Browsing by Author "Kara, Adem"

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18β-Glycyrrhetinic Acid-Loaded Silver Nanoparticles Mitigate Neuroinflammation and Endoplasmic Reticulum Stress in the Brain Tissue of Diabetic Rats
(Mashhad University of Medical Sciences, 2026) Parlak, Secil Nazife; Yakut, Seda; Kara, Adem; Demir, Ozlem; Sebin, Saime Ozbek
Objective(s): Diabetes mellitus (DM) causes oxidative stress, neuroinflammation, and endoplasmic reticulum (ER) dysfunction that contribute to neurodegeneration. This study investigated the effects of 18 beta-glycyrrhetinic acid-loaded silver nanoparticles (18 beta-GA-AgNPs) on brain injury in diabetic rats. Materials and Methods: Fifty-six male Wistar rats were divided into eight groups: Sham, 18 beta-GA, AgNPs, 18 beta-GA-AgNPs, DM, DM+18 beta-GA, DM+AgNPs, and DM+18 beta-GA-AgNPs. Diabetes was induced by alloxan (120 mg/kg, IP), and treatments were administered orally for 14 days. Biochemical markers (MDA, GSH, SOD), histopathology, and expression of ER stress and apoptotic proteins (ATF6, IRE1, Caspase-3, BCL-2, CREB, TNF-alpha, and IL-1 beta) were evaluated. Results: The DM group exhibited significant increases in MDA, TNF-alpha, IL-1 beta, ATF6, and Caspase-3 with reduced GSH, SOD, and BCL-2, indicating oxidative stress, inflammation, apoptosis, and ER stress. In contrast, IRE1 levels remained unchanged in DM rats but showed a slight elevation in the AgNPs group. Treatment with 18 beta-GA-AgNPs markedly reduced MDA, TNF-alpha, IL-1 beta, ATF6, and Caspase-3, while restoring GSH, SOD, BCL-2, and CREB expression. Histopathological analysis confirmed neuronal apoptosis and perivascular and extracellular space enlargement in DM rats, whereas 18 beta-GA-AgNPs substantially attenuated these changes. Overall, 18 beta-GA-AgNPs provided synergistic neuroprotection by suppressing oxidative stress, inflammation, and ER stress while enhancing antioxidant and anti-apoptotic defenses. Conclusion: These findings suggest that 18 beta-GA-AgNPs may represent a promising therapeutic strategy against diabetes-associated neurodegeneration, although further long-term, ultrastructural, and sex-inclusive studies are warranted.
Alleviation of LPS-Induced Acute Lung Injury by Propolis-Based Nanocomposites Through the TLR4/NFκB and P2X7/Akt Pathways: Randomized-Controlled Experimental Study
(Pergamon-Elsevier Science Ltd, 2025) Ustundag, Hilal; Kara, Adem; Tas, Necip Gokhan; Kalindemirtas, Ferdane Danisman; Kurt, Nezahat; Erbas, Elif; Kariper, Ishak Afsin
Sepsis-associated acute lung injury continues to pose a significant medical challenge with substantial morbidity and mortality rates. In this study, we investigated the therapeutic potential of propolis-based treatments and their nanocomposites in modulating inflammation and apoptosis using a lipopolysaccharide (LPS)-induced rat model of sepsis. Forty-two Sprague-Dawley rats were divided into seven groups (n = 6): control, LPS (5 mg/kg, i. p.), LPS + Propolis (100 mg/kg, i.p.), LPS + NanoPropolis (100 mg/kg, i.p.), LPS + silver nanoparticles propolis (AgNPsPro) (50 mg/kg), and a negative propolis group (100 mg/kg, i.p.). The rats were assessed for inflammatory, oxidative stress, and apoptotic markers through Western blot, histopathological analyses, and biochemical measurements. The LPS group exhibited significantly higher levels of pro-inflammatory cytokines (IL-1 beta, TNF-alpha) and the systemic infection marker presepsin (PRSN) in blood, as well as the oxidative stress marker malondialdehyde (MDA) in lung tissue. The treatment groups, particularly LPS + AgNPsPro, showed significant reductions in these markers, with decreased levels of MDA, IL-1 beta, TNF-alpha, NF-kappa B, and TLR4, and increased GSH content in lung tissue (p < 0.05). The anti-apoptotic protein BCL-2 was upregulated, while proapoptotic BAX expression was reduced, indicating enhanced cell survival. The P2X7 receptor, a key inflammation regulator, and the AKT signaling pathway, involved in cell survival, were positively modulated by the treatments. Histopathological findings corroborated these results, showing less lung tissue damage. In conclusion, propolisbased treatments, especially in combination with nanoparticles, demonstrate therapeutic potential in reducing inflammation, oxidative stress, and apoptosis in sepsis-induced lung injury.
Alleviation of LPS-Induced Acute Lung Injury by Propolis-Based Nanocomposites Through the TLR4/NFκB and P2X7/Akt Pathways: Randomized-Controlled Experimental Study (Vol 258, 108330, 2025)
(Pergamon-Elsevier Science Ltd, 2025) Ustundag, Hilal; Kara, Adem; Tas, Necip Gokhan; Kalindemirtas, Ferdane Danisman; Kurt, Nezahat; Erbas, Elif; Kariper, Ishakshak Afsin
Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against Mcf-7 and A549 Cells
(Springer Nature, 2024) Yesildag, Ali; Kiziloglu, Halime Topal; Dirican, Ebubekir; Erbas, Elif; Gelen, Volkan; Kara, Adem
Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-alpha was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 mu M and 10 mu g/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-alpha and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments.
Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against MCF-7 and A549 Cells (Feb, 10.1007/S12011-024-04090-y, 2024)
(Springer Nature, 2025) Yesildag, Ali; Kiziloglu, Halime Topal; Dirican, Ebubekir; Erbas, Elif; Gelen, Volkan; Kara, Adem
Astaxanthin-Loaded Silver Nanoparticles Mitigate 6-Ohda Parkinson's Via Er Stress and Pi3k/Akt Signaling
(Springer, 2025) Kara, Hulya; Tekiner, Deniz; Ustundag, Hilal; Bayram, Cemil; Sebin, Saime Ozbek; Ozkanlar, Seckin; Kara, Adem
Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss, with oxidative stress and neuroinflammation as critical pathological mechanisms. The blood-brain barrier presents a significant challenge for therapeutic delivery, while current treatments provide only symptomatic relief without halting disease progression. This study investigated the neuroprotective effects of astaxanthin-loaded citrate-coated silver nanoparticles (AST-AgNPs), leveraging their potent antioxidant properties, anti-inflammatory capacity, and enhanced blood-brain barrier penetration. In vitro cytotoxicity analyses were performed using 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y neuroblastoma cells, while in vivo experiments utilized a unilateral 6-OHDA-induced rat model. Following 14 days of treatment, comprehensive evaluations included behavioral assessments, biochemical analyses (MDA, GSH, SOD, TNF-alpha, IL-1 beta, IFN-gamma), histopathology, immunohistochemistry (BrdU, tyrosine hydroxylase), and molecular analyses. Western blot measured CHOP, IRE1, ATF6, p-AKT, total AKT, caspase-3, and cleaved caspase-3, while RT-PCR quantified caspase-3, Bcl-2, Bax, PI3K, mTOR, Akt, CREB, and NF-kappa B-p65 expression. AST-AgNP treatment significantly ameliorated motor dysfunction, reduced neuroinflammation (TNF-alpha, IL-1 beta), improved oxidative stress parameters (MDA, GSH, SOD), and preserved dopaminergic neurons (all p < 0.05). Western blot revealed significant downregulation of ER stress markers (CHOP, IRE1, ATF6) and cleaved caspase-3, while restoring p-AKT and total AKT levels (p < 0.05). RT-PCR demonstrated decreased pro-apoptotic gene expression (caspase-3, NF-kappa B-p65) and increased anti-apoptotic Bcl-2 expression (p < 0.05). These findings demonstrate that AST-AgNPs provide neuroprotection through simultaneous modulation of ER stress and PI3K/Akt/mTOR pathways, representing a novel dual-pathway therapeutic strategy for PD addressing multiple pathological mechanisms through enhanced nanoparticle-mediated delivery.
Baş-Boyun Kanser Hücrelerinde SALL4 Geninin Direnç Genleri ile Olan İlişkilerinin Araştırılması
(2025) Yılmaz, Arzugül Tanas; Kara, Adem
Sal benzeri protein 4 (SALL4), embriyonik kök hücrelerinde bulunan bir transkripsiyon faktörüdür ancak baş ve boyun skuamöz hücreli karsinomlar da (BBSHK) dahil olmak üzere kanser hücrelerinde aşırı ifade edildiği ve kanser gelişimi, ilerlemesi ve metastaz ile ilişkili olduğu gösterilmiştir. Bu nedenle bu tez çalışmasında SALL4 geninin BBSHK'de ilaç direnci gelişimi veya direnç geliştirilmiş hücreler üzerindeki etkilerinin aydınlatılması hedeflenmiştir. Çalışmamızda FaDu hücreleri normal ve ilaç direnci geliştirilmiş formlarda kullanılmış ve deneyler pozitif kontrol grubu, inhibisyon grubu, PTX uygulanan grup, hem inhibisyon hem de ilaç uygulaması yapılan grup ve negatif kontrol grubu olmak üzere 6 grup üzerinden yürütülmüştür. Hem normal hem de ilaç direnci geliştirilmiş hücrelerde SALL4 inhibisyonu gerçek zamanlı polimeraz zincir reaksiyonu (qRT-PZR) ve Western Blot (WB) ile kontrol edilmiş ardından SALL4 geninin direnç genleriyle olan ilişkisi moleküler genetik analizler ile detaylandırılmış. Daha sonra hücre hatlarında hücre döngüsü, hücre migrasyonu ve apoptotik durum incelenmiştir. Analiz sonuçlarında SALL4'ün her iki hücre hattında da başarıyla inhibe edildiği ayrıca, SALL4 baskılanmasının PTX'in apoptozu artırıcı etkisini güçlendirdiği, hücre döngüsü üzerine antiproliferatif etki yaptığı ve özellikle dirençli hücrelerde PTX ile birlikte uygulandığında sinerjik etki oluşturduğu belirlenmiştir. Elde edilen bulguların, BBSHK'de yeni terapötik stratejilerin geliştirilmesine ve hastaların tedaviye daha iyi yanıt vermesine yardımcı olabileceği düşünülmektedir.
Blockade of P2x7 Receptor-Mediated Purinergic Signaling with A438079 Protects Against LPS-Induced Liver Injury in Rats
(Wiley, 2023) Kara, Adem; Ozkanlar, Seckin
The study aimed to investigate the hepatoprotective effects of purinergic receptor (P2X7R) antagonism by A438079 in liver damage. An experimental model of inflammation was performed by intraperitoneal (i.p.) lipopolysaccharide (LPS) administration in the rat. The groups were Control, A438079, dimethyl sulfoxide (DMSO), LPS, LPS + DMSO, and LPS + A438079. Following LPS (8 mg/kg) injection, A438079 (15 mg/kg) and DMSO (0.1 mL) were administrated (i.p) in the study groups. The blood and the liver tissues were removed for histological, biochemical, and western blot analyses. In the biochemical analysis, serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, the tissue glutathione (GSH) level, and superoxide dismutase (SOD) activity dramatically decreased and malondialdehyde (MDA) level increased in the LPS and LPS + DMSO groups compared to the LPS + A438079 group. In the histological analysis, severe sinusoidal dilatation, necrotic hepatocytes, and inflammatory cell infiltration were observed in the LPS and LPS + DMSO groups while these effects were lessened in the LPS + A438079 group. The relative protein expression levels of P2X7R, Nf-kB-p65, IL-6, and Caspase-3 were significantly higher in the LPS and the LPS + DMSO groups than in the LPS + A438079 group. On the other hand, these protein expressions were considerably lower in the Control, A438079, and DMSO groups compared to the LPS + A438079 group. In addition, Bcl-2 protein expression was significantly lower in the LPS and the LPS + DMSO groups and higher in the LPS + A438079 group compared to the other groups. The protective effect of A438079 against LPS-induced hepatic inflammation may be related to P2X7R antagonism, inflammatory mediators, and apoptotic cell death.
BRCP Geni Suturulmuş Meme Kanseri Hücrelerinde Doksorubisin Yüklenmiş Kitosan-Gümüş Nanopartikülünün Tedavi Etkinliğinin Araştırılması
(2025) Candemiş, Derya; Kara, Adem; Erbaş, Elif
Bu tez çalışmasında, BRCP (Breast Cancer Resistance Protein) geninin inhibisyonunun meme kanseri tedavisindeki etkileri araştırılmış ve doksorobusin (DOX) yüklü kitosan gümüş nanopartiküllerinin (K-AgNP-DOX NP) karakterizasyonu ile terapötik etkinliği değerlendirilmiştir. Karakterizasyon aşamasında, Kitosan-Gümüş Nanopartikülü (K-AgNP) ve Doksorubisin yüklü Kitosan-Gümüş Nanopartiküllerinin (K-AgNP-DOX) boyutları TEM ve SEM analizi ile belirlenmiştir. FTIR analizi ile doksorubisin başarılı şekilde yüklendiğini gösteren karakteristik pikler ile belirlenmiştir. Hücre bazlı çalışmalarda, canlılık analiz sonucunda DOX içeren ve içermeyen K-AgNP'lerin yarı inhibisyon değerleri (IC50) değerleri belirlenmiştir. K-AgNP'nin 80 µg/mL, DOX içeren K-AgNP'nin 40µg/mL konsantrasyon olacak şekilde bütün deneylerde uygulamaları gerçekleştirilmiştir. Uygulamaların sonrasında hücre ölüm mekanizmaları değerlendirilmiştir, PCR ve Western blot analizleri ile gen ifadeleri ve protein seviyelerindeki değişimler incelenmiştir. Sonuç olarak K-AgNP-DOX'un meme kanseri tedavisinde bir hedeflenmiş ilaç taşıyıcı sistem olarak değerlendirilebileceği düşünülmektedir.
Cetuximab ve Agomelatin İlaçlarının Prostat Kanseri Hücrelerindeki Proliferasyon ve Apoptoza Etkisinin İncelenmesi
(2024) Kara, Adem; Kızıloğlu, Halime Topal; Albayrak, Kevser; Köse, Rukiye; Güney, Betül Nur
Kanser, hücrelerin kontrolsüz bölünmesi sonucu ortaya çıkan, delillere ve çevresel faktörlere bağlı bir dizi hastalığı kapsayan karmaşık bir sağlık sorunudur. Dünya çapında bilinen 100'den fazla kanser türü vardır. Bu çalışmada, yılda 1.600.000 vaka ve 366.000 ölümle sonuçlanan ve erkeklerde en sık görülen prostat kanseri hücreleri kullanılmıştır. Kanser tedavisi sürecinde çoğu kanser hastasında farklı ilaçlar kullanılmaktadır. Bu bağlamda kemoterapötik ajan Cetuximab (CTX) ve antidepresan ajan Agomelatin ilaçları ile prostat kanseri PC3 hücre hattı üzerindeki proliferasyon ve apoptoz üzerindeki etki ile tedavinin önemine odaklandı. Prostat kanserinin özelliklerine ve yaygınlığına odaklanılarak Cetuximab ve Agomelatin'in prostat kanseri hücreleri üzerindeki etkileri incelendi. Bu araştırma, Cetuximab ve Agomelatin ilaçlarının prostat kanseri hücrelerinde proliferasyonu ve apoptozu nasıl etkilediğini anlamak amacıyla yapıldı. Bulgular, bu ilaçların prostat kanseri tedavisinde potansiyel etkiler sağlayabileceğini düşündürmektedir.
Çinko Fosfat Kaplı, Cisplatin Yüklü Silika Nanopartiküllerinin Üretimi ve MDR1 Gen İnhibisyonu Sağlanmış Baş-boyun Kanseri Hücrelerinde Etkimekanizmasının İncelenmesi
(2025) Öztürk, Emre; Kara, Adem
Bu tez çalışmasında, FaDu hücre hattında MDR1 geninin siRNA ile inhibisyonu sağlanarak, yeşil sentez yöntemiyle üretilen ZnP kaplı, SiO2 nanopartiküllerine yüklenen cisplatinin (ZnP+SiO2+CIS) tedavi etkinliği değerlendirilmiştir. Sentezlenen nanopartiküller, Zeta Potansiyeli, XRD, FTIR, SEM ve TEM analizleriyle yapısal ve morfolojik olarak karakterize edilmiştir. İlaç yükleme kapasitesi ve yüklenmiş ilaç miktarı, HPLC analizleriyle belirlenmiş; farklı pH koşullarında gerçekleştirilen in vitro salım testleriyle cisplatinin salım profili detaylı şekilde incelenmiştir. Hücre kültürü deneylerinde, ZnP+SiO2+CIS uygulamasının FaDu hücre hattında IC50 değeri 15 µg/mL bulunmuştur. MDR1 gen susturulmasının tek başına hücre canlılığı üzerinde sınırlı etkiye sahip olduğu belirlenirken, ZnP+SiO2+CIS uygulamasının hücre canlılığında anlamlı bir azalmaya neden olduğu ve tedavi etkinliğinde belirgin bir artış sağladığını göstermiştir. Ayrıca, RT-PCR ve Western blot analizleri ile MDR1 inhibisyonu ve nanopartikül tedavilerinin hücre ölümü, proliferasyonu ve sinyal iletim yolaklarındaki moleküler etkileri detaylı şekilde ortaya konmuştur. Elde edilen veriler, çoklu ilaç direncini geçip nanopartikül destekli kemoterapi yaklaşımlarının potansiyelini vurgulamıştır.
Citrate-Coated Silver Nanoparticles Loaded with Agomelatine Provide Neuronal Therapy in Acute Cerebral Ischemia/Reperfusion of Rats by Inhibiting the Oxidative Stress, Endoplasmic Reticulum Stress, and P2x7 Receptor-Mediated Inflammasome
(Wiley, 2024) Gelen, Volkan; Ozkanlar, Seckin; Kara, Adem; Yesildag, Ali
Cerebral ischemia and reperfusion are related to various situations like injuries after various traumas, oxidative stress, increased calcium ion, capillary hypoperfusion, microvascular hyperpermeability, leukocyte infiltration, and blood-brain barrier disruption. An antidepressant Agomelatine which is a melatonin receptor (MT1/MT2) agonist and serotonin receptor (5-HT2C) antagonist has been reported by studies to have antioxidant and anti-inflammatory effects. In our study, we aimed to detect the effects of citrate-coated silver nanoparticle-loaded agomelatine application on neurodegeneration, endoplasmic reticulum stress, autophagic and apoptotic cell death, inflammation, and P2X7R expression in the cerebral ischemia-reperfusion model to facilitate the passage of blood-brain barrier. Forty two Sprague-Dawley rats in total were divided into six equal groups (n:7) and applications were performed. Acute cerebral injury in the ischemia-reperfusion model was created 2 h after internal carotid artery ligation in rats and then at the 2nd hour of reperfusion citrate-coated silver nanoparticles loaded with Agomelatine were applied. Twenty four hours later, neurologic analysis on animals in experimental groups was performed, animals were decapitated and GSH, GPx, SOD, CAT, MDA, IL-1 beta, and TNF-alpha parameters were examined after taking blood and the cerebral tissue samples. As a result, it was determined that ischemia-reperfusion caused endoplasmic reticulum stress in the cerebral tissues and thus caused cellular injury.
Coenzyme Q10 Protects Against Glyphosate-Based Herbicide-Induced Testicular and Sperm Toxicity by Modulating Nrf2/Keap1 and Tlr4/Nf-κb Pathways
(Springer, 2025) Mutluay, Duygu; Ozbek, Kader Coban; Tenekeci, Gozde Yucel; Gungor, Sukru; Yakut, Seda; Denk, Baris; Kara, Adem
Roundup, the most widely used glyphosate-based herbicide (GBH), contains glyphosate (GLY) as its main active ingredient and was used to model GBH-induced reproductive toxicity in this study. We aimed to investigate the protective effect of coenzyme Q10 (CoQ10) against GLY-induced testicular and sperm damage, focusing on oxidative stress, inflammation, and apoptosis. Unlike previous studies, this work provides the first integrated evidence combining histopathological, biochemical, hormonal, and molecular assessments with functional sperm analyses, and uniquely demonstrates how CoQ10 modulates both antioxidant (Nrf2/Keap1/HO-1) and inflammatory (TLR4/NF-kappa B) pathways in GBH-induced testicular injury. Forty-two adult male ICR mice were assigned to five groups: control, sham, CoQ10 (200 mg/kg/day), GLY (500 mg/kg/day), and GLY + CoQ10 (500 + 200 mg/kg/day). The treatments were administered orally for 35 days, corresponding to one spermatogenesis cycle. GLY reduced testicular weight, disrupted histoarchitecture, increased oxidative stress (up arrow MDA, TOS, OSI; down arrow GSH, TAS), suppressed Nrf2/Keap1/HO-1 signaling, upregulated TLR4/NF-kappa B, and triggered apoptosis (up arrow Bax, down arrow Bcl-2). It also impaired sperm parameters (concentration, motility, morphology, viability, membrane integrity) and increased mitochondrial ROS, while reducing testosterone and elevating LH. CoQ10 co-treatment alleviated these alterations by restoring redox balance, normalizing signaling pathways, improving sperm quality, and correcting hormonal changes. In conclusion, CoQ10 mitigates GLY-induced testicular toxicity by modulating oxidative stress, inflammation, and apoptosis, highlighting its novel therapeutic potential for protecting male fertility against GBH exposure.
D-Carvone Attenuates LPS-Induced Acute Lung Injury via TLR4/NF-κB and NRF2/HO-1 Signaling Pathways in Rats
(Springer, 2025) Ulas, Nergis; Ustundag, Hilal; Ozkanlar, Seckin; Erbas, Elif; Kara, Adem; Ozkanlar, Yunusemre
Acute lung injury (ALI) is a severe respiratory disorder associated with high morbidity and mortality. Lipopolysaccharide (LPS) is widely used to induce ALI in animal models. D-carvone, a natural monoterpene, has been reported to possess anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effects of D-carvone on LPS-induced ALI in rats. Thirty-six male rats were randomly divided into six groups (n = 6): control, D-carvone (10 mg/kg and 20 mg/kg p.o.), LPS (10 mg/kg E. coli lipopolysaccharide i.p.), and LPS + D-carvone (LPS with either 10 or 20 mg/kg D-carvone). D-carvone was administered orally once daily for 10 days. On day 10, sepsis was induced with LPS administration, and samples were collected after 6 h under deep anesthesia. LPS administration caused significant lung injury, as evidenced by increased histopathological scores, upregulation of pro-inflammatory markers (TLR4, IL-1 beta, TNF-alpha), and oxidative stress (increased MDA, decreased GSH and SOD). Treatment with D-carvone at both doses significantly attenuated these changes. D-carvone downregulated pro-inflammatory markers, upregulated anti-inflammatory (NRF2) and anti-apoptotic (Bcl-2) proteins, and reduced the levels of pro-inflammatory cytokines (IL-1 beta, TNF-alpha, IL-8) in lung tissues. In conclusion, D-carvone protects against LPS-induced ALI in rats, possibly through its anti-inflammatory and antioxidant properties. These findings suggest that D-carvone could be a potential therapeutic candidate for preventing and treating ALI.
Doksorubisin Yüklü Fe3O4@PDA Nanopartiküllerinin Sentezi ve Kaspaz-8 ile Rıpk1 Genleri Susturulmuş Hepatosellülerkarsinom Hücrelerinde Tedavi Etkinliğinin Araştırılması
(2025) Çalık, Fatma; Kara, Adem; Solak, Kübra
Bu tez çalışmasında, doksorubisin (DOX) yüklü polidopamin (PDA) kaplı demir oksit manyetik nanopartiküllerinin (Fe3O4 MNP) hepatosellüler karsinom (HCC) tedavisindeki etkinliği, kaspaz-8 ve RIPK1 gen ekspresyonlarının baskılandığı HEP G2 hücre modeli üzerinden araştırılmıştır. Bu kapsamda sentezlenen Fe3O4 MNP'ler PDA ile kaplanarak (Fe3O4@PDA) DOX yüklenmiştir (Fe3O4@PDA-DOX). Yapısal ve morfolojik karakterizasyon TEM, SEM, XRD ve zeta potansiyeli ile gerçekleştirilmiş; kaplama ve ilaç yükleme başarıları FTIR ve UV-Vis spektroskopisiyle doğrulanmıştır. Fe3O4@PDA-DOX'un IC50 değeri CVDK-8 testiyle 47 µg/mL olarak hesaplanmıştır. Gen inhibisyonu siRNA aracılığıyla gerçekleştirilmiştir. siRNA ve MNP uygulanan hücrelerdeki biyolojik yanıtlar flow sitometri, gerçek zamanlı PCR ve Western blot ile incelenmiştir. Bulgular, kaspaz-8 inhibisyonu ve Fe3O4@PDA-DOX uygulaması yapıldığında kaspaz-8, PI3K, mTOR ve Beclin-1 düzeylerinin azaldığını, LC3B ve kaspaz-3 protein düzeylerinin arttığını ortaya çıkarmıştır. Benzer şekilde, RIPK1 inhibisyonu ile desteklenen uygulamada PI3K, mTOR, Beclin-1 ve p53 protein düzeylerinde azalma, LC3B'de artış gözlenmiştir. Sonuç olarak, bu ikili uygulamanın HCC tedavisinde otofaji, apoptoz ve nekroptozu birlikte aktive edebildiği ve Fe3O4@PDA-DOX'un potansiyel hedeflenmiş ilaç taşıyıcısı olabileceği düşünülmektedir.
Effects of Bromelain on Growth Performance, Biochemistry, Antioxidant Metabolism, Meat Quality, and Intestinal Morphology of Broilers
(Inst Tecnologia Parana, 2023) Yenice, Guler; Atasever, Mustafa; Kara, Adem; Ozkanlar, Seckin; Gelen, Sevda Urcar; Iskender, Hatice Akyuz; Gedikli, Semin
Bromelain is a mix of proteolytic enzymes obtained from the pineapple plant's fruit or stem. The effect of various rates of bromelain supplementation on broiler growth and carcass performance, meat quality, antioxidant metabolism, and blood profiles were examined in this study. In total, 288 male broiler chicks ( Ross 308) one-day-old were used to determine the effects of different doses of bromelain (0, 0.15, 0.30, and 0.45 g / kg diet) during the six-week trial period. The trial groups consisted of six replicates of twelve animals each. Bromelain (30g/kg diet) improved the feed conversion ratio (FCR) and increased final body weight (BW) and body weight gain (BWG) (P<0.05). Bromelain increased malondialdehyde (MDA) levels in the drumstick tissue (P<0.05). Bromelain decreased serum cholesterol (COL), High-density lipoprotein (HDL), and Low-density lipoprotein (LDL). Bromelain did not affect drumstick and breast meats' pH value but had shown a limited and variable effect on the color parameters and Thiobarbituric acid reactive substances (TBARS) during the storage period. Bromelain increased goblet cell number (GCN), crypt depth (CD), villus length (VL), and epithelial height (EH) (P<0.05) in the small intestine. In conclusion, bromelain had a minor impact on meat microbiological quality but improved intestinal morphology and final performance parameters.
The Effects of Cetuximab with Agomelatine on Gene Expression in Colon Cancer Cells
(2024) Erbaş, Elif; Kara, Adem; Ustundag, Hilal; Albayrak, Kevser; Köse, Rukiye
This study investigated the combined effects of agomelatine, a melatonergic antidepressant, and cetuximab, an EGFR inhibitor, on the colorectal cancer cell line (Caco-2). Caco-2 cells were treated with agomelatine (0.3 μg/ml and 3 μg/ml) and cetuximab (50 μg/ml), individually and in combination, for 24 and 48 hours. Cell viability was assessed using the MTT assay. Gene expression analysis of EGFR, BCL2, PIK3CA, BAX, mTOR, and AKT3 was performed using real-time PCR. All treatment groups showed significant decreases in cell viability compared to the control (p<0.05), with enhanced effects in combined treatments. EGFR expression was significantly reduced in drug-treated groups, particularly with cetuximab (p<0.05). While changes were observed in BCL2, PIK3CA, BAX, mTOR, and AKT3 expression, these were not statistically significant (p>0.05). This study demonstrates the potential synergistic cytotoxic effects of agomelatine and cetuximab on Caco-2 colorectal cancer cells. The significant reduction in EGFR expression suggests a potential mechanism of action. These findings provide insights into combining chemotherapeutic agents with drugs addressing circadian rhythm disorders in CRC treatment strategies. Further research is warranted to elucidate the clinical implications of these observations.
Effects of Dietary Thyme and Rosemary Essential Oils on Biochemical Parameters, Anti-Oxidant Metabolism, Small Intestinal Morphology and Myofiber Structure of Superficial Pectoral and Biceps Femoris Muscles in Broilers
(Urmia Univ, 2023) Gumus, Recep; Kara, Adem; Ozkanlar, Seckin; Imik, Halit; Celep, Nevra Aydemir
This study was aimed at determining the effects of dietary supplementation with thyme essential oil (TEO) and rosemary essential oil (REO) on blood parameters, the anti-oxidant metabolism in the liver, breast and drumstick muscle tissues, the morphology of the small intestine, and the myofibril structure of the superficial pectoral and biceps femoris muscles. For this purpose, 400 three-day-old male Ross 308 chicks were used. Five groups, each comprising 80 broilers, were established. The control group was fed on a basal diet alone and groups thyme -1, thyme-2, rosemary-1 and rosemary-2 received basal diets supplemented with 0.15 g kg-1 of TEO, 0.30 g kg-1 of TEO, 0.10 g kg-1 of REO and 0.20 g kg-1 of REO, respectively. The serum total cholesterol and low-density lipoprotein levels were decreased significantly in group thyme-1. Dietary TEO and REO significantly increased glutathione levels in all tissues. Drumstick catalase activity was significantly increased in groups thyme-1, thyme-2 and rosemary-2. Superoxide dismutase activity was significantly increased in the breast muscle of all groups that received dietary TEO and REO. Histomorphometrical analyses demonstrated that dietary supplementation with TEO and REO increased both crypt depth and villus height in the small intestine. In result, the tested doses of dietary TEO and REO were ascertained to improve the intestinal morphology and to increase the anti-oxidant metabolism mainly in the breast muscle, the drumstick muscle and liver. (c) 2023 Urmia University. All rights reserved.
Effects of Graphite Incorporation and Annealing on the Structural, Tribological, and Functional Properties of Electroless Ni-B Coatings
(Springer, 2026) Bulbul, Ferhat; Kara, Adem; Bulbul, Leman Elif; Gunes, Kubra
This study explores the synergistic effects of graphite nanoparticles (0.1 wt.%) and thermal annealing (100-600 degrees C) on electroless Ni-B coatings for AISI 4140 steel. Graphite-enabled multifunctional performance-crystallization control, friction reduction, and antibacterial activity-are unlike conventional Ni-B systems. XRD showed amorphous-to-crystalline (Ni3B/Ni2B) transformation, with graphite acting as a nucleation agent below 300 degrees C before degrading at 600 degrees C. The 300 degrees C-annealed composite achieved optimal properties: 0.2 friction coefficient (75% lower than uncoated steel), 60% higher wear resistance, and hardness of 777 HV (+ 3.6% over as-deposited), attributed to graphite lubrication and nanocrystalline Ni3B formation. Antibacterial tests revealed a 3.4-mm inhibition zone against E. coli, though efficacy declined at higher temperatures due to graphite oxidation. All composites maintained superhydrophilicity (contact angle approximate to 0 degrees) without mechanical compromise. By correlating annealing temperature with microstructure, this work provides a design framework for Ni-B/graphite coatings combining low friction (mu = 0.2), high hardness (785 HV), and antibacterial functionality-addressing critical needs for wear-resistant, hygienic surfaces in biomedical and industrial applications.
Effects of Silver Nanoparticle-Loaded 18β-Glycyrrhetinic Acid on P2x7 Receptor and Endoplasmic Reticulum Stress-Mediated Nlrp3 Inflammasome Activation in Testicular Tissue in an Animal Diabetes Model
(Wiley, 2025) Gelen, Volkan; Yesildag, Ali; Akarsu, Serkan Ali; Kara, Hulya; Tekiner, Deniz; Kara, Adem
Diabetes, a metabolic disease characterized by high blood sugar, causes damage to many organs in the body. Accordingly, the present study investigates the effects of silver nanoparticle-loaded 18 beta-glycyrrhetinic acid (AgNP+18 beta-GA) on P2X7 receptor and ER stress-mediated NLRP3 inflammasome activation in testicular tissue. 42 Wistar-Albino rats aged 6 months were used. The rats were divided into the following seven groups: Control, AgNP+18 beta-GA100, DM, DM-18 beta-GA100, DM-AgNP+18 beta-GA50, DM-AgNP+18 beta-GA100, and DM-AgNP. After the experiment, sperm samples obtained from the rats were evaluated. Oxidative stress markers, serum IL-1 beta, and TNF-alpha levels were determined in the testicular tissue samples taken separately. In addition, Caspase-1, NLRP3, P2X7, Caspase-3, NF-kappa B, IRE1, ATF6, and CHOP protein expression levels were evaluated using Western blot analysis of histopathological examinations. Specifically, the most significant decrease was observed in NLRP3, Caspase-1, P2X7, and NF-kappa B levels in the DM-AgNP+18 beta-GA100 group (p < 0.05). About sperm parameters, while sperm motility and viability significantly decreased in diabetic groups (p < 0.05), a significant improvement in these values was observed in the AgNP+18 beta-GA applied groups (p < 0.05). AgNP+18 beta-GA improved sperm morphology and histopathological damage in diabetes-induced testicular damage, as well as inhibited P2X7 receptor and endoplasmic reticulum stress-mediated NLRP3 inflammasome activation.