Epididymosomes: the black box of Darwin's pangenesis?

Darwin, in the pangenesis theory, imagined particles, named as 'gemmules', which are released from all ('pan') cells of the body. By cell-cell communication and also circulation through the body, they finally reach the germ cells to participate in the generation ('genesis') of the new individual. It has been shown that circulatory exosomes are affected by environmental stressors and they can reach the parental germ cells. Therefore, in the mirror of his theory, circulatory exosomes could interact with epididymosomes: epididymis-derived exosomes which have a wide spectrum of variation in content and size, are very sensitive to environmental stressors, and may be involved in translating external information to the germ cells. The protein and RNA cargo would be transferred by epididymosomes to sperm during sperm maturation, which would be then delivered to the embryo at fertilization and inherited by offspring. Therefore, in this study, we will briefly discuss Darwin's pangenesis theory and its possible relation with epididymosomes. We believed that epididymosomes could be considered as an attractive candidate for the storage of RNA contents, changing the epigenome of the next generations, and allowing the reappearance acquired characteristics of ancestors. Therefore, epididymosomes, as a black box of Darwin's pangenesis, may unravel parental life history and also disclose the historical events that affect the life of offspring.

Lactoferrin suppresses LPS-induced expression of HMGB1, microRNA 155, 146, and TLR4/MyD88/NF-кB pathway in RAW264.7 cells.

OBJECTIVE: This current study evaluated the underlying mechanisms of LF against the inflammatory microRNAs (miRNAs), HMGB1 expression, and TLR4-MyD88-NF-кB pathway in LPS-activated murine RAW264.7 cells. METHODS: MTT assay was used to assess cell metabolism and the cell culture levels of the cytokines (TNF-α, IL-6) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The expression of miRNAs was quantified by using qPCR and the expression of HMGB1, TLR4, MyD88, and phosphorylated NF-κB (P-p65) were determined with Western blot and qPCR, respectively. RESULTS: The results indicated that LF downregulates IL-6 and TNF-α expression. LF exhibited the degradation of P-p65 and reduced the production of HMGB1, TLR4, and MyD88 in LPS-induced inflammatory response. Importantly, in parallel with the suppression of cytokines and HMGB1-TLR4-MyD88-NF-кB pathway, LF could induce a decrease in inflammatory selected miRNAs, mmu-mir-155, and mmu-mir-146a expression. CONCLUSIONS: Altogether, these findings provide LF as a prominent anti-inflammatory agent that could modulate HMGB1, mmu-mir-155, mmu-mir-146a, and TLR4/MyD88/NF-кB pathway.

A glimpse into molecular mechanisms of embryonic stem cells pluripotency: Current status and future perspective.

Embryonic stem cells have potential differentiation ability into a large variety of cell lineages and proved to be an effective therapeutic modality. However, prolonged in vitro and ex-vivo expansions impair embryonic stem cells multipotentiality, and thereby limit their clinical application. In the past few years, research collected attempts to explore new insights into the molecular mechanisms participate in the stemness capacity of embryonic stem cells. Along with these comments, modalities and strategies with the potential to maintain embryonic stem cells multipotentiality are of great interest. In this review, the authors attempted to discuss the pathways participating in the preservation of embryonic stem cells multipotentiality and emphasized the novel strategies that help to harness regenerative potential.

Application of ɑ-Tocotrienol-Loaded Biocompatible Precirol in Attenuation of Doxorubicin Dose-Dependent Behavior in HUH-7 Hepatocarcinoma Cell Line.

Tumor-targeted nanoparticle delivery system has been known as a substitute and capable achievement in cancer treatment compared to conventional methods. In this study, we examined potential application of ɑ-tocotrienol-Precirol formulation to enhance efficiency of doxorubicin (DOX) in induction of apoptosis in HUH-7 hepatocarcinoma cells. ɑ-tocotrienol-loaded nanoparticles were characterized at the point of zeta potential, particle size, scanning electron microscope (SEM), and cell internalization. To evaluate antiproliferative effects of formulation, apoptosis, cell cycle procedure, flow cytometry, and MTT assays were employed. Optimum size of the ɑ-tocotrienol formulation revealed narrow size distribution with mean average of 78 ± 3 nm. IC50 values for ɑ-tocotrienol and ɑ-tocotrienol-nano structured lipid carriers after 24 h were 15 ± 0.6 and 10 ± 0.03 µM, respectively. After incubation of cells with ɑ-tocotrienol-loaded careers, the rate of cell proliferation decreased from 53 ± 6.1 to 34 ± 7.1% (P < 0.05). A significant improvement in the apoptosis percentage was revealed after treatment of the HUH-7 cell line with DOX and ɑ-tocotrienol careers (P < 0.05). Gene expression results demonstrated a marked decrease in survivin and increase in Bid and Bax levels. Our findings suggest that ɑ-tocotrienol-loaded nanoparticles elevate DOX efficacy in HUH-7 hepatocarcinoma cell.

Vascular mimicry: changing the therapeutic paradigms in cancer.

Cancer is a major problem in the health system, and despite many efforts to effectively treat it, none has yet been fully successful. Angiogenesis and metastasis are considered as major challenges in the treatment of various cancers. Researchers have struggled to succeed with anti-angiogenesis drugs for the effective treatment of cancer, although new challenges have emerged in the treatment with the emergence of resistance to anti-angiogenesis and anti-metastatic drugs. Numerous studies have shown that different cancers can resist anti-angiogenesis drugs in a new process called vascular mimicry (VM). The studies have revealed that cells resistant to anti-angiogenesis cancer therapies are more capable of forming VMs in the in vivo and in vitro environment, although there is a link between the presence of VM and poor clinical outcomes. Given the importance of the VM in the challenges facing cancer treatment, researchers are trying to identify factors that prevent the formation of these structures. In this review article, it is attempted to provide a comprehensive overview of the molecules and main signaling pathways involved in VM phenomena, as well as the agents currently being identified as anti-VM and the role of VM in response to treatment and prognosis of cancer patients.

Association of IL-10, IL-18, and IL-33 genetic polymorphisms with recurrent pregnancy loss risk in Iranian women.

Recurrent pregnancy loss (RPL) is a heterogeneous disease with three or more consecutive abortions before 20 weeks of pregnancy. Recently, inflammatory factors such as interleukins (IL) have been found to be a significant factor in the RPL. The objective of this study was to investigate the association between RPL and IL-10 (rs1800896), IL-18 (rs1946518) and IL-33 (rs1929992) genes polymorphisms in Iranian women. The study participants consisted of 300 women with RPL and the control group comprised of 300 healthy women with successful delivery. Genomic DNA was extracted from peripheral blood, and genotyping was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). There were no significant differences in the frequencies of genotype and allele in IL-10 gene polymorphism (rs1800896) between patients and control group (p > .005). In contrast, there were significant differences in the frequencies of CC genotype in IL-18 gene polymorphism (rs1946518) between patients and the control groups (p = .004; OR =0.990; 95% CI: 0.320-8.855). Also, there were significant differences in the frequencies of GA genotype in IL-33 gene polymorphism (rs1929992) between patients and the control groups (p = .001; OR =0.955; 95% CI: 0.239-9.807). Present study showed that the rs1800896 polymorphism (IL-10) might not play role in RPL in the Iranian population; whereas rs1946518 (IL-18) and rs1929992 (IL-33) polymorphisms may be associated with the risk of RPL in the Iranian women.

In vivo and in vitro impact of miR-31 and miR-143 on the suppression of metastasis and invasion in breast cancer.

PURPOSE: The microRNA (miR)-31 and miR-143 are pleiotropic anti-metastatic miRs, with an expression that decreases significantly in metastatic breast cancer cells. The aim of this study was to investigate the effect of miR-31 and miR-143 inhibition on metastasis and invasion in both MDA-MB231, MDA-MB468 as well as the MCF-7 breast cancer cell lines and 5-week old female mice. METHODS: Following the cloning of miR-31 and miR-143 into vectors, their expressions were determined before treatment with constructs of miR-31 and miR-143 in cancer cell lines and normal breast cells. Then miR-31 and miR-143 were transfected to the cell lines and the expression was assessed after 48 hrs. Moreover, the levels of migration and invasion were determined in cell lines. These experiments were performed in 5-week old female mice. RESULTS: The results showed that miR-31 expression before the transfection of miR-31 construct was decreased 4, 70 and 100 times in MCF-7, MDA-MB468 and MDA-MB231 cell lines, respectively, in comparison to normal breast cells; but after the transfection of miR-31 construct, the expression of miR-31 increased 80 times. Additionally, invasion and migration decreased by 15 and 10 times in MDAMB-468. All of the modifications in miR-143 were low in comparison to miR-31. The results of the in vivo experiments were approximately the same as in the in vitro experiments. CONCLUSIONS: It appears that the use of miR-31 is highly efficient than miR-143 in the inhibition of invasion and metastasis in breast cancer. Our study improved our conception about miR-31 and miR-143 and their roles in the identification and therapy of breast cancer.

The evaluation of melatonin and EGF interaction on breast cancer metastasis.

OBJECTIVES: Metastasis in breast cancer is the first cause of death in patients. The epidermal growth factor (EGF) increases cancer cells' invasion, and migration. Melatonin's inhibitory effects on various types of cancer were confirmed. This study aimed to investigate whether melatonin could apply its impact through the EGF-related pathways or not. METHODS: First, MDA-MB-231 and MCF7 cells were cultured, and then melatonin effects on cell viability were determined by MTT assay. Transwell invasion assay was applied to identify the invasiveness of these breast cancer cell lines under treatment of EGF and melatonin. Real-time RT-PCR then investigated the expression of MMP9 and MMP2 in determined groups. Cell proliferation was also assayed under EGF and melatonin treatment using Ki67 assessment by flow cytometry. RESULTS: The rate of invasion and migration of EGF-treated cells increased in both groups, in which melatonin caused increased invasion by EGF just in MCF7 cells. MMP9 and MMP2 expression increased significantly in both cell lines under EGF treatment, and melatonin increased these genes' expression in both cell lines (p<0.05). EGF increased the MMP9 and MMP2 gene expression, and melatonin increased EGF-induced expression (p<0.05). The EGF reduced the expression of the Ki67 protein in the MCF7 cell line, which was negatively affected by melatonin and EGF. In contrast, along with melatonin, EGF did not affect the proliferation of the MDA-MB-231 cell line. CONCLUSIONS: The results of this study show that melatonin in the presence of EGF does not show the anti-cancer properties previously described for this substance.

N1-Methylnicotinamide: Is it Time to Consider it as a Dietary Supplement for Athletes?

Exercise is considered to be a "medicine" due to its modulatory roles in metabolic disorders, such as diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP) increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, as a vitamin B3 metabolite, reduces serum levels and liver contents of triglycerides and cholesterol, and induces lipolysis. It stimulates gluconeogenesis and prohibits liver cholesterol and fatty acid synthesis through the expression of sirtuin1 (SIRT1). It seems that MNAM is not responsible for the actions of NNMT in the adipose tissues as MNAM inhibits the activity of NNMT in the adipose tissue and acts as an inhibitor of its activity.NNMT-MNAM axis is more activated in the muscles of individuals undergoing the high-volume-low-intensity exercise and caloric restriction. Therefore, MNAM could be an important myokine during exercise and fasting where it provides the required energy for muscles through the induction of lipolysis and gluconeogenesis in the liver and adipose tissues, respectively. Increased levels of MNAM in exercise and fasting led us to propose that the consumption of MNAM during training, especially endurance training, could boost exercise capacity and improve performance. Therefore, in this review, we shed light on the potential of MNAM as a dietary supplement in sports medicine.

Therapeutic potentials of Apatinib in cancer treatment: Possible mechanisms and clinical relevance.

Metastasis is one of the main issues in cancer treatment and it has been documented that angiogenesis plays an important role in this process. Studies showed that vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have elevated expression in tumors and are involved in tumor progression and metastasis; suggesting their potential for being a therapeutic target. In this regard, Apatinib or YN968D1, a specific inhibitor of VEGFR-2 has been suggested as a promising therapeutic agent for cancer that can prevent tumor angiogenesis and metastasis. Furthermore, this drug can sensitize resistant tumor cells to chemotherapy drugs and increase the effectiveness of conventional chemotherapy drugs. Recent studies have shown that Apatinib has beneficial implications as a post-second and third-line therapy agent in a variety of cancers. Furthermore, Apatinib has the capacity to promote the overall survival and progression-free survival of cancer patients. This review discussed about, the molecular mechanisms and clinical relevance underlying the therapeutic potential of Apatinib in cancer treatment.

ß-Lapachone attenuates cognitive impairment and neuroinflammation in beta-amyloid induced mouse model of Alzheimer's disease.

Oxidative stress and neuroinflammation are critically involved in amyloid beta (Aß) induced cognitive impairments. ß-Lapachone (ß-LAP) is a natural activator of NAD(P)H quinone oxidoreductase 1 (NQO1) which has antioxidant and anti-inflammatory properties.This study investigated the effect of ß-LAP administration on Aß-induced memory deficit, oxidative stress, neuroinflammation, and apoptosis cell death in the hippocampus. Forty BALB/c mice were allocated into control, sham, ß-LAP (ßL), Aß, and Aß + ßL groups. Intracerebroventricular injection of Aß1-42 was used to induce Alzheimer's disease (AD) model. Mice in the ßL and Aß + ßL groups were treated with ß-LAP (10 mg/kg, i.p) for 4 days. Results revealed that ß-LAP attenuated memory impairment in the Aß-received mice, as measured in the novel object recognition (NOR) and Barnes maze tests. Moreover, Aß resulted in inflammasome activation evident by enhanced caspase-1 immunoreactivity and interleukin-1 beta (IL-1ß) protein levels. However, ß-LAP could markedly reduce reactive oxygen species (ROS) production and down-regulate mRNA expression of NLRP3 inflammasome and protein levels of cleaved caspase 1 and IL-1ß. Additionally, ß-LAP-treated mice showed increased SIRT1 levels and NAD+/NADH ratio in the hippocampus. These results were followed by fewer number of TUNEL-positive cell, reduced hippocampal atrophy and neuronal loss in the hippocampal dentate gyrus (DG). These results indicated that the protective effect of ß-LAP against AD-associated cognitive deficits is partially through its strong antioxidant and anti-inflammatory actions.

An evaluation on potential anti-inflammatory effects of ß-lapachone.

Inflammation plays a significant role in the pathogenesis of chronic diseases. Inflammatory diseases such as bacterial diseases, Alzheimer's disease, rheumatoid arthritis, multiple sclerosis, and so on, impose huge costs on the health systems. On the other hand, some side effects have been reported for the classic drugs used to treat these diseases. Plants phytochemicals have revealed important prospects in the handling and controlling of human diseases. ß-lapachone, is a derivative of the naturally occurring element lapachol, from Tabebuia avellanedae and its anti-inflammatory effects have been reported in several reports. This review summarized the evidence from cell and animal studies supporting the anti-inflammatory role of ß-lapachone and discussed its potential mechanisms.

N1-Methylnicotinamide: An Anti-Ovarian Aging Hormetin?

Ovarian aging occurs due to the reduction of the quality and quantity of the oocytes, and is regulated by mitochondrial survival and apoptotic signals. Reactive Oxygen Species (ROS) are one of those signals considered detrimental to cellular homeostasis. Nowadays, ROS are regarded as a regulatory factor at low levels as it induces the stress resistance which in turn increases the longevity. It is believed that the main mechanism for the life-promoting role of the ROS mediated by the 5' Adenosine Monophosphate-activated Protein Kinase (AMPK). N1-Methylnicotinamide (MNAM) is well known for its anti-diabetic, anti-thrombotic, and anti-inflammatory activity. Aldehyde oxidase 1 (AOX1) is a detoxifying enzyme, which metabolizes the MNAM and produces two metabolites including N1-methyl-2-pyridone-5- carboxamide (2py) and N1-methyl-4-pyridone-3-carboxamide (4py). The activity of AOX1 enhances the production of ROS and improves the longevity. It has been reported that the MNAM could postpone the aging through the induction of low-level stress. It has been documented that the production of MNAM is significantly higher in the cumulus cells of the patients with Polycystic Ovary Syndrome (PCOS) and its administration on the rat model of PCOS has been shown to alleviate the hyperandrogenism and successfully activate the ovarian AMPK. Therefore, it can be hypothesized that the anti-ovarian aging effects of the MNAM are possibly based on the activation of AMPK through transient elevation of the ROS.

Association of rs1946518 C/A Polymorphism in Promoter Region of Interleukin 18 Gene and Breast Cancer Risk in Iranian Women: A Case-control Study.

Breast cancer (BC) is the most frequently diagnosed cancer among women in the world. Genetic polymorphisms in Interleukin (IL) genes are one of the most important risk factors in BC. The aim of this study was to investigate the association of rs1946518 C/A polymorphism in the promoter region of the IL-18 gene and BC risk in Iranian women. In this case-control study, we recruited 140 women with BC as a case group and 140 age and ethnically matched women as healthy controls from East Azerbaijan, Tabriz in Iran. The genomic DNA was extracted using a salting-out method from peripheral blood leukocytes. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype distribution in BC patients was 37.86% CC, 47.14% CA, and 15.00% AA, whereas in healthy controls these were 40.72% CC, 42.85% CA, and 16.43% AA. Statistical analysis showed that the genotype and allele frequencies of IL-18 rs1946518 C/A polymorphism were not significantly different between BC patients and healthy controls (p>0.05). The only significant difference between cases and controls was related to family history (p=0.023). In conclusion, our study indicated that IL-18 rs1946518 C/A polymorphism was not associated with BC in the Iranian women population. However, more studies on different races and geographic areas are required to determine the exact role of rs1946518 C/A polymorphism in prognosis, diagnosis, and risk of BC.

Different expression of Micro RNA-126, 133a and 145 in aorta and saphenous vein samples of patients undergoing coronary artery bypass graft surgery.

Introduction: microRNAs (miRNAs) are highly conserved, noncoding RNA molecules that regulate gene expression on the post-transcriptional level. Some evidence indicates that microRNAs dysfunction plays a crucial role in human disease development. The role of microRNAs in cardiac growth, hypertrophy, heart failure, cardiovascular complications in diabetes and many other hearth conditions are demonstrated. In this study we aimed to evaluate the expression of six microRNAs (mir-100, mir-126, mir-127, mir-133a, mir-133b and mir-145) that have been shown to overexpress in aortic and carotid plaques. Methods: Thirty Coronary Artery Disease patients who underwent elective coronary artery bypass graft surgery were enrolled in the study. The expression patterns of six miRNAs (mir-100, mir-126, mir-127, mir-133a, mir-133b, and mir-145) were examined in 30 patients of whom we obtained aorta and saphenous vein samples. Results: In three miRNAs, mir-100, mir-127 and mir-133b, we did not obtain expression data from real-time experiments. We found that the expression level of mir-126, mir-133a and mir145 were lower in aorta in comparison with saphenous vein. Mir-126 was highly expressed in saphenous vein samples (13.8±1.1) when compared with aorta samples (20.2±1.1), although mir133a was highly expressed in saphenous vein samples (16.1±0.5) when compared with the aorta (17.9±1.5). Expression of mir-145 saphenous vein samples was also dramatically higher than aorta (7.2±0.5 versus 10.8±0.6) that was statistically significant (P<0.05). Conclusion: Understanding the role of miRNAs in cardiovascular physiology and diseases might suggest miRNA- based therapeutic methods in the management of coronary artery disease.

Decreasing serum homocysteine and hypocholesterolemic effects of Bovine lactoferrin in male rat fed with high-cholesterol diet.

Introduction: Lipid metabolism disorder or hyperlipidemia is known as a risk factor for cardiovascular disease, the increase in serum homocysteine and leptin are associated with atherosclerotic disease. The purpose of the present study was to examine the effects of bovine lactoferrin (bLF) on serum homocysteine (Hcy), apolipoproteinA-I (ApoA-I) and B (ApoB), leptin and lipid profile changes in high-cholesterol-diet (HCD) fed rats. Methods: The Healthy Adult Sprague-Dawley (SD) male rats were randomly assigned into three experimental groups. Each group consisted of eleven male rats including control group, HCD rats and hypercholesterolemic rats, which were treated with bLF (HCD+bLF). bLF was given by gavage (200 mg/kg/d). After 4 weeks of feeding and overnight fasting, total blood samples were collected. Results: The results showed the elevated level of Hcy, leptin, total cholesterol, low density lipoprotein cholesterol (LDL-C), ApoB and decrease in ApoA-I in non-treated HCD group compared to the control rats. Administration of bLF significantly ameliorated the Hcy and leptin levels with decrease in LDL-C and total cholesterol in rats fed with a high-cholesterol diet. bLF also tended to increase low serum concentration of ApoA-I and high density lipoprotein cholesterol (HDL-C) in HCD rats. Meanwhile, upon bLF-treated rats, there was a significant decrease in ApoB in HCD group. Conclusion: The findings indicated that bLF can improve the alteration of serum Hcy, leptin, apolipproteins and lipid changes in male rats fed with high-cholesterol diet. So, bLF can counteract with HCD elicited hyper-homocysteinemia and hyper-leptinemia, suggesting it to have the useful therapeutic potential in patients with atherosclerosis and lipid disorder.

The potential therapeutic effect of melatonin on human ovarian cancer by inhibition of invasion and migration of cancer stem cells.

There is an urgent need to identify targeting molecules to control invasion and metastasis in cancer patients. We first isolated cancer stem cells (CSCs) from SKOV3 ovarian cancer cells and then investigated the role of melatonin in invasiveness and migration of CSCs compared to SKOV3 cells. The proportion of CSCs in SKOV3 cells was as low as 1.28% with overexpression of both CD133 and CD44. The ability of spheroid formation along with SOX2 overexpression revealed a high self-renewal potential in isolated cells. Melatonin (3.4 mM) inhibited proliferation of CSCs by 23% which was confirmed by a marked decrease in protein expression of Ki67, as a proliferation marker. Applying luzindole, a melatonin receptor 1, 2 inhibitor, partially abolished anti-proliferative effect of melatonin. Melatonin also decreased Epithelial mesenchymal transition (EMT) related gene expressions including ZEB1, ZEB2, snail and vimentin with increase in E-cadherin as a negative EMT regulator. Incubation of CSCs with melatonin showed a marked decrease in matrix metalloproteinase 9 (MMP9) expression and activity. Melatonin also inhibited CSCs migration in a partially receptor dependent and PI3k and MAPK independent manner. Melatonin can be considered as an important adjuvant to control invasion and metastasis especially in patients with high melatonin receptor expression.

Effects of High and Low Doses of Folic Acid on the Soluble Receptor Activator of Nuclear Factor-kappa B Ligand/Osteoprotegerin Ratio during Pregnancy.

BACKGROUND: Pregnancy Associated Osteoporosis (PAO) can lead to serious difficulties such as fragility fractures, elongated back pain and height loss in affected women. Soluble Receptor Activator of Nuclear Factor-Kappa B ligand (sRANKL) to Osteoprotegerin (OPG) ratio is chosen as a bone metabolism equation in many bone diseases characterized by bone resorption, such as post-menopausal osteoporosis and would be modified with folic acid supplementation. This study was done to compare the effects of high dose (5mg/day) and low dose (0.5 mg/day) folic acid in the RANKL/OPG ratio and Tumor Necrosis Factorα (TNFα) concentration during pregnancy. METHODS: Forty-five pregnant women who visited the AL-Zahra Hospital, Tabriz Iran, from September 2013 to November 2014 were assigned into two groups in this randomized, double-blind, clinical trial, included women who took 5 mg/day (group1) and who took 0.5 mg/day (Group 2) folic acid supplementation before pregnancy until 36th pregnancy. The biochemical variables in serum of pregnant women were measured before and at the end of the study. The study was registered in the Iranian Registry of Clinical Trials (IRCT) as ID, IRCT2013122315903N1. RESULTS: OPG levels were significantly higher compared with the baseline value (P=0.008), although sRANKL (P<0.001), TNFα (P=0.005) and sRANKL/OPG ratio (P<0.001) reduced significantly with high dose of folic acid supplementation. A significant positive correlation was observed between the decreased RANKL and TNFα levels (r=0.451, P=0.031) at the end of study in high dose group. CONCLUSION: High dose of folic acid supplementation could decrease bone resorptive biomarkers and may prevent PAO in pregnant women by increasing OPG and decreasing sRANKL and TNFα.

Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy.

INTRODUCTION: There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. METHODS: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. RESULTS: Supplementation of the patients with FA for 36 week decreased the median (minimum- maximum) levels of serum Hcy from 11.40 µmol/L (4.40-28.70) to 9.70 (1.60-20.80) µmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. CONCLUSION: Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women.