Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Conference Object Investigation of the role of Wnt/β-catenin signaling in development of Alzheimer's disease in a zebrafish model of mmyloid-β toxicity(Wiley, 2024) Nazlı, Dilek; Ipekgil, D.; Poyraz, Y. K.; Catak, B.; Sahin, E. Turhanlar; Özhan, GüneşThe Wnt/β-catenin signaling pathway, an evolutionarily conserved and pivotal pathway associated with synapse formation in adulthood, plays a crucial role in Alzheimer's disease (AD). AD, marked by various pathologies, is primarily linked to the accumulation of extracellular beta-amyloid plaques. The interplay between this accumulation and disruptions in the Wnt/β-catenin signaling pathway triggers synaptic degeneration, resulting in synaptic dysfunction and AD progression. In this study, we modeled AD induced by the Aβ42 peptide using adult transgenic (6XTCF) zebrafish. To establish the zebrafish AD model, we employed cerebroventricular microinjection (CVMI) with the Aβ42 peptide. Fish, anesthetized prior to CVMI, were positioned on a stable platform, and the Aβ42 peptide was injected into the telencephalon region of the brain by a capillary needle. Brain samples were collected on 1, 3, 4, 7, and 14 days post-CVMI (dpi) to analyze changes in Aβ42 peptide accumulation, the immune system response, synaptic degeneration, apoptosis, and the expression of genes related to proliferation using qPCR and immunofluorescent staining. To examine the role of the Wnt/β-catenin signaling pathway in the molecular mechanism of AD development, fish exhibiting high levels of regeneration on days 7 and 14 were treated with the IWR-1 drug, which inhibits the Wnt/β-catenin signaling by stabilizing the Axin2 protein, thereby suppressing the regenerative response. Our results revealed that the AD model manifested on 3dpi, with the regenerative response reaching its peak on 7dpi and 14dpi. Treatment with IWR-1 resulted in increased Aβ42 accumulation, accelerated synaptic degeneration, and elevated cell deaths in fish where the Wnt signaling pathway was inhibited. In conclusion, our adult zebrafish AD model is poised to elucidate the molecular mechanisms connecting the Wnt signaling pathway and AD, thereby contributing to the development of alternative therapeutic approaches for AD patients.Article Citation - Scopus: 11Μdacs Platform: a Hybrid Microfluidic Platform Using Magnetic Levitation Technique and Integrating Magnetic, Gravitational, and Drag Forces for Density-Based Rare Cancer Cell Sorting(Elsevier, 2023) Keçili, Seren; Yılmaz, Esra; Özçelik, Özge Solmaz; Anıl İnevi, Müge; Günyüz, Zehra Elif; Yalçın Özuysal, Özden; Özçivici, Engin; Tekin, Hüseyin CumhurCirculating tumor cells (CTCs) are crucial indicators of cancer metastasis. However, their rarity in the bloodstream and the heterogeneity of their surface biomarkers present challenges for their isolation. Here, we developed a hybrid microfluidic platform (microfluidic-based density-associated cell sorting (µDACS) platform) that utilizes density as a biophysical marker to sort cancer cells from the population of white blood cells (WBCs). The platform utilizes the magnetic levitation technique on a microfluidic chip to sort cells based on their specific density ranges, operating under a continuous flow condition. By harnessing magnetic, gravitational, and drag forces, the platform efficiently separates cells. This approach involves a microfluidic chip equipped with a microseparator, which directs cells into top and bottom outlets depending on their levitation heights, which are inversely proportional to their densities. Hence, low-density cancer cells are collected from the top outlet, while high-density WBCs are collected from the bottom outlet. We optimized the sorting efficiency by varying the flow rates, and concentrations of the sorting medium's paramagnetic properties using standard densities of polymeric microspheres. To demonstrate the platform's applicability, we performed hybrid microfluidic sorting on MDA-MB-231 human breast cancer cells and U-937 human monocytes. The results showed efficient sorting of rare cancer cells (≥100 cells/mL) from serum samples, achieving a sorting efficiency of ∼70% at a fast-processing speed of 1 mL h−1. This label-free approach holds promise for rapid and cost-effective CTC sorting, facilitating in-vitro diagnosis and prognosis of cancer. © 2023 The Author(s)Review Citation - WoS: 6Citation - Scopus: 8Molecular Trojan Horses for Treating Lysosomal Storage Diseases(Academic Press, 2023) Leal, Andres Felipe; Rintz, Estera; Çelik, Betül; Ago, Yasuhiko; León, Daniel; İnci, Orhan Kerim; Seyrantepe, VolkanLysosomal storage diseases (LSDs) are caused by monogenic mutations in genes encoding for proteins related to the lysosomal function. Lysosome plays critical roles in molecule degradation and cell signaling through interplay with many other cell organelles, such as mitochondria, endoplasmic reticulum, and peroxisomes. Even though several strategies (i.e., protein replacement and gene therapy) have been attempted for LSDs with promising results, there are still some challenges when hard-to-treat tissues such as bone (i.e., cartilages, ligaments, meniscus, etc.), the central nervous system (mostly neurons), and the eye (i.e., cornea, retina) are affected. Consistently, searching for novel strategies to reach those tissues remains a priority. Molecular Trojan Horses have been well-recognized as a potential alternative in several pathological scenarios for drug delivery, including LSDs. Even though molecular Trojan Horses refer to genetically engineered proteins to overcome the blood-brain barrier, such strategy can be extended to strategies able to transport and deliver drugs to specific tissues or cells using cell-penetrating peptides, monoclonal antibodies, vesicles, extracellular vesicles, and patient-derived cells. Only some of those platforms have been attempted in LSDs. In this paper, we review the most recent efforts to develop molecular Trojan Horses and discuss how this strategy could be implemented to enhance the current efficacy of strategies such as protein replacement and gene therapy in the context of LSDs. © 2023Article Citation - WoS: 4Citation - Scopus: 4Mitigation Potential of Zingerone and Rutin on Toxicity Mechanisms of Nickel To Zebrafish Based on Morphological, Dna Damage and Apoptosis Outcome Analysis(Elsevier, 2023) Köktürk, Mine; Yıldırım, Serkan; Atamanalp, Muhammed; Kılıçoğlu, Metin; Uçar, Arzu; Özhan, Güneş; Alak, GoncaAlthough nickel (Ni) is an important cofactor for various enzymes in biological systems, it can cause serious problems when insufficient or excessive in an organism. Therefore, it is very important to investigate Ni in biological systems, especially in cells with its related pathogenic mechanism. This study was carried out to demonstrate the effects of zingerone (ZO) and rutin (RN) administration against nickel chloride (NiCl2) toxicity on neurobehavioral performance and brain oxidative status in zebrafish (Danio rerio) embryos/larvae on histological perspective. The experimental design of the study, which included twenty groups of fish, each containing 10 embryos, was prepared as semi-static and the trial continued for 96 hpf. In the obtained findings, it was determined that ZO and RN had a mitigating effect in this toxicity table where Ni caused oxidative stress in zebrafish larvae, induced DNA damage and apoptosis. A similar picture is valid for malformation processes as well as survival and hatching rates. These results showed that nickel is toxic to developing embryos via acting different mechanisms. In conclusion, we observed that ZO and RN have a greater effect on physiology, DNA damage and apoptosis than gross morphology, with a significant ameliorative effect.Conference Object Elimination of the B4galnt1 Gene Normalizes Lifespan and Prevents Pathology in Tay-Sachs Disease Mice(Elsevier, 2023) Seyrantepe, VolkanTay-Sachs disease is a neurodegenerative lysosomal storage disorder caused by mutations in the Hexa gene, which encodes the alpha subunit of lysosomal ß-hexaminidase A (HEXA). HEXA is responsible for the conversion of GM2 to GM3, therefore the deficiency leads to the accumulation of GM2 in the lysosomes, neurodegeneration, and eventual death. Currently, there is no efficient therapy for the disease yet.Article Citation - WoS: 5Citation - Scopus: 5De-Sealing Reverses Habitat Decay More Than Increasing Groundcover Vegetation(MDPI, 2023) Couch, Virginia; Salata, Stefano; Saygın, Nicel; Frary, Anne; Arslan, BertanModeling ecosystem services is a growing trend in scientific research, and Nature-based Solutions (NbSs) are increasingly used by land-use planners and environmental designers to achieve improved adaptation to climate change and mitigation of the negative effects of climate change. Predictions of ecological benefits of NbSs are needed early in design to support decision making. In this study, we used ecological analysis to predict the benefits of two NbSs applied to a university masterplan and adjusted our preliminary design strategy according to the first modeling results. Our Area of Interest was the IZTECH campus, which is located in a rural area of the eastern Mediterranean region (Izmir/Turkey). A primary design goal was to improve habitat quality by revitalizing soil. Customized analysis of the Baseline Condition and two NbSs scenarios was achieved by using local values obtained from a high-resolution photogrammetric scan of the catchment to produce flow accumulation and habitat quality indexes. Results indicate that anthropogenic features are the primary cause of habitat decay and that decreasing imperviousness reduces habitat decay significantly more than adding vegetation. This study creates a method of supporting sustainability goals by quickly testing alternative NbSs. The main innovation is demonstrating that early approximation of the ecological benefits of NbSs can inform preliminary design strategy. The proposed model may be calibrated to address specific environmental challenges of a given location and test other forms of NbSs.Review Citation - WoS: 5Citation - Scopus: 5Noncoding Rnas: a New Layer of Functional Rnas(Bentham Science Publishers, 2023) Gürer, Dilek Cansu; Akgül, BünyaminThe conventional central dogma of molecular biology dictates that the genetic information contained within deoxyribonucleic acid (DNA) is passed onto messenger ribonucleic acids (mRNAs), which are then used as templates to synthesize proteins. Although these types of protein-coding genes have been historically prioritized in typical phenotype-genotype studies with a parallel disregard to the rest of the genome, the completion of genome projects has unveiled a surprising layer of genetic information that can play critical roles in cellular processes without coding for proteins. These types of genes are called noncoding genes as they do not code for proteins. Noncoding genes come in different sizes and shapes, and they are just as versatile in carrying out cellular biochemical processes as proteins. In this review, we cover a comprehensive review of housekeeping and regulatory noncoding genes and their mode of action.Review Citation - WoS: 8Citation - Scopus: 8Long Noncoding Rnas in Human Cancer and Apoptosis(Bentham Science Publishers, 2023) Erdoğan, İpek; Sweef, Osama; Akgül, BünyaminGenome annotations have uncovered the production of at least one transcript from nearly all loci in the genome at some given time throughout the development. Surprisingly, many of these transcripts do not code for proteins and are relatively long in size, thus called long noncoding RNAs (lncRNAs). Next- and third-generation sequencing technologies have amassed numerous lncRNAs expressed under different phenotypic conditions, yet many remain to be functionally characterized. LncRNAs regulate gene expression by functioning as scaffold, decoy, signaling, and guide molecules both at the transcriptional and post-transcriptional levels, interacting with different types of macromolecules, such as proteins, DNA, and RNA. Here, we review the potential regulatory role of lncRNAs in apoptosis and cancer as some of these lncRNAs may have the diagnostic and therapeutic potential in cancer.Review Citation - WoS: 14Citation - Scopus: 14Recent Advances in Lab-On Systems for Breast Cancer Metastasis Research(Royal Society of Chemistry, 2023) Fıratlıgil Yıldırır, Burcu; Yalçın Özuysal, Özden; NonappaBreast cancer is the leading cause of cancer-related deaths in women. Multiple molecular subtypes, heterogeneity, and their ability to metastasize from the primary site to distant organs make breast cancer challenging to diagnose, treat, and obtain the desired therapeutic outcome. As the clinical importance of metastasis is dramatically increasing, there is a need to develop sustainable in vitro preclinical platforms to investigate complex cellular processes. Traditional in vitro and in vivo models cannot mimic the highly complex and multistep process of metastasis. Rapid progress in micro- and nanofabrication has contributed to soft lithography or three-dimensional printing-based lab-on-a-chip (LOC) systems. LOC platforms, which mimic in vivo conditions, offer a more profound understanding of cellular events and allow novel preclinical models for personalized treatments. Their low cost, scalability, and efficiency have resulted in on-demand design platforms for cell, tissue, and organ-on-a-chip platforms. Such models can overcome the limitations of two- and three-dimensional cell culture models and the ethical challenges involved in animal models. This review provides an overview of breast cancer subtypes, various steps and factors involved in metastases, existing preclinical models, and representative examples of LOC systems used to study and understand breast cancer metastasis and diagnosis and as a platform to evaluate advanced nanomedicine for breast cancer metastasis.Article Citation - WoS: 4Citation - Scopus: 3Boron Stress Signal Is Transmitted Through the Tor Pathway(Elsevier, 2023) Uluışık, İrem; Koç, AhmetAlthough boron is an essential element for many organisms, an excess amount of it can cause toxicity, and the mechanism behind this toxicity is not yet fully understood. The Gcn4 transcription factor plays a crucial role in the boron stress response by directly activating the expression of the boron efflux pump Atr1. More than a dozen transcription factors and multiple cell signaling pathways have roles in regulating the Gcn4 transcription factor under various circumstances. However, it is unknown which pathways or factors mediate boron signaling to Gcn4. Using the yeast Saccharomyces cerevisiae as a model, we analyzed the factors that converge on the Gcn4 transcription factor to assess their possible roles in boron stress signaling. Our findings show that the GCN system is activated by uncharged tRNA stress in response to boron treatment and that GCN1, which plays a role in transferring uncharged tRNAs to Gcn2, is necessary for the kinase activity of Gcn2. The SNF and PKA pathways were not involved in mediating boron stress, even though they interact with Gcn4. Mutations in TOR pathway genes, such as GLN3 and TOR1, abolished Gcn4 and ATR1 activation in response to boric acid treatment. Therefore, our study suggests that the TOR pathway must be functional to form a proper response against boric acid stress.