فهرست مطالب

  • Volume:10 Issue: 2, 2020
  • تاریخ انتشار: 1399/02/02
  • تعداد عناوین: 8
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  • Morteza Mahmoudi*, Sherry Moss Pages 63-64

    Currently, victims of discrimination and sexual harassment have institutional reporting systems and legal remedies which support them in finding justice for these crimes. However, victims of academic bullying, who suffer similar repercussions, have no legal or institutional remedies. Because academic bullying is not a crime, targets often suffer in silence because there is no recourse. It is time for institutions to ask for governmental support to create legislation, similar to that for sexual harassment and discrimination, which will bring justice to academic bullies and relief to their victims. In the absence of legislation, institutions should create reporting procedures and educational programs which mirror those they have in place for sexual harassment and discrimination.

    Keywords: Academic bullying, Law, Harassment
  • Hadi Maleki, Kakelar, Jaber Dehghani, Abolfazl Barzegari, Jaleh Barar, Masoud Shirmohamadi, Javid Sadeghi, Yadollah Omidi* Pages 65-72
    Introduction

    Gastric cancer is considered the second prevalent cause of death around the world. This type of cancer is generally induced by Helicobacter pylori which could colonize within the gastric mucosa of the infected cases. To date, triple antibiotic therapy has routinely been utilized for controlling the H. pylori-induced infection. However, this strategy has been unsuccessful, in large part because of issues such as occurring point mutations in the H. pylori genome that can induce resistance to the antibiotics administered. Recently, it has been shown that different probiotics may have strong anti-cancer effects, in which they are capable of inhibiting H. pylori by both immunological and non-immunological mechanisms. Here, we aimed at finding possible anti-cancer impacts of the probiotic bacterium Lactobacillus plantarum on gastric cancer, AGS cells.

    Methods

    The anti-cancer effects of the conditioned media of the locally isolated L. plantarum on the AGS cells were evaluated by different analyses such as flow cytometry, DNA ladder assay, DAPI staining, and RT-PCR.

    Results

    Our findings showed that the conditioned media of L. plantarum can inhibit both H. pylori and AGS cells through up-/down-regulation of PTEN, Bax, TLR4, and AKT genes. The exudates of the probiotic L. plantarum bacteria can increase the expression of PTEN, Bax, and TLR4, and also decrease the expression of AKT gene.

    Conclusion

    In agreement with different reports, our results proved the anti-cancer effects of the locally isolated L. plantarum through some immunological cell signaling pathways. Accordingly, it seems the probiotics could be considered as at least a complementary treatment for different types of malignancies.

    Keywords: Gastric cancer, Helicobacter pylori, Lactobacillus, plantarum, Apoptosis, PTEN, AKT
  • Maryam Sadat Khoramgah, Javad Ranjbari, Hojjat, Allah Abbaszadeh, Fatemeh Sadat Tabatabaei Mirakabad, ShadieHatami, Simzar Hosseinzadeh*, Hossein Ghanbarian Pages 73-85
    Introduction

    Simulating hydrophobic-hydrophilic composite face with hierarchical porous and fibrous architectures of bone extracellular matrix (ECM) is a key aspect in bone tissue engineering. This study focused on the fabrication of new three-dimensional (3D) scaffolds containing polytetrafluoroethylene (PTFE), and polyvinyl alcohol (PVA), with and without graphene oxide (GO) nanoparticles using the chemical cross-linking and freeze-drying methods for bone tissue application. The effects of GO on physicochemical features and osteoinduction properties of the scaffolds were evaluated through an in vitro study.

    Methods

    After synthesizing the GO nanoparticles, two types of 3D scaffolds, PTFE/PVA (PP) and PTFE/PVA/GO (PPG), were developed by cross-linking and freeze-drying methods. The physicochemical features of scaffolds were assessed and the interaction of the 3D scaffold types with human adipose mesenchymal stem cells (hADSCs) including attachment, proliferation, and differentiation to osteogenic like cells were investigated.

    Results

    GO nanoparticles were successfully synthesized with no agglomeration. The blending of PTFE as a hydrophobic polymer with PVA polymer and GO nanoparticles (hydrophilic compartments) were successful. Two types of 3D scaffolds had nano topographical structures, good porosities, hydrophilic surfaces, thermal stabilities, good stiffness, as well as supporting the cell attachments, proliferation, and osteogenic differentiation. Notably, GO incorporating scaffolds provided a better milieu for cell behaviors.

    Conclusion

    Novel multiscale porous nanofibrous 3D scaffolds made from PTFE/ PVA polymers with and without GO nanoparticles could be an ideal candidate for bone tissue engineering as a 3D template.

    Keywords: Freeze drying, Nanofiber, Nanopore, 3D scaffold, Polytetrafluoroethylene, Bone tissue engineering
  • Ashkan Hassankhani Rad, Farshid Asiaee, Sevda Jafari, Ali Shayanfar, Afsaneh Lavasanifar, OmmoleilaMolavi* Pages 87-95
    Introduction

    Silibinin is a naturally occurring compound with known positive impacts on prevention and treatment of many types of human illnesses in general and cancer in particular. Silibinin is poorly water soluble which results in its insufficient bioavailability and lack of therapeutic efficacy in cancer. Here, we proposed to examine the potential of micelles composed of poly(ethylene glycol) (PEG) as the hydrophilic block and poly(ε-caprolactone) (PCL), poly(α-benzylcarboxylate-ε-caprolactone) (PBCL), or poly(lactide)-(PBCL) (PLA-PBCL) as hydrophobic blocks for enhancing the water solubility of silibinin and its targeted delivery to tumor.

    Methods

    Co-solvent evaporation method was used to incorporate silibinin into PEG-PCL based micelles. Drug release profiles were assessed using dialysis bag method. MTT assay also was used to analyze functional activity of drug delivery in B16 melanoma cells.

    Results

    Silibinin encapsulated micelles were shown to be less than 60 nm in size. Among different structures under study, the one with PEG-PBCL could incorporate silibinin with the highest encapsulation efficiency being 95.5%, on average. PEG-PBCL micelles could solubilize 1 mg silibinin in 1 mL water while the soluble amount of silibinin was found to be 0.092 mg/mL in the absence of polymeric micelles. PEG-PBCL micelles provided the sustained release of silibinin indicated with less than 30% release of silibinin within 24 hours. Silibinin encapsulated in PEG-PBCL micelles resulted in growth inhibitory effect in B16 cancer cells which was significantly higher than what observed with free drug.

    Conclusion

    Our findings showed that PEG-PBCL micellar nanocarriers can be a useful vehicle for solubilization and targeted delivery of silibinin.

    Keywords: Silibinin, Micelle, Copolymer, PEG-PCL, Melanoma
  • Reza Ferdousi, Ali Akbar Jamali, Reza Safdari* Pages 97-104
    Introduction

    Drug-drug interactions (DDIs) are the main causes of the adverse drug reactions and the nature of the functional and molecular complexity of drugs behavior in the human body make DDIs hard to prevent and threat. With the aid of new technologies derived from mathematical and computational science, the DDI problems can be addressed with a minimum cost and effort. The Market Basket Analysis (MBA) is known as a powerful method for the identification of co-occurrence of matters for the discovery of patterns and the frequency of the elements involved.

    Methods

    In this research, we used the MBA method to identify important bio-elements in the occurrence of DDIs. For this, we collected all known DDIs from DrugBank. Then, the obtained data were analyzed by MBA method. All drug-enzyme, drug-carrier, drug-transporter and drug-target associations were investigated. The extracted rules were evaluated in terms of the confidence and support to determine the importance of the extracted bio-elements.

    Results

    The analyses of over 45 000 known DDIs revealed over 300 important rules from 22 085 drug interactions that can be used in the identification of DDIs. Further, the cytochrome P450 (CYP) enzyme family was the most frequent shared bio-element. The extracted rules from MBA were applied over 2 000 000 unknown drug pairs (obtained from FDA approved drugs list), which resulted in the identification of over 200 000 potential DDIs.

    Conclusion

    The discovery of the underlying mechanisms behind the DDI phenomena can help predict and prevent the inadvertent occurrence of DDIs. Ranking of the extracted rules based on their association can be a supportive tool to predict the outcome of unknown DDIs.

    Keywords: Drug-drug interaction, Market Basket Analysis, Rule discovery, Biological targets
  • Mohammad A. Rafi, Paola Luzi, David A. Wenger** Pages 105-115
    Introduction

    Krabbe disease (KD) is an autosomal recessive lysosomal disorder caused by mutations in the galactocerebrosidase (GALC) gene. This results in defective myelination in the peripheral and central nervous systems due to low GALC activity. Treatment at this time is limited to hematopoietic stem cell transplantation (HSCT) in pre-symptomatic individuals. While this treatment extends the lives of treated individuals, most have difficulty walking by the end of the first decade due to peripheral neuropathy. Studies in the murine model of KD, twitcher (twi) combining bone marrow transplantation (BMT) with AAVrh10-mGALC showed a great extension of life from 40 days to about 400 days, with some living a full life time.

    Methods

    In order to find the optimum conditions for dosing and timing of this combined treatment, twi mice were injected with five doses of AAVrh10-mGALC at different times after BMT. Survival, as well as GALC expression were monitored along with studies of sciatic nerve myelination and possible liver pathology.

    Results

    Dosing had a pronounced effect on survival and measured GALC activity. There was window of time after BMT to inject the viral vector and see similar results, however delaying both the BMT and the viral injection shortened the lifespans of the treated mice. Lowering the viral dose too much decreased the correction of the sciatic nerve myelination. There was no evidence for hepatic neoplasia.

    Conclusion

    These studies provide the conditions optimum for successfully treating the murine model of KD. There is some flexibility in dosing and timing to obtain a satisfactory outcome. These studies are critical to the planning of a human trial combining the "standard of care", HSCT, with a single iv injection of AAVrh10-GALC.

    Keywords: Krabbe disease, AAVrh10 gene therapy, Twitcher mice, Bone marrow transplantation, Combined therapy, Myelination
  • Fatemeh Rahimi, Sherbaf, Samad Nadri, Ali Rahmani, Atousa Dabiri Oskoei* Pages 117-122
    Introduction

    Transplantation of stem cells with a nanofibrous scaffold is a promising approach for spinal cord injury therapy. The aim of this work was to differentiate neural-like cells from placenta-derived mesenchymal stem cells (PDMSCs) using suitable induction reagents in three (3D) and two dimensional (2D) culture systems.

    Methods

    After isolation and characterization of PDMSCs, the cells were cultivated on poly-L-lactide acid (PLLA)/poly caprolactone (PCL) nanofibrous scaffold and treated with a neuronal medium for 7 days. Electron microscopy, qPCR, and immunostaining were used to examine the differentiation of PDMSCs (on scaffold and tissue culture polystyrene [TCPS]) and the expression rate of neuronal markers (beta-tubulin, nestin, GFAP, and MAP-2).

    Results

    qPCR analysis showed that beta-tubulin (1.672 fold; P ≤ 0.0001), nestin (11.145 fold; P ≤ 0.0001), and GFAP (80.171; P ≤ 0.0001) gene expressions were higher on scaffolds compared with TCPS. Immunofluorescence analysis showed that nestin and beta-tubulin proteins were recognized in the PDMSCs differentiated on TCPS and scaffold after 7 days in the neuroinductive differentiation medium.

    Conclusion

    Taken together, these results delegated that PDMSCs differentiated on PLLA/PCL scaffolds are more likely to differentiate towards diversity lineages of neural cells. It proposed that PDMSCs have cell subpopulations that have the capability to be differentiated into neurogenic cells.

    Keywords: Placenta-derived stem cells, Differentiation, Neural-like cells, Fibrous scaffold
  • Bhavya Somalapura Gangadharappa, Sharath Rajashekarappa*, Gajanan Sathe Pages 123-135
    Introduction

    Serratia marcescens, an opportunistic human pathogen, is reported as an important cause of nosocomial infection and outbreaks. Although the genome of S. marcescens (ATCC 13880) was completely sequenced by 2014, there are no studies on the proteomic profile of the organism. The objective of the present study is to analyze the protein profile of S. marcescens (ATCC 13880) using a high resolution mass spectrometry (MS).

    Methods

    Serratia marcescens ATCC 13880 strain was grown in Luria-Bertani broth and the protein extracted was subjected to trypsin digestion, followed by basic reverse phase liquid chromatography fractionation. The peptide fractions were then analysed using Orbitrap Fusion Mass Spectrometry and the raw MS data were processed in Proteome Discoverer software.

    Results

    The proteomic analysis identified 15 009 unique peptides mapping to 2541 unique protein groups, which corresponds to approximately 54% of the computationally predicted protein-coding genes. Bioinformatic analysis of these identified proteins showed their involvement in biological processes such as cell wall organization, chaperone-mediated protein folding and ATP binding. Pathway analysis revealed that some of these proteins are associated with bacterial chemotaxis and beta-lactam resistance pathway.

    Conclusion

    To the best of our knowledge, this is the first high-throughput proteomics study of S. marcescens (ATCC 13880). These novel observations provide a crucial baseline molecular profile of the S. marcescens proteome which will prove to be helpful for the future research in understanding the host-pathogen interactions during infection, elucidating the mechanism of multidrug resistance, and developing novel diagnostic markers or vaccine for the disease.

    Keywords: Proteomics, Serratia marcescens, Proteome discoverer, Orbitrap fusion