Genome duplications within the Xenopodinae do not increase the multiplicity of antimicrobial peptides in Silurana paratropicalis and Xenopus andrei skin secretions

A putative genome duplication event within the Silurana lineage has given rise to the tetraploid frog S. paratropicalis and a second polyploidization within the Xenopus lineage has produced the octoploid frog X. andrei. Peptidomic analysis of norepinephrine-stimulated skin secretions of S. paratropicalis and X. andrei led to identification of multiple peptides with growth-inhibitory activity against Escherichia coli and Staphylococcus aureus. Structural characterization demonstrated that the S. paratropicalis components comprised three peptides belonging to the caerulein-precursor fragment family (CPF-SP1, -SP2 and -SP3), two peptides from the xenopsin-precursor fragment family (XPF-SP1 and -SP2), and one peptide orthologous to peptide glycine-leucine-amide (PGLa-SP1). The CPF peptides showed potent, broad-spectrum antimicrobial activity. The X. andrei components comprised two peptides from the magainin family, (magainin-AN1 and -AN2), two from the XPF family (XPF-AN1 and -AN2), two from the PGLa family(PGLa-AN1 and -AN2), and one caerulein-precursor fragment (CPF-AN1).The primary structures of these peptides indicate a close phylogenetic relationship between X. andrei and the octoploid frog X. amieti. Under the same experimental conditions, seven orthologous antimicrobial peptides were previously isolated from the diploid frog S. tropicalis, nine from the tetraploid frog X. borealis, and five from the tetraploid frog X. clivii. The data indicate, therefore, that nonfunctionalization (gene deletion) has been the most common fate of duplicated antimicrobial peptide genes following polyploidization events in the Silurana and Xenopus lineages.     

Exome Sequencing of Only Seven Qataris Identifies Potentially Deleterious Variants in the Qatari Population

The Qatari population, located at the Arabian migration crossroads of African and Eurasia, is comprised of Bedouin, Persian and African genetic subgroups. By deep exome sequencing of only 7 Qataris, including individuals in each subgroup, we identified 2,750 nonsynonymous SNPs predicted to be deleterious, many of which are linked to human health, or are in genes linked to human health. Many of these SNPs were at significantly elevated deleterious allele frequency in Qataris compared to other populations worldwide. Despite the small sample size, SNP allele frequency was highly correlated with a larger Qatari sample. Together, the data demonstrate that exome sequencing of only a small number of individuals can reveal genetic variations with potential health consequences in understudied populations.     

A molecular model for the differential activation of STAT3 and STAT6 by the herpesviral oncoprotein tip

Constitutive STAT signaling provides growth promoting signals in many forms of malignancy. We performed molecular modeling and molecular dynamics studies of the interaction between the regulatory Src homology 2 (SH2) domains of STAT3 and 6 with phosphorylated peptides of the herpesviral oncoprotein Tip, which facilitates Src kinase mediated STAT-activation and T cell proliferation. The studies give insight into the ligand binding specificity of the STAT SH2 domains and provide the first model for the differential activation of STAT3 or STAT6 by two distinct regions of the viral Tip protein. The biological relevance of the modeled interactions was then confirmed by activation studies using corresponding recombinant oncoproteins, and finally by respective recombinant viruses. The functional data give experimental validation of the molecular dynamics study, and provide evidence for the involvement of STAT6 in the herpesvirus induced T cell proliferation.     

OPTIMIZATION OF SOME HEAVY METALS BIOSORPTION BY REPRESENTATIVE EGYPTIAN MARINE ALGAE1

Marine algae—as inexpensive and renewable natural biomass—have attracted the attention of many investigators to be used to preconcentrate and biosorb many heavy metal ions. Impressed by this concept, the metal uptake capacity of Egyptian marine algae was examined using representatives of green and brown algae, namely, Ulva lactuca L. and Sargassum latifolium (Turner) C. Agardh, respectively. The biosorption efficiencies of Cu²⁺, Co²⁺, Ni²⁺, Cd²⁺, Hg²⁺, Ag²⁺, and Pb²⁺ ions seem to depend on the type of the algae used as well as the conditions under which the uptake processes were conducted. It was demonstrated that a pH range of 7.5–8.8 was optimum for the removal of the tested metals. Similarly, the uptake process was markedly accelerated during the first 2 h using relatively low metal level and sufficient amounts of the dried powdered tested algae.     

In vitro upregulation of erythrocytes glucose uptake by Rhaphnus sativa extract in diabetic patients

In diabetes, both the increase in the oxidative stress and the decrease in the antioxidant defense may elevate the susceptibility of diabetic patients to many pathological complications. So, the aim of the present study was to investigate the effect of superoxide dismutase (SOD) like activity protein, partially purified from radish (Rhaphnus sativa) on uptake of glucose in vitro by erythrocytes of diabetic patients. In hyperglycemic patients, erythrocytes malondialdehyde level was highly significantly increased (P < 0.0001) than that of the control. However, the erythrocytes glutathione content and glutathione reductase activity, were both highly significantly decreased (P < 0.0001) compared to that corresponding control values. The glucose uptake by erythrocytes of diabetic patients was highly significantly decreased (P < 0.0001) with increasing hyperglycemia, while it was highly significantly elevated (p < 0.0001) after addition of the partially purified SOD like activity protein. On the other hand, the malondialdehyde concentration was highly significantly reduced (p < 0.001) on adding the partially purified protein. It thus can be concluded that, an appropriate support for enhancing antioxidant supply, such as SOD like activity protein from natural sources, may help control blood glucose level and may prevent clinical complications of diabetes.     

The role of activation of KАTP channels on hydrogen sulfide induced renoprotective effect on diabetic nephropathy

This work aims to investigate the renal effect of hydrogen sulfide (H₂S), in the experimentally induced diabetic nephropathy, besides the role of activation of АТP-sensitive potassium (K_АTP) channel in that effect. Thirty-two adult male albino rats randomly divided into four groups: Control, streptozotocin-induced diabetic (diabetic nephropathy [DN]), DN+NaHS (the H₂S inducer), and DN+NaHS+Glibenclamide (a selective K_АTP channel blocker) groups. Results showed that kidney functions in the diabetic group improved by NaHS proved by the significant decrease in the measured renal injury markers when compared with the diabetic group with an obvious role of inflammation and oxidative stress. However, the improved kidney functions produced by NaHS was reduced by the combination with Glibenclamide. Glibenclamide combination led also to a significant increase in renal total antioxidant capacity, in addition to a significant decrease in renal total nitric oxide (NO) level. Аccordingly, the results from the present work revealed that the renoprotective effects of H₂S in the case of DN through its effects on renal tissue antioxidants and NO can be partially dependent on activation of K_АTP channels, while its effect on renal tissue proinflammatory cytokines is independent of it.     

Association of MicroRNA-196a2 Variant with Response to Short-Acting β2-Agonist in COPD: An Egyptian Pilot Study

Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic respiratory disease, characterized by an obstructive pattern. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that modulate the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules. Emerging evidences demonstrated the potential use of miRNAs as a disease biomarker. This pilot study aimed to investigate the association of the MIR-196a2 rs11614913 (C/T) polymorphism with COPD susceptibility, the clinical outcome and bronchodilator response to short-acting β₂-agonist. Genotyping of rs11614913 polymorphism was determined in 108 COPD male patients and 116 unrelated controls using real-time polymerase chain reaction technology. In silico target prediction and network core analysis were performed. COPD patients did not show significant differences in the genotype distribution (p = 0.415) and allele frequencies (p = 0.306) of the studied miRNA when compared with controls. There were also no associations with GOLD stage, dyspnea grade, disease exacerbations, COPD assessment test for estimating impact on health status score, or the frequency of intensive care unit admission. However, COPD patients with CC genotype corresponded to the smallest bronchodilator response after Salbutamol inhalation, the heterozygotes (CT) had an intermediate response, while those with the TT genotype showed the highest response (p < 0.001). In conclusion MIR-196a2 rs11614913 polymorphism is associated with the bronchodilator response of COPD in our sample of the Egyptian population, generating hypothesis of the potential use of MIR-196a2 variant as a pharmacogenetic marker for COPD.     

Synthesis and biological evaluations of new nitric oxide-anti-inflammatory drug hybrids

Three novel series of nitroso derivatives (11–15), isoxazolopyrazoles (17a–c) and isoxazolo[3,4-d]pyridazines (18a–c) were prepared from the hydroxyimoyl chloride 10. In vitro COX1?2 inhibition activities were evaluated, both of 17b and 18a proved a promising inhibitory activity with IC₅₀ = 1.12, 0.78 μM in sequent. Carrageenan induced Paw edema, ulcer liability, nitric oxide (NO) release and histopathological study were determined. Most of the prepared compounds showed excellent activities. Reactions of 2-aminopyridine and enaminone with hydroxyimoyl chloride 10 were investigated and proved by 2D NMR. Molecular docking for most active compounds was operated giving a hint for compound–receptor interactions.     

Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

Background: Ischemia-modified albumin (IMA) is an altered type of serum albumin that forms under conditions of oxidative stress and an independent predictor of major adverse cardiovascular events.

Objectives: To measure the levels of IMA in 45 children and adolescents with β-thalassemia major (β-TM) compared with 30 healthy controls and assess its relation to lipid peroxidation, vascular complications and subclinical atherosclerosis.

Methods: β-TM patients without symptoms of heart disease were studied focusing on transfusion history, chelation therapy, serum ferritin, malondialdehyde (MDA) and IMA levels. Echocardiography was performed and carotid intima media thickness (CIMT) was assessed.

Results: IMA and MDA levels were significantly higher in β-TM patients compared with controls (p?Conclusion: Our results highlight the role of oxidative stress in the pathophysiology of vascular complications in thalassemia. IMA could be useful for screening of β-TM patients at risk of cardiopulmonary complications and atherosclerosis because its alteration occurs in early subclinical disease.