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Öğe 2-Phenylethyne-1-Sulfonamide Derivatives as New Drugs Candidates for Heat Shock Protein 70 and Doublecortin-like Kinase(DergiPark, 2021) Ergul, Mustafa; Sayin, Koray; Ataseven, HilmiUnder physiological conditions HSP70 plays crucial roles in protein homeostasis. This protein is overexpressed in many types of cancer cells and increased levels of HSP70 is closely associated with tumorigenesis and poor clinical outcomes. The present study was designed to evaluate in silico assessment of newly designed 30 different 2-Phenylethyne-1-Sulfonamide derivatives potential heat shock protein 70 inhibitors. The mentioned structures were optimized at B3LYP/6-31+G(d, p) level in water and active sites of them are determined. Then, molecular docking calculations were done between the related structures and 4PO2 and 5JZN. It is found that compound (5), (12) and (20) were found as the better ones than those of compound (1) and (2). Drug likeness studies were performed via pharmacological ADME (absorption, distribution, metabolism, and excretion) properties estimation and the drug properties of (5) and (12) were found as the better than those of compound (1), (2) and (20). © 2021. All Rights Reserved.Öğe Alpha-Fetoprotein Response After Locoregional Therapy for Hepatocellular Carcinoma(AMER SOC CLINICAL ONCOLOGY, 2010) Kilickap, Saadettin; Arslan, Cagatay; Senel, Soner; Ataseven, Hilmi…Öğe Anticancer activity of sinapic acid by inducing apoptosis in HT-29 human colon cancer cell line(Canadian Science Publishing, 2023) Tastemur, Seyma; Hacisuleyman, Levent; Karata, Ozhan; Yulak, Fatih; Ataseven, HilmiColorectal cancer is the third most lethal and fourth most commonly diagnosed cancer worldwide. Sinapic acid, a derivative of hydroxycinnamic acid, is a promising phytochemical exhibiting numerous pharmacological activities in various systems. It is a substantial chain-breaking antioxidant that operates as a radical scavenger. The aim of this research was to investigate the antiproliferative effect of sinapic acid on the HT-29 cell line besides the mechanisms underlying this activity. The effect of sinapic acid on the viability of HT-29 cell line was investigated using XTT assay. The levels of BCL-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG were measured using ELISA. Gamma-H2AX and cytochrome c expressions were assessed semiquantitatively using immunofluorescence staining. Sinapic acid at 200 & mu;m and higher doses produced a significant antiproliferative effect on HT-29 cells. The IC50 value was found to be 317.5 & mu;m for 24 h. Sinapic acid (317.5 & mu;m) significantly elevated cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG levels. The levels of gamma-H2AX foci are significantly higher, while the levels of cytochrome c are lower in sinapic acid-treated HT-29 cells. These results indicate that sinapic acid has antiproliferative, apoptotic, and genotoxic effects on colon cancer cells.Öğe Comparison and Evaluation of CTGF and P2/MS as Noninvasive Markers in Fibrosis Evaluation in Chronic Liver Diseases(Sivas Cumhuriyet University, 2022) Çiftel, Serpil; Yönem, Naciye Özlem Saygılı; Ataseven, Hilmi; Çiftel, Sedat; Altun, AhmetBackground/Aims: To compare CTGF (connective tissue growth factor) and P2/MSÖğe Could Momordica Charantia Be Effective In The Treatment of COVID19?(2022) Tüzün, Burak; Sayın, Koray; Ataseven, HilmiOne of the deadliest diseases is the SARS-CoV-2 virus, today. The rate of spread of this virus is very high. Momordica Charantia extracts studied for this virus. The inhibitory activities of 96 components in the extract of Momordica Charantia were compared against the SARS-CoV-2 virus. Molecular docking method was initially used for this comparison. ADME/T analysis of the inhibitors with the highest inhibitory activity was performed using the results obtained from these calculations. The molecular docking calculations of the molecule with the highest inhibitory activity were tried to be supported by MM-PBSA calculations. The molecular mechanics Poisson-Boltzmann surface binding free energy values of area (MM-PBSA) calculations study interactions between inhibitor molecules and SARS-CoV-2 virus proteins at 100 ps. Finally, the molecules with the highest inhibitory activity were compared with FDA approved drugs. As a result of the made molecular docking calculations, the docking score parameter is Karaviloside III with -9.36, among the extracts of momordica charantia, which has the most negative value. The Gibbs free energy value of the Karaviloside III against 6X6P protein with the best docking score value was calculated. This value is -477143.61±476.53. As a result of the comparison of inhibitory activities of extracts of Momordica charantia against SARS-CoV-2 virus, it has been observed that the Karaviloside III molecule has higher inhibitory activity than other melodies and FDA drugs.Öğe Could Momordica Charantia Be Effective In The Treatment of COVID19?(Sivas Cumhuriyet University, 2022) Tüzün, Burak; Sayin, Koray; Ataseven, HilmiOne of the deadliest diseases is the SARS-CoV-2 virus, today. The rate of spread of this virus is very high. Momordica Charantia extracts studied for this virus. The inhibitory activities of 96 components in the extract of Momordica Charantia were compared against the SARS-CoV-2 virus. Molecular docking method was initially used for this comparison. ADME/T analysis of the inhibitors with the highest inhibitory activity was performed using the results obtained from these calculations. The molecular docking calculations of the molecule with the highest inhibitory activity were tried to be supported by MM-PBSA calculations. The molecular mechanics Poisson-Boltzmann surface binding free energy values of area (MM-PBSA) calculations study interactions between inhibitor molecules and SARS-CoV-2 virus proteins at 100 ps. Finally, the molecules with the highest inhibitory activity were compared with FDA approved drugs. As a result of the made molecular docking calculations, the docking score parameter is Karaviloside III with -9.36, among the extracts of momordica charantia, which has the most negative value. The Gibbs free energy value of the Karaviloside III against 6X6P protein with the best docking score value was calculated. This value is -477143.61±476.53. As a result of the comparison of inhibitory activities of extracts of Momordica charantia against SARS-CoV-2 virus, it has been observed that the Karaviloside III molecule has higher inhibitory activity than other melodies and FDA drugs.Öğe Design, synthesis, in vitro and computational analyses of anticancer nicotinamide derivatives(Natl Inst Science Communication & Policy Research-Niscpr, 2024) Gomec, Muhammed; Nasif, Vesim; Kafa, Ayse Huemeyra Taskin; Sayin, Koray; Gezegen, Hayreddin; Ataseven, HilmiThe search for ideal treatment continues for many health problems such as cancer and infection. In this context, new synthesis compounds have been promising and the nicotinamide derivative compounds, which is an important heterocyclic derivative, has attracted the attention of many researchers. Nowdays, anticancer, antifungal, antimicrobial, antibacterial and antibiofilm effects of some nicotinamide derivatives have been demonstrated. In this study, nine new nicotinamide derivative compounds have been designed and synthesized. The characterization of these synthesized compounds have been done by in silico methods. The anticancer effects of the compounds have been investigated in four different cancer types and compared with their effects on healthy fibroblast cells. N4 has been found to have a cytotoxic effect on MCF-7 human breast cancer, and the IC50 value has been calculated as 12.1 mu M. In addition, antibacterial, antifungal and antibiofilm activities were investigated by in vitro methods and they have been shown to be effective. As a result, it is observed that N4, one of the newly synthesized nicotinamide derivative compounds, has a serious cytotoxic effect in MCF-7 human breast cancer cells compared to healthy fibroblast cells. Pharmacophore map and ADME analyses of studied compound are performed in detail.Öğe Does mean platelet volume influence the attack or attack-free period in the patients with Familial Mediterranean fever?(INFORMA HEALTHCARE, 2013) Sahin, Safak; Senel, Soner; Ataseven, Hilmi; Yalcin, IlkerFamilial Mediterranean fever (FMF) is an autosomal recessive hereditary disease which is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease. Mean platelet volume (MPV) is a sign of platelet activation. There are limited studies in the literature about MPV levels in FMF patients. We aimed to investigate MPV levels during the attack period (group 1) and attack-free periods (group 2) in FMF patients, and to compare them with healthy controls (group 3). The study consisted of the data of: 60 group 1 patients, 120 group 2 patients, and 75 group 3 patients. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded from patient files. Statistical analyses showed that MPV was significantly lower in FMF patients both in group 1 and group 2 than in group 3 (p = 0.004, p = 0.002, respectively); however, there was no difference among group 1 and group 2 in patients with FMF (p = 0.279). The mean platelet count of group 1 was higher than that of group 3 (p = 0.010). In conclusion, this study results suggested that MPV level did not increase on the contrary, it decreased in patients with FMF both in group 1 and/or group 2 when compared to group 3. It was concluded that the lower MPV level was an expected result of secondary thrombocytosis in FMF patients.Öğe Effects of dexpanthenol on 5-fluorouraci-induced nephrotoxicity, hepatotoxicity, and intestinal mucositis in rats: a clinical, biochemical, and pathological study(Walter De Gruyter Gmbh, 2025) Tastemur, Seyma; Ekici, Mehmet; Mendil, Ali Sefa; Ozkaraca, Mustafa; Ataseven, HilmiBackground5-fluorouracil (5-FU) is a broad-spectrum drug that has a wide range of side effects. Patients may experience severe comorbidities as a result of these toxic side effects, making it impossible for them to continue chemotherapy. Despite the fact that various molecules have been experimented, there is no literature data on the efficacy of dexpanthenol (DXP) for mitigating the toxic effects of 5-FU.ObjectiveTo investigate the protective effects of DXP on nephrotoxicity, hepatotoxicity, and intestinal toxicity induced by 5-FU in rats.MethodsTwenty-eight male Wistar-Albino rats aged 16 weeks were randomly assigned to four groups. We created a rat model of intestinal mucositis, nephrotoxicity, and hepatotoxicity through intraperitoneal 5-FU (35 mg/kg for 4 d) injection. 500 mg/kg and 1000 mg/kg of DXP were administered to the treatment groups. The effects of dexpanthenol were evaluated clinically, biochemically, histopathologically, and immunohistochemically (inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2], 8-hydroxyguanosine [8-OHdG], and nuclear factor kappa B [NF-kappa B]).Results5-FU caused a decrease in body weight and food intake, and an increase in diarrhea scores in rats. 5-FU led to significant disruptions in the hepatic biochemical markers (aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase [ALP], total bilirubin, direct bilirubin, and lactate dehydrogenase [LDH]), renal biochemical markers (blood urea nitrogen [BUN], creatinine, and uric acid), and protein and albumin, which are markers of both hepatic and renal functions. Severe pyknosis and mononuclear cell infiltrations were observed in the liver, and mononuclear cell infiltration and tubular degeneration in the kidneys. Jejunum and colon showed villous hyperemia and hemorrhage, respectively, along with mononuclear cell infiltration. Furthermore, 5-FU increased the immunohistochemical expressions of iNOS, COX-2, 8-OHdG, and NF-kappa B in the examined tissues. The administration of DXP at doses of 500 mg/kg and 1000 mg/kg demonstrated significant mitigation of the toxic effects induced by 5-FU on the liver, kidney, jejunum, and colon.ConclusionDXP showed protective effects against nephrotoxicity, hepatotoxicity, and intestinal toxicity caused by 5-FU. These findings suggest that DXP may serve as a potential therapeutic agent to alleviate the severe side effects of 5-FU chemotherapy, thereby improving patient tolerance and quality of life. Further clinical studies are warranted to validate these results and explore the translational potential of DXP in human cancer therapy.Öğe Exosome: an emerging participant in liver disease progression(Wiley, 2021) Kilgoz, Havva Ozgen; Ozcan, Seda Sabah; Gokcan, Hale; Yilmaz, Neziha; Ataseven, Hilmi; Akdogan, Meral; Kayacetin, Ertugrul[Abstract Not Available]Öğe Farklı bir bakış açısı ile plazma değişiminin hiperbilirubinemideki rolü(Sivas Cumhuriyet University, 2019) Terzi, Hatice; Korkmaz, Serdal; Şencan, Mehmet; Yönem, Özlem; Yılmaz, Abdulkerim; Ataseven, HilmiAmaç: Bu retrospektif çalışmada hiperbilirubinemiyi yönetme deneyimimizi sunmayı amaçladık.Yöntem: Çalışmaya Sivas Cumhuriyet Üniversitesi Tıp Fakültesi aferez ünitesinde 2006-2017 yılları arasında aferez tedavisi alan 21 hiperbilirubinemili hasta alındı. Hastaların dosyaları retrospektif olarak değerlendirildi ve şu veriler toplandı: hastanın yaşı, cinsiyeti, semptomları, plazma değişimi sayısı, adjuvan tedavi yöntemleri, sıvı replasmanı kullanımı, tedavi sonuçları ve plazma değişim komplikasyonları.Bulgular: Hastaların yaş ortalaması 57 idi (dağılım; 18-82). Ortalama plazma değişim sayısı 5,5'tir (aralık; 1-25). Sıvı değişimi için sadece taze donmuş plazma kullanıldı. Plazma öncesi ve sonrası değişim bilirubin düzeyleri arasında istatistiksel olarak anlamlı fark vardı (p <0.05). Toksik hepatit, hasta popülasyonumuzda en sık görülen hiperbilirubinemi nedeni idi. Hastalar plazma değişiminin yanı sıra, altta yatan durumuna uygun şekilde tedavi edildiler. Komplikasyon olarak, 2 hastada(% 8.69) allerjik reaksiyon ve 3 hastada(% 13) hipotansiyon gözlemledik. Sonuç: Plazma değişimi, bilirubinin uzaklaştırılması için güvenli bir yöntemdir. Ancak, plazma değişimi ve altta yatan durumun uygun tedavisi ile birlikte azalan hiperbilirubinemi, tedavide birincil amaç olmalıdır.Öğe Hipertansif hastalarda anjiyotensin konverting enzim inhibitörü (fosinopril) ve anjiyotensin reseptör blokeri (irbesartan)’nın serum ve idrar elektrolitleri üzerine etkileri(Cumhuriyet Üniversitesi, 2002) Ataseven, Hilmi; Candan, FerhanVH.Ö2ET Hipertansiyon, sık görülen, morbidite ve mortalitesi yüksek olan önemli bir toplum sağlığı sorunudur. Patogenezinde, bir çok sebep rol almakla birlikte hem neden ve hem de sonuç olarak böbrekler ve renin-anjiyotensin-aldosteron sistemi önemlidir. Bu sistemi herhangi bir aşamada inhibe eden antihiperlansiflerin öncelikli kullanımı mantıklı görünmektedir. Bu çalışmada hipertansif hastalarda A II antagonist irbesartan ile ACE inhibitörü fosinoprilin 1. haftada ve 3. ay sonunda, kan basınçları ve renal etkilerini değerlendirdik. Bu çalışmada, 15 kadın ve 6 erkek olmak üzere toplam 21 hastaya 450- 300 mg/gün irbesartan; 17 kadın ve 5 erkek olmak üzere top, lam 22 hastaya da 10-20 mg/gün fosinopril verdik. Çalışma başlangıcında, ilâç kullanımından bir hafta ve üç ay sonra sistolik ve diyastolik kan basıncı, dakikalık kalp hızı, kan üre azotu, serum kreatinin, ürik asit, elektrolit ve mineral düzeylerine ve idrarda ürik asit, elektrolit ve mineraller ile albümin atılımına etkisine baktık. Her iki grupta da kan basınçları anlamlı şekilde düştü. Kalp hızı, kan üre azotu, serum kreatinin, potasyum, kalsiyum, fosfor, magnezyum seviyeleri anlamlı değişmedi. İdrarla albümin, potasyum, kalsiyum ve magnezyum atılımında her iki grupta da azalma olduğu gözlendi. İdrar sodyum ve klor atılımı birinci haftada arttı, üçüncü ay sonunda birinci haftaya göre bir değişiklik olmadı; buna paralel olarak serum düzeylerinde birinci haftada düşme gözlendi, üçüncü ay sonunda ise değişiklik olmadı. Fosinopril grubunda idrarla ürik asit atılımında artma, serum düzeylerinde azalma olurken irbesartan grubunda böyle bir etki görülmedi. Sonuç olarak her iki ilacın antihipertansif ve renal etkilerinin - ürik asit atılımı dışında - benzer olduğu gözlendi. Bu da her iki tedavi rejiminin asıl etkilerini anjiyötensin II üzerinden oluşturduğunu desteklemektedir. Ancak bu konuda net bir şeyler söylemek için daha ileri çalınmalara ihtiyaç vardır. 72Öğe Iatrogenic pneumoscrotum after colonoscopy(TURKISH SOC GASTROENTEROLOGY, 2011) Cakmak, Erol; Koyuncu, Ayhan; Yilmaz, Abdulkerim; Yonem, Ozlem; Ataseven, Hilmi; Sarkis, Cihat…Öğe Investigation of Antiparasitic Properties of Benzimidazole Derivatives Against Amebiasis(DergiPark, 2022) Ataş, Ahmet Duran; Ataseven, Hilmi; Sayin, KorayEntamoeba histolytica is one of the common causes of infection in humans around the world. It causes clinically significant infection due to the fact that it causes morbidity and mortality. There is a need for new and safe drugs in the treatment of amebiasis. In this study, the activity of proton pump inhibitors against this parasite were investigated. Pantoprazole, lansoprazole, omeprazole, esomeprazole and rabeprazole were examined in detail. Initially, related drugs are optimized at M062X/6-31+G(d) level in water. Then, 3JS5, 3IDO and 3ILY were minimized at OPLS3e method. The docking calculations were performed and it is found that pantoprazole could be a significant candidate in the inhibiting of Entamoeba histolytica. Then, the interaction between pantoprazole and the target parasite were examined in the range of 0 - 100 nanoseconds (ns). The interaction energies in each one ns were calculated. As a result, the interaction was found as stronger than 88 ns. Pantoprazole was clinged to Entamoeba histolytica to inhibiting it. © 2022. All Rights Reserved.Öğe Investigation of Antiparasitic Properties of Benzimidazole Derivatives Against Amebiasis(Koray SAYIN, 2022) Ataş, Ahmet Duran; Ataseven, Hilmi; Sayın, KorayEntamoeba histolytica is one of the common causes of infection in humans around the world. It causes clinically significant infection due to the fact that it causes morbidity and mortality. There is a need for new and safe drugs in the treatment of amebiasis. In this study, the activity of proton pump inhibitors against this parasite were investigated. Pantoprazole, lansoprazole, omeprazole, esomeprazole and rabeprazole were examined in detail. Initially, related drugs are optimized at M062X/6-31+G(d) level in water. Then, 3JS5, 3IDO and 3ILY were minimized at OPLS3e method. The docking calculations were performed and it is found that pantoprazole could be a significant candidate in the inhibiting of Entamoeba histolytica. Then, the interaction between pantoprazole and the target parasite were examined in the range of 0 – 100 nanoseconds (ns). The interaction energies in each one ns were calculated. As a result, the interaction was found as stronger than 88 ns. Pantoprazole was clinged to Entamoeba histolytica to inhibiting it.Öğe Is it possible to use Proton Pump Inhibitors in COVID-19 treatment and prophylaxis?(Elsevier, 2020) Tastemur, Seyma; Ataseven, HilmiCoronaviruses (CoV), discovered after 1960, caused human life-threatening outbreaks. SARS-CoV2, which appeared in Wuhan, China in December 2019, causing Severe Acute Respiratory Syndrome and has different features than other coronaviruses, has been determined and the disease caused by the virus has been called Coronavirus Disease-2019 (COVID-19). This disease activates both the natural and acquired immune system. The cytokin storm, in which blood levels of proinflammatory cytokines are detected excessively high is developing and the uncontrolled inflammatory response causes local and systemic tissue damages. Although a spesific drug has not been found yet, the medications currently in use for other indications, whose pharmacokineticpharmacodynamic properties and toxic doses are already known; are included in the treatment practice of COVID-19. These drugs affect the entry of the virus into the cell and its intracellular distribution. They also have anti-inflammatory and immunomodulating effects too. Therefore, we think that Proton Pump Inhibitors (PPI's) with similar mechanisms of action may also be involved in COVID-19 treatment and prophylaxis.Öğe Long-term clinical outcomes of Entecavir and .tenofovir in hepatitis B cirrhosis(WILEY-BLACKWELL, 2012) Koklu, Seyfettin; Tuna, Yasar; Gulsen, Murat T.; Demir, Mehmet; Koksal, Aydin S.; Kockar, Muhammed C.; Aygun, Cem; Coban, Sahin; Ozdil, Kamil; Ataseven, Huseyin; Akin, Ebru; Purnak, Tugrul; Yuksel, Ilhami; Ataseven, Hilmi; Ibis, Mehmet; Yildirim, Beytullah; Nadir, Isilay; Kucukazman, Metin; Akbal, Erdem; Yuksel, Osman…Öğe Long-term Efficacy and Safety of Lamivudine, Entecavir, and Tenofovir for Treatment of Hepatitis B Virus-Related Cirrhosis(ELSEVIER SCIENCE INC, 2013) Koklu, Seyfettin; Tuna, Yasar; Gulsen, Murat Taner; Demir, Mehmet; Koksal, Aydin Seref; Kockar, Muhammet Cem; Aygun, Cem; Coban, Sahin; Ozdil, Kamil; Ataseven, Huseyin; Akin, Ebru; Purnak, Tugrul; Yuksel, Ilhami; Ataseven, Hilmi; Ibis, Mehmet; Yildirim, Beytullah; Nadir, Isilay; Kucukazman, Metin; Akbal, Erdem; Yuksel, Osman; Basar, Omer; Alkan, Erhan; Baykal, OzlemBACKGROUND & AIMS: Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS: We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 +/- 9.7 mo), 77 patients received entecavir (followed up for 24.0 +/- 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 +/- 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS: Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS: Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.Öğe Mechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinoma(Humana Press Inc, 2023) Joha, Ziad; Ozturk, Aysegul; Yulak, Fatih; Karatas, Ozhan; Ataseven, HilmiGambogic acid has demonstrated inhibitory effects on the growth of various cancer cell types, such as breast cancer, pancreatic cancer, prostate cancer, lung cancer, and osteosarcoma. This study aims to investigate the antiproliferative activity of Gambogic acid on SNU-16 cells derived from gastric signet ring cell carcinoma and elucidate the underlying mechanisms. The cytotoxic effect of gambogic acid was evaluated in SNU-16 cells by treating them with different concentrations of the compound, and the XTT cell viability assay was employed to assess cell viability. ELISA was used to measure bax, BCL-2, caspase 3, PARP, and 8-oxo-dG levels. Additionally, immunofluorescence staining was applied to assess 8-oxo-dG and LC3 & beta; levels in SNU-16 cells. It was observed that gambogic acid exerted a dose-dependent and statistically significant antiproliferative effect on SNU-16 cells. The IC50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 h. Subsequent investigations conducted using the IC50 dose revealed a significant upregulation of apoptotic proteins including cleaved caspase 3, Bax, and cleaved PARP (p < 0.001), along with a downregulation of BCL-2 (p < 0.001), an anti-apoptotic protein. Moreover, the administration of this drug led to an upregulation of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicating oxidative damage in DNA, as well as an increase in LC3 & beta; levels (p < 0.05), a marker associated with autophagy. The antiproliferative effect of gambogic acid against gastric signet ring cell carcinoma is attributed to its ability to induce apoptosis and autophagy. This discovery highlights the promising potential of gambogic acid as a treatment option for gastric signet ring cell carcinoma.Öğe Methylation profile of CD247 and FOXP3 genes and frequency of certain HLA-DQ haplotypes in Celiac disease(Elsevier Masson, Corp Off, 2025) Yildirim, Malik Ejder; Ataseven, Hilmi; Kurtulgan, Hande Kucuk; Tastemur, Seyma; Sirin, AhmetBackground: Celiac disease is an autoimmune disorder that affects the small intestine in people with gluten intolerance. HLA-DQ2 and DQ8 have been associated with Celiac Disease. CD247 is a subunit of the T cell receptor complex and Forkhead box P3 (FOXP3) is a transcription factor involved in the regulation of the immune response. Expression levels of these two markers in various diseases, including autoimmune disorders, are controversial. In this context, we aimed to shed light on the etiopathogenesis of Celiac disease by determining the methylation profile of CD247 and FOXP3 genes, and to calculate the frequency of HLA-DQ haplotypes in this disease. Methods: Methylated and unmethylated copy numbers of the CD247 and FOXP3 genes in samples were calculated using the methylation-specific qPCR method. The records regarding HLA-DQ2 and DQ8 genotypes previously detected from our patients by Real Time PCR and tissue transglutaminase IgA (TTG-IgA) by ELISA, were analyzed. Results: CD247 methylation rate in our patients was significantly lower than in controls. According to the Marsh classification, the methylation level in Marsh type 2-3 patients was statistically lower than in type 1. On the contrary, FOXP3 had a significantly higher methylation rate in the patient group compared to healthy controls, and this gene was also found to be more methylated in Marsh type 2-3 patients than in Marsh type 1. In the patient group, HLA-DQ2 positivity was 82.5% and HLA-DQ8 positivity was 37.5%. Conclusion: The data suggest that CD247 expression is upregulated, whereas FOXP3 expression is downregulated in Celiac disease. Among HLA haplotypes, HLA-DQ2 heterodimer came to the forefront with its frequency in terms of celiac predisposition.
