فهرست مطالب
Biolmpacts
Volume:7 Issue: 1, Mar 2017
- تاریخ انتشار: 1395/12/18
- تعداد عناوین: 8
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Pages 1-3Reactive oxygen species (ROS) are produced under normal physiological conditions and involved in several cellular biochemical processes. Their external or endogenous overproduction induces a disruption of redox signaling and control known as oxidative stress. Under oxidative stress, the cell membrane structures, enzyme functions and gene expression are compromised leading to the pathogenesis of several chronic inflammatory diseases including the cardiovascular pathologies. Attempts to find new therapeutic molecules capable of blocking the oxidative stress are of crucial importance.
Owing to their anti-inflammatory and antioxidant properties, carotenoids have been proposed for the prevention and treatment of chronic diseases. In particular, microalgae carotenoids such as astaxanthin and lutein have shown promising results. Due to their protective action, these carotenoids could have a high potential to treat ROS-related pathologies. However, a better understanding of their biological mechanisms of action and the appropriate administration and uses of delivery systems are needed in the prevention and treatment of chronic pathologies.Keywords: Oxidative stress, Carotenoids, Reactive Oxygen Species, Microalgae -
Pages 5-12IntroductionThe potential of combining liquisolid and co-grinding technologies (liquiground technique) was investigated to improve the dissolution rate of a water-insoluble agent (glibenclamide) with formulation-dependent bioavailability.MethodsTo this end, different formulations of liquisolid tablets with a wide variety of non-volatile solvents contained varied ratios of drug: solvent and dissimilar carriers were prepared, and then their release profiles were evaluated. Furthermore, the effect of size reduction by ball milling on the dissolution behavior of glibenclamide from liquisolid tablets was investigated. Any interaction between the drug and the excipient or crystallinity changes during formulation procedure was also examined using X-ray diffraction (XRD) and differential scanning calorimetry (DSC).ResultsThe present study revealed that classic liquisolid technique did not significantly affect the drug dissolution profile as compared to the conventional tablets. Size reduction obtained by co-grinding of liquid medication was more effective than the implementation of liquisolid technique in enhancing the dissolution rate of glibenclamide. The XRD and DSC data displayed no formation of complex or any crystallinity changes in both formulations.ConclusionAn enhanced dissolution rate of glibenclamide is achievable through the combination of liquisolid and co-grinding technologies.Keywords: Glibenclamide, Liquisolid, Liquiground, Dissolution rate, Co-grinding
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Pages 13-23IntroductionThe addition of herbs into hot sesame oil could increase the oil-pulling efficiency of sesame oil. The aim of present study was to modify the proportion of herbs and sesame oil with the addition of other ingredients including menthol, camphor, and borneol and improve the medicinal properties and the scent of the oil.MethodsMacerated herbal oil was prepared by heat extraction of five species of herbs (Zingiber cassumunar, Zingiber zerumbet, Plantago major Linn, Citrus hystrix, and Amomum biflorum) with hot sesame oil. The study was performed to evaluate the anti-oxidant, anti-inflammatory, and anti-bacterial properties of this macerated herbal oil.ResultsMacerated herbal oil was evaluated for antioxidant activity using DPPH and ABTS assays. It was shown that at dilution 1:2 in DMSO, the macerated herbal oil had DPPH and ABTS radical scavenging activities equal to 63% and 22%, respectively. Macerated herbal oil dilution 1:8 in DMSO demonstrated ferric reducing capacity equivalent to ascorbic acid (0.208 µM) and had reducing power equivalent to butylated hydroxytoluene (BHT) 7.41 µg/mL. MTT assay was performed using immortalized human mesenchymal stem cells (HMSCs) as a cell culture model. The result indicated that the cytotoxic concentration of the macerated herbal oil was ≥ 2.5 µL/mL in complete DMEM. Anti-inflammatory effects were evaluated using the nitrite assay and RT-PCR. It was found that the macerated herbal oil could inhibit nitrite accumulation in culture media. Change in the expression of COX-2, Nrf2, and NF-kB in RT-PCR confirmed the anti-inflammatory activity of the macerated herbal oil.ConclusionIt could be concluded that the macerated herbal oil could inhibit nitrite accumulation in culture media, which might be the inhibitory effect of the macerated herbal oil on COX-2 or Nrf2, the downstream modulator of the COX-2 pathway. Further intensive studies are needed for the optimization before bringing this macerated herbal oil into clinical application.Keywords: Macerated herbal oil, Antioxidant, Anti-inflammatory, Antibacterial, HMSCs
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Pages 25-30IntroductionDrug transporters are key determinants of pharmacokinetic and pharmacodynamic profiles of certain drugs. SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin. Our study was proposed to determine the normative frequencies of the single nucleotide polymorphisms (SNPs) rs2289669 and rs12943590 in the SLC47A1 and SLC47A2 genes, respectively, in South Indian population and also to compare those with those of the HapMap populations.MethodsOne hundred two unrelated healthy volunteers from South India were enrolled in the study. Genomic DNA was extracted by phenol-chloroform extraction method from the peripheral blood leucocytes and genotyping was accomplished by real-time polymerase chain reaction using TaqMan SNP genotyping assay method.ResultsIn contrast to other populations, the minor allele in SLC47A1 gene was found to be "G" with a frequency of 46.6% in South Indian population. The populations of Hans Chinese in Beijing (HCB) [P = 0.017] and Japanese in Tokyo (JPT) [PConclusionThus, the allele and genotype distributions of SLC47A1 and SLC47A2 gene polymorphisms were established in South Indian population and were found to be different from the frequencies of other ethnicities.Keywords: Drug transporters, Single nucleotide polymorphisms, SLC47A1, SLC47A2, MATE1, MATE2
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Pages 31-39IntroductionCancer cells are critically correlated with lipid molecules, particularly fatty acids, as structural blocks for membrane building, energy sources, and related signaling molecules. Therefore, cancer progression is in direct correlation with fatty acid metabolism. The aim of this study was to investigate the potential effects of common chemotherapeutic agents on the lipid metabolism of hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cells, with a focus on alterations in cellular fatty acid contents.MethodsHuman HepG2 and SW480 cell lines as HCC and CRC cells were respectively cultured in RPMI-1640 medium supplemented with non-toxic doses of 5-fluorouracil and doxorubicin for 72 hours. Oil Red O dye was used to estimate intracellular lipid vacuole intensity. Fatty acid analysis of isolated membrane phospholipids and cytoplasmic triglycerides (TG) was performed by gas-liquid chromatography (GLC) technique.ResultsOil red O staining represented significantly higher lipid accumulation and density in cancer cells after exposure to the chemotherapeutic agents as compared to non-treated control cells. Doxorubicin and 5-fluorouracil treatment promoted the channeling of saturated fatty acids (SFAs) from phospholipids to triglyceride pool in both HepG2 (.91% and .50%, PConclusionOur data showed that common chemotherapeutic agents of HCC and CRC can induce significant changes in cellular lipid accumulation and distribution of fatty acids through producing highly saturated and unsaturated lipid droplets and membrane lipids, respectively. These metabolic side effects may be associated with gastrointestinal cancers treatment failure.Keywords: Chemotherapy, Doxorubicin, Fatty acids, Fluorouracil, Lipid droplets
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Pages 41-47IntroductionSubstrate stiffness regulates cellular behavior as cells experience different stiffness values of tissues in the body. For example, endothelial cells (ECs) covering the inner layer of blood vessels are exposed to different stiffness values due to various pathologic and physiologic conditions. Despite numerous studies, cells by time span sense mechanical properties of the substrate, but the response is not well understood. We hypothesized that time is a major determinant influencing the behavior of cells seeded on substrates of varying stiffness.MethodsWe monitored cell spreading, internal structure, 3D topography, and the viability of ECs over 24 hours of culture on polydimethylsiloxane (PDMS) substrates with two different degrees of elastic modulus.ResultsDespite significant differences in cell spreading after cell seeding, cells showed a similar shape and internal structure after 24 hours of culture on both soft and stiff substrates. However, 3D topographical images confirmed existence of rich lamellipodia and filopodia around the cells cultured on stiffer PDMS substrates.ConclusionIt was concluded that the response of ECs to the substrate stiffness was time dependent with initial enhanced cellular spreading and viability on stiffer substrates. Results can provide a better comprehension of cell mechanotransduction for tissue engineering applications.Keywords: Time dependency, HUVECs, Substrate stiffness, Morphology, 3D topography
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Pages 49-57IntroductionPolymeric nanoparticles (NPs) formulated using biodegradable polymers offer great potential for development of de novo drug delivery systems (DDSs) capable of delivering a wide range of bioactive agents. They can be engineered as advanced multifunctional nanosystems (NSs) for simultaneous imaging and therapy known as theranostics or diapeutics.MethodsA brief prospective is provided on biomedical importance and applications of biodegradable polymeric NSs through reviewing the recently published literature.ResultsBiodegradable polymeric NPs present unique characteristics, including: nanoscaled structures, high encapsulation capacity, biocompatibility with non-thrombogenic and non-immunogenic properties, and controlled-/sustained-release profile for lipophilic and hydrophilic drugs. Once administered in vivo, all classes of biodegradable polymers (i.e., synthetic, semi-synthetic, and natural polymers) are subjected to enzymatic degradation; and hence, transformation into byproducts that can be simply eliminated from the human body. Natural and semi-synthetic polymers have been shown to be highly stable, much safer, and offer a non-/less-toxic means for specific delivery of cargo drugs in comparison with synthetic polymers. Despite being biocompatible and enzymatically-degradable, there are some drawbacks associated with these polymers such as batch to batch variation, high production cost, structural complexity, lower bioadhesive potential, uncontrolled rate of hydration, and possibility of microbial spoilage. These pitfalls have bolded the importance of synthetic counterparts despite their somewhat toxicity.ConclusionTaken all, to minimize the inadvertent effects of these polymers and to engineer much safer NSs, it is necessary to devise biopolymers with desirable chemical and biochemical modification(s) and polyelectrolyte complex formation to improve their drug delivery capacity in vivo.Keywords: Biodegradable polymers, Synthetic, semi-synthetic polymers, Natural polymers, Targeted therapy, Advanced drug delivery systems
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Pages 59-71IntroductionIn the recent decades, a number of studies have highlighted the importance of Helicobacter pylori in the initiation and development of peptic ulcer and gastric cancer. Some potential virulence factors (e.g., urease, CagA, VacA, BabA) are exploited by this microorganism, facilitating its persistence through evading human defense mechanisms. Among these toxins and enzymes, vacuolating toxin A (VacA) is of a great importance in the pathogenesis of H. pylori. VacA toxin shows different pattern of cytotoxicity through binding to different cell surface receptors in various cells.MethodsTo highlight attempts in treatment for H. pylori infection, here, we discussed the VacA potential as a candidate for development of vaccine and targeted immunotherapy. Furthermore, we reviewed the related literature to provide key insights on association of the genetic variants of VacA with the toxicity of the toxin in cells.ResultsA number of investigations on the receptor(s) binding of VacA toxin confirmed the pleiotropic nature of VacA that uses a unique mechanism for internalization through some membrane components such as lipid rafts and glycophosphatidylinositol (GPI)-anchored proteins (GPI-AP). Considering the high potency of VacA toxin in the clinical presentations in infection and assisting persistence and colonization of H. pylori, it is considered as one of the pivotal components in production vaccines and monoclonal antibodies (mAbs).ConclusionIt is possible to generate mAbs with a considerable potential to convert into secretory immunoglobulins that could penetrate into the niche of H. pylori and inhibit its normal functionalities. Further, conjugation of H. pylori targeting Ab fragments with the toxic agents or drug delivery systems (DDSs) offers new generation of H. pylori treatments.Keywords: Helicobacter pylori, VacA, Cell receptor, Vaccine, Immunotherapy