Characterization of the Putative Acylated Cellulose Synthase Operon in Komagataeibacter xylinus E25.

Bacterial cellulose is a natural polymer with an expanding array of applications. Because of this, the main cellulose producers of the Komagataeibacter genus have been extensively studied with the aim to increase its synthesis or to customize its physicochemical features. Up to now, the genetic studies in Komagataeibacter have focused on the first cellulose synthase operon (bcsI) encoding the main enzyme complex. However, the role of other accessory cellulose operons has been understudied. Here we aimed to fill this gap by performing a detailed analysis of the second cellulose synthase operon (bcsII), which is putatively linked with cellulose acylation. In this study we harnessed the genome sequence, gene expression and protein structure information of K. xylinus E25 and other Komagataeibacter species to discuss the probable features of bcsII and the biochemical function of its main protein products. The results of our study support the previous hypothesis that bcsII is involved in the synthesis of the acylated polymer and expand it by presenting the evidence that it may also function in the regulation of its attachment to the cell surface and to the crystalline cellulose fibers.

Structural investigations of stereoselective profen binding by equine and leporine serum albumins.

Serum albumin, the most abundant transport protein of mammalian blood, interacts with various nonsteroidal anti-inflammatory drugs (NSAIDs) affecting their disposition, metabolism, and excretion. A big group of chiral NSAIDs transported by albumin, profens, is created by derivatives of 2-arylpropionic acid. The chiral center in the structures of profens is adjacent to the carboxylate moiety and often determines different pharmacological properties of profen enantiomers. This study describes crystal structures of two albumins, isolated from equine and leporine serum, in complexes with three profens: ibuprofen, ketoprofen, and suprofen. Based on three-dimensional structures, the stereoselectivity of albumin is discussed and referred to the previously published albumin complexes with drugs. Drug Site 2 (DS2) of albumin, the bulky hydrophobic pocket of subdomain IIIA with a patch of polar residues, preferentially binds (S)-enantiomers of all investigated profens. Almost identical binding mode of all these drugs clearly indicates the stereoselectivity of DS2 towards (S)-profens in different albumin species. Also, the affinity studies show that DS2 is the major site that presents high affinity towards investigated drugs. Additionally, crystallographic data reveal the secondary binding sites of ketoprofen in leporine serum albumin and ibuprofen in equine serum albumin, both overlapping with previously identified naproxen binding sites: the cleft formed between subdomains IIIA and IIIB close to the fatty acid binding site 5 and the niche created between subdomains IIA and IIIA, called fatty acid site 6.

Can vitamin D help in achieving asthma control? Vitamin D "revisited'': an updated insight.

Asthma - a prolonged respiratory disease related with hyper-responsiveness and increased inflammation of airways; affects millions peoples worldwide. Vitamin D possess anti-inflammatory and immunomodulatory activities. Its deficiency (the level less than 20 ng/mL in the serum) is found to be related to occurrence of pulmonary diseases including bacterial and viral infections and asthma. Some studies indicate that low levels of vitamin D in the serum are related to reduced lung function and increased airway inflammation as well as overall poor results in asthmatic patients. Thus, it provides positive relation between vitamin D and asthma. Increased prevalence of asthma over the past decades causes elevated interest in vitamin D supplementation that is even reported as a ,,potential therapeutic option''. Unfortunately, results of clinical trials are inconsistent and do not provide supportive information about positive role of vitamin D in asthma. Little or even no effect of supplementation of vitamin D in improvement of onset, symptoms or progression of asthma was found in comprehensive interventional studies in adults, children and pregnant woman. This review critically summarized the last years evidence of a relation between vitamin D and asthma in adults, children and pregnant women.

Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk.

BACKGROUND: Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development. An often proposed model is defects in DNA repair in terms of efficiency and genetic variations that modulate the response to stimuli from the environment. The objectives of this research were to determine whether nucleotide excision repair (NER) might affect CRC risk. MATERIALS AND METHODS: The first part of the study concerns NER efficiency. In the second part we selected 2 common single nucleotide polymorphisms within genes involved in NER (Xeroderma pigmentosum group C (XPC) Lys939Gln, Xeroderma pigmentosum group D (XPD) Lys751Gln) to determine the relation between them and CRC risk. The restriction fragment length polymorphism-polymerase chain reaction method was used for genotyping of 221 CRC patients vs. 270 cancer-free individuals. The isotopic labeling in vitro assay was used to evaluate NER capacity in lymphocytes and tissue protein extracts. RESULTS: We observed a significantly decreased level of NER capacity (P = .025) in lymphocytes delivered from CRC patients compared with healthy ones. Polymorphism screening points to higher CRC risk for the Gln939Gln genotype (P = .02) and Gln allele (P = .002) of the XPC gene. CONCLUSION: Taken together, our findings suggest a potential role for NER in CRC.

Correlation between IL36α and IL17 and Activity of the Disease in Selected Autoimmune Blistering Diseases.

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury.

Molecular Background of miRNA Role in Asthma and COPD: An Updated Insight.

Inflammatory airway diseases are a significant health problems requiring new approaches to the existing therapies and addressing fundamental issues. Difficulties in developing effective therapeutic strategies might be caused by lack of understanding of their exact molecular mechanism. MicroRNAs (miRNAs) are a class of regulators that already revolutionized the view of gene expression regulation. A cumulating number of investigations show a pivotal role of miRNAs in the pathogenesis of asthma, chronic obstructive pulmonary disease (COPD), or airway remodeling through the regulation of many pathways involved in their pathogenesis. Expression changes of several miRNAs have also been found to play a role in the development and/or improvement in asthma or COPD. Still, relatively little is known about the role of miRNAs in inflammatory disorders. The microRNA profiles may differ depending on the cell type or antigen-presenting cell. Based on the newest literature, this review discusses the current knowledge concerning miRNA contribution and influence on lung inflammation and chosen inflammatory airway diseases: asthma and COPD.

DNA damage and efficacy of DNA repair in patients with type 2 diabetes and coexisting colorectal cancer.

INTRODUCTION:  Numerous epidemiological studies have indicated that the frequency of developing certain types of cancer, including colorectal cancer (CRC), is higher in patients with type 2 diabetes. The possible causes of this association have not been fully clarified. It has been suggested that chronic hyperglycemia­related oxidative stress leading to oxidative DNA damage and impaired DNA repair may contribute to increased risk of cancer in type 2 diabetes. OBJECTIVES:  The aim of the study was to evaluate the level of DNA damage and efficacy of DNA repair in patients with CRC with and without type 2 diabetes in comparison with healthy controls. PATIENTS AND METHODS:  The alkaline comet assay was used to assess the level of endogenous oxidative and H2O2­induced DNA damage and the efficacy of DNA repair in the lymphocytes of patients with type 2 diabetes, with CRC, with type 2 diabetes and CRC, and of healthy people (a total of 32 patients). RESULTS:  The highest levels of endogenous oxidative and H2O2­induced DNA damage were found in the lymphocytes of patients with type 2 diabetes and CRC. Additionally, the capacity of DNA repair was significantly decreased in patients with CRC with and without type 2 diabetes. CONCLUSIONS:  Our findings support the hypothesis that an increased risk of cancer in type 2 diabetes may be associated with oxidative DNA damage; however, impaired DNA repair seems to play a major role in carcinogenesis in people with and without type 2 diabetes.