DNA interaction studies of a cobalt(III) complex containing ß-amino alcohol ligand by spectroscopic and molecular docking methods.

In the present research, the feasibility of a Cobalt(III) complex containing ß-amino alcohol ligands for affinity with the target calf thymus DNA is demonstrated. In the title complex, [Co(C11H15N2O2)2]Cl, the Co(III) atom is six-coordinated with four N atoms and two O atoms from (2-[(E)-({2-[(2-Hydroxyethyl) amino]ethyl}imino)methyl]phenol) ligand (L). To investigate the molecular interaction between the synthesized complex and DNA, some multi-spectroscopic approaches associated with molecular docking were employed in the physiological buffer (pH 7.4). The results indicated that the Co(III) complex proved to be a minor groove binder with a preference for the A-T region, which was substantiated by displacement studies with Hoechst33258 and Methylene blue (MB) as minor groove binder and intercalator. In addition, the results of the molecular docking study revealed that the Co(III) complex approached the gap between the DNA minor grooves near the spot where the Hoechst was. Furthermore, the results of the cytotoxicity and apoptosis tests for the MCF-7 cell line were also indicative of the positive effects of the complex on controlling the growth and viability of breast cancer.Communicated by Ramaswamy H. Sarma.

Leukemia Inhibitory Factor Suppresses NKG2D mRNA Expression and Presentation on Human Natural Killer Cells.

Leukemia inhibitory factor (LIF) is a multi-functional cytokine secreted from cells such as lymphocytes and hepatocytes. This study aimed to evaluate the effect of LIF on natural killer group 2 member D (NKG2D) receptors' expression and presentation on natural killer (NK) cells.  For this purpose, peripheral blood mononuclear cells taken from 4 young male healthy blood donors were isolated and the effect of LIF (25 ng/mL) after 12, 24, and 48 hours of incubation, on NKG2D receptors expression and presentation was investigated using flow cytometry and real-time-polymerase chain reaction (PCR). All of the steps of the experiment were performed in duplicate. After periods of 12, 24, and 48 hours, LIF reduced both the expression and presentation of the NKG2D receptor on NK cells. The results suggest that this cytokine has a direct modulating activity on the body's immune response through suppression of NKG2D receptor expression and presentation on NK cells.

Vitamin D3 Induced Decrease in IL-17 and Malondialdehyde, and Increase in IL-10 and Total Antioxidant Capacity Levels in Patients with Irritable Bowel Syndrome.

BACKGROUND: Given the variations in clinical presentation and physiopathological mechanisms in irritable bowel syndrome (IBS) subtypes, it is an acknowledged fact that the response to treatments can be disparate. OBJECTIVE: To assess the effect of vitamin D on inflammatory cytokines (IL-17, IL-10, TNF-α), and biomarkers of oxidative stress (total antioxidant capacity (TAC), and malondialdehyde (MDA)) among IBS patients. METHODS: A double-blind, randomized, placebo-controlled 6-month intervention study was carried out on 90 IBS patients (85 were analyzed), as defined by the Rome III criteria. Study participants were randomly assigned to receive either 50,000 IU vitamin D3 or a placebo fortnightly. RESULTS: Vitamin D supplementation significantly reduced the IL-17 and MDA serum levels (P<0.05) and observably increased the TAC and IL-10 serum levels (P<0.05), compared with the placebo group. Comparing different bowel habit subtypes, we observed that it was only in diarrhea predominant IBS (IBS-D) that vitamin D supplementation was able to significantly reduce the serum levels of TNF-α and IL-17 (P<0.05). However, in all subtypes, IL-10 and TAC increased, while MDA decreased (P<0.05) in vitamin D group, compared to the placebo group. CONCLUSION: Vitamin D3 supplementation reduces the serum IL-17 and MDA levels, and augments the serum IL-10 and TAC levels in IBS patients, particularly in IBS-D subtype. Thus, the present study demonstrates the beneficial effects of vitamin D on patients with IBS-D.

Malignant Transformation in Leukoplakia and Its Associated Factors in Southern Iran: A Hospital Based Experience.

BACKGROUND: We evaluated factors that affect malignant transformation of leukoplakia in a sample of the Iranian population. METHODS: The records of patients with a clinical diagnosis of leukoplakia during a 20-year period from 1989-2009 referred to two of the largest referral centers in southern Iran were studied. Patients that developed malignant transformation were compared with patients that did not have malignant changes. RESULTS: Of 522 patients, female patients, those over 50 yr old and with lesions located on the tongue had the highest rate of malignant changes. Female patients with malignant changes were mostly non-smokers (76.4%), while male patients with malignant changes were mostly smokers (63.8% in non-smokers) (P<0.001). In our univariate analysis, male sex and smoking showed lower chances for malignant transformation (OR: 0.57; CI=0.397-0.822 and OR: 0.025; CI=0.141-0.299, respectively), while age above 50 was a risk factor for malignant transformation (OR: 3.57; CI=2.32-5.42). In the multivariate analysis, smoking (OR: 0.317; 95% CI=0.16-0.626) and morphological presentation as erythroplakia (OR: 0.025; 95% CI=0.005-0.131) had low chances for developing malignant changes, while site of lesion on the tongue (OR: 774; 95% CI=60-9838) and morphological presentation as erythroleukoplakia (OR: 6.26; 95% CI=3.16-12.38) were a risk factor for developing malignant changes. CONCLUSION: A follow-up program and further work-up should be considered for Iranian patients who have a leukoplakia lesion that is flat and are white patch or plaques with red components, in addition for patients who have lesions located on the tongue and for nonsmokers who develops leukoplakia lesions.

Comparison of antimicrobial effects of titanium tetrafluoride, chlorhexidine, xylitol and sodium fluoride on streptococcus mutans: An in-vitro study.

INTRODUCTION: No studies have yet documented the bactericidal effects of TiF4, and its role in the treatment of dental caries, and no definite protocol has been introduced to regulate its use. The aim of this study was to determine the antimicrobial/bactericidal effects of TiF4 on Streptococcus Mutans (S. Mutans) and to compare it with chlorhexidine (Chx), sodium fluoride (NaF) and xylitol. METHODS: This study was conducted at the Shiraz University of Medical Sciences microbiology laboratory during March 2015 to September 2015. In this in-vitro study, first a bacterial suspension was prepared and adjusted to a 0.5 McFarland standard (equivalent to 1×108 CFU/ml). The minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) of TiF4, Chx, NaF and xylitol were assessed using broth microdilution assay and disk diffusion methods. In order to neutralize the acidic nature of TiF4, we used a sodium hydroxide preparation to obtain a pH of 7.2 and repeated all of the previous tests with the neutralized TiF4 solution. We reported the final results as percentages where appropriate. RESULTS: The MIC of TiF4, NaF and Chx for S. Mutans were 12.5%, 12.5% and 6.25%, respectively. At a concentration of 12.5% the inhibition zone diameters were 9 mm, 15mm and 14mm for TiF4, NaF and Chx, respectively. The MBC was 25%, 12.5% and 12.5% for TiF4, NaF and Chx, respectively. Xylitol failed to show any bactericidal or growth inhibitory effect in all of its concentrations. When we repeated the tests with an adjusted pH, identical results were obtained. CONCLUSION: TiF4 solutions have anti-growth and bactericidal effects on S. Mutans at a concentration of 12.5% which is comparable with chlorhexidine and NaF, indicating the possible use of this solution in dental practice as an anti-cariogenic agent, furthermore the antimicrobial activity is unaffected by pH of the environment.

The Effect of G2 Adjuvant on Gene Expression and Delivery of NKG2D Receptor on NK Cells in Peripheral Blood.

INTRODUCTION: Natural killer (NK) cells are a subset of lymphocytes in humans that release cytokines such as tumor necrosis factor alpha and interferon gamma-γ during infection. NKG2D is one of the most important stimulating NK receptors binding MIC-A, MIC-B, and ULBPs, which leads to activation of NK cells against tumor cells. In this study, the authors evaluated the effect of G2 adjuvant on gene expression and delivery of NKG2D receptor on NK cells in peripheral blood. MATERIALS AND METHODS: Peripheral blood mononuclear cells were isolated from venous blood obtained from healthy volunteers after adding G2 adjuvant within 12, 24, and 48 hours of incubation. Then, total RNA was extracted from the cells, cDNA synthesis was performed, and gene expression was evaluated by real-time PCR. In addition, NK cells were stained with the appropriate monoclonal antibodies, and the receptors expressed on cell surface were quantified. RESULTS: G2 adjuvant leads to upregulation of gene expression and increases the expression of NKG2D receptor on the surface of NK cells after incubation. CONCLUSION: The findings of this study demonstrated that G2 adjuvant can increase NK cell cytotoxicity. It may play an important role in killing tumor cells, preventing tumor growth and metastasis.

Assessment of Relationship between Wilms' Tumor Gene (WT1) Expression in Peripheral Blood of Acute Leukemia Patients and Serum IL-12 and C3 Levels.

BACKGROUND: Leukemia is a common cancer among children and adolescents. Wilms' tumor gene (WT1) is highly expressed in patients with acute leukemia. It is found as a tumor associated antigen (TAA) in various types of hematopoietic malignancies and can be employed as a useful marker for targeted immunotherapy and monitoring of minimal residual disease (MRD). In this regard, WT1 is a transcription factor that promotes gene activation or repression depending on cellular and promoter context. The purpose of this study was assessment of WT1 gene expression in patients with acute leukemia, measurement of IL-12 and C3 levels in serum and evaluation of the relationship between them. MATERIALS AND METHODS: We evaluated the expression of WT1 mRNA using real-time quantitative RT-PCR and serum levels of IL-12 and C3 using ELISA and nephelometry in peripheral blood of 12 newly diagnosed patients with acute leukemia and 12 controls. RESULTS: The results of our study showed that the average wT1 gene expression in patients was 7.7 times higher than in healthy controls (P <0.05). In addition, IL-12 (P = 0.003) and C3 (P <0.0001) were significantly decreased in the test group compared to controls. CONCLUSIONS: WT1 expression levels are significantly higher in patients compared with control subjects whereas serum levels of interleukin-12 and C3 are significantly lower in patients. Wt1 expression levels in patients are inversely related with serum levels of IL-12 and C3.