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Efficacy of Combinatorial Inhibition of Hedgehog and Autophagy Pathways on the Survival of AML Cell Lines
(Academic Press inc Elsevier Science, 2025) Sansacar, Merve; Pepe, Nihan Aktas; Akcok, Emel Basak Gencer; El Khatib, Mona
Acute myeloid leukemia (AML) is a common hematopoietic disease that results from diverse genetic abnormalities. Dysregulation of important signaling pathways, including the PI3K/AKT/mTOR, Wnt and Hedgehog pathways, plays crucial roles in the development of AML. Hedgehog pathway (Hh) is a conserved signaling pathway that is crucial throughout embryogenesis. Hh plays an important role in the regulation of autophagy, known as the cellular recycling process of organelles and unwanted proteins. Many studies have noted that the modulation of autophagy could act as a survival mechanism in AML. Considering the pivotal role of autophagy and Hh signaling in AML, understanding the relationship between these pathways is important for overcoming leukemia. Therefore, we examined the efficacy of Hh inhibition by GLI-ANTagonist 61 (GANT61) in MOLM-13 and CMK cells via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenil-2H-tetrazolium bromide (MTT) cell viability assays. GANT61 resulted in decreased cell viability in both cell lines. Therefore, we focused on the outcome of autophagy modulation in AML cells. We observed that the autophagy inhibitors ammonium chloride (NH4CI), chloroquine (CQ), and nocodazole led to a significant reduction in the proliferation of both cell lines. Cotreatment with autophagy pathway inhibitors and GANT61 synergistically affected both AML cell lines. Moreover, dual targeting of these pathways resulted in arrest at the G0/G1 phase in MOLM-13 cells but not in CMK cells. Furthermore, the combination of nocodazole and GANT61 increased the expression level of LC3B-II in both cell lines. Compared with that in the untreated control cells, the GLI1 gene expression level in both cell lines was significantly lower after GANT61 and autophagy cotreatment. In conclusion, targeting Hh and autophagy could be a favorable option to combat AML.
Citation - WoS: 30
Citation - Scopus: 46
A Survey on Information Security Threats and Solutions for Machine to Machine (M2M) Communications
(Academic Press inc Elsevier Science, 2017) Tuna, Gurkan; Kogias, Dimitrios G.; Gungor, V. Cagri; Gezer, Cengiz; Taskin, Erhan; Ayday, Erman
Although Machine to Machine (M2M) networks allow the development of new promising applications, the restricted resources of machines and devices in the M2M networks bring several constraints including energy, bandwidth, storage, and computation. Such constraints pose several challenges in the design of M2M networks. Furthermore, some elements that contributed to the rise of M2M applications have caused several new security threats and risks, typically due to the advancements in technology, increasing computing power, declining hardware costs, and freely available software tools. Due to the restricted capabilities of M2M devices, most of the recent research efforts on M2M have focused on computing, resource management, sensing, congestion control and controlling technologies. However, there are few studies on security aspects and there is a need to introduce the threats existing in M2M systems and corresponding solutions. Accordingly, in this paper, after presenting an overview of potential M2M applications, we present a survey of security threats against M2M networks and solutions to prevent or reduce their impact. Then, we investigate security-related challenges and open research issues in M2M networks to provide an insight for future research opportunities. Moreover, we discuss the oneM2M standard, one of the prominent standard initiatives for more secure and smoother M2M networks and the Internet of Things. (C) 2017 Elsevier Inc. All rights reserved.
Citation - WoS: 10
Citation - Scopus: 11
Novel High-Pressure Phase of ZrO2: An ab initio Prediction
(Academic Press inc Elsevier Science, 2015) Durandurdu, Murat
The high-pressure behavior of the orthorhombic cotunnite type ZrO2 is explored using an ab initio constant pressure technique. For the first time, a novel hexagonal phase (Ni2In type) within P6(3)/mmc symmetry is predicted through the simulation. The Ni2In type crystal is the densest high-pressure phase of ZrO2 proposed so far and has not been observed in other metal dioxides at high pressure before. The phase transformation is accompanied by a small volume drop and likely to occur around 380 GPa in experiment. (C) 2015 Elsevier Inc. All rights reserved.

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