Evidence of natural Wolbachia infections and molecular identification of field populations of Culex pipiens complex (Diptera: Culicidae) mosquitoes in western Turkey

Establishing reliable risk projection information about the distribution pattern of members of the Culex pipiens complex is of particular interest, as these mosquitoes are competent vectors for certain disease‐causing pathogens. Wolbachia, a maternally inherited bacterial symbiont, are distributed in various arthropod species and can induce cytoplasmic incompatibility, i.e., reduced egg hatch, in certain crosses. It is being considered as a tool for population control of mosquito disease vectors. The Aegean region is characterized by highly populated, rural, and agricultural areas and is also on the route of the migratory birds. In this study, a fragment of the 658 bp of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene, which includes the barcode region, was employed to differentiate Cx. pipiens complex species found in this region. Moreover, for the first time, the prevalence of Wolbachia endobacteria in these natural populations was examined using PCR amplification of a specific wsp gene. Our results revealed a widespread (more than 90%, n=121) presence of the highly efficient West Nile virus vector Cx. quinquefasciatus in the region. We also found that Wolbachia infection is widespread; the average prevalence was 62% in populations throughout the region. This study provided valuable information about the composition of Cx. pipiens complex mosquitoes and the prevalence of Wolbachia infection in these populations in the Aegean region. This information will be helpful in tracking mosquito‐borne diseases and designing and implementing Wolbachia‐based control strategies in the region.     

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis

In acute pancreatitis, endoplasmic reticulum (ER) stress prompts an accumulation of malfolded proteins inside the ER, initiating the unfolded protein response (UPR). Because the ER chaperone tauroursodeoxycholic acid (TUDCA) is known to inhibit the UPR in vitro, this study examined the in vivo effects of TUDCA in an acute experimental pancreatitis model. Acute pancreatitis was induced in Wistar rats using caerulein, with or without prior TUDCA treatment. UPR components were analyzed, including chaperone binding protein (BiP), phosphorylated protein kinase-like ER kinase (pPERK), X-box binding protein (XBP)-1, phosphorylated c-Jun NH(2)-terminal kinase (pJNK), CCAAT/enhancer binding protein homologues protein, and caspase 12 and 3 activation. In addition, pancreatitis biomarkers were measured, such as serum amylase, trypsin activation, edema formation, histology, and the inflammatory reaction in pancreatic and lung tissue. TUDCA treatment reduced intracellular trypsin activation, edema formation, and cell damage, while leaving amylase levels unaltered. The activation of myeloperoxidase was clearly reduced in pancreas and lung. Furthermore, TUDCA prevented caerulein-induced BiP upregulation, reduced XBP-1 splicing, and caspase 12 and 3 activation. It accelerated the downregulation of pJNK. In controls without pancreatitis, TUDCA showed cytoprotective effects including pPERK signaling and activation of downstream targets. We concluded that ER stress responses activated in acute pancreatitis are grossly attenuated by TUDCA. The chaperone reduced the UPR and inhibited ER stress-associated proapoptotic pathways. TUDCA has a cytoprotective potential in the exocrine pancreas. These data hint at new perspectives for an employment of chemical chaperones, such as TUDCA, in prevention of acute pancreatitis.     

Ex vivo protective effects of nicotinamide and 3‐aminobenzamide on rat synaptosomes treated with Aβ(1–42)

Alzheimer's disease (AD) is the most common form of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles, along with synaptic loss. The underlying mechanisms of AD are not clarified yet, but oxidative stress and mitochondrial dysfunction are important factors. Overactivation of poly(adenosine diphosphate ribose) polymerase‐1 (PARP‐1) enzyme has been known to cause neuroinflammation and cell death in neurodegenerative processes. The aim of the present study was to investigate the protective effects of the PARP‐1 inhibitors, 3‐aminobenzamide (3‐AB) and nicotinamide (NA), against amyloid β peptide (1–42) (Aβ(1–42))‐induced oxidative damage and mitochondrial reduction capacity on isolated synaptosomes. Rats were injected intraperitoneally with 3‐AB (30–100 mg kg^?1), NA (100–500 mg kg^?1) or with saline for 7 days. Synaptosomes were incubated with 10–30 μM Aβ(1–42) or saline for 6 h at 37 °C. Ex vivo Aβ(1–42) treatment significantly induced oxidative stress and mitochondrial dysfunction in synaptosomes of the saline group, while synaptosomes of 3‐AB and NA groups showed significant decreases in lipid peroxidation, reactive oxygen species production and protein oxidation. Moreover, both NA and 3‐AB were able to improve the mitochondrial reduction capacity against Aβ(1–42). These data suggest that NA and 3‐AB may have protective effects in neurodegenerative processes because of the reduced levels of oxidative stress and the improvement of mitochondrial function. Copyright © 2014 John Wiley & Sons, Ltd.     

A novel knowledge-based approach to design inorganic-binding peptides

MOTIVATION: The discovery of solid-binding peptide sequences is accelerating along with their practical applications in biotechnology and materials sciences. A better understanding of the relationships between the peptide sequences and their binding affinities or specificities will enable further design of novel peptides with selected properties of interest both in engineering and medicine. RESULTS: A bioinformatics approach was developed to classify peptides selected by in vivo techniques according to their inorganic solid-binding properties. Our approach performs all-against-all comparisons of experimentally selected peptides with short amino acid sequences that were categorized for their binding affinity and scores the alignments using sequence similarity scoring matrices. We generated novel scoring matrices that optimize the similarities within the strong-binding peptide sequences and the differences between the strong- and weak-binding peptide sequences. Using the scoring matrices thus generated, a given peptide is classified based on the sequence similarity to a set of experimentally selected peptides. We demonstrate the new approach by classifying experimentally characterized quartz-binding peptides and computationally designing new sequences with specific affinities. Experimental verifications of binding of these computationally designed peptides confirm our predictions with high accuracy. We further show that our approach is a general one and can be used to design new sequences that bind to a given inorganic solid with predictable and enhanced affinity.     

Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity. Several studies suggest that supplementation with an antioxidant can influence cisplatin-induced hepatotoxicity. The present study was designed to determine the effects of cisplatin on the liver oxidant/antioxidant system, and the possible protective effects of caffeic acid phenethyl ester (CAPE) on liver toxicity induced by cisplatin. Twenty-four adult female Wistar albino rats were divided into four groups of six rats each: control, cisplatin, CAPE, and cisplatin+CAPE. Cisplatin and CAPE were injected intraperitoneally. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), xanthine oxidase (XO), adenosine deaminase (ADA), and the levels of malondialdehyde and nitric oxide (NO). The activities of SOD and GSH-Px increased in the cisplatin+CAPE and CAPE groups compared with the cisplatin group. CAT activity was higher in the cisplatin +CAPE group than the other three groups. XO activity was lower in the cisplatin group than the control group. MPO activity was also increased in the cisplatin group compared to the control and CAPE groups. It can be concluded that CAPE may prevent cisplatin-induced oxidative changes in liver by strengthening the antioxidant defence system by reducing reactive oxygen species and increasing antioxidant enzyme activities.     

MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population

Background: The mouse double minute 2 (MDM2) gene represents one of the central nodes in the p53 pathway. A naturally occurring T/G single nucleotide polymorphism (SNP) in the intronic promoter of MDM2, SNP309 (rs2279744), was shown to influence MDM2 expression and p53 activity. SNP in the promoter region of MDM2 gene has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. In this study, we aim to evaluate the association of SNP309 with the risk of hepatocellular carcinoma (HCC) development among Turkish population. Methods: MDM2 SNP309 polymorphism was investigated in 110 confirmed subjects with HCC and 110 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Results: The allele frequencies of case subjects (T, 0.48; G, 0.52) were significantly different from those of control subjects (T, 0.65; G, 0.35) (p = 0.003). The proportion of GG genotype of the SNP309 in patients with HCC (26%) was significantly higher than that in patients without HCC (14%). We observed that compared with the TT genotype, the genotypes containing G allele [TG (OR, 2.19; 95% CI, 1.18–4.07; p = 0.013) or GG (OR, 3.63; 95% CI, 1.65–8.00; p = 0.001)] were associated with significant increased susceptibility to HCC. Conclusion: Our findings suggest that the MDM2 promoter SNP309 G allele is associated with presence of HCC in Turkish population.