Browsing by Author "Yurdacan, Beste"
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Publication Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease(Elsevier, 2020-09-28) Eryılmaz, Işıl Ezgi; Erer, Sevda; Zarifoğlu, Mehmet; Egeli, Ünal; Karakuş, Ece; Yurdacan, Beste; Çeçener, Gülşah; Tunca, Berrin; Çolakoğlu, Beril; Tokcaer, Ayşe Bora; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Doğu, Okan; Kaleağası, Hakan; Kenangil, Gülay; Çakmur, Raif; Elibol, Bülent; ERYILMAZ, IŞIL EZGİ; ERER ÖZBEK, ÇİĞDEM SEVDA; ZARİFOĞLU, MEHMET; EGELİ, ÜNAL; Karakuş, Ece; Yurdacan, Beste; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0002-3316-316X; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; GWV-3548-2022; DVY-9744-2022; EHN-5825-2022; AAH-1420-2021; FDA-2023-2022; AEA-0144-2022; AAP-9988-2020; ABI-6078-2020In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.Publication Evaluation of the clinical features accompanied by the gene mutations the 2 novel PSEN1 variants in a Turkish early-onset alzheimer disease cohort(Lippincott Williams & Wilkins, 2021-07-01) Eryılmaz, Işıl E.; Bakar, Mustafa; Egeli, Ünal; Çeçener, Gülşah; Yurdacan, Beste; Çolak, Dilara K.; Tunca, Berrin; ERYILMAZ, IŞIL EZGİ; BAKAR, HACI MUSTAFA; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Yurdacan, Beste; Çolak, Dilara K.; TUNCA, BERRİN; Bursa Uludağ Üniversite/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0002-1619-6680; GWV-3548-2022; AEA-0144-2022; AAH-1420-2021; EKN-8251-2022; AAP-9988-2020; HXB-1173-2023; ABI-6078-2020Introduction: Early-onset Alzheimer disease (EOAD) is an earlier Alzheimer disease form which is characterized by the mutations in the amyloid precursor protein, presenilin-1/2 (PSEN1/2), and triggering receptor expressed on myeloid cells 2 (TREM2). However, it is still necessary to report mutational screening in multiethnic groups to improve the genetic background of EOAD due to the variant classification challenge. Methods: We performed targeted sequencing for the amyloid precursor protein, PSEN1, PSEN2, and TREM2 genes in 74 patients and 1 family diagnosed with EOAD. Results: Among the detected variants, 8 were coding and 6 were noncoding in 15 of 74 patients. In PSEN1, 2 pathogenic coding variants (T274K and L364P) detected in 2 patients were novel and 3 coding variants (G183V, E318G, and L219P) detected in 2 patients were previously reported. We found 4 patients with the compound heterozygosity for the PSEN2 A23= and N43= and a family with the coexistence of them, and 1 patient with TREM2 Y38C. The coding variation frequency was 12.1%. In silico analysis indicated pathogenic potentials and clinical interpretations of the detected variants. Conclusion: Our study reveals the rare gene variants including novel ones from the Turkish EOAD cohort and provides to clinicians the list of detected variants in the screened genes, which may also be useful for accurate genetic counseling.Item Hepatosellüler karsinomada üsnik asit ve sorafenib'in kombin tedavi olarak anti-tümöral etkilerinin araştırılması(Uludağ Üniversitesi, 2017-06-12) Yurdacan, Beste; Egeli, Ünal; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıbbi Biyoloji Anabilim Dalı.Günümüzde hepatasellüler karsinomanın (HSK) tümörün heterojen yapısı ve tedavide tek bir kemoterapik ajan olarak sorafenibin (SOR) kullanılması, HSK tedavisinde başarıyı kısıtlamakta olup güncel tedavi sorunlarını oluşturmaktadır. Bu nedenle HSK'da mevcut kemoterapik ajanlar ile birlikte çeşitli kemoterapik ilaç kombinasyonlarının, bitkisel özütlerin ve etken maddelerinin terapötik etkilerinin araştırıldığı çalışmalar önem kazanmaktadır. Bu nedenle, mevcut tez kapsamında HSK'da güncel tedavi sorunlarına çözüm getirmek, SOR'un kontrol hücrelerinde sitotoksik etkisi azaltmak ve HSK hücrelerinde terapötik etkisini arttırmak amacıyla ilk kez üsnik asit (UA) ile SOR'un kombin terapötik etkisinin belirlenmesi hedeflenmiştir. Mevcut tez kapsamında belirlenen süre ve konsantrasyonlarda UA ve SOR'un ayrı ayrı ve kombin uygulamalarının HSK ve kontrol hücre hatlarında hücre proliferasyonu üzerindeki etkileri WST-1 analizi ile belirlenmiş olup, apoptotik etkilerinin ve hücre siklusu üzerindeki etkilerinin belirlenmesi için Annexin V ve hücre siklusu analizleri gerçekleştirilmiştir. Ayrıca, hücrelerde meydana gelen morfolojik değişimler akridin oranj-etidyum bromür floresan boyaması ile görüntülenmiştir. WST-1 analizi sonuçlarına göre, UA ve SOR kombin uygulanan HSK hücrelerinde canlılık oranının tek SOR ve UA uygulanan hücrelere göre daha fazla oranda azaldığı ve HUVEC kontrol hücrelerinde SOR'un toksik etkisinin azaldığı belirlenmiştir. Ayrıca, kombin SOR ve UA'nın HSK hücrelerinde geç apoptotik ve nekrotik ölüme neden olarak, HSK hücrelerinin özelliklerine göre G0/G1 ve G2/M evresinde hücre miktarında artış tespit edilmiştir. Son olarak, SOR ve UA kombin uygulanan HSK hücrelerinde geç apoptotik ve nekrotik ölümün yanı sıra vakuol sayısında belirgin seviyede artış görüntülenmiştir Sonuç olarak, mevcut tez çalışmasında ilk kez SOR ve UA'nın HSK hücrelerinde sitotoksik ve apoptotik etkileri in vitro olarak değerlendirilerek sinerjik etkiye sahip oldukları belirlenmiştir.Item In vitro cytotoxic and antiproliferative effects of usnic acid on hormone-dependent breast and prostate cancer cells(Wiley, 2018-10) Eskiler, Gamze Güney; Eryılmaz, Işıl Ezgi; Egeli, Ünal; Yurdacan, Beste; Çeçener, Gülşah; Tunca, Berrin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-3316-316X; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-3820-424X; GWV-3548-2022; AAH-1656-2021; AAH-1420-2021; ABI-6078-2020; AAP-9988-2020; 57189380840; 55665145000; 57203621058; 6508156530; 6602965754The aim of the current study was first to investigate cytotoxic activity of usnic acid (UA) on hormone-dependent breast and prostate cancer, and normal cells. Cells were treated with increasing concentrations (25 to 150 mu M) of UA for 48hours and cell viability, quantitative and morphological analysis of cell death, and cell cycle analysis were performed. UA was shown to have selective cytotoxicity on hormone-dependent cancer cells with the IC50 levels of 71.4 and 77.5 mu M for MCF7 and LNCaP cells, respectively. UA induced apoptotic cell death and G0/G1 cell cycle arrest without damaging normal cells. MCF7 cells were more sensitive to UA than LNCaP cells. Our results first revealed that UA is a promising candidate as an alternative agent for hormone-dependent breast and prostate cancers. However, molecular mechanism underlying the UA-mediated cell death in cancer cells should be investigated further.Item Investigation of new treatment option for hepatocellular carcinoma: A combination of sorafenib with usnic acid(Oxford University, 2019-07) Yurdacan, Beste; Eskiler, Gamze Güney; Egeli, Ünal; Eryılmaz, Işıl Ezgi; Çeçener, Gülşah; Tunca, Berrin; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Temel Tıp Bilimleri/Tıbbi Biyoloji Bölümü.; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0002-3316-316X; 0000-0002-3316-316X; 0000-0001-7904-883X; ABI-6078-2020; AAP-9988-2020; GWV-3548-2022; AAH-1656-2021; AAH-1420-2021; 55665145000; 57189380840; 6508156530; 6602965754Objectives Sorafenib (SOR) is an orally administered molecular targeted agent in the systemic chemotherapy of hepatocellular carcinoma (HCC). However, the partial response of SOR is limited due to its adverse side effect and high heterogeneity and resistant phenotype of HCC. In the current study, we investigated synergistic effects of SOR and usnic acid (UA) on HCC cell lines including HepG2 and SNU-449, and a normal cell line, HUVEC. Methods The antiproliferative and apoptotic effects of combination therapy and SOR alone were analysed by WST-1 and Annexin V analysis, respectively. Furthermore, cell cycle, gene expression analysis of SOR-targeted kinases and acridine orange-ethidium bromide staining were also performed in combined treatments. Key findings Our results demonstrated that SOR and UA combination indicated a strong synergism in HCC cell lines and reduced SOR toxicity in HUVEC cells. Additionally, the combination treatment SOR and UA significantly induced much more apoptotic cell death and G0/G1 arrest through downregulation of SOR-targeted kinases. Conclusions Consequently, SOR and UA combination could be a new therapeutic strategy for HCC treatment.Item The role of usnic acid-induced apoptosis and autophagy in hepatocellular carcinoma(Sage Publications, 2018-08-07) Eskiler, G. Güney; Yurdacan, Beste; Egeli, Ünal; Eryilmaz, Işıl Ezgi Eryılmaz; Çeçener, Gülşah; Tunca, Berrin; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-3820-424X; 0000-0002-3316-316X; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3316-316X; AAP-9988-2020; GWV-3548-2022; ABI-6078-2020; AAH-1420-2021; AAH-1656-2021; 57189380840; 6602965754; 6508156530; 55665145000; 57203621058Usnic acid (UA) is a multifunctional bioactive lichen secondary metabolite with potential anti-cancer properties. Although the promising therapeutic effects of UA have been investigated in different cancer cell lines, the mechanism driving UA-induced cell death has yet to be elucidated. As the type of cell death (apoptosis or autophagy) induced by UA may vary depending on the cancer cell type, we first studied the cytotoxic effects of UA in HEPG2 (HBV(-)) and SNU-449(HBV(+)) hepatocellular carcinoma (HCC) cell lines. HCC cell viability was considerably reduced in a dose-dependent manner at 12, 24, and 48 h after treatment with UA (p < 0.05). However, SNU-449 cells were more sensitive to UA than HEPG2 cells. UA also induced apoptotic cell death in HCC cells with cell cycle arrest at G0/G1 and G2/M phase depending on the genetic profile of each cell type. On the other hand, we observed acidic vesicular organelles in HCC cells after 36 h of UA treatment. Taken together, these findings suggest that UA stimulates apoptosis and autophagy in HEPG2 and SNU-449 cells without damaging normal control cells. Thus, UA might be a potential therapeutic compound for HCC treatment. However, there is a need for further studies investigating the death-promoting or preventing roles for autophagy and the molecular signaling mechanisms induced by UA treatment.