A critical review of the recent concept of regulatory performance of DNA Methylations, and DNA methyltransferase enzymes alongside the induction of immune microenvironment elements in recurrent pregnancy loss.

Recurrent pregnancy Loss (RPL)is a frequent and upsetting condition. Besides the prevalent cause of RPL including chromosomal defects in the embryo,the effect of translational elements like alterations of epigenetics are of great importance. The emergence of epigenetics has offered a fresh outlook on the causes and treatment of RPL by focusing on the examination of DNA methylation. RPL may arise as a result of aberrant DNA methylation of imprinted genes, placenta-specific genes, immune-related genes, and sperm DNA, which may have a direct or indirect impact on embryo implantation, growth, and development. Moreover, the distinct immunological tolerogenic milieu established at the interface between the mother and fetus plays a crucial role in sustaining pregnancy. Given this, there has been a great deal of interest in the regulation of DNA methylation and alterations in the cellular components of the maternal-fetal immunological milieu. The research on DNA methylation's role in RPL incidence and the control of the mother-fetal immunological milieu is summed up in this review.

microRNAs, oxidative stress, and genotoxicity as the main inducers in the pathobiology of cancer development.

Cancer is one of the most serious leading causes of death in the world. Many eclectic factors are involved in cancer progression including genetic and epigenetic alongside environmental ones. In this account, the performance and fluctuations of microRNAs are significant in cancer diagnosis and treatment, particularly as diagnostic biomarkers in oncology. So, microRNAs manage and control the gene expression after transcription by mRNA degradation, or also they can inhibit their translation. Conspicuously, these molecular structures take part in controlling the cellular, physiological and pathological functions, which many of them can accomplish as tumor inhibitors or oncogenes. Relatively, Oxidative stress is defined as the inequality between the creation of reactive oxygen species (ROS) and the body's ability to detoxify the reactive mediators or repair the resulting injury. ROS and microRNAs have been recognized as main cancer promoters and possible treatment targets. Importantly, genotoxicity has been established as the primary reason for many diseases as well as several malignancies. The procedures have no obvious link with mutagenicity and influence the organization, accuracy of the information, or fragmentation of DNA. Conclusively, mutations in these patterns can lead to carcinogenesis. In this review article, we report the impressive and practical roles of microRNAs, oxidative stress, and genotoxicity in the pathobiology of cancer development in conjunction with their importance as reliable cancer biomarkers and their association with circulating miRNA, exosomes and exosomal miRNAs, RNA remodeling, DNA methylation, and other molecular elements in oncology.

Identification of Lilium ledebourii antiproliferative compounds against skin, bone and oral cancer cells.

Objective: This study aimed at the evaluation of anti antiproliferative activity of Lonicera nummularifolia, Lilium ledebourii, Campsis radicans and Parthenocissus quinquefolia extracts. Materials and Methods: The extract was taken from the fresh leaves and bulbs of the plants by maceration method in the dark. After separating the solvent, the remaining dry matter was added to the culture medium containing G292, A431 and KB cancer and HGF-1 normal cells. Cytotoxicity tests, as well as cell cycle and apoptosis tests were performed on cells treated with dry substances and untreated cells. Finally, the most effective extract was separated into fractions by preparative HPLC and the effective fraction was characterized by Triple-Quad LC/MS connected to the UHPLC system. Results: All extracts significantly enhanced cell death rate in the three cancer cell lines more than the HGF-1 line. The Methanolic extract of L. ledebourii bulbs exhibited considerable efficacy on apoptosis induction in the cancer cell lines. It seems that the mode of action for L. ledebourii methanolic extract is mediated through increased BID/MAPK14 expression and decreased MDM2/BCL2/MYC expression, which led to activation of the p53 protein-induced apoptosis. It was also determined that the effective fraction of L. ledebourii methanolic extract consists of substances such as caffeic acid, ferulic acid, coumarin acid, catechin and apigenin. Conclusion: Overall, the findings suggest that L. ledebourii is a promising source of bioactive compounds with anticancer properties.

Analytical and therapeutic profiles of DNA methylation alterations in cancer; an overview of changes in chromatin arrangement and alterations in histone surfaces.

DNA methylation is the most important epigenetic element that activates the inhibition of gene transcription and is included in the pathogenesis of all types of malignancies. Remarkably, the effectors of DNA methylation are DNMTs (DNA methyltransferases) that catalyze de novo or keep methylation of hemimethylated DNA after the DNA replication process. DNA methylation structures in cancer are altered, with three procedures by which DNA methylation helps cancer development which are including direct mutagenesis, hypomethylation of the cancer genome, and also focal hypermethylation of the promoters of TSGs (tumor suppressor genes). Conspicuously, DNA methylation, nucleosome remodeling, RNA-mediated targeting, and histone modification balance modulate many biological activities that are essential and indispensable to the genesis of cancer and also can impact many epigenetic changes including DNA methylation and histone modifications as well as adjusting of non-coding miRNAs expression in prevention and treatment of many cancers. Epigenetics points to heritable modifications in gene expression that do not comprise alterations in the DNA sequence. The nucleosome is the basic unit of chromatin, consisting of 147 base pairs (bp) of DNA bound around a histone octamer comprised of one H3/H4 tetramer and two H2A/H2B dimers. DNA methylation is preferentially distributed over nucleosome regions and is less increased over flanking nucleosome-depleted DNA, implying a connection between nucleosome positioning and DNA methylation. In carcinogenesis, aberrations in the epigenome may also include in the progression of drug resistance. In this report, we report the rudimentary notes behind these epigenetic signaling pathways and emphasize the proofs recommending that their misregulation can conclude in cancer. These findings in conjunction with the promising preclinical and clinical consequences observed with epigenetic drugs against chromatin regulators, confirm the important role of epigenetics in cancer therapy.

Performance of DNA Methylation on the Molecular Pathogenesis of Helicobacter pylori in Gastric Cancer; targeted therapy approach.

Gastric cancer (GC) is a significant cause of cancer mortality which has led to focused exploration of the pathology of GC. The advent of genome-wide analysis methods has made it possible to uncover genetic and epigenetic fluctuation such as abnormal DNA methylation in gene promoter regions that is expected to play a key role in GC. The study of gastric malignancies requires an etiological perspective, and Helicobacter pylori (H. pylori) was identified to play a role in GC. H. pylori infection causes chronic inflammation of the gastric epithelium causing abnormal polyclonal methylation, which might raise the risk of GC. In the last two decades, various pathogenic factors by which H. pylori infection causes GC have been discovered. Abnormal DNA methylation is triggered in several genes, rendering them inactive. In GC, methylation patterns are linked to certain subtypes including microsatellite instability. Multiple cancer-related processes are more usually changed by abnormal DNA methylation than through mutations, according to current general and combined investigations. Furthermore, the amount of acquired abnormal DNA methylation is heavily linked to the chances of developing GC. Therefore, we investigated abnormal DNA methylation in GC and the link between methylation and H. pylori infection.

Novel Biomarkers of microRNAs in Gastric Cancer: An Overview from Diagnosis to Treatment.

Gastric cancer (GC) is the fourth most frequent disease in the world and the second cause of cancer-related death. In this way, over 80% of diagnoses are made in the middle to advanced degrees of the disease, underscoring the requirement for innovative biomarkers that can be identified quickly. Meaningly, biomarkers that can complement endoscopic diagnosis and be used to detect patients with a high risk of GC are desperately needed. These biomarkers will allow for the accurate prediction of therapy response and prognosis in GC patients, as well as the development of an optimal treatment strategy for each individual. Conspicuously, microRNAs (miRNAs) and small noncoding RNA regulate the expression of target mRNA, thereby modifying critical biological mechanisms. According to the data, abnormally miRNAs expression in GC is linked to tumor growth, carcinogenesis, aggression, and distant metastasis. Importantly, miRNA expression patterns and nextgeneration sequencing (NGS) can also be applied to analyze different kinds of tissues and cancers. Given the high death rates and poor prognosis of GC, and the absence of a clinical diagnostic factor that is adequately sensitive to GC, research on novel sensitive and specific markers for GC diagnosis is critical. In this review, we examine the latest research findings that suggest the feasibility and clinical utility of miRNAs in GC.

Adjuvant Effects of Pseudomonas aeruginosa Flagellin on the Immunological Patterns of the HIV-1 Vaccine Candidate: Vaccine Formulations Versus Different Routes of Immunization.

New strategies to increase the immune response to HIV-1 vaccine using immunological adjuvants such as Toll-like receptor agonists are needed. In this study, HIV-1 p24-Nef and conjugated form of the vaccine candidate to type-A flagellin (FLA) were injected in the BALB/c mice in different routes. Two weeks after the last immunization, lymphocyte proliferation was measured by the BrdU method. The IL-4 and IFN-γ levels, as well as the total IgG antibody and its isotypes titer, were evaluated by the enzyme-linked immunosorbent assay method. The IFN-γ ELISPOT was also performed. Our data showed that the HIV-1 p24-Nef alone and conjugated to type-A flagellin (FLA) significantly increased lymphocyte proliferation responses as well as higher levels of cytokines and IFN-γ producing lymphocytes and the level of humoral immune responses compared with the control groups. The cell-mediated immune responses through the subcutaneous route and humoral immune responses through the intramuscular route were significantly higher in the conjugated form than in the mere vaccine candidate. In conclusion, when the FLA as an adjuvant is constructed in the HIV-1 vaccine candidate, it could effectively improve both humoral and cellular immune responses. Furthermore, modification in the vaccine formulation could change the optimal route of vaccine inoculation.

Liothyronine could block the programmed death-ligand 1 (PDL1) activity: an e-Pharmacophore modeling and virtual screening study.

PURPOSE: The interaction between PD-L1 on tumor cells and the programmed death 1 (PD1) on immune cells helps them to escape the immune system elimination. Therefore, developing therapeutic agents to block this interaction has garnered a lot of attention as a therapeutic approach. In the present study, we have tried to screen for an inhibitory compound to inhibit the interaction between the PD1/PD-L1 molecules. METHODS: In this regard, the structure of PD-L1 and its inhibitor were prepared and employed to generate an e-Pharmacophore model. A library of approved compounds was prepared and toxicity analysis using Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictor was performed. The built e-Pharmacophore model was validated and used to screen the prepared compound library. Ligand docking and binding energy calculation were performed on the screened ligands. RESULTS: A seven-feature e-Pharmacophore model was generated using the PD-L1 complex. All of the compounds within the library passed the ADMET criteria. Performing the virtual screening, only 79 compounds have survived the criteria to fit four pharmacophoric features. The compound with the highest binding energy was the liothyronine (T3). CONCLUSION: The ability of T3 in PD1/PD-L1 checkpoint blockade along with its potential in T4 reduction could be a desirable combination in cancer treatment. These abilities of T3 could be used to restore the ability of the immune system to eliminate tumor cells.

Mechanisms of cancer stem cell therapy.

Cancer stem cells (CSCs) are responsible for carcinogenesis and tumorigenesis and are involved in drug and radiation resistance, metastasis, tumor relapse and initiation. Remarkably, they have other abilities such as inheritance of self-renewal and de-differentiation. Hence, targeting CSCs is considered a potential anti-cancer therapeutic strategy. Recent advances in the identification of biomarkers to recognize CSCs and the development of new techniques to evaluate tumorigenic and carcinogenic roles of CSCs are instrumental to this approach. Elucidation of signaling pathways that regulate CSCs colony progression and drug resistance are critical in establishing effective targeted therapies. CSCs play a central key role in immunomodulation, immune evasion and effector immunity, which alters immune system balancing. These include mTOR, SHH, NOTCH and Wnt/ß-catering in cancer progression. In this review article, we discuss the importance of these CSCs pathways in cancer therapy.

Challenging TaqMan probe-based real-time PCR and loop-mediated isothermal amplification (LAMP): the two sensitive molecular techniques for the detection of toxoplasmosis, a potentially dangerous opportunistic infection in immunocompromised patients.

Due to defects and drawbacks of most conventional diagnostic methods including serology for the diagnosis of toxoplasmosis as a dangerous opportunistic infection in immunocompromised individuals, the accurate, rapid, and sensitive detection of infection in such patients is essential. In this study, the TaqMan probe-based real-time PCR and, a relatively new nucleic acid amplification method, the loop-mediated isothermal amplification (LAMP) technique was compared based on the repetitive elements (RE) sequence to detect Toxoplasma gondii (T. gondii) DNA in blood samples of immunocompromised individuals. During this study, 119 blood samples from immunocompromised cancer patients with renal failure, undergoing dialysis were studied. After DNA extraction from blood samples using the salt extraction method, the molecular techniques of TaqMan probe-based real-time PCR and LAMP were used to investigate the contamination of the samples with T. gondii, based on the 529 bp (RE) sequence of T. gondii. The analytical sensitivity of LAMP and real-time PCR was evaluated by duplicating the five-step serial dilutions of T. gondii tachyzoites from 0.25 to 5×105 spiked tachyzoites per milliliter of the Toxoplasma seronegative blood sample. The extracted DNA from other parasites and human chromosomal DNA were used to determine the specificity of the molecular methods. The obtained results were analyzed using Kappa statistical test and SPSS22 software. Out of 119 studied samples, 7 (5.8%) and 5 (4.2%) samples were positive for Toxoplasma by TaqMan probe-based real-time PCR and LAMP, respectively. The limits of detection of TaqMan probe-based real-time PCR and RE-LAMP in negative serum samples were one and five tachyzoites (CT 38), respectively. Both real-time PCR and LAMP methods were 100% specific for Toxoplasma detection. Positive results were obtained only with T. gondii DNA, while other DNA samples were negative. The TaqMan probe-based real-time PCR based on the RE sequence showed higher sensitivity to T. gondii DNA detection in blood samples of cancer patients and serial dilutions of parasitic tachyzoites. The results show that TaqMan probe-based real-time PRC is a sensitive and specific method for the detection of toxoplasmosis in immunocompromised individuals, as well as the LAMP assay, which can be used as a suitable alternative diagnostic method for the detection of toxoplasmosis in such patients, without need the for any expensive equipment.

Urtica Dioica and Lamium Album Decrease Glycogen Synthase Kinase-3 beta and Increase K-Ras in Diabetic Rats.

OBJECTIVES: The aim of the present work is evaluating the special effects of Urtica Dioica and Lamium Album on the serum level of K-Ras and GSK-3 beta in diabetic rats. METHODS: In the present experimental study, 32 male Wistar rats randomly divided into 4 groups (Group I: normal control rats; receiving daily PBS, Group 2: diabetic control rats; receiving single dose of streptozotocin (60 mg/kg) and daily PBS, Group 3: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of the U. dioica, Group 4: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of L. Album. Diabetes-induced by an intraperitoneal injection of streptozotocin (60 mg/ kg). On the 14 th day of treatment, the weight, fasting blood sugar (FBS) and on 28 th day blood glucose, K-Ras and GSK3 beta was measured. RESULTS: In diabetic group blood GSK-3 beta increase in comparison to control group (P < 0.05), also blood K-Ras decrease in the diabetic group (P < 0.05). Both extracts reduced GSK-3 beta level, however, this reduction was only statistically significant by U. dioica (P < 0.05). Compared to diabetic group, blood K-Ras level increased by both extract (P < 0.05). Also diabetes induction increase blood glucose levels and both extracts decrease its level significantly (P < 0.05). there is no significant differences among both extract effects on blood glucose, and K-Ras. CONCLUSION: For the first time shown that both extracts by regulating GSK-3 beta and K-Ras improve blood glucose level. More studies are needed to determine all the effects of these herbs.

Association of OPRD1 Gene Variants with Opioid Dependence in Addicted Male Individuals Undergoing Methadone Treatment in the North of Iran.

Genetic association of rs678849 along with neuroimaging and biomarker phenotypes, parallel with the known involvements of the OPRD1 in drug abuse, provided additional support for targeting these receptors as potential therapeutic targets in both neurodegenerative diseases and neuropsychiactric disorders such as Alzheimer's disease. Samples were selected among 202 opium-addicted participants undergoing methadone treatment and 202 healthy controls. Genomic DNA of all subjects was extracted from whole blood samples through a Salting Out procedure. Four variants (rs678849, 2236857, 2236855, and 760589) were genotyped in the studied subjects using ARMS-PCR. The analysis was performed using SNPalyze and SPSS ver.20 software. According to single locus analysis, rs678849 under dominant model (p < 0.001), rs2236857 under recessive model (p = 0.006), and the two variants, rs2236855 and rs760589 under co-dominant model, showed significant contributions between groups (p = 0.001 and p = 0.009, respectively). rs2236855 was associated with the development of libido dysfunction in opium-addicted patients undergoing methadone treatment (p = 0.011). Through haplotype analyses, five haplotypes with frequency of more than 5% displayed significant association with opioid dependence in study participants. In conclusion, the four studied OPRD1 gene variants and their haplotypes can play important roles in susceptibility to opioid dependence.

Preparation of Pseudomonas aeruginosa alginate-flagellin immunoconjugate.

Mucoid strains of Pseudomonas aeruginosa are closely associated with chronic pulmonary infections. In this report we describe a straightforward approach to conjugate high molecular weight alginate to type b-flagellin (FLB) and investigation of its bioactivity. The conjugation process was performed by using ADH and EDAC. The endotoxin was eliminated from the candidate vaccine by LPS removal resin followed by LAL test. The bioconjugate molecules were verified by simultaneously determination of polysaccharide/protein content followed by gel filtration chromatography and FTIR spectroscopy. Groups of eight BALB/c mice were injected intranasally with 5 µg (per each nostril) of purified alginate, FLB and conjugated alginate-FLB with two week intervals. The functional activity of the vaccine was evaluated by ELISA and opsonophagocytosis tests. Vaccination with the alginate-FLB conjugate induced a significant (P = 0.0033) rise in alginate specific IgG in mice. At all dilution ranges, the opsonic activity of the conjugate vaccine antisera was significantly higher than alginate alone (61.9% vs. 17.3% at 1:4 dilution; P = 0.0067). The alginate-FLB conjugate could elicit high specific antibodies titer against alginate by improving its immunogenicity. In addition, the antisera raised against conjugate vaccine act as a suitable opsonin for phagocytosis of the mucoid strains of P. aeruginosa.

Soluble CD44 concentration in the serum and peritoneal fluid samples of patients with different stages of endometriosis.

PURPOSE: Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity, most commonly implanted over visceral and peritoneal surface within the female pelvis. CD44 is a membrane protein expressed by human endometrial cells, and it has been shown to promote the adhesion of endometrial cells. The aim of this study was to determine the levels of soluble CD44 (sCD44) in the serum and peritoneal fluid (PF) samples of patients with different stages of endometriosis. METHODS: 39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s-cMet in the serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant change in the TPC was seen in the serum of patients with endometriosis when compared to normal controls. Results obtained demonstrated that all serum and peritoneal fluid samples, presented sCD44 expression, whereas, starting from stages I to IV endometriosis, a significant increase of sCD44 expression was observed as compared to control group. CONCLUSIONS: The results of this study show that a high expression of sCD44 is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and/or peritoneal fluid sCD44 may be useful in classifying endometriosis.

Soluble VEGFR1 concentration in the serum of patients with colorectal cancer.

PURPOSE: VEGFR is involved in complex biological processes, including inflammation and cancer development, progression and metastasis. Many proteins, including VEGFR, are proteolytically released from the surface of cells by a process known as ectodomain shedding. The aim of this study was to assess the expression of soluble VEGFR1 (sVEGFR1) in the serum of patients with colorectal cancer (CRC). METHODS: Sixty-two serum samples from healthy controls and 88 samples from patients with different stages of CRC were included in this study. The total protein concentration (TPC) was measured using a Bio-Rad protein assay, and the expression and concentration of sVEGFR1 was determined by a Western blot analysis and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant difference in the serum TPC of patients with and without CRC was seen. The relative s-VEGFR1 expression and concentration of sVEGFR1 in the serum of patients with CRC were significantly increased compared to those in controls (P < 0.001). CONCLUSIONS: The results of this study suggest that VEGFR1 shedding may provide a reliable and practical indicator of the malignant potential, tumor progression and overall tumor burden. The findings also suggest that sVEGFR1 might be involved in the pathophysiology of CRC, and the detection of serum sVEGFR1 may be useful in classifying CRC.

Hyperhomocysteinemia and assessment of its associated factors in renal transplant recipients: a single-center study in northern Iran.

INTRODUCTION: Hyperhomocysteinemia (hyperHcy) is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients (RTRs). The aim of this study was to determine the associated factors of hyperHcy in RTRs in northern Iran. METHODS: In 148 stable RTRs, total serum homocysteine (tHcy) level, folate, serum albumin and creatinine, creatinine clearance, lipid status, body mass index (BMI), and blood cyclosporine levels (C0 and C2) were determined. The mean doses of cyclosporine A (mg/kg/day) were recorded. RESULTS: In this analytic cross-sectional study the prevalence of hyperHcy was 70.3%. Hyperhomocysteinemia was defined as total serum homocysteine of 12 µmol/L or greater. The comparison of the group of 44 patients with tHcy level less than 12 and the group of 104 patients with tHcy level of 12 µmol/L or greater revealed that those subjects with hyperHcy were mostly younger, male, with lower BMI, history of glomerulonephritis, higher serum level of uric acid, and blood cyclosporine trough level (C0) and used higher doses of cyclosporine A. Significant correlation was found between tHcy level and recipients age, serum creatinine, BUN, folate concentrations, and creatinine clearance. However, multivariate analysis indicated that serum folate (P=0.01), vitamin B12 (P=0.05), creatinine (P=0.03), and BUN (P=0.05), and blood cyclosporine trough level (C0, P=0.005) were independently associated with tHcy levels. CONCLUSION: HyperHcy persists after successful kidney transplantation in the majority of RTRs. Serum creatinine, BUN, folate and vitamin B12, and blood cyclosporine trough level (C0) are independently associated with tHcy levels.

Soluble c-Met expression in the peritoneal fluid and serum of patients with different stages of endometriosis.

INTRODUCTION: Hepatocyte growth factor (HGF), also known as scatter factor, and its receptor c-Met have been shown to be implicated in endometriosis. HGF acts as a mitogen, motogen, and morphogen on endometrial epithelial cells. The expression of c-Met on human endometrial cells has been reported. Many proteins are proteolytically released from the surface by a process known as ectodomain shedding. The aim of this study was to determine the levels of soluble c-Met (s-cMet) in the peritoneal fluid (PF) and serum samples of patients with different stages of endometriosis. MATERIAL AND METHODS: 39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s-cMet in the PF and serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant change in the TPC was seen in the serum and PF of patients with endometriosis when compared with normal controls. Results obtained demonstrated that all PF and serum samples presented s-cMet expression, whereas, starting from stages I to IV endometriosis, a significant increase of s-cMet expression was observed as compared to controls. CONCLUSION: The results of this study show that a high expression of s-cMet is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and PF s-cMet may be useful in classifying endometriosis.

Expression of insulin-like growth factor-1 and insulin-like growth factor binding proteins in the serum and cerebrospinal fluid of patients with Parkinson's disease.

Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra. Insulin like growth factor-1 (IGF-1) promotes the survival of dopaminergic neurons and protects them from toxin-induced damage in vitro. IGF-1 is produced by a wide variety of cells and is found in many physiological fluids, including cerebrospinal fluid (CSF). IGFs in physiological fluids are associated with insulin-like growth factor binding proteins (IGFBPs), which bind to them and modulate their bioactivity at the cellular level. Since the CSF is in contact with the extracellular space of the brain, biochemical brain modifications are, to some extent, reflected in the CSF, and peptides and growth factors in the CSF can be used as biomarkers of PD. The aim of this study was to determine the concentrations of IGF-1 and IGFBPs in the serum and CSF of patients with PD. Concentrations were measured in a total of 76 CSF samples from patients with PD (n=38) and controls (n=38). Serum and CSF IGF-1 and IGFBP concentrations were higher in patients with PD than in controls (p<0.001). We conclude that IGF-1 and IGFBPs are always present in human serum and CSF, and may be involved in the pathophysiology of PD.