Application of sparse linear discriminant analysis and elastic net for diagnosis of IgA nephropathy: statistical and biological viewpoints

Background: IgA nephropathy [IgAN] is the most common primary glomerulonephritis diagnosed based on renal biopsy. Mesangial IgA deposits along with the proliferation of mesangial cells are the histologic hallmark of IgAN. Non-invasive diagnostic tools may help to prompt diagnosis and therapy. The discovery of potential and reliable urinary biomarkers for diagnosis of IgAN depends on applying robust and suitable models. Applying two multivariate modeling methods on a urine proteomic dataset were obtained from IgAN patients, and comparison of the results of these methods were the purpose of this study

Methods: Two models were constructed for urinary protein profiles of 13 patients and 8 healthy individuals, based on sparse linear discriminant analysis [SLDA] and elastic net [EN] regression methods. A panel of selected biomarkers with the best coefficients were proposed and further analyzed for biological relevance using functional annotation and pathway analysis

Results: Transferrin, a1-antitrypsin, and albumin fragments were the most important up-regulated biomarkers, while fibulin-5, YIP1 family member 3, prasoposin, and osteopontin were the most important down-regulated biomarkers. Pathway analysis revealed that complement and coagulation cascades and extracellular matrix-receptor interaction pathways impaired in the pathogenesis of IgAN

Conclusion: SLDA and EN had an equal importance for diagnosis of IgAN and were useful methods for exploring and processing proteomic data. In addition, the suggested biomarkers are reliable candidates for further validation to non-invasive diagnose of IgAN based on urine examination

Urinary proteomics in nephrotic syndrome

Nephrotic syndrome is the commonest glomerular disease. Typical symptoms could be proteinuria, low serum albumin and oedema. The mechanism of proteinuria in nephrotic syndrome is a defective glomerular ?ltration barrier. Renal biopsy is the gold standard for diagnosis of nephrotic syndrome currently which is invasive and based on histopathological features, therefore it seems to be necessary to search for noninvasive biomarkers to be used as the complementary tests in the diagnostics and prognostics of glomerular diseases, particularly when renal biopsy is limited or contraindicated. While a big proportion of urinary proteins originate from kidney tissue and these tissue specific proteins excrete more in kidney injury, therefore the identification of urinary proteins can further our understanding of renal dysfunction and renal disease including nephrotic syndrome. The interest of scientist to urinary proteomics is also growing for biomarker discovery. This review focuses on some types of nephrotic syndrome and proteomic studies applying urine specimen which have been reported

Dietary habits and nutrient intake in adolescent girls living in Northern Iran

Rapid changes in lifestyle and industrialization of communities have an important effect on food intake pattern of society. Regarding the lack of enough data about dietary habits and nutrient intake of adolescents in our society, this study was performed in a group of adolescent girls in Lahijan, North of Iran. In this cross-sectional study, 400 high school girls aged 14-17 years selected by random stratified sampling. Nutritional data were collected by 24-hour dietary recall, food habits and food frequency questionnaires for all samples. The mean energy intake was 2338+/-611 kcal/d. The contributions of carbohydrate, protein and fat to the total energy intake were 59.3, 11.9 and 28.8%, respectively. The daily intake of energy obtained from breakfast, lunch, dinner and snacks were 16.3, 23.5, 25.9 and 34.3%, respectively. The mean intakes of vitamin A, vitamin D, calcium, phosphorous and zinc were below the Recommended Daily Allowances. The consumption of fresh vegetables and fruit was generally low. Twelve percent in total did not drink milk at all. Almost all the subjects had a prepared meal, most often in the evening, at least four times a week. Regarding the undesirable food pattern and proportions of nutrient intakes, it is necessary to development means of motivating adolescents to eat nutritionally rich foods, good for health and well-being

Fluoxetine competes with cortisol for binding to human serum albumin

Human serum albumin [HSA] is an important protein that carries variety of substances like some hormones and drugs in blood. Pharmacological studies of the interaction of many drugs and HSA are reported during several decades, specially recently years. Interaction of cortisol and fluoxetine hydrochloride [FLX] [as a common anti-stress drug] with HSA [as their carrier in blood] has been studied separately by using different spectroscopic techniques. Here, considering the increment of anti-stress drugs consumption, conformational change of HSA in presence of cortisol and FLX in 50 mM tris buffer, at pH = 7.5 and 37°C, is investigated via pH meter, UV absorption and fluorescence spectroscopy and circular dichroism methods. pH meter findings indicate that the acid denaturation of HSA in the presence of drug and cortisol occurs in the similar manner and this pattern is different relative to the denaturation of HSA in the absence of two reagents. The results of the other techniques consistent with the pH meter findings show that FLX effects on the physiochemical properties of HSA are as that of Cortisol. In-vivo study in Rats confirms in-vitro findings which means blood cortisol level increased in the presence of FLX. Experimental results indicate that FLX and cortisol alter the structural aspects of HSA in similar manner, so, this findings lead to the following reasonable "FLX is a competitive ligand for the binding of cortisol to HSA. Binding of FLX to HSA interferes to the interaction of cortisol-HSA"

Proteomics analysis of MKN45 cell line before and after treatment with lavender aqueous extract

In this study the anticancer activity of Lavender aqueous extract against MKN45 cell line was evaluated. Plant-based drugs are regarded as promising therapies. Lavender is a plant that has been cultivated from ancient times. An aqueous extract of Lavender has shown therapeutic effects on the nervous system in the high doses based on in-vivo studies. Gastric cancer is one of the frequent cancers in Iranian population. We therefore assessed the effect of Lavender upon a gastric cancer cell line. The MKN45 cancer cell line was selected for treatment with aqueous extract of Lavender Survival of MKN45 cell line was studied in the presence of various concentrations of Lavender extract by MTT assay method. Morphological studies were performed via microscopic analyses. Flow cytometry and proteomics techniques were applied to determining pharmaceutical mechanism of lavender cytotoxic effects. The survival and morphological studies revealed anticancer characteristics of extract. Flow cytometry findings indicate that Lavender extract had a cytotoxic effect upon the cell line. Proteomics analysis identified a significant spots showed changes in protein expression levels by informatics analysis. Of the proteins, expression of three cancer biomarkers, Annexin1, Anolase1 and HSP70 were suppressed by extract. This study suggest that Lavender extract is cytotoxic and alter protein expression in a gastric cancer cell line

[Effects of different therapeutical doses of ibuprofen on the adenosine deaminase activity at physiologic and pathologic temperatures]

Adenosine deaminase [ADA] is a purine catabolic enzyme that removes amino group of adenosine or 2' deoxyadenosine irreversibly. ADA enhances immune system and also intervenes the inflammation process. In this study, the effect of ibuprofen as an anti- inflammatory drug has been studied on the ADA activity in the physiologic and pathologic temperatures. ADA was assessed in the presence of 3 different doses of ibuprofen at 37 [degree sign] C and 42 [degree sign] C via spectrometry in 265 nm. Ibuprofen at high and low doses had an activation effect on the ADA activity at 37 [degree sign]C and moderated the sensitivity of enzyme activity to its substrate. It also decreased the anti-inflammatory effect of adenosine via decrease of its concentration and had a positive effect on immune system as well. The activation of the enzyme by Ibuprofen was decreased at 42 [degree sign]C and also Ibuprofen moderated the effect of temperature on dependency of enzyme activity to its substrate. Ibuprofen effects on immune system and anti-inflammatory effects of adenosine decreased at 42[degree sign]c Ibuprofen is a putative activator for adenosine deaminase and administration of this drug could be useful for immune deficiency. Since there is no activator for ADA so far, this drug is important. Ibuprofen decreases anti-inflammatory effect of adenosine. In-vivo studies would be needed

study on the activity and thermal stability of adenosine deaminase in the presence of spermine

Adenosine Deaminase is an amino hydrolase [EC 3.5.4.4] which participates in the purine metabolism where it degrades either adenosine or 2'-deoxyadenosine producing inosine or 2'- deoxy inosine, respectively. The enzyme contains a parallel alpha/beta -barrel motif with eight central beta strands and eight peripheral alpha helices. ADA is located both in the cytosol and on the cell membrane. Since spermine, a natural metabolite, exists in all cells and tissues and its effect on the cell proliferation and enzyme regulation have been reported, thermal inactivation of the ADA and spermine regulatory effect on the ADA activity have been investigated in this study. Percentage of ADA activity in the presence and absence of spermine [1000 microM] in Tris buffer 50 mM, pH 7.5 at physiologic and pathologic temperatures have been reported in the present study. Thermal inactivation curves for ADA in the absence and presence of spermine [1000 microM] in different temperatures ranging from 55 degreeC to 70 degreeC have been drawn. Our data showed that spermine activates the enzyme in the low concentrations of adenosine at 37 degreeC. However, it inhibits ADA activity at 42 degreeC in the same concentrations of substrate. It is concluded that spermine regulatory effect depends on combined influence of temperature and adenosine concentration. Furthermore, thermal stability of the enzyme also depends on temperature in presence of spermine. Binding site of spermine on the enzyme has been identified by docking analysis

[Effects of Scrophularia striata extract on human fibroblast cells]

Several studies have been performed on rapid wound healing. Because of minimal side effects of herbal drugs and role of firoblast cells in wound healing, in this study the effect of Scrophularia striata extract on human firoblast cell proliferation was evaluate. In this basic-applied study, Scrophularia striata seed extract was prepared by water based extraction methods. Foreskin fibroblast [Ffk] cells, maintaining in DMEM culture medium supplemented with 10% FBS in a humidified incubator [37°C and 5% CO2] were used. 100000 Ffk cells per well were exposed to different concentrations of Scrophularia striata extract [1, 3, 5, 7, 10 and 20 microg/ml] at 24, 48, 72, 96 hours. MTT assay was used to evaluate effects of extract on cell proliferation. S. Striata seed extract had stimulatory effects on human fibroblast cells proliferation. Incubation time was effective on cell proliferation, so that cell proliferation was diminished with increasing incubation time. This study showed that different doses of S. striata seed extract has various effects on improvement of wound healing and anti-tumor activity. Further investigations are recommended to detect optimum dose and mode of clinical applications