero-prevalence and prevalence of CD in general population was significantly higher in children compared with adults and it was significantly greater in female vs. male (P < 0.05). Our results suggest high risk individuals of CD are key group that should be specifically targeted for prevention and control measures, and screening may prove to have an optimal cost-benefit ratio.

Prevalence of gluten-related disorders in Asia-Pacific region: a systematic review.

BACKGROUND AND AIMS: The epidemiology of gluten-related disorders (GRDs) is still an open field to be explored. We conducted this systematic review based on the current epidemiology knowledge of GRDs, focusing on the changing prevalence of GRDs reported in the Asia-Pacific region. METHODS: We searched Medline, PubMed, Scopus, Web of Science and Cochrane database with the following MeSH terms and keywords: celiac disease (CD), wheat allergy (WA), non-celiac gluten sensitivity (NCGS), dermatitis herpetiformis (DH) and gluten ataxia (GA) and the prevalence studies published from January 1991 to January 2018. Each article was cross-referenced with "Asia-Pacific region" and countries in this region such as Australia, New Zealand, India, Pakistan, Turkey, Iran and others. RESULTS: We included 66 studies, which reported the prevalence of GRDs in the Asia-Pacific region. Prevalence of celiac disease was 0.32%-1.41% in healthy children and 0.05%-1.22% in the adult population, while the prevalence in the high risk population was higher (0.6%-11.8%). Previous studies have shown a very low incidence of dermatitis herpetiformis (DH) (<0.001%) and gluten ataxia (GA) in this area. Few studies on NCGS outbreaks have been found in this area due to the lack of specific diagnostic biomarkers. Wheat allergy (WA), although uncommon in most Asian-Pacific countries, is the most common cause of anaphylaxis in this region. CONCLUSION: The results of this systematic review suggest the need to plan further proper epidemiological studies in order to understand the natural history of GRDs and to assess its burden on health systems.

Dental pulp stem cell transplantation ameliorates motor function and prevents cerebellar atrophy in rat model of cerebellar ataxia.

Cerebellar ataxias (CA) include a range of neurodegenerative disorders hallmarked by deterioration of the cerebellum. Cell replacement therapy (CRT) offers a potential remedy for the diseases associated with the central nervous system (CNS). This study was designed to assess the neurorestorative/protective effects of dental pulp stem cell (DPSC) implantation on a rat model of CA induced by 3-acetylpyridine (3-AP) as a neurotoxin. To begin, human DPSCs were extracted, cultured and phenotypically characterized. Then, experimental ataxia was induced in 20 male adult rats by a single injection of 3-AP and bilateral DPSC transplantation was performed 3 days after 3-AP administration, followed by stereological analysis of cerebellar layers along with assessment of motor skills and inflammatory response. The findings showed that transplantation of DPSCs in a 3-AP model of ataxia ameliorated motor coordination and muscle activity, increased cerebellar volumes of molecular and granular layers plus white matter, reduced the levels of inflammatory cytokines and thwarted the degeneration of Purkinje cells against 3-AP toxicity. Taken together, human DPSCs could be considered as a suitable candidate for CRT-based therapies with a specific focus on CA.

Introducing Transthyretin as a Differentially Expressed Protein in Washing Subtype of Obsessive-Compulsive Disorder.

INTRODUCTION: Obsessive-Compulsive Disorder (OCD) as one of the important mental problems is valuable topic for proteomic research studies to better understand the underlying mechanisms of this disorder. METHODS: In this paper, gel-based proteomic was used to investigate the proteome profile of 16 female patients with OCD, washing subtype before and after treatment with fluoxetine and comparing them with 20 healthy female controls. RESULTS: One of the abnormally expressed protein spots in this study was introduced and examined for protein-protein interaction network analysis via Cytoscape and its plug-ins. Transthyretin (TTR) protein showed significant expression changes (fold change=1.7, P<0.05). While the expression level of TTR is significantly decreased in OCD patients before any treatments, the trend is partially normalized after treatment with fluoxetine in positive responders. Furthermore, TTR interaction profile shows that the proteins interacting with this protein may get affected as this protein expression trend changes in OCD patients. CONCLUSION: TTR can be considered for further studies to be validated as a potential biomarker for OCD.

Lavandula angustifolia Effects on Rat Models of Alzheimer's Disease Through the Investigation of Serum Metabolic Features Using NMR Metabolomics.

BACKGROUND: Alzheimer's Disease (AD) is the most prevalent cause of memory impairment in the elderly population, but the diagnosis and treatment of the disease is still challenging. Lavender aqueous extract has recently been shown to have the potential in clearing Amyloid-beta plaques from AD rat hippocampus. To elucidate the therapeutic mechanisms of lavender, serum metabolic fingerprint of Aß-induced rat Alzheimer's models was investigated through nuclear magnetic resonance spectrometry. METHODS: For the establishment of rat Alzheimer's models, 10 µg of Amyloid beta 1-42 was injected to male Wistar rats. The lavender aqueous extract was injected 20 days after the establishment of the models, once daily for 20 days. Serum samples were collected and metabolite fingerprints were obtained using 500 MHz 1H-NMR spectrometry, following multivariate statistical analyses. The resulted metabolites were then subjected to pathway analysis tools to reveal metabolic pathways affected by the lavender extract treatment. RESULTS: Levels of 10 metabolite markers including alanine, glutamine, serine, isoleucine, valine, carnitine, isobutyrate, pantothenate, glucose and asparagine were reversed nearly to control values after treatment with lavender extract. The results revealed that the most significantly affected pathways during treatment with lavender extract belonged to carbohydrate and amino acid metabolism, including pantothenate and CoA metabolism, glyoxilate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism. CONCLUSION: As lavender extract reversed the direction of changes of some metabolites involved in AD pathogenesis, it was concluded that the extract might play a role in the disease improvement and serve as a potential therapeutic option for the treatment of AD. Moreover, the metabolites which were found in AD rats could serve as a potential marker panel for the disease; however, much further investigation and validation of the results is needed.

Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer's disease.

OBJECTIVES: Neurodegenerative Alzheimer's disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. MATERIALS AND METHODS: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. RESULTS: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. CONCLUSION: The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

Bone reconstruction in rat calvarial defects by chitosan/hydroxyapatite nanoparticles scaffold loaded with unrestricted somatic stem cells.

Calcium phosphates are one of the biomaterials that are used for bone regeneration. In this study, Hydroxyapatite (HAp) nanoparticles with chitosan gel filled with unrestricted somatic stem cells (USSCs) were used for healing calvarial bone in rat model. The healing effects of these injectable scaffolds with and without stem cells for bone regeneration were investigated by computed tomography (CT) analysis and pathology assays after 28 days of grafting. The results of CT analysis showing bone regeneration on the scaffolds, also the amounts of regenerated new bone for USSC scaffold was significantly greater than the scaffold without cell and untreated controls. Therefore, the combination of scaffold especially with USSC is considered as a useful method for bone regeneration.

Regeneration of full-thickness skin defects using umbilical cord blood stem cells loaded into modified porous scaffolds.

In this study, we have demonstrated the ability of cord blood (CB)-derived unrestricted somatic stem cells (USSCs) and chitosan-modified poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffold to promote skin regeneration. Afterward, the scaffolds were evaluated by structural, microscopic, physical, and mechanical assays and cell culture analyses. Results of structural, physical, and mechanical analyses also showed a good resilience and compliance with movement as a skin graft. Cellular experiments showed a better cell adhesion, growth, and proliferation inside the modified scaffolds compared with unmodified ones. In animal models with histological examinations, all groups, excluding the control group especially the groups treated with stem cells, exhibited the most pronounced effect on wound closure, with the statistically significant improvement in wound healing being seen at postoperative day 21. These data suggest that chitosan-modified PHBV scaffold loaded with CB-derived USSCs could significantly contribute to wound repair and be potentially used in the tissue engineering.

Targeting of the signal transducer Smo links microRNA-326 to the oncogenic Hedgehog pathway in CD34+ CML stem/progenitor cells.

Aberrant expression and function of microRNAs (miRNAs) in leukemia have added a new layer of complexity to the understanding of development and progression of the disease state. However, their targeting of specific signaling pathways responsible for the maintenance and survival properties of leukemic stem cell (LSC) still remains to be further clarified. Hedgehog (Hh) signaling, a highly conserved developmental pathway, has been proven as a functional pathway for LSCs, and loss of this pathway impairs the development of BCR-ABL-induced chronic myeloid leukemia (CML) and depletes CML stem cells. Here, we revealed that upregulation of the Hh smoothened (Smo) signal transducer was associated with reduced expression of miR-326 in the CD34(+) cells from a group of patients with CML at diagnosis. Additionally, overexpression of miR-326 led to downregulation of Smo, resulted in decreased cell proliferation and elevated rate of apoptosis in CML CD34(+) cells. Interestingly, restoration of Smo expression levels reversed the effect of miR-326 and rescued K562 cells from the antiproliferative effects of this miRNA. Thus, Smo appears to be an essential target of miR-326 during the pathogenesis of CML. These findings lead us to suggest that downregulation of miR-326 may be a possible mechanism for unrestricted activation of Smo signal transducer of the oncogenic Hh pathway in CML; therefore, the restoration of miR-326 expression could be of benefit in eradicating CD34(+) CML stem/progenitor cells that represent a potential source of relapse in patients suffering CML.

Aberrant microRNA expression and its implications in the pathogenesis of leukemias.

BACKGROUND: MicroRNAs (miRNAs) are a class of non-coding, endogenous, small RNAs that negatively regulate gene expression by inducing degradation or translational inhibition of target mRNAs. Aberrant expression of miRNAs appears to be a common characteristic of hematological malignancies including leukemias. AIM: Here we review the available data supporting a role of aberrant expression of miRNAs in the pathogenesis of leukemias including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). CONCLUSIONS: The expression signatures of miRNAs provide exciting opportunities in the diagnosis, prognosis, and therapy of leukemia. Since miRNAs can function as either oncogenes or tumor suppressor genes in leukemogenesis, the potential of using these small RNAs as therapeutic targets opens up new opportunities for leukemia therapy by either inhibiting or augmenting their activity.

Evaluation of unrestricted somatic stem cells as a feeder layer to support undifferentiated embryonic stem cells.

The use of unrestricted somatic stem cells (USSCs) holds great promise for future clinical applications. Conventionally, mouse embryonic fibroblasts (MEFs) or other animal-based feeder layers are used to support embryonic stem cell (ESC) growth; the use of such feeder cells increases the risk of retroviral and other pathogenic infection in clinical trials. Implementation of a human-based feeder layer, such as hUSSCs that are isolated from human sources, lowers such risks. Isolated cord blood USSCs derived from various donors were used as a novel, supportive feeder layer for growth of C4mES cells (Royan C4 ESCs). Complete cellular characterization using immunocytochemical and flow cytometric methods were performed on murine ESCs (mESCs) and hUSSCs. mESCs cultured on hUSSCs showed similar cellular morphology and presented the same cell markers of undifferentiated mESC as would have been observed in mESCs grown on MEFs. Our data revealed these cells had negative expression of Stat3, Sox2, and Fgf4 genes while showing positive expression for Pou5f1, Nanog, Rex1, Brachyury, Lif, Lifr, Tert, B2m, and Bmp4 genes. Moreover, mESCs cultured on hUSSCs exhibited proven differentiation potential to germ cell layers showing normal karyotype. The major advantage of hUSSCs is their ability to be continuously cultured for at least 50 passages. We have also found that hUSSCs have the potential to provide ESC support from the early moments of isolation. Further study of hUSSC as a novel human feeder layer may lead to their incorporation into clinical methods, making them a vital part of the application of human ESCs in clinical cell therapy.

Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is one of the most important neurodegenerative disorders. It is characterized by dementia including deficits in learning and memory. The present study aimed to evaluate the effects of aqueous extract of lavender (Lavandula angustifolia) on spatial performance of AD rats. METHODS: Male Wistar rats were first divided into control and AD groups. Rat model of AD was established by intracerebroventricular injection of 10 µg Aß1-42 20 d prior to administration of the lavender extract. Rats in both groups were then introduced to 2 stages of task learning (with an interval of 20 d) in Morris water maze, each followed by one probe test. After the first stage of spatial learning, control and AD animals received different doses (50, 100 and 200 mg/kg) of the lavender extract. RESULTS: In the first stage of experiment, the latency to locate the hidden platform in AD group was significantly higher than that in control group. However, in the second stage of experiment, control and AD rats that received distilled water (vehicle) showed similar performance, indicating that the maze navigation itself could improve the spatial learning of AD animals. Besides, in the second stage of experiment, control and AD rats that received lavender extract administration at different doses (50, 100, and 200 mg/ kg) spent less time locating the platform (except for the AD rats with 50 mg/kg extract treatment), as compared with their counterparts with vehicle treatment, respectively. In addition, lavender extract significantly improved the performance of control and AD rats in the probe test, only at the dose of 200 mg/kg, as compared with their counterparts with vehicle treatment. CONCLUSION: The lavender extract can effectively reverse spatial learning deficits in AD rats.

Proteomic analysis in human fibroblasts by continuous exposure to extremely low-frequency electromagnetic fields.

Most people are Exposed to Extremely Low-Frequency Electromagnetic Fields (ELF-EMF). A number of studies have indicated association between exposure to extremely low frequency electromagnetic fields and a variety of cancers. Recently some therapeutic techniques such as repetitive Transcranial Magnetic Stimulation (rTMS) have been used to study localization of brain function, connectively of brain regions and pathophysiology of neuropsychiatric disorders (rTMS utilize low frequency-electromagnetic field). Here, the effect of continuous ELF electromagnetic fields (3 Hz, sinusoidal, 3 h and 4 mT) on the protein expression of human fibroblast cells is investigated via proteomics. The comparison of the 2-DE separated proteins from the exposed and sham (control) cells showed that some protein expressions are affected by radiation. The two proteins that their expression are reduced about 50% are determined as alpha 1 antitrypsin (A1AT) and Transthyretin (TTR). As it is reported that the amounts of these proteins reduced in the pathological conditions it can be concluded that application of ELF-EMF in therapeutic aspects may be to accompanying with their side effects.