Impact of the C1' configuration of abasic sites on DNA duplex structure

Naturally occurring abasic sites in DNA exist as an equilibrium mixture of the aldehyde, the hydrated aldehyde, and the hemiacetal forms (dominant). The influence of the configuration of the C1' hydroxyl group of the hemiacetal form on duplex structure and abasic site repair has been examined using novel carbocyclic analogues. Both the alpha- and beta-forms of this novel abasic site were introduced into oligomeric DNA using the standard DMT-phosphoramidite approach in an automated solid-phase synthesizer. Solution structures of the d(CGTACXCATGC).d(GCATGAGTACG) duplex (where X is the alpha- or beta-anomer of the carbocyclic abasic site analogue) were determined by NMR spectroscopy and restrained molecular dynamics simulations. The structures were only minimally perturbed by the presence of either anomer of the abasic site. All residues adopted an anti conformation, and Watson-Crick alignments were observed on all base pairs of the duplexes. At the lesion site, the abasic residues and their partner adenines showed increased dynamic behavior but adopted intrahelical positions in the final refined structures. Incision of duplexes having the alpha- or beta-anomer of the carbocyclic abasic site by human AP endonuclease showed that the enzyme recognizes both configurations of the lesion and nicks the DNA backbone with similar efficiency. Our results challenge the suggestion that Ape1 is stereoselective and imply a plasticity at the active site of the enzyme for accommodating either anomer of the lesion.     

Mesenchymal stem cell therapy: A promising cell‐based therapy for treatment of myocardial infarction

For decades, mesenchymal stem (MSCs) cells have been used for cardiovascular diseases as regenerative therapy. This review is an attempt to summarize the types of MSCs involved in myocardial infarction (MI) therapy, as well as its possible mechanisms effects, especially the paracrine one in MI focusing on the studies (human and animal) conducted within the last 10 years. Recently, reports showed that MSC therapy could have infarct‐limiting effects after MI in both experimental and clinical trials. In this context, various types of MSCs can help cardiac regeneration by either revitalizing the cardiac stem cells or revascularizing the arteries and veins of the heart. Furthermore, MSCs could produce paracrine growth factors that increase the survival of nearby cardiomyocytes, as well as increase angiogenesis through recruitment of stem cell from bone marrow or inducing vessel growth from existing capillaries. Recent research suggests that the paracrine effects of MSCs could be mediated by extracellular vesicles including exosomes. Exosomal microRNAs (miRNAs) released by MSCs are promising therapeutic hotspot target for MI. This could be attributed to the role of miRNA in cardiac biology, including cardiac regeneration, stem cell differentiation, apoptosis, neovascularization, cardiac contractility and cardiac remodeling. Furthermore, gene‐modified MSCs could be a recent promising therapy for MI to enhance the paracrine effects of MSCs, including better homing and effective cell targeted tissue regeneration. Although MSC therapy has achieved considerable attention and progress, there are critical challenges that remains to be overcome to achieve the most effective successful cell‐based therapy in MI.     

Adenovirus Entry From the Apical Surface of Polarized Epithelia Is Facilitated by the Host Innate Immune Response

Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAR^Ex8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAR^Ex8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAR^Ex8 via activation of AKT/S6K and inhibition of GSK3β. Apical CAR^Ex8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apical-epithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAR^Ex8, to allow the initial infection the intact epithelium. In addition, CAR^Ex8 is a new target for the development of novel therapeutics for both respiratory inflammatory disease and adenoviral infection.     

Myocardial and metabolic dysfunction in type 2 diabetic rats: impact of ghrelin

Diabetes mellitus (DM) is commonly associated with metabolic and cardiac dysfunctions. The aim of this study was to examine the effect of ghrelin on metabolic and cardiac dysfunctions in a type-2 diabetes mellitus (T2DM) rat model. For this, 48 male adult Sprague-Dawley rats were divided equally into 4 groups: Group I, fed normal chow, served as normal control group; Groups II-IV, were fed a high-fat diet for 2?weeks followed by injection of streptozotocin (STZ) (35?mg/kg body mass) to create a model of T2DM; Group II, were not treated; Group III, were treated with the vehicle (saline); Group IV, were treated with ghrelin (40?μg/kg body mass) twice daily for 10 days. The untreated diabetic rats showed a significant increase in serum fasting blood glucose, insulin homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), total serum cholesterol (TC), and body mass, with a decrease in high-density lipoprotein cholesterol (HDL-C) (p?< 0.05). Hearts isolated from diabetic rats showed a significant increase in myocardial fat content, a significant decrease in GLUT4, and an increase in acyl-CoA oxidase enzyme mRNA (p?< 0.05). Ghrelin administration for 10?days caused a significant improvement in lipid profile, HOMA index, and body mass, and significantly corrected the myocardial mass, significantly reduced the fat content of the myocardium, significantly increased GLUT4, and decreased acyl CoA oxidase mRNA (p?< 0.05). Thus, ghrelin improves both the metabolic functions and the disturbed energy metabolism in the cardiac muscle of obese diabetic rats.     

Platform-basin transect of a middle to late Jurassic large-scale carbonate platform system (Shotori mountains,Tabas area,east-central Iran)

Summary Following a phase of predominantly siliciclastic sedimentation in the Early and Middle Jurassic, a large-scale, low-latitude carbonate depositional system was established in the northern part of the Tabas Block, part of the central-east Iranian microplate, during the Callovian and persisted until the latest Oxfordian/Early Kimmeridgian. Running parallel to the present eastern block margin, a NNW/SSE-trending carbonate platform developed in an area characterized by reduced subsidence rates (Shotori Swell). The growth of this rimmed, flat-topped barrier platform strongly influenced the Upper Jurassic facies pattern and sedimentary history of the Tabas Block. The platform sediments, represented by the predominantly fine-grained carbonates of the Esfandiar Limestone Formation, pass eastward into slope to basin sediments of the Qal'eh Dokhtar Limestone Formation (platform-derived allochthonites, microbialites, and peri-platform muds). Towards the west, they interfinger with bedded limestones and marlstones (Kamar-e-Mehdi Formation), which were deposited in an extensive shelf lagoon. In a N−S direction, the Esfandiar Platform can be traced for about 170 km, in an E-W direction, the platform extended for at least 35–40 km. The width of the eastern slope of the platform is estimated at 10–15 km, the width of the western shelf lagoon varied considerably (>20–80 km). During the Late Callovian to Middle Oxfordian, the Esfandiar Platform flourished under arid climatic conditions and supplied the slope and basinal areas with large amounts of carbonates (suspended peri-platform muds and gravitational sediments). Export pulses of platform material, e.g. ooids and aggregate grains, into the slope and basinal system are interpreted as highstand shedding related to relative sealevel variations. The high-productivity phase was terminated in the Late Oxfordian when the eastern platform areas drowned and homogeneous deep water marls of the Upper Oxfordian to Kimmeridgian Korond Formation onlapped both the Qal'eh Dokhtar Limestone Formation and the drowned Esfandiar Limestone Formation. Tectonic instability, probably caused by faulting at the margins of the Tabas Block in connection with rotational movements of the east-central Iranian block assemblage, was responsible for the partial drowning of the eastern platform areas. In some areas, relicts of the platform persisted to produce shallow-water sediments into the Kimmeridgian.     

Boosted Growth Performance,Mucosal and Serum Immunity,and Disease Resistance Nile Tilapia ( Oreochromis niloticus ) Fingerlings Using Corncob-Derived Xylooligosaccharide and Lactobacillus plantarum CR1T5

The present work, herein, studied the effects of corncob-derived xylooligosaccharides (CDXOS) and Lactobacillus plantarum CR1T5 (LP) integrated into fish d     

Spectrofluorimetric determination of certain biologically active phenothiazines in commercial dosage forms and human plasma

A validated simple and sensitive spectrofluorimetric method was developed for the determination of chlorpromazine hydrochloride, promethazine hydrochloride, trifluperazine hydrochloride, thioridazine hydrochloride, perazine maleate and oxomemazine. The method was based on condensation of malonic acid/acetic anhydride (MAA) under the catalytic effect of the tertiary amine moiety of the studied phenothiazines to provide a deep yellow to brown colour with green florescence. Relative fluorescence intensity of the products was measured at λ_exc 398 nm and λ_em 432 nm. Different variables affecting the reaction were studied and optimized. The method was successfully applied for the determination of the studied drugs in commercial dosage forms. The lower detection limits allowed the application of this method for the determination of the compounds in plasma as an example of a biological fluid. In addition, the method was considered specific for the determination of tertiary amines in the presence of primary and secondary amines; as a result, it was deemed suitable for the determination of the cited drugs in the presence of their degradation products resulting from N‐dealkylation or oxidation of the corresponding sulphoxides or sulphones. Copyright © 2012 John Wiley & Sons, Ltd.     

Comparative immunomodulatory properties of adipose‐derived mesenchymal stem cells conditioned media from BALB/c,C57BL/6, and DBA mouse strains

Adipose tissue‐derived mesenchymal stem cells (AD‐MSCs) have been shown to be capable of differentiating into multiple cell type and exert immunomodulatory effects. Since the selection of ideal stem cell is apparently crucial for the outcome of experimental stem cell therapies, therefore, in this study we compared AD‐MSCs conditioned media (CM) from BALB/c, C57BL/6, and DBA mouse strains. No significant difference was found in the morphology, cell surface markers, in vitro differentiation and proliferation potentials of AD‐MSCs isolated from C57BL/6, BALB/c, and DBA mice. The immunological assays showed some variation among the strains in the cytokines, nitric oxide (NO), and indoleamine 2,3‐dioxygenase (IDO) production and immunomodulatory effects on splenocytes functions. Our results indicated a suppression of splenocytes proliferation in the presence of AD‐MSC CM from the three inbred mouse strains. However, BALB/c CM exerted a higher suppression of splenocytes proliferation. AD‐MSCs isolated from C57BL/6 and BALB/c mice produced higher levels of TGF‐β than those from DBA mice. Furthermore, IL‐17 and IDO production was higher in AD‐MSCs isolated from BALB/c mice. Our results indicated an increased production of TGF‐β, IL‐4, IL‐10, NO, and IDO by splenocytes in response to CM from BALB/c AD‐MSCs. In conclusion, our results showed that the immunomodulatory properties of mouse AD‐MSCs is strain‐dependent and this variation should be considered during selection of appropriate stem cell source for in vivo experiments and stem cell therapy strategies. J. Cell. Biochem. 114: 955–965, 2013. © 2012 Wiley Periodicals, Inc.