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Article ; Online: Hyaluronan-Sphingosine Polymersomes for Treatment of Ocular Neovascularization: Synthesis and Evaluation.

Yetisgin, Abuzer Alp / Durak, Saliha / Kutlu, Ozlem / Cetinel, Sibel

2024 , Page(s) e2300531

Abstract: Ocular neovascularization is a hallmark of several sight-threatening diseases, including diabetic retinopathy and age-related macular degeneration. Currently, available treatments are limited and often associated with side effects. Therefore, a novel ... ...

Abstract	Ocular neovascularization is a hallmark of several sight-threatening diseases, including diabetic retinopathy and age-related macular degeneration. Currently, available treatments are limited and often associated with side effects. Therefore, a novel approach to ocular neovascularization treatment through utilization of polymersomes from self-assembled sphingosine-grafted hyaluronic acid (HA-Sph) amphiphilic polymers is presented. The polymersomes are generated in spherical morphologies and sizes between 97.95 - 161.9 nm with homogenous size distributions. Experiments reveal that HA-Sph polymersomes, with concentrations ≥150 µg mL
Language	English
Publishing date	2024-02-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2039130-4
ISSN	1616-5195 ; 1616-5187
ISSN (online)	1616-5195
ISSN	1616-5187
DOI	10.1002/mabi.202300531
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases.

Celebi, Gizem / Kesim, Hale / Ozer, Ebru / Kutlu, Ozlem

International journal of molecular sciences

2020 Volume 21, Issue 17

Abstract: Ubiquitination is a multi-step enzymatic process that involves the marking of a substrate protein by bonding a ubiquitin and protein for proteolytic degradation mainly via the ubiquitin-proteasome system (UPS). The process is regulated by three main ... ...

Abstract	Ubiquitination is a multi-step enzymatic process that involves the marking of a substrate protein by bonding a ubiquitin and protein for proteolytic degradation mainly via the ubiquitin-proteasome system (UPS). The process is regulated by three main types of enzymes, namely ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Under physiological conditions, ubiquitination is highly reversible reaction, and deubiquitinases or deubiquitinating enzymes (DUBs) can reverse the effect of E3 ligases by the removal of ubiquitin from substrate proteins, thus maintaining the protein quality control and homeostasis in the cell. The dysfunction or dysregulation of these multi-step reactions is closely related to pathogenic conditions; therefore, understanding the role of ubiquitination in diseases is highly valuable for therapeutic approaches. In this review, we first provide an overview of the molecular mechanism of ubiquitination and UPS; then, we attempt to summarize the most common diseases affecting the dysfunction or dysregulation of these mechanisms.
MeSH term(s)	Animals ; Disease/etiology ; Humans ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligase Complexes/metabolism ; Ubiquitination
Chemical Substances	Ubiquitin ; Ubiquitin-Protein Ligase Complexes (EC 2.3.2.23)
Language	English
Publishing date	2020-09-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21176335
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Article: A feasibility study of different commercially available serum-free mediums to enhance lentivirus and adeno-associated virus production in HEK 293 suspension cells.

Celebi Torabfam, Gizem / Yetisgin, Abuzer Alp / Erdem, Cem / Cayli, Aziz / Kutlu, Ozlem / Cetinel, Sibel

Cytotechnology

2022 Volume 74, Issue 6, Page(s) 635–655

Abstract: Lentivirus and adeno-associated viruses are invaluable tools for biotechnology applications due to their genetic material delivery abilities both in vitro and in vivo. However, their large-scale productions with Good Manufacturing Practices yield low ... ...

Abstract	Lentivirus and adeno-associated viruses are invaluable tools for biotechnology applications due to their genetic material delivery abilities both in vitro and in vivo. However, their large-scale productions with Good Manufacturing Practices yield low efficiency when adherent and serum dependent HEK293 (Human Embryonic Kidney) cells are used as the host. To increase production efficiency, HEK293 cells are adapted to grow in suspension using commercially available and chemically defined serum-free mediums. Suspended cells can be transiently transfected for viral vector production; however, significant improvements are still needed to increase yield and thereby cost effectiveness. Here, we evaluated four most preferred commercially available mediums that are IVY, FreeStyle293, LV-MAX, and BalanCD HEK293 for the transient transfection feasibility of lentiviral (LV) and adeno-associated virus serotype 2 (AAV2) production in FlorabioHEK293 suspension cells. The highest transfection efficiency was over 90% and obtained by using polyethyleneimine (PEI) 25 K and by media adaptation in IVY without using any transfection enhancer. For the first time the feasibility of HEK293 cells, which were adapted to grow in suspension culture by Florabio and IVY media, were tested for virus production. This study demonstrates the best transfection medium for scalable and optimized production of Lentivirus and Adeno-Associated Virus in suspended HEK293 cell culture. Supplementary information: The online version contains supplementary material available at 10.1007/s10616-022-00551-1.
Language	English
Publishing date	2022-10-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1035772-5
ISSN	0920-9069
ISSN	0920-9069
DOI	10.1007/s10616-022-00551-1
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Zs.A 2604: Show issues

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Article ; Online: Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression.

Kaleli, Humeyra Nur / Ozer, Ebru / Kaya, Veysel Ogulcan / Kutlu, Ozlem

Cells

2020 Volume 9, Issue 3

Abstract: Protein kinase C (PKC) isozymes are members of the Serine/Threonine kinase family regulating cellular events following activation of membrane bound phospholipids. The breakdown of the downstream signaling pathways of PKC relates to several disease ... ...

Abstract	Protein kinase C (PKC) isozymes are members of the Serine/Threonine kinase family regulating cellular events following activation of membrane bound phospholipids. The breakdown of the downstream signaling pathways of PKC relates to several disease pathogeneses particularly neurodegeneration. PKC isozymes play a critical role in cell death and survival mechanisms, as well as autophagy. Numerous studies have reported that neurodegenerative disease formation is caused by failure of the autophagy mechanism. This review outlines PKC signaling in autophagy and neurodegenerative disease development and introduces some polyphenols as effectors of PKC isozymes for disease therapy.
MeSH term(s)	Autophagy/drug effects ; Disease Progression ; Humans ; Isoenzymes/metabolism ; Neurodegenerative Diseases/enzymology ; Neurodegenerative Diseases/pathology ; Polyphenols/pharmacology ; Protein Kinase C/metabolism
Chemical Substances	Isoenzymes ; Polyphenols ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	2020-02-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9030553
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Article ; Online: The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease.

Akkiz, Hikmet / Taskin, Emre / Karaogullarindan, Umit / Delik, Anil / Kuran, Sedef / Kutlu, Ozlem

Medicine

2021 Volume 100, Issue 19, Page(s) e25893

Abstract: Abstract: We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic ... ...

Abstract	Abstract: We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.
MeSH term(s)	Adult ; Blood Glucose ; Body Mass Index ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lipase/genetics ; Liver Function Tests ; Male ; Membrane Proteins/genetics ; Middle Aged ; Non-alcoholic Fatty Liver Disease/genetics ; Polymorphism, Single Nucleotide ; Real-Time Polymerase Chain Reaction ; Turkey/epidemiology
Chemical Substances	Blood Glucose ; Membrane Proteins ; Lipase (EC 3.1.1.3) ; adiponutrin, human (EC 3.1.1.3)
Language	English
Publishing date	2021-06-09
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000025893
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Ua VI Zs.171: Show issues

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Article ; Online: Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related Hepatocellular Carcinoma.

Kutlu, Ozlem / Kaleli, Humeyra Nur / Ozer, Ebru

Canadian journal of gastroenterology & hepatology

2018 Volume 2018, Page(s) 8543763

Abstract: The proportion of obese or diabetic population has been anticipated to increase in the upcoming decades, which rises the prevalence of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). Recent evidence ... ...

Abstract	The proportion of obese or diabetic population has been anticipated to increase in the upcoming decades, which rises the prevalence of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). Recent evidence indicates that NASH is the main cause of chronic liver diseases and it is an important risk factor for development of hepatocellular carcinoma (HCC). Although the literature addressing NASH-HCC is growing rapidly, limited data is available about the etiology of NASH-related HCC. Experimental studies on the molecular mechanism of HCC development in NASH reveal that the carcinogenesis is relevant to complex changes in signaling pathways that mediate cell proliferation and energy metabolism. Genetic or epigenetic modifications and alterations in metabolic, immunologic, and endocrine pathways have been shown to be closely related to inflammation, liver injury, and fibrosis in NASH along with its subsequent progression to HCC. In this review, we provide an overview on the current knowledge of NASH-related HCC development and emphasize molecular signaling pathways regarding their mechanism of action in NASH-derived HCC.
MeSH term(s)	Animals ; Carcinoma, Hepatocellular/etiology ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Disease Progression ; Epigenesis, Genetic ; Humans ; Liver Neoplasms/etiology ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/metabolism ; Signal Transduction
Language	English
Publishing date	2018-08-29
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	2762182-0
ISSN	2291-2797 ; 1916-7237 ; 0835-7900
ISSN (online)	2291-2797 ; 1916-7237
ISSN	0835-7900
DOI	10.1155/2018/8543763
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Zs.A 2360: Show issues

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Article ; Online: Hydrodynamic Cavitation on a Chip: A Tool to Detect Circulating Tumor Cells.

Namli, Ilayda / Seyedmirzaei Sarraf, Seyedali / Sheibani Aghdam, Araz / Celebi Torabfam, Gizem / Kutlu, Ozlem / Cetinel, Sibel / Ghorbani, Morteza / Koşar, Ali

ACS applied materials & interfaces

2022 Volume 14, Issue 36, Page(s) 40688–40697

Abstract: Circulating tumor cells (CTCs) are essential biomarkers for cancer diagnosis. Although various devices have been designed to detect, enumerate, and isolate CTCs from blood, some of these devices could have some drawbacks, such as the requirement of ... ...

Abstract	Circulating tumor cells (CTCs) are essential biomarkers for cancer diagnosis. Although various devices have been designed to detect, enumerate, and isolate CTCs from blood, some of these devices could have some drawbacks, such as the requirement of labeling, long process time, and high cost. Here, we present a microfluidic device based on the concept of "hydrodynamic cavitation-on-chip (HCOC)", which can detect CTCs in the order of minutes. The working principle relies on the difference of the required inlet pressure for cavitation inception of working fluids when they pass through the microfluidic device. The interface among the solid/floating particles, liquid, and vapor phases plays an important role in the strength of the fluid to withstand the rupture and cavitation formation. To this end, four experimental groups, including the "cell culture medium", "medium + Jurkat cells", "medium + Jurkat cells + CTCs", and "medium + CTCs", were tested as a proof of concept with two sets of fabricated microfluidic chips with the same geometrical dimensions, in which one set contained structural sidewall roughness elements. Jurkat cells were used to mimic white blood cells, and MDA-MB-231 cells were spiked into the medium as CTCs. Accordingly, the group with CTCs led to detectable earlier cavitation inception. Additionally, the effect of the CTC concentration on cavitation inception and the effect of the presence of sidewall roughness elements on the earlier inception were evaluated. Furthermore, CTC detection tests were performed with cancer cell lines spiked in blood samples from healthy donors. The results showed that this approach, HCOC, could be a potential approach to detect the presence of CTCs based on cavitation phenomenon and offer a cheap, user-friendly, and rapid tool with no requirement for any biomarker or extensive films acting as a biosensor. This approach also possesses straightforward application procedures to be employed for detection of CTCs.
MeSH term(s)	Cell Line, Tumor ; Cell Separation/methods ; Humans ; Hydrodynamics ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques ; Neoplastic Cells, Circulating/pathology
Language	English
Publishing date	2022-09-01
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.2c12356
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Hydrodynamic Cavitation on a Chip: A Tool to Detect Circulating Tumor Cells

Namli, Ilayda / Seyedmirzaei Sarraf, Seyedali / Sheibani Aghdam, Araz / Celebi Torabfam, Gizem / Kutlu, Ozlem / Cetinel, Sibel / Ghorbani, Morteza / Koşar, Ali

ACS applied materials & interfaces. 2022 Sept. 01, v. 14, no. 36

2022

Abstract	Circulating tumor cells (CTCs) are essential biomarkers for cancer diagnosis. Although various devices have been designed to detect, enumerate, and isolate CTCs from blood, some of these devices could have some drawbacks, such as the requirement of labeling, long process time, and high cost. Here, we present a microfluidic device based on the concept of “hydrodynamic cavitation-on-chip (HCOC)”, which can detect CTCs in the order of minutes. The working principle relies on the difference of the required inlet pressure for cavitation inception of working fluids when they pass through the microfluidic device. The interface among the solid/floating particles, liquid, and vapor phases plays an important role in the strength of the fluid to withstand the rupture and cavitation formation. To this end, four experimental groups, including the “cell culture medium”, “medium + Jurkat cells”, “medium + Jurkat cells + CTCs”, and “medium + CTCs”, were tested as a proof of concept with two sets of fabricated microfluidic chips with the same geometrical dimensions, in which one set contained structural sidewall roughness elements. Jurkat cells were used to mimic white blood cells, and MDA-MB-231 cells were spiked into the medium as CTCs. Accordingly, the group with CTCs led to detectable earlier cavitation inception. Additionally, the effect of the CTC concentration on cavitation inception and the effect of the presence of sidewall roughness elements on the earlier inception were evaluated. Furthermore, CTC detection tests were performed with cancer cell lines spiked in blood samples from healthy donors. The results showed that this approach, HCOC, could be a potential approach to detect the presence of CTCs based on cavitation phenomenon and offer a cheap, user-friendly, and rapid tool with no requirement for any biomarker or extensive films acting as a biosensor. This approach also possesses straightforward application procedures to be employed for detection of CTCs.
Keywords	biomarkers ; biosensors ; blood ; cell culture ; culture media ; hydrodynamics ; liquids ; neoplasm cells ; neoplasms ; processing time ; roughness ; vapors
Language	English
Dates of publication	2022-0901
Size	p. 40688-40697.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021/acsami.2c12356
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Therapeutic Nanoparticles and Their Targeted Delivery Applications.

Yetisgin, Abuzer Alp / Cetinel, Sibel / Zuvin, Merve / Kosar, Ali / Kutlu, Ozlem

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 9

Abstract: Nanotechnology offers many advantages in various fields of science. In this regard, nanoparticles are the essential building blocks of nanotechnology. Recent advances in nanotechnology have proven that nanoparticles acquire a great potential in medical ... ...

Abstract	Nanotechnology offers many advantages in various fields of science. In this regard, nanoparticles are the essential building blocks of nanotechnology. Recent advances in nanotechnology have proven that nanoparticles acquire a great potential in medical applications. Formation of stable interactions with ligands, variability in size and shape, high carrier capacity, and convenience of binding of both hydrophilic and hydrophobic substances make nanoparticles favorable platforms for the target-specific and controlled delivery of micro- and macromolecules in disease therapy. Nanoparticles combined with the therapeutic agents overcome problems associated with conventional therapy; however, some issues like side effects and toxicity are still debated and should be well concerned before their utilization in biological systems. It is therefore important to understand the specific properties of therapeutic nanoparticles and their delivery strategies. Here, we provide an overview on the unique features of nanoparticles in the biological systems. We emphasize on the type of clinically used nanoparticles and their specificity for therapeutic applications, as well as on their current delivery strategies for specific diseases such as cancer, infectious, autoimmune, cardiovascular, neurodegenerative, ocular, and pulmonary diseases. Understanding of the characteristics of nanoparticles and their interactions with the biological environment will enable us to establish novel strategies for the treatment, prevention, and diagnosis in many diseases, particularly untreatable ones.
MeSH term(s)	Drug Delivery Systems ; Humans ; Nanoparticles/adverse effects ; Nanoparticles/therapeutic use ; Nanotechnology
Language	English
Publishing date	2020-05-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25092193
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Zs.MO 81: Show issues

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Article ; Online: Autophagy as a molecular target for cancer treatment.

Kocaturk, Nur Mehpare / Akkoc, Yunus / Kig, Cenk / Bayraktar, Oznur / Gozuacik, Devrim / Kutlu, Ozlem

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

2019 Volume 134, Page(s) 116–137

Abstract: Autophagy is an evolutionarily conserved catabolic mechanism, by which eukaryotic cells recycle or degrades internal constituents through membrane-trafficking pathway. Thus, autophagy provides the cells with a sustainable source of biomolecules and ... ...

Abstract	Autophagy is an evolutionarily conserved catabolic mechanism, by which eukaryotic cells recycle or degrades internal constituents through membrane-trafficking pathway. Thus, autophagy provides the cells with a sustainable source of biomolecules and energy for the maintenance of homeostasis under stressful conditions such as tumor microenvironment. Recent findings revealed a close relationship between autophagy and malignant transformation. However, due to the complex dual role of autophagy in tumor survival or cell death, efforts to develop efficient treatment strategies targeting the autophagy/cancer relation have largely been unsuccessful. Here we review the two-faced role of autophagy in cancer as a tumor suppressor or as a pro-oncogenic mechanism. In this sense, we also review the shared regulatory pathways that play a role in autophagy and malignant transformation. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.
MeSH term(s)	Animals ; Antineoplastic Agents ; Autophagy/drug effects ; Autophagy/physiology ; Genes, Tumor Suppressor ; Humans ; Molecular Targeted Therapy ; Neoplasms/metabolism ; Neoplasms/therapy ; Oncogenes ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2019-04-11
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1154366-8
ISSN	1879-0720 ; 0928-0987
ISSN (online)	1879-0720
ISSN	0928-0987
DOI	10.1016/j.ejps.2019.04.011
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Zs.A 3705: Show issues

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