Temel Tıp Bilimleri Bölümü Makale Koleksiyonu

Bu koleksiyon için kalıcı URI

https://hdl.handle.net/20.500.12418/286

Listeleniyor 1 - 20 / 49

Leukotriene metabolism and proiflammatory cytokines in Crimean Congo hemorrhagic fever
(01.01.2023) Kübra Doğan; Serkan Bolat; Caner Öksüz; Seyit Ali Büyüktuna
Crimean–Congo hemorrhagic fever (CCHF) is an emerging acute viral infection disease, yet its pathophysiology remains largely uncharacterized. Lipid mediators are molecules that play numerous roles in the physiologic and pathophysiologic conditions in certain viral diseases. No previous study evaluated the status of cysteinyl leukotrienes (CYSLT) and 5-lipoxygenase (5-LO) and their relationship with proinflammatory cytokines in CCHF. A total of 90 subjects including 60 CCHF patients and 30 healthy controls were enrolled the study. Serum CYSLT, 5-LO, interleukin-6 (IL-6), and ferritin levels were determined in the study population. Lower median 5-LO level was determined in patients compared to healthy controls (p = 0.0004). Higher ferritin (p < 0.001) and IL-6 (p < 0.001) levels in patients than healthy controls. No statistically significant difference was observed between patients and controls in terms of CYSLT levels. No statistically significant differences were observed between mild, moderate, and severe groups in terms of both 5-LO and CYSLT levels. IL-6 and ferritin levels were higher in severe group compared mild and moderate groups. In conclusion, changes in 5-LO enzyme and increased inflammation are related with the disease molecular mechanism. Higher inflammatory status contributes to the impaired hemostatic balance in CCHF. Thus, treatment strategies to reduce inflammation may help to prevent bleeding and DIC in patients. IL-6 and ferritin can be used to as an additional biomarker in the estmation of the prognosis and diagnosis of the patients.
Biological evaluation and in silico molecular docking studies of Abies cilicica (Antoine & Kotschy) Carrière) resin
(Elsevier, 2023/9/15) Guclu, Gulsen; Tas, Ayca; Dincer, Emine; Ucar, Esra; Kaya,Savaş; Berisha, Avni; Dural, Emrah; Silig, Yavuz
Abies cilicica (Antoine & Kotschy) Carri`ere) is an endemic species of industrial and medicinal importance. The resin obtained from this plant is effective for different diseases. The chemical content of the ethanol extract of Abies cilicica resin by GC-MS method, its antimicrobial activity on 12 different microorganisms by MIC value, antibiofilm activity on six microorganisms by Christensen method and biological activities on three different cancer cell lines by MTT method were investigated in this study. The findings showed that antimicrobial and antibiofilm activity was high in L. monocytogenes. The resin extract showed strong anticancer activity on all three DU-145, HeLa and SaOS-2 cells. The major component of the resin was abietic acid. A molecular docking simulation of the major compounds from resin extracts was conducted. In this study, in which the strong bio logical properties of A.cilicica resin were revealed, which suggests that the resin can increase the inhibition of cancer cell growth while strengthening the immune system against pathogenic microorganisms. Molecular docking analysis performed supported the experimental observations. Further extensive studies will support the possibility of using this resin as a therapeutic agent.
Experimental and theoretical insights about the effect of some newly designed azomethine group?contained macroheterocycles on oxidative stress and DNA repair gene profiles in neuroblastoma cell lines
(Elsevier, 2023/8/5) Cinar, Gulcihan; Agbektas, Tugba; Huseynzada, Alakbar; Aliyeva, Gunel; Aghayev, Mirjavid; Hasanova, Ulviyya; Kaya, Savas; Chtita, Samir; Nour, Hassan; Tas, Ayca; Silig, Yavuz
We report herein the synthesis of new azomethine group containing forty-, sixty-eight- and seventy- two-membered macroheterocyclic compounds and the investigation of their activity against the neurob- lastoma cell line. The synthesis of targeted compounds was done by condensation of dialdehydes with polyamines and their structures were investigated by 1 H and 13 C NMR and MALDI MS methods. Anti- cancer activity of these newly synthesized molecules was studied in the neuroblastoma (SH-SY5Y) cell line at eight different concentrations (1–100 μg/ml) for 24 h, 48 hrs and 72 h by MTT method. In ad- dition to it, oxidative stress (GPX1, PRDX1, CAT, SOD1, NQO1) and DNA repair (ATR, ERCC1, CDKN1A, PRKDC) gene profiles were also investigated by RT-PCR method. It was found that all synthesized compounds showed the highest activity after 72 h of incubation. PRDX1 gene expression in the case of all investi- gated compounds was found to be higher than the control group, whereas ABCB1 (MDR) gene expression increased only in the case of molecule 1. Results also demonstrate that the expression levels of GPX and SOD1 genes were high in the case of molecule 2, whereas molecule 1 manifested low expression levels of ERCC1, ATR, CDKN1A, PRKDC, GPX1, ABCB1(MDR), CAT, SOD1 and NQO1 genes. Along with experimen- tal studies, theoretical studies were also carried out. The String v11 program was used to determine the interaction of proteins involved in oxidative stress and DNA repair mechanisms with other proteins. The results of the molecular docking analysis were found to be in good agreement with the experiments.
Anticancer activity, hTERT expression and telomere length analysis in SH-SY5Y neuroblastoma cell lines applied to docetaxel
(Elsevier, 05.02.2023) Inandiklioglu, Nihal; Tas, Ayca; Agbektas, Tugba; Tuncbilek, Zuhal; Raheem, Kayode Yomi; Cinar, Gulcihan; Silig, Yavuz
Neuroblastoma is the most common extracranial solid tumor of infancy in a broad range of clinical courses, ranging from spontaneous regression to fatal progression. Telomere maintenance plays an impor- tant role in genome stability and cell proliferation. Telomerase reverse transcriptase (hTERT in humans) is a catalytic subunit of the enzyme telomerase. In this study, it was aimed to determine the anticancer ac- tivity of the docetaxel chemotherapeutic agent in neuroblastoma cell line (SH-SY5Y) and to investigate its effect on hTERT gene expression level and telomere length. Molecular docking studies were performed on docetaxel with the crystal structure of telomerase. The electronic properties of docetaxel were calculated using the density functional theory (DFT) method. SH-SY5Y cells were treated for 24, 48 and 72 h with specific concentrations of docetaxel drug ranging from 1 to 100 μg/ml. IC50 doses of docetaxel were de- termined and administered to SH-SY5Y cells, followed by RNA isolation. hTERT and MYC gene expression levels and telomere length were measured in the docetaxel-treated sample using the RT-PCR method. In addition, theoretical analyzes were made. The IC50 values of docetaxel after 24, 48 and 72 h were 8.32 ±1.45 μg/ml, 7.67 ±2.56 μg/ml and 5.51 ±1.24 μg/ml, respectively. According to the results obtained, docetaxel was found to have the highest activity in 72 h of incubation. It was determined that the do- cetaxel drug decreased the expression level of the hTERT gene in SH-SY5Y cells. Telomere lengths were significantly reduced in the docetaxel treated SH-SY5Y cell line compared to the control group ( p < 0.05). Molecular docking analysis results were in agreement with the experiments. Analysis results indicated a good interaction between docetaxel and the active site of telomerase. The results of this study, reinforced by molecular docking analyzes, might be proved valuable for the development of potent telomerase in- hibitors.
The Effect of Cycle Threshold Value on Predicting Prognosis in CrimeanCongo Hemorrhagic Fever Disease
(22.12.2023)
Introduction: Crimean-Congo hemorrhagic fever (CCHF) disease is characterized by symptoms such as fever, headache, muscle aches, and bleeding. In severe cases, it can lead to death. Clinical and biochemical parameters, severity scoring systems, and some new biomarkers are used to predict the course of the disease. The cycle threshold (Ct) value is a measure used to indicate the number of cycles required for the target gene to reach a certain level of fluorescence in the polymerase chain reaction (PCR) test. This study aimed to evaluate the relationship between Ct values detected in PCR tests and disease prognosis. Materials and Methods: This study was conducted between May 2021 and September 2021. Adult patients with positive CCHF PCR test results were included in the study. The presence of CCHF virus-specific RNA in the serum samples of the patients at the time of admission was determined qualitatively by the RT-PCR method. The study aimed to assess the relationship between Ct values and clinical outcomes, including mortality. Results: A total of 168 patients, 62 (36.9%) female, and 106 (63.1%) male, were included in the study. A mortal course was observed in nine patients (5.4%). The Ct threshold value for predicting prognosis in CCHF disease was calculated as 19 using ROC analysis. Among the 39 patients with a Ct value of ≤19, the disease resulted in death in eight (20.5%) cases, while in the group of 129 patients with a Ct value >19, only one (0.8%) patient experienced mortality (p< 0.001). Conclusion: Ct values provide valuable information about the presence and amount of target genes in the sample. In cases where quantitative determination of viral load is not possible, the Ct threshold value is considered a guide for predicting disease prognosis.
The experiences and thoughts of Turkish family physicians about COVID-19 pandemic: A qualitative study
(14.02.2023) Ayhan Başer, Duygu; Döner Güner, Pınar; Gümüştakım, Raziye Şule; Ağadayı, Ezgi; Aksoy, Hilal; Fidancı, İzzet
Background: Efforts to contain the SARS-CoV-2 virus would fall short without strong primary health care. Objectives: In this study, we aimed to determine the experiences, views and suggestions of family physicians regarding their roles, primary care health systems’ preparedness and the challenges/ needs for a better organisation during the pandemic via in-depth exploration. Methods: Twenty-one family physicians working in different cities of Turkey participated in semi-structured interviews between 15/08/2020-21/01/2021. Convenience sampling was used. We did this qualitative study through interviews by telephone. Participants were asked seven open-ended questions. Thematic analysis was used, which included reading the transcript, identifying significant phrases and formulating meanings and validating meanings through research team discussions to reach consensus, identifying themes. Results: Ten of the participants were female and the average age of the participants was 39.5 (SD ¼ 10.5) years. Twelve of the family physicians are specialists in family medicine. Four themes were identified: role of primary care in the pandemic, pandemic preparedness of primary care, challenges of working in primary care centres during the COVID-19 pandemics, and approaches to future pandemics. Conclusion: Our study showed that, despite unprepared primary care and undefined roles of family physicians in pandemic planning, family physicians played a significant role in pandemic management.
Medical Students' Views and Attitudes toward Vaccine Refusal during the COVID-19 Pandemic: A Multicenter Study
(20.04.2024) Çınar Tanrıverdi, Esra; Ağadayı, Ezgi; Layık, Mehmet Emin; Nas, Mehmet Akif; Karahan, Seher; Çalıkoğlu, Elif Okşan
Background: The rapid development and production of COVID-19 vaccines have raised concerns about their safety and efficacy, which have contributed to vaccine hesitancy among some people. Objectives: This study aimed to determine the opinions and attitudes of medical students about COVID-19 vaccines and vaccine hesitancy. Methods: Nine hundred seventy-seven volunteer students from three medical faculties participated in this study, and data were collected via an online survey. A questionnaire consisting of 40 items and four parts, including sociodemographic information, COVID-19 vaccines, vaccine rejection, and vaccine hesitancy was used for data collection. In the questionnaire, the students were asked about their desire to be vaccinated, whether they want to be vaccinated for their families, vaccination indecision or rejection, and the reasons for not wanting to be vaccinated. Results: Among the students, the rate of vaccine rejection was 15.4% (n=150), and the rate of vaccine hesitancy was 18.9% (n=185). While 65.7% (n=642) wanted to be vaccinated against COVID-19, the rate of those who wanted their families to be vaccinated was 54.1% (n=529). Age and being in the preclinical period positively affected the vaccination decision, while a history of COVID-19 and being affected by vaccine technology negatively influenced the decision to be vaccinated. The vaccine acceptance rate was significantly higher in men than in women (P=0.002), in preclinical students than in clinical year students (P=0.049), and in those without a history of COVID-19 than in those who had COVID-19 (P<0.001). Conclusion: The attitudes of medical students toward COVID-19 vaccines were positive. However, considering that some students were hesitant to be vaccinated or against vaccination, we think it would be beneficial to integrate positive attitude development programs into the medical education curriculum.
The Turkish version of the problem areas in diabetes-parents of teens (P-PAID-T): Cross-cultural adaptation, reliability, and validity
(10.08.2023) Sarı, Aybüke Sarı; Ağadayı, Ezgi; Çelik, Nurullah; Karahan, Seher; Kömürlüoğlu Tan, Ayça; Döğer, Esra
Objective: To examine the Turkish validity and reliability of the Problem Areas in Diabetes- Parents of Teens (PPAID-T) scale and its psychometric properties for determining the parents’ diabetes-related distress. Methods: The study included the parents of 200 adolescents with T1DM for at least a year. P-PAID-T and a demographic data form were used for data collection. Davis technique was used for the content validity of the scale. The scale’s reliability was tested using test-retest, and its internal reliability was analyzed with Cronbach’s alpha test. Exploratory Factor Analysis (EFA) was used to analyze the factor structure. Confirmatory Factor Analysis (CFA) was used to evaluate the fit of the scale. Results: 69.5% (n = 139) of the participants were mothers. Compared to the fathers, the mothers’ mean P-PAID-T score was significantly higher. Parents of sons, who used insulin injections for their children, and had a college degree or higher education level had higher P-PAID-T scores. The test-retest correlation coefficient of the scale was 0.977. The Cronbach α value of the scale was 0.901. The results of confirmatory factor analysis were x2/df = 2.931, GFI = 0.736, CFI = 0.711, NFI = 0.628, NNFI = 0.660, RMSEA = 0.141. Conclusion: The Turkish version of P-PAID-T was a valid and reliable screening tool for measuring diabetes stress in parents of adolescents with T1DM. Practice implications: Nurses could use the Turkish version of P-PAID-T to monitor parental diabetes distress and organize interventions; also Turkish P-PAID-T could facilitate research on diabetes distress for parents of adolescents with T1DM.
Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia
(2023) ZEYNEP DENİZ ŞAHİN İNAN
Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinoci ceptive efect is an important clinical problem. Aspirin is an analgesic and antiapoptotic drug used in combination with morphine as an adjuvant in diabetic neuropathy. Our aim in this study was to investigate the efects of aspirin on mor phine-induced neuronal apoptosis and analgesic tolerance in rats with diabetic neuropathy. The antinociceptive efects of aspirin (50 mg/kg) and morphine (5 mg/kg) were evaluated by thermal pain tests. Streptozotocin (65 mg/kg) was injected intraperitoneally to induce diabetic neuropathy. To evaluate apoptosis, ELISA kits were used to measure caspase-3, Bax and Bcl-2 levels. Apoptotic cells were detected histologically by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. Study results indicate that prior administration of aspirin to diabetic rats signifcantly increased the antinociceptive efcacy of morphine compared to morphine alone. Thermal pain tests showed that aspirin signifcantly reduced morphine tolerance in rats with diabetic neuropathy. Biochemical analysis revealed that aspirin sig nifcantly decreased the levels of pro-apoptotic proteins, caspase-3 and Bax, while increasing the anti-apoptotic Bcl-2 in DRG neurons. Semiquantitative scoring demonstrated that aspirin provided a signifcant reduction in apoptotic cell counts in diabetic rats. In conclusion, these data suggested that aspirin attenuated morphine antinociceptive tolerance through anti-apoptotic activity in diabetic rat DRG neurons.
Preventive effects of Capparis Spinose extract on experimental periodontitis in rats: a histopathological and biochemical study
(2023) ZEYNEP DENİZ ŞAHİN İNAN
This study aimed to assess the effectiveness of Capparis Spinose (CS) in preventing the initiation and pro gression of experimental periodontitis and to evaluate the effect of its on systemic oxidative stress in rats by experimental periodontitis model. Twenty-four male rats were equally divided into; Ligatured (L), non-liga tured (NL), and Ligatured with CS (11 days/day per 20 mg/kg) (LC) groups. Experimental periodontitis was induced with the silk suture technic. Alveolar bone loss was examined, and total antioxidant capacity(TAOC), total oxidant status(TOS), and oxidative stress index(OSI) were analyzed in rat serum. Although; alveolar bone loss showed statistically significant lower values in the LC group compared to L (p < 0.05), not NL. In the LC group, osteoclast and osteoblast numbers were statistically significant compared to L, but there were no statistical differences between LC and NL. Serum TAOC levels were significantly lower in group L compared to others and also LC group showed significant differences from NL. TOS and OSI levels were significantly higher in group L than in other groups. Within the limitation of the present study, it can be said that the destruc tion via local inflammation that may occur after the experimental periodontitis can be prevented by using CS
The mechanism of anticancer effects of some pyrrolopyrimidine derivatives on HT-29 human colon cancer cells
(2023) mustafa ergül; zuhal kılıç kurt; yeliz aka; özgür kütük; ZEYNEP DENİZ ŞAHİN İNAN
In the present work, the mechanism of anticancer activity of some pyrrolopyrimidine derivatives was evaluated. Compounds 5 and 8 exhibiting significant antiproliferative activity against HT-29 cells with IC50 values of 4.17 μM and 2.96, arrested the cells at the G2/M phase and significantly induced apoptosis. The apoptotic potential of the compounds has been verified via ELISA assay, which resulted in increased BAX, PUMA, BIM, and cleaved caspase 3 expression and decreased BCL-XL and MCL-1 protein levels in HT-29 cells. Moreover, the immuno fluorescence technique showing that compounds 5 and 8-treatment reduced Ki67 immunolocalization and increased the caspase 3 and p53 immunolocalization confirmed the apoptotic activity. While treatment of HT-29 cells to compounds 5 and 8 inhibited Akt and ERK1/2, there are no alterations in JNK and p38 signaling pathways. According to molecular docking results, compounds 5 and 8 occupied the active site of Akt kinase and showed important hydrogen bonding interactions with key amino acids. Also, siRNA-mediated depletion of BIM, PUMA, and BAX/BAK expression decreased apoptotic response in HT-29 cells upon exposure to compound 5 and compound 8. Compounds 5 and 8 trigger the activation of mitochondrial apoptosis in HT-29 cells. Additionally, we found that proapoptotic BH3-only proteins BIM and PUMA are required for the full engagement of mito chondrial apoptosis signaling. However, p53 was dispensable for compound 5- or compound 8-induced apoptosis in HT-29 cells.
Investigating the Healing Effect of Hyperici Oleum and Triticum vulgare on Septal Perforation in Rats: A Preliminary Study
(2023) ZEYNEP DENİZ ŞAHİN İNAN; adem bora; kasım durmuş; yasin aslan; emine elif altuntaş
Objective: The aim of this study was to investigate histopathologically the possible beneficial effects of hyperici oleum and Triticum vulgare, having anti-inflammatory, antioxidant, and antiproliferative properties, on the healing process of nasal septum perforation experimentally. Methods: Circular perforations of 2 mm diameter were performed at the nasal septum of 32 rats. Intranasal administration of hyperici oleum (HO), Triticum vulgare (TV), and thiocilline (T) was carried out twice a day for 7 days. After the rats were sacrificed at the end of the seventh day, their nasal septum specimens were sent for histological examination. The groups were compared in terms of epithelial regeneration, presence of fibroblasts and inflammatory cells, and capillary density parameters. Results: There was a statistically significant increase in the epithelialization mean scores in groups HO and TV compared to group P. When the groups were examined in terms of inflammation, a statistically significant increase was found in group HO. In terms of the fibroblast scores, a statistically significant increase was seen between group P and groups HO and T. The vascularization mean scores both in group HO and group TV were statistically significant when they were compared with groups C and P. Conclusion: The present study provides clues for preferring the use of TV and HO as a healer for the perforation area in the treatment of septum perforation. Based on the findings, widening the experiment and including additional parameters for understanding the healing mechanism will contribute to the clarification of the healing mechanism and thus to the development of the treatment options.
Toxoplasma gondii and multiple sclerosis: a population-based case-control seroprevalence study, Central Anatolia, Turkey
(2023) Sevimligül, Gülgün; Akın Polat, Zübeyda; Gökçe, Şeyda Figül
Background: Toxoplasma gondii, an obligate intracellular parasite, is prevalent in various mammalian species, as well as certain avian, reptilian, and cold-blooded organisms. While immunocompetent individuals generally remain asymptomatic, immunocompromised individuals may experience severe and life-threatening conditions. Multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system (CNS), is characterized by inflammation, demyelination, and axonal damage. Despite extensive research, the etiology and pathogenesis of MS remain incompletely understood. Given the strong affinity of T. gondii for the CNS, researchers have explored the potential association between T. gondii and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and MS. This study aimed to investigate the possible relationship between MS and T. gondii. Methods: A population-based incident cohort of MS patients in Sivas, Turkey, was used to randomly select MS patients. Age- and sex-matched controls were also randomly selected from the general population. A total of 182 MS patients and 182 controls were included in the study. Clinical and socio-demographic variables were recorded using a structured questionnaire. Blood samples were collected from MS patients, and Toxoplasma IgG and IgM antibodies were measured using the enzyme-linked immunosorbent assay technique. Results: Anti-Toxoplasma IgG antibodies were detected in 78 cases (42.9%) and 73 controls (40.1%) (p>0.05). Age, female sex, and consumption of raw meat were identified as risk factors for toxoplasmosis in both MS patients and controls. Conclusion: In contrast to previous studies, this study did not find a significant difference in T. gondii seropositivity between the control group and MS patients. Further investigations are recommended to elucidate the precise relationship between MS patients and T. gondii.
Increased endoplasmic reticulum stress might be related to brain damage in hepatic ischemia-reperfusion injury
(2023) Halef Okan Dogan
Objectives: Our study aimed to investigate the role of endoplasmic reticulum stress (ER) in brain damage following hepatic ischemia-reperfusion (HIR) injury. Specifically, we characterized the expression of markers of ER stress and histopathologic changes in the brain following HIR. Methods: Twelve adults female Wistar rats were divided into two experimental groups equally. Group 1 was designed as the control group, and Group 2 was designed as the HIR group. Blood, liver, and brain tissue samples were collected during the sacrifice. The quantitative ELISA kits were used to detect glucose-regulated protein 78 (GRP-78), activating transcription factor 4 (ATF-4), eukaryotic initiation factor 2 alpha (EIF2-A), caspase-3, caspase-9, and CCAAT/enhancer-binding protein (CEBP) in plasma. Histopathological examination was performed for liver and brain tissues.Results: Higher levels of GRP-78 (p=0.006), ATF4 (p=0.001), and EIF2-Α (p=0.007) were detected in group 2. More damage was detected in liver and brain samples in the histopathological examination of group 2 than in group 1. Conclusions: Our results demonstrate that ER stress is involved in developing brain damage following hepatic ischemia-reperfusion injury, as evidenced by increased expression of markers of ER stress and neuronal injury.
Role of lncRNAs in Remodeling of the Coronary Artery Plaques in Patients with Atherosclerosis
(2023) Bayyurt, Burcu
Abstract Introduction Cardiovascular diseases (CVDs) are the leading cause of death worldwide according to World Health Organi zation (WHO) data. Atherosclerosis is considered as a chronic infammatory disease that develops in response to damage to the vascular intima-media layer in most cases. In recent years, epigenetic events have emerged as important players in the development and progression of CVDs. Since noncoding RNA (ncRNAs) are important regulators in the organization of the pathophysiological processes of the cardiovascular system, they have the potential to be used as therapeutic targets, diagnostic and prognostic biomarkers. In this study long noncoding RNA (lncRNA) and mRNA gene expression were com pared between coronary atherosclerotic plaques (CAP) and the internal mammary artery (IMA) which has the same genetic makeup and is exposed to the same environmental stress conditions with CAP in the same individual. Methods lncRNA and mRNA gene expressions were determined using the microarray in the samples. Microarray results were validated by RT-qPCR. Diferentially expressed genes (DEGs; lncRNAs and mRNAs) were determined by GeneSpring (Ver 3.0) [p values < 0.05 and fold change (FC) > 2]. DAVID bioinformatics program was used for Gene Ontology (GO) annotation and enrichment analyses of statistically signifcant genes between CAP and IMA tissue. Results and Conclusions In our study, 345 DEGs were found to be statistically signifcant (p < 0.05; FC > 2) between CAP and IMA. Of these, 65 were lncRNA and 280 were mRNA. Thirty-three lncRNAs were upregulated, while 32 lncRNAs were downregulated. Some of the important mRNAs are SPP1, CYP4B1, CHRDL1, MYOC, and ALKAL2, while some of the lncRNAs are LOC105377123, LINC01857, DIO3OS, LOC101928134, and KCNA3 between CAP and IMA tissue. We also identifed genes that correlated with statistically signifcant lncRNAs. The results of this study are expected to be an important source of data in the development of new genetically based drugs to prevent atherosclerotic plaque. In addition, the data obtained may contribute to the explanation of the epigenetic mechanisms that play a role in the pathological basis of the process that protects the IMA from atherosclerosis.
PENTİLENTETRAZOL İLE OLUŞTURULAN DENEYSEL EPİLEPSİ MODELLERİ
(Efe Akademik Yayıncılık, 2022) Şahin Bilal; Ergül Mustafa
Epilepsi, normal beyin işleyişini kesintiye uğratan öngörülemeyen ve tekrarlayan nöbetler içeren; dünya genelindeki nüfusun yaklaşık % 1 'ini etkileyen en yaygın nörolojik klinik bozukluklardan biridir. Nöbet aktivitesi mevcut anti-epileptik tedavi yöntemleri ile kontrol edilebilmekle birlikte epilepsiyi önlemekte veya iyileştirmekte yetersiz kalmaktadır. Ayrıca terapötik etkilerinin yanında anti-epileptik ilaçların nöroprotektif etki güçleri zayıftır ve uzun dönem kullanımları yan etkilerin oluşmasına yol açmaktadır. Bu nedenle, güncel yaklaşım çeşitli bileşenlerin nöroprotektif etkilerine odaklanmaktadır. Bununla birlikte önemli sayıda klinik ve epidemiyolojik çalışma, yetişkin epilepsi hastalarının yaklaşık üçte birinin (%20-30) ilaca veya cerrahi tedaviye yanıt vermeyen dirençli epilepsi türünde olduğunu göstermektedir. İnsan beyninde mikrokimyasal analizlerin ve hücre içi kayıtların alınması etik nedenlerden dolayı yapılamadığından epilepside deneysel hayvan modelleri hastalığın altta yatan mekanizmalarının aydınlatılması ve yeni anti-epileptik ilaçların (AEİ) keşfi için sıklıkla kullanılmaktadır. Bu amaçla gama aminobütirik asit-A (GABAA) iyon kanalı antagonisti olan pentilentetrazol (PTZ) epilepsi ve nöbet modelleri oluşturmak için yaygın olarak kullanılmaktadır. Mevcut çok sayıdaki hayvan nöbet modeli arasında, akut PTZ ile indüklenen miyoklonik nöbet modeli, olası AEİ'lerin antikonvülzan etkisini değerlendiren en yaygın kullanılan modeldir, Buna karşın kronik olarak PTZ'nin subkonvülsif dozlarda uygulanması ile oluşturulan kronik PTZ-kindling (tutuşma) modeli, insan epilepsisindekine benzer şekilde nöbet aktivitesinin yoğunlaşmasına veya nöbet duyarlılığının artmasına neden olmakta ve tekrarlayan nöbetlerin olduğu kronik epilepsi modellerini temsil etmektedir.
The 5-HT7 receptor antagonist SB-269970 alleviates seizure activity and downregulates hippocampal c-Fos expression in pentylenetetrazole-induced kindled rats
(NEUROLOGICAL RESEARCH, 2022) Şahin Bilal; Özdemir Ercan; Gümüş Erkan; Ergül Mustafa; Taşkıran Ahmet Şevki
Objectives: Recently, studies have demonstrated that serotonin type 7 receptors (5-HT7) have conflincting effects on neuronal excitability in different brain regions. However, the effect of 5-HT7 on seizures has not been exactly elucidated yet. Therefore, our aim in this study was to investigate the effects of 5-HT7 antagonist SB-269970 on pentylenetetrazole (PTZ) induced fully kindled rats. Methods: In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. Rats were injected with PTZ (35 mg/kg) intraperitoneally every other day to generate kindling model. 5-CT (0.1 mg/kg) and SB-269970 (1 mg/kg) were administered 30 min before acute seizure induction with PTZ (35 mg/kg). Seizure stages were determined according to the Racine scale. After electrocorticography (ECoG) recordings of seizure-induced rats were obtained, the animals were sacrificed by decapitation. The hippocampal GABA levels were determined by ELISA kit and the number of c-Fos positive neurons in the hippocampal dentate gyrus (DG), CA1 and CA3 areas were measured by immunohistochemical method. Results: The results showed that SB-269970 reduced the number of spikes, percent seizure duration and duration of generalized tonic-clonic seizures (dGTCS), while increasing the onset time of generalized tonic-clonic seizures (oGTCS). The hippocampal GABA levels were significantly increased in the SB-269970 group compared with the PTZ group. In addition, SB-269970 reduced the number of c-Fos positive cells in hippocampal CA1 area. Discussion: 5-HT7 antagonist SB-269970 displays anticonvulsant effects on PTZ-induced seizures in fully kindled rats and these effects may be related to GABAergic activity in the hippocampus.
Investigation of the mechanisms involved in anticancer effect of glucosamine sulfate on SH-SY5Y cell line
(Bratislavske lekarske listy, 2022) Şahin Bilal; Güneş Handan; Öztürk Ayşegül
Aim: Glucosamine derivatives have been found to have anticancer effects in many cancer cell lines in previous investigations. The effect of glucosamine sulfate on neuroblastoma, however, is uncertain. The potential cytotoxic effects of glucosamine sulfate on the SH-SY5Y cell line were investigated in this study. The underlying mechanisms of this cytotoxicity have also been studied. Material and methods: In this study, the SH-SY5Y cell lines were used. The cells were treated with various concentrations of glucosamine sulfate (0.3125, 0.625, 1.25 and 2.5 μg/mL) and the viability of the cells was determined using the XTT assay after 24 hours. The quantities of cleaved PARP, BCL-2, 8-Hydroxy-desoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant, and total antioxidant in the cells were determined by ELISA kits. Results: At doses of 0.3125, 0.625, 1.25 and 2.5 μg/mL, glucosamine sulfate dramatically reduced cell viability in SH-SY5Y cells (p<0.001). ELISA tests demonstrated that 1.25 μg/mL glucosamine sulfate considerably increased the amounts of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP and total oxidant. However, 1.25 μg/mL glucosamine sulfate treatment did not change the quantity of BCL-2 protein. Conclusions: Altogether, glucosamine sulfate produced considerable cytotoxicity in SH-SY5Y cells by triggering oxidative stress, inducing DNA damage, and finally causing apoptosis. In addition, more research is needed to determine the efficacy of glucosamine sulfate as an anticancer drug in the treatment of neuroblastoma
Captopril exhibits protective effects through anti-inflammatory and anti-apoptotic pathways against hydrogen peroxide-induced oxidative stress in C6 glioma cells
(Metabolic Brain Disease, 2022) Şahin Bilal; Ergül Mustafa
Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors have reduced oxidative damage in the central nervous system (CNS). Accumulating evidence have also demonstrated that captopril, an ACE inhibitor, has protective effects on the CNS. However, its effects on hydrogen peroxide (H2O2)-induced oxidative damage in glial cells and interaction with the inflammatory system are still uncertain. Therefore, this study was aimed to investigate the protective effect of captopril on glial cell damage after H2O2-induced oxidative stress involved in the inflammatory and apoptotic pathways. The control group was without any treatment, and the H2O2 group was treated with 0.5 mM H2O2 for 24 h. The captopril group was treated with various concentrations of captopril for 24 h. The captopril + H2O2 group was pre-treated with captopril for 1 h and then exposed to 0.5 mM H2O2 for 24 h. In the captopril + H2O2 group, captopril at all concentrations significantly increased the cell viability in C6 cells. It also significantly increased the TAS and decreased the TOS levels which are an indicator of oxidative stress. Moreover, captopril significantly reduced the inflammation markers including NF-kB, IL-1 β, COX-1, and COX-2 levels. Flow cytometry results also exhibited that captopril pretreatment significantly decreased the apoptosis rate. Besides, captopril significantly reduced apoptotic Bax and raised anti-apoptotic Bcl-2 protein levels. In conclusion, captopril has protective effects on C6 cells after H2O2-induced oxidative damage by inhibiting oxidative stress, inflammation, and apoptosis. However, further studies need to be conducted to evaluate the potential of captopril as a neuroprotective agent.
Galium aparine L. protects against acetaminophen-induced hepatotoxicity in rats
(Elsevier, 2022) Şahin Bilal; Karabulut Sebahattin; Filiz Ahmet Kemal; Özkaraca Mustafa; Gezer Arzu; Akpulat Aşkın Hüseyin; Ataseven Hilmi
The toxicity of acetaminophen (N-acetyl-para-aminophenol (APAP)) is the most frequent cause of drug-induced liver damage. Galium aparine L. (GA) is traditionally used to treat jaundice. We aimed to investigate the hepatoprotective potential of GA in the APAP-induced hepatic encephalopathy (HE) rat model. Qualitative phytochemical characterization of GA was performed by LC/Q-TOF/MS analysis. Wistar rats were pretreated with GA (250 and 500 mg/kg b.wt. per oral) for five days. On the 6th day, the rats were exposed to APAP (1500 mg/kg b.wt. oral gavage) and behavioral tests (open field and passive avoidance tests) were applied on the 7th and 8th days. The animals were killed, and biochemical and histopathological parameters were assessed in blood and hepatic specimens. GA pretreated rats exhibited a significant reduction in APAP-induced liver damage, evidenced by the reduction in liver necrosis and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (BIL). GA demonstrated an anxiolytic effect, as seen in the acquisition trial and grooming behavior. The short-term memory performances of animals were not changed in all groups, suggesting that APAP intoxication did not affect hippocampal function. These results show that GA extract markedly exerts hepatoprotective activity, while its effect on hepatic encephalopathy was limited.

Güncel Gönderiler