Acar, Büşra
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Acar, B.
Acar, Busra
Büşra Acar
Acar, Busra
Büşra Acar
Job Title
Arş. Gör.
Email Address
busra.acar@agu.edu.tr
Main Affiliation
04.02. Moleküler Biyoloji ve Genetik
Status
Current Staff
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ORCID ID
Scopus Author ID
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WoS Researcher ID
Sustainable Development Goals
2
ZERO HUNGER
1
Research Products
3
GOOD HEALTH AND WELL-BEING
2
Research Products
Documents
5
Citations
3
h-index
1
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Scholarly Output
12
Articles
5
Views / Downloads
34/0
Supervised MSc Theses
0
Supervised PhD Theses
1
WoS Citation Count
3
Scopus Citation Count
3
WoS h-index
1
Scopus h-index
1
Patents
0
Projects
1
WoS Citations per Publication
0.25
Scopus Citations per Publication
0.25
Open Access Source
2
Supervised Theses
1
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Now showing 1 - 10 of 12
Article Role of Long Non-Coding RNA X-Inactive Transcript (XIST) in Neuroinflammation and Myelination: Insights From Cerebral Organoids and Implications for Multiple Sclerosis(MDPI, 2025) Pepe, Nihan Aktas; Acar, Busra; Zararsiz, Gozde Erturk; Guner, Serife Ayaz; Sen, AlaattinBackground/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. Results: XIST-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in XIST-silenced organoids. Furthermore, XIST silencing reduced the concentration of alpha-synuclein from 300 to 100 pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of XIST in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer's and Parkinson's diseases and may be a promising therapeutic target.Conference Object Investigating the Anti-Inflammatory Activities of the New Hybrid Compound 4-((1-(3-Nitrobenzyl)-4,5-Dihydro-1H-1,2,3-Triazol-4-yl) Methoxy)Benzohydrazide(Wiley, 2023) Pepe, N. Aktas; Atalay, T. N.; Acar, B.; Senol, H.; Sen, A.Conference Object Investigating Multitargeting Effect of Fingolimod/Ciproxifan Butterfly Derivatives for Multiple Sclerosis on Brain Organoids(Wiley, 2023) Acar, B.; Stark, H.; Sen, A.Article Neuroinflammatory Human Brain Organoids Enable Comprehensive Drug Screening Studies: Fingolimod and Its Analogues in Focus(Bentham Science Publishing Ltd, 2026) Acar, Busra; Pepe, Nihan Aktas; Zivkovic, Aleksandra; Stark, Holger; Sen, AlaattinIntroduction The absence of physiologically relevant models for neuroinflammatory brain disorders, such as multiple sclerosis (MS), highlights the need for improved drug screening platforms. To bridge this gap, this study aimed to develop a human brain organoid (hBO) model incorporating essential neural cell types, including astrocytes, microglia, and oligodendrocytes.Methods hBOs were generated from H9 stem cells, and neuroinflammatory characteristics were elicited by lipopolysaccharide (LPS). The expression of specific neuronal and inflammatory markers was assessed through qRT-PCR, immunofluorescence staining (IFS), and ELISA.Results IFS of mature hBOs with anti-SOX2, anti-SATB2, anti-MAPT, anti-GFAP, anti-MBP, and anti-IBA1 antibodies and images collected with the confocal microscope confirmed the differentiation of H9 cells into cortical neurons, astrocytes, microglia, and oligodendrocyte cell types. Elevated GFAP, IBA1, NF-kappa B, and IL-6 levels, along with reduced CNPase expression with LPS treatment, were considered reflective of MS-like pathology and were used to test fingolimod and its derivatives. Fingolimod and all its derivatives, specifically ST-1505, decreased MAPT (2.1-fold in ELISA, 1.7-fold in IFS), GFAP (1.8-fold in IFS), TNF alpha (5.4-fold in qRT-PCR), and FABP (1.5-fold in ELISA) levels, and increased IL-10 (11-fold in qRT-PCR) and MBP (2.9-fold in IFS) levels.Discussion The present data collectively showed LPS to evoke neuroinflammation in the hBO model, while fingolimod and its derivatives, particularly ST-1505, exhibited significant anti-inflammatory and neuroprotective properties by counteracting these evoked changes in the hBO model.Conclusion The findings supported the applicability of brain organoids as a model system for drug screening studies for neuroinflammatory brain diseases.Conference Object Microwave-Assisted Gelatin Methacryloyl Hydrogel (GelMA): A Reliable Extracellular Matrix for Brain Organoid Generation(Wiley, 2025) Acar, B.; Kaya, M.; Pepe, N. Aktas; Demirtas, T. T.; Sen, A.Article Interaction of Inula Viscosa (L.) Aiton with IBA1 via Rosmarinic Acid and Rutin: Insights from Computational Models and Biological Effects(Wiley-VCH verlag GmbH, 2025) Aktas Pepe, Nihan; Acar, Busra; Ceylan Ekiz, Yagmur; Senol, Ayse Merve; Semiz, Gurkan; Sen, Alaattin; Celik Turgut, GurbetInula viscosa (L.) Aiton is a traditional medicinal plant extensively utilized in Mediterranean nations for the treatment of rheumatic pain, inflammatory disorders, diabetes, anemia, and cancer. This study further explored its anti-inflammatory mechanisms through the highest components, chlorogenic acid, rosmarinic acid, and rutin, on the expression of the ionized calcium-binding adapter molecule 1 (Iba1) on monocyte-derived macrophage-like cells. Iba1 is known to contribute pathogenesis of diverse inflammatory diseases. HPLC analysis identified 13 major phenolic compounds, with rosmarinic acid, chlorogenic acid, and rutin as major components. The aqueous extract of the plant and its major components exhibited dose-dependent antiproliferative activity on pTHP-1, RAW264.7, and PCS-201-012 cells. Immunofluorescence staining revealed a significant reduction in Iba1 protein expression, which is associated with inflammation, at the high dose of I. viscosa and rutin. Molecular docking studies indicated that rosmarinic acid and rutin had the strongest predicted interactions with Iba1, with docking scores of -12.403 and -12.301 kcal/mol and MM/GBSA binding energies of -64.47 and -84.20 kcal/mol, respectively. I. visoca and its major components were observed to significantly suppress iNOS activity in LPS-stimulated cells; these findings were also supported by RT-PCR results. Treatment with the high dose of I. viscosa resulted in 9.45% necrotic cells and caused cell cycle arrest in the S phase (59.2 +/- 5.23%). This suggests that it may potentially reduce the proliferation of activated macrophages. In the fibroblast migration assays, the relative wound closure rate was found to be significant 27.06 +/- 18.09% at the low dose of I. viscosa and 31.59 +/- 22.42% at the high dose of I. viscosa. Although the relatively low wound closure rate limits tissue repair, it may benefit chronic wounds and fibrosis by suppressing excessive cell proliferation and inflammation. These results suggest that I. viscosa is a promising natural source of bioactive compounds with potential applications in anti-inflammatory drug development.Article Citation - WoS: 3Citation - Scopus: 3Evaluation of Selected Plant Phenolics Via Beta-Secretase Inhibition, Molecular Docking, and Gene Expression Related to Alzheimer's Disease(MDPI, 2024) Akyurek, Tugba Ucar; Orhan, Ilkay Erdogan; Deniz, F. Sezer Senol; Eren, Gokcen; Acar, Busra; Sen, AlaattinBackground: The goal of the current study was to investigate the inhibitory activity of six phenolic compounds, i.e., rosmarinic acid, gallic acid, oleuropein, epigallocatechin gallate (EGCG), 3-hydroxytyrosol, and quercetin, against beta-site amyloid precursor protein cleaving enzyme-1 (BACE1), also known as beta-secretase or memapsin 2, which is implicated in the pathogenesis of Alzheimer's disease (AD). Methods and Results: The inhibitory potential against BACE1, molecular docking simulations, as well as neurotoxicity and the effect on the AD-related gene expression of the selected phenolics were tested. BACE1 inhibitory activity was carried out using the ELISA microplate assay via fluorescence resonance energy transfer (FRET) technology. Molecular docking experiments were performed in the human BACE1 active site (PDB code: 2WJO). Neurotoxicity of the compounds was carried out in SH-SY5Y, a human neuroblastoma cell line, by the Alamar Blue method. A gene expression analysis of the compounds on fourteen genes linked to AD was conducted using the real-time polymerase chain reaction (RT-PCR) method. Rosmarinic acid, EGCG, oleuropein, and quercetin (also used as the reference) were able to inhibit BACE1 with their respective IC50 values 4.06 +/- 0.68, 1.62 +/- 0.12, 9.87 +/- 1.01, and 3.16 +/- 0.30 mM. The inhibitory compounds were observed to occupy the non-catalytic site of the BACE1. However, hydrogen bonds were found to be present between rosmarinic acid and EGCG and aspartic amino acid D228 in the catalytic site. Oleuropein and quercetin effectively suppressed the expression of PSEN, APOE, and CLU, which are recognized to be linked to the pathogenesis of AD. Conclusions: The outcomes of the work bring quercetin, EGCG, and rosmarinic acid to the forefront as promising BACE1 inhibitors.Conference Object Therapeutic Potential of Pyrvinium Pamoate in Multiple Sclerosis Applying Brain Organoids(Wiley, 2025) Demirkol, N. M.; Ayten, M. N.; Acar, B.; Pepe, N. Aktas; Sen, A.Doctoral Thesis Multipl Skleroz ve Bilişsel Bozuklukta Çok Hedefli Farmasötik İlaçları Test Etmek için Beyin Organoidi Modelinin Geliştirilmesi ve Beyin Organoidi Oluşturulması için Alternatif Ekstraselüler Matrisin İncelenmesi(2025) Acar, Büşra; Şen, Alaattin; Demirtaş, Tuğrul TolgaBeyin organoidleri, immün aracılı nörodejeneratif hastalıkların modellenmesi için değerli bir platform sunar. Merkezi sinir sistemini hedef alan otoimmünite, nöroenflamasyon ve demiyelinizasyon ile karakterize edilen multipl skleroz (MS), güçlü in vitro modellerden ve etkili tedavi seçeneklerinden yoksundur. Bu eksiklikleri gidermek amacıyla, ticari ekstraselüler matriks (Matrigel) ve metakrilatlı jelatin (JelMA) kullanılarak MS modellenmiş beyin organoidleri oluşturulmuş; LPS uygulaması ile MS patolojisi indüklenmiş ve fingolimod türevleri terapötik potansiyelleri açısından incelenmiştir. Bulgular ışık ve immünofloresan mikroskobu, Raman spektroskopisi, qRT-PCR ve ELISA ile analiz edilmiştir. Sonuçlara göre, JelMA'nın, farklı hücre organizasyonları sergilemesine rağmen, astrositler, nöral projenitör hücreler ve olgun nöronlar gibi çeşitli nöron tiplerine sahip beyin organoidleri oluşturmakta Matrigel kadar etkili olduğu belirlenmiştir. LPS ile MS modeli başarıyla indüklenmiş; bu da miyelinleşmede azalma (CNPaz'da 2,4 kat) ve inflamasyonda artış (IBA1'de 1,7 kat, GFAP'ta 1,6 kat, NF-κB'de 4,4 kat ve IL-6'da 6,7 kat) ile sonuçlanmıştır. Test edilen bileşiklerden en az biri, ST-1505, miyelinleşmeyi artırdığı (MBP'de 2,9 kat), inflamasyonu azalttığı (GFAP'ta 2,6 kat, TNF-α'da 4 kat, FOXP3'te 2,3 kat, CSF-1'de 2,5 kat) ve bilişsel bozulma ile ilişkili belirteçlerini düşürdüğü (TAU, 1,9 kat) için umut verici bir ilaç adayı olarak öne çıkmıştır.Conference Object Co-Culture Spheroid Model for Neurodevelopment and Disease Modeling(Wiley, 2025) Ayten, M. N.; Demirkol, N. M.; Pepe, N. Aktas; Acar, B.; Sen, A.
