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Abstract: Leukemia or blood cancer was initially discovered in 1845 and this malignancy was reported in patients who had an amplified number of blood cells, in particular, white blood cells (WBC), due to this disease. The event of leukemia was further identified as a malignant hematopoietic disorder due to both uncontrolled and unlimited proliferation in combination with lack of differentiation of the leukemic stem cells.Furethermore, 75 to 80% of the global population use herbal remedies as primary therapy, mainly because of their better efficiency and satisfaction, which elevate the human body symmetry with the minimum unwanted adverse effects. For the control of cancer, plant products, and fruits have been considered promising tools and are being consumed for centuries. Several plant extracts are also being used for the therapy and prevention of different types of known cancers. Indole-3-carbinol (I3C) is a natural material obtained from Brassica diversity of vegetables and has been reported to serve as a promising cancer preventative agent. In the present review, theauthors mainly tried to focus and emphasize I3C applications in the leukemia treatment.

Hyperglycemia during the first trimester leads to an increased risk of innate malformations as well as death at times close to delivery dates. The methylated genes include those from paternal H19 and PEG3 and those from maternal MEST and MEG3 that are necessary for the growth and regulation of the human fetus and its placenta. The aim of this study was to evaluate and compare the expression of these genes in the cord blood of healthy infants born to mothers with gestational diabetes mellitus (GDM) and healthy mothers.This case-control study was conducted on the cord blood of 40 infants born to mothers with GDM and 35 infants born to healthy mothers. Mothers were identified by measuring oral glucose tolerance in the 24th–26th week of pregnancy. Cord blood was obtained post-delivery, and cord blood mononuclear cells were immediately extracted, using Ficoll solution. Then, RNA extraction and cDNA synthesis were performed, and gene expression of MEG3, PEG3, H19, and MEST was assessed through quantitative real-time PCR.Findings show that the expression levels of MEG3, PEG3, H19, and MEST genes were significantly decreased in mononuclear cord blood cells of infants born to mothers with GDM when compared to those of the healthy control group.These findings reveal that the reduction of imprinted genes in mothers with GDM is most likely due to changes in their methylation by an epigenetic process. Considering the importance of GDM due to its high prevalence and its side effects both for mother and fetus, recognizing their exact mechanisms is of high importance. This has to be studied more widely.

Background: Anti-cancer effects of almond nuts or oil have been approved, but there are a few pieces of research that have evaluated, in detail, almond and other seeds' effects on cancer. Therefore, in the present project, the aim was to explore the regulatory effect of the bitter almond extract (Prunus amygdalus Batsch) on the apoptotic and anti-cancer potency of MCF-7 cells. Objectives: In the current experimental research, the Almond effect on MCF7 cells was evaluated by investigating the expression and the balance between Bcl-2, Bax genes to unmark the potential molecular mechanism. Methods: For 24 and 48h, the MCF7 cells were treated with the bitter almond extract (187.5-3000 μg/mL). MTT assay was used to assess the viability, and Real-time-PCR was applied to determine the expression of Bax and Bcl-2, facing β-actin. Results: Our results revealed a significant difference between different extract concentrations on the viability of MCF7 cell lines in 24 and 48 h; cell viability decreased time-dependently (P < 0.05). After 24 and 48h of extract facing MCF7 cells, the evaluated IC50 value was 3000 and 1500 μg/mL, respectively. Based on Real Time-PCR analysis, after 24 and 48 h, the mRNA levels of BCL-2 decreased by the extract, whereas Bax was in the MCF-7 cell line. Conclusion: From the results, it can be concluded that bitter almond extract has anti-cancer properties that may influence the apoptotic pathways by regulating relative gene expression.

Background: Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats Methods: I Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats Results: According to the findings of this study, similar to morphine treated group, methadone maintenance in morphine treated animals led to significant reduction in the expression of BDNF and CREB genes at VTA as well as BDNF serum level compared with control group. Conclusion: It was concluded that methadone, like morphine, causes significant reduction in the expression of BDNF and CREB genes in brain VTA area of rat as well as BDNF serum level compared with control group.

Background: Type-1 diabetes mellitus (T1DM) has been described as an autoimmune and heterogeneous disorder. In the present study, we aimed to examine whether there exists an association between serum CXCL10 (IP-10) level and its promoter polymorphism at position-1443 as an angiostasis alongside CXCL12 and its known SDF-1 3′ A genetic variant as an angiogenesis chemokine in T1DM patients. Methods: Blood specimens were collected from 209 unrelated T1DM patients, as well as from 189 healthy subjects. The DNA samples were extracted from the subjects and analyzed for CXCL10 and CXCL12 polymorphisms by employing PCR-RLFP. The serum concentrations of CXCL10 and CXCL12 were also analyzed with ELISA. Results: Following expert opinion and data analysis, we found significant differences between A/A, A/G, and G/G genotypes with A and G alleles of polymorphisms at position +801 (SDF-1α3′A) in CXCL12. We did not observe an association between CXCL10/-1443 promoter polymorphism and T1DM. In our assessment of promoter polymorphism, both T1DM patients and controls had GG genotype in CXCL10/-1443. When patients were compared with controls, both serum CXCL10 and CXCL12 levels are increased in type 1 diabetes with complications. Levels were not increased in patients without complications. Conclusion: Both CXCL10 and CXCL12 play fundamental roles in T1DM pathogenesis. Only the CXCL12 3′A (SDF-1α3′A) polymorphism is possibly necessary for the pathogenesis of T1DM, while the CXCL10-1443 promoter polymorphism is not.

Background and Objective: Orlistat drug is one of the most criticalanti-obesity drugs that widely used around the world. The aim of this study was evaluation the effect of orlistat on the expression of OCT4, Nanog, SOX2, and KLF4 genes in the colorectal cancer SW40 cell line. Materials and Methods: SW40 cell line was cultured in DMEM medium contained orlistat for 24h, and cell viability was assessed by MTT assay. The fold changes of expression of OCT4, NANOG, KLF4, and SOX2 at mRNA level against β-actin were determined by real-timePCR. Two-sample t-test and one-way ANOVA were used to compare the mean of expression of different genes in different groups and different concentrations; a significant level of 0.05 was considered in all tests. Results: Our results showed a significant difference in cell viability, when different doses of Orlistat were used for 24 hour. concentrations of 25 and 100 μM reduce significantly the expression of OCT4 (p

Aim and objectives: Brucellosis is common in most parts of the world between humans and domestic animals. The causative agent is bacteria from the Brucella family, which are intracellular pathogens. Despite, Brucella spp. Is able to infect humans, their ability to induce production of chemokines by lung cells is unknown. In this study, we showed an association between brucellosis and CXCL9, 10 and 11chemokinesMethods:We have totally recruited 71 brucella patients who have referred to the either local health centers or hospitals of kerman province. Diagnosis of acute brucellosis was made based on a brief history of the disease,clinical examinations results of serological tests,antibody titration in serums was performed by bacterial wright method, agglutination and 2ME with antigen. Brucellosis patients CXCL9, CXCL10 and CXCL11 serum levels were detected by sandwich ELISA using paired chemokine-specific mAbs, according to the manufacturer’s guidelines. Transcription levels of mRNA for the CXCR3 as the chemokine receptor for CXCL9, CXCL10 and CXCL11 was examined by QRT-PCR using primers. Results: We have found that there was a positive correlation between the level of chemokines and their receptor. Here ELISA test showed that B. abortus induces expression of some IFN-γ induced CXCL9, 10 and 11chemokines in brucellosis patients. We have also showed the increased expression of CXCR3 as their shared receptors in brucellosis patients with real time-PCR. Conclusion: According to these findings there was a positive correlation between the level of chemokines and their receptor. We have found that there was a positive correlation between the level of chemokines and their receptor.

The aim of this study was to evaluate the therapeutic effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) and their efficacy to attenuate inflammation in multiple sclerosis (MS). This study was a randomized, double-blind, placebo-controlled clinical trial phase I. The level of docosahexaenoic and eicosapentaenoic acid was significantly increased and the level of matrix metallopeptidase-9 was significantly decreased in MS patients treated with PEGNLPUOs. The level of cytokine showed a Th2-biased response with attenuation of inflammation after treatment with PEGNLPUOs. The number of relapses, disability scores, and T2 lesions was significantly decreased after treatment with PEGNLPUOs.

Background: Several studies demonstrated the regulatory effects of vitamin D3 on the immune system. The aim of this study was to investigate the serum levels of IL-12, IL-6, IL-10, IL-17 and IFN-g cytokines in 11-17 year-old female students with 25-hydroxyvitamin D3 (25-(OH) D3) (VitD3) deficiency. Methods: 100 subjects with VitD3 deficiency were selected as the case group and an equal number of individuals with sufficient levels of VitD3 were selected as a control group. The serum levels of IL-10, IL-6, IL-12, IFN-g and IL-17 were measured by ELISA method. Results: The results showed that the serum concentrations of IL-12 (P= 0.005) and IFN-g (P= 0.019) were significantly lower in VitD3-deficient group compared to control group. There were no significant differences in serum levels of IL-6 (P= 0.66), IL-10 (P= 0.647) and IL-17 (P= 0.159) between cases and controls.Conclusion: These results suggest that VitD3deficiency may result in decreased inflammatory cytokines production, which are required for proper immune functions. However, the effects of VitD3 on IL-6 and IL-17A, as the pro-inflammatory and IL-10, as anti-inflammatory cytokines needs more investigations.

Leukemia or blood cancer was initially discovered in 1845 and this malignancy was reported in patients who had an amplified number of blood cells, in particular, white blood cells (WBC), due to this disease. The event of leukemia was further identified as a malignant hematopoietic disorder due to both uncontrolled and unlimited proliferation in combination with lack of differentiation of the leukemic stem cells.Furethermore, 75 to 80% of the global population use herbal remedies as primary therapy, mainly because of their better efficiency and satisfaction, which elevate the human body symmetry with the minimum unwanted adverse effects. For the control of cancer, plant products, and fruits have been considered promising tools and are being consumed for centuries. Several plant extracts are also being used for the therapy and prevention of different types of known cancers. Indole-3-carbinol (I3C) is a natural material obtained from Brassica diversity of vegetables and has been reported to serve as a promising cancer preventative agent. In the present review, theauthors mainly tried to focus and emphasize I3C applications in the leukemia treatment.

Background The disorder of pre-eclampsia is described as a complicated gestational state in which some of bio-molecules, including cytokines and chemokines are involved. The main purpose of the current study was examining of the circulating levels of CXCL9, CXCL10 as inducible, angiostasis chemokines as well as CXCL12 as an angiogenesis, homeostatic chemokine, in pregnant women with and without pre-eclampsia and their neonates. Methods Peripheral blood and cord samples were collected from 53 preeclampsia patients and 53 normal pregnant women without preeclampsia and their related neonates. The differences in serum levels of CXCL9, CXCL10 and CXCL12 and the placental tissue expression of these chemokines were investigated by ELISA and western blot analysis, respectively. Results Findings of the present study demonstrated that the levels of CXCL9 chemokine in parallel with CXCL12 as homeostatic chemokine were induced in pre-eclamptic women compared with normal pregnant women while CXCL10 remained unchanged. The CXCL9 and CXCL10 were both decreased in neonates who were delivered by pre-eclamptic women in compare to normal pregnant women. A CXCL12 level was elevated in neonates and has followed a similar fashion as mothers. Conclusion According to the results, the CXC chemokines are involved in pathogenesis of pre-eclampsia and play important roles in several processes such as neovascularization, embryonic development and inflammatory responses that are mediated by pre-eclampsia.

Background: Heterocyclic compounds are generally introduced as important valuable sources of pharmacologically active compounds. Amongst these compounds, the indole is largely distributed within the bioactive molecules, containing antitumor agents. Due to their unique physiochemical and biological properties, indole and its derivatives have been used as privileged scaffolds for designing antitumor agents. Objectives: The current experimental study aimed to evaluate the anti-cancer effects of a novel compound with indole-core-base on acute myeloid leukemia (AML) cells. Methods: Following being cultured, AML cells that had been multiplicities were treated by the demonstrated concentration of novel indole compounds (at doses of 100-300µg/mL) for 24 h. The percentage of living and dead cells was subsequently determined by trypan bluedye (MERK, Germany). The survival rate of treated cells was also examined by MTT assay. The calculated fold changes of the studied genes expression against β-actin were determined by the real-time polymerase chain reaction (PCR) technique. The collected data were statistically analyzed by student t-test and repeated measure test. Results: Results showed that the intended novel indole-core-based derivative (C18H10N2F6O) followed both dose-dependent cytotoxic and anti-proliferative patterns on the AML cell line. The compound was able to induce apoptosis in 50% of the cells at the dose of 250µg/mL. Real-time PCR analysis indicated that in compound-treated cells the gene expression level of Bcl-2 has been downregulated, while Bax was upregulated, compared to untreated control cells. Conclusion: Despite the lack of knowledge in this regard, in this study, results of this leading mechanism(s) that may run by the compound indicated that indole3carbaldehyde derivative has cytotoxic effects on AML cells in a dose-dependent fashion.

Background: The purpose of this study was to investigate the role of eotaxin family members including C-C motif chemokine 11 (CCL11), C-C motif chemokine 24 (CCL24), and C-C motif chemokine 26 (CCL26) as the subgroups of CC-chemokine in patients affected with osteoporosis and osteopenia. Methods: Overall, 19 osteoporotic patients, 18 osteopenic individuals, and 20 healthy subjects were recruited in this study. The bone mineral density (BMD) was then measured at the lumbar spine (L1-L4) and the hip (femoral neck and total hip) using dual-energy X-ray absorptiometry for diagnosis of bone density and related disorders. Additionally, enzyme-linked immunosorbent assay (ELISA) technique was employed to measure the serum levels of CCL11, CCL24, and CCL26. Results: The circulating levels of CCL11, CCL24, and CCL26 had been increased in both groups of patients with osteopenia and osteoporosis compared to those in healthy subjects (P

The aim of this study was to investigate the effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) to attenuate the inflammatory response in the EAE model by modulating of NFKB and oxidative stress signaling pathway. Real-time PCR demonstrated that the administration of 10%v/v PEGNLPUOs significantly decreased the expression level of AKT1, MAPK, and NFKB genes from NFKB signaling pathway and MGST1, NOS2, and HO-1 genes from oxidative stress signaling pathway. This study showed that the administration of pistachio oil and PEGNLPUOs at a concentration of 10%v/v decreased the number and percentage of Th1(CD4+) and increased Th2(CD8+) cells.

Aim and objectives: Natural products and derivatives of medicinal vegetation can play an important role to the cure tumor. The Present study was focused to determine the effect of Cornus mass L. extract on the induction of apoptosis in AGS gastric carcinoma cell line in compared to L929 cells. Methods: In this experimental study, AGS and L929 cells were cultured and treated with different concentrations (0–10 mg/ml) of Cornus mass L. extract for 48 and 72 hours. Cell proliferation was assessed by MTT assay. The optical density of the colored solution was quantified at 570 nm wavelengths by an ELISA Reader. Making use of the apoptosis detection kit of Annexin V-FITC, PI and double staining with Annexin V-FITC were carried out for flow cytometry investigations. Data were analyzed by ANOVA. Variations with a P-value less than 0.05 were considered significant. Results: shows a noticeable deviation among various concentrations of extract when cells were treated for 48, 72 h declined cell viability in AGS cell line in comparison L929 cell lines in a dose and time-dependent manner (P < 0.05). This extract also displayed approximately several-fold increased anti-cancer potency in AGS compared to L929 cells. The IC50 value in AGS cells (evaluated after 48,72h) of the extract against AGS cells was 5/44, 2/44 mg/ml (p≤0.05). The analysis results of flow cytometry indicated that apoptosis was induced by the extract in AGS cells treated, compared with L929 cells. Conclusion: Each of our results implicates the reality that Cornus mass L. extract acts as a novel, potent inhibitor of cancer proliferation in in vitro. This may result in developing a promising therapeutic agent for the treatment of indole-sensitive cancers.

OBJECTIVE: Diabetes mellitus (DM) is typically a disorder of carbohydrate, fat, and protein metabolism. It develops due to a lack of or loss associated with insulin and/or resistance to insulin. Regarding complications of chemical substance use, drugs with few complications and high-reliability tannins are needed. This study aimed to determine the effect and mechanism of action of Citrullus colocynthis extract on the formation of glycated hemoglobin (HbA1c). MATERIALS AND METHODS: A solution containing hemoglobin and glucose was incubated for 1, 2, 3, 4, 30, and 60 days by adding Citrullus colocynthis extract or glutathione. Quantitative measurement of HbA1c was performed using ion-exchange chromatography. Data were analyzed using ANOVA and two-way repeated measures test. A p

The potential exists to improve treatment through characterization of tumor stem cells and identification of therapeutic targets Using OCT-4 and NANOG genes. Here we have synthesized and investigated the potential of; New Indole-3-carbaldehyde derivative (NI-3-CD) in inhibiting the expression of self-renewal regulatory factors and cancer stem cell gene in a leukemia cell line NB4.The NB4 cells were cultured in RPMI1640 medium contained NI-3-CD and I3F (15.12-1000μg/mL) for 24, 48 and 72h. Inhibition of cell proliferation was assessed by trypan blue staining technique and MTT assay. The percentage of apoptotic cells was determined by flow cytometry analysis using Annexin V/PI apoptosis detection kit. The fold changes of NANOG/OCT4 expression against β-actin were determined by real-time-PCR technique. Western blotting analysis was also applied for evaluating the expression of NANOG/OCT4 at protein level. Data were analyzed by student t and repeated measure tests. Differences were considered significant if (P0.01).There was a significant difference in cell viability, when various concentrations of NI-3- were used for 24, 48 and 72h in comparison to I3C regarding the cellular viability. Furthermore, the NI-3-CD, had markedly elevated anticancer activity than I3C (IC50 values for novel I3C in 24, 48 and 72h were 225.77, 123.13 and 63.72M respectively while for I3C were 728.05, 407.82 and 277.92M respectively). Flow cytometry results exhibited an obviously significant augmentation in apoptotic NB4 cells. Real Time- PCR analysis indicated that the expression of NANOG/OCT4 was down regulated in compare to untreated control cells and I3C treated cells (P0.05). In concert with RT-PCR, western blot analysis showed that the OCT4 expression in NI-3-CD treated cells was also significantly decreased in compare to both untreated control cells and I3C treated cellular populations.Our results imply that NI-3-CD treatment decreases the sphere-forming ability of NB4 cells. In summary, this study provides valuable information on the presence of stem-cell genes expression in NB4 cells.

Type I diabetes (TID) is defined as an autoimmune disease resulting from the destruction of insulin-producing beta-cells by autoreactive T cells. It is believed that TID resulted from the immune-mediated destruction of insulin-producing β-cells in pancreatic islets of Langerhans. Chemokines are small glycoproteins (weighing 8–10 kDa) that are attractive chemotactive factors for a wide variety of cell types, especially immune system cells and their target cells which express appropriate G protein receptors. It has been well established that chemokines as the main arms of the immune system play key roles in the regulation of immune responses which is evidenced to be important in the pathogenesis of the diseases. Several other environmental and genetic components of the immune systems also confirmed to influence the onset of immune-related diseases. The CXC chemokine CXCL12 is involved in the development of immune responses. Previous studies reported that the known genetic variation SDF1–3′A regulates the expression of CXCL12. Hence, the aim of this study was to address the latest findings regarding the relation between the serum concentrations and CXCL12 genetic variation, in SDF1–3′A in T1D.

s Background The aim of the current study was to determine the effects of various concentrations of saffron distillate (Crocus sativus) on expression of some self-renewal genes including OCT4, KLF, SOX2, NANOG and Nucleostemin in AGS (gastric adenocarcinoma) cell line. Material and methods The AGS cells were cultured in RPMI1640 medium contained saffron (20, 40 and 100 μg/mL) for 24, 48 and 72 h. Inhibition of cell proliferation was assessed by MTT. The percentage of apoptotic cells was determined by flow cytometry analysis using Annexin V/PI apoptosis detection kit. Total cellular RNA extracted and subjected to and cDNA synthesis and then, the expression of the desired genes was extracted and subjected to in both the control and test groups, using real time- PCR (RT-PCR). Data were analyzed by student t and repeated measure tests. Differences were considered significant if (P Findings There was a significant difference in cell viability, when various concentrations of saffron were used for 24, 48 and 72 h of incubation and apoptosis increased in a time-dependent manner. Flow cytometry results exhibited an obviously significant augmentation in apoptotic AGS cells. Real time- PCR our RT-PCR based findings indicated that saffron distillate has reduced the expression of OCT4, KLF, SOX2, NANOG and Nucleostemin genes in compare to untreated control cells. Conclusion According to the results of this study it may be concluded that saffron distillate can be considered as an inhibitor of cell division and regardingly inhibit cancer progression.

BACKGROUND: The present study was aimed and designed to determine the serum levels of CXCL1 and CXCL12 as angiogenesis along with CXCL9 and CXCL10 as angiostasis, chemokines in, Gestational diabetes mellitus mothers (GDMM) and normal pregnancy mothers (NPM) and neonates who delivered by them. METHODS: We have recruited 63 pregnant GDMM and 63 normal pregnant mothers at the third trimester of pregnancy to this cross-sectional study. Cord blood specimens were obtained from neonates who were delivered from GDMM and NPM. The serum and cord blood levels of chemokines were measured by ELISA in studied groups. Data were analyzed by chi-square and student’s t test between two groups. The P-values less than 0.05 were considered significant. RESULTS: Our results revealed that the serum levels of CXCL1, CXCL9 and CXCL12 were increased in GDMM, while no alteration was found in the serum levels of CXCL10 when compared to NPM. We have observed that in neonates the serum levels of angiogeneic chemokines followed an inverse fashion when compared to angiostasis chemokines. Interestingly, CXCL1 and CXCL12 were both increased in neonates who were delivered by GDMM, while, CXCL9 and CXCL10 were decreased in neonates delivered by GDMM.

Acute myeloblastic leukemia (AML) is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia (APL) is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein (SALL4) is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line. This study was aimed to evaluate the effects of basal indole and its new derivative, 2-(1-((2, 4-Aril)imino)-2,2,2-trifluoroethyl) phenyl-1H Indole-3- carbaldehyde (TFPHC), on the expression of SALL4.Cells were cultured and treated with different concentrations (75, 150, and 300 µg/mL) of the new indole derivative and DMSO, as a vehicle control, for 24 and 48 hours. Cell proliferation was evaluated by using Trypan blue exclusion and MTT assays. The percentage of apoptotic cells was determined by flowcytometry analysis using the Annexin V/PI apoptosis detection kit; mRNA expression of SALL4 was studied using absolute quantitative RT-PCR. Data were analyzed by student's t-test. P0.05 were considered statistically significant.Our findings demonstrated the effects of new indole derivatives on SALL4 mRNA expression. Expression of SALL4 mRNA was significantly decreased at 75, 150, and 300 µg/mL concentrations.SALL4 plays a role in the survival of APL cells. SALL4 expression could be suppressed by the novel indole derivative. Additionally, SALL4 gene suppression can serve as a target in APL therapy.

Balancing between Bax and Bcl-2 plays critical roles in both proliferation and self-renewal activation of cancer cells. Indole-3-formaldehyde derivatives limit the growth and facilitate cell death in different cell systems. In this study, we introduced a novel indole derivative (2-AITFEI-3-F) with tendency to facilitate apoptosis in NB4 line in comparison to basal Indole-3-formaldehyde (I3F).The NB4 cells were cultured in RPMI1640 medium contained 2-AITFEI-3-F and I3F (15.12-1000μg/mL) for 24, 48 and 72h. Inhibition of cell proliferation was assessed by trypan blue staining technique and MTT assay. The fold changes of Bax/Bcl-2 expression against β-actin were determined by real-time-PCR technique. Western blotting analysis was also applied for evaluating the expression of Bax and Bcl2 at protein level. Data were analyzed by student t and repeated measure tests. Differences were considered significant if (P0.01).There was a significant difference in cell viability, when various concentrations of 2-AITFEI-3-F (but similar to I3F) were used for 24, 48 and 72h in comparison to I3F regarding the cellular viability (P0.05). Real time PCR and Western blotting analysis indicated that the gene and protein expression level of Bcl-2 down-regulated while Bax was up-regulated in compare to untreated control cells and cells treated with I3F (P0.01).According to these findings, the novel indole derivative 2-AITFEI-3-F probably triggered apoptosis of NB4 cells by modulating Bax/Bcl-2 ratio. Furthermore, the 2-AITFEI-3-F had markedly displayed anti-cancer activity than I3F.

Immune responses are extensively accepted as primitive etiological leading causes involved in immune system diseases. It is now well established that chemokines as the main arms of the immune system play critical roles in the regulation of immune responses in the pathogenesis of different diseases. Several environmental and genetic elements of the immune system are also believed to potentially affect both the onsets of immunological diseases. The stromal cell-derived factor-1 alpha (SDF-1α) which in new nomenclature is nominated as C-X-C motif ligand 12 (CXCL12) is involved in the development and progression of immune responses. The CXCL12 is an extensively active chemokine that serves as a recruiter for migration and trafficking of leukocytes and hematopoietic progenitor cells. Patients suffering type 2 diabetes (T2D) that ascribe heterozygous SDF-1 3'A genotype (801G/A in the 3' untranslated region) have increased insulin-dependent mobilization of adult progenitor cells, which are known to participate in angiogenesis and vascular repair. Conversely, homing of progenitor cells contributes to the diabetes vascular complications. Because carriers of the SDF-1 3'A genotype show increased levels of the CXCL12 messenger RNA (mRNA) in their peripheral blood mononuclear cells. Genetic variations of CXCL12 gene might affect trafficking of inflammatory cells or defected precursors and hence induced tendency to diabetic complications. The SDF-1 3'A genetic variation of CXCL12 influences the development of late vascular diabetic complications, and previous studies reported that this genetic variation regulates the expression of CXCL12. Therefore, the main goal of the present study was to collect the most recent reports regarding the relation between serum concentrations and SDF-1 3'A genetic variation of CXCL12 in T2D.

BACKGROUND AND OBJECTIVES: β-thalassemia major is one of the most frequent hematological genetic disorders, worldwide. Chemokines are the main components of the immune system and play fundamental roles in pathogenesis of inflammatory disorders. Therefore, the present study aimed to examine whether serum CXC chemokines are altered in β-thalassemia major patients. DESIGN AND SETTINGS: We enrolled 63 β-thalassemia patients and 80 controls in this cross-sectional study, which was performed during 2012-2013 in Kerman, Iran. METHODS: We enrolled 63 β-thalassemia patients and 80 controls in the present study. Patients were selected from referrals to Samenolhojaj clinic for thalassemia, Kerman, Iran. The circulating levels of CXCL1, CXCL9, CXCL10, and CXCL12 were detected by enzyme-linked immunosorbent assay in thalassemia patients and healthy controls immediately after blood collection. Data were analyzed by χ2, t-test, and analysis of variance statistical methods and using SPSS, version 13 (SPSS Inc., Chicago, IL). RESULTS: The results of the study demonstrated a significant elevation of CXCL1, CXCL9, CXCL10, and CXCL12 in thalassemia patients than in control. These results also demonstrated that serum chemokine levels are related to transfusion duration and post-transfusion viral infections. CONCLUSION: According to the results obtained, it can probably be concluded that chemokines are also involved in the pathogenesis of β-thalassemia major and its clinical complications in addition to several other parameters.

Objective Hyperglycemia in patients with Diabetic Mellitus (DM) results from the demolition of islet β cells in the pancreas as well as failure in insulin action or poor response to insulin secretion and there are no further methods to treat diabetes apart from insulin injection and oral hypoglycemic medicines. Thus, the main objective of the current research investigates hydro-alcoholic extracts of Prosopis farcta on impact on the Pyruvate kinase (Pk), Phospho fructo kinase (PFK), Gluco kinase (GK) and signaling insulin Phosphotidylinositol 3-Kinase (PI3K), Insulin Receptor Substrate (IRS1), Glucose Transporter type2 (GLUT2) in HepG2 cells. Method By various concentrations (0–10 mg/ml) of the extract (leaf-root – fruit) for 24 and 48 h, HepG2 cells were cultured and treated in this experimental research. MTT test evaluated cell proliferation by ELISA Reader measured the optical density of the colored solution at 570 nm wavelengths. Real-time-PCR method defined the fold changes of genes expression against β-actin. Data were analyzed by ANOVA. Variations with a P-value Results Our results showed cells were treated with various concentrations of extract (leaf-root – fruit) for 24 and 48 h had markedly declined cell viability in HepG2 cell line as compared to controls in a time and dose-dependent methods, an evident deviation is seen between different concentrations of the extracts. Real Time-PCR analysis showed that the expression of glucokinase, phosphofructo and pyruvate kinase were down regulated and expression of IRS1-PI3K-GLUT2 genes were up regulated in compare to control cells (P Conclusion It appears the anti-diabetic impact of the Prosopis farcta plant not to be over the glycolysis path. This acts mechanisms via enhancing the gene expression in the insulin signaling pathway. The plant, thus, may serve to enhance the insulin secretion function through triggering insulin signaling paths and, in turn, inhibiting increased blood glucose impact on diabetic patients. It is, therefore, expected that the various extracts of such plant may have an impact on diabetic patients, type-2 diabetes in particular.

Immunological factors are important in pathogenesis of various malignancies, including neural cancers. The CXC chemokine CXCL12 is involved in the immune responses. Therefore, the aim of the present study was to investigate the association between tumor tissue and circulating concentrations of CXCL12 as well as its genetic variation at position +801 known as(the SDF-1 3'A), in Iranian patients suffering from malignant glial tumors. In this study, stereotactic tumor biopsy specimens in parallel with peripheral blood samples were collected from 123 patients and 189 healthy controls. The serum level of CXCL12 was measured by ELISA and tumor tissues were subjected to Western blotting for intra-tumor CXCL12 detection; we also employed PCR-RFLP to detect the SDF-1 3'A polymorphism. Demographic data were collected by a researcher-designed questionnaire. These results demonstrated a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of CXCL12. We also indicated elevated levels of CXCL12 in circulation and tumor tissue obtained from in patients suffering from malignant glial tumors. Based upon the results of this investigation, we propose that CXCL12 and its SDF-1 3'A polymorphism play a fundamental part in the pathogenesis of malignant glial tumors. It is also noteworthy that CXCL12 could probably be utilized as a beneficial biological marker in the diagnosis of these tumors.

The indole-3-carbinol (I3C) displays anti-cancer/proliferative activities against human cancer cells. Cellular proliferation is an event associated with the progress and its continuation. This manifest is described by variation in expression and/or functions of genes that are related with cell cycle relevant proteins. The constitutive activation of several signal transduction pathways stimulates cells proliferation as well. The immediate stages in cancer development are accompanied by a fibrogenic response and the progression of the hypoxic environment is in favor of survival and proliferatory functions of cancer stem cells. A main part for prevention of in cancer cells death may manifest through altering cell metabolism. Cellular proliferation and metastasis are reported to be supported with increased generation of responsible hormones (in hormone dependent malignancies), and further promotion the angiogenesis, with epithelial to mesenchymal transition. This may be facilitated by progression of autophagy phenomenon, as well as via taking cues from neighboring stromal cells. Several signaling pathways in association with various factors specific for cellular viability, including hypoxia inducible factor 1, NF-κB, insulin-like growth factor 1 (IGF-1) receptor, Human foreskin fibroblasts (HFF-1), phosphoinositide 3 kinase/Akt, Wnt, cell cycle related protein, with androgen and estrogen receptor signaling are reported to be inhibited by I3C. These evidences, in association with bioinformatics data represent very important information for describing signaling pathways in parallel with molecular targets that may serve as markers for early diagnosis and/or critical targets for designing and development of novel therapeutic regimes alone or combined with drugs, to prevent tumor formation and further progression. In particular, I3C and DIM have been extensively investigated for their importance against numbers human cancers both in vitro and in vivo. We aimed the present manuscript, current study, to review anticancer properties and the miscellaneous mechanisms underlying the antitumorigenicity in an in-depth study for broadening the I3C treating marvel.

Background Hepatitis B virus (HBV) is one of the leading causes of acute and chronic liver diseases and in turn responsible for a million of worldwide annual deaths. HBVhas been classified into eight main groups, designated as A–H with different geographical distribution. Some genotypes are associated with different clinical outcomes and particular viral mutations. Current study was aimed to investigate the genotype and prevalence of HBV in blood donors of south of Iran. Methods This experimental study investigated the prevalence of HBVpositivity in 198,289 Iranian blood donors from south of Iran by both ELISA- and PCR-based methods. Within 198,289 donors, 120 HBsAg+ cases were selected, HBV-DNAwas extracted, and the p gene sequences were amplified by nested-PCR. The HBVgenotypes were determined by direct sequencing of the polymerase gene of HBV. Phylogenetic trees also were constructed by the neighbor-joining (NJ) method. Results Findings of this study indicated that 0.184%, 0.329%, and 0.215% of blood donors were HBsAg+ among Isfahan, Kerman, and Yazd provinces, respectively. Only 69 (57.5%) cases of 120 HBsAg+ donors were HBV-DNA+. Sequencing analysis revealed that all of HBV-infected donors had the D genotype of HBV. Conclusions In conclusion, the prevalence of genotype D was 100% in Iranian HBVblood donors. These findings may have an impact on the immunological and genetic diagnosis of HBV, selection of diagnostic kits, and viral quality control panels to evaluate diagnostic methods.

The immune system plays an important role in the development of leukemia. CXC chemokines, as the molecular members of this system, are involved in the immune responses. Therefore, this study was designed to examine and compare the levels of CXCL1 (Gro-α), CXCL10 (IP-10) and CXCL12 (SDF-1) in ALL patients prior to and post bone marrow transplantation (BMT). In this experimental study, samples were obtained from ALL patients and controls, and subjected to ELISA for detection of chemokines. Demographic data were also collected by a questionnaire. Data were analyzed using SPSS software. Our results showed that the serum levels of CXCL1 (Gro-α), CXCL10 (IP-10) and CXCL12 (SDF-1) were significantly increased in ALL patients compared to the controls. We also showed that the CXCL10 (IP-10) level was increased after BMT in ALL patients, while CXCL1 (Gro-α) and CXCL12 (SDF-1) were inversely decreased. Our results allow for the conclusion that CXCL1 (Gro-α), CXCL10 (IP-10) and CXCL12 (SDF-1) are important for the pathogenesis of ALL. Notably, these chemokines might be used as pivotal biological markers in the diagnosis of leukemia. Recombinant CXCL1 (Gro-α), CXCL10 (IP-10) and CXCL12 (SDF-1) may be applied as a therapeutic approach in the treatment of leukemia patients.

Immune system-related factors are important in pathogenesis of multiple sclerosis. The CXC chemokine SDF-1α (CXCL12) is involved in the immune responses. Hence, the aim of this study was to investigate the association between serum levels of SDF-1α (CXCL12) and its gene polymorphisms at position +801 with multiple sclerosis. In this experimental study, blood samples were collected from 100 multiple sclerosis patients and 100 healthy controls on EDTA pre-coated tubes. DNA was extracted and DNA samples were analyzed for SDF-1α (CXCL12) polymorphisms using PCR-RLFP in patients and controls. The serum levels of SDF-1α (CXCL12) were measured by ELISA. Demographic data were also collected by a questionnaire which was designed specifically for this study. Our results showed a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of SDF-1α (CXCL12). Our results also showed that serum levels of SDF-1α (CXCL12) were markedly higher in patients than healthy controls, but no association was observed between SDF-1α (CXCL12) polymorphism and its serum levels. The results of this study might suggest the serum levels of SDF-1α (CXCL12) and its polymorphism play an important role in pathogenesis of multiple sclerosis. It is also worth noting that these factors could probably use as pivotal biological markers in the diagnosis of MS.

Several environmental and genetic factors are believed to influence the onset of diabetes and its complications. It has also been established that cytokines play a key role in the pathogenesis of type 2 diabetes. Previous studies have revealed that the polymorphism at the stromal-derived factor 1β (SDF-1β) 3'A regulates the expression of SDF-1 (CXCL12). This study was aimed to explore this polymorphism in parallel with SDF-1 serum levels in type 2 diabetic patients. In this assessment, peripheral blood samples were collected from 200 type 2 diabetic patients and 200 healthy controls. DNA was extracted, and a PCR-RFLP screening was applied to examine the SDF-1β 3'A polymorphism. We also applied the ELISA technique to measure serum levels of SDF-1. Our results showed that there were no significant correlations between SDF-1β 3'Α polymorphism in type 2 diabetic patients when compared to controls. However, our results showed that the serum levels of SDF-1 were significantly increased in the patients when compared to controls. Based on the results of this study, we concluded that SDF-1β 3'Α polymorphism does not play a role in the pathogenesis of type 2 diabetes but that elevated serum levels of SDF-1 may be important for the etiology of type 2 diabetes but are unrelated to the SDF-1β 3'Α polymorphism.

Objective: To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile on HepG2 cell line. Methods: HepG2 cells were treated with hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat. IC20 was calculated using the MTT method. The cells were then pre-treated with IC20 concentrations for 24 and 48 h. Real time PCR was employed to measure expression of liver X receptor alpha (LXR α ), sterol regulatory element-binding protein-1C (SREBP-1C), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fibroblast growth factor 21 (FGF21), peroxisome proliferator-activated receptor gamma (PPAR γ ), and low-density lipoprotein receptor (LDLR). Results: The results showed that LXR α (P=0.003, P

Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area (VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats (200-250 g) were used in 5 experimental groups: 1) non morphine treat rats (control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid (i.p., for 21 d); 3) morphine treated rats (10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression (P

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Dear Editor, We read carefully the article by Zehedi et al., (1) which determined the prevalence of hepatitis B (HBV), C (HCV), and D (HDV) viruses as well as the human immunodeficiency virus (HIV) in hemodialysis (HD) patients within Kerman province, located in south-east region of Iran (1). It is now well established that the prevalence of various types of hepatitis viruses among HD patients is higher than the general population (2). According to the important role playing by viral infections in the pathogenesis of HD health status, the prevalence of the viral infections was evaluated in the HD patients by the authors. They have reported that the prevalence of HBV and HCV was moderate to low, while, HIV-Ab and HDV-Ab were both negative in all patients of Kerman province (1). The Authors of this letter believe that zahedi and co-worker`s results need to be interpreted more cautiously, because possible confounders and limitations of their study need to be considered. Zahedi et al., have evaluated the prevalence of HBV and also HCV using ELISA dependent technique and studied the HCV-RNA and HBV-DNA in the HCV-Ab and HBsAg positive patients, respectively, via Real-Time PCR. Based on the previous reports, it is obvious that a proportion of the HCV infected patients are unable to produce detectable antibody against HCV due to several reasons including humeral immunodeficiency (3), impaired Th2 system (4) as well as insufficient stimulation by innate immunity (5, 6). Additionally, the infected patients need enough time from the initiation point of the infection to produce anti-HCV antibodies (latent phase). Therefore, considerable cases of HCV infected individuals have been missed where merely ELISA technique is used to detect HCV infection. In contrast with Zahedi et al.’ results, our research team has reported already a high rate may be the cause of HCV infection in the HD patients within Kerman province of Iran (2). Interestingly, we have used RT-PCR to detect HCV-RNA in the patients, hence; it is likely that the prevalence of HCV infection may be in contrast to Zahedi et al., which is reported not following a moderate to low fashion in Kermanian HD patients. The controversy can also be considered for prevalence of HBV infection in the HD patients. We have also previously demonstrated that the prevalence of occult HBV infection (OBI), HBsAg-/HBV-DNA+ patients, was high in a population of Iranian blood donors, hence, again it seems that the prevalence of this form of disease could be elevated in the HD patients, who are among the mostly recipients of blood and its components. In parallel with our claim, several researchers reported this form of disease in the Iranian and worldwide HD patients (7-9). Due to the fact that, OBI is a form of hepatitis B, hence, evaluation of the HBsAg cannot be sufficient for reporting of HBV infection prevalence in the HD patients and the role played by OBI in the spread of infection in the HD patients may need more attentions. Finally, in order to collect more accurate and valid data regarding the real prevalence of HBV and HCV infection, we suggest re-evaluating the Kerman province HD patients using quantitative PCR technique.

SUMMARY Background: Type-1 diabetes (T1D) is defined as a heterogeneous autoimmune disease. Immune system related factors are important in the pathogenesis of T1D. Chemokines are important factors in the pathogenesis of several autoimmune diseases, including T1D. They are potent chemotactic cytokines with various functions such as maturation, trafficking of leukocytes, angiogenesis, and homing of stem cells. Therefore, the current study was aimed to examine whether expression of CC chemokines CCL2, CCL5, and CXCL11 is associated with disease duration and complications in Iranian T1D patients. Methods: In this experimental study, blood samples were collected from 108 T1D patients and 189 healthy controls in EDTA pre-coated tubes. The serum levels of CC chemokines were measured by ELISA. Demographic data were also collected along with experimental examinations in a questionnaire which was designed specifically for this study. Results: Results of the present study demonstrated that the expression of CCL2 was decreased while CCL5 and CCL11 were increased in T1D patients in comparison to controls. These results demonstrated that CCL2, CCL5, and CCL11 were elevated in T1D patients with duration of disease. Again, our findings demonstrated that CCL2, CCL5, and CCL11 were elevated in T1D patients with age. But there was not a significant difference between circulating level of CC chemokines studied in T1D patients regarding their gender and they have followed a similar pattern of expression in both genders. Our findings also showed that all three CC chemokines were elevated in T1D patients suffering from diabetes complications. Conclusions: According to the results of our study, elevated levels of CCL5 and CCL11 are in parallel with decreased level of CCL2 and are useful tools in the differential diagnosis of T1D from other types of metabolic disorders. Elevated levels of these CC chemokines probably could be implicated as predictive factors for occurrence of T1D complications. These results may also re-emphasize the prominent therapeutic role(s) of these CC chemokines in control of either T1D or its associated complications. (Clin. Lab. 2013;59:993-1001. DOI: 10.7754/Clin.Lab.2012.120810)