Farooqi, A.A. | Adylova, A. | Sabitaliyevich, U.Y. | Attar, Rukset | Sohail, M.I. | Yilmaz, S.

Review | 2020 | Gene737

There has always been a quest to search for synthetic and natural compounds having premium pharmacological properties and minimum off-target and/or side effects. Therefore, in accordance with this approach, scientists have given special attention to the molecules having remarkable ability to target oncogenic protein network, restore drug sensitivity and induce apoptosis in cancer cells. The mechanisms through which general anesthetics modulated wide-ranging deregulated cell signaling pathways and non-coding RNAs remained unclear. However, rapidly accumulating experimentally verified evidence has started to resolve this long-standing . . . mystery and a knowledge about these important molecular targets has surfaced and how these drugs act at the molecular level is becoming more understandable. In this review we have given special attention to available evidence related to ability of propofol to modulate Wnt/ß-catenin, JAK/STAT and mTOR-driven pathway. Excitingly, great strides have been made in sharpening our concepts related to potential of propofol to modulate non-coding RNAs in different cancers. Collectively, these latest findings offer interesting, unexplored opportunities to target deregulated signaling pathways to induce apoptosis in drug-resistant cancers. © 2020 Elsevier B.V Daha fazlası Daha az

Ozbey, U. | Attar, Rukset | Romero, M.A. | Alhewairini, S.S. | Afshar, B. | Sabitaliyevich, U.Y. | Farooqi, A.A.

Article | 2019 | Journal of Cellular Biochemistry120 ( 2 ) , pp.1060 - 1067

Wealth of information gleaned from decades of high-impact research work; scientists have disentangled the complicated web of versatile regulators that underlie cancer development and progression. Use of structural biology approaches and functional genomics have helped us to gain new insights into complex nature of cancer, and it is now clear that genetic/epigenetic mutations, overexpression of oncogenes, inactivation of tumor suppressors, loss of apoptosis, and versatility of protein binding partners have contributory roles in carcinogenesis and metastatic spread. It is becoming progressively more understandable that reprogramming o . . .f gene expression during and nontranscriptional changes during cancer development and progression are initiated and controlled by deregulated signal transduction cascades, all of which collectively create an incalculable complexity. Data obtained through preclinical and clinical trials revealed that alterations in the targeted oncogenes and other downstream, and parallel pathways played a central role in the development of resistance against different therapeutics. Phytochemicals have regained limelight, and different natural products are currently being tested for efficacy in preclinical studies. Apigenin, a plant-derived flavonoid has considerable pharmacological value and is reportedly involved in the regulation of different signaling cascades. In this review, we have attempted to summarize rapidly evolving understanding of molecular biologists and pharmacologists about the potential of apigenin in the regulation of deregulated signaling pathways in different cancers. We have emphasized on the regulation of WNT/ß-catenin and janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. We also comprehensively discuss how apigenin restored apoptosis in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant cancers. The review also gives a snapshot of microRNAs (miRNAs) that regulate wide-ranging biological processes, and it is now clear that each miRNA can control hundreds of gene targets. Apigenin was noted to upregulate miR-520b and miR-101 in different cancers to inhibit tumor growth. Moreover, apigenin-induced apoptotic rate was significantly higher when used in combination with miR-423-5p inhibitors or miR-138 mimics. Better comprehension of linear and integrated signaling pathways will be helpful in effective therapeutic targeting of deregulated signaling pathways to inhibit/prevent cancer. © 2018 Wiley Periodicals, Inc Daha fazlası Daha az

Yildirim, G. | Ficicioglu, C. | Akcin, O. | Attar, Rukset | Tecellioglu, N. | Yencilek, F.

Article | 2009 | Archives of Gynecology and Obstetrics279 ( 2 ) , pp.213 - 215

Primary ciliary dyskinesia (PCD), previously known as immotile cilia syndrome, can cause respiratory and reproductive problems. Because of the impaired motion of microtubules the patients suffer upper respiratory tract problems. Infertility is an other issue of these patients. Several attempt have been proposed to bring back sperm motion and to improve intracytoplasmic sperm injection (ICSI) results. With our case we have described the management of a male infertility that causes from immotile cilia. The role of ICSI with incubated and activated ejaculatory sperm by pentoxifylline in the patient of PCD or as commonly named immotile . . .cilia syndrome. © 2008 Springer-Verlag Daha fazlası Daha az

Narin, R. | Attar, Rukset | Narin, M.A. | Koyuncu, D. | Yencilek, E.

Article | 2014 | Archives of Gynecology and Obstetrics290 ( 5 ) , pp.913 - 917

Results: After TOT procedure, the mean value of IIQ-7 and UDI-6 questionnaires was lower than the mean scores that measured before treatment (p 

Bostancı, M.S. | Bakacak, M. | İnanc, F. | Yaylalı, A. | Serin, S. | Attar, Rukset | Yildirim, G.

Article | 2016 | Archives of Gynecology and Obstetrics293 ( 4 ) , pp.789 - 795

Objective: This experimental study was designed to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) in ovarian ischemia and ischemia/reperfusion (I/R) injury. Study design: Forty-eight female adult Sprague–Dawley albino rats were divided into six groups as Group 1: sham, Group 2: torsion, Group 3: detorsion, Group 4: sham + G-CSF, Group 5: torsion + G-CSF, and Group 6: detorsion + G-CSF. Except for Groups 1 and 4, all groups underwent adnexal torsion bilaterally for 3 h. Adnexal detorsion was applied to Groups 3 and 6 for 3 h after a 3-h torsion period. The intraperitoneal injection of G-CSF (100 IU/kg) was admin . . .istered 30 min previously in Group 4, 5 and 6. At the end of the study process the animals were euthanized and their ovaries were removed for histopathological and biochemical analysis. Total oxidant status (TOS), total antioxidative status and oxidative stress index (OSI) concentrations were determined and compared. Histopathological examination of ovaries was performed for the presence of interstitial edema, congestion, hemorrhage and loss of cohesion to determine tissue damage. Results: In Group 3, 4, 5 and 6, TOS, OSI and total histopathological scores of ovarian tissue were higher than in the sham group (p Daha fazlası Daha az

Butt, G. | Shahwar, D. | Qureshi, M.Z. | Attar, Rukset | Akram, M. | Birinci, Y. | Farooqi, A.A.

Book Part | 2019 | Advances in Experimental Medicine and Biology1152 , pp.283 - 292

Based on the insights gleaned from decades of research, it seems clear that mechanistic target of rapamycin (mTOR) is an essential signaling node that integrates environmental clues for regulation of cell survival, metabolism and proliferation of the cells. However, overwhelmingly increasing scientific evidence has added a new layer of intricacy to already complicated and versatile signaling pathway of mTOR. Deregulation of spatio-temporally controlled mTOR-driven pathway played contributory role in breast cancer development and progression. Pharmacologists and molecular biologists have specifically emphasized on the identification . . .and development of mTOR-pathway inhibitors. In this chapter we have attempted to provide an overview of the most recent findings related to therapeutic targeting of mTOR-associated mTORC1 and mTORC2 in breast cancer. We have also comprehensively summarized regulation of mTOR and its partners by microRNAs in breast cancer. © 2019, Springer Nature Switzerland AG Daha fazlası Daha az

Attar, Rukset | Agachan, B. | Kucukhuseyin, O. | Toptas, B. | Attar, E. | İşbir, Turgay

Article | 2010 | Molecular Biology Reports37 ( 1 ) , pp.369 - 374

Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women didnot have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fra . . .gment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women. © 2009 Springer Science+Business Media B.V Daha fazlası Daha az

Kumbak, B. | Atak, I.E. | Attar, Rukset | Yildirim, G. | Yesildaglar, N. | Ficicioglu, C.

Article | 2010 | Journal of Reproductive Medicine for the Obstetrician and Gynecologist55 ( 10 ) , pp.417 - 422

OBJECTIVE: To investigate the psychologic impact of male factor infertility on men in couples undergoing assisted reproductive treatment in Turkey. STUDY DESIGN: A prospective study was carried out in a total of 105 men: 43 with male factor, 31 with female factor and 31 with unexplained infertility diagnoses. The men answered questionnaires-State Trait Anxiety Inventory, State Trait Anger Expression Inventory and Beck Depression Inventory-during treatment. The scores from each questionnaire were analyzed and compared according to the infertility diagnosis. RESULTS: No significant differences were found in measures of anxiety, anger . . .or depression among men with male factor, female factor and unexplained infertility. CONCLUSION: In the current preliminary study performed on a group of Turkish men who applied for in vitro fertilization treatment, it was found that male factor infertility as the cause of the couple's infertility problem did not have an adverse effect on the psychologic status of men undergoing assisted reproductive treatment. It is suggested that men's psychologic adjustment to their own infertility diagnosis does not indicate that they are psychologically ill. © Journal of Reproductive Medicine®, Inc Daha fazlası Daha az

Yildirim, G. | Attar, Rukset | Ozkan, F. | Kumbak, B. | Ficicioglu, C. | Yesildaglar, N.

Article | 2010 | Fertility and Sterility93 ( 6 ) , pp.1787 - 1792

Objective: To determine the effects of letrozole and melatonin on surgically induced endometriosis in a rat endometriosis model. Design: Prospective, randomized, controlled, experimental study. Setting: Experimental Research Center of Yeditepe University (YUDETAM). Animal(s): Thirty female, nonpregnant, nulligravid Wistar-Hannover albino rats. Intervention(s): Surgical induction of endometriosis, administration of estrogen for 2 weeks, and laparotomy; administration of letrozole or melatonin for 2 weeks after induction of endometriosis, and laparotomy; administration of estrogen for 2 weeks and necropsy. Main Outcome Measure(s): The . . . volume and histopathologic scores of endometriotic foci, and levels of superoxide dismutase, catalase, and malondialdehyde in the peritoneal fluid. Result(s): The mean volumes of the endometriotic foci were 99.6 ± 18.8 mm3, 21.5 ± 7.4 mm3, and 29.2 ± 17.5 mm3, and histopathologic scores were 2.5 ± 0.7, 2.0 ± 0.8, and 1.7 ± 0.9 in the melatonin group at the end of the second, fourth, and sixth weeks, respectively. The mean volumes of the endometriotic foci were 75.9 ± 26.3 mm3, 29.8 ± 14.7 mm3, and 121.2 ± 35.1 mm3 and the histopathologic scores were 2.5 ± 0.5, 2.2 ± 0.8, and 2.7 ± 0.4 in the letrozole group at the end of the second, fourth, and sixth weeks, respectively. In the melatonin group, peritoneal fluid superoxide dismutase and catalase levels increased statistically significantly. Conclusion(s): Melatonin caused more pronounced regression of endometriotic foci when compared with letrozole in a rat model. After the cessation of melatonin treatment, the recurrence rate was lower than that observed after the cessation of letrozole treatment. © 2010 American Society for Reproductive Medicine Daha fazlası Daha az

Agachan, B. | Attar, Rukset | Isbilen, E. | Aydogan, H.Y. | Sozen, S. | Gurdol, F. | İşbir, Turgay

Article | 2010 | Journal of Interferon and Cytokine Research30 ( 9 ) , pp.673 - 676

Preeclampsia complicates 10% of pregnancies in developing countries. It is one of the leading causes of maternal and fetal/neonatal mortality and morbidity worldwide. It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. According to immune maladaptation hypothesis, preeclampsia is due to an inappropriate regulation of normally Th2-deviated maternal immune responses, leading to a shift toward harmful Th1 immunity. Several studies indicate that monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) are involved in Th1 and Th2 immunity. I . . .n this study, we investigated the association between MCP-1 A-2518G and CCR2-V64I polymorphisms and preeclampsia. One hundred eighty preeclamptic pregnant women and 145 healthy controls were included in the study. We observed that in preeclamptic women, MCP-1 G: CCR2 Val haplotype was significantly higher when compared with other haplotypes. In conclusion, we stated that MCP-1 and CCR2 gene variants might be associated with preeclampsia. © Mary Ann Liebert, Inc Daha fazlası Daha az

Yılmaz, Seda Güleç | Gül, Tuğçe | Attar, Rukset | Yıldırım, Gazi | İşbir, Turgay

Article | 2018 | Journal of the Turkish-German Gynecological Association19 ( 3 ) , pp.128 - 131

Objective: The aim of this research was to determine the association between the fok1 polymorphism and uterine leiomyomas.Material and Methods: For genotyping the fok1 polymorphism of the vitamin D receptor, real-time polymerase chain reaction was performedon blood samples of uterine leiomyoma (n27) and control (n33) groups. For statistical analyses, SPSS v.23 software (SPSS Inc., Chicago, IL,USA) was used.Results: A statistically significant difference was observed for the frequency of the CC genotype between the uterine leiomyoma and controlgroups, and the frequencies of the T allele in the uterine leiomyoma groups were significan . . .tly higher than in the control group.Conclusion: The presence of the fok1 CC genotype may be a risk-reducing factor and the T allele may be a potential risk factor for developinguterine leiomyoma. (J Turk Ger Gynecol Assoc 2018; 19: 128-31 Daha fazlası Daha az

Fıçıcıoğlu, Cem | Kumbak, Banu | Akcin, Oya | Attar, Rukset | Yıldırım, Gazi | Tecellioğlu, Nihan | Yeşildağlar, Narter

Other | 2009 | Journal of the Turkish-German Gynecological Association10 ( 3 ) , pp.132 - 136

Amaç: Folikül sıvısı içindeki sitokinlerin ve nitrik oksitin matur oosit gelişimi üzerindeki etkisi tartışmalıdır. Bu çalışmanın amacı, tüp bebek tadavisi alan hastaların folikül sıvısı (FF) ve serumunda (S) interlökinleri IL-1?, IL-6, IL-8, IL-12, tümor nekrozis faktör (TNF)-? ve NO düzeylerini saptamak ve bunların başarı ile ilişkisini araştırmaktır. Gereç ve Yöntemler: Bir üniversite hastanesinin tüp bebek merkezinde retrospektif çalışma planlandı. 85 kadın çalışmaya dahil edildi. IL-1?, IL-6, IL-8, IL-12, tümor nekrozis faktör (TNF)-? düzeyleri ELISA ile, NO düzeyleri ise nitrat/nitrit kolorometrik assay ile saptandı. Bulgular: . . .Gebe kalan ve kalamayan kadınların S ve FF sitokin ve NO konsantrasyonları arasında fark bulunamadı. Sonuç: Serum ve folüküler sıvı IL-1?, IL-6, IL-8, IL-12, tümör nekrozis faktör (TNF)-? ve NO düzeyleri tüp bebek tedavilerinde başarıyı predikte etmez. Objective: The role of cytokines and nitric oxide (NO) in ovarian folliculogenesis and the development of mature and fertilizable oocytes is controversial. The aim of this study is to determine the concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-α and NO in the follicular fluid (FF) and blood serum (S) of patients undergoing assisted reproductive treatment (ART) and to investigate whether these cytokines could be used as a predictive parameter for ART outcome. Material and Methods: A retrospective clinical study was performed at a university hospital including a total of 85 women who underwent ART. FF and serum samples were collected at the time of oocyte retrieval and measured for interleukin (IL)-1β, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-α by the enzyme-linked immunosorbant assay (ELISA) technique, using commercially available kits and NO by the nitrate/nitrite colorimetric assay. The results were compared between the women who became pregnant and those who did not following ART. Results: No significant difference was found in the FF and blood serum concentrations of the cytokines and NO between pregnant and non-pregnant women. Conclusion: Follicular fluid and blood serum concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α and NO do not predict pregnancy achievement following ART Daha fazlası Daha az