Leishmania major: effects of proteophosphoglycan on reactive oxygen species, IL-12, IFN-gamma and IL-10 production in healthy individuals

Protozoan parasites of the genus Leishmania secrete a range of proteophosphoglycans (PPG) known to be important for successful colonization of Leishmania in the sandfly and for virulence in the mammalian host. PPGs are a large family of extensively glycosylated proteins with some unusual and unique features. In this study we purified PPG from culture supernatant of Leishmania major metacyclic promastigotes. In discontinuous SDS-PAGE, PPG could not enter the resolving gel but after mild acid hydrolysis several bands resolved. Agarose gel electrophoresis and immunoblot analysis using monoclonal antibody (WIC 79.3) indicated that the PPG preparation consisted of heterogeneous molecules. Compositional analysis showed that the PPG preparation contained 67% glycan, 28% protein and 5% phosphate. Additionally, the effect of PPG on reactive oxygen species (ROS) production and induction of IL-10, IL-12 and IFN-γ secretion by human peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals was investigated. The water-soluble secreted form of PPG at a concentration of 1 μg glycan/ml seems to be a potent inducer of ROS and IL-10 and to a lesser extent of IFN-γ and IL-12. Cytokines and ROS production was decreased in a dose-dependent manner as the concentration of PPG was increased to 100 μg glycan/ml.     

Association of mitochondrial dysfunction and lipid metabolism with type 2 diabetes mellitus: A review of literature

Background

Diabetes mellitus (DM) is one of the most prevalent chronic diseases, and its prevalence continues to increase globally. The impact of mitochondrial dysfunction and lipid metabolism on diabetes mellitus and insulin resistance (IR) has been implicated in several previous reports; however, the results of studies are confusing despite four decades of study.

Methods/Results

This review has evaluated updated understanding of the role of mitochondrial dysfunction and lipid metabolism on type 2 diabetes, and found that mitochondrial dysfunction and lipid metabolism disorder induce the dysregulation of liver and pancreatic beta cells, insulin resistance, and type 2 diabetes.

Conclusion

Mitochondrial dysfunction and lipid metabolism induce metabolic dysregulation and finally increasing the possibility of diabetes.

     

Genetics of Iranian Alpha-Thalassemia Patients: A Comprehensive Original Study

Alpha thalassemia is the most prevalent monogenic gene disorder in the world, especially in Mediterranean countries. In the current hematological phenotype of patients with different genotypes, the effects of missense mutations on the protein function and also stability were evaluated in a large cohort study. A total of 1,560 subjects were enrolled in the study and divided into two groups: 259 normal subjects; and 1301 alpha-thalassemia carriers. Genomic DNA was extracted and analyzed using ARMS PCR, Multiplex Gap, and direct sequencing. The effects of single nucleotide change on the protein function and stability were predicted by freely available databases of human polymorphisms. Sixty-three different genotypes were seen in the patients. The more prevalent was heterozygote form of ?α3.7 (41.4%) followed by ?α3.7 homozygote (11.6%) and ?MED (3.8%). The significant differences were seen in mean hemoglobin level [F?=?20.5, p?<?0.001] between the Alpha-globin genotypes, when adjusted for gender. Moreover, 28 different mutations were found in our study. A significant relationship was seen between ethnicity and the alpha-globin mutation frequency χ² (df;8)?=?38.36, p?<?0.0001). Different genotypes could display as different phenotypes. The mutation frequency distributions in our region are different from those of other parts of Iran. Significant differences are seen in the spectrum of mutation frequency among various ethnicities. Finally, some missense mutations might not have considerable effect on the proteins, and they could be neutral mutations.     

Leukocyte Gene Expression and Plasma Concentration in Multiple Sclerosis: Alteration of Transforming Growth Factor-βs,Claudin-11, and Matrix Metalloproteinase-2

Multiple sclerosis is a neurodegenerative disease characterized by the present of leukocytes in the brain tissue and subsequently the formation of sclerotic plaques. Leukocytes penetration into the blood–brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics. In this frame, we explore alteration of matrix metalloproteinase-2 (MMP-2), transforming growth factor beta (TGF-β) family, and Claudin-11 (as a main myelin structural protein) in leukocytes and blood plasma of multiple sclerosis patients compared to the normal group. Blood samples were collected from thirteen men affected by MS and fifteen healthy men. Leukocyte gene expression was measured using real-time PCR and plasma parameters were examined by ELISA. The results of this study showed that the gene expression of Claudin-11 was significantly higher in MS group compared with normal. Interestingly, the MMP-2 pattern was similar to Claudin-11 and correlated positively with it. It was observed that, although the expressions of TGF-β1 and TGF-β2 are down-regulated in the leukocytes of subjects with MS, they showed higher levels of these cytokines in blood plasma. The plasma level of TGF-β3 in MS patients was higher than normal and correlated with Claudin-11 concentration. In conclusion, the aberrant pattern of Claudin-11, TGF-βs family, and MMP-2 expression in leukocytes of the MS patients was observed in this study. Moreover, the plasma levels of TGF-βs family increased in the MS group. The findings of this study provide clues for further investigations to assay MS pathogenesis.     

Effect of soil texture and its organic content on the efficacy of Trichoderma harzianum (MIAU 145 C) in controlling Meloidogyne javanica and stimulating the growth of kidney beans

The efficiency of Trichoderma harzianum (MIAU 145 C) in promoting kidney bean (cv. Goli) growth in different soil texture (sandy loam, loam and clay loam) and organic matter content (0.5 and 2% of leaf litter) was assessed in a factorial experiment in the absence of Meloidogyne javanica. In another factorial experiment, the effect of soil texture, soil organic content and control measure (no control, 10?ml of T. harzianum containing 10⁶ spore ml^?1 and 2?mg ai cadusafos kg^?1 soil) was determined on nematode-infected kidney bean’s growth, fungus controlling activity and M. javanica reproduction. Except for the shoot length, the fungus improved plant growth. Clay loam was not a proper soil type for the cultivation of kidney bean plants (even in the soil without nematode), but the plant grew better in sandy loam and loam soil. The presence of leaf litter in the soil enhanced plant growth, increased fungal efficiency and increased nematode reproduction. It seems that T. harzianum can activate the plant defence system in sandy loam soil. T. harzianum was more effective in sandy loam or loam soil containing 2% organic matter (leaf litter) and reduced the reproduction factor of the nematode in the tested soil textures equally to the chemical nematicide treatment.     

Lack of association between interleukin-13 gene polymorphisms (−1055 C/T and +2044 G/A) in Iranian patients with lung cancer

Lung cancer is one of the leading causes of death from cancer. Both immune cells and tumor cells play a key role in lung cancer immunity by secretion of cytokines and developing type-2 cell-mediated immune response. IL-13 is an immunoregulatory cytokine affecting tumor immunosurveillance by deviation of immune response from Th1 to Th2. In the present study we sought to determine the association of single nucleotide polymorphisms (SNPs) of IL-13 gene at positions +2044 (G/A) and −1055 (C/T) and lung cancer. One hundred forty one patients and 113 controls were recruited; control group was subdivided into smoker and nonsmoker individuals for serum detection. Genotyping was carried out by PCR-RFLP assay and IL-13 detection by ELISA method. No statistically significant difference was found in the frequency of genotypes, alleles, and haplotypes at positions +2044 (G/A) and −1055 (C/T) of IL-13 gene between lung cancer patients and controls. Serum level of IL-13 was not detectable in both groups. The results of this study reveal that although +2044 (G/A) and −1055 (C/T) SNPs in IL-13 are implicated in some pulmonary processes, they do not confer susceptibility to lung cancer in Iranian population.     

Mucor hiemalis: a new source for uricase production

Summary One hundred and sixty-five strains of microorganisms with the ability to grow in a medium containing uric acid as a major source of nitrogen were isolated from soil samples during a screening program. Among them, a zygomycete fungus with well-developed columellae was recognized to produce high levels of the enzyme in a short time. Classification of the isolated fungus was carried out according to the morphological and culture characteristics of the organism, and it was identified as Mucor hiemalis. The fungus was able to produce an intracellular urate oxidase in a fermentation medium mainly containing uric acid. Optimized composition of the medium consisted of (l⁻¹ of distilled water) uric acid, 7.0 g; maltose, 6.0 g; Vogel stock solution, 20 and 1 ml of 0.5 M copper sulphate. The optimum pH and temperature for uricase production in the optimized medium were pH 6 and 30 °C, respectively.