37 research outputs found
Fuzzy Expert Ants to speed up big TSP Problems using ACS
Ant colony algorithms are a group of heuristic optimization algorithms that have been inspired by behavior of real ants foraging for food. In these algorithms some simple agents (i.e. ants), search the solution space for finding the suitable solution. Ant colony algorithms have many applications to computer science problems especially in optimization, such as machine drill optimization, and routing. This group of algorithms have some sensitive parameters controlling the behavior of agents, like relative pheromone importance on trail and pheromone decay coefficient. Convergence and efficiency of algorithms is highly related to these parameters. Optimal value of these parameters for a specific problem is determined through trial and error and does not obey any rule. Some approaches proposed to adapt parameter of these algorithms for better answer. The most important feature of the current adaptation algorithms are complication and time overhead. In this paper we have presented a simple and efficient approach based on fuzzy logic for optimizing ACS algorithm and by using different experiments efficiency of this proposed approach has been evaluated and we have shown that the presented concept is one of the most important reasons in success for parameter adapting algorithms
Combined 3D-QSAR modeling and molecular docking study on multi-acting quinazoline derivatives as HER2 kinase inhibitors
A series of new quinazoline derivatives has been recently reported as potent multi-acting histone deacetylase (HDAC), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2) inhibitors. HER2 is one of the major targets for the treatment of breast cancer and other carcinomas. Three-dimensional structure-activity relationship (3DQSAR) is a well-known technique, which is used to drug design and development. This technique
is used for quantitatively predicting the interaction between a molecule and the active
site of a specific target. For each 3D-QSAR study, a three-dimensional model is created from a large curve fit to find a fitting between computational descriptors and biological activity. This model could be used as a predictive tool in drug design. The best model has the highest correlation between theoretical and experimental data. Self-Organizing Molecular Field Analysis
(SOMFA), a grid-based and alignment-dependent 3D-QSAR method, is employed to
study the correlation between the molecular properties and HER2 inhibitory potency of the
quinazoline derivatives. Before presentation of inhibitor structures to SOMFA study, conformation of inhibitors was determined by AutoDock4, HyperChem and AutoDock Vina, separately. Overall, six independent models were produced and evaluated by the statistical partial least square (PLS) analysis. Among the several generated 3D-QSARs, the best model was selected on the basis of its statistical significance and predictive potential. The model derived
from the superposition of docked conformation with AutoDock Vina with reasonable crossvalidated q2 (0.767), non cross-validated r2 (0.815) and F-test (97.22) values showed a desirable
predictive capability. Analysis of SOMFA model could provide some useful information
in the design of novel HER2 kinase inhibitors with better spectrum of activity
The effect of adding Rosmarinic and Ascorbic acids to vitrification media on fertilization rate of the mice oocyte: An experimental study
Background: Oocytes vitrification is a pivotal step for the widespread and safekeeping of animal genetic resources. Oocytes endure notable morphological and functional damage during cryopreservation. Oxidative stress is one of the adverse effects that vitrification imparts on oocytes.Objective: In the present study, we investigated the antioxidant effect of Rosmarinic and Ascorbic acids on the quality and fertilizing ability of frozen-thawed mice oocyte.Materials and Methods: In this experimental study, germinal vesicle oocytes obtained from two-months-old (30–40gr) NMRI mice were randomly divided into four groups. The basic cryoprotectants were 7.5% (v/v) ethylene glycol+7.5% (v/v) Propanediol as an equilibration media. Vitrification medium contained 15% (v/v) ethylene glycol+15% (v/v) propanediol, and 0.5 M sucrose. In the first group (Control), nothing was addedto vitrification mediums, whereas, in the second and third groups, 0.5 mmol/L of Ascorbic acid and 105 µmol/L of Rosmarinic acid were added into vitrification medium, respectively. The cumulative concentration of Rosmarinic and Ascorbic acids were added to group 4. Mouse oocytes were vitrified and preserved for one month. The thawed oocytes were transferred into the α-MEM medium (Alpha Minimum Essential Medium) and maintained in this medium for 24 hr, to be matured and reach the metaphase II stage.Results: The addition of Rosmarinic and Ascorbic acids to the vitrification solution improved the survival, maturation of Germinal vesicles, fertilization rate, and finally development to 4-cell stage. Maturation rates to 4-cell stage for Ascorbic acid, Rosmarinic acid, and both of them together were 80%, 80.76%, and 86.61%, respectively.Conclusion: These results indicate that the addition of a cumulative concentration of 0.5 mmol/L Ascorbic acid and 105 µmol/L of Rosmarinic acid to the cryopreservation solution for the mouse immature oocytes would be of significant value (p< 0.01)
The effects of supplemented sericin on in vitro maturation and preimplantation development of mouse embryos: An experimental study
Background: Mouse embryo culture condition is an essential part of transgenic, reproductive and developmental biology laboratories. Mouse embryonic culture media may have a high risk of serum contamination with pathogens.
Objective: To investigate the effect of sericin as an embryo culture medium supplement on in vitro maturation (IVM), in vitro fertilization (IVF), and development of the preimplantation embryo in mice.
Materials and Methods: The effects of sericin at three concentrations (subgroups) of 0.1%, 0.5%, and 1% as a medium supplement on IVM, IVF, and in vitro development of mouse embryos were separately investigated and compared with a sericin-free (control) group. The cumulative effect of the three concentrations was evaluated for IVM + in vitro development and IVF + in vitro development as follow-up groups.
Results: In the IVM group, compared to the control group, the number of oocysts reaching the MII stage was significantly higher when 1% sericin was used (161/208 = 77.4%). No significant results were observed in the IVF and in vitro development groups with different concentrations of sericin compared to the control group. Among the follow-up groups, in the IVM + in vitro development group, the number of oocytes was higher after passing the IVM and IVF and reaching the blastocysts stage when 1% sericin was used, compared with other sericin subgroups. A significant difference was also noted when compared with the control group (p = 0.048). The IVF + in vitro development study group, on the other hand, did not show any significant relationship.
Conclusion: It can be concluded that 1% sericin can be used as a supplement in mouse embryo cultures to improve the IVM rate. Also, based on the findings, sericin appears to be an effective supplement which can have a positive effect on the development of embryos derived from IVM.
Key words: Sericin, In vitro maturation, In vitro fertilization, Preimplantation embryo, Culture medium, Mice
Production of hepatocyte-like cells from human umbilical vein mesenchymal stem cells
The human umbilical vein, as a readily available stem cell source, is a good alternative to harvest mesenchymal stem cells. Human umbilical cord vein mesenchymal stem cells have recently been isolated and have demonstrated the ability to differentiate into various cell types such as fat, bone, cartilage and neuronal cells. In this study, we have investigated whether human umbilical cord vein mesenchymal stem cells are also able to differentiate into hepatocyte-like cells. Hepatic differentiation was performed with a 2-step protocol and the use of hepatocyte growth factor and oncostatin M for cell culture. During four weeks of induction, most cells displayed a cuboidal morphology. Immunological analysis indicated that umbilical cord vein mesenchymal stem cells-derived hepatocyte-like cells expressed liver-specific protein markers such as albumin and cytokeratin-18. The hepatocyte-like cells also displayed several characteristics of hepatocytes, including expression of transthyretin, glucose 6-phosphatase, cytokeratin-8,18, alpha-fetoprotein, hepatocyte nuclear factor-3β and albumin. The result of indocyanine green cell uptake, as a test substance to evaluate hepatocyte-like cell function, was positive for differentiated cells. Glycogen storage was examined by periodic acid-Schiff staining. Accumulation of intracellular glycogen was detected in the hepatocyte-like cells. Based on these observations, we have concluded that umbilical cord vein mesenchymal stem cells are endowed with hepatogenic potential and may provide a stem cell source to be used as cell therapy for liver diseases
Biological Effects of Magnetic Resonance Imaging on Testis Histology and Seminiferous Tubules Morphometry.
OBJECTIVES:
Spermatogenesis is a regular and lengthy process in which the function of testicular cells may potentially be influenced by several extrinsic and intrinsic stressors, including environmental factors such as magnetic resonance imaging (MRI) waves and radiation. Our study aimed to investigate the effects of MRI waves and fields on the testicular histology and morphometry of seminiferous tubules in mice.
METHODS:
The experiment was conducted on 40 adult Naval Medical Research Institute mice. The control group was located in the center of the MRI bore while it was turned off, while the exposed group was exposed to the active scanner for 36 minutes once a week for three weeks. Our study included four groups: group I (control group at one hour after last exposure), group II (experimental group at one hour after last exposure), group III (control group at 35 days after last virtual exposure), and group IV (experimental group at 35 days after last exposure). We then assessed the tube and lumen diameters, as well as epithelium thickness of the seminiferous tubules.
RESULTS:
Our data showed that MRI waves partially reduced testicular weight one hour after the last exposure (group II) compared to group I (p = 0.240). On the other hand, in group II the Johnson's score (score 10, complete spermatogenesis and perfect tubules) was 87.5% which was slightly less than recorded in groups I, III, and IV (91.4%, 92.2%, and 90.5%, respectively). Furthermore, the MRI in group II revealed induces vacuolization in the epithelium, arrest in primary spermatocytes in the pachytene stage as well as disruption in the testicular parenchyma.
CONCLUSIONS:
Long-term exposure to MRI waves has deleterious effects on the male reproductive system, fertility parameters, and the quantity of germ cells in the seminiferous tubules with the exception of the number of round spermatid cells and epithelial thickness. All these effects were reversible after a new period of spermatogenesis.
The OMJ is Published Bimonthly and Copyrighted 2019 by the OMSB.
KEYWORDS:
Fertility; Magnetic Resonance Imaging; Mice; Seminiferous Tubules; Spermatogenesis; Testi
Isolation of cancer stem cells by selection for miR-302 expressing cells
Background Cancer stem cells are believed to be a major reason for long-term therapy failure because they are multi-drug resistant and able to rest mitotically inactive in the hypoxic center of tumors. Due to their variable number and their often low proliferation rate, cancer stem cells are difficult to purify in decent quantities and to grow in cell culture systems, where they are easily outcompeted by faster growing more ‘differentiated’, i.e., less stem cell-like tumor cells. Methods Here we present a proof of principle study based on the idea to select cancer stem cells by means of the expression of a stem cell-specific gene. A selectable egfp-neo coding sequence was inserted in the last exon of the non-coding murine miR-302 host gene. As a stem cell specific regulatory element, 2.1 kb of the genomic region immediately upstream of the miR-302 host gene transcription start site was used. Stable transgenic CJ7 embryonic stem cells were used to induce teratomas. Results After three weeks, tumors were removed for analysis and primary cultures were established. Stem cell-like cells were selected from these culture based on G418 selection. When the selection was removed, stem cell morphology and miR-302 expression were rapidly lost, indicating that it was not the original ES cells that had been isolated. Conclusions We show the possibility to use drug resistance expressed from a regulatory sequence of a stem cell-specific marker, to isolate and propagate cancer stem cells that otherwise might be hidden in the majority of tumor cells
Hydrogen Peroxide Preconditioning Promotes Protective Effects of Umbilical Cord Vein Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis
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 pM for 24 h) of H2O2 in vitro. One week following the injection of bleomycin, 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\u27s 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 () and collagen deposition. Additionally, it is determined that lung tissue in the PF+pMSC group has increased alveolar space () 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
CTLA-4 Blockade of Natural Killer Cells Increases Cytotoxicity against Acute Lymphoid Leukaemia Cells Neda
Objective: There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers.Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and naturalkiller (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 toblock the Nalm-6 leukaemia cell line.Materials and Methods: In this experimental study, NK cells were purified from the peripheral blood mononuclear cells(PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activatedovernight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4,activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells wasassessed after the CTLA-4 blockade.Results: The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantlyhigher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patientswith ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression(P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released moreIFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cellkilling potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically differentbetween the blocked and non-blocked groups.Conclusion: Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity ofNK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatmentusing blocking anti-CTLA-4 mAbs
Metformin therapy attenuates pro-inflammatory Microglia by inhibiting NF-κB in cuprizone demyelinating mouse model of multiple Sclerosis
Multiple sclerosis (MS) is a chronic disorder characterized by reactive gliosis, inflammation, and demyelination. Microglia plays a crucial role in the pathogenesis of MS and has the dynamic plasticity to polarize between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Metformin, a glucose-lowering drug, attenuates inflammatory responses by activating adenosine monophosphate protein kinase (AMPK) which suppresses nuclear factor kappa B (NF-κB). In this study, we indirectly investigated whether metformin therapy would regulate microglia activity in the cuprizone (CPZ)-induced demyelination mouse model of MS via measuring the markers associated with pro- and anti-inflammatory microglia. Evaluation of myelin by luxol fast blue staining revealed that metformin treatment (CPZ + Met) diminished demyelination, in comparison to CPZ mice. In addition, metformin therapy significantly alleviated reactive microgliosis and astrogliosis in the corpus callosum, as measured by Iba-1 and GFAP staining. Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-α) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice. Furthermore, protein levels of iNOS (pro-inflammatory marker) were significantly decreased in the metformin group, while those of Trem2 (anti-inflammatory marker) were increased. In addition, metformin significantly increased AMPK activation in CPZ mice. Finally, metformin administration significantly reduced the activation level of NF-κB in CPZ mice. In summary, our data revealed that metformin attenuated pro-inflammatory microglia markers through suppressing NF-κB activity. The positive effects of metformin on microglia and remyelination suggest that it could be used as a promising candidate to lessen the incidence of inflammatory neurodegenerative diseases such as MS