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Citation Count: 225
2019 EACTS Expert Consensus on long-term mechanical circulatory support
(European Association for Cardio-Thoracic Surgery, 2019) Potapov,E.V.; Antonides,C.; Crespo-Leiro,M.G.; Combes,A.; Färber,G.; Hannan,M.M.; Gustafsson,F.
Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many - sometimes contradictory - observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device. © 2019 The Author(s).
Citation Count: 487
Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology
(John Wiley and Sons Ltd, 2018) Crespo-Leiro,M.G.; Metra,M.; Lund,L.H.; Milicic,D.; Costanzo,M.R.; Filippatos,G.; Ruschitzka,F.
This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology
Citation Count: 17
Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells
(Sage Publications Ltd, 2016) Kiraz, Yagmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, Yusuf; Baran, Yusuf
Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.
Citation Count: 20
Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells
(Springer Science and Business Media B.V., 2016) Baran, Yusuf; Neergheen-Bhujun,V.S.; Rummun,N.; Baran,Y.
Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Citation Count: 19
Apoptotic Effects of Resveratrol, a Grape Polyphenol, on Imatinib-Sensitive and Resistant K562 Chronic Myeloid Leukemia Cells
(int inst Anticancer Research, 2012) Can, Geylani; Cakir, Zeynep; Kartal, Melts; Gunduz, Ufuk; Baran, Yusuf; Baran, Yusuf
Aim: To examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. Materials and Methods: Antiproliferative effects of resveratrol were determined by the 3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) cell proliferation assay. Apoptotic effects of resveratrol on sensitive K562 and resistant K562/IMA-3 cells were determined through changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and apoptosis by annexin V-(FITC). Results: The concentrations of resveratrol that inhibited cell growth by 50% (IC50) were calculated as 85 and 122 mu M for K562 and K562/IMA-3 cells, respectively. There were 1.91-, 7.42- and 14.73-fold increases in loss of MMP in K562 cells treated with 10, 50, and 100 mu M resveratrol, respectively. The same concentrations of resveratrol resulted in 2.21-, 3.30- and 7.65-fold increases in loss of MMP in K562/IMA3 cells. Caspase-3 activity increased 1.04-, 2.77- and 4.8-fold in K562 and 1.02-, 1.41- and 3.46-fold in K562/IMA3 cells in response to the same concentrations of resveratrol, respectively. Apoptosis was induced in 58.7%- and 43.3% of K562 and K562/IMA-3 cells, respectively, in response to 100 mu M resveratrol. Conclusion: Taken together these results may suggest potential use of resveratrol in CML, as well as in patients with primary and/or acquired resistance to imatinib.
Citation Count: 5
Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias
(Bentham Science Publ Ltd, 2011) Ekiz, Huseyin Atakan; Baran, Yusuf; Baran, Yusuf
Sphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that have important roles in the regulation of cell death, survival and chemotherapeutic resistance. Some of those species are known to accumulate in the cells upon chemotherapy while some others are known to exhibit an opposite pattern. Even though the length of fatty acid chain has a deterministic effect, in general, upregulation of ceramides and sphingosine is known to induce apoptosis. However, S1P, C1P and GluCer are proliferative for cells and they are involved in the development of chemoresistance. Therefore, sphingolipid metabolism appears as a good target for the development of novel therapeutics or supportive interventions to increase the effectiveness of the chemotherapeutic drugs currently in hand. Some approaches involve manipulation of the synthesis pathways yielding the increased production of apoptotic sphingolipids while the proliferative ones are suppressed. Some others are trying to take advantage of cytotoxic sphingolipids like short chain ceramide analogs by directly delivering them to the malignant cells as a distinct chemotherapeutic intervention. Numerous studies in the literature show the feasibility of those approaches especially in acute and chronic leukemias. This review compiles the current knowledge about sphingolipids and their roles in chemotherapeutic response with the particular attention to leukemias.
Citation Count: 25
Caffeic acid phenethyl ester triggers apoptosis through induction of loss of mitochondrial membrane potential in CCRF-CEM cells
(Springer, 2011) Avci, Cigir Biray; Gunduz, Cumhur; Baran, Yusuf; Sahin, Fahri; Yilmaz, Sunde; Dogan, Zeynep Ozlem; Saydam, Guray; Baran, Yusuf
CAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic cells and at determining the roles of mitochondrial membrane potential (MMP) in cell death. Trypan blue and XTT methods were used to evaluate the cytotoxicity. Apoptosis was examined by ELISA-based oligonucleotide and acridine orange/ethidium bromide dye techniques. Loss of mitochondrial membrane potential was evaluated using JC-1 dye by flow cytometric analysis and under fluorescent microscope. We detected the time- and dose-dependent increases in cytotoxic effect of CAPE on CCRF-CEM cells. ELISA and acridine orange/ethidium bromide results showed that apoptotic cell population increased significantly in CCRF-CEM cells exposed to increasing concentrations of CAPE. On the other hand, there was significant loss of MMP determined in response to CAPE in CCRF-CEM cells. This in vitro data by being supported with clinical data may open the way of the potential use of CAPE for the treatment of leukemia.
Citation Count: 8
The case of a cyst hydatid localized within the interatrial septum
(2004) Karabay,Ö.; Önen,A.; Yildiz,F.; Yilmaz,E.; Erdal,A.C.; Şanli,A.; Açikel,Ü.
The ratio of cardiac involvement of Echinoccocus granulosus is 0.02-2% and although seen rarely, involvement of the interatrial septum has also been reported in the published literature. The present case was a 19-year-old male university student admitted to hospital with complaints of headache and dizziness. Computerized tomography of the cranium revealed a cystic mass located at the frontal region and enucleation of the cyst was performed during surgery. A cystic lesion 5 × 4 cm in size was detected within the interatrial septum on two-dimensional transthoracic echocardiography during the postoperative period and the patient was referred to our clinic. Open heart surgery was performed and a hydatid cyst that involved the interatrial septum was enucleated. The cyst wall was sutured to the interatrial septum. No complications developed during the postoperative period. The patient was discharged on the fifth day of hospitalization and medical therapy was started with albendazole. Copyright © 2004 by the Japanese Heart Journal.
Citation Count: 255
Cell proliferation and cytotoxicity assays
(Bentham Science Publishers B.V., 2016) Baran, Yusuf; Kiraz,Y.; Baran,Y.
Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes. © 2016 Bentham Science Publishers.
Citation Count: 17
Changes in molecular biology of chronic myeloid leukemia in tyrosine kinase inhibitor era
(E-century Publishing Corp, 2013) Comert, Melda; Baran, Yusuf; Saydam, Guray; Baran, Yusuf
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by a reciprocal translocation between long arms of chromosomes 9 and 22 t(9; 22) that generates the BCR-ABL fusion gene. If left untreated, newly diagnosed chronic phase CML patients finally progress to accelerated and blastic phase. After the introduction of tyrosine kinase inhibitors (TKIs), treatment strategies of CML changed dramatically. However, the development of resistance to TKIs started to create problems over time. In this review, the current information about CML biology before and after imatinib mesylate treatment is summarized.
Citation Count: 38
Clinical and laboratory features, complications and treatment outcome of brucellosis in childhood and review of the literature
(2011) Uluǧ,M.; Yaman,Y.; Yapici,F.; Can-Uluǧ,N.
Brucellosis, whether in an endemic region or not, remains a diagnostic puzzle due to occasional misleading unusual presentations and non-specific symptoms. The aim of this study was to evaluate the clinical and laboratory findings, complications and treatment outcome of brucellosis in children in southeastern Anatolia, Turkey. This study focuses on the frequency of clinical and laboratory findings and complications in cases with brucellosis. Of 22 patients, 8 (36.3%) were female and 14 (63.7%) were male. Fever, malaise, lack of appetite, arthralgia, and night sweating were the main presenting symptoms overall. Hematologic complications (n=13, 59.1%) were most common, followed by skeletal (n=7, 31.8%) and cutaneous system (n=1, 4.5%). Brucellosis may affect any organ system and imitate a variety of clinical entities. Diagnosis of brucellosis should be considered whenever there is a febrile illness associated with rheumatological complaints. Consequently, early recognition of the infection, prolonged antibiotic treatment and careful long-term follow-up should improve the patient outcome.
Citation Count: 13
Cumulative clinical experience from a decade of use: imatinib as first-line treatment of chronic myeloid leukemia
(Dove Medical Press Ltd, 2012) Baran, Yusuf; Saydam, Guray; Baran, Yusuf
Chronic myeloid leukemia (CML) is a malignant disease that originates in the bone marrow and is designated by the presence of the Philadelphia (Ph+) chromosome, a translocation between chromosomes 9 and 22. Targeted therapy against CML commenced with the development of small-molecule tyrosine kinase inhibitors (TKIs) exerting their effect against the oncogenic breakpoint cluster region (BCR)-ABL fusion protein. Imatinib emerged as the first successful example of a TKI used for the treatment of chronic-phase CML patients and resulted in significant improvements in response rate and overall survival compared with previous treatments. However, a significant portion of patients failed to respond to the therapy and developed resistance against imatinib. Second-generation TKIs nilotinib and dasatinib were to have higher efficiency in clinical trials in imatinib-resistant or intolerant CML patients compared with imatinib. Identification of novel strategies such as dose escalation, drug combination therapy, and use of novel BCR-ABL inhibitors may eventually overcome resistance against BCR-ABL TKIs. This article reviews the history of CML, including the treatment strategies used prediscovery of TKIs and the preclinical and clinical data obtained after the use of imatinib, and the second-generation TKIs developed for the treatment of CML.
Citation Count: 11
Effect of Alkali Metal Hydroxides on the Morphological Development and Optical Properties of Ceria Nanocubes Under Hydrothermal Conditions
(Amer Scientific Publishers, 2011) Kepenekci, Ozlem; Emirdag-Eanes, Mehtap; Demir, Mustafa M.; Demir, Mustafa
Nanocrystalline cerium(IV) oxide (CeO2, ceria) particles were produced via the hydrothermal treatment of cerium nitrate hexahydrate with various alkali metal hydroxides (MOH: M = Li, Na, K) Experimental conditions such as [MOH], reaction temperature, and reaction time were studied Particle morphology as well as size of crystallites was precisely controlled by choice of experimental conditions. While rod-shaped particles were obtained at 120 degrees C, well-defined nanocubes were formed at higher temperatures regardless of the choice of MOH. Examination of particle growth kinetics, in the final stages of crystallization, showed that particle growth rate is controlled by two different mechanisms. Grain boundary diffusion controls the particle growth in the presence of NaOH with an activation energy of 113.8 kj/mol and surface diffusion for LiOH ad KOH with the activation energy of 43.0-150.9 kj/mol, respectively. In addition, the particles exhibit strong violet and blue emissions at 400 nm and 370 nm. The former emission originates from excitation of a wide band gap of CeO2. The latter one is attributed to the trivalency of the cerium ion and appears to be sensitive to all the experimental conditions studied. Both extending reaction time and increasing temperature reduce the intensity of the 370 nm emission and increase the intensity of the 400 nm emission.
Citation Count: 6
Effect of cobalt-60 (γ radiation) on multidrug-resistant multiple myeloma cell lines
(Portland Press Ltd, 2011) Mutlu, Pelin; Baran, Yusuf; Ural, A. Ugur; Avcu, Ferit; Dirican, Bahar; Beyzadeoglu, Murat; Gunduz, Ufuk; Baran, Yusuf
Emergence of resistance to chemotherapy and radiotherapy is a major obstacle for the successful treatment of MM (multiple myeloma). Prednisone, vincristine and melphalan are commonly used chemotherapeutic agents for the treatment of MM. In the current study, we examined the presence of possible cross-resistance between these drugs and gamma (gamma) radiation. Prednisone, vincristine and melphalan resistant RPMI-8226 and U-266 MM cells were generated by stepwise increasing concentrations of the drugs. The sensitive and resistant cells were exposed to 200- and 800 cGy gamma radiation, and proliferation was examined by XTT {2,3-bis(2-methoxy-4-nitro-5-sulfopheny1)-5-Rphenylamino)carbonyl]-2H-tetrazolium hydroxide) assay. The results showed that Prednisone- and melphalan-resistant RPMI-8226 cells were also cross-resistant to 200 and 800 cGy gamma radiation application, while vincristine-resistant cells did not show resistance. On the other hand, Prednisone-, vincristine- and melphalan-resistant U-266 cells showed cross-resistance to 200- and 800 cGy gamma radiation application. These results demonstrated that MM cells resistant to anticancer agents respond to radiation in different levels. These findings may be important in the clinical applications of radiation therapy in the treatment of vincristine resistant MM.
Citation Count: 2
Effects of Intraperitoneal Injection of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells on Bronchiolitis Obliterans in Mice Model
(Iranian Scientific Society Medical Entomology, 2017) Isik, Sakine; Uzuner, Nevin; Karaman, Meral; Karaman, Ozkan; Kiray, Muge; Kozanoglu, Ilknur; Baran, Yusuf; Baran, Yusuf
Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x10(6) BMSCs-injected group (Group II), non-BO, 1x10(6) BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bronchiole and periterminal bronchiolar collagen deposition were significantly lower in group II compared to the group IV (p<0.05). Furthermore, according to the immunohistochemical staining results, CD3, CD4, CD8, CD20, CD68 and neutrophil elastase positive immune cells of group II were stained more positive than group IV cells (p<0.05). IFN-gamma IL-2 and TNF-alpha levels in bronchoalveolar lavage fluid (BALF) were significantly lower in group II compared to group IV (p<0.05). The findings of this study indicate that intraperitoneally administered BMSCs have potent effects on histopatological changes of the lung tissue and cytokine levels in the murine model of BO.
Citation Count: 29
Electrospun GelMA fibers and p(HEMA) matrix composite for corneal tissue engineering
(Elsevier, 2021) Arica, Tugce A.; Guzelgulgen, Meltem; Yildiz, Ahu Arslan; Demir, Mustafa M.; Demir, Mustafa
The development of biocompatible and transparent three-dimensional materials is desirable for corneal tissue engineering. Inspired from the cornea structure, gelatin methacryloyl-poly(2-hydroxymethyl methacrylate) (GelMA-p(HEMA)) composite hydrogel was fabricated. GelMA fibers were produced via electrospinning and covered with a thin layer of p(HEMA) in the presence of N,N'-methylenebisacrylamide (MBA) as cross-linker by drop-casting. The structure of resulting GelMA-p(HEMA) composite was characterized by spectrophotometry, microscopy, and swelling studies. Biocompatibility and biological properties of the both p(HEMA) and GelMA-p (HEMA) composite have been investigated by 3D cell culture, red blood cell hemolysis, and protein adsorption studies (i.e., human serum albumin, human immunoglobulin and egg white lysozyme). The optical transmittance of the GelMA-p(HEMA) composite was found to be approximately 70% at 550 nm. The GelMA-p(HEMA) composite was biocompatible with tear fluid proteins and convenient for cell adhesion and growth. Thus, as prepared hydrogel composite may find extensive applications in future for the development of corneal tissue engineering as well as preparation of stroma of the corneal material.
Citation Count: 35
Electrospun polystyrene fibers knitted around imprinted acrylate microspheres as sorbent for paraben derivatives
(Elsevier B.V., 2018) Demirkurt M.; Olcer Y.A.; Demir M.M.; Eroglu, A.E.
Parabens are used as antimicrobial preservatives in food, cosmetic products and pharmaceuticals regardless of their endocrine disrupting effect. In this study, highly selective molecular imprinted polymers (MIPs) were synthesized in submicron-sizes and converted to an SPME fiber coating through electrospinning process in order to determine parabens in water samples. Conversion of MIP to a fiber is achieved via creation of spacial knitting around MIP by polystyrene. The selectivity and extraction ability of the fibers were compared with the commercial fibers and the corresponding non-imprinted polymer (NIP) coated fiber. The coated fiber showed better extraction ability among them. Also, the results revealed that the fiber has better selectivity for benzyl paraben and the other structurally-related compounds, such as methyl and propyl paraben. Extraction efficiency of prepared fibers for three parabens has been tested by spiking bottled, tap and sea water samples. The recoveries changed between 92.2 ± 0.8 and 99.8 ± 0.1 for three different water types. This method could be used for selective and sensitive determination of parabens in aqueous samples. © 2018 Elsevier B.V.
Citation Count: 10
Enalapril-induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves STAT5A
(int inst Anticancer Research, 2012) Purclutepe, Ozlem; Iskender, Guniz; Kiper, Hatice Demet; Tezcanli, Burcin; Selvi, Nur; Avci, Cigir Biray; Saydam, Guray
Background: In this study, we aimed at evaluating the cytotoxic and apopotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death. Materials and Methods: Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the Annexin V-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose- and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls. Conclusion: Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia.
Citation Count: 38
Endogenous miRNA Sponges
(Humana Press Inc., 2022) Akgül, Bünyamin; Akgül,B.
MicroRNAs (miRNAs) are a class of noncoding RNAs of 17–22 nucleotides in length with a critical function in posttranscriptional gene regulation. These master regulators are themselves subject to regulation both transcriptionally and posttranscriptionally. Recently, miRNA function has been shown to be modulated by exogenous RNA molecules that function as miRNA sponges. Interestingly, endogenous transcripts such as transcribed pseudogenes, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and mRNAs may serve as natural miRNA sponges. These transcripts, which bind to miRNAs and competitively sequester them away from their targets, are naturally existing endogenous miRNA sponges, called competing endogenous RNAs (ceRNAs). Here we present a historical background of miRNAs, exogenous and endogenous miRNA sponges as well as some examples of endogenous miRNA sponges involved in regulatory mechanisms associated with various diseases, developmental stages, and other cellular processes. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.
Citation Count: 13
Experimental MicroRNA Detection Methods
(Humana Press Inc., 2022) Akgül, Bünyamin; Akgül,B.
MicroRNAs (miRNAs) are considerably small yet highly important riboregulators involved in nearly all cellular processes. Due to their critical roles in posttranscriptional regulation of gene expression, they have the potential to be used as biomarkers in addition to their use as drug targets. Although computational approaches speed up the initial genomewide identification of putative miRNAs, experimental approaches are essential for further validation and functional analyses of differentially expressed miRNAs. Therefore, sensitive, specific, and cost-effective microRNA detection methods are imperative for both individual and multiplex analysis of miRNA expression in different tissues and during different developmental stages. There are a number of well-established miRNA detection methods that can be exploited depending on the comprehensiveness of the study (individual miRNA versus multiplex analysis), the availability of the sample and the location and intracellular concentration of miRNAs. This review aims to highlight not only traditional but also novel strategies that are widely used in experimental identification and quantification of microRNAs. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.

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