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Article ; Online: Polyamidoamine Dendron-Bearing Lipids as Drug-Delivery Excipients.

Sarigul, Ender / Zaim, Merve / Senel, Mehmet / Sagir, Tugba / Isik, Sevim

2022 Volume 27, Issue 22

Abstract: An amine-terminated polyamidoamine (PAMAM) dendron and two long alkyl groups were designed as a novel drug carrier that possesses an interior for the encapsulation of drugs and a biocompatible surface. We synthesized three dendron-bearing lipids, DL-G1, ... ...

Abstract	An amine-terminated polyamidoamine (PAMAM) dendron and two long alkyl groups were designed as a novel drug carrier that possesses an interior for the encapsulation of drugs and a biocompatible surface. We synthesized three dendron-bearing lipids, DL-G1, DL-G2, and DL-G3, which included first, second, and third generation polyamidoamine dendrons, respectively. The synthesized dendrimer encapsulating anticancer drug, 5-fluorouracil (5-FU), was prepared by extraction with chloroform from mixtures of the dendrimers and varying amounts of the drug. In vitro cytotoxicity of PAMAM conjugated di-n-dodecylamine micelles (G1, G2, G3) were analyzed on human gastric adenocarcinoma cells (AGS) by water-soluble tetrazolium-1 (WST-1) cell proliferation assay. Upon exposure to 5-FU loaded micelles, the viability of the cells decreased gradually in all generations. Cytotoxicity increased with increasing generation and reached its highest rate of 69.8 ± 3.2% upon 15 µM 5FU-loaded 25 µM PAMAM DL-3 micelle treatment. These results demonstrate that 5FU-loaded PAMAM conjugated di-n-dodecylamine treatment inhibits the proliferation of AGS cells in a generation-dependent manner.
MeSH term(s)	Humans ; Dendrimers/pharmacology ; Excipients ; Micelles ; Lipids ; Fluorouracil/pharmacology
Chemical Substances	PAMAM Starburst ; Dendrimers ; Poly(amidoamine) ; dodecylamine (YWY9OD6A2K) ; Excipients ; Micelles ; dendron ; Lipids ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2022-11-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27227817
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Article ; Online: The paradigm in minimal invasive aortic surgery: how optimistic are we?

Zaim, Sevim / Chan, Jeffrey Shi Kai / Harky, Amer

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2020 Volume 58, Issue 3, Page(s) 660

MeSH term(s)	Aortic Valve/surgery ; Heart Valve Prosthesis Implantation ; Humans ; Minimally Invasive Surgical Procedures ; Sternotomy ; Treatment Outcome
Language	English
Publishing date	2020-05-25
Publishing country	Germany
Document type	Letter
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezaa134
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Article ; Online: DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression.

Zaim, Merve / Isik, Sevim

Stem cell research & therapy

2018 Volume 9, Issue 1, Page(s) 114

Abstract: Background: DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon ... ...

Abstract	Background: DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. Methods and results: For this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ. Conclusion: Our results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.
MeSH term(s)	Cells, Cultured ; DNA Topoisomerases, Type II/metabolism ; Humans ; Mesenchymal Stem Cells/metabolism ; Neuronal Outgrowth/drug effects ; Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism ; rho GTP-Binding Proteins
Chemical Substances	NR4A2 protein, human ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; rho GTP-Binding Proteins (EC 3.6.5.2) ; DNA Topoisomerases, Type II (EC 5.99.1.3)
Language	English
Publishing date	2018-04-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-018-0859-4
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Article ; Online: DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression

Merve Zaim / Sevim Isik

Stem Cell Research & Therapy, Vol 9, Iss 1, Pp 1-

2018 Volume 14

Abstract: Abstract Background DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of ... ...

Abstract	Abstract Background DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. Methods and results For this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ. Conclusion Our results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.
Keywords	Human mesenchymal stem cells ; Neural differentiation ; Neurite outgrowth ; DNA topoisomerase IIβ ; Rho GTPases ; Neurodegeneration ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	571
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: COVID-19 and Multiorgan Response.

Zaim, Sevim / Chong, Jun Heng / Sankaranarayanan, Vissagan / Harky, Amer

Current problems in cardiology

2020 Volume 45, Issue 8, Page(s) 100618

Abstract: Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement. Comorbidities such as cardiovascular diseases have been the most common risk ... ...

Abstract	Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Betacoronavirus/physiology ; COVID-19 ; Cardiovascular Diseases/epidemiology ; Comorbidity ; Coronavirus Infections/complications ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Humans ; Multiple Organ Failure/etiology ; Multiple Organ Failure/immunology ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/complications ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Risk Factors ; SARS-CoV-2
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-04-28
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	441230-8
ISSN	1535-6280 ; 0146-2806
ISSN (online)	1535-6280
ISSN	0146-2806
DOI	10.1016/j.cpcardiol.2020.100618
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Article ; Online: Optimizing outcomes in infective endocarditis: A comprehensive literature review.

Harky, Amer / Zaim, Sevim / Mallya, Apeksha / George, Joel Jacob

Journal of cardiac surgery

2020 Volume 35, Issue 7, Page(s) 1600–1608

Abstract: Background: Despite being rare, infective endocarditis (IE) is a life-threatening disease with poor prognosis. New diagnostic and therapeutic strategies are emerging; however, predisposing factors and microbiology of the disease are also changing with ... ...

Abstract	Background: Despite being rare, infective endocarditis (IE) is a life-threatening disease with poor prognosis. New diagnostic and therapeutic strategies are emerging; however, predisposing factors and microbiology of the disease are also changing with time. Because of this, there has been a lack of reduction in the disease's incidence and new challenges for clinicians have arisen such as an increasingly aging population and growing antimicrobial resistance. Aims: In this paper, we aim to provide an overview of the changing trends in IE, current diagnosis, and management strategies, as well as the emerging role of the infective endocarditis teams in the care of patients with this disease. Materials & methods: A comprehensive electronic search was done utilizing PubMed, Ovid, SCOPUS, Embase and google scholar. The search terms included 'Endocarditis', 'IE', 'Infection', 'Vegetation', 'Duke criteria', 'native valve infection', 'prosthetic valve', 'valve infection', 'endocarditis outcome' and 'endocarditis bacteriology'. The references of the identified articles were then searched for any potential articles that can be included. The inclusion criteria were any article that discussed the evidence behind incidence and management of IE including the role of endocarditis team. The exclusion criteria were case reports, expert opinion, and editorials. Results: All the relevant findings are summarized in specified tables and within appropriate sections. Discussion: It is vital to determine the current trends in the epidemiology and microbiology of the condition so that the diagnostic threshold can be adapted, to identify new at-risk groups and achieve an accelerated evaluation strategy that allows for earlier diagnosis and treatment. Conclusion: Management of IE can benefit from the input of different specialties, such as cardiology, cardiothoracic surgery, infectious disease, and microbiology. Therefore, adopting a multidisciplinary approach towards treatment is crucial to reduce morbidity and mortality from preventable complications of this pathology.
MeSH term(s)	Early Diagnosis ; Endocarditis/diagnosis ; Endocarditis/epidemiology ; Endocarditis/microbiology ; Endocarditis/therapy ; Humans ; Interdisciplinary Communication ; Patient Care Team ; Prognosis
Language	English
Publishing date	2020-06-29
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	639059-6
ISSN	1540-8191 ; 0886-0440
ISSN (online)	1540-8191
ISSN	0886-0440
DOI	10.1111/jocs.14656
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Article ; Online: At the heart of COVID-19.

Khan, Inayat Hussain / Zahra, Syeda Anum / Zaim, Sevim / Harky, Amer

Journal of cardiac surgery

2020 Volume 35, Issue 6, Page(s) 1287–1294

Abstract: Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the ... ...

Abstract	Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the presence of comorbidities are associated with severe form of the disease and poor outcomes. Although the prevalence of COVID-19 in patients with cardiovascular disease is under-reported, there is evidence that pre-existing cardiac disease can render individuals vulnerable. It is thought that COVID-19 may have both a direct and indirect effect on the cardiovascular system; however, the primary mechanism of underlying cardiovascular involvement is still uncertain. Of particular interest is the role of angiotensin-converting enzyme 2, which is well known for its cardiovascular effects and is also considered to be important in the pathogenesis of COVID-19. With a range of different drug candidates being suggested, effective anti-virals and vaccines are an area of on-going research. While our knowledge of COVID-19 continues to rapidly expand, this review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system.
MeSH term(s)	COVID-19 ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; China/epidemiology ; Comorbidity ; Coronavirus Infections/diagnosis ; Coronavirus Infections/epidemiology ; Female ; Global Health ; Humans ; Male ; Pandemics/prevention & control ; Pandemics/statistics & numerical data ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/epidemiology ; Risk Assessment ; Survival Analysis
Keywords	covid19
Language	English
Publishing date	2020-05-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639059-6
ISSN	1540-8191 ; 0886-0440
ISSN (online)	1540-8191
ISSN	0886-0440
DOI	10.1111/jocs.14596
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Article ; Online: COVID-19 and Multiorgan Response

Zaim, Sevim / Chong, Jun Heng / Sankaranarayanan, Vissagan / Harky, Amer

Current Problems in Cardiology

2020 Volume 45, Issue 8, Page(s) 100618

Keywords	Cardiology and Cardiovascular Medicine ; General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	441230-8
ISSN	0146-2806
ISSN	0146-2806
DOI	10.1016/j.cpcardiol.2020.100618
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Article ; Online: At the heart of COVID‐19

Khan, Inayat Hussain / Zahra, Syeda Anum / Zaim, Sevim / Harky, Amer

Journal of Cardiac Surgery

2020 Volume 35, Issue 6, Page(s) 1287–1294

Keywords	Surgery ; Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
ZDB-ID	639059-6
ISSN	1540-8191 ; 0886-0440
ISSN (online)	1540-8191
ISSN	0886-0440
DOI	10.1111/jocs.14596
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Article: COVID-19 and Multiorgan Response

Zaim, Sevim / Chong, Jun Heng / Sankaranarayanan, Vissagan / Harky, Amer

Curr Probl Cardiol

Abstract	Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #694853
Database	COVID19

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