New emerging roles of CD133 in cancer stem cell: Signaling pathway and miRNA regulation

Cancer stem cells (CSC) are rare immortal cells within a tumor that are able to initiate tumor progression, development, and resistance. Advances studies show that, like normal stem cells, CSCs can be both self-renewed and given rise to many cell types, therefore form tumors. A number of cell surface markers, such as CD44, CD24, and CD133 are frequently used to identify CSCs. CD133, a transmembrane glycoprotein, either alone or in collaboration with other markers, has been mainly considered to identify CSCs from different solid tumors. However, the exactness of CD133 as a cancer stem cell biomarker has not been approved yet. The clinical importance of CD133 is as a CSC marker in many cancers. Also, it contributes to shorter survival, tumor progression, and tumor recurrence. The expression of CD133 is controlled by many extracellular or intracellular factors, such as tumor microenvironment, epigenetic factors, signaling pathways, and miRNAs. In this study, it was attempted to determine: 1) CD133 function; 2) the role of CD133 in cancer; 3) CD133 regulation; 4) the therapeutic role of CD133 in cancers.     

Castration Eliminates the Impairment Effects of Nandrolone on Passive Avoidance Learning of Adolescent Male Rats

Neurophysiology - In recent years, the misuse of nandrolone decanoate (ND) among non-athletes, especially adolescent males, has become a growing problem due to the adverse effects of this drug. In...     

Otomycosis in the South of Iran with a High Prevalence of Tympanic Membrane Perforation: A Hospital-Based Study

Mycopathologia - Otomycosis is a superficial infection of the external ear caused by fungal pathogens. The genera Aspergillus and Candida are considered the main fungal causative agents, with the...     

Compensatory Role of Insulin in the Extinction but Not Reinstatement of Morphine-Induced Conditioned Place Preference in the Streptozotocin-Induced Diabetic Rats

Neurochemical Research - Insulin receptors are distributed in the whole brain, including different parts of the reward circuit that modulate dopamine as the primary neurotransmitter implicated in...     

Peroxidase-producing actinobacteria from Algerian environments and insights from the genome sequence of peroxidase-producing Streptomyces sp. S19

International Microbiology - Unique environments often serve as a source of novel microorganisms with novel chemistries. In this study, telluric samples collected from different regions of Algeria...     

Should We Have Blind Faith in Bioinformatics Software? Illustrations from the SNAP Web-Based Tool

Bioinformatics tools have gained popularity in biology but little is known about their validity. We aimed to assess the early contribution of 415 single nucleotide polymorphisms (SNPs) associated with eight cardio-metabolic traits at the genome-wide significance level in adults in the Family Atherosclerosis Monitoring In earLY Life (FAMILY) birth cohort. We used the popular web-based tool SNAP to assess the availability of the 415 SNPs in the Illumina Cardio-Metabochip genotyped in the FAMILY study participants. We then compared the SNAP output with the Cardio-Metabochip file provided by Illumina using chromosome and chromosomal positions of SNPs from NCBI Human Genome Browser (Genome Reference Consortium Human Build 37). With the HapMap 3 release 2 reference, 201 out of 415 SNPs were reported as missing in the Cardio-Metabochip by the SNAP output. However, the Cardio-Metabochip file revealed that 152 of these 201 SNPs were in fact present in the Cardio-Metabochip array (false negative rate of 36.6%). With the more recent 1000 Genomes Project release, we found a false-negative rate of 17.6% by comparing the outputs of SNAP and the Illumina product file. We did not find any ‘false positive’ SNPs (SNPs specified as available in the Cardio-Metabochip by SNAP, but not by the Cardio-Metabochip Illumina file). The Cohen’s Kappa coefficient, which calculates the percentage of agreement between both methods, indicated that the validity of SNAP was fair to moderate depending on the reference used (the HapMap 3 or 1000 Genomes). In conclusion, we demonstrate that the SNAP outputs for the Cardio-Metabochip are invalid. This study illustrates the importance of systematically assessing the validity of bioinformatics tools in an independent manner. We propose a series of guidelines to improve practices in the fast-moving field of bioinformatics software implementation.     

Improved Assay for Quantifying a Redox Form of Angiotensinogen as a Biomarker for Pre-Eclampsia: A Case-Control Study

Objective

Angiotensinogen exists in two distinct redox forms in plasma, the oxidized sulfhydryl-bridge form and the reduced, unbridged, free thiol form. The oxidized form of angiotensinogen compared to the free thiol form preferentially interacts with renin resulting in increased generation of angiotensin. The predictive potential of the ratio of free-thiol to oxidized angiotensinogen in the plasma for pre-eclampsia was first suggested by the Read group in ref 10. We propose an improved method for determining the ratio and validate the method in a larger cohort of pregnant women.

Methods

Plasma samples from 115 individuals with pre-eclampsia and from 55 healthy pregnant control subjects were collected sequentially over a 2 year period. Using two distinct enzyme-linked immunosorbent assays (ELISAs) the plasma levels of total and free thiol angiotensinogen were quantified. The oxidized angiotensinogen plasma level is derived by subtracting the level of free thiol, reduced angiotensinogen from the total angiotensinogen levels in the plasma.

Results

The relative proportion of free thiol angiotensinogen, expressed as a percentage of that observed with an in-house standard, is significantly decreased in pre-eclamptic patients (70.85% ± 29.49%) (mean ± SD) as compared to healthy pregnant controls (92.98 ± 24.93%) (mean ± SD) p ≤ 0.0001. The levels of total angiotensinogen did not differ between the two groups.

Conclusion

Patients with pre-eclampsia had substantially lower levels of free thiol angiotensinogen compared to healthy pregnant controls, whilst maintaining similar total angiotensinogen levels in the plasma. Hence, elevated levels of plasma oxidized angiotensinogen may be a contributing factor to hypertension in the setting of pre-eclampsia.     

In silico analysis and modeling of ACP-MIP–PilQ chimeric antigen from Neisseria meningitidis serogroup B

Background:

Neisseria meningitidis, a life-threatening human pathogen with the potential to cause large epidemics, can be isolated from the nasopharynx of 5–15% of adults. The aim of the current study was to evaluate biophysical and biochemical properties and immunological aspects of chimeric acyl-carrier protein-macrophage infectivity potentiator protein-type IV pilus biogenesis protein antigen (ACP-MIP-PilQ) from N. meningitidis serogroup B strain.

Methods:

Biochemical properties and multiple alignments were predicted by appropriate web servers. Secondary molecular structures were predicted based on Chou and Fasman, Garnier-Osguthorpe-Robson, and Neural Network methods. Tertiary modeling elucidated conformational properties of the chimeric protein. Proteasome cleavage and transporter associated with antigen processing (TAP) binding sites, and T- and B-cell antigenic epitopes, were predicted using bioinformatic web servers.

Results:

Based on our in silico and immunoinformatics analyses, the ACP-MIP-PilQ protein (AMP) can induce high-level cross-strain bactericidal activity. In addition, several immune proteasomal cleavage sites were detected. The 22 epitopes associated with MHC class I and class II (DR) alleles were confirmed in the AMP. Thirty linear B-cell epitopes as antigenic regions were predicted from the full-length protein.

Conclusion:

All predicted properties of the AMP indicate it could be a good candidate for further immunological in vitro and in vivo studies.Key Words: Chimeric protein, In silico, Neisseria meningitides, serogroup B, Vaccine