Incidence of Chronic Kidney Disease and Its Risk Factors,Results of Over 10 Year Follow Up in an Iranian Cohort

To examine, the predictors of incident chronic kidney disease (CKD) in a community-based cohort of Middle East population, during a mean follow-up of 9.9 years. In a sample of 3313 non-CKD Iranian adults ≥20 years the estimated glomerular filtration rate (eGFR) was calculated at baseline and at three year intervals during three consecutive phases. The eGFR <60 mL/min/1.73 m2 was defined as CKD. Multivariate Logistic regression analysis was used to determine the independent variables associated with incident CKD. The incidence density rates of CKD were 285.3 and 132.6 per 10,000 person-year, among women and men, respectively. Female gender per se was associated with higher risk of CKD, compared with males. Among women, age, eGFR, known diabetes, being single or divorced/widowed, hypertension (marginally significant) and current smoking were independent risk factors for CKD; however the intermediate degree of education and family history of diabetes decreased the risk by 40% (P<0.05). Among male subjects, independent predictors of developing CKD included aging and hypertension (with significantly higher risk than in women, P for interaction<0.05), eGFR, new diagnosed diabetes, high normal blood pressure; abdominal obesity decreased the risk of CKD about 30% which was marginally significant. In the Iranian population,>2% of individuals develops CKD each year. Our findings confirmed that sex- specific risk predictors should be considered in primary prevention for incident CKD.     

Active immunization using exotoxin A confers protection againstPseudomonas aeruginosa infection in a mouse burn model

Background  

Pseudomonas aeruginosa is an important cause of nosocomial infection and may lead to septicemia and death. We evaluated the immunogenicity of semi-purified exotoxin A from the bacterium in a mouse burn model.     

Mathematical modeling of ethanol production in solid-state fermentation based on solid medium’ dry weight variation

In this work, mathematical modeling of ethanol production in solid-state fermentation (SSF) has been done based on the variation in the dry weight of solid medium. This method was previously used for mathematical modeling of enzyme production; however, the model should be modified to predict the production of a volatile compound like ethanol. The experimental results of bioethanol production from the mixture of carob pods and wheat bran by Zymomonas mobilis in SSF were used for the model validation. Exponential and logistic kinetic models were used for modeling the growth of microorganism. In both cases, the model predictions matched well with the experimental results during the exponential growth phase, indicating the good ability of solid medium weight variation method for modeling a volatile product formation in solid-state fermentation. In addition, using logistic model, better predictions were obtained.     

Integrative analysis of OIP5-AS1/HUR1 to discover new potential biomarkers and therapeutic targets in multiple sclerosis

Multiple sclerosis (MS) is a devastating autoimmune disease of the central nervous system associated with demyelination and axonal injury. This study was designed to find potential lncRNAs and their targets that are associated with the molecular basis of MS pathogenesis. In this study, peripheral blood samples were obtained from 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls. lncRNAs and their target were selected for validation using TaqMan Real-Time PCR. Interactions were studied based on approaches that used to investigation biological functions and signaling pathways affected by differentially expressed messenger RNAs (mRNAs). The results of this study indicate an increase in the expression of HUR1 (p = 0.0001), CPSF7 (p = 0.02), and reduction of CSTF2 expression (p = 0.04). Also, an increase in the expression of OIP5-AS1 (p = 0.01) was observed in men less than 30 years old. We performed a comparative analysis of the long noncoding RNAs (lncRNAs), and then we ranked them as candidate biomarkers according to a decreasing area under the receiver operating characteristic (ROC) curve (AUC) and plotted the results. Dysregulation of lncRNA expression has been linked to diseases. Further studies on the HUR1 gene can be used as diagnostic tools for the identification of high-risk individuals in families with a history of disease before, during, and even after treatment. Our data uncovered the expression profiles of lncRNAs and mRNAs in MS patients, which will help delineate the molecular mechanisms in MS pathogenesis. However, further studies need to determine the precise role of these genes in the pathological process in MS.     

Immunocytochemical distribution of polygalacturonase and pectins in styles of distylous and homostylous Turneraceae

Distyly is a plant breeding system in which two self-incompatible, but cross-compatible, floral morphs occur within populations. The morphs differ in having a reciprocal arrangement of styles and anthers. Little or nothing is known of the proteins involved in self-incompatibility for any distylous species. Here we show that a 35 kDa putative polygalacturonase is specific to the transmitting tissue of short-styled plants of five species in series Turnera. The polygalacturonase was not detected in styles of long-styled plants, or in styles of five homostylous self-compatible species in this series of the genus. It is also absent from two X-ray generated mutants and a spontaneous somatic homostylous mutant that arose on a short-styled plant and whose style does possess this polygalacturonase. Three more distantly related species in the Turneraceae were investigated. Turnera weddelliana (series Salicifoliae) does possess the polygalacturonase; however, T. diffusa (series Microphyllae), and Piriqueta caroliniana, showed no evidence of possessing this polygalacturonase using immunocytochemistry. Polygalacturonase assays revealed activity in styles of long- and short-styled plants, but showed no activity of the 35 kDa style polygalacturonase. The distribution of pectins in styles and pollen tubes revealed no difference between the long- and short-styled morphs. Methyl-esterified pectins occur throughout the style tissues, except in the transmitting tissue. The transmitting tissue possesses unesterified pectins that could provide a substrate for polygalacturonase activity. We propose that the style polygalacturonase might act in a complementary manner, allowing pollen of long-styled plants to grow through short styles or, alternatively, oligogalacturonide products of polygalacturonase activity might play a role in signalling compatible responses.     

Interaction of hemin with quadruplex DNA

A DNA enzyme with peroxidase activity is a G-quadruplex-based DNAzyme formed by hemin and G-quadruplex DNA. Activity of peroxide DNAzymes can be influenced by the structure of quadruplex DNA. In this investigation, the interaction of hemin with T30695 G-quadruplex DNA is evaluated. Molecular dynamic simulation indicates that the binding mode of hemin to G-quadruplex DNA is end-stacking, which is consistent with absorption spectroscopy. Based on fluorescence spectroscopy, hemin ejects thiazole orange from bases of four-strand DNA. Circular dichroism spectra showed that no alteration occurs in this type of DNA structure.

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Graphical Abstract Peroxidase DNAzyme is formed by hemin and G-quadruplex DNA.

     

Responses of pomegranate cultivars to severe water stress and recovery: changes on antioxidant enzyme activities,gene expression patterns and water stress responsive metabolites

The biochemical and molecular responses of five commercially well-known pomegranate cultivars to severe water stress were studied. The cultivars were subjected to 14-day water stress by withholding irrigation, followed by re-watering for 7 days. Results showed clear differences in metabolites contents and activities of antioxidant enzymes among various pomegranate cultivars during severe water stress and recovery. According to our results, increased accumulation of proline in pomegranate was not related to osmotic adjustment during severe water stress. Except for ‘Ghojagh’, leaves grown under severe water stress conditions showed symptoms of oxidative stress such as reduced chlorophyll concentration. The improved performance of ‘Ghojagh’ under drought stress may be associated with an efficient osmotic adjustment. The up- or down regulated expression of cytosolic glutathione reductase (cytosolic GR) and glutathione peroxidase were observed under drought conditions. Moreover, the suppressed expression of cytosolic GR was also noted. Comparatively, ‘Rabab’ exhibited higher antioxidant capacity and an efficient ROS-scavenging mechanism under drought stress. Lower levels of membrane lipid peroxidation in ‘Ghojagh’ and ‘Rabab’ under drought stress and the marked reduction of malondialdehyde concentration after re-watering represents that these cultivars have a good tolerance to drought stress. As a first step towards the study of the biochemical and molecular responses of pomegranate plants to water stress, this research provides new information into the mechanisms of drought tolerance in the plants.     

Identification of potential predictive markers of dexamethasone resistance in childhood acute lymphoblastic leukemia

Response to dexamethasone (DEXA), as a hallmark drug in the treatment of childhood acute lymphoblastic leukemia (ALL), is one of the pivotal prognostic factors in the prediction of outcome in ALL. Identification of predictive markers of chemoresistance is beneficial to selecting of the best therapeutic protocol with the lowest effect adverse. Hence, we aimed to find drug targets using the 2DE/MS proteomics study of a DEXA-resistant cell line (REH) as a model for poor DEXA responding patients before and after drug treatment. Using the proteomic methods, three differentially expressed proteins were detected, including voltage dependent anion channel 1 (VDAC1), sorting Nexin 3 (SNX3), and prefoldin subunit 6 (PFDN6). We observed low expression of three proteins after DEXA treatment in REH cells. We subsequently verified low expression of resulted proteins at the mRNA level using the quantitative PCR method. These proteins are promising proteins because of their important roles in drug resistance and regulation of apoptosis (VDAC1), protein trafficking (SNX3), and protein folding (PFDN6). Additionally, mRNA expression level of these proteins was assessed in 17 bone marrow samples from children with newly diagnosed ALL and 7 non-cancerous samples as controls. The results indicated that independent of the molecular subtypes of leukemia, mRNA expression of VDAC1, SNX3, and PFDN6 decreased in ALL samples compared with non-cancerous samples particularly in VDAC1 (p?<?0.001). Additionally, mRNA expression of three proteins was also declined in high-risk samples compared with standard risk cases. These results demonstrated diagnostic and prognostic value of these proteins in childhood ALL. Furthermore, investigation of protein-protein interaction using STRING database indicated that these proteins involved in the signaling pathway of NR3C1 as dexamethasone target. In conclusion, our proteomic study in DEXA resistant leukemic cells revealed VDAC1, SNX3, and PFDN6 are promising proteins that might serve as potential biomarkers of prognosis and chemotherapy in childhood ALL.