Global estimate of gastric cancer in Helicobacter pylori–infected population: A systematic review and meta-analysis

There is information regarding the rates of gastric cancer (GC) in different populations and the important role of Helicobacter pylori in GC development; however, no comprehensive study has yet been performed to investigate the prevalence of GC in H. pylori–infected patients. PubMed, Embase, and Cochrane Library through January 1, 2000 were searched without language restrictions. Quality of included studies was assessed with a critical appraisal checklist recommended by the Joanna Briggs Institute. All of the analyses were conducted using Comprehensive Meta-Analysis Software Version 2.0 and Stata 14.0. Forty-four studies from 17 countries were included. The pooled frequency of GC was 17.4% (95% confidence interval: 16.4–18.5) in H. pylori–infected population. The frequency of GC among H. pylori–infected population varied markedly across countries. The highest rate of GC was observed in H. pylori–infected individuals from Asian countries. The frequency of GC was relatively high in H. pylori–infected population in the world. However, the eradication of H. pylori might be a promising strategy for GC prevention, especially in high-risk populations such as Asian countries.     

microRNAs: Key players in virus-associated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.     

Small interfering RNA–mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the lethal and difficult-to-cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence-specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA-mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti-HCC agents is the subject of the current review. siRNA-based gene therapies could be one of the main feasible approaches for HCC therapy in the future.     

The effect of the diameter of cyclic peptide nanotube on its chirality discrimination

In this work, the transport behaviors of the enantiomers of lactic acid (LA) in two cyclic peptide nanotubes (CPNTs) with different diameters were studied using steered molecular dynamic (SMD) simulation to investigate the effect of the diameter of CPNT on the discrimination of the enantiomers of LA. For this purpose, two cyclic peptides with two different sizes ([Ala-_D-Ala-_L]₅ and [Ala-_D-Ala-_L]₄) were used for constructing two CPNTs so that each CPNT was composed of eight cyclic peptide units. The docking calculations were performed to obtain the appropriate position of each enantiomer at the lumen of each CPNT. The variation of the pulling force versus time, exerted on the enantiomers moving in the CPNTs was calculated using the SMD simulations with two different strategies (positional and directional).The obtained results showed that the diameter of CPNT has considerable effect on the discrimination of the LA enantiomers so that the increase of the diameter of CPNT, increased the velocity difference between two enantiomers and improved the performance of CPNT for the chirality discrimination. The SMD simulations indicated that the velocity of S-enantiomer became more than R-enantiomer and its motion became more comfortable than R-enantiomer when the diameter of CNPT increased. The RDFs of the H and O atoms of the LA enantiomers relative to the O atoms of CPNT were calculated and it was found that the increase of the diameter of CPNT creates the significant changes in the RDFs of H1, H2 and H3 atoms of the enantiomers.     

A combination of bioactive and nonbioactive alkyl-peptides form a more stable nanofiber structure for differentiating neural stem cells: a molecular dynamics simulation survey

Self-assembling alkyl-peptides are important molecules due to their ability to construct nano-level structures such as nanofibers to be utilized as tissue engineering scaffolds. The bioactive epitope of FAQRVPP which acts as neural stem cells (NSCs) outgrowth inducing factor is used in nanofiber structures. Based on previous experimental studies the density and distribution pattern of the epitopes on the surface of the nanofibers plays an important role in the differentiation function efficiency. We decided to survey and compare the stability of two pre-constructed fiber structures in the forms of all-functionalized nanofiber (containing only bioactive alkyl-peptides) and distributed functionalized nanofiber (a combination of nonbioactive and bioactive alkyl-peptides with ratio 2:1). Our findings reveal that the all-functionalized fiber shows an unstable structure and is split into intermediate micelle-like structures to reduce compactness and steric hindrance of functional epitopes whereas the distributed functionalized fiber shows an integrated stable nanofiber with a more amount of beta sheets that are well-organized and oriented around the hydrophobic core. The hydrogen bonds and energy profiles of the structures indicate the role of hydrophobic interactions during the alkyl-chain core formation and the important role of electrostatic interactions and hydrogen bond network in the stability of the final structures. Finally, it seems that the possibility of the presence of intermediate structure is increased in the all-functionalized nanofiber environment, and it can reduce functional efficiency of the scaffolds. These findings can help to design more efficient nanofiber structures with different goals in scaffolds for tissue engineering. Abbreviations MD Molecular Dynamics

NSCs Neural Stem Cells

PME Particle mesh Ewald

RDF Radial Distribution Function

RG Radius of gyration

RASA Relative Accessible Surface Area

RMSD Root Mean Square Deviations

SASA Solvent Accessible Surface Area.

Communicated by Ramaswamy H. Sarma     

Promoter methylation and functional variants in arachidonate 5-lipoxygenase and forkhead box protein O1 genes associated with coronary artery disease

Coronary artery disease (CAD) is a multifactorial chronic inflammatory disease, which is the most common form of heart disease. This is one of the main causes of death in the United States. Inflammation is one of the key drivers of atherosclerotic plaque development. Forkhead box protein O1 (FOXO1s) family and 5-lipoxygenase make an important contribution to atherosclerosis. The aim of this study was to investigate the methylation pattern and polymorphism analysis of FOXO1 and arachidonate 5-lipoxygenase (ALOX5) promoter genes. We studied 50 patients with CAD and 50 age- and sex-matched healthy controls by high resolution melt technique. Overall, we found significant differences between patients and controls in terms of the promoter methylation of ALOX5 (P > 0.05). But there was no significant difference in FOXO1 promoter methylation between patient and controls. Single nucleotide polymorphisms genotyping of rs12762303 and rs2297627, in ALOX5 and FOXO1 genes were demonstrated a significant correlation between mutant allele and the risk of CAD, respectively. Furthermore, there were significant associations between CT + CC genotype and ALOX5 expression. Our findings demonstrated functional effects of single nucleotide polymorphisms (SNPs) and DNA methylation in ALOX5 on mentioned genes expression and they resulted in CAD progression.     

A simple and highly efficient method for transduction of human adipose-derived mesenchymal stem cells

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into a wide range of cell types and provide a potential to transfer therapeutic protein in vivo, making them valuable candidates for gene therapy and cell therapy. However, using MSCs in in vivo is limited due to the low rate of transfection and transduction efficacy. Therefore, developing methods to efficiently transfer genes into MSCs would provide a number of opportunities for using them in the clinic. Here, we introduce a simple and robust method for efficient transduction of human adipose-derived MSCs by modification under the culture condition of human embryonic kidney cells 293 (HEK293T) and MSCs. Moreover, as a transduction enhancer, polybrene was replaced with Lipofectamine, a cationic lipid. Therefore, we showed that transduction of primary cells can be increased efficiently by modifying the culture condition.     

Affinity maturation and characterization of the ofatumumab monoclonal antibody

CD20 molecule, a phosphoprotein with 297 amino acids and four transmembrane domains, is a member of MS4A protein family. Anti-CD20 antibodies such as ofatumumab, which have been developed for cancer treatment and has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. Rational engineering methods can be applied with reasonable success to improve functional characteristics of antibodies. Considering the importance of this issue, we have used in silico modeling approach for the improvement of ofatumumab monoclonal antibody. Four mutated variants of ofatumumab were developed and expressed in Chinese hamster ovary (CHO) cells along with the unmodified antibody. Analysis of affinity of the purified antibodies with CD20 showed significant improvement in antigen-binding characteristics of one of the variants compared with the control antibody. This study represents the first step toward development of the second generation ofatumumab antibody with improved affinity.     

Dysregulated expression of STAT1, miR-150, and miR-223 in peripheral blood mononuclear cells of coronary artery disease patients with significant or insignificant stenosis

Coronary artery disease (CAD) is a multicellular disease characterized by chronic inflammation. Peripheral blood-mononuclear cells (PBMCs), as a critical component of immune system, actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in perturbed PBMC expression. STAT1 is believed to be relevant to CAD pathogenesis through regulating key inflammatory processes and modulating STAT1 expression play key roles in fine-tuning CAD-related inflammatory processes. This study evaluated PBMC expressions of STAT1, and its regulators (miR-150 and miR-223) in a cohort including 72 patients with CAD with significant ( ≥ 50%) stenosis, 30 patients with insignificant ( < 50%) coronary stenosis (ICAD), and 74 healthy controls, and assessed potential of PBMC expressions to discriminate between patients and controls. We designed quantitative real-time polymerase chain reaction (RT-qPCR) assays and identified stable reference genes for normalizing PBMC quantities of miR-150, miR-223, and STAT1 applying geNorm algorithm to six small RNAs and five mRNAs. There was no significant difference between CAD and ICAD patients regarding STAT1 expression. However, both groups of patients had higher levels of STAT1 than healthy controls. miR-150 and miR-223 were differently expressed across three groups of subjects and were downregulated in patients compared with healthy controls, with the lowest expression levels being observed in patients with ICAD. ROC curves suggested that PBMC expressions may separate between different groups of study subjects. PBMC expressions also discriminated different clinical manifestations of CAD from ICADs or healthy controls. In conclusion, the present study reported PBMC dysregulations of STAT1, miR-150, and miR-223, in patients with significant or insignificant coronary stenosis and suggested that these changes may have diagnostic implications.