Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is one of the most common causes of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be >90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study's purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (χ(2)=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLA-B2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Polymorphisms of IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS.     

Reduction of Winter Wheat Yield Losses Caused by Stripe Rust through Fungicide Management

Stripe rust of winter bread wheat (Triticum aestivum L.) causes substantial grain yield loss in Central Asia. This study involved two replicated field experiments undertaken in 2009–2010 and 2010–2011 winter wheat crop seasons. The first experiment was conducted to determine grain yield reductions on susceptible winter wheat cultivars using single and two sprays of fungicide at Zadoks growth stages Z61–Z69 in two farmers’ fields in Tajikistan and one farmer's field in Uzbekistan. In the second experiment, four different fungicides at two concentrations were evaluated at Zadoks growth stage Z69. These included three products from BASF – Opus (0.5 l/ha and 1.0 l/ha), Platoon (0.5 l/ha and 1.0 l/ha) and Opera (0.75 l/ha and 1.5 l/ha) – and locally used fungicide Titul 390 (0.5 l/ha and 1.0 l/ha). One and two sprays of fungicides did not differ significantly (P > 0.05) in increasing grain yield. Stripe rust reduced grain yield and 1000‐kernel weight (TKW) from 24 to 39% and from 16 to 24%, respectively. The benefits from the two concentrations of the same fungicide did not consistently resulted in significantly higher grain yield, suggesting that the lower concentrations could be more cost effective. Our study provides important information about the selection of fungicides, spray concentrations and number of spray to control stripe rust and increase grain yield. The findings could play an important role in developing stripe rust management approaches such as fungicide rotation and strategic fungicide applications in Central Asian countries.     

TGF-β1 receptor blockade attenuates unilateral ureteral obstruction-induced renal fibrosis in C57BL/6 mice through attenuating Smad and MAPK pathways

Journal of Molecular Histology - Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal...     

Pre-and Post-Transplant Serum Lactate Dehydrogenase Levels as a Predictive Marker for Patient Survival and Engraftment in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Background:The discovery of biomarkers to predict the development of complications associated with hematopoietic stem cell transplantation (HSCT) offers a potential avenue for the early identification and treatment of these life-threatening consequences. Serum lactate dehydrogenase (sLDH) has been identified as a potential biomarker for determining the outcome of allogenic HSCT (allo-HSCT).Methods:A retrospective study was performed using data collected from 204 allo-HSCT recipient patients to examine the predictive value of sLDH levels pre- and post-allo-HSCT on patient survival, graft-versus-host-disease (GVHD) incidence, and time to platelet/white blood cells (WBC) engraftment.Results:Our findings show that neither pre- (p= 0.61) nor post-transplantation (p= 0.55) sLDH levels were associated with GVHD incidence. However, elevated sLDH levels pre- and post-transplantation (≥ 386 and ≥ 409 IU/mL, respectively) were found to be adverse risk factors for patient survival (p= 0.16, p= 0.20, respectively). Furthermore, a median sLDH level ≥ 400 IU/mL from day +5 to day +15 post-transplantation had a significant positive association with enhanced time to platelet and white blood cell (WBC) engraftment, compared to patients with sLDH levels < 400 IU/mL (p< 0.001).Conclusion:Our data suggests that high sLDH levels pre- and post-allo-HSCT could be considered a predictor of poor patient survival. Furthermore, high levels of sLDH days 5-15 post-allo-HSCT could be associated with improved time to platelet and WBC engraftment; however, this appears to come at the cost of increased mortality risk.Key Words: Engraftment, Graft versus host disease, Hematopoietic stem cell transplantation, Lactate dehydrogenase     

Fe3O4 and bimetal–organic framework Zn/Mg composite peroxide-like catalyze luminol chemiluminescence for specific measurement of atropine in Datura plant

Atropine (AT) is an anticholinergic drug. AT is abundantly in Datura plant seeds. Fe₃O₄@Zn/Mg MOF (Fe₃O₄@MOF) composite was synthesized. The compound had a high peroxidase-like activity in a chemiluminescence (CL) reaction. Addition of AT quenched CL. The linear range and limit of detection were 5–600 μg L⁻¹ and 2 × 10⁻² μg L⁻¹. This method is fast, reversible, and selective, without biodegradability effects, high accuracy, and precision for measuring AT in the Datura plant.     

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.     

Association of Mood Disorders with Serum Zinc Concentrations in Adolescent Female Students

Among various factors influencing mood disorders, the impact of micronutrient deficiencies has attracted a great attention. Zinc deficiency is considered to play a crucial role in the onset and progression of mood disorders in different stages of life. The main objective of this study was to assess the correlation between serum zinc levels and mood disorders in high school female students. This cross-sectional study was conducted on a random sample of 100 representative high school female students. The participants completed 24-h food recall questionnaires to assess the daily zinc intakes. Serum zinc status was assessed using flame atomic absorption spectrometry, and zinc deficiency was defined accordingly. Mood disorders were estimated by calculating the sum of two test scores including Beck’s depression inventory (BDI) and hospital anxiety depression scale (HADS) tests. General linear model (GLM) and Pearson’s regression test were applied to show the correlation of serum zinc levels and mood disorder scores and the correlation between zinc serum levels and BDI scores, respectively. Dietary zinc intake was higher in subjects with normal zinc concentrations than that of zinc-deficient group (p = 0.001). Serum zinc levels were inversely correlated with BDI and HADS scores (p < 0.05). Each 10 μg/dL increment in serum zinc levels led to 0.3 and 0.01 decrease in depression and anxiety scores, respectively (p < 0.05). Serum zinc levels were inversely correlated with mood disorders including depression and anxiety in adolescent female students. Increasing serum levels of zinc in female students could improve their mood disorders.     

Suicide-peroxide inactivation of horseradish peroxidase in the presence of sodium n-dodecyl sulphate: a study of the enzyme deactivation kinetics

In the presence of the anionic surfactant sodium n-dodecyl sulphate (SDS), horseradish peroxidase (HRP) undergoes a deactivation process. Suicide inactivation of horseradish peroxidase by hydrogen peroxide(3 mM) was monitored by the absorbance change in product formation in the catalytic reaction cycle. The progress curve of the catalytic reaction cycle was obtained at 27degrees C and phosphate buffer 2.5 mM (pH = 7.0). The corresponding kinetic parameters i.e., intact enzyme activity (alpha i); the apparent rate constant of suicide inactivation by peroxide (ki); and the apparent rate constants of enzyme deactivation by surfactant (kd) were evaluated from the obtained kinetic equations. The experimental data are accounted for by the equations used in this investigation. Addition of SDS to the reaction mixture intensified the inactivation process. The deactivation ability of denaturant could be resolved from the observed inactivation effect of the suicide substrate by applying the proposed model. The results indicate that the deactivation and the inactivation processes are independent of each other.     

Truncated pStat5B is associated with the Idd4 locus in NOD mice

We investigate JAK-STAT5 activation and its relationship to full-length Stat5B (FL-Stat5) and constitutive phosphorylated carboxy-truncated Stat5B (ct-pStat5) in four different strains of mouse. Our electrophoresis mobility shift assays data indicate constitutive phosphorylation of full-length-Stat5 (p<0.001) and DNA binding in NOD but not in B6 mice. Our data suggest that the relative ratio of FL-Stat5: ct-Stat5 in NOD is 5- to 8-fold lower (p<0.0001) when compared with normal B6 mice. Additionally, EMSAs data from B6.NOD/c11 suggest contribution of Idd4 susceptibility locus on chromosome 11 in constitutive phosphorylation of Stat5 in NOD mice. The presence of ct-pStat5 in regulatory T cells of NOD mice suggests this form of Stat5 is associated with impaired function of Tregs in NOD mouse. In agreement with our previous report the JAK-Stat5B defective pathway in NOD mice along with other defective factors is associated with the pathogenesis of autoimmune type 1 diabetes in NOD mice.     

Chloroplast‐derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery

Cholera and malaria are major diseases causing high mortality. The only licensed cholera vaccine is expensive; immunity is lost in children within 3 years and adults are not fully protected. No vaccine is yet available for malaria. Therefore, in this study, the cholera toxin‐B subunit (CTB) of Vibrio cholerae fused to malarial vaccine antigens apical membrane antigen‐1 (AMA1) and merozoite surface protein‐1 (MSP1) was expressed in lettuce and tobacco chloroplasts. Southern blot analysis confirmed homoplasmy and stable integration of transgenes. CTB‐AMA1 and CTB‐MSP1 fusion proteins accumulated up to 13.17% and 10.11% (total soluble protein, TSP) in tobacco and up to 7.3% and 6.1% (TSP) in lettuce, respectively. Nine groups of mice (n = 10/group) were immunized subcutaneously (SQV) or orally (ORV) with purified antigens or transplastomic tobacco leaves. Significant levels of antigen‐specific antibody titres of immunized mice completely inhibited proliferation of the malarial parasite and cross‐reacted with the native parasite proteins in immunoblots and immunofluorescence studies. Protection against cholera toxin challenge in both ORV (100%) and SQV (89%) mice correlated with CTB‐specific titres of intestinal, serum IgA and IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. Increasing numbers of interleukin‐10⁺ T cell but not Foxp3⁺ regulatory T cells, suppression of interferon‐γ and absence of interleukin‐17 were observed in protected mice, suggesting that immunity is conferred via the Tr1/Th2 immune response. Dual immunity against two major infectious diseases provided by chloroplast‐derived vaccine antigens for long‐term (>300 days, 50% of mouse life span) offers a realistic platform for low cost vaccines and insight into mucosal and systemic immunity.