فهرست مطالب

Advanced Pharmaceutical Bulletin - Volume:10 Issue: 1, 2020
  • Volume:10 Issue: 1, 2020
  • تاریخ انتشار: 1398/10/30
  • تعداد عناوین: 20
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  • Sharon Kunnath Joseph, Mangalath Sabitha*, Sreeja Chandrasekharan Nair Pages 1-12

    An ideal colon specific drug delivery system needs to perform multiple functions like greater bio availability, less toxicity and higher therapeutic efficacy, all of which require high degree of smartness. This article focuses on the overview of the stimuli-responsive polymers and various nanodrug delivery systems which have found applications in colon specific delivery of drugs as this system provide a link between therapeutic need and drug delivery. These polymers exhibit a non-linear response to a small stimulus leading to a macroscopic alteration in their structure/properties. Stimuli responsive polymers display a significant physio chemical change in response to small changes in their environment (temperature, pH, light etc.). Colonic drug delivery has gained increased importance in treating diseases like Crohn’s disease, ulcerative colitis, colon cancer etc. The expansion in the development of polymers based system with greater flexibility, versatility and unexplored potential enables new opportunities for them in uplifting bio medicine. Applying the concepts of smartness in the context of clinically relevant therapeutic and diagnostic systems, it can prelude in a new era of ‘smart’ therapeutics that can improve the health care fields. In particular, due to its high sensitivity to the stimuli, this system has been identified as a sensible platform for releasing drug at suitable site and at appropriate time.

    Keywords: Nanopolymers, Stimuli responsive polymers, Controlled release, Nano platform, Smart polymers, Colon specific drug delivery
  • Mahdi Mashhadi Akbar Boojar* Pages 13-19

    Considering the remarkable application of radiotherapy in the treatment and diagnosis of various diseases and even nuclear war, it is important to protect healthy tissues and people at risk from the radiation. Currently, there is no ideal and safe radioprotective agent available and we are seeing a great effort to find these agents from natural sources. Phenolic compounds, as well as flavonoid, are presented widely as the second metabolite in plants and they have been considered for investigation according to their benefits for human health, healing and preventing many disorders. The major bioactive benefits of flavonoids include antioxidant, anti-inflammatory, anti-tumor, anti-aging, anti-bacterial and viral, neuroprotection and radioprotective effects. Their lower toxicity and oral administration have made it suitable for radiotherapy patient, radiation, military forces, and even the general public. This review attempts to provide a summary of the main molecular mechanisms involved in flavonoid radio-protective effects. Data of these studies will provide a comprehensive perspective to flavonoids and can help to optimize their effects in radioprotection procedures.

    Keywords: Ionizing radiation, Radio-protector, Flavonoids
  • Sara Salatin, Jaleh Barar*, Mohammad Barzegar Jalali, Khosro Adibkia, Mitra Alami Milani, Mitra Jelvehgari Pages 20-29
    Purpose

    Rivastigmine hydrogen tartrate (RHT) is commonly used for the treatment of mild to moderate Alzheimer’s disease (AD). The aim of this work was to formulate in-situ pluronic F-127 (PF-127) hydrogels containing Eudragit RL-100 (EU-RL) nanoparticles (NPs) in order to improve the therapeutic efficacy of RHT through the nasal route.

    Methods

    The NPs were prepared using different polymer to drug ratios and evaluated for their physicochemical characteristics, cellular uptake and in vitro cytotoxicity against lung adenocarcinoma cells (A459). PF-127 nanoformulations were prepared via cold method and analyzed in terms of physicochemical properties and drug release profiles. The nanoformulations and plain drug gel were then assessed by ex vivo permeation studies across the sheep nasal mucosa.

    Results

    The EU-RL NPs exhibited a particle size within the range of 118 to 154 nm and positive zeta potential values of 22.5 to 30 mV with an approximately spherical shape. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) suggested no drug to polymer interaction through the preparation of nanoformulations. The RHT-loaded NPs exhibited an acceptable cytocompatibility with a time- and dose-dependent cellular internalization.

    Conclusion

    Our results clearly indicated the potential of nanoformulations as controlled release systems to improve the therapeutic efficacy of RHT through the intranasal administration.

    Keywords: Cytotoxicity, Eudragit, Hydrogel, Nanoparticle, Nasal, Rivastigmine
  • Sepideh Khodaverdi, Alireza Jafari*, Farahnaz Movahedzadeh, Fateme Madani, Arshid Yousefi Avarvand, Siavash Falahatkar Pages 30-38
    Purpose

    Paclitaxel (PTX) has transpired as a significant agent in the treatment of breast cancer. Meanwhile, polylactic glycolic acid (PLGA) nanoparticles (NPs) are able to increase the anticancer effect of the PTX in the blood.

    Methods

    Nano-precipitation was used to prepare the PLGA-PTX-VitD3 co-delivery NPs. Drug loading, encapsulation efficiency, in vitro release profile, cell viability, migration, apoptosis, and bcl2 expression of NPs were evaluated.

    Results

    The average size of co-delivery NPs was 231 ± 46 nm. Observed was a controlled release of the PTX and vitamin D3 from co-delivery NPs between 0.5 and 240 hours. MTT showed the ability of 8 μg.mL-1 of co-delivery NPs to kill 50 % of the MCF-7; likewise, the co-delivery NPs prevented MCF-7 migration. The co-delivery NPs led 46.35 % MCF-7 to enter primary apoptosis. 60.8% of MCF-7 in the control group were able to enter the G (1) phase of the cell cycle. The co-delivery NPs increased expression of bax. In addition to its higher toxicity against MCF-7 than that of PTX, co-delivery NPs were able to release drugs continuously for a long period, which indeed increased the efficiency of the drugs.

    Conclusion

    The effect of co-delivery NPs on MCF-7 cell viability was different from that in other drugs. In fact, the co-deliver NPs were able to release drugs continuously for a long time, this could induce primary apoptosis in the MCF-7 and decrease the metastasis and toxicity of drugs.

    Keywords: Breast cancer, Anzatax, 25-Hydroxyvitamin D2, PLGA compound, Nanoparticle, bax genes, MCF-7 cell
  • Azam Akbari, Azim Akbarzadeh*, Morteza Rafiee Tehrani, Reza Ahangari Cohan, Mohsen Chiani, Mohammad Reza Mehrabi Pages 39-45
    Purpose

    Hydroxyurea (HU) is a well-known chemotherapy drug with several side effects which limit its clinical application. This study was conducted to improve its therapeutic efficiency against breast cancer using liposomes as FDA-approved drug carriers.

    Methods

    PEGylated nanoliposomes-containing HU (NL-HU) were made via a thin-film hydration method, and assessed in terms of zeta potential, size, morphology, release, stability, cellular uptake, and cytotoxicity. The particle size and zeta potential of NL-HU were specified by zeta-sizer. The drug release from liposomes was assessed by dialysis diffusion method. Cellular uptake was evaluated by flow cytometry. The cytotoxicity was designated by methyl thiazolyl diphenyl-tetrazolium bromide (MTT) test.

    Results

    The size and zeta value of NL-HU were gotten as 85 nm and -27 mV, respectively. NL-HU were spherical.NL-HU vesicles were detected to be stable for two months. The slow drug release and Weibull kinetic model were obtained. Liposomes considerably enhanced the uptake of HU into BT-474 human breast cancer cells. The cytotoxicity of NL-HU on BT-474 cells was found to be significantly more than that of free HU.

    Conclusion

    The results confirmed these PEGylated nanoliposomes containing drug are potentially suitable against in vitro model of breast cancer.

    Keywords: Breast neoplasms, Drug carriers, Hydroxyurea, Liposomes
  • Nada Farouk Atta*, Ahmed Galal, Ekram Hamdy El, Ads, Aya Essam Galal Pages 46-55
    Purpose

    Herein we introduce a simple and sensitive sensor for the electrochemical determination of neurotransmitters compounds and anti-Parkinson drugs.

    Methods

    The electrochemical sensor (Au/CILCE) based on gold nanoclusters modified carbon ionic liquid crystal (ILC) electrode was characterized using scanning electron microscopy and voltammetry measurements.

    Results

    The effect of ionic liquid type in the carbon paste composite for the electro-catalytic oxidation of L-dopa was evaluated. Highest current response was obtained in case of ILC compared to other studied kinds of ionic liquids. The effective combination of gold nanoclusters and ILC resulted in extra advantages including large surface area and high ionic conductivity of the nanocomposite. L-dopa is considered one of the most important prescribed medicines for treating Parkinson’s disease. Moreover, a binary therapy using L-dopa and carbidopa proved effective and promising as it avoids the short comings of L-dopa mono-therapy for Parkinson’s patients. The Au/CILCE can detect L-dopa in human serum in the linear concentration range of 0.1 μM to 90 μM with detection and quantification limits of 4.5 nM and 15.0 nM, respectively. Also, the Au/CILCE sensor can simultaneously and sensitively detect L-dopa in the presence of carbidopa with low detection limits.

    Conclusion

    The sensor is advantageous to be applicable for electrochemical sensing of other biologically electroactive species.

    Keywords: Neurotransmitters, Anti-Parkinson drugs, Gold nanoclusters, Carbon ionic liquid crystal electrode, L-dopa, Carbidopa
  • Mahmood Alizadeh Sani, Hamed Hamishehkar, Arezou Khezerlou, Mohammad Maleki, Maryam AziziLalabadi, Vahid Bagheri, Payam Safaei, Taher Azimi, Mohammad Hashemi, Ali Ehsani* Pages 56-64
    Purpose

    The increase of bacterial resistance to common antibacterial agents is one of the major problems of health care systems and hospital infection control programs. In this study, antimicrobial activity of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) was investigated against E. coli, Salmonella enteritidis, Listeria monocytogenes, and Staphylococcus aureus pathogenic bacteria by determining sensitivity coefficient and kinetics of bacterial death.

    Methods

    Antimicrobial tests were performed with ~106 CFU/mL of each bacterium at baseline. At first, minimum inhibitory concentration (MIC) was concluded by the dilution method and then, death kinetic and susceptibility coefficient of NPs suspensions was determined at 0 to 360 min. treatment time.

    Results

    The results of this study revealed that, the highest susceptibility was observed for L. monocytogenes (Z=0.025 mL/μg) to TiO2 NPs, whereas the lowest susceptibility was obtained in the reaction of ZnO NPs with S. enteritidis (Z = 0.0033 mL/μg). The process of bacterial death in NPs suspension was assumed to follow first-degree kinetic and the survival ratio of bacteria decreased by the increase in treatment time. An increase in the concentration of NPs was seen to enhance the bactericidal action.

    Conclusion

    Results showed that L. monocytogenes had higher sensitivity compared to S. enteritidis. The results of this study also demonstrated that TiO2 NPs have a strong antimicrobial effect in comparison with ZnO NPs and it could be employed to aid the control of pathogenic bacteria.

    Keywords: Pathogenic bacteria, ZnO, TiO2, Kinetics, Susceptibility coefficient
  • Khalil Hajiasgharzadeh, Mohammad Hossein Somi, Behzad Mansoori, Mohammad Amin Doustvandi, Fatemeh Vahidian, Mohsen Alizadeh, Ahad Mokhtarzadeh, Dariush Shanehbandi, Behzad Baradaran* Pages 65-71
    Purpose

    The cytotoxic properties upon treatment with nicotine have been reported in several studies, but the underlying mechanisms remain not fully defined. The alpha7 nicotinic acetylcholine receptor (α7nAChR) is one of the important nicotinic receptors, which nicotine partly by binding to this receptor exerts its effects. The current study aimed to investigates the influences of nicotine on cellular proliferative and apoptotic activities and tried to determine the involvement of α7nAChR in these functions.

    Methods

    Human hepatocellular carcinoma (HepG2) cell line was used to determine the individual or combined effects of treatments with nicotine (10 μM) and specific siRNA (100 nM) targeting α7nAChR expression. The MTT assay, DAPI staining assay, and flow cytometry assay were applied to measure the cell viability, apoptosis and cell cycle progression of the cells, respectively. In addition, the changes in the mRNA level of the genes were assessed by qRT-PCR.

    Results

    Compared to control groups, the cells treated with nicotine exhibited significant dosedependent decreases in cell viability (log IC50 = -5.12 ± 0.15). Furthermore, nicotine induced apoptosis and cell cycle arrest especially at G2/M Phase. The qRT-PCR revealed that nicotine increased the mRNA levels of α7nAChR as well as caspase-3 and suppressed the expression of cyclin B1. Treatment with α7-siRNA abolished these effects of nicotine.

    Conclusion

    These experiments determined that upregulation of α7nAChR by nicotine inhibits HepG2 cells proliferation and induces their apoptosis. These effects blocked by treatment with α7-siRNA, which indicates the involvement of α7nAChR pathways in these processes.

    Keywords: Alpha7 nicotinic acetylcholine receptor, Small interfering RNA, Nicotine, HepG2, Apoptosis
  • Tayebeh Mahmoudi, Kamal Abdolmohammadi*, Hamed Bashiri, Mehdi Mohammadi, Mohammad Jafar Rezaie, Fardin Fathi, Shohreh Fakhari, Mohammad Ali Rezaee, Ali Jalili, Mohammad Reza Rahmani, Lobat Tayebi Pages 72-80
    Purpose

    Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder with few available treatments. Mesenchymal stem cell therapy (MSCT), an innovative approach, has high therapeutic potential when used to treat IPF. According to recent data, preconditioning of MSCs can improve their therapeutic effects. Our research focuses on investigating the anti-inflammatory and antifibrotic effects of H2O2-preconditioned MSCs (p-MSCs) on mice with bleomycin-induced pulmonary fibrosis (PF).

    Methods

    Eight-week-old male C57BL/6 mice were induced with PF by intratracheal (IT) instillation of bleomycin (4 U/kg). Human umbilical cord vein-derived MSCs (hUCV-MSCs) were isolated and exposed to a sub-lethal concentration (15 μM for 24 h) of H2O2 in vitro. One week following the injection of bleomycin, 2×105 MSCs or p-MSCs were injected (IT) into the experimental PF. The survival rate and weight of mice were recorded, and 14 days after MSCs injection, all mice were sacrificed. Lung tissue was removed from these mice to examine the myeloperoxidase (MPO) activity, histopathological changes (hematoxylin-eosin and Masson’s trichrome) and expression of transforming growth factor beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) through immunohistochemistry (IHC) staining.

    Results

    Compared to the PF+MSC group, p-MSCs transplantation results in significantly decreased connective tissue (P < 0.05) and collagen deposition. Additionally, it is determined that lung tissue in the PF+pMSC group has increased alveolar space (P < 0.05) and diminished expression of TGF-β1 and α-SMA.

    Conclusion

    The results demonstrate that MSCT using p-MSCs decreases inflammatory and fibrotic factors in bleomycin-induced PF, while also able to increase the therapeutic potency of MSCT in IPF.

    Keywords: Pulmonary fibrosis (PF), Bleomycin (BLM), Mesenchymal stem cells (MSCs), Myeloperoxidase (MPO), Hydrogen peroxide (H2O2)
  • Kobra Shojaei Moghadam, Majid Farshdousti Hagh, Mohammad Reza Alivand, Masoumeh Fardi, Ali Akbar Movassaghpour, Ali Mohammadi, Maryam Moghadasi, Saeed Solali* Pages 81-87
    Purpose

    Sepantronium bromide (YM155) is a Survivin inhibitor which recently advanced as an anticancer agent in phase II clinical trials. Survivin belongs to IAP (inhibitor of apoptosis) gene family and is a pivotal target for treatment due to its overexpression and oncogenic function in many malignancies, including acute lymphoblastic leukemia (ALL). Although survivin is a specific target for YM155, recent reports have shown that it has many other crucial targets that regulate its anti-apoptotic effects. The aim of this study was to investigate whether YM155 could have an effect on cell death-inducing genes as well as inducing apoptosis in T-ALL MOLT4- cell line.

    Methods

    We treated MOLT-4 cells with increasing concentrations of YM155 and then cell viability was determined using MTT (methyl thiazolyl tetrazolium) assay. Also, the rate of induction of apoptosis in MOLT-4 cells and the target genes expression levels were evaluated by Annexin V/PI and real-time PCR, respectively.

    Results

    YM155 inhibited cell growth in MOLT-4 cells. This outcome is achieved by inducing apoptosis and a significant increase in the expression level of P53, MiR-9, caspase 3 and decreasing the mRNA expression levels of survivin, Sirtuin1(SIRT1), member of anti-apoptotic proteins family (Bcl-2), and epithelial-to-mesenchymal transition (EMT) initiating factors Snail1and Zeb2.

    Conclusion

    The results showed that use of YM155 can be a potential drug therapy in T-ALL patients with promising effects on apoptosis induction.

    Keywords: Apoptosis, Cancer, Drug, Survivin, MOLT-4, YM155
  • Ghazal Keshavarz, Cyrus Jalili, Mona Pazhouhi, Mozafar Khazaei* Pages 88-96
    Purpose

    Adipose stem cells (ASCs) are pluripotent cells with the ability of self-renewal and differentiation into different types of mesenchymal cells. As cartilage repair is difficult due to lack of blood capillary, resveratrol (Res) is a polyphenolic compound with diverse biological properties to be possibly used in this case. The aim of the present study was to investigate the effect of Res on differentiation of ASCs into chondrocyte in a three-dimensional (3D) culture model.

    Methods

    Subcutaneous adipose tissues were prepared and digested enzymatically, and passed through cell strainer. ASCs were harvested in the fourth passage, and divided into five groups. The control group received chondrogenic differentiation medium (CDM) while the experimental groups received CDM plus different doses of Res (1, 10, 20, and 50 µM) for 21 days. Expression of cartilage specific genes and Sirtuin1 (SIRT 1), cell viability, apoptosis and ferric reducing antioxidant power (FRAP) were detected using reverse transcription polymerase chain reaction (RT-PCR), MTT assay, TUNEL and acridine orange/ethidium bromide (AO/EB) staining. One-way ANOVA and non-parametric Mann-Whitney U test were used for data analyses.

    Results

    ASCs were differentiated to chondrocyte by CDM in a three-dimensional culture. 10 and 20 µM doses of Res showed the most proliferating effect on ADSCs. The SIRT 1 genes expression and FRAP level also increased significantly compared to the control group (P < 0.05). Also, OD of cell increased whereas apoptosis decreased.

    Conclusion

    3D culture was a suitable condition for ASCs differentiation to chondrocyte, and lower doses of Res exert proliferation effect on ASCs.

    Keywords: Adipose stem cells, Chondrocyte, Resveratrol, Three-dimensional culture
  • Faegheh Golabi, Mousa Shamsi*, Mohammad Hosein Sedaaghi, Abolfazl Barzegar, Mohammad Saeid Hejazi Pages 97-105
    Purpose

    Riboswitches are special non-coding sequences usually located in mRNAs’ un-translated regions and regulate gene expression and consequently cellular function. Furthermore, their interaction with antibiotics has been recently implicated. This raises more interest in development of bioinformatics tools for riboswitch studies. Herein, we describe the development and employment of novel block location-based feature extraction (BLBFE) method for classification of riboswitches.

    Methods

    We have already developed and reported a sequential block finding (SBF) algorithm which, without operating alignment methods, identifies family specific sequential blocks for riboswitch families. Herein, we employed this algorithm for 7 riboswitch families including lysine, cobalamin, glycine, SAM-alpha, SAM-IV, cyclic-di-GMP-I and SAH. Then the study was extended toward implementation of BLBFE method for feature extraction. The outcome features were applied in various classifiers including linear discriminant analysis (LDA), probabilistic neural network (PNN), decision tree and k-nearest neighbors (KNN) classifiers for classification of the riboswitch families. The performance of the classifiers was investigated according to performance measures such as correct classification rate (CCR), accuracy, sensitivity, specificity and f-score.

    Results

    As a result, average CCR for classification of riboswitches was 87.87%. Furthermore, application of BLBFE method in 4 classifiers displayed average accuracies of 93.98% to 96.1%, average sensitivities of 76.76% to 83.61%, average specificities of 96.53% to 97.69% and average f-scores of 74.9% to 81.91%.

    Conclusion

    Our results approved that the proposed method of feature extraction; i.e. BLBFE method; can be successfully used for classification and discrimination of the riboswitch families with high CCR, accuracy, sensitivity, specificity and f-score values.

    Keywords: Riboswitch, Non-coding RNA, Sequential blocks, Block location-based feature extraction, BLBFE, Classification, Performance measures
  • Nahideh Tahmasebpour, Mohammad Ali Hosseinpour Feizi, Nasrin Ziamajidi, Naser Pouladi, Vahid Montazeri, Maryam Farhadian, Roghayeh Abbasalipourkabir* Pages 106-113
    Purpose

    Breast cancer (BC) is globally the main reason of cancer-related deaths in women. Omentin-1, an anti-inflammatory and antioxidant adipokine, plays different roles in tumorigenesis and anti-oncogenic pathways. In present study, we investigated the association of omentin-1 with oxidative stress and clinical significances in healthy controls and BC patients to assess the prognostic and diagnostic value of omentin-1 in this cancer.

    Methods

    This case-control study included 88 BC patients and 86 healthy controls. The serum levels of omentin-1 were assessed by enzyme-linked immunosorbent assays methods. Also, total antioxidant capacity (TAC), total oxidant status (TOS) and malondialdehyde (MDA) serum levels were measured by spectrophotometer. quantitative real-time polymerase chain reaction (qRT-PCR) was applied to the measurement of gene expression of omentin-1.

    Results

    the serum levels of omentin-1 were significantly lower in the BC patients compared to the healthy controls (P < 0.001). Moreover, gene expression of omentin-1was significantly downregulated in the BC tissues compared to the adjacent normal tissues (P < 0.001). Gene expression of omentin-1and its serum levels were significantly higher in grade I compared with grade II and III (P = 0.001, P < 0.001, respectively). Additionally, the serum levels of omentin-1 in the p53-positive BC patients were significantly higher than the p53-negative BC patients (P = 0.001). There was an inverse correlation between the serum levels of MDA and TOS with the serum levels of omentin-1 (r=-0.436, r=-461, respectively).

    Conclusion

    We conclude that omentin-1 may have a good prognostic and diagnostic roles in the BC patients and decreases oxidative stress in these patients.

    Keywords: Breast neoplasms, Omentin-1, Clinical, Antioxidant, Prognosis, Gene expression
  • Bita Shahrami, Farhad Najmeddin, Mohammad Reza Rouini, Atabak Najafi, Kourosh Sadeghi, Shahideh Amini, Seyedeh Sana Khezrnia, Hamid Reza Sharifnia, Mojtaba Mojtahedzadeh* Pages 114-118
    Purpose

    Although the current widespread use of amikacin is in intra-abdominal sepsis treatment, its pharmacokinetic changes in the present setting are not yet well known. This study was aimed to evaluate the amikacin pharmacokinetic profile in critically ill patients with intraabdominal sepsis compared to pneumosepsis.

    Methods

    Adult septic patients received amikacin therapy were studied. Patients with intraabdominal sepsis were enrolled in group 1 (n=16), and patients with pneumosepsis were enrolled in group 2 (n=13). The amikacin serum concentrations were evaluated in the first, second, fourth and sixth hours after initiating 30-minute infusion. The pharmacokinetic parameters were calculated for each patient.

    Results

    There was no significant difference in the volume of distribution between the two groups (0.33±0.08 vs. 0.28±0.10 L/kg, P = 0.193). The amikacin clearance was significantly lower in group 1 compared to group 2 (58.5±21.7 vs. 83.9±37.0 mL/min, P = 0.029). There was no significant correlation between amikacin clearance and creatinine clearance estimated by Cockcroft-Gault formula in all patients (P = 0.206). The half-life was significantly longer in group 1 compared to group 2 (5.3±2.8 vs. 3.4±3.2 hours, P = 0.015).

    Conclusion

    Pathophysiologic changes following intra-abdominal sepsis can affect amikacin pharmacokinetics behavior. The clearance and half-life may change, but the alteration of the volume of distribution is not significantly different in comparison with pneumosepsis. Further studies are required to evaluate the pharmacokinetic variables of amikacin in critically ill patients with intra-abdominal sepsis.

    Keywords: Amikacin, Aminoglycoside, Critical Illness, Intra-abdominal Infection, Pharmacokinetics, Sepsis
  • Gilberto de Sousa, William Gustavo Lima, Flávio José dos Santos, Francisco A. Macías, José María González Molinillo, Rafael Gonçalves Teixeira Neto, João Máximo de Siqueira, Eduardo Sérgio da Silva* Pages 119-124
    Purpose

    Here, we aim to evaluate the antileishmanial activity of compounds with a benzoxazinoid (BX) skeleton, previously synthesized by our group, against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum promastigotes.

    Methods

    Anti-promastigote activity, as well as cytotoxicity, were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays. The selectivity index (SI) for each compound was calculated using a ratio of the cytotoxicity of compounds and the geometric mean (GM) of antileishmanial concentrations to each species tested. The comparisons between groups were carried out using a t test or analysis of variance (one-way ANOVA). A P value of less than 0.05 was considered significant.

    Results

    All the compounds tested were active, with IC50 falling between 92 ± 6.19 µg/mL and 238±6.57 µg/mL for L. braziliensis, and 89 ± 6.43 µg/mL and 188 ± 3.58 µg/mL against L. infantum. Bex2, Bex3, Pyr1, Pyr2, and Pyr4 were compounds that showed activity similar to the drug Glucantime®, exhibited low cytotoxicity against splenic hamster cells (CC50 raging between >400 and 105.7±2.26 µg/mL) and had favorable selectivity indices (SI 1.12 to 3.96).

    Conclusion

    The analogs in question are promising prototypes for the pharmaceutical development of novel, safer and more effective leishmanicidal agents.

    Keywords: Benzoxazinone core, Leishmanicidal agents, Neglected disease, Pharmacology, Pyridoxazinone core, Splenic hamster cells
  • Mitra Rabiei, Gholamreza Zarrini*, Majid Mahdavi Pages 125-129
    Purpose

    The present study was mainly designed to assess anti-cancer effects of lactobacilli isolated from traditional dairy products, on HCT116 colorectal cancer cell lines.

    Methods

    Traditional dairy products samples were collected from the region of Azarbayjan and the suspensions were cultured in MRS agar medium. The isolates were identified by biochemical and molecular methods. Isolated bacteria were cultured in MRS broth. Supernatants of the isolates cultures were collected and their cytotoxicity was evaluated on HCT116 cancer cells. Morphological changes of the treated cells by supernatant were observed using an inverted microscope. Cell metabolic activity was assessed by MTT assay. The morphology of apoptotic cells was examined using a fluorescent microscope. In cell cycle analysis, content measurement of DNA was performed by flow cytometry.

    Results

    Out of 30 lactobacilli were isolated from dairy products samples, six isolates belong to curd samples. Cell-based assays showed that culture supernatant of one isolate (UT1) had a significant anticancer effect on colorectal HCT116 cell lines (P < 0.05). The 16S rRNA sequence analysis revealed that the isolate UT1 was 99% compatible with Lactobacillus casei.

    Conclusion

    It is noteworthy that the supernatant of L. casei UT1 can be candidate for studies on compounds having anti-cancer effect.

    Keywords: Apoptosis, HCT116 cells, Lactobacillus, Probiotic
  • Saeed Noorolyai, Elham Baghbani, Leili Aghebati Maleki, Amir Baghbanzadeh Kojabad, Dariush Shanehbansdi, Vahid Khaze Shahgoli, Ahad Mokhtarzadeh*, Behzad Baradaran Pages 130-134
    Purpose

    Colorectal cancer (CRC) remains a universal and lethal cancer owing to metastatic and relapsing disease. Currently, the role of microRNAs has been checked in tumorigeneses. Numerous studies have revealed that between the tumor suppressor miRNAs, the reduced expression of miR-146a-5p and -193a-5p in several cancers including CRC tissues are related with tumor progression and poor prognosis of patients. The purpose of this study is to examine the role of miR-146 a-5p and -193 a-5p in CRC cell cycle progression.

    Methods

    The miR-193a-5p and -146 a-5p mimics were transfected into HT-29 CRC cells via jetPEI transfection reagent and their impact was assessed on p53, cyclin B, and NF-kB gene expression. The inhibitory effect of these miRNAs on cell cycle was assessed by flow cytometry. The consequence of miR-193a-5p and miR-146 a-5p on the protein expression level of Murine double minute 2 (MDM2) was assessed by western blotting.

    Results

    miR193a-5p and -146a-5p regulated the expression of MDM2 protein and p53, cyclin B, and NF-kB gene expression in CRC cells. Treatment of HT-29 cells with miRNA-146a-5p and -193a-5p induced G1 cell cycle arrest.

    Conclusion

    The findings of our study suggest that miR146a-5p and -193a-5p may act as a potential tumor suppressor by their influence on cell cycle progression in CRC cells. Thus, miRNA-146a-5p and -193a-5p restoration may be recommended as a potential therapeutic goal in the treatment of CRC patients.

    Keywords: Colorectal cancer, miRNA-193a-5p, miRNA-146a-5p, MDM2, p53, Cell cycle, Restoration
  • Mazyar Hashemilar, Mohammad Khalili*, Nasim Rezaeimanesh, Elyar Sadeghi Hokmabadi, Sevin Rasulzade, Seyed Morteza Shamshirgaran, Aliakbar Taheraghdam, Mehdi Farhoudi, Sheyda Shaafi, Seyed Kazem Shakouri, Daryoush Savadi Osgouei Pages 135-140
    Purpose

    Malnutrition is extensively prevalent amongst critically ill patients afflicted by ischemic stroke (IS). This study purpose was to evaluate the protein whey effect on inflammatory and antioxidant markers and functional prognosis in acute IS patients.

    Methods

    out of 42 patients with acute IS who were referred to Imam Reza Educational Hospital, Tabriz, Iran, 40 patients participated in the study. Twenty-one patients as control group received the hospital routine formula, and 19 patients as intervention group received 20 g/daily of whey protein through oral gavage. Inflammation and oxidative stress indicators (e.g., albumin, malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high sensitivity C reactive protein (hs-CRP)and clinical variables included in were evaluated using National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) during admission and also 3 weeks after intervention.

    Results

    Whey protein supplementation significantly decreased the NIHSS and mRS scores, TNF-α, IL-6, and hs-CRP by passing 3 weeks from intervention (P < 0.05). However, whey formula had no significant effect on other markers including albumin, and MDA. The hs-CRP (P = 0.02) reduction was significantly higher in whey protein group in comparison with control group.

    Conclusion

    Whey protein supplementation reduced inflammation markers in those patients with IS. However, these changes should be studied in larger-scale trials.

    Keywords: Inflammation, Stroke, Brain ischemia, Malnutrition, Oxidative stress, Whey protein
  • Shirin Saberianpour, Arezoo Rezaie Nezhad Zamani, Abbas Karimi, Mahdi Ahmadi, Neda Khatami, Ayda Pouyafar, Reza Rahbarghazi*, Mohammad Nouri Pages 141-154
    Purpose

    Today, there is an urgent need to develop a three-dimentional culture systems mimicking native in vivo condition in order to screen potency of drugs and possibly any genetic alterations in tumor cells. Due to the existence of limitations in animal models, the development of three dimensional systems is highly recommended. To this end, we encapsulated human colon adenocarcinoma cell line HT29 with alginate-poly-L-lysine (Alg-PLL) microspheres and the rate of epithelial-mesenchymal transition was monitored.

    Methods

    Cells were randomly divided into three groups; control, alginate and Alg-PLL. To encapsulate cells, we mixed HT-29 cells (1 × 106) with 1 mL of 0.05% PLL and 1% Alg mixture and electrosprayed into CaCl2 solution by using a high-voltage power. Cells from all groups were maintained at 37˚C in a humidified atmosphere containing 5% CO2 for 7 days. Cell viability was assessed by MTT assay. To monitor the stemness feature, we measured the transcription of genes such as Snail, Zeb, and Vimentin by using real-time PCR analysis.

    Results

    Addition of PLL to Alg in a hallowed state increased the cell survival rate compared to the control and Alg groups (P<0.05). Cells inside Alg-PLL tended to form microcellular aggregates while in Alg microspheres an even distribution of HT-29 cells was found. Real-time PCR analysis showed the up-regulation of Snail, Zeb, and Vimentin in Alg-PLL microspheres compared to the other groups, showing the acquisition of stemness feature (P<0.05).

    Conclusion

    This study showed that hallow Alg-PLL microspheres increased the epithelialmesenchymal transition rate after 7 days in in vitro condition. Such approaches could be touted as appropriate in vitro models for drug screening.

    Keywords: Alginate, Epithelial-mesenchymal transition, Human colon adenocarcinoma cell line HT29, Poly-L-lysine, Microspheres
  • Maryam Hosseindokht Khujin, Hamed Zare* Pages 146-149
    Purpose

    Organic selenium compound such as selenomethionine plays a significant function in the response to oxidative stress. Saccharomyces cerevisiae have the ability to accumulate selenium and selenium biotransformation. Selection of indigenous selenium tolerant yeast is our goals. The relationship between cell growth and selenium biotransformation was also investigated.

    Methods

    The screening of the yeast cell was carried out at two steps in order to select yeast with high capacity for resistance and accumulation of selenium. The isolates were selected according to produced high biomass at different concentrations of selenium. Secondly, best yeast strains from previous step were grown in presence of 25 mg/L of sodium selenite and organic selenium content was measured.

    Results

    The S17 isolate showed had maximum organic selenium accumulation (2515 ppm) and biomass production (2.73 g/L) compared to the other isolates. The biomass production and organic selenium accumulation of the S17 during 120 hours was shown a direct relationship between growth and biotransformation.

    Conclusion

    This increase in organic selenium content was achieved with yeast screening. It is interesting to know that organic selenium has high bioavailability and low toxicity compared with inorganic selenium. Therefore, finding yeast strains which are resistant to selenium can be very helpful in cancer prevention.

    Keywords: Yeast, Selenium, Biotransformation, Screening, Saccharomyces cerevisiae