Effects of Date Palm Pollen Supplementations on The Expression of PRDX1 and PRDX6 Genes in Infertile Men: A Controlled Clinical Trial.

BACKGROUND: Accumulating evidences suggest that date palm pollen (DPP) induces antioxidant activity and improves semen parameters in male rats. However, there is a few scientific evidences in support of the DPP effects on human male fertility. Hence, the effect of oral consumption of DPP on sperm parameters and expression pattern of Peroxiredoxin- 1 (PRDX1) and Peroxiredoxin-6 (PRDX6) genes was evaluated in men with infertility. MATERIALS AND METHODS: The current controlled clinical trial included 40 men with infertility (DPP group) and 10 normospermic fertile men as controls. The DPP group received gelatinous capsules of DPP (400 mg/kg) for 74 days. Semen sampling was done before and after treatment in the both groups. Semen analysis and 8-isoprostane concentration assessments were performed by computer-assisted sperm analysis and ELISA methods, respectively. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were employed to explore expression of PRDX1 and PRDX6 genes. RESULTS: DPP consumption significantly improved semen volume (P=0.030), count (P<0.001) and morphology of sperm (P=0.023). Concentration of 8-isoprostane was significantly decreased after intervention in the DPP group (P<0.001). DPP consumption led to a significant elevation in the expression of PRDX1 and PRDX6 genes (P<0.001). Elevated gene expression of PRDX6 and PRDX1 was positively correlated with improved parameters of sperm including count, volume, motility and morphology. CONCLUSION: Taken together, DPP seems to promote sperm quality through a decrease in reactive oxygen species (ROS) by increasing expression of antioxidant genes. Further large-scale studies are required to challenge this hypothesis (registration number: IRCT2015021221014N2).

Clinical significance of long non-coding RNA ZEB2-AS1 and EMT-related markers in ductal and lobular breast cancer.

BACKGROUND: Breast cancer is considered the most prevalent type of cancer in women and accounts for a high rate of death. A body of research has demonstrated that lncRNAs have a regulatory function in human diseases, especially cancers. ZEB2-AS1 is known as an oncogenic lncRNA in various types of cancers, and its deregulation may contribute to cancer development and progression. Therefore, we aimed to reveal the association of ZEB2-AS1 expression with epithelial-mesenchymal transition (EMT) markers, as a hallmark of cancer progression, in a clinical setting. METHODS: A recent study suggested that ZEB2-AS1 is significantly involved in EMT. Here we intended to explore the roles of lncRNA ZEB2-AS1 in breast cancer (BC) using bioinformatics tools and laboratory settings. We first evaluated the expression of ZEB2-AS1 mRNA in tumor and healthy control tissues by lnCAR database. Furthermore, ZEB2-AS1 expression level, ZEB2, E-cadherin, and vimentin was measured via qRT-PCR in 30 paired ductal and lobular carcinoma tissues from breast cancer patients and the normal adjacent ones. The correlation between the lncRNA ZEB2-AS1 expression and clinicopathological characteristics of the breast cancer patients was evaluated. RESULTS: ZEB2-AS1 showed an upregulation in breast cancer tissues (p = .04) compared to normal adjacent samples. In addition, its level was higher in breast cancer patients with advanced Stages (III & IV) (n = 18) compared to early Stages (I & II) (n = 12) (p = .04). Moreover, ZEB2 (p = .01) and vimentin (p = .02) expression were upregulated in the BC sample, but the expression level of E-cadherin (p = .02) was downregulated when compared with the adjacent normal tissues. By comparison of the expression of EMT-markers between different stages of breast cancer, overexpression of ZEB2 (p = .04) and vimentin (p = .04) and down expression of E-cadherin (p = .03) was observed in advance stages. CONCLUSIONS: Collectively, our findings suggest that ZEB2-AS1 expression is significantly upregulated in tumor tissues, especially in advanced stages and ZEB2-AS1 is associated with the aggressiveness of tumors by functioning as putative oncogenic lncRNA. In addition, a combination of ZEB2-AS1 and these EMT markers in breast cancer potentiates these genes as biomarkers for tumor progression.

CBCT Assessment of the Anatomical Characteristics of Gubernacular Canal in Impacted Teeth.

Statement of the Problem: Gubernacular canal (GC) is a canal that extends from the follicle of unerupted permanent teeth to the alveolar bone crest filled with remnants of the dental lamina. This canal is thought to guide tooth eruption and be related to some pathologic conditions. Purposes: This study aimed to determine the presence of GC and its anatomical characteristics in teeth, which failed to erupt normally on cone beam computed tomography (CBCT) images. Materials and Method: This cross-sectional study evaluated CBCT images of 77 impacted permanent and supernumerary teeth obtained from 29 females and 21 males. The frequency of GC detection, its location in relation to the crown and root, the anatomical surface of the tooth from which the canal has originated, and the adjacent cortical table to which the canal opens, along with the length of the GC were studied. Results: GC was observed in 53.2% of teeth. The anatomical tooth aspect of origin was occlusal/ incisal in 41.5% and crown in 82.9% of teeth. Moreover, 51.2% of GCs opened in palatal/lingual cortex and 63.4% of canals were not located along the tooth long axis. Finally, GC was detected in 85.7% of teeth undergoing the crown formation stage. Conclusion: Although GC was introduced as an eruption pathway, this canal is also present in impacted teeth. This means that presence of this canal does not promise the normal eruption of tooth and the anatomical characteristics of GC may influence the eruption process.

Long non-coding RNA NR2F2-AS1: its expanding oncogenic roles in tumor progression.

Long non-coding RNA (LncRNA) is a new type of non-coding RNA whose transcription is more than 200 nucleotides in length and can be up to 100 kb. The crucial regulatory function of lncRNAs in different cellular processes is now notable in many human diseases, especially in different steps of tumorigenesis, making them clinically significant. This research tried to collect all evidence obtained so far regarding Nuclear Receptor subfamily 2 group F member 2 Antisense RNA 1 (NR2F2-AS1) to explore its role in carcinogenesis and molecular mechanism in several cancers. Collecting evidence value an oncogenic role for NR2F2-AS1, whose dysregulation changes the status for cancerous cells to gain the supremacy toward cellular proliferation, dissemination, and ultimately migration. The NR2F2-AS1 acts as competitive endogenous RNA (ceRNA) and contains several microRNA response elements (MREs) for different microRNAs involved in various pathways such as PI3K/AKT, Wnt/ß-catenin, and TGF-ß. This clinically makes NR2F2-AS1 a remarkable lncRNA which contributes to cancer progression and invasion and perhaps could be a candidate as a prognostic marker or even a therapeutic target.

The Inhibitory Effect of Sulforaphane on The Proliferation of Acute Myeloid Leukemia Cell Lines through Controlling miR-181a.

OBJECTIVE: The present study investigated the role of miR-181a as a small non-coding RNA molecule in acute myeloid leukemia (AML) pathogenesis and reflected on the effects of Sulforaphane (SFN) on AML progression. MATERIALS AND METHODS: This experimental study had two parts. In vivo study, the miR-181a levels was measured in patients with symptoms of AML and compared to healthy controls (HCs) to investigate its role in AML pathogenesis. Afterward, an in vitro study was performed to examine the effects of SFN on the growth, apoptosis and proliferation rate of AML cell lines. Finally, the effect of SFN on miR-181a was evaluated as a major miRNA involved in hematopoiesis. RESULTS: The results of this study showed an increasing trend (2.9-fold, P=0.0019) in miR-181a expression levels in AML patients as compared with HCs. The data associated with MTT assay and flow cytometry (FCM) additionally demonstrated the anti-proliferative effects of SFN against AML cell lines, with a reduction in miR-181a levels. As well, no significant difference was noted between 24 hours and 48 hours treatments by SFN. It was deduced that modulation of miR-181a expression levels could be one of the mechanisms associated with the anti-proliferative effects of SFN against AML. CONCLUSION: MiR-181a levels contribute to AML pathogenesis and thus they can be considered as a strategy in controlling AML progression in patients. Accordingly, SFN can arrest cell proliferation and induce apoptosis in AML cell lines through retardation expression of miR-181a and affecting miR-181a pathway, which already clarified its role in the differentiation of hematopoietic stem cells and indicates another mode of anti-cancer action of sulforaphane.

Corrigendum to "The effect of Phoenix dactylifera pollen on the expression of NRF2, SOD2, CAT, and GPX4 genes, and sperm parameters of fertile and infertile men: A controlled clinical trial" [Int J Reprod BioMed 2021; 19: 545-558].

[This corrects the article DOI: 10.18502/ijrm.v19i6.9376.].

The effect of Phoenix dactylifera pollen on the expression of NRF2, SOD2, CAT, and GPX4 genes, and sperm parameters of fertile and infertile men: A controlled clinical trial.

BACKGROUND: Oxidative stress is caused by the imbalance occurring between the creation and clearance of the reactive oxygen species (ROS), which is responsible for 30-40% of male infertility. The positive impact of phoenix dactylifera pollen (Date palm pollen, DPP) on the improvement of sperm parameters has been well documented in animal models. OBJECTIVE: For evaluating the effect(s) of DPP on sperm parameters, ROS levels, expression of antioxidant genes, and activity of antioxidant enzymes of infertile men. MATERIALS AND METHODS: In this controlled clinical trial, a total of 60 male case with infertility and 20 normospermic fertile men were recruited. Before and after the treatment with DPP, the case were administered 400 mg/kg of gelatinous capsules daily for 30 consecutive days and semen samples were taken. Quantitative real-time polymerase chain reaction was applied for the evaluation of the mRNA expression levels of Nuclear factor erythroid 2-related factor 2(NRF2), superoxide dismutase (SOD2), glutathione peroxidase 4(GPX4), and catalase (CAT) genes. RESULTS: The mRNA expression levels of NRF2, SOD2, GPX4, and CAT (p < 0.05 for all) and significantly increased after treatment with DPP. The increased expressions of all antioxidant genes and enzymes significantly correlated with improvement in semen parameters including count (p = 0.01), motility (p = 0.05), and morphology (p = 0.01) of sperm. A significant correlation between the alteration of SOD2 gene expression and SOD activity, GPX4 and GPX, and CAT were also observed (p = 0.05). CONCLUSION: DPP can increase the expressions of NRF2, GPX4, SOD2, and CAT genes and also improve the semen quality in infertile men.

The Effect of HBB: c.-121C>T Variant [-71 (C>T)] on the ß-Globin Promoter: Case Series Study.

One of the effective strategies in controlling thalassemia is recognition of carriers, followed by prenatal diagnosis (PND) to prevent the occurrence of new cases. There are some rare mutations and variants, for which there are not enough evidences of their effects, and can lead to misdiagnosis and even cause confusion in decision about termination of pregnancy. That is why it is very critical to know the effect of each mutation on the ß chain gene. The variant of HBB: c.-121C>T [-71 (C>T)] located in the CAAT box of the promoter region, is a rare mutation. We report seven patients in Hormozagn Province, Iran, who were referred to the PND Center of Hormozgan University of Medical Science (HUMS), Bandar Abbas, Iran during 10 years (2010-2020). Briefly, this mutation causes minor changes in blood indices [mean corpuscular volume (MCV): 75.0 ± 4.0 fL; mean corpuscular hemoglobin (MCH): 25.8 ± 2.5 pg; Hb A2: 3.4 ± 0.5%] showed anemia with a trait milder than minor ß-thalassemia (ß-thal). Though the existence of α mutations (deletions/point mutations) along with HBB: c.-121C>T can change blood indices due to the changes in α/ß ratio. The phenotype of ß-thal intermedia (ß-TI) was observed in one case, who was a compound heterozygosity for codon 15 (G>A)/-71(C>T) (HBB: c.48G>A/HBB: c.-121C>T. The analysis of transcription level by real-time polymerase chain reaction (real-time PCR) confirmed that this allele induces a mild ß+ phenotype due to a decrease in the transcription level.

The outstanding role of miR-132-3p in carcinogenesis of solid tumors.

MicroRNAs are a group of short non-coding RNAs (miRNAs), which are epigenetically involved in gene expression and other cellular biological processes and can be considered as potential biomarkers for cancer detection and support for treatment management. This review aims to amass the evidence to reach the molecular mechanism and clinical significance of miR-132 in different types of cancer. Dysregulation of miR-132 level in various types of malignancies, including hepatocellular carcinoma, breast cancer, colorectal cancer, gastric cancer, lung cancer, prostate cancer, osteosarcoma, pancreatic cancer, and ovarian cancer have reported, significantly decrease in its level, which can be indicated to its function as a tumor suppressor. miR-132 is involved in cell proliferation, migration, and invasion through cell cycle pathways, such as PI3K, TGFß or hippo signaling pathways, or on oncogenes such as Ras, AKT, mTOR, glycolysis. miR-132 could be potentially a candidate as a valuable biomarker for prognosis in various cancers. Through this study, we proposed that miR-132 can potentially be a candidate as a prognostic marker for early detection of tumor development, progression, as well as metastasis.

Synthesizing efficacious genistein in conjugation with superparamagnetic Fe3O4 decorated with bio-compatible carboxymethylated chitosan against acute leukemia lymphoma.

BACKGROUND: Genistein (C15H10O5) is a soy isoflavone with anti-cancer properties such as inhibition of cell growth, proliferation and tumor invasion, but effective dosage against hematopoietic malignant cells was not in non-toxic range. This property cause to impede its usage as chemotherapeutic agent. Therefore, this hypothesis raised that synthesizing biocompatible nanoparticle could assist to prevail this struggle. METHODS: Genistein covalently attached on Fe3O4 nanoparticles decorated with carboxymethylated chitosan to fabricate Fe3O4-CMC-genistein in alkaline circumstance. This obtained nanoparticles were evaluated by TEM, DLS, FTIR, XRD and VSM and its anti-cancer effect by growth rate and MTT assays as well as flow cytometer on ALL cancer cell lines. RESULTS: Different evaluations indicated that the drug delivery vehicle had a mean diameter size around 12ƞm with well bounded components. This system presented high degree of magnetization and superparamagnetic properties as well as good water solubility. In comparison with pure genistein, significant growth inhibition on hematopoietic cancer cells in lower dose of genistein nano-conjugated onto Fe3O4-CMC. It increased long lasting effect of genistein in cancer cells also. CONCLUSION: This delivery system for genistein could be remarkably promised and futuristic as biocompatible chemotherapeutic agent against hematopoietic malignant cells.

Arsenic Trioxide and Thalidomide Combination Induces Autophagy Along with Apoptosis in Acute Myeloid Cell Lines.

OBJECTIVE: Autophagy and apoptosis play key roles in cancer survival and pathogenesis and are governed by specific genes which have a dual role in both cell death and survival. Arsenic trioxide (ATO) and thalidomide (THAL) are used for treatment of many types of hematologic malignancies. ATO prevents the proliferation of cells and induces apoptosis in some cancer cells. Moreover, THAL has immunomodulatory and antiangiogenic effects in malignant cells. The aim of present study was to examine the effects of ATO and THAL on U937 and KG-1 cells, and evaluation of mRNA expression level of VEGFs genes, PI3K genes and some of autophagy genes. MATERIALS AND METHODS: In this in vitro experimental study, U937 and KG-1 cells were treated by ATO (0.4-5 µM) and THAL (5-100 µM) for 24, 48 and 72 hours. Cell viability was measured by MTT assay. The apoptosis rate and cell cycle arrest were evaluated by flow cytometry (Annexin/PI) and cell cycle flow cytometry analysis, respectively. The effect of ATO/THAL on mRNAs expression was evaluated by real-time polymerase chain reaction (PCR). RESULTS: ATO/THAL combination enhanced cell apoptosis in a dose-dependent manner. Also, ATO/THAL induced SubG1/ G1 phase arrest. mRNA expression levels of VEGFC (contrary to other VEGFs isoform), PI3K, AKT, mTOR, MEK1, PTEN, IL6, LC3 and P62 genes were upregulated in acute myeloid leukemia (AML) cells following treatment with ATO/THAL. CONCLUSION: Combined treatment with ATO and THAL can inhibit proliferation and invasion of AML cells by down-regulating ULK1 and BECLIN1 and up-regulating PTEN and IL6, and this effect was more marked than the effects of ATO and THAL alone.

Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy?

OBJECTIVE: Acute myeloid leukemia (AML) is a clonal disorder of hemopoietic progenitor cells. The Raf serine/threonine (Ser/Thr) protein kinase isoforms including B-Raf and RAF1, are the upstream in the MAPK cascade that play essential functions in regulating cellular proliferation and survival. Activated autophagy-related genes have a dual role in both cell death and cell survival in cancer cells. The cytotoxic activities of arsenic trioxide (ATO) were widely assessed in many cancers. Sorafenib is known as a multikinase inhibitor which acts through suppression of Ser/Thr kinase Raf that was reported to have a key role in tumor cell signaling, proliferation, and angiogenesis. In this study, we examined the combination effect of ATO and sorafenib in AML cell lines. MATERIALS AND METHODS: In this experimental study, we studied in vitro effects of ATO and sorafenib on human leukemia cell lines. The effective concentrations of compounds were determined by MTT assay in both single and combination treatments. Apoptosis was evaluated by annexin-V FITC staining. Finally, mRNA levels of apoptotic and autophagy genes were evaluated using real-time polymerase chain reaction (PCR). RESULTS: Data demonstrated that sorafenib, ATO, and their combination significantly increase the number of apoptotic cells. We found that the combination of ATO and sorafenib significantly reduces the viability of U937 and KG-1 cells. The expression level of selective autophagy genes, ULK1 and Beclin1 decreased but LC3-II increased in U937. CONCLUSION: The expression levels of apoptotic and autophagy activator genes were increased in response to treatment. The crosstalk between apoptosis and autophagy is a complicated mechanism and further investigations seem to be necessary.

The relationship of miR-181a expression level and AML: A systematic review protocol.

INTRODUCTION: The most common type of leukemia is acute myeloid leukemia (AML) with the lowest survival rate among all of the leukemias particularly in adults. The evidence has shown that dysregulation of miRNA expression is associated with AML. Therefore, the aim of this systematic review was to clarify the role of miR-181a expression in AML. METHODS AND ANALYSIS: In the present study, observational studies of the roles of miR-181a expression in patients with AML will be included. Standards and indicators test should be performed for all patients. We will search PubMed, SCOPUS and ISI Web of Science with no restriction of language. The outcomes will be reviewed for association between miR-181a level and AML progression and the strength of this relationship with AML will be investigated. Selection of articles and data extraction will be performed by two independent reviewers. STROBE will be used for assessment of study quality. Publication bias and data synthesis will be an assessment by funnel plots and Beggs and Egger's tests using Stata software V.12.1. ETHICS AND DISSEMINATION: There are no ethical issues. TRIAL REGISTRATION NUMBER: This systematic review protocol is registered in the PROSPERO (International Prospective Register of Systematic Reviews), and registration number CRD42016040080.

The impact of variations in transcription of DICER and AGO2 on exacerbation of childhood B-cell lineage acute lymphoblastic leukaemia.

The expression of microRNA in eukaryotic cells is subject to tightly regulated processing. The altered expression of microRNAs in a number of cancers suggests their contribution to disease pathogenesis, where processing pathways may be involved in disease pathogenesis. In the present study, we evaluated changes in the profile of two main components of microRNA biogenesis, AGO2 and DICER, and assessed their correlation with disease progression in childhood acute lymphoblastic leukaemia (ALL). To achieve this aim, 25 patients afflicted with ALL were included in the study along with 25 healthy subjects as control. The expression level of AGO2 and DICER was evaluated by real-time PCR. The results revealed an increase in the expression of DICER and a decrease in AGO2 in patients. The correlation between the alteration levels of these genes with pathologic events was also studied. This increase or decrease proved to be directly correlated with the progression of the disease particularly in L1 to L2. According to the obtained results, it can be deduced that dysregulation in transcription of DICER and AGO2, involved in the formation of mature microRNAs in cytoplasm of ALL cancer cells, is a part of the pathological molecular mechanism implicated in the exacerbation of this malignancy. Therefore, the genes involved in microRNAs biogenesis that have been studied here could be considered as candidate prognostic markers especially in childhood ALL which will help towards a better understanding of the molecular basis of ALL.

Restraining the Proliferation of Acute Lymphoblastic Leukemia Cells by Genistein through Up-regulation of B-cell Translocation Gene-3 at Transcription Level.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a highly prevalent pediatric cancer accounting for approximately 78% of leukemia cases in patients younger than 15 years old. Different studies have demonstrated that B-cell translocation gene 3 (BTG3) plays a suppressive role in the progress of different cancers. Genistein is considered a natural and biocompatible compound and a new anti-cancer agent. In this study, we evaluate the effect of genistein on BTG3 expression and proliferation of ALL cancer cells. MATERIALS AND METHODS: ALL cell lines (MOLT4, MOLT17, and JURKAT) were cultured in standard conditions. Cytotoxicity of genistein was detected using MTT assay. The cells were treated with different concentrations of genistein (10, 25, 40, and 55µM) for 24, 48, and 72 hours, and then cell viability and growth rate were measured. The quantitative real-time polymerase chain reaction was applied to investigate the effect of genistein on BTG3 expression. RESULTS: The percentage of vital cells treated with genistein significantly decreased compared to the non-treated cells, showed an inverse relationship with an increasing genistein concentration. The present study suggests a dose of 40µM for genistein as a potent anticancer effect. Genistein could elevate BTG3 for 1.7 folds in MOLT4 and JURKAT and 2.7 folds in MOLT17 cell lines at transcription level conveged with 60 to 90% reduction in the proliferation rate of cancer cells. CONCLUSION: Up-regulation of BTG3 as a tumor suppressor gene can be induced by genistein. It seems that BTG3 reactivation can be introduced as another mechanism of anti-proliferative effect of genistein and could be considered as a retardant agent candidate against hematopoietic malignancy.

Effect of oral magnesium sulfate administration on lectin-like oxidized low-density lipoprotein receptor-1 gene expression to prevent atherosclerosis in diabetic rat vessels.

AIMS/INTRODUCTION: The purpose of the present study was to investigate the possible effect of oral magnesium sulfate (MgSO4 ) in the reduction of atherosclerosis plaques through inhibition of lectin-like low-density lipoprotein receptor-1 (LOX-1) gene expression in diabetic vessels. MATERIALS AND METHODS: A total of 50 rats were divided into five groups, including non-diabetic control, Mg-treated non-diabetic control, chronic diabetic, Mg-treated chronic diabetic and insulin-treated chronic diabetic. The induction of diabetes was carried out by streptozotocin. The Mg-treated chronic diabetic and Mg-treated non-diabetic control groups were treated with 10 g/L of MgSO4 added to their drinking water. The insulin-treated chronic diabetic group received 2.5 U/kg of insulin twice per day. The fasting blood glucose level and bodyweight were determined weekly. Blood pressure measurement and the intraperitoneal glucose tolerance test were carried out after 16 weeks, and the plasma levels of Mg, lipid profile and oxidized low-density lipoprotein cholesterol (oxLDL) were determined. The mesenteric bed was isolated and perfused according to the McGregor method. The aorta was isolated for LOX-1 genes and proteins expression, and pathological investigation. RESULTS: MgSO4 administration improved blood pressure, sensitivity to phenylephrine, intraperitoneal glucose tolerance test, lipid profile and plasma ox-LDL level, and also lowered the blood glucose level to the normal range, and decreased LOX-1 gene and protein expressions. Insulin decreased blood pressure, sensitivity to phenylephrine, blood glucose, lipid profiles and plasma oxLDL level, but it did not decrease LOX-1 gene and protein expressions. CONCLUSIONS: The present findings suggested that MgSO4 improves blood pressure and vessel structure through decreasing oxLDL, and LOX-1 gene and protein expressions; however, insulin did not repair vessel structure, and LOX-1 gene and protein expressions.

Effect of Long-term Administration of Oral Magnesium Sulfate and Insulin to Reduce Streptozotocin-Induced Hyperglycemia in Rats: the Role of Akt2 and IRS1 Gene Expressions.

The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. Fifty rats were randomly divided into five experimental groups: 1, non-diabetic control (NDC); 2, Mg2+-treated non-diabetic control (Mg-NDC); 3, chronic diabetic (CD); 4, Mg2+-treated chronic diabetic (Mg-CD); and 5, insulin-treated chronic diabetic (Ins-CD). Streptozotocin was used to induce diabetes. The Mg-CD and Mg-NDC groups received 10 g/l of MgSO4 added to drinking water. The Ins-CD group received 2.5 U/kg of insulin twice a day. Blood glucose level and body weight were measured every week. The intraperitoneal glucose tolerance test (IPGTT) was performed after 16 weeks. MgSO4 administration improved the blood glucose level and IPGTT. It also increased Akt2 and IRS1 genes as well as protein expression. Insulin lowered the blood glucose level and increased IRS1 gene and protein expression, but did not affect Akt2 gene and protein expression. Glucose reduction after Mg therapy may be mediated, at least partially, via IRS1 and Akt2 genes and protein stimulation. In insulin-treated rats, insulin resistance was not significant due to the absence of Akt2 gene expression.

Effect of oral magnesium sulfate administration on blood glucose hemostasis via inhibition of gluconeogenesis and FOXO1 gene expression in liver and muscle in diabetic rats.

The present study was designed to investigate the possible role of Mg2+ in suppression of phosphoenolpyruvate carboxy kinase (PEPCK) enzyme via inhibition of FOXO1gene expression in liver and we also examined whether Mg contributes to decrease blood glucose in muscle via inhibiting FOXO1 gene and protein expression. Fifty rats in five groups of experiment were considered as; non-diabetic control (NDC), Mg2+-treated non-diabetic control (Mg2+-NDC), chronic diabetic (CD), Mg2+-treated chronic diabetic (Mg2+-CD), and insulin-treated chronic diabetic (Ins-CD). Streptozotocin (STZ) was used for diabetes induction. The Mg2+-CD and Mg2+-NDC groups received 10 g/l of magnesium sulfate (MgSO4) added to drinking water, and Ins-CD group received 2.5 U/kg of insulin. The blood glucose level and body weight were measured weekly. After 16 weeks, intraperitoneal glucose tolerance test (IPGTT) was done and blood samples were taken to determine the plasma levels of Mg and gastrocnemius muscle legs, and liver were isolated for both Forkhead transcription factor (FOXO1) and PEPCK enzyme genes and proteins expression. Administration of MgSO4 improved IPGTT, lowered blood glucose levels and decreased FOXO1 and PEPCK genes and proteins expression in muscle and liver, while insulin just could decrease FOXO1 gene and protein expression in the muscle. These findings illustrated that MgSO4 improved hyperglycemia via inhibition of FOXO1 gene and protein level in the muscle and liver, and it also decreased blood glucose level by prohibition of gluconeogenesis pathway in the liver. However, long time administration of insulin did not have any effect on liver.

Alleviating the progression of acute myeloid leukemia (AML) by sulforaphane through controlling miR-155 levels.

Acute myeloid leukemia (AML) has the highest rate of mortality among the leukemias. Disruption in miRNAs level is involved in the pathogenesis of the disease. The miR-155 has a role in primary differentiation of myeloid progenitor. Meanwhile, there is little knowledge about the effects of sulforaphane against leukemia. The present study tried to evaluate pathologic effect of miR-155 in patients in various subgroups of AML, and then pioneered in assessing miR-155 levels by the effect of sulforaphane in different AML cell lines. The miR-155 level was significantly higher in patients with AML compared to the controls. Interestingly, the increase in miR-155 was converged with raising the subtype of AML (from M1 to M5). The miR-155 levels increased by 1.2 times in patients with M1, but this increase reached 2.5 times in the patients in the M5 subgroup. Sulforaphane reduced the number of live cells and increased the mortality rate of AML cells particularly by induction of apoptosis. However, the anti-proliferative effect of this agent was more dominant and could dose-dependently lessen miR-155 levels in myeloid leukemia cells. More or less, about 80% reduction in miR-155 expression was almost observed after 48 h treatment with 60 µM sulforaphane in all four studied cell lines. The obtained results indicated that miR-155 might function as an oncomir in AML and can potentially be considered as a prognosis biomarker for AML. The anti-cancer effects of sulforaphane can be correlated with reduction of miR-155 levels. These findings suggested that sulforaphane could induce more differentiation in myeloid progenitor cells through controlling the miR-155, thereby mitigating the progress of AML.