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   Table of Contents - Current issue
January-February 2019
Volume 14 | Issue 1
Page Nos. 1-92

Online since Wednesday, February 13, 2019

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Effect of cellulose derivative matrix and oligosaccharide on the solid state and physical characteristics of dimethyldioctadecylammonium-liposomes for vaccine Highly accessed article p. 1
Helmy Yusuf, Raditya Weka Nugraheni, Dwi Setyawan
The present study was to investigate the effect of cellulose matrix and oligosaccharide on solid state and morphology characteristics of freeze-dried cationic dimethyldioctadecylammonium (DDA)-based liposomes encapsulating ovalbumin (OVA). The OVA-containing liposomes were protected using cellulose derivative matrix and oligosaccharide. Despite the fact that saccharides are known to preserve protein and lipid membranes during drying, however, collapse structure are often addressed. In other side, cellulose matrix potentially prevents collapsing as it has been widely used for matrix in drug delivery formulations to increase the mass for compact matrices of resultant products. Their solid state characteristics were determined in terms of their crystallinity using X-Ray diffraction (XRD), thermal properties and detection of phase separation using differential scanning calorimetry (DSC). Furthermore, their morphology was observed using scanning electron microscopy and transmission electron microscopy. The study revealed that formulation with either oligosaccharide and cellulose matrix demonstrated a miscible mixture with DDA and soy phosphatidylcholine (SPC) that might construct stable dried liposomal formulation. Phase separation was not observed in formula with combination of oligosaccharide and cellulose matrix where their DSC thermograms showed glass transition indicating amorphous structure and miscible mixture. XRD confirmed the absence of crystal-like properties, demonstrating prevented crystallization. The dry products were porous with spherical liposomes trapped in the matrices, signifying the ease in reconstitution. Furthermore, OVA were well-preserved as its recovery was more than 80%. The preservation of both liposomes and protein antigen were found to be dependent upon the incorporation of both oligosaccharide and cellulose matrix included in the formulation.
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Mas receptor antagonist (A799) alters the renal hemodynamics responses to angiotensin II administration after renal moderate ischemia/reperfusion in rats: gender related differences p. 12
Maryam Maleki, Mehdi Nematbakhsh
Moderate renal ischemia/reperfusion (I/R) injury is one of the major causes of kidney failure. We examined the role of Mas receptor (MasR) antagonist (A779) alone and combined with angiotensin II (Ang II) type 2 receptor (AT2R) antagonist (PD123319) on renal hemodynamic responses to Ang II after moderate I/R in male and female rats. Anaesthetized Wistar rats underwent 30 min partial ischemia by reduction of renal perfusion pressure (RPP) and subjected to block vasodepressor receptors followed by Ang II (100 and 300 ng/kg/min) infusion. Mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) responses were assessed during graded Ang II infusion at controlled RPP. Thirty min post reperfusion, the Ang II infusion reduced RBF and increased RVR in a dose-related fashion (P < 0.05). However, A779 alone or A779 plus PD123319 infusion increased the RBF and RVR responses to Ang II infusion significantly (P < 0.05) in female but not in the male rats. MasR antagonist altered the RBF and RVR responses to Ang II infusion in female, and these responses were not altered statistically in dual blockade of MasR and AT2R. These findings suggest the important role of Mas receptor in renal vascular response to Ang II in female rats after moderate I/R.
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Design and molecular dynamic simulation of a new double-epitope tolerogenic protein as a potential vaccine for multiple sclerosis disease p. 20
Fatemeh Banisharif-Dehkordi, Mohsen Mobini-Dehkordi, Mostafa Shakhsi-Niaei, Karim Mahnam
One of the debilitating diseases affecting the central nervous system is multiple sclerosis (MS). As there is no definitive treatment for MS, researchers have mainly consented with optimization of strategies which slows down the progression of the disease such as specific auto-antigens tolerance induction. In this regard, the aim of this study was design of a new double-epitope protective vaccine based on interleukin (IL)-16-neuroantigens fusion proteins. First, we selected highly antigenic epitopes of myelin basic protein (MBP) (aa 84-104) and myelin oligodendrocyte glycoprotein (MOG) (aa 99-107) from available literature and our bioinformatics analysis. The correct cleavage of our constructs and major histocompatibility complex class II binding affinities of cleaved epitopes were checked and evaluated using Pepcleave and IEDB servers, respectively. Then, different combination of MOG and MBP epitopes with or without fusion to C-terminal active part of IL-16 were designed as constructs. Afterward, Modeller and Gromacs softwares used for the investigation of the MBP, and MOG epitopes antigenicity in these constructs. The results of molecular dynamics simulations showed that IL-16 in MOG + linker + MBP + IL-16 construct does not interfere with final epitopes antigenicity of MOG + linker + MBP construct. To sum up, the construct with IL-16 is suggested as a new double-epitope tolerogenic vaccine for prevention and amelioration of MS in human.
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Cytotoxic effect of dual fluorescent-labeled oncolytic herpes simplex virus type 1 on mouse tumorigenic cell lines p. 27
Shahriyar Abdoli, Farzin Roohvand, Ladan Teimoori-Toolabi, Sara Shayan, Mohammad Ali Shokrgozar
The increasing incidences of cancer at the global scale have recently resulted in the invention of various biotechnology approaches among which the oncolytic virotherapy is a new strategy for the treatment of multiple tumors. Herpes simplex virus (HSV) based vectors are one of the most studied oncolytic agents, worldwide. Moreover, syngeneic animal models are the principal parts of the oncolytic virotherapies investigation. The effects of a dual fluorescent γ34.5 deleted vector-HSV-GR- on three mouse tumor cell lines were studied in this work. We previously generated a dual fluorescent labeled oncolytic HSV-HSV-GR- (both copies of γ34.5 were inactivated by insertion of two distinct fluorescent dyes, GFP and mCherry) in our laboratory; subsequently, they were used as oncolytic viruses. The three 4T1, TC-1, and CT26 cell lines were infected with HSV-GR. The infection efficacy and the elimination potency of HSV-GR were analyzed by photomicrography and flow cytometry methods. HSV-GR showed a significant efficiency to infect the cell lines examined. Flow cytometry analyses demonstrated that HSV-GR infected 89.3%, 86.1%, and 92.4% of 4T1, TC-1, and CT26 cells, respectively. Moreover, propidium iodide (PI) staining of infected cells indicated that HSV-GR could kill 27.9%, 21.2%, and 21.3% of 4T1, TC-1, and CT26 cells, respectively. Interestingly, HSV-GR infected cells were capable of expressing both GFP and mCherry at the same time. The promising effects of the oncolytic virus HSV-GR in the mouse syngeneic tumor cell system have shed more light on the therapeutic potential of this anti-cancer approach.
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Regulatory effects of hemp seed/evening primrose oil supplement in comparison with rapamycin on the expression of the mammalian target of rapamycin-complex 2 and interleukin-10 genes in experimental autoimmune encephalomyelitis p. 36
Soheila Rezapour-Firouzi, Fatemeh kheradmand, Sharam Shahabi, Ali Asghar Tehrani, Ebrahim Mazloomi, Adel Mohammadzadeh
The mammalian target of rapamycin (mTOR) signaling plays a critical role in lipid synthesis and immune responses. The T regulatory cells (Treg) as suppressor of T cells, are a subset of T cells that modulate the immune system, maintain tolerance, and prevent autoimmune diseases.. The interleukin (IL) -10 derived from the Treg and T helper (Th) 2 is an anti-inflammatory cytokine in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Due to the exclusive roles of rapamycin (RAPA) in mTOR inhibition, we evaluated the regulatory effect of the hemp seed oil/evening primrose oil (HSO/EPO) supplement in comparison with RAPA in EAE. EAE was induced by using myelin oligodendrocyte glycoprotein peptide and complete freund’s adjuvant (CFA) in C57BL/6 mice, total mRNA was extracted from local lymph nodes and real-time polymerase chain reaction was used to evaluate the expression level of the rapamycin-insensitive companion of mTOR complex 2 (RICTOR) and IL-10 genes. The expression of IL-10 and RICTOR genes were significantly increased in HSO/EPO group. In contrast with RAPA groups, histological findings have shown that the HSO/EPO treated group remarkably reduced cell infiltration and promoted remyelination. The EPO/HSO has beneficial effects on the repair of myelin, which was confirmed by immunological and histological findings.
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Acute and chronic effects of morphine on Low-Mg2+ ACSF-induced epileptiform activity during infancy in mice hippocampal slices p. 46
Yousef Panahi, Ehsan Saboory, Shiva Roshan-Milani, Leila Drafshpoor, Yousef Rasmi, Ali Rassouli, Goudarz Sadeghi-Hashjin
Interaction of morphine and seizure is complex. Mouse brain hippocampal slices were used to estimate how acute and chronic morphine treatment alters the low-magnesium artificial cerebrospinal fluid (LM-ACSF)-induced seizure activity. Hippocampal slices were taken from the normal and morphine-treated mice. The normal mice received saline while the other group (morphine-treated mice) received morphine daily for 5 consecutive days. Saline/morphine administration was performed subcutaneously (s.c, 0.1 mL) at postnatal days 14-18. Hippocampal slices of all animals were perfused with LM-ACSF followed by different morphine concentrations (0, 10, 100, and 1000 μM) or naloxone (10 μM). Changes in the spike count were considered as indices for quantifying the seizure activity in the slices. In hippocampus of both groups perfused with 10 or 1000 μM morphine, epileptiform activity was suppressed while it was potentiated at 100 μM morphine. The excitatory effect of morphine at 100 μM was stronger in normal mice (acute exposure) than in dependent mice (chronic exposure). Naloxone suppressed the epileptiform activities in both groups. Suppressive effect of naloxone was more significant in morphine-treated mice than in normal mice. The seizure activity in morphine-dependent mice was more labile than that of normal mice. It can be concluded that morphine had a biphasic effect on LM-ACSF-induced epileptiform activities in both groups. The occurrence of seizure was comparable in acute and chronic exposure of morphine but strength of the effect was considerably robust in normal mice. The down regulation of opioid receptors in chronic exposure is likely to be responsible for these differences.
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Pterostilbene increases Fas expression in T-lymphoblastic leukemia cell lines p. 55
Gelareh Ramezani, Batoul Pourgheysari, Hedayatollah Shirzad, Zahra Sourani
Treatment of acute lymphoblastic leukemia (ALL) has been promising in last decades, but side effects still persist and searching for the least toxic agents continue. Pterostilbene (PTE) is a natural compound with several anti-cancer and anti-oxidant properties. Fas, as a member of death inducing family of tumor necrosis factor (TNF) receptors with an intracellular death domain, can initiate the extrinsic apoptosis signaling pathway. Here after the half maximal inhibitory concentration (IC50) determination in cell lines, we searched for PTE effects on Fas, both in mRNA and surface levels in two ALL cell lines, Jurkat and Molt-4. After harvesting cells in optimum situations, MTS assay was used to determine IC50 concentrations. Real-time polymerase chain reaction (RT-PCR) and flow cytometry were performed for Fas mRNA and surface expression variations after exposure to PTE. The findings showed that PTE decreases cell viability with different extent in two ALL cell lines. In addition to inducing apoptosis, it can increase Fas in both gene and cell surface expression in the same concentrations. Pterostilbene as a natural anti-cancer agent can increase Fas expression both in mRNA and surface levels that results in apoptosis signal transduction improvement which sensitizes cells to apoptosis by immune effector cells. As a result, abnormal cells removal would be more efficiently with the minimum side effects on normal cells.
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Effect of pentoxifylline on kidney damage induced by nitrosamine in male rats p. 64
Cyrus Jalili, Delnia Moradi, Shiva Roshankhah, Mohammad Reza Salahshoor
Nitrosamines are well-known carcinogenic agents. Humans are exposed to nitrosamines in various ways, the most important of which is the diet. Pentoxifylline is a xanthine derivative, which is used as a drug that inhibits inflammatory factors, reduces blood viscosity, improves peripheral blood flow, and increases oxygenation of tissue. This study was designed to evaluate the effects of pentoxifylline against damage induced by nitrosamine to the kidneys of rats. In this study, 48 male rats were randomly assigned to 8 groups: control normal group and nitrosamine control treated group (40 mg/kg); pentoxifylline groups (25, 50, 100 mg/kg) and nitrosamine + pentoxifylline treated groups (25, 50, 100 mg/kg). Treatments were administered either intraperitoneally (nitrosamine) or orally (pentoxifylline) on a daily basis for 28 days. The normalized kidney weight, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators, and serum nitrite oxide levels were investigated. Nitrosamine administration increased kidney malondialdehyde (MDA) level, kidney weight, blood urea nitrogen (BUN), creatinine, and nitrite oxide levels and decreased significantly glomeruli number and tissue ferric reducing/antioxidant power (FRAP) level compared to the control normal group (P < 0.05). The pentoxifylline and pentoxifylline + nitrosamine treatments reduced BUN, kidney MDA level, creatinine, glomerular diameter, and nitrite oxide levels significantly at all doses and increased the glomeruli number, kidney weight, and tissue FRAP level compared to the nitrosamine control group (P < 0.05). It seems that pentoxifylline administration improved kidney injury induced by nitrosamine in rats.
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Searching for new cytotoxic agents based on chromen-4-one and chromane-2,4-dione scaffolds p. 74
Alexandra Gaspar, Maryam Mohabbati, Fernando Cagide, Nima Razzaghi-Asl, Ramin Miri, Omidreza Firuzi, Fernanda Borges
Cancer is a major cause of death worldwide and novel anticancer agents for its better management are much needed. Benzopyrone-based compounds, such as chromones, possess several distinctive chemical and biological properties, of which the cytotoxicity against cancer cells seems to be prominent. In this study, two series of compounds based on chromen-4-one (3-10) and chromane-2,4-dione (11-18) scaffolds were synthesized in moderate/high yields and evaluated for cytotoxicity against HL-60, MOLT-4, and MCF-7 cancer cells using MTT assay. In general, the compounds exhibited moderate cytotoxic effects against the cancer cell lines, among which, a superior potency could be observed against MOLT-4 cells. Chroman-2,4-dione (11-18) derivatives had overall higher potencies compared to their chromen-4-one (3-10) counterparts. Compound 13 displayed the lowest IC50 values against HL-60 (IC50, 42.0 ± 2.7 μM) and MOLT-4 cell lines (IC50, 24.4 ± 2.6 μM), while derivative 11 showed the highest activity against MCF-7 cells (IC50, 68.4 ± 3.9 μM). In conclusion, this study provides important information on the cytotoxic effects of chromone derivatives. Benzochroman-2,4-dione has been identified as a promising scaffold, which its potency can be modulated by tailored synthesis with the aim of finding novel and dissimilar anticancer compounds.
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Therapeutic drug monitoring of vancomycin by AUCτ-MIC ratio in patients with chronic kidney disease p. 84
Ahmad Khoei, Rasool Soltani, Jaber Emami, Shirinsadat Badri, Shahram Taheri
In this study which was conducted in Alzahra University Hospital (Isfahan, I.R. Iran), the therapeutic drug monitoring of vancomycin focused on determining area under the concentration-time curve at dosing interval (τ) at steady state/minimum inhibitory concentration (AUCτ/MIC) was carried out in chronic kidney disease (CKD) patients. The study population was selected from patients with the history of CKD (stages 3 or 4) treated by intravenous vancomycin. To determine vancomycin AUCτ, blood samples were taken at four different occasions (trough-1, peak, random, trough-2) between the fourth and fifth doses of vancomycin. Drug concentration was determined by fluorescence polarization technique, and the E-TEST technique was used to determine the MIC. Nineteen patients were included. For 8 (42%), 7 (37%), and 4 (21%) patients, trough concentration levels were found to be less than 10 mg/L, 10-20 mg/L, and more than 20 mg/L, respectively. The mean value of AUCτ for studied patients was 470.7 ± 228.3 mg.h/L and the mean MIC values was 1.04 ± 0.43 mg/L. Ten patients (53%) and 9 patients (47%) had the AUCτ/MIC ratios above 400 and below 400, respectively, with the average of 519.4 ± 391.3 h. Vancomycin dosing based on patient glomerular filtration rate (GFR), as a traditional method, is not accurate enough to gain the most desired vancomycin concentration in patients with decreased or changing kidney function. Measuring drug concentration and observing its therapeutic effects accordingly is inevitable in susceptible populations receiving vital drugs such as vancomycin.
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