Hepatitis C virus genotypes in patients with chronic hepatitis C infection in southern Iran from 2016 to 2019

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The treatment of HCV infection has become more complicated due to various genotypes and subtypes of HCV. The treatment of HCV has made significant advances with direct-acting antivirals. However, for the choice of medicine or the combination of drugs for hepatitis C, it is imperative to detect and discriminate the crucial HCV genotypes. The main objective of this study was to determine the pattern of circulating HCV genotypes in southern Iran, from 2016 until 2019. The other aim of the study was to determine possible associations of patients’ risk factors with HCV genotypes. A total of 803 serum samples were collected in 4 years (2016–2019) from patients with HCV antibody positive results. A total of 728 serum samples were HCV-RNA positive. The prevalence of HCV genotypes was detected using the genotype-specific RT-PCR test for serum samples obtained from 615 patients. The HCV genotype 1 (G1) was the most prevalent (48.8%) genotype in the area, with G1a, G1b, and mixed G1a/b representing 38.4%, 10.1%, and 0.3%, respectively. Genotype 3a was the next most prevalent (47.2%). Mixed genotypes 1a/3a were detected in 22 (3.6%) and finally G4 was found in 3 (0.5%) patients. The other HCV genotypes were not detected in any patient. Genotype 1 (1a and 1b alone, 1a/1b and 1a/3a coinfections) is the most prevalent HCV genotype in southern Iran. HCV G1 shows a significantly higher rate in people under 40 years old.     

Movement of a spherical cell in capillaries using a boundary element method

This study aims to investigate the translation and rotation of a spherical particle in capillaries and overcomes limitations in previous studies by using a boundary element method. The capillary, a straight cylindrical tube, is filled with a Newtonian viscous fluid. A spherical particle is arbitrarily positioned in the capillary either co-centrically or eccentrically and is free to translate and rotate. Flow in the capillary is first assumed to be caused solely by the movement of the sphere under the gravity. When a steady state is reached, the net force and torque on the sphere are zero. The translating velocity and rotation of the particle are calculated from equilibrium equations. For a co-centric sphere, our result agrees to Bohlin's analytical solution (Bohlin, 1960) and the difference is less than 1%. For an eccentrically positioned sphere in the tube, there are no analytical solutions unless the eccentricity is infinitesimal. Results by boundary element method (BEM) give an improved estimations on the velocity and rotation of the sphere than earlier results by a boundary singularity method (BSM), particularly when the clearance between the tube and the sphere becomes small. Movement of a spherical particle in a capillary driven by a pressure gradient is further investigated, which has closer relevance to movement of blood cells in capillaries. The current study using BEM enables investigation on cell movement in close proximities of the capillary wall.     

Effective Non-Viral Delivery of siRNA to Acute Myeloid Leukemia Cells with Lipid-Substituted Polyethylenimines

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ～0.5 and led to siRNA/polymer complexes of ～100 nm size. While the native PEI2 did not display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification on PEI2 slightly increased the cytotoxicity, which was consistent with increased interaction of polymers with cell membranes. Cellular delivery of siRNA was dependent on the nature of lipid substituent and the extent of lipid substitution, and varied among the three AML cell lines used. Linoleic acid-substituted polymers performed best among the prepared polymers and gave a siRNA delivery equivalent to better performing commercial reagents. Using THP-1 cells and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without adversely affecting subsequent cell growth. We conclude that lipid-substituted PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be employed in molecular therapy of leukemia.     

Escape from Gregarine Parasites Affects the Competitive Interactions of an Invasive Mosquito

When a species is introduced into a new location, it may escape, at least temporarily, from its natural enemies. In field surveys, we found that when the exotic, invasive mosquito, Aedes albopictus, invades new sites, it initially experiences reduced infection by its gut parasite, Ascogregarina taiwanensis. To determine the effect of this escape from parasitism on the competitive ability of A. albopictus, we performed a laboratory competition experiment in which infected and uninfected A. albopictus larvae were reared in microcosms alone and in competition with larvae of the native mosquito, Ochlerotatus triseriatus. We analyzed the effect of parasitism by A. taiwanensis on A. albopictus performance when subjected to intra- and interspecific competition across a range of larval densities, as well as the effect of A. albopictus parasitism by A. taiwanensis on the competitive impact of A. albopictus on O. triseriatus. At a density of 30 O. triseriatus larvae, O. triseriatus survivorship was significantly reduced by the addition of 30 unifected A. albopictus, but not by addition of 30 infected A. albopictus, and not by addition of 15 A. albopictus whether infected or uninfected. Although estimated finite rate of population increase (') showed similar trends, and was significantly affected by treatments, no pairwise differences in rate of increase were significant. Infection by A. taiwanensis also significantly prolonged A. albopictus female development time and reduced the intraspecific competitive effect of increased density of A. albopictus, but did not affect A. albopictus survivorship, mass, or estimated finite rate of population increase. Thus, when A. albopictus escapes from this parasite as it colonizes new sites, this escape may give it a small, but significant, added competitive advantage over O. triseriatus, which may facilitate range expansion of A. albopictus and enhance A. albopictus's initial impact on resident species.     

In Silico Designing a Candidate Vaccine Against Breast Cancer

International Journal of Peptide Research and Therapeutics - Breast cancer (BC) is the most common type of women’s cancer with a prevalence of about 25%, although it is rare in men...     

Design and Synthesis of Novel Cytotoxic Indole‐Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study

In this work, two novel series of indole‐thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF‐7, A‐549, and Hep‐G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A‐549 and Hep‐G2 than MCF‐7. Among them, (2E)‐2‐{[2‐(4‐chlorophenyl)‐1H‐indol‐3‐yl]methylidene}‐N‐(4‐methoxyphenyl)hydrazinecarbothioamide ( 8l ) was found to be the most potent compound against A‐549 and Hep‐G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A‐549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.     

A novel nuclear protein which binds to G gamma and A gamma globin promoters and modulates hemoglobin synthesis in K562 cells.

Nuclear extract of human erythroleukemic cell line K562 contains a 70 kDa protein which is gradually reduced when cells are induced to express globin genes by 25 microM hemin. When globin synthesis was inhibited by cycloheximide (100 micrograms/ml) or Actinomycin D (1 microgram/ml), the disappearance of this protein was prevented. The 70 kDa nuclear protein exhibited strong binding to G gamma and A gamma globin promoters but not to beta-globin promoter. This suggests that this 70 kDa nuclear protein may be involved in the regulation of fetal globin gene expression.     

Associated effects of sodium butyrate on histone acetylation and estrogen receptor in the human breast cancer cell line MCF-7

Sodium butyrate at a concentration of 5mM causes significant hyperacetylation of the core histones in the human breast cancer cell line MCF-7. Histone hyperacetylation was achieved in rapidly-growing cells at 40% confluency after 24 hours in 5mM sodium butyrate. More nearly confluent cells did not reach as high a level of histone hyperacetylation. Upon assaying the estrogen receptors, both cytosolic and KCl-extractable nuclear, we found that butyrate treatment had lowered the estrogen receptor levels in both compartments. To our knowledge this is the first report of an effect of sodium butyrate on estrogen receptor levels.