After a disruption of skin integrity, the body produces an immediate response followed by a funct... more After a disruption of skin integrity, the body produces an immediate response followed by a functional and comparable regeneration period, referred to as wound healing. Although normal wounds do not need much attention during the healing period, chronic (non-healing) wounds are the major challenge of current dermatological applications. Therefore, developing new, safe, and effective wound healing drugs has always been an attractive area of international research. In the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and F127), and their combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results revealed that NaB significantly increased migration capacity and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important growth factor and cytokines (vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α)). NaB containing hydrogel co-formulated with pluronics was also investigated for their wound healing activities using a full thickness wound model in rats. Macroscopic and histopathological analysis confirmed that wounds in combination gel-treated groups healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic wounds. However, further studies should be conducted to explore its exact action of mechanism and effects of this formulation on chronic wounds.
Burn injuries, the most common and destructive
forms of wounds, are generally accompanied with li... more Burn injuries, the most common and destructive forms of wounds, are generally accompanied with lifethreatening infections, inflammation, reduced angiogenesis, inadequate extracellular matrix production, and lack of growth factor stimulation. In the current study, a new antimicrobial carbopol-based hydrogel formulated with boron and pluronic block copolymers was evaluated for its healing activity using in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process.Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.
Stem cells with high proliferation, selfrenewal and differentiation capacities are promising for ... more Stem cells with high proliferation, selfrenewal and differentiation capacities are promising for tissue engineering approaches. Among stem cells, human tooth germ stem cells (hTGSCs) having mesenchymal stem cell characteristics are highly proliferative and able to differentiate into several cell lineages. Researchers have recently focused on transplanting stem cells with bioconductive and/or bioinductive materials that can provide cell commitment to the desired cell lineages. In the present study, effects of pluronic block copolymers (F68, F127 and P85) on in vitro myo- and neurogenic differentiation of human tooth germ stem cells (hTGSCs) were investigated. As P85 was found to exert considerable toxicity to hTGSCs even at low concentrations, it was not evaluated for further differentiation experiments. Immunocytochemical analysis, gene and protein expression studies revealed that while F68 treatment increased lineage-specific gene expression in both myo- and neuro-genically differentiated cells, F127 did not result in any remarkable difference compared to cells treated with differentiation medium. Subsequent studies are required to explore the exact mechanisms of how F68 increases the myogenic and neurogenic differentiation of hTGSCs. The present work indicates that pluronic F68 might be used in functional skeletal and neural tissue engineering applications.
Boron, a vital micronutrient for plant metabolism,
is not fully elucidated for embryonic and adul... more Boron, a vital micronutrient for plant metabolism, is not fully elucidated for embryonic and adult body development, and tissue regeneration. Although optimized amount of boron supplement has been shown to be essential for normal gestational development in zebrafish and frog and beneficial for bone regeneration in higher animals, effects of boron on myogenesis and myo-regeneration remains to be solved. In the current study, we investigated dose-dependent activity of boric acid on myogenic differentiation of human adipose-derived stem cells (hADSCs) using immunocytochemical, gene, and protein expression analysis. The results revealed that while low- (81.9 μM) and high-dose (819.6 μM) boron treatment increased myogenic gene expression levels such as myosin heavy chain (MYH), MyoD, myogenin, and desmin at day 4 of differentiation, high-dose treatment decreased myogenic-related gene and protein levels at day 21 of differentiation, confirmed by immunocytochemical analysis. The findings of the study present not only an understanding of boron’s effect on myogenic differentiation but also an opportunity for the development of scaffolds to be used in skeletal tissue engineering and supplements for embryonic muscle growth. However, fine dose tuning and treatment period arranging are highly warranted as boron treatment over required concentrations and time might result in detrimental outcomes to myogenesis and myo-regeneration.
Hepatocellular carcinoma is one of the most prevalent
cancers, with a high morbidity rate, even i... more Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II)Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/ day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dosedependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-κB p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-κB (NF-κB p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined.
Scaffold-based bone defect reconstructions still face many challenges due to their inadequate ost... more Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calciummineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highlywarranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.
The field of stem-cell biology has emerged as a key technology for the treatment of various disor... more The field of stem-cell biology has emerged as a key technology for the treatment of various disorders and tissue regeneration applications. However, a major problem remains in clinical practice, which is the question of whether stem cells preserve their self-renewal and differentiation potential in the culture conditions or not. In the current study, effects of boron on the cryopreservation of human tooth germ stem cells (hTGSCs) were evaluated for the first time. The impacts of various boron concentrations (sodium pentaborate pentahydrate (NaB)) were tested on characterized hTGSCs viability for different time intervals (24, 48, and 72 h). 20 lg/ml NaB with lower Me2SO concentration was found to display positive effects on hTGSCs during repeated freezing and defrosting cycles, and long-term cryopreservation. After thawing, cells were analyzed for their surface antigens and differentiation capacity. hTGSCs were successfully cryopreserved without any change in their mesenchymal stem cell characteristics as they were treated with boron containing freezing medium. In addition, fatty acid composition was examined to demonstrate membrane fatty acid profiles after freeze-thawing. Besides, NaB treatment extended osteogenic and chondrogenic differentiation of hTGSCs remarkably after long-term cryopreservation with respect to control groups. The study clearly suggests that NaB has a protective role on the survival of hTGSCs in short- and long-term cryopreservation. Due to the possible storage of hTGSCs at early ages, development of a functional and reliable cryopreservation media can be designed as a future solution to the dental stem cell banking.
Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (... more Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin- treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood–brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with rosuvastatin in human epilepsy patients with hypercholesterolemia.
Current clinical techniques in dental practice include stem cell and tissue engineering applicati... more Current clinical techniques in dental practice include stem cell and tissue engineering applications. Dental stem cells are promising primary cell source for mainly tooth tissue engineering. Interaction of mesenchymal stem cell with epithelial and endothelial cells is strictly required for an intact tooth morphogenesis. Therefore, it is important to investigate whether human tooth germ stem cells (hTGSCs) derived from wisdom tooth are suitable for endothelial and epithelial cell transformation in dental tissue regeneration approaches. Differentiation into endothelial and epithelial cell lineages were mimicked under defined conditions, confirmed by real time PCR, western blotting and immunocytochemical analysis by qualitative and quantitative methods. HUVECs and HaCaT cells were used as positive controls for the endothelial and epithelial differentiation assays, respectively. Immunocytochemical and western blotting analysis revealed that terminally differentiated cells expressed cell-lineage markers including CD31, VEGFR2, VE-Cadherin, vWF (endothelial cell markers), and cytokeratin (CK)-17, CK-19, EpCaM, vimentin (epithelial cell markers) in significant levels with respect to undifferentiated control cells. Moreover, high expression levels of VEGFR1, VEGFR2, VEGF, CK-18, and CK-19 genes were detected in differentiated endothelial and epithelial-like cells. Endothelial-like cells derived from hTGSCs were cultured on Matrigel, tube-like structure formations were followed as an indication for functional endothelial differentiation. hTGSCs successfully differentiate into various cell types with a broad range of functional abilities using an in vitro approach. These findings suggest that hTGSCs may serve a potential stem cell source for tissue engineering and cell therapy of epithelial and endothelial tissue.
After a disruption of skin integrity, the body produces
an immediate response followed by a funct... more After a disruption of skin integrity, the body produces an immediate response followed by a functional and comparable regeneration period, referred to as wound healing. Although normal wounds do not need much attention during the healing period, chronic (non-healing) wounds are the major challenge of current dermatological applications. Therefore, developing new, safe, and effective wound healing drugs has always been an attractive area of international research. In the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and F127), and their combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results revealed that NaB significantly increased migration capacity and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important growth factor and cytokines (vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α)). NaB containing hydrogel co-formulated with pluronics was also investigated for their wound healing activities using a full thickness wound model in rats. Macroscopic and histopathological analysis confirmed that wounds in combination gel-treated groups healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic wounds. However, further studies should be conducted to explore its exact action of mechanism and effects of this formulation on chronic wounds.
Secondary dental caries are one of the major reasons for restoration replacements. Incorporating ... more Secondary dental caries are one of the major reasons for restoration replacements. Incorporating antimicrobial properties into dental materials would limit the initiation and progression of dental caries. In the current study, dental composites having 1%, 5%, and 10% (w/w) sodium pentaborate pentahydrate were prepared and analyzed for their mechanical properties, degree of monomer conversion (DC) rate, antibacterial effects against Streptococcus mutans, and biocompatibility with human dental pulp stem cells (hDPSCs). Incorporation of boron into the composites significantly decreased flexural strength and DC in a dose-dependent manner, but the value for 1% boron-containing composite still remained within acceptable levels. Compressive strength and diametral tensile strength were not found to be different from those of controls. Although no inhibition zone was detected in an agar-well diffusion assay for any materials tested, significant bacterial growth inhibition was obtained in a direct contact test for boron-containing composites. Immunocytochemical and lineage-specific gene expression analysis revealed that composites with boron content increased the osteogenic and odontogenic capacity of hDPSCs. Boron-containing dental composites showed promising results for future clinical applications, displaying nontoxic, osteogenic, and odontogenic-inducing characteristics with remarkable antibacterial activity against S. mutans, and are hence potentially able to prevent secondary caries.
Saccharomyces cerevisiae, industrial yeast isolate, has been of great interest in recent years fo... more Saccharomyces cerevisiae, industrial yeast isolate, has been of great interest in recent years for fuel ethanol production. The ethanol yield and productivity depend on many inhibitory factors during the fermentation process such as temperature, ethanol, compounds released as the result of pretreatment procedures, and osmotic stress. An ideal strain should be able to grow under different stress conditions occurred at different fermentation steps. Development of tolerant yeast strains can be achieved by reprogramming pathways supporting the ethanol metabolism by regulating the energy balance and detoxicification processes. Complex gene interactions should be solved for an in-depth comprehension of the yeast stress tolerance mechanism. Genetic engineering as a powerful biotechnological tool is required to design new strategies for increasing the ethanol fermentation performance.Upregulation of stress tolerance genes by recombinant DNA technology can be a useful approach to overcome inhibitory situations. This review presents the application of several genetic engineering strategies to increase ethanol yield under different stress conditions including inhibitor tolerance, ethanol tolerance, thermotolerance, and osmotolerance.
The present work involves development of stable antimicrobial materials containing silver- and zi... more The present work involves development of stable antimicrobial materials containing silver- and zinc-ion–exchanged zeolites. Faujasite X and Linde type A zeolites were synthesized, and following ion exchange with Ag+ and Zn++ ions they were found to exhibit antimicrobial effects against bacteria (E. coli, P. aeruginosa, and S. aureus), yeast (C. albicans and C. glabrata), and fungi (A. niger and P. expansum). Zeolites-X and -A containing silver and zinc ions were then mixed with various coating materials, including paints and polypropylene, to develop antimicrobial composites. The long-term antimicrobial characteristics of zeolite-containing composite materials were investigated by inoculating selected microorganisms onto the surface of the materials. The results indicated that the higher the zeolite concentration present in the composite, the more long-term antimicrobial activity was achieved. Silver-ion–exchanged zeolites were more effective against bacterial and candidal species, while zinc zeolites exhibited noticeable antifungal properties. Materials manufactured with metal-ion–exchanged zeolites would prevent microbial growth on surfaces, reducing cross-contamination and infection risk as well as the microbial degradation of products.
Zeolites are nanoporous alumina silicates composed of silicon, aluminum, and oxygen in a framewor... more Zeolites are nanoporous alumina silicates composed of silicon, aluminum, and oxygen in a framework with cations, water within pores. Their cation contents can be exchanged with monovalent or divalent ions. In the present study, the antimicrobial (antibacterial, anticandidal, and antifungal) properties of zeolite type X and A, with different Al/Si ratio, ion exchanged with Ag+, Zn2+, and Cu2+ ions were investigated individually. The study presents the synthesis and manufacture of four different zeolite types characterized by scanning electron microscopy and X-ray diffraction. The ion loading capacity of the zeolites was examined and compared with the antimicrobial characteristics against a broad range of microorganisms including bacteria, yeast, and mold. It was observed that Ag+ ion-loaded zeolites exhibited more antibacterial activity with respect to other metal ion-embedded zeolite samples. The results clearly support that various synthetic zeolites can be ion exchanged with Ag+, Zn2+, and Cu2+ ions to acquire antimicrobial properties or ion-releasing characteristics to provide prolonged or stronger activity. The current study suggested that zeolite formulations could be combined with various materials used in manufacturing medical devices, surfaces, textiles, or household items where antimicrobial properties are required.
Increasing multiple drug resistance of microorganisms to certain antibiotics is a major health pr... more Increasing multiple drug resistance of microorganisms to certain antibiotics is a major health problem of the current clinical practice. Therefore, development of novel broad range antimicrobial agents and increasing efficiency of existing antibiotics are under great interest among scientists. Some psychotropic drugs not only reverse microbial antibiotic resistance but also exhibit direct antimicrobial activity against several biological targets. In the present study, 16 different psychotropic drugs including sertraline, paroxetine, aripiprazole, fluvoxamine, moclobemide, venlafaxine, mianserin, trazodone, mirtazapine, clomipramine, alprazolam, escitalopram, citaloprame, fluoxetine, gabapentin and reboxetine have been examined for their antimicrobial properties against wide range of bacteria, yeast and fungi using disc-diffusion and micro-well dilution assays. The results revealed that except FOR gabapentin, venlafaxine, moclobemide and alprazolam, the remaining drugs tested in this study showed various antimicrobial activities. Selective serotonin reuptake inhibitor group drugs including sertraline, paroxetine, fluvoxamine and fluoxetine displayed broad range antibacterial activity compared to other psychotropic drugs. Among them, sertraline was also found to be effective against Candida albicans and Aspergillus niger. Exploring antimicrobial activities will increase the use and application of these psychotropic drugs in clinical approaches. However, in vivo studies and clinical trials are strictly required to evaluate efficiencies of these chemicals for the treatment of systemic microbial infections.
The impact of boron on the development of obesity
remains controversial in the analysis of experi... more The impact of boron on the development of obesity remains controversial in the analysis of experimental and clinical data. The objective of this study was to investigate the relationship between blood and urine boron concentrations and obesity in normal, overweight, obese, and morbidly obese subjects in different age groups. A total of 105 subjects were categorized into 12 groups based on body mass index and three different age levels: as young adult (18 to 34 years old), adult (35 to 54 years old), and older adult (greater than 55 years old). Age, gender, body mass index, and blood and urine boron concentrations were recorded for each subject. There were 50 women and 55 men, with a mean age of 44.63 ± 17.9 years. Blood and urine boron concentrations were similar among the groups (p = 0.510 and p = 0.228, respectively). However, a positive correlation between age and blood boron concentration (p = 0.001) was detected in contrast to the presence of a negative correlation between age and urine boron concentration (p = 0.027). Multiple linear regression analysis showed that there was no significant relationship between gender, age, and quantitative values of body mass index for each subject, and blood and urine boron concentrations. Although the relationship between boron and obesity has not been confirmed, changes of blood and urine boron concentrations with age may have some physiologic sequences to cause obesity.
The field of cancer research has been emerged in recent years for the development of specific dru... more The field of cancer research has been emerged in recent years for the development of specific drugs to cancer treatment. New agents with the ability to provide efficient treatment by reducing side effects has led to new opportunities for improving agents for cytotoxic therapies. While there are several drugs for colon cancer treatment, researchers are trying to evaluate new agents or combinations of existing ones which can be used efficiently. Schiff bases with a wide range of variety and biological properties including anticancer activity might be used for colon cancer treatment. In the current study, a novel schiff base derivative synthesized by our group was tested in vivo for colon cancer. In a model of azoxymethane (AOM) induced colorectal cancer, chemopreventive properties of schiff base was also analyzed in rats. While AOM induced de novo crypt formation, adenocarcinoma and dysplasia development, schiff base application reduced the number of aberrant crypt foci (ACF), dysplasia or adenocarcinoma. Analysis of the intestinal mucosa showed that peritoneal administration of SB complex not only decreased the protein expression of COX-2, Bcl-2 and NF-κB but also enhanced the Bax expression suggesting the apoptotic and anti-proliferative effects for this compound. Our findings showed that SB complex might be used for the colorectal cancer treatment. Further studies are highly warranted to obtain additional insights and identify mode of action for the schiff base.
There is a huge demand for developing new technologies for alternative energy sources due to the ... more There is a huge demand for developing new technologies for alternative energy sources due to the elevated costs of petroleum and its by-products, depletion of nonrenewable fuel sources, and to eliminate the disadvantages of geopolitical location and environmental pollution caused by high levels of carbon dioxide release. Science is striving to meet this demand and as molecular biology techniques have progressed, genetic engineering tools have been presented as promising future solutions in the form of optimizing the fermentation process to increase the ethanol yield from different carbon sources such as starch. As Saccharomyces cerevisiae is not naturally able to ferment starch, it can be genetically manipulated and modulated to improve the fuel production from starchy materials and the amount of cost that is required to produce ethanol would be decreased with these manipulations. General modifications in S. cerevisiae include specific gene expressions to gain new properties or improve existing pathways. This review aims to elicit the current status of ethanol production thorough alternative techniques from starch using current genetic engineering applications and to give further directions for high-throughput fermentations using genetically modified S. cerevisiae strains.
Verbascum speciosum is a biennial herb used as traditional folk medicine in the Black Sea region ... more Verbascum speciosum is a biennial herb used as traditional folk medicine in the Black Sea region of Turkey for the treatment of various skin wounds. The underlying mechanisms of wound healing activity of V. speciosum are completely unknown. In the current study, methanol extract of V. speciosum was investigated for its efficacy on viability, migration, apoptosis, cell cycle and some (p53, caspase-3 and collagen type I) gene expression patterns in fibroblast and endothelial cells. Results revealed that 200μg/ml plant extract had remarkable proliferative and migratory effect on human and mouse fibroblasts. While apoptotic gene levels, p53 and caspase-3, decreased in plant extract treated group, collagen type I gene level was found significantly higher compared to that of control group. Annexin V staining and cell cycle analysis showed that plant extract decreased apoptotic cell number without affecting cell cycle distributions of fibroblast cells. In addition, tube-like structure formation by human umbilical vein endothelial cells cultured on matrigel increased in the presence of plant extract. The present study suggested that V. speciosum might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation, migration and angiogenesis, corroborating its traditional use. Industrial relevance: V. speciosum is used as a wound healing agent in folk medicine without any scientific proofs. The current study was conducted to explore its potential activity in wound healing using in vitro approaches. Further studies are highly warranted to identify active molecules in the extract that need to be examined in in vivo and clinical studies for an efficient wound healing drug development. Determining active constituents in the extract would be an economical and safe option for clinical wound healing approaches. Keywords. Verbascum speciosum; methanol extract; wound healing; fibroblast cells; angiogenesis
After a disruption of skin integrity, the body produces an immediate response followed by a funct... more After a disruption of skin integrity, the body produces an immediate response followed by a functional and comparable regeneration period, referred to as wound healing. Although normal wounds do not need much attention during the healing period, chronic (non-healing) wounds are the major challenge of current dermatological applications. Therefore, developing new, safe, and effective wound healing drugs has always been an attractive area of international research. In the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and F127), and their combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results revealed that NaB significantly increased migration capacity and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important growth factor and cytokines (vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α)). NaB containing hydrogel co-formulated with pluronics was also investigated for their wound healing activities using a full thickness wound model in rats. Macroscopic and histopathological analysis confirmed that wounds in combination gel-treated groups healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic wounds. However, further studies should be conducted to explore its exact action of mechanism and effects of this formulation on chronic wounds.
Burn injuries, the most common and destructive
forms of wounds, are generally accompanied with li... more Burn injuries, the most common and destructive forms of wounds, are generally accompanied with lifethreatening infections, inflammation, reduced angiogenesis, inadequate extracellular matrix production, and lack of growth factor stimulation. In the current study, a new antimicrobial carbopol-based hydrogel formulated with boron and pluronic block copolymers was evaluated for its healing activity using in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process.Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.
Stem cells with high proliferation, selfrenewal and differentiation capacities are promising for ... more Stem cells with high proliferation, selfrenewal and differentiation capacities are promising for tissue engineering approaches. Among stem cells, human tooth germ stem cells (hTGSCs) having mesenchymal stem cell characteristics are highly proliferative and able to differentiate into several cell lineages. Researchers have recently focused on transplanting stem cells with bioconductive and/or bioinductive materials that can provide cell commitment to the desired cell lineages. In the present study, effects of pluronic block copolymers (F68, F127 and P85) on in vitro myo- and neurogenic differentiation of human tooth germ stem cells (hTGSCs) were investigated. As P85 was found to exert considerable toxicity to hTGSCs even at low concentrations, it was not evaluated for further differentiation experiments. Immunocytochemical analysis, gene and protein expression studies revealed that while F68 treatment increased lineage-specific gene expression in both myo- and neuro-genically differentiated cells, F127 did not result in any remarkable difference compared to cells treated with differentiation medium. Subsequent studies are required to explore the exact mechanisms of how F68 increases the myogenic and neurogenic differentiation of hTGSCs. The present work indicates that pluronic F68 might be used in functional skeletal and neural tissue engineering applications.
Boron, a vital micronutrient for plant metabolism,
is not fully elucidated for embryonic and adul... more Boron, a vital micronutrient for plant metabolism, is not fully elucidated for embryonic and adult body development, and tissue regeneration. Although optimized amount of boron supplement has been shown to be essential for normal gestational development in zebrafish and frog and beneficial for bone regeneration in higher animals, effects of boron on myogenesis and myo-regeneration remains to be solved. In the current study, we investigated dose-dependent activity of boric acid on myogenic differentiation of human adipose-derived stem cells (hADSCs) using immunocytochemical, gene, and protein expression analysis. The results revealed that while low- (81.9 μM) and high-dose (819.6 μM) boron treatment increased myogenic gene expression levels such as myosin heavy chain (MYH), MyoD, myogenin, and desmin at day 4 of differentiation, high-dose treatment decreased myogenic-related gene and protein levels at day 21 of differentiation, confirmed by immunocytochemical analysis. The findings of the study present not only an understanding of boron’s effect on myogenic differentiation but also an opportunity for the development of scaffolds to be used in skeletal tissue engineering and supplements for embryonic muscle growth. However, fine dose tuning and treatment period arranging are highly warranted as boron treatment over required concentrations and time might result in detrimental outcomes to myogenesis and myo-regeneration.
Hepatocellular carcinoma is one of the most prevalent
cancers, with a high morbidity rate, even i... more Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II)Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/ day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dosedependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-κB p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-κB (NF-κB p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined.
Scaffold-based bone defect reconstructions still face many challenges due to their inadequate ost... more Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calciummineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highlywarranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.
The field of stem-cell biology has emerged as a key technology for the treatment of various disor... more The field of stem-cell biology has emerged as a key technology for the treatment of various disorders and tissue regeneration applications. However, a major problem remains in clinical practice, which is the question of whether stem cells preserve their self-renewal and differentiation potential in the culture conditions or not. In the current study, effects of boron on the cryopreservation of human tooth germ stem cells (hTGSCs) were evaluated for the first time. The impacts of various boron concentrations (sodium pentaborate pentahydrate (NaB)) were tested on characterized hTGSCs viability for different time intervals (24, 48, and 72 h). 20 lg/ml NaB with lower Me2SO concentration was found to display positive effects on hTGSCs during repeated freezing and defrosting cycles, and long-term cryopreservation. After thawing, cells were analyzed for their surface antigens and differentiation capacity. hTGSCs were successfully cryopreserved without any change in their mesenchymal stem cell characteristics as they were treated with boron containing freezing medium. In addition, fatty acid composition was examined to demonstrate membrane fatty acid profiles after freeze-thawing. Besides, NaB treatment extended osteogenic and chondrogenic differentiation of hTGSCs remarkably after long-term cryopreservation with respect to control groups. The study clearly suggests that NaB has a protective role on the survival of hTGSCs in short- and long-term cryopreservation. Due to the possible storage of hTGSCs at early ages, development of a functional and reliable cryopreservation media can be designed as a future solution to the dental stem cell banking.
Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (... more Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin- treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood–brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with rosuvastatin in human epilepsy patients with hypercholesterolemia.
Current clinical techniques in dental practice include stem cell and tissue engineering applicati... more Current clinical techniques in dental practice include stem cell and tissue engineering applications. Dental stem cells are promising primary cell source for mainly tooth tissue engineering. Interaction of mesenchymal stem cell with epithelial and endothelial cells is strictly required for an intact tooth morphogenesis. Therefore, it is important to investigate whether human tooth germ stem cells (hTGSCs) derived from wisdom tooth are suitable for endothelial and epithelial cell transformation in dental tissue regeneration approaches. Differentiation into endothelial and epithelial cell lineages were mimicked under defined conditions, confirmed by real time PCR, western blotting and immunocytochemical analysis by qualitative and quantitative methods. HUVECs and HaCaT cells were used as positive controls for the endothelial and epithelial differentiation assays, respectively. Immunocytochemical and western blotting analysis revealed that terminally differentiated cells expressed cell-lineage markers including CD31, VEGFR2, VE-Cadherin, vWF (endothelial cell markers), and cytokeratin (CK)-17, CK-19, EpCaM, vimentin (epithelial cell markers) in significant levels with respect to undifferentiated control cells. Moreover, high expression levels of VEGFR1, VEGFR2, VEGF, CK-18, and CK-19 genes were detected in differentiated endothelial and epithelial-like cells. Endothelial-like cells derived from hTGSCs were cultured on Matrigel, tube-like structure formations were followed as an indication for functional endothelial differentiation. hTGSCs successfully differentiate into various cell types with a broad range of functional abilities using an in vitro approach. These findings suggest that hTGSCs may serve a potential stem cell source for tissue engineering and cell therapy of epithelial and endothelial tissue.
After a disruption of skin integrity, the body produces
an immediate response followed by a funct... more After a disruption of skin integrity, the body produces an immediate response followed by a functional and comparable regeneration period, referred to as wound healing. Although normal wounds do not need much attention during the healing period, chronic (non-healing) wounds are the major challenge of current dermatological applications. Therefore, developing new, safe, and effective wound healing drugs has always been an attractive area of international research. In the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and F127), and their combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results revealed that NaB significantly increased migration capacity and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important growth factor and cytokines (vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α)). NaB containing hydrogel co-formulated with pluronics was also investigated for their wound healing activities using a full thickness wound model in rats. Macroscopic and histopathological analysis confirmed that wounds in combination gel-treated groups healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic wounds. However, further studies should be conducted to explore its exact action of mechanism and effects of this formulation on chronic wounds.
Secondary dental caries are one of the major reasons for restoration replacements. Incorporating ... more Secondary dental caries are one of the major reasons for restoration replacements. Incorporating antimicrobial properties into dental materials would limit the initiation and progression of dental caries. In the current study, dental composites having 1%, 5%, and 10% (w/w) sodium pentaborate pentahydrate were prepared and analyzed for their mechanical properties, degree of monomer conversion (DC) rate, antibacterial effects against Streptococcus mutans, and biocompatibility with human dental pulp stem cells (hDPSCs). Incorporation of boron into the composites significantly decreased flexural strength and DC in a dose-dependent manner, but the value for 1% boron-containing composite still remained within acceptable levels. Compressive strength and diametral tensile strength were not found to be different from those of controls. Although no inhibition zone was detected in an agar-well diffusion assay for any materials tested, significant bacterial growth inhibition was obtained in a direct contact test for boron-containing composites. Immunocytochemical and lineage-specific gene expression analysis revealed that composites with boron content increased the osteogenic and odontogenic capacity of hDPSCs. Boron-containing dental composites showed promising results for future clinical applications, displaying nontoxic, osteogenic, and odontogenic-inducing characteristics with remarkable antibacterial activity against S. mutans, and are hence potentially able to prevent secondary caries.
Saccharomyces cerevisiae, industrial yeast isolate, has been of great interest in recent years fo... more Saccharomyces cerevisiae, industrial yeast isolate, has been of great interest in recent years for fuel ethanol production. The ethanol yield and productivity depend on many inhibitory factors during the fermentation process such as temperature, ethanol, compounds released as the result of pretreatment procedures, and osmotic stress. An ideal strain should be able to grow under different stress conditions occurred at different fermentation steps. Development of tolerant yeast strains can be achieved by reprogramming pathways supporting the ethanol metabolism by regulating the energy balance and detoxicification processes. Complex gene interactions should be solved for an in-depth comprehension of the yeast stress tolerance mechanism. Genetic engineering as a powerful biotechnological tool is required to design new strategies for increasing the ethanol fermentation performance.Upregulation of stress tolerance genes by recombinant DNA technology can be a useful approach to overcome inhibitory situations. This review presents the application of several genetic engineering strategies to increase ethanol yield under different stress conditions including inhibitor tolerance, ethanol tolerance, thermotolerance, and osmotolerance.
The present work involves development of stable antimicrobial materials containing silver- and zi... more The present work involves development of stable antimicrobial materials containing silver- and zinc-ion–exchanged zeolites. Faujasite X and Linde type A zeolites were synthesized, and following ion exchange with Ag+ and Zn++ ions they were found to exhibit antimicrobial effects against bacteria (E. coli, P. aeruginosa, and S. aureus), yeast (C. albicans and C. glabrata), and fungi (A. niger and P. expansum). Zeolites-X and -A containing silver and zinc ions were then mixed with various coating materials, including paints and polypropylene, to develop antimicrobial composites. The long-term antimicrobial characteristics of zeolite-containing composite materials were investigated by inoculating selected microorganisms onto the surface of the materials. The results indicated that the higher the zeolite concentration present in the composite, the more long-term antimicrobial activity was achieved. Silver-ion–exchanged zeolites were more effective against bacterial and candidal species, while zinc zeolites exhibited noticeable antifungal properties. Materials manufactured with metal-ion–exchanged zeolites would prevent microbial growth on surfaces, reducing cross-contamination and infection risk as well as the microbial degradation of products.
Zeolites are nanoporous alumina silicates composed of silicon, aluminum, and oxygen in a framewor... more Zeolites are nanoporous alumina silicates composed of silicon, aluminum, and oxygen in a framework with cations, water within pores. Their cation contents can be exchanged with monovalent or divalent ions. In the present study, the antimicrobial (antibacterial, anticandidal, and antifungal) properties of zeolite type X and A, with different Al/Si ratio, ion exchanged with Ag+, Zn2+, and Cu2+ ions were investigated individually. The study presents the synthesis and manufacture of four different zeolite types characterized by scanning electron microscopy and X-ray diffraction. The ion loading capacity of the zeolites was examined and compared with the antimicrobial characteristics against a broad range of microorganisms including bacteria, yeast, and mold. It was observed that Ag+ ion-loaded zeolites exhibited more antibacterial activity with respect to other metal ion-embedded zeolite samples. The results clearly support that various synthetic zeolites can be ion exchanged with Ag+, Zn2+, and Cu2+ ions to acquire antimicrobial properties or ion-releasing characteristics to provide prolonged or stronger activity. The current study suggested that zeolite formulations could be combined with various materials used in manufacturing medical devices, surfaces, textiles, or household items where antimicrobial properties are required.
Increasing multiple drug resistance of microorganisms to certain antibiotics is a major health pr... more Increasing multiple drug resistance of microorganisms to certain antibiotics is a major health problem of the current clinical practice. Therefore, development of novel broad range antimicrobial agents and increasing efficiency of existing antibiotics are under great interest among scientists. Some psychotropic drugs not only reverse microbial antibiotic resistance but also exhibit direct antimicrobial activity against several biological targets. In the present study, 16 different psychotropic drugs including sertraline, paroxetine, aripiprazole, fluvoxamine, moclobemide, venlafaxine, mianserin, trazodone, mirtazapine, clomipramine, alprazolam, escitalopram, citaloprame, fluoxetine, gabapentin and reboxetine have been examined for their antimicrobial properties against wide range of bacteria, yeast and fungi using disc-diffusion and micro-well dilution assays. The results revealed that except FOR gabapentin, venlafaxine, moclobemide and alprazolam, the remaining drugs tested in this study showed various antimicrobial activities. Selective serotonin reuptake inhibitor group drugs including sertraline, paroxetine, fluvoxamine and fluoxetine displayed broad range antibacterial activity compared to other psychotropic drugs. Among them, sertraline was also found to be effective against Candida albicans and Aspergillus niger. Exploring antimicrobial activities will increase the use and application of these psychotropic drugs in clinical approaches. However, in vivo studies and clinical trials are strictly required to evaluate efficiencies of these chemicals for the treatment of systemic microbial infections.
The impact of boron on the development of obesity
remains controversial in the analysis of experi... more The impact of boron on the development of obesity remains controversial in the analysis of experimental and clinical data. The objective of this study was to investigate the relationship between blood and urine boron concentrations and obesity in normal, overweight, obese, and morbidly obese subjects in different age groups. A total of 105 subjects were categorized into 12 groups based on body mass index and three different age levels: as young adult (18 to 34 years old), adult (35 to 54 years old), and older adult (greater than 55 years old). Age, gender, body mass index, and blood and urine boron concentrations were recorded for each subject. There were 50 women and 55 men, with a mean age of 44.63 ± 17.9 years. Blood and urine boron concentrations were similar among the groups (p = 0.510 and p = 0.228, respectively). However, a positive correlation between age and blood boron concentration (p = 0.001) was detected in contrast to the presence of a negative correlation between age and urine boron concentration (p = 0.027). Multiple linear regression analysis showed that there was no significant relationship between gender, age, and quantitative values of body mass index for each subject, and blood and urine boron concentrations. Although the relationship between boron and obesity has not been confirmed, changes of blood and urine boron concentrations with age may have some physiologic sequences to cause obesity.
The field of cancer research has been emerged in recent years for the development of specific dru... more The field of cancer research has been emerged in recent years for the development of specific drugs to cancer treatment. New agents with the ability to provide efficient treatment by reducing side effects has led to new opportunities for improving agents for cytotoxic therapies. While there are several drugs for colon cancer treatment, researchers are trying to evaluate new agents or combinations of existing ones which can be used efficiently. Schiff bases with a wide range of variety and biological properties including anticancer activity might be used for colon cancer treatment. In the current study, a novel schiff base derivative synthesized by our group was tested in vivo for colon cancer. In a model of azoxymethane (AOM) induced colorectal cancer, chemopreventive properties of schiff base was also analyzed in rats. While AOM induced de novo crypt formation, adenocarcinoma and dysplasia development, schiff base application reduced the number of aberrant crypt foci (ACF), dysplasia or adenocarcinoma. Analysis of the intestinal mucosa showed that peritoneal administration of SB complex not only decreased the protein expression of COX-2, Bcl-2 and NF-κB but also enhanced the Bax expression suggesting the apoptotic and anti-proliferative effects for this compound. Our findings showed that SB complex might be used for the colorectal cancer treatment. Further studies are highly warranted to obtain additional insights and identify mode of action for the schiff base.
There is a huge demand for developing new technologies for alternative energy sources due to the ... more There is a huge demand for developing new technologies for alternative energy sources due to the elevated costs of petroleum and its by-products, depletion of nonrenewable fuel sources, and to eliminate the disadvantages of geopolitical location and environmental pollution caused by high levels of carbon dioxide release. Science is striving to meet this demand and as molecular biology techniques have progressed, genetic engineering tools have been presented as promising future solutions in the form of optimizing the fermentation process to increase the ethanol yield from different carbon sources such as starch. As Saccharomyces cerevisiae is not naturally able to ferment starch, it can be genetically manipulated and modulated to improve the fuel production from starchy materials and the amount of cost that is required to produce ethanol would be decreased with these manipulations. General modifications in S. cerevisiae include specific gene expressions to gain new properties or improve existing pathways. This review aims to elicit the current status of ethanol production thorough alternative techniques from starch using current genetic engineering applications and to give further directions for high-throughput fermentations using genetically modified S. cerevisiae strains.
Verbascum speciosum is a biennial herb used as traditional folk medicine in the Black Sea region ... more Verbascum speciosum is a biennial herb used as traditional folk medicine in the Black Sea region of Turkey for the treatment of various skin wounds. The underlying mechanisms of wound healing activity of V. speciosum are completely unknown. In the current study, methanol extract of V. speciosum was investigated for its efficacy on viability, migration, apoptosis, cell cycle and some (p53, caspase-3 and collagen type I) gene expression patterns in fibroblast and endothelial cells. Results revealed that 200μg/ml plant extract had remarkable proliferative and migratory effect on human and mouse fibroblasts. While apoptotic gene levels, p53 and caspase-3, decreased in plant extract treated group, collagen type I gene level was found significantly higher compared to that of control group. Annexin V staining and cell cycle analysis showed that plant extract decreased apoptotic cell number without affecting cell cycle distributions of fibroblast cells. In addition, tube-like structure formation by human umbilical vein endothelial cells cultured on matrigel increased in the presence of plant extract. The present study suggested that V. speciosum might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation, migration and angiogenesis, corroborating its traditional use. Industrial relevance: V. speciosum is used as a wound healing agent in folk medicine without any scientific proofs. The current study was conducted to explore its potential activity in wound healing using in vitro approaches. Further studies are highly warranted to identify active molecules in the extract that need to be examined in in vivo and clinical studies for an efficient wound healing drug development. Determining active constituents in the extract would be an economical and safe option for clinical wound healing approaches. Keywords. Verbascum speciosum; methanol extract; wound healing; fibroblast cells; angiogenesis
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Papers by Selami Demirci
forms of wounds, are generally accompanied with lifethreatening infections, inflammation, reduced angiogenesis,
inadequate extracellular matrix production, and lack of growth
factor stimulation. In the current study, a new antimicrobial
carbopol-based hydrogel formulated with boron and pluronic
block copolymers was evaluated for its healing activity using
in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process.Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.
lineages. Researchers have recently focused on transplanting
stem cells with bioconductive and/or bioinductive materials that can provide cell commitment to the desired cell lineages. In the present study, effects of pluronic block copolymers (F68, F127 and P85) on in vitro myo- and neurogenic differentiation of human tooth germ stem cells (hTGSCs) were investigated. As
P85 was found to exert considerable toxicity to hTGSCs even at low concentrations, it was not evaluated for further differentiation experiments. Immunocytochemical analysis, gene and protein expression studies revealed that while F68 treatment increased lineage-specific gene expression in both
myo- and neuro-genically differentiated cells, F127 did not result in any remarkable difference compared to cells treated with differentiation medium. Subsequent studies are required to explore the exact mechanisms of how F68 increases the myogenic and neurogenic differentiation of hTGSCs. The present work indicates that pluronic F68 might be used in
functional skeletal and neural tissue engineering applications.
is not fully elucidated for embryonic and adult body development, and tissue regeneration. Although optimized amount of boron supplement has been shown to be essential for normal gestational development in zebrafish and frog and beneficial for bone regeneration in higher animals, effects of boron on myogenesis and myo-regeneration remains to be solved. In the current study, we investigated dose-dependent activity of boric acid on myogenic differentiation of human adipose-derived stem cells (hADSCs) using immunocytochemical, gene, and protein expression analysis. The results revealed that while low- (81.9 μM) and high-dose (819.6 μM) boron treatment increased myogenic gene expression levels such as myosin heavy chain (MYH), MyoD, myogenin, and desmin at day 4 of differentiation, high-dose treatment decreased myogenic-related gene and protein levels at day 21 of differentiation, confirmed by immunocytochemical analysis. The findings of the study present not only an understanding of boron’s effect on myogenic differentiation but also an opportunity for the development of scaffolds to be used in skeletal tissue engineering and supplements for embryonic muscle growth. However, fine dose tuning and treatment period arranging are highly warranted as boron treatment over required concentrations and time might result in detrimental outcomes to myogenesis and myo-regeneration.
cancers, with a high morbidity rate, even in developed
countries. In the present study, the curative effect of the
Schiff base (SB) heterodinuclear copper(II)Mn(II) complex
on diethylnitrosamine (DEN)-induced liver carcinoma was
investigated. Hepatocarcinoma was initiated by an injection
of DEN and promoted by phenobarbital (0.05%) in the diet.
In addition, the potential nephrotoxicity of SB was evaluated
in a cisplatin-induced nephrotoxicity model. Rats were
administered the SB complex (1 and 2 mg/kg body weight/
day) for 24 weeks, and cancer progression was investigated
by macroscopic, histopathological, and western blot
examinations. The administration of SB decreased the
incidence and the number of hepatic nodules in a dosedependent manner by regulating inflammation response
and the apoptotic pathway. Western blot analyses from the
livers of rats treated with SB after DEN induction showed
significantly enhanced Bax and caspase-3 levels, with a
marked decrease in the levels of Bcl-2, NF-κB p65 and
cyclooxygenase (COX)-2. Results from the nephrotoxicity
study showed that, whereas cisplatin increased serum urea
nitrogen and creatinine levels, no increase in serum
biochemical parameters was detected in SB-treated
animals. Moreover, protein levels of NF-E2-related factor-2
(Nrf2) and heme oxygenase-1 were lower, whereas nuclear
factor-κB (NF-κB p65) and activator protein-1 levels were
higher in the kidneys of cisplatin-treated animals compared
with that of the SB groups. Therefore, the SB complex could
be an alternative chemotherapeutic option for liver cancer
treatment once its safety in clinical applications has been
examined.
osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type
and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In
the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calciummineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highlywarranted for
the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics.
The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.
conditions or not. In the current study, effects of boron on the cryopreservation of human tooth germ stem cells (hTGSCs) were evaluated for the first time. The impacts of various boron concentrations (sodium pentaborate pentahydrate (NaB)) were tested on characterized hTGSCs viability for different time intervals (24, 48, and 72 h). 20 lg/ml NaB with lower Me2SO concentration was found to display positive effects on hTGSCs during repeated freezing and defrosting cycles, and long-term cryopreservation. After thawing, cells were analyzed for their surface antigens and differentiation capacity. hTGSCs were successfully cryopreserved without any change in their mesenchymal stem cell characteristics as they were treated with boron containing freezing medium. In addition, fatty acid composition was examined to demonstrate membrane fatty acid profiles after freeze-thawing. Besides, NaB treatment extended osteogenic and chondrogenic differentiation of hTGSCs remarkably after long-term cryopreservation with
respect to control groups. The study clearly suggests that NaB has a protective role on the survival of hTGSCs in short- and long-term cryopreservation. Due to the possible storage of hTGSCs at early ages, development of a functional and reliable cryopreservation media can be designed as a future solution
to the dental stem cell banking.
reductase inhibitors exert neuroprotective functions in animal
models of neurodegenerative disorders. In view of these
promising observations, we were interested in whether
HMG-CoA reductase inhibition would affect epileptiform
activity in the brain. To elucidate this issue, atorvastatin,
simvastatin and rosuvastatin were administered orally at a
dose of 20 mg/kg each for 3 days and their anti-epileptic
activities were tested and compared in rats. Epileptiform
activity in the brain was induced by an intracortical
penicillin G injection. Among HMG-CoA reductase inhibitors,
simvastatin-treatment was less effective in terms of
spike frequency as compared with atorvastatin- and rosuvastatin-
treated animals. Atorvastatin treatment reduced
spike frequencies and amplitudes significantly throughout
the experiment. However, the most pronounced anti-epileptic
effect was observed in rosuvastatin-treated animals, which
was associated with improved blood–brain barrier (BBB)
integrity, increased expression of endothelial nitric oxide
synthase (eNOS) mRNA and decreased expressions of
pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition
of eNOS activity with L-NG-Nitroarginine Methyl Ester
(L-NAME) reversed the anti-epileptic effect of rosuvastatin
significantly. However, L-NAME did not alter the effect of
rosuvastatin on the levels of p53, Bax and caspase-3 mRNA
expression. Here, we provide evidence that among
HMG-CoA reductase inhibitors, rosuvastatin was the most
effective statin on the reduction of epileptiform activity,
which was associated with improved BBB permeability,
increased expression of eNOS and decreased expressions
of pro-apoptotic p53, Bax and caspase-3. Our observation
also revealed that the anti-epileptic effect of rosuvastatin
was dependent on the increased expression level of eNOS.
The robust anti-epileptic effect encourages proof-of-concept
studies with rosuvastatin in human epilepsy patients with
hypercholesterolemia.
promising primary cell source for mainly tooth tissue engineering. Interaction of mesenchymal stem cell with epithelial and
endothelial cells is strictly required for an intact tooth morphogenesis. Therefore, it is important to investigate whether human tooth germ stem cells (hTGSCs) derived from wisdom tooth are suitable for endothelial and epithelial cell transformation in
dental tissue regeneration approaches. Differentiation into endothelial and epithelial cell lineages were mimicked under
defined conditions, confirmed by real time PCR, western blotting and immunocytochemical analysis by qualitative and
quantitative methods. HUVECs and HaCaT cells were used as positive controls for the endothelial and epithelial
differentiation assays, respectively. Immunocytochemical and western blotting analysis revealed that terminally differentiated
cells expressed cell-lineage markers including CD31, VEGFR2, VE-Cadherin, vWF (endothelial cell markers), and cytokeratin
(CK)-17, CK-19, EpCaM, vimentin (epithelial cell markers) in significant levels with respect to undifferentiated control cells.
Moreover, high expression levels of VEGFR1, VEGFR2, VEGF, CK-18, and CK-19 genes were detected in differentiated
endothelial and epithelial-like cells. Endothelial-like cells derived from hTGSCs were cultured on Matrigel, tube-like structure
formations were followed as an indication for functional endothelial differentiation. hTGSCs successfully differentiate into various cell types with a broad range of functional abilities using an in vitro approach. These findings suggest that hTGSCs may serve a potential stem cell source for tissue engineering and cell therapy of epithelial and endothelial tissue.
an immediate response followed by a functional and
comparable regeneration period, referred to as wound healing.
Although normal wounds do not need much attention during
the healing period, chronic (non-healing) wounds are the
major challenge of current dermatological applications.
Therefore, developing new, safe, and effective wound healing
drugs has always been an attractive area of international
research. In the current study, sodium pentaborate
pentahydrate (NaB), pluronics (Plu; F68 and F127), and their
combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results
revealed that NaB significantly increased migration capacity
and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important
growth factor and cytokines (vascular endothelial growth
factor (VEGF), transforming growth factor beta (TGF-β),
and tumor necrosis factor alpha (TNF-α)). NaB containing
hydrogel co-formulated with pluronics was also investigated
for their wound healing activities using a full thickness wound
model in rats. Macroscopic and histopathological analysis
confirmed that wounds in combination gel-treated groups
healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic
wounds. However, further studies should be conducted to
explore its exact action of mechanism and effects of this
formulation on chronic wounds.
applications, displaying nontoxic, osteogenic, and odontogenic-inducing characteristics with remarkable antibacterial activity against S. mutans, and are hence potentially able to prevent secondary caries.
factors during the fermentation process such as temperature, ethanol, compounds released as the result of pretreatment procedures, and osmotic stress. An ideal strain should be able to grow under different stress conditions occurred at different fermentation steps. Development of tolerant yeast strains can be achieved by reprogramming pathways supporting the ethanol metabolism by regulating the energy balance and detoxicification processes. Complex gene interactions should
be solved for an in-depth comprehension of the yeast stress tolerance mechanism. Genetic engineering as a powerful biotechnological tool is required to design new strategies for increasing the ethanol fermentation performance.Upregulation of stress tolerance genes by recombinant DNA technology can be a useful approach to overcome inhibitory situations. This review presents the application of several genetic engineering strategies to increase ethanol yield under different stress
conditions including inhibitor tolerance, ethanol tolerance, thermotolerance, and osmotolerance.
Faujasite X and Linde type A zeolites were synthesized, and following ion exchange with Ag+ and Zn++ ions they were found to exhibit
antimicrobial effects against bacteria (E. coli, P. aeruginosa, and S. aureus), yeast (C. albicans and C. glabrata), and fungi (A. niger and
P. expansum). Zeolites-X and -A containing silver and zinc ions were then mixed with various coating materials, including paints and polypropylene, to develop antimicrobial composites. The long-term antimicrobial characteristics of zeolite-containing composite materials were investigated by inoculating selected microorganisms onto the surface of the materials. The results indicated that the higher the zeolite concentration present in the composite, the more long-term antimicrobial activity was achieved. Silver-ion–exchanged zeolites were more effective against bacterial and candidal species, while zinc zeolites exhibited noticeable antifungal properties. Materials manufactured with metal-ion–exchanged zeolites would prevent microbial growth on surfaces, reducing cross-contamination and infection risk as well as the microbial degradation of products.
ratio, ion exchanged with Ag+, Zn2+, and Cu2+ ions were investigated individually. The study presents the synthesis and manufacture of four different zeolite types characterized by scanning electron microscopy and X-ray diffraction. The ion loading capacity of the zeolites was examined and compared with the antimicrobial characteristics against a broad range of
microorganisms including bacteria, yeast, and mold. It was observed that Ag+ ion-loaded zeolites exhibited more antibacterial activity with respect to other metal ion-embedded zeolite samples. The results clearly support that various synthetic zeolites can be ion exchanged with Ag+, Zn2+, and Cu2+ ions to acquire antimicrobial properties or ion-releasing characteristics to provide prolonged or stronger activity. The current study suggested that zeolite formulations could be combined with various materials used in manufacturing medical devices, surfaces, textiles, or household items where antimicrobial properties are required.
range antimicrobial agents and increasing efficiency of existing antibiotics are under great interest among scientists. Some psychotropic drugs not only reverse microbial antibiotic
resistance but also exhibit direct antimicrobial activity against several biological targets. In the present study, 16 different psychotropic drugs including sertraline, paroxetine,
aripiprazole, fluvoxamine, moclobemide, venlafaxine, mianserin, trazodone, mirtazapine, clomipramine,
alprazolam, escitalopram, citaloprame, fluoxetine, gabapentin and reboxetine have been examined for their antimicrobial properties against wide range of bacteria, yeast and fungi using disc-diffusion and micro-well dilution assays. The results revealed that except FOR gabapentin, venlafaxine, moclobemide and alprazolam, the remaining drugs tested in this study showed various antimicrobial activities. Selective serotonin reuptake inhibitor group drugs including sertraline, paroxetine, fluvoxamine and fluoxetine displayed broad range
antibacterial activity compared to other psychotropic drugs. Among them, sertraline was also found to be effective against Candida albicans and Aspergillus niger. Exploring antimicrobial activities will increase the use and application of these psychotropic drugs in clinical approaches. However, in vivo studies and clinical trials are strictly required to evaluate efficiencies of these chemicals for the treatment of systemic microbial infections.
remains controversial in the analysis of experimental and clinical data. The objective of this study was to investigate the
relationship between blood and urine boron concentrations
and obesity in normal, overweight, obese, and morbidly obese
subjects in different age groups. A total of 105 subjects were
categorized into 12 groups based on body mass index and
three different age levels: as young adult (18 to 34 years
old), adult (35 to 54 years old), and older adult (greater than
55 years old). Age, gender, body mass index, and blood and
urine boron concentrations were recorded for each subject.
There were 50 women and 55 men, with a mean age of
44.63 ± 17.9 years. Blood and urine boron concentrations
were similar among the groups (p = 0.510 and p = 0.228,
respectively). However, a positive correlation between age
and blood boron concentration (p = 0.001) was detected in
contrast to the presence of a negative correlation between
age and urine boron concentration (p = 0.027). Multiple linear
regression analysis showed that there was no significant relationship between gender, age, and quantitative values of body mass index for each subject, and blood and urine boron
concentrations. Although the relationship between boron and
obesity has not been confirmed, changes of blood and urine
boron concentrations with age may have some physiologic
sequences to cause obesity.
Industrial relevance: V. speciosum is used as a wound healing agent in folk medicine without any scientific proofs. The current study was conducted to explore its potential activity in wound healing using in vitro approaches. Further studies are highly warranted to identify active molecules in the extract that need to be examined in in vivo and clinical studies for an efficient wound healing drug development. Determining active constituents in the extract would be an economical and safe option for clinical wound healing approaches.
Keywords. Verbascum speciosum; methanol extract; wound healing; fibroblast cells; angiogenesis
forms of wounds, are generally accompanied with lifethreatening infections, inflammation, reduced angiogenesis,
inadequate extracellular matrix production, and lack of growth
factor stimulation. In the current study, a new antimicrobial
carbopol-based hydrogel formulated with boron and pluronic
block copolymers was evaluated for its healing activity using
in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process.Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.
lineages. Researchers have recently focused on transplanting
stem cells with bioconductive and/or bioinductive materials that can provide cell commitment to the desired cell lineages. In the present study, effects of pluronic block copolymers (F68, F127 and P85) on in vitro myo- and neurogenic differentiation of human tooth germ stem cells (hTGSCs) were investigated. As
P85 was found to exert considerable toxicity to hTGSCs even at low concentrations, it was not evaluated for further differentiation experiments. Immunocytochemical analysis, gene and protein expression studies revealed that while F68 treatment increased lineage-specific gene expression in both
myo- and neuro-genically differentiated cells, F127 did not result in any remarkable difference compared to cells treated with differentiation medium. Subsequent studies are required to explore the exact mechanisms of how F68 increases the myogenic and neurogenic differentiation of hTGSCs. The present work indicates that pluronic F68 might be used in
functional skeletal and neural tissue engineering applications.
is not fully elucidated for embryonic and adult body development, and tissue regeneration. Although optimized amount of boron supplement has been shown to be essential for normal gestational development in zebrafish and frog and beneficial for bone regeneration in higher animals, effects of boron on myogenesis and myo-regeneration remains to be solved. In the current study, we investigated dose-dependent activity of boric acid on myogenic differentiation of human adipose-derived stem cells (hADSCs) using immunocytochemical, gene, and protein expression analysis. The results revealed that while low- (81.9 μM) and high-dose (819.6 μM) boron treatment increased myogenic gene expression levels such as myosin heavy chain (MYH), MyoD, myogenin, and desmin at day 4 of differentiation, high-dose treatment decreased myogenic-related gene and protein levels at day 21 of differentiation, confirmed by immunocytochemical analysis. The findings of the study present not only an understanding of boron’s effect on myogenic differentiation but also an opportunity for the development of scaffolds to be used in skeletal tissue engineering and supplements for embryonic muscle growth. However, fine dose tuning and treatment period arranging are highly warranted as boron treatment over required concentrations and time might result in detrimental outcomes to myogenesis and myo-regeneration.
cancers, with a high morbidity rate, even in developed
countries. In the present study, the curative effect of the
Schiff base (SB) heterodinuclear copper(II)Mn(II) complex
on diethylnitrosamine (DEN)-induced liver carcinoma was
investigated. Hepatocarcinoma was initiated by an injection
of DEN and promoted by phenobarbital (0.05%) in the diet.
In addition, the potential nephrotoxicity of SB was evaluated
in a cisplatin-induced nephrotoxicity model. Rats were
administered the SB complex (1 and 2 mg/kg body weight/
day) for 24 weeks, and cancer progression was investigated
by macroscopic, histopathological, and western blot
examinations. The administration of SB decreased the
incidence and the number of hepatic nodules in a dosedependent manner by regulating inflammation response
and the apoptotic pathway. Western blot analyses from the
livers of rats treated with SB after DEN induction showed
significantly enhanced Bax and caspase-3 levels, with a
marked decrease in the levels of Bcl-2, NF-κB p65 and
cyclooxygenase (COX)-2. Results from the nephrotoxicity
study showed that, whereas cisplatin increased serum urea
nitrogen and creatinine levels, no increase in serum
biochemical parameters was detected in SB-treated
animals. Moreover, protein levels of NF-E2-related factor-2
(Nrf2) and heme oxygenase-1 were lower, whereas nuclear
factor-κB (NF-κB p65) and activator protein-1 levels were
higher in the kidneys of cisplatin-treated animals compared
with that of the SB groups. Therefore, the SB complex could
be an alternative chemotherapeutic option for liver cancer
treatment once its safety in clinical applications has been
examined.
osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type
and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In
the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calciummineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highlywarranted for
the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics.
The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.
conditions or not. In the current study, effects of boron on the cryopreservation of human tooth germ stem cells (hTGSCs) were evaluated for the first time. The impacts of various boron concentrations (sodium pentaborate pentahydrate (NaB)) were tested on characterized hTGSCs viability for different time intervals (24, 48, and 72 h). 20 lg/ml NaB with lower Me2SO concentration was found to display positive effects on hTGSCs during repeated freezing and defrosting cycles, and long-term cryopreservation. After thawing, cells were analyzed for their surface antigens and differentiation capacity. hTGSCs were successfully cryopreserved without any change in their mesenchymal stem cell characteristics as they were treated with boron containing freezing medium. In addition, fatty acid composition was examined to demonstrate membrane fatty acid profiles after freeze-thawing. Besides, NaB treatment extended osteogenic and chondrogenic differentiation of hTGSCs remarkably after long-term cryopreservation with
respect to control groups. The study clearly suggests that NaB has a protective role on the survival of hTGSCs in short- and long-term cryopreservation. Due to the possible storage of hTGSCs at early ages, development of a functional and reliable cryopreservation media can be designed as a future solution
to the dental stem cell banking.
reductase inhibitors exert neuroprotective functions in animal
models of neurodegenerative disorders. In view of these
promising observations, we were interested in whether
HMG-CoA reductase inhibition would affect epileptiform
activity in the brain. To elucidate this issue, atorvastatin,
simvastatin and rosuvastatin were administered orally at a
dose of 20 mg/kg each for 3 days and their anti-epileptic
activities were tested and compared in rats. Epileptiform
activity in the brain was induced by an intracortical
penicillin G injection. Among HMG-CoA reductase inhibitors,
simvastatin-treatment was less effective in terms of
spike frequency as compared with atorvastatin- and rosuvastatin-
treated animals. Atorvastatin treatment reduced
spike frequencies and amplitudes significantly throughout
the experiment. However, the most pronounced anti-epileptic
effect was observed in rosuvastatin-treated animals, which
was associated with improved blood–brain barrier (BBB)
integrity, increased expression of endothelial nitric oxide
synthase (eNOS) mRNA and decreased expressions of
pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition
of eNOS activity with L-NG-Nitroarginine Methyl Ester
(L-NAME) reversed the anti-epileptic effect of rosuvastatin
significantly. However, L-NAME did not alter the effect of
rosuvastatin on the levels of p53, Bax and caspase-3 mRNA
expression. Here, we provide evidence that among
HMG-CoA reductase inhibitors, rosuvastatin was the most
effective statin on the reduction of epileptiform activity,
which was associated with improved BBB permeability,
increased expression of eNOS and decreased expressions
of pro-apoptotic p53, Bax and caspase-3. Our observation
also revealed that the anti-epileptic effect of rosuvastatin
was dependent on the increased expression level of eNOS.
The robust anti-epileptic effect encourages proof-of-concept
studies with rosuvastatin in human epilepsy patients with
hypercholesterolemia.
promising primary cell source for mainly tooth tissue engineering. Interaction of mesenchymal stem cell with epithelial and
endothelial cells is strictly required for an intact tooth morphogenesis. Therefore, it is important to investigate whether human tooth germ stem cells (hTGSCs) derived from wisdom tooth are suitable for endothelial and epithelial cell transformation in
dental tissue regeneration approaches. Differentiation into endothelial and epithelial cell lineages were mimicked under
defined conditions, confirmed by real time PCR, western blotting and immunocytochemical analysis by qualitative and
quantitative methods. HUVECs and HaCaT cells were used as positive controls for the endothelial and epithelial
differentiation assays, respectively. Immunocytochemical and western blotting analysis revealed that terminally differentiated
cells expressed cell-lineage markers including CD31, VEGFR2, VE-Cadherin, vWF (endothelial cell markers), and cytokeratin
(CK)-17, CK-19, EpCaM, vimentin (epithelial cell markers) in significant levels with respect to undifferentiated control cells.
Moreover, high expression levels of VEGFR1, VEGFR2, VEGF, CK-18, and CK-19 genes were detected in differentiated
endothelial and epithelial-like cells. Endothelial-like cells derived from hTGSCs were cultured on Matrigel, tube-like structure
formations were followed as an indication for functional endothelial differentiation. hTGSCs successfully differentiate into various cell types with a broad range of functional abilities using an in vitro approach. These findings suggest that hTGSCs may serve a potential stem cell source for tissue engineering and cell therapy of epithelial and endothelial tissue.
an immediate response followed by a functional and
comparable regeneration period, referred to as wound healing.
Although normal wounds do not need much attention during
the healing period, chronic (non-healing) wounds are the
major challenge of current dermatological applications.
Therefore, developing new, safe, and effective wound healing
drugs has always been an attractive area of international
research. In the current study, sodium pentaborate
pentahydrate (NaB), pluronics (Plu; F68 and F127), and their
combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results
revealed that NaB significantly increased migration capacity
and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important
growth factor and cytokines (vascular endothelial growth
factor (VEGF), transforming growth factor beta (TGF-β),
and tumor necrosis factor alpha (TNF-α)). NaB containing
hydrogel co-formulated with pluronics was also investigated
for their wound healing activities using a full thickness wound
model in rats. Macroscopic and histopathological analysis
confirmed that wounds in combination gel-treated groups
healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic
wounds. However, further studies should be conducted to
explore its exact action of mechanism and effects of this
formulation on chronic wounds.
applications, displaying nontoxic, osteogenic, and odontogenic-inducing characteristics with remarkable antibacterial activity against S. mutans, and are hence potentially able to prevent secondary caries.
factors during the fermentation process such as temperature, ethanol, compounds released as the result of pretreatment procedures, and osmotic stress. An ideal strain should be able to grow under different stress conditions occurred at different fermentation steps. Development of tolerant yeast strains can be achieved by reprogramming pathways supporting the ethanol metabolism by regulating the energy balance and detoxicification processes. Complex gene interactions should
be solved for an in-depth comprehension of the yeast stress tolerance mechanism. Genetic engineering as a powerful biotechnological tool is required to design new strategies for increasing the ethanol fermentation performance.Upregulation of stress tolerance genes by recombinant DNA technology can be a useful approach to overcome inhibitory situations. This review presents the application of several genetic engineering strategies to increase ethanol yield under different stress
conditions including inhibitor tolerance, ethanol tolerance, thermotolerance, and osmotolerance.
Faujasite X and Linde type A zeolites were synthesized, and following ion exchange with Ag+ and Zn++ ions they were found to exhibit
antimicrobial effects against bacteria (E. coli, P. aeruginosa, and S. aureus), yeast (C. albicans and C. glabrata), and fungi (A. niger and
P. expansum). Zeolites-X and -A containing silver and zinc ions were then mixed with various coating materials, including paints and polypropylene, to develop antimicrobial composites. The long-term antimicrobial characteristics of zeolite-containing composite materials were investigated by inoculating selected microorganisms onto the surface of the materials. The results indicated that the higher the zeolite concentration present in the composite, the more long-term antimicrobial activity was achieved. Silver-ion–exchanged zeolites were more effective against bacterial and candidal species, while zinc zeolites exhibited noticeable antifungal properties. Materials manufactured with metal-ion–exchanged zeolites would prevent microbial growth on surfaces, reducing cross-contamination and infection risk as well as the microbial degradation of products.
ratio, ion exchanged with Ag+, Zn2+, and Cu2+ ions were investigated individually. The study presents the synthesis and manufacture of four different zeolite types characterized by scanning electron microscopy and X-ray diffraction. The ion loading capacity of the zeolites was examined and compared with the antimicrobial characteristics against a broad range of
microorganisms including bacteria, yeast, and mold. It was observed that Ag+ ion-loaded zeolites exhibited more antibacterial activity with respect to other metal ion-embedded zeolite samples. The results clearly support that various synthetic zeolites can be ion exchanged with Ag+, Zn2+, and Cu2+ ions to acquire antimicrobial properties or ion-releasing characteristics to provide prolonged or stronger activity. The current study suggested that zeolite formulations could be combined with various materials used in manufacturing medical devices, surfaces, textiles, or household items where antimicrobial properties are required.
range antimicrobial agents and increasing efficiency of existing antibiotics are under great interest among scientists. Some psychotropic drugs not only reverse microbial antibiotic
resistance but also exhibit direct antimicrobial activity against several biological targets. In the present study, 16 different psychotropic drugs including sertraline, paroxetine,
aripiprazole, fluvoxamine, moclobemide, venlafaxine, mianserin, trazodone, mirtazapine, clomipramine,
alprazolam, escitalopram, citaloprame, fluoxetine, gabapentin and reboxetine have been examined for their antimicrobial properties against wide range of bacteria, yeast and fungi using disc-diffusion and micro-well dilution assays. The results revealed that except FOR gabapentin, venlafaxine, moclobemide and alprazolam, the remaining drugs tested in this study showed various antimicrobial activities. Selective serotonin reuptake inhibitor group drugs including sertraline, paroxetine, fluvoxamine and fluoxetine displayed broad range
antibacterial activity compared to other psychotropic drugs. Among them, sertraline was also found to be effective against Candida albicans and Aspergillus niger. Exploring antimicrobial activities will increase the use and application of these psychotropic drugs in clinical approaches. However, in vivo studies and clinical trials are strictly required to evaluate efficiencies of these chemicals for the treatment of systemic microbial infections.
remains controversial in the analysis of experimental and clinical data. The objective of this study was to investigate the
relationship between blood and urine boron concentrations
and obesity in normal, overweight, obese, and morbidly obese
subjects in different age groups. A total of 105 subjects were
categorized into 12 groups based on body mass index and
three different age levels: as young adult (18 to 34 years
old), adult (35 to 54 years old), and older adult (greater than
55 years old). Age, gender, body mass index, and blood and
urine boron concentrations were recorded for each subject.
There were 50 women and 55 men, with a mean age of
44.63 ± 17.9 years. Blood and urine boron concentrations
were similar among the groups (p = 0.510 and p = 0.228,
respectively). However, a positive correlation between age
and blood boron concentration (p = 0.001) was detected in
contrast to the presence of a negative correlation between
age and urine boron concentration (p = 0.027). Multiple linear
regression analysis showed that there was no significant relationship between gender, age, and quantitative values of body mass index for each subject, and blood and urine boron
concentrations. Although the relationship between boron and
obesity has not been confirmed, changes of blood and urine
boron concentrations with age may have some physiologic
sequences to cause obesity.
Industrial relevance: V. speciosum is used as a wound healing agent in folk medicine without any scientific proofs. The current study was conducted to explore its potential activity in wound healing using in vitro approaches. Further studies are highly warranted to identify active molecules in the extract that need to be examined in in vivo and clinical studies for an efficient wound healing drug development. Determining active constituents in the extract would be an economical and safe option for clinical wound healing approaches.
Keywords. Verbascum speciosum; methanol extract; wound healing; fibroblast cells; angiogenesis