Browsing by Subject "Rats"

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Open Access
4,5-dianilinophtalimide protects neuroendocrine cells against serum deprivation-induced stress and apoptosis
(2013) Ergin V.; Erdogan, M.; Karasu Ç.; Menevşe, A.
OBJECTIVE: The aim of this study was to reveal the effects of 4,5-dianilinophthalimide (DAPH), which inhibits amyloid β fibrillization, against serum deprivation (SD)-induced apoptosis and the possible mechanisms in differentiated PC12 neuron cells. METHODS: Firstly, we evaluated whether DAPH protects cell viability exposed to SD by MTT assay. Next, we examined the changes of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73) and cleaved-CASP3 (Asp175) profiles by immunoblotting, in PC12 cells exposed to SD. Intracellular reactive oxygen species (ROS) level was also measured. RESULTS: SD induced apoptosis accompanied by up-regulation of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73), cleaved-CASP3 (Asp175) and intracellular ROS content. Co-treatment with nontoxic doses of DAPH prevented apoptosis by the attenuation of activated proteins and reduction of ROS level. These results suggest that serum deprivation-induced apoptosis inhibited by DAPH administration. CONCLUSION: We have provided for the first evidence that DAPH has a neuroprotective effect on SD-caused stress, probably via contributing the reestablishment of redox homeostasis. © 2013 Neuroendocrinology Letters.
Open Access
Amphiphilic peptide coated superparamagnetic iron oxide nanoparticles for in vivo MR tumor imaging
(Royal Society of Chemistry, 2016) Ozdemir, A.; Ekiz, M. S.; Dilli, A.; Güler, Mustafa O.; Tekinay, A. B.
Magnetic resonance imaging (MRI) is a noninvasive imaging technique that provides high spatial resolution and depth with pronounced soft-tissue contrast for in vivo imaging. A broad variety of strategies have been employed to enhance the diagnostic value of MRI and detect tissue abnormalities at an earlier stage. Superparamagnetic iron oxide nanoparticles (SPIONs) are considered to be suitable candidates for effective imaging due to their small size, versatile functionality and better biocompatibility. Here, we demonstrate that coating SPIONs with proline-rich amphiphilic peptide molecules through noncovalent interactions leads to a water-dispersed hybrid system suitable as an MRI contrast agent. Cellular viability and uptake of amphiphilic peptide coated SPIONs (SPION/K-PA) were evaluated with human vascular endothelial cells (HUVEC) and estrogen receptor (ER) positive human breast adenocarcinoma (MCF-7) cells. The efficiency of SPION/K-PA as MRI contrast agents was analyzed in Sprague-Dawley rats with mammary gland tumors. MR imaging showed that SPION/K-PA effectively accumulated in tumor tissues, enhancing their imaging potential. Although nanoparticles were observed in reticuloendothelial system organs (RES) and especially in the liver and kidney immediately after administration, the MR signal intensity in these organs diminished after 1 h and nanoparticles were subsequently cleared from these organs within two weeks. Histological observations also validated the accumulation of nanoparticles in tumor tissue at 4 h and their bioelimination from the organs of both healthy and tumor-bearing rats after two weeks.
Open Access
Angiogenic peptide nanofibers repair cardiac tissue defect after myocardial infarction
(Acta Materialia Inc, 2017) Rufaihah, A. J.; Yasa, I. C.; Ramanujam, V. S.; Arularasu, S. C.; Kofidis, T.; Güler, Mustafa O.; Tekinay, A. B.
Myocardial infarction remains one of the top leading causes of death in the world and the damage sustained in the heart eventually develops into heart failure. Limited conventional treatment options due to the inability of the myocardium to regenerate after injury and shortage of organ donors require the development of alternative therapies to repair the damaged myocardium. Current efforts in repairing damage after myocardial infarction concentrates on using biologically derived molecules such as growth factors or stem cells, which carry risks of serious side effects including the formation of teratomas. Here, we demonstrate that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization in cardiovascular tissue after myocardial infarction, without the addition of any biologically derived factors or stem cells. When the GAG mimetic nanofiber gels were injected in the infarct site of rodent myocardial infarct model, increased VEGF-A expression and recruitment of vascular cells was observed. This was accompanied with significant degree of neovascularization and better cardiac performance when compared to the control saline group. The results demonstrate the potential of future clinical applications of these bioactive peptide nanofibers as a promising strategy for cardiovascular repair. Statement of Significance We present a synthetic bioactive peptide nanofiber system can enhance cardiac function and enhance cardiovascular regeneration after myocardial infarction (MI) without the addition of growth factors, stem cells or other biologically derived molecules. Current state of the art in cardiac repair after MI utilize at least one of the above mentioned biologically derived molecules, thus our approach is ground-breaking for cardiovascular therapy after MI. In this work, we showed that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization and cardiomyocyte differentiation for the regeneration of cardiovascular tissue after myocardial infarction in a rat infarct model. When the peptide nanofiber gels were injected in infarct site at rodent myocardial infarct model, recruitment of vascular cells was observed, neovascularization was significantly induced and cardiac performance was improved. These results demonstrate the potential of future clinical applications of these bioactive peptide nanofibers as a promising strategy for cardiovascular repair.
Open Access
Antiangiogenic response after 70% hepatectomy and its relationship with hepatic regeneration and angiogenesis in rats
(2010) Dogrul, A.B.; Colakoglu, T.; Kosemehmetoglu, K.; Birben, E.; Yaman, E.; Gedikoglu G.; Abbasoglu O.
Background: The aim of this study was to evaluate the antiangiogenic response and its relation to regeneration and angiogenesis after 70% hepatectomy in a rat model. Methods: Sixty-four Wistar albino rats were included in the study. Animals were allocated into 8 groups (n = 8). After a 70% hepatectomy, liver regeneration, angiogenesis, and antiangiogenic response were evaluated in the remnant liver on days 0, 1, 2, 3, 5, 7, 10, and 14. Regeneration and angiogenesis were determined with immunoreactivity to proliferating cell nuclear antigen and vascular endothelial growth factor. Antiangiogenic response was evaluated by detecting collagen 18 m RNA with reverse transcriptase polymerase chain reaction. Results: We showed that liver regeneration peaked at day 1, whereas angiogenesis in the periportal and perisinusoidal areas reached their peak values on days 3 and 7, respectively. Both regeneration and angiogenic activity around perisinusoidal hepatocytes returned to basal activity on the day 10. Antiangiogenic response first appeared on day 5, reached a peak on day 10, and returned to basal values on day 14. Conclusion: Collagen18 mRNA expression is present in the normal liver during the regenerative process. We suggest that the stimulus that causes the cessation of regeneration process may come from hepatocytes, and collagen 18 produced by hepatocytes may modulate this event by inhibiting the angiogenesis. © 2010 Mosby, Inc. All rights reserved.
Open Access
Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells
(2004) Konu Ö.; Xu X.; Ma J.Z.; Kane J.; Wang J.; Shi, S.J.; Li, M.D.
Maintenance of cellular homeostasis is integral to appropriate regulation of cellular signaling and cell growth and division. In this study, we report the development and quality assessment of a pathway-focused microarray comprising genes involved in cellular homeostasis. Since nicotine is known to have highly modulatory effects on the intracellular calcium homeostasis, we therefore tested the applicability of the homeostatic pathway-focused microarray on the gene expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the untreated control cells. We first provided a detailed description of the focused array with respect to its gene and pathway content and then assessed the array quality using a robust regression procedure that allows for the exclusion of unreliable measurements while decreasing the number of false positives. As a result, the mean correlation coefficient between duplicate measurements of the arrays used in this study (control vs. nicotine treatment, three samples each) has increased from 0.974±0.017 to 0.995±0.002. Furthermore, we found that nicotine affected various structural and signaling components of the AKT/PKB signaling pathway and protein synthesis and degradation processes in PC-12 cells. Since modulation of intracellular calcium concentrations ([Ca2+]i) and phosphatidylinositol signaling are important in various biological processes such as neurotransmitter release and tissue pathogenesis including tumor formation, we expect that the homeostatic pathway-focused microarray potentially can be used for the identification of unique gene expression profiles in comparative studies of drugs of abuse and diverse environmental stimuli, such as starvation and oxidative stress. © 2003 Elsevier B.V. All rights reserved.
Open Access
Chitosan scaffolds with BMP-6 loaded alginate microspheres for periodontal tissue engineering
(2012) Soran, Z.; Aydin, R.S.T.; Gumusderelioglu, M.
The aim of this study is to develop an effective growth factor releasing scaffold-microsphere system for promoting periodontal tissue engineering. Bone morphogenetic protein-6 (BMP-6)-loaded alginate microspheres in narrow size distribution were produced by optimising electrospraying conditions. The addition of these microspheres to chitosan gels produced a novel scaffold in which not only the pore sizes and interconnectivity were preserved, but also a controlled release vehicle was generated. Loading capacity was adjusted as 50ng or 100ng BMP-6 for each scaffold and the controlled release behaviour of BMP-6 from chitosan scaffolds was observed during seven days. Cell culture studies were carried out with rat mesenchymal stem cells derived from bone marrow in three groups; chitosan scaffolds, chitosan scaffolds containing BMP-6-loaded alginate microspheres and chitosan scaffolds with free BMP-6 in culture medium. Results showed that controlled delivery of BMP-6 from alginate microspheres has a significant effect on osteogenic differentiation. © 2012 Informa UK Ltd All rights reserved.
Open Access
Development of a thulium (Tm:YAP) laser system for brain tissue ablation
(2011) Bilici, T.; Mutlu, S.; Kalaycioglu H.; Kurt, A.; Sennaroglu, A.; Gulsoy, M.
In this study, a thulium (Tm:YAP) laser system was developed for brain surgery applications. As the Tm:YAP laser is a continuous-wave laser delivered via silica fibers, it would have great potential for stereotaxic neurosurgery with highest local absorption in the IR region. The laser system developed in this study allowed the user to set the power level, exposure time, and modulation parameters (pulse width and on-off cycles). The Tm:YAP laser beam (200-600 mW, 69-208 W/cm 2) was delivered from a distance of 2 mm to cortical and subcortical regions of ex-vivo Wistar rat brain tissue samples via a 200-μm-core optical fiber. The system performance, dosimetry study, and ablation characteristics of the Tm:YAP laser were tested at different power levels by maximizing the therapeutic effects and minimizing unwanted thermal side-effects. The coagulation and ablation diameters were measured under microscope. The maximum ablation efficiency (100 × ablation diameter/coagulation diameter) was obtained when the Tm:YAP laser system was operated at 200 mW for 10 s. At this laser dose, the ablation efficiency was found to be 71.4% and 58.7% for cortical and subcortical regions, respectively. The fiber-coupled Tm:YAP laser system in hence proposed for the delivery of photothermal therapies in medical applications. © 2011 Springer-Verlag London Ltd.
Open Access
Effect of double growth factor release on cartilage tissue engineering
(2013) Ertan, A.B.; Yilgor P.; Bayyurt, B.; Çalikoǧlu, A.C.; Kaspar Ç.; Kök F.N.; Kose G.T.; Hasirci V.
The effects of double release of insulin-like growth factor I (IGF-I) and growth factor β1 (TGF-β1) from nanoparticles on the growth of bone marrow mesenchymal stem cells and their differentiation into cartilage cells were studied on PLGA scaffolds. The release was achieved by using nanoparticles of poly(lactic acid-co-glycolic acid) (PLGA) and poly(N-isopropylacrylamide) (PNIPAM) carrying IGF-I and TGF-β1, respectively. On tissue culture polystyrene (TCPS), TGF-β1 released from PNIPAM nanoparticles was found to have a significant effect on proliferation, while IGF-I encouraged differentiation, as shown by collagen type II deposition. The study was then conducted on macroporous (pore size 200-400μm) PLGA scaffolds. It was observed that the combination of IGF-I and TGF-β1 yielded better results in terms of collagen type II and aggrecan expression than GF-free and single GF-containing applications. It thus appears that gradual release of a combination of growth factors from nanoparticles could make a significant contribution to the quality of the engineered cartilage tissue. © 2011 John Wiley & Sons, Ltd.
Open Access
A glycosaminoglycan mimetic peptide nanofiber gel as an osteoinductive scaffold
(Royal Society of Chemistry, 2016) Tansik, G.; Kilic, E.; Beter, M.; Demiralp, B.; K.Sendur, G.; Can, N.; Ozkan, H.; Ergul, E.; Güler, Mustafa O.; Tekinay, A. B.
Biomineralization of the extracellular matrix (ECM) plays a crucial role in bone formation. Functional and structural biomimetic native bone ECM components can therefore be used to change the fate of stem cells and induce bone regeneration and mineralization. Glycosaminoglycan (GAG) mimetic peptide nanofibers can interact with several growth factors. These nanostructures are capable of enhancing the osteogenic activity and mineral deposition of osteoblastic cells, which is indicative of their potential application in bone tissue regeneration. In this study, we investigated the potential of GAG-mimetic peptide nanofibers to promote the osteogenic differentiation of rat mesenchymal stem cells (rMSCs) in vitro and enhance the bone regeneration and biomineralization process in vivo in a rabbit tibial bone defect model. Alkaline phosphatase (ALP) activity and Alizarin red staining results suggested that osteogenic differentiation is enhanced when rMSCs are cultured on GAG-mimetic peptide nanofibers. Moreover, osteogenic marker genes were shown to be upregulated in the presence of the peptide nanofiber system. Histological and micro-computed tomography (Micro-CT) observations of regenerated bone defects in rabbit tibia bone also suggested that the injection of a GAG-mimetic nanofiber gel supports cortical bone deposition by enhancing the secretion of an inorganic mineral matrix. The volume of the repaired cortical bone was higher in GAG-PA gel injected animals. The overall results indicate that GAG-mimetic peptide nanofibers can be utilized effectively as a new bioactive platform for bone regeneration. © 2016 The Royal Society of Chemistry.
Open Access
Identification of novel neutralizing single-chain antibodies against vascular endothelial growth factor receptor 2
(2011) Erdag, B.; Koray Balcioglu, B.; Ozdemir Bahadir, A.; Serhatli, M.; Kacar O.; Bahar, A.; Seker, U.O.S.; Akgun, E.; Ozkan, A.; Kilic, T.; Tamerler, C.; Baysal, K.
Human vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2/kinase domain receptor [KDR]) play a crucial role in angiogenesis, which makes the VEGFR-2 signaling pathway a major target for therapeutic applications. In this study, a single-chain antibody phage display library was constructed from spleen cells of mice immunized with recombinant human soluble extracellular VEGFR-2/KDR consisting of all seven extracellular domains (sKDR D1-7) to obtain antibodies that block VEGF binding to VEGFR-2. Two specific single-chain antibodies (KDR1.3 and KDR2.6) that recognized human VEGFR-2 were selected; diversity analysis of the clones was performed by BstNI fingerprinting and nucleotide sequencing. The single-chain variable fragments (scFvs) were expressed in soluble form and specificity of interactions between affinity purified scFvs and VEGFR-2 was confirmed by ELISA. Binding of the recombinant antibodies for VEGFR-2 receptors was investigated by surface plasmon resonance spectroscopy. In vitro cell culture assays showed that KDR1.3 and KDR2.6 scFvs significantly suppressed the mitogenic response of human umbilical vein endothelial cells to recombinant human VEGF 165 in a dose-dependent manner, and reduced VEGF-dependent cell proliferation by 60% and 40%, respectively. In vivo analysis of these recombinant antibodies in a rat cornea angiogenesis model revealed that both antibodies suppressed the development of new corneal vessels (p < 0.05). Overall, in vitro and in vivo results disclose strong interactions of KDR1.3 and KDR2.6 scFvs with VEGFR-2. These findings indicate that KDR1.3 and KDR2.6 scFvs are promising antiangiogenic therapeutic agents. © 2011 International Union of Biochemistry and Molecular Biology, Inc.
Open Access
Naringenin inhibits neointimal hyperplasia following arterial reconstruction with interpositional vein graft
(Lippincott Williams & Wilkins, 2010) Cayci, C.; Wahlquist, T. C.; Seckin, S. I.; Ozcan, V.; Tekinay, A. B.; Martens, T. P.; Oz, M. C.; Ascherman, J. A.
Vessels respond to injury by a healing process that includes the development of neointima. Stenosis secondary to neointima formation is the main cause of failure following arterial reconstructions. Vessel wall homeostasis is regulated by proinflammatory cytokines that affect smooth muscle cell proliferation, growth, migration, and death. We assessed the hypothesis that naringenin, a flavinoid possessing anti-inflammatory, antioxidant, and antiproliferative activities, reduces neointimal hyperplasia (NIH) following vascular injury.Arterial injury was created by interposition grafting of autologous right superficial epigastric vein graft into the right femoral artery (FA) in 48 male Sprague-Dawley rats. Following injury, the rats were divided into 4 groups (n = 12). Two groups were treated with naringenin (100 mg/kg intraperitoneal q daily) for 2 and 4 weeks each while 2 control groups received normal saline for the same durations. For Sham group (n = 10), the FA and vein were isolated without any additional procedure. Rats were killed at the end of treatment regimen in all groups, and FAs were harvested. Thickness of intima was measured in histologic sections, and levels of platelet derived growth factor (PDGF)-BB, TNFα, and Ki67 labeling index (Ki67 LI) were quantified in immunohistochemical analyses to assess the amount of NIH and mechanisms underlying its formation.Although there was no significant difference between the groups at 2 weeks, neointima thickness was lower in the naringenin treated group at 4 weeks (23.7 ± 2.3 vs. 35.6 ± 2.6 μm in control group; P < 0.001). The levels of PDGF-BB, and TNFα were lower in naringenin treated groups at both 2 weeks (PDGF-BB [0.21% ± 0.03% versus 0.39% ± 0.05% in control group, P < 0.001), TNFα (21.2% ± 0.8% vs. 36.1% ± 1.9% in control group, P < 0.001]) and 4 weeks (PDGF-BB [0.25% ± 0.03% vs. 0.57% ± 0.09% in control group, P < 0.001], TNFα [25.5% ± 1.8% vs. 45.0% ± 2.9% in control group, P < 0.001]). Ki67 LI was lower in naringenin treated groups at 2 weeks (13.9% ± 2.8% vs. 18.7% ± 3.7% in control group, P < 0.05), and at 4 weeks (17.5% ± 2.6% vs. 31.1% ± 4.7% in control group, P < 0.001), indicating a lower level of cellular proliferation.Naringenin reduces NIH following arterial reconstruction. This may be mediated by a decrease in PDGF-BB and TNFα levels and the resulting down-regulation of smooth muscle cells' migration and proliferation.
Open Access
Presentation of functional groups on self-assembled supramolecular peptide nanofibers mimicking glycosaminoglycans for directed mesenchymal stem cell differentiation
(Royal Society of Chemistry, 2017) Yasa, Oncay; Uysal, Ozge; Ekiz, Melis Sardan; Güler, Mustafa O.; Tekinay, Ayse B.
Organizational complexity and functional diversity of the extracellular matrix regulate cellular behaviors. The extracellular matrix is composed of various proteins in the form of proteoglycans, glycoproteins, and nanofibers whose types and combinations change depending on the tissue type. Proteoglycans, which are proteins that are covalently attached to glycosaminoglycans, contribute to the complexity of the microenvironment of the cells. The sulfation degree of the glycosaminoglycans is an important and distinct feature at specific developmental stages and tissue types. Peptide amphiphile nanofibers can mimic natural glycosaminoglycans and/or proteoglycans, and they form a synthetic nanofibrous microenvironment where cells can proliferate and differentiate towards different lineages. In this study, peptide nanofibers were used to provide varying degrees of sulfonation mimicking the natural glycosaminoglycans by forming a microenvironment for the survival and differentiation of stem cells. The effects of glucose, carboxylate, and sulfonate groups on the peptide nanofibers were investigated by considering the changes in the differentiation profiles of rat mesenchymal stem cells in the absence of any specific differentiation inducers in the culture medium. The results showed that a higher sulfonate-to-glucose ratio is associated with adipogenic differentiation and a higher carboxylate-to-glucose ratio is associated with osteochondrogenic differentiation of the rat mesenchymal stem cells. Overall, these results demonstrate that supramolecular peptide nanosystems can be used to understand the fine-tunings of the extracellular matrix such as sulfation profile on specific cell types. © 2017 The Royal Society of Chemistry.
Open Access
Protein-releasing conductive anodized alumina membranes for nerve-interface materials
(Elsevier Ltd, 2016) Altuntas, S.; Buyukserin, F.; Haider, A.; Altinok, B.; Bıyıklı, Necmi; Aslim, B.
Nanoporous anodized alumina membranes (AAMs) have numerous biomedical applications spanning from biosensors to controlled drug delivery and implant coatings. Although the use of AAM as an alternative bone implant surface has been successful, its potential as a neural implant coating remains unclear. Here, we introduce conductive and nerve growth factor-releasing AAM substrates that not only provide the native nanoporous morphology for cell adhesion, but also induce neural differentiation. We recently reported the fabrication of such conductive membranes by coating AAMs with a thin C layer. In this study, we investigated the influence of electrical stimulus, surface topography, and chemistry on cell adhesion, neurite extension, and density by using PC 12 pheochromocytoma cells in a custom-made glass microwell setup. The conductive AAMs showed enhanced neurite extension and generation with the electrical stimulus, but cell adhesion on these substrates was poorer compared to the naked AAMs. The latter nanoporous material presents chemical and topographical features for superior neuronal cell adhesion, but, more importantly, when loaded with nerve growth factor, it can provide neurite extension similar to an electrically stimulated CAAM counterpart.
Open Access
Regulation of Homer and group I metabotropic glutamate receptors by nicotine
(Wiley-Blackwell Publishing Ltd., 2005) Kane, J. K.; Hwang, Y.; Konu, O.; Loughlin, S. E.; Leslie, F. M.; Li, M. D.
The present study focuses on the nicotine-induced modulation of mRNA and protein expression of a number of genes involved in glutamatergic synaptic transmission in rat brain over different time periods of exposure. A subchronic (3 days) but not the chronic (7 or 14 days) administration of nicotine resulted in the up-regulation of Homer2a/b mRNA in the amygdala while in the ventral tegmental area (VTA) no change in expression of either Homer2a/b or Homer1b/c was observed. Although the increase in Homer2a/b mRNA was not translated into the protein level in the amygdala, a slight but significant up-regulation of Homer1b/c protein was observed in the same region at day 3. Both Homer forms were up-regulated at the protein level in the VTA at day 3. In the nucleus accumbens, 14 days of nicotine treatment up-regulated mRNA of Homer2b/c by 68.2% (P < 0.05), while the short form Homer1a gene was down-regulated by 65.0% at day 3 (P < 0.05). In regard to other components of the glutamatergic signalling, we identified an acute and intermittent increase in the mRNA and protein levels of mGluR1 and mGluR5 in the amygdala. In the VTA, however, the effects of nicotine on mGluR mRNA expression were long-lasting but rather specific to mGluR1. Nevertheless, mGluR1 protein levels in the VTA area were up-regulated only at day 3, as in the amygdala. These data provide further evidence for the involvement of nicotine in the glutamatergic neuronal synaptic activity in vivo, suggesting a role for the newly identified Homer proteins in this paradigm.
Open Access
SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome
(Lippincott Williams & Wilkins, 2008) Sabater, L.; Titulaer, M.; Saiz, A.; Verschuuren, J.; Güre, A. O.; Graus, F.
BACKGROUND/OBJECTIVE: We reported that 43% of patients with Lambert-Eaton myasthenic syndrome (LEMS) and small cell lung cancer (SCLC) had an antibody called anti-glial nuclear antibody (AGNA), defined by the immunoreaction with the nuclei of the Bergmann glia of the cerebellum. This study was undertaken to identify the antigen recognized by AGNA and to confirm the association with paraneoplastic LEMS in a larger series. METHODS: We probed a fetal brain cDNA library with AGNA-positive sera. The presence of antibodies against the isolated antigen was detected by immunoblot of phage plaques from two positive clones. We studied 105 patients with LEMS (55 with SCLC), 50 with paraneoplastic neurologic syndromes, SCLC, and Hu antibodies, and 50 with only SCLC. RESULTS: Probing of the fetal brain expression library with AGNA sera resulted in the isolation of SOX1, a highly immunogenic tumor antigen in SCLC. IgG eluted from SOX1 clones produced the same cerebellar immunoreactivity as of AGNA sera. SOX1 antibodies were present in 64% of patients with LEMS and SCLC but in none of the 50 with idiopathic LEMS (p < 0.0001). Compared with paraneoplastic LEMS, the frequency of SOX1 antibodies was significantly lower in patients with Hu antibodies (32%, p = 0.002) and in those with only SCLC (22%). CONCLUSIONS: SOX1 is the antigen recognized by anti-glial nuclear antibody-positive sera. The detection of SOX1 antibodies in patients with Lambert-Eaton myasthenic syndrome (LEMS) predicts the presence of small cell lung cancer and may be used to follow more closely those LEMS patients with no evidence of cancer at the initial workup.
Open Access
Spatial organization of functional groups on bioactive supramolecular glycopeptide nanofibers for differentiation of mesenchymal stem cells (MSCs) to brown adipogenesis
(American Chemical Society, 2016-12) Caliskan, O. S.; Sardan, Ekiz M.; Tekinay, A. B.; Güler, Mustafa O.
Spatial organization of bioactive moieties in biological materials has significant impact on the function and efficiency of these systems. Here, we demonstrate the effect of spatial organization of functional groups including carboxylate, amine, and glucose functionalities by using self-assembled peptide amphiphile (PA) nanofibers as a bioactive scaffold. We show that presentation of bioactive groups on glycopeptide nanofibers affects mesenchymal stem cells (MSCs) in a distinct manner by means of adhesion, proliferation, and differentiation. Strikingly, when the glutamic acid is present in the glycopeptide backbone, the PA nanofibers specifically induced differentiation of MSCs into brown adipocytes in the absence of any differentiation medium as shown by lipid droplet accumulation and adipogenic gene marker expression analyses. This effect was not evident in the other glycopeptide nanofibers, which displayed the same functional groups but with different spatial organization. Brown adipocytes are attractive targets for obesity treatment and are found in trace amounts in adults, which also makes this specific glycopeptide nanofiber system an attractive tool to study molecular pathways of brown adipocyte formation.