Fine-Scale Dissection of Functional Protein Network Organization by Statistical Network Analysis

Revealing organizational principles of biological networks is an important goal of systems biology. In this study, we sought to analyze the dynamic organizational principles within the protein interaction network by studying the characteristics of individual neighborhoods of proteins within the network based on their gene expression as well as protein-protein interaction patterns. By clustering proteins into distinct groups based on their neighborhood gene expression characteristics, we identify several significant trends in the dynamic organization of the protein interaction network. We show that proteins with distinct neighborhood gene expression characteristics are positioned in specific localities in the protein interaction network thereby playing specific roles in the dynamic network connectivity. Remarkably, our analysis reveals a neighborhood characteristic that corresponds to the most centrally located group of proteins within the network. Further, we show that the connectivity pattern displayed by this group is consistent with the notion of “rich club connectivity” in complex networks. Importantly, our findings are largely reproducible in networks constructed using independent and different datasets.     

Melatonin ameliorates cardiac remodelling in fructose-induced metabolic syndrome rat model by using genes encoding cardiac potassium ion channels

Molecular Biology Reports - Metabolic syndrome comprises a group of disorders, including cardiac abnormalities. Ventricular arrhythmias observed in metabolic syndrome are due to the impaired...     

In-depth review: is hepcidin a marker for the heart and the kidney?

Iron is an essential trace element involved in oxidation–reduction reactions, oxygen transport and storage, and energy metabolism. Iron in excess can be toxic for cells, since iron produces reactive oxygen species and is important for survival of pathogenic microbes. There is a fine-tuning in the regulation of serum iron levels, determined by intestinal absorption, macrophage iron recycling, and mobilization of hepatocyte stores versus iron utilization, primarily by erythroid cells in the bone marrow. Hepcidin is the major regulatory hormone of systemic iron homeostasis and is upregulated during inflammation. Hepcidin metabolism is altered in chronic kidney disease. Ferroportin is an iron export protein and mediates iron release into the circulation from duodenal enterocytes, splenic reticuloendothelial macrophages, and hepatocytes. Systemic iron homeostasis is controlled by the hepcidin–ferroportin axis at the sites of iron entry into the circulation. Hepcidin binds to ferroportin, induces its internalization and intracellular degradation, and thus inhibits iron absorption from enterocytes, and iron release from macrophages and hepatocytes. Recent data suggest that hepcidin, by slowing or preventing the mobilization of iron from macrophages, may promote atherosclerosis and may be associated with increased cardiovascular disease risk. This article reviews the current data regarding the molecular and cellular pathways of systemic and autocrine hepcidin production and seeks the answer to the question whether changes in hepcidin translate into clinical outcomes of all-cause and cardiovascular mortality, and cardiovascular and renal end-points.

     

Identification of copy number variants in children and adolescents with autism spectrum disorder: a study from Turkey

Molecular Biology Reports - Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorder (ASD). Therefore, recent guidelines recommend chromosomal microarrays (CMAs) as...     

Protective Effect of Nigella sativa and Nigella damascena Fixed Oils Against Aflatoxin Induced Mutagenicity in the Classical and Modified Ames Test

The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography–mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC². The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin.     

Protective role of zinc in liver damage in experimental diabetes demonstrated via different biochemical parameters

Diabetes mellitus is a serious worldwide metabolic disease, which is accompanied by hyperglycaemia and affects all organs and body system. Zinc (Zn) is a basic cofactor for many enzymes, which also plays an important role in stabilising the structure of insulin. Liver is the most important target organ after pancreas in diabetic complications. In this study, we aimed to investigate the protective role of Zn in liver damage in streptozotocin (STZ)‐induced diabetes mellitus. There are four experimental groups of female Swiss albino rats: group I: control; group II: control + ZnSO₄; group III: STZ‐induced diabetic animals and group IV: STZ‐diabetic + ZnSO₄. To induce diabetes, STZ was injected intraperitoneally (65 mg/kg). ZnSO₄ (100 mg/kg) was given daily to groups II and IV by gavage for 60 days. At the end of the experiment, rats were killed under anaesthesia and liver tissues were collected. In the diabetic group, hexose, hexosamine, fucose, sialic acid levels, arginase, adenosine deaminase, tissue factor activities and protein carbonyl levels increased, whereas catalase, superoxide dismutase, glutathione‐S‐transferase, glutathione peroxidase, glutathione reductase and Na⁺/K⁺‐ATPase activities decreased. The administration of Zn to the diabetic group reversed all the negative effects/activities. According to these results, we can suggest that Zn has a protective role against STZ‐induced diabetic liver damage.     

The effects of aflatoxin B1 on growth hormone regulated gene-1 and interaction between DNA and aflatoxin B1 in broiler chickens during hatching

Many types of aflatoxin cause problems for both public and animal health. Aflatoxin B₁ (AFB₁) is the most toxic and commonly encountered fungal toxin that appears in poultry feed and in feeds stored under unsuitable conditions. AFB₁ decreases feed quality, egg production and fertility of hatching eggs. Also, AFB₁ alters the development of embryos by infecting eggs. We investigated using sequence analysis the changes caused by different concentrations of AFB₁ on the promoter sequences of the growth hormone regulated gene-1 (GHRG-1) in chick embryo at 13, 17, 19 and 21 days incubation. DNA isolated from the liver of chick embryos treated with different concentrations of AFB₁ was separated using agarose gel electrophoresis to detect apoptosis, and DNA interaction with AFB₁ was investigated using plasmids to detect changes in electrophoretic mobility and their effects on DNA. Base changes of the promoter sequences of GHRG-1 in 5 ng/egg, 15 ng/egg and 40 ng/egg doses of AFB₁ were increased on day 19 compared to base changes of the same AFB₁ doses on day 13. We also found that AFB at different concentrations changed the mobility of DNA by binding to it, and that high doses of AFB1 destroyed DNA. The DNA interaction study using plasmid demonstrated that AFB₁ at high doses was bound to plasmid DNA, slowed its mobility and inhibited restriction cuts.     

Effects of some drugs on the activity of glucose 6-phosphate dehydrogenase from rainbow trout (Oncorhynchus mykiss) erythrocytes in vitro

Inhibitory effects of some drugs on glucose 6-phosphate dehydrogenase from the erythrocytes of rainbow trout (Oncorhynchus mykiss Walbaum, 1792) were investigated. The enzyme was purified 2488-fold in a yield of 76.8% using ammonium sulfate precipitation and 2′,5′-ADP Sepharose 4B affinity gel at 4°C. The drugs pental sodium, MgSO₄, vancomycin, metamizol, marcaine, and prilocaine all exhibited inhibitory effects on the enzyme. While MgSO₄ (K_i = 12.119 mM), vancomycin (K_i = 1.466 mM) and metamizol (K_i = 0.392 mM) showed competitive inhibition, pental sodium (K_i = 0.748 mM) and marcaine (K_i = 0.0446 mM) displayed noncompetitive inhibition.     

Effects of nicotine and vitamin E on glucose 6-phosphate dehydrogenase activity in some rat tissues in vivo and in vitro

Effects of nicotine, and nicotine + vitamin E on glucose 6-phosphate dehydrogenase (G-6PD) activity in rat muscle, heart, lungs, testicle, kidney, stomach, brain and liver were investigated in vivo and in vitro on partially purified homogenates. Supplementation period was 3 weeks (n = 8 rats per group): nicotine [0.5 mg/kg/day, intraperitoneal (ip)]; nicotine + vitamin E [75 mg/kg/day, intragastric (ig)]; and control group (receiving only vehicle). The results showed that nicotine (0.5 mg/kg, ip) inhibited G-6PD activity in the lungs, testicle, kidney, stomach and brain by 12.5% (p < 0.001), 48% (p < 0.001), 20.8% (p < 0.001), 13% (p < 0.001) and 23.35% (p < 0.001) respectively, and nicotine had no effects on the muscle, heart and liver G6PD activity. Also, nicotine + vitamin E inhibited G-6PD activity in the testicle, brain, and liver by 32.5% (p < 0.001), 21.5% (p < 0.001), and 16.5% (p < 0.001) respectively, and nicotine + vitamin E activated the muscle, and stomach G-6PD activity by 36% (p < 0.05), and 20% (p < 0.001) respectively. In addition, nicotine + vitamin E did not have any effects on the heart, lungs, and kidney G-6PD activity. In addition, in vitro studies were also carried out to elucidate the effects of nicotine and vitamin E on G-6PD activity, which correlated well with in vivo experimental results in lungs, testicles, kidney, stomach, brain and liver tissues. These results show that vitamin E administration generally restores the inactivation of G-6PD activity due to nicotine administration in various rat tissues in vivo, and also in vitro.