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Article: Omics Analyses in a Neural Stem Cell Model of Familial Parkinson's Disease.

Notopoulou, Sofia / Gkekas, Ioannis / Petrakis, Spyros

Advances in experimental medicine and biology

2023 Volume 1423, Page(s) 149–160

Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of people worldwide. Despite considerable efforts, the underlying pathological mechanisms remain elusive, and yet, no treatment has been developed to ... ...

Abstract	Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of people worldwide. Despite considerable efforts, the underlying pathological mechanisms remain elusive, and yet, no treatment has been developed to efficiently reverse or modify disease progression. Thus, new experimental models are required to provide insights into the pathology of PD. Small-molecule neural precursor cells (smNPCs) are ideal for the study of neurodegenerative disorders due to their neural identity and stem cell properties. Cytoplasmic aggregates of α-synuclein (αSyn) are considered a hallmark of PD and a point mutation in the gene encoding p.A53T is responsible for a familial PD form with earlier and robust symptom onset. In order to study the cellular pathology of PD, we genetically modified smNPCs to inducibly overexpress EYFP-SNCA A53T. This cellular model was biochemically characterized, while dysregulated biological pathways and key regulators of PD pathology were identified by computational analyses. Our study indicates three novel genes, UBA52, PIP5K1A, and RPS2, which may mediate PD cellular pathology.
MeSH term(s)	Humans ; Parkinson Disease/metabolism ; Neural Stem Cells/metabolism ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism ; Neurodegenerative Diseases ; Neurons/metabolism
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	410187-X
ISSN	0065-2598
ISSN	0065-2598
DOI	10.1007/978-3-031-31978-5_12
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Article ; Online: Digitalt assisterad laparoskopisk bridlösning – ett finger med i spelet.

Löfgren, Niklas / Gkekas, Ioannis

Lakartidningen

2021 Volume 118

Abstract: Mechanical intestinal obstruction is an important diagnosis and a common cause of acute abdominal pain. Adhesions and scar tissue in the abdomen after previ-ous surgery is a frequent source. Small bowel obstruction caused by adhesions can be treated ... ...

Title translation	Digital assisted laparoscopy with adhesiolysis in mechanical intestinal obstruction.
Abstract	Mechanical intestinal obstruction is an important diagnosis and a common cause of acute abdominal pain. Adhesions and scar tissue in the abdomen after previ-ous surgery is a frequent source. Small bowel obstruction caused by adhesions can be treated conservatively, but surgery may be needed. Laparotomy is usually the approach for adhesiolysis, but laparoscopy is an option. This case rapport describes a man in his 50s being admitted with severe abdominal pain and vomiting. Further investigation showed a small bowel obstruction caused by adhesions. After two days expectation, surgery be-came necessary. During laparoscopy, the surgeon's finger was introduced intraabdominally and used to release the adhesion. We here present a possible approach to a situation encountered during laparoscopic adhesiolysis and encourage creativity and laparoscopy in selected patients with mechanical small bowel obstruction.
MeSH term(s)	Humans ; Intestinal Obstruction/etiology ; Intestinal Obstruction/surgery ; Intestine, Small/diagnostic imaging ; Intestine, Small/surgery ; Laparoscopy ; Male ; Postoperative Complications ; Tissue Adhesions/complications ; Tissue Adhesions/surgery ; Treatment Outcome
Language	Swedish
Publishing date	2021-04-12
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	391010-6
ISSN	1652-7518 ; 0023-7205
ISSN (online)	1652-7518
ISSN	0023-7205
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Article: Microfluidic Single-Cell Study on

Seidel, Thorsten / Artmann, Philipp Johannes / Gkekas, Ioannis / Illies, Franziska / Baack, Anna-Lena / Viefhues, Martina

Plants (Basel, Switzerland)

2024 Volume 13, Issue 2

Abstract: Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and ...

Abstract	Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and targeted manipulation of small batches of cells down to single-cell analysis. To provide controlled conditions for protoplast fusions and achieve high reproducibility, we developed and characterized a microfluidic device to reliably trap some
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants13020295
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Article: Fabrication and Optimization of 3D-Printed Silica Scaffolds for Neural Precursor Cell Cultivation.

Kastrinaki, Georgia / Pechlivani, Eleftheria-Maria / Gkekas, Ioannis / Kladovasilakis, Nikolaos / Gkagkari, Evdokia / Petrakis, Spyros / Asimakopoulou, Akrivi

Journal of functional biomaterials

2023 Volume 14, Issue 9

Abstract: The latest developments in tissue engineering scaffolds have sparked a growing interest in the creation of controlled 3D cellular structures that emulate the intricate biophysical and biochemical elements found within versatile in vivo microenvironments. ...

Abstract	The latest developments in tissue engineering scaffolds have sparked a growing interest in the creation of controlled 3D cellular structures that emulate the intricate biophysical and biochemical elements found within versatile in vivo microenvironments. The objective of this study was to 3D-print a monolithic silica scaffold specifically designed for the cultivation of neural precursor cells. Initially, a preliminary investigation was conducted to identify the critical parameters pertaining to calcination. This investigation aimed to produce sturdy and uniform scaffolds with a minimal wall-thickness of 0.5 mm in order to mitigate the formation of cracks. Four cubic specimens, with different wall-thicknesses of 0.5, 1, 2, and 4 mm, were 3D-printed and subjected to two distinct calcination profiles. Thermogravimetric analysis was employed to examine the freshly printed material, revealing critical temperatures associated with increased mass loss. Isothermal steps were subsequently introduced to facilitate controlled phase transitions and reduce crack formation even at the minimum wall thickness of 0.5 mm. The optimized structure stability was obtained for the slow calcination profile (160 min) then the fast calcination profile (60 min) for temperatures up to 900 °C. In situ X-ray diffraction analysis was also employed to assess the crystal phases of the silicate based material throughout various temperature profiles up to 1200 °C, while scanning electron microscopy was utilized to observe micro-scale crack formation. Then, ceramic scaffolds were 3D-printed, adopting a hexagonal and spherical channel structures with channel opening of 2 mm, and subsequently calcined using the optimized slow profile. Finally, the scaffolds were evaluated in terms of biocompatibility, cell proliferation, and differentiation using neural precursor cells (NPCs). These experiments indicated proliferation of NPCs (for 13 days) and differentiation into neurons which remained viable (up to 50 days in culture). In parallel, functionality was verified by expression of pre- (SYN1) and post-synaptic (GRIP1) markers, suggesting that 3D-printed scaffolds are a promising system for biotechnological applications using NPCs.
Language	English
Publishing date	2023-09-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2648525-4
ISSN	2079-4983
ISSN	2079-4983
DOI	10.3390/jfb14090465
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Article: Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases

Gkekas, Ioannis / Gioran, Anna / Boziki, Marina Kleopatra / Grigoriadis, Nikolaos / Chondrogianni, Niki / Petrakis, Spyros

Antioxidants. 2021 Sept. 13, v. 10, no. 9

2021

Abstract: Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which ...

Abstract	Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these mutant proteins are associated with oxidative stress, proteasome impairment and microglia activation. These events may correlate with the induction of inflammation in the nervous system and disease progression. Here, we review the effect of polyQ-induced oxidative stress in cellular and animal models of polyQ diseases. Furthermore, we discuss the interplay between oxidative stress, neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease, Multiple Sclerosis. Finally, we review some of the pharmaceutical interventions which may delay the onset and progression of polyQ disorders by targeting disease-associated mechanisms.
Keywords	animals ; disease progression ; inflammation ; microsatellite repeats ; mutants ; neurodegenerative diseases ; neuroglia ; oxidative stress ; proteasome endopeptidase complex ; sclerosis
Language	English
Dates of publication	2021-0913
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10091450
Database	NAL-Catalogue (AGRICOLA)

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Article: Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases.

Gkekas, Ioannis / Gioran, Anna / Boziki, Marina Kleopatra / Grigoriadis, Nikolaos / Chondrogianni, Niki / Petrakis, Spyros

Antioxidants (Basel, Switzerland)

2021 Volume 10, Issue 9

Abstract	Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these mutant proteins are associated with oxidative stress, proteasome impairment and microglia activation. These events may correlate with the induction of inflammation in the nervous system and disease progression. Here, we review the effect of polyQ-induced oxidative stress in cellular and animal models of polyQ diseases. Furthermore, we discuss the interplay between oxidative stress, neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease, Multiple Sclerosis. Finally, we review some of the pharmaceutical interventions which may delay the onset and progression of polyQ disorders by targeting disease-associated mechanisms.
Language	English
Publishing date	2021-09-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10091450
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Article ; Online: Vandrande mjälte – ovanlig men viktig differentialdiagnos vid akut buksmärta hos barn.

Hurtig, Jennie / Gkekas, Ioannis / Näsvall, Pia

Lakartidningen

2018 Volume 115

Abstract: Wandering spleen is a rare reason for acute abdominal pain in pediatric patients caused by laxity of the splenic ligaments. It can be complicated by torsion of the pedicle, leading to ischemia, a situation that in most cases results in acute abdominal ... ...

Title translation	Torsion of wandering spleen - unusual cause to acute abdominal pain in pediatric patients.
Abstract	Wandering spleen is a rare reason for acute abdominal pain in pediatric patients caused by laxity of the splenic ligaments. It can be complicated by torsion of the pedicle, leading to ischemia, a situation that in most cases results in acute abdominal surgery. To prevent ischemia of a mobile spleen caused by a total occlusion of the pedicle, splenopexy can be considered. We present an unusual case where changes in the position of the operating table during diagnostic laparoscopy might have caused a total occlusion of the pedicle.
MeSH term(s)	Abdomen, Acute/diagnosis ; Adolescent ; Diagnosis, Differential ; Female ; Humans ; Laparoscopy ; Patient Positioning/adverse effects ; Splenectomy ; Tomography, X-Ray Computed ; Wandering Spleen/diagnosis ; Wandering Spleen/diagnostic imaging ; Wandering Spleen/etiology ; Wandering Spleen/surgery
Language	Swedish
Publishing date	2018-11-20
Publishing country	Sweden
Document type	Case Reports
ZDB-ID	391010-6
ISSN	1652-7518 ; 0023-7205
ISSN (online)	1652-7518
ISSN	0023-7205
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Article ; Online: Mismatch repair status predicts survival after adjuvant treatment in stage II colon cancer patients.

Gkekas, I / Novotny, J / Fabian, P / Nemecek, R / Palmqvist, R / Strigård, K / John, S / Pecen, L / Reginacova, K / Gunnarsson, U

Journal of surgical oncology

2019 Volume 121, Issue 2, Page(s) 392–401

Abstract: Background and objectives: Stage II colon cancer is primarily a surgical disease. Only a still not well-defined subset of patients may benefit from postoperative adjuvant chemotherapy. The relationship between adjuvant chemotherapy and survival after ... ...

Abstract	Background and objectives: Stage II colon cancer is primarily a surgical disease. Only a still not well-defined subset of patients may benefit from postoperative adjuvant chemotherapy. The relationship between adjuvant chemotherapy and survival after relapse is furthermore still not definitely explored in this group of patients. A number of reports suggest some association between defective mismatch repair (dMMR) and colorectal cancer stage II prognosis, but due to contradictory results from existing studies, the exact predictive role is still not fully understood. Methods: Retrospective multicenter study including 451 stage II colon cancer patients. The proficiency or deficiency of mismatch repair was tested using immunohistochemistry and analyzed in relationship to two survival outcomes: overall survival (OS) and postrelapse survival. Results: Patients with dMMR (20.4%) derived no OS benefit from adjuvant chemotherapy (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.47-2.38; P = .897). Patients with proficient mismatch repair (pMMR) tumors receiving adjuvant chemotherapy had the significantly better OS in comparison to those not receiving chemotherapy (HR, 0.54; 95% CI, 0.35-0.82; P = .004). This relationship remained significant in multivariable analysis (HR, 0.42; 95% CI, 0.22-0.78; P = .007). Patients with pMMR relapsing after adjuvant treatment lived significantly longer than those relapsing without previous adjuvant treatment (HR, 0.55; 95% CI, 0.32-0.96; P = .033) and this result remained significant in the multivariable model (HR, 0.49; 95% CI, 0.26-0.93; P = .030). Conclusion: In stage II CC patients, adjuvant chemotherapy improves therapeutic outcomes only in patients with pMMR tumors. Survival after relapse in patients having received adjuvant chemotherapy is significantly longer for patients with pMMR. No survival benefit from adjuvant chemotherapy was seen among patients with dMMR tumors.
Language	English
Publishing date	2019-12-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	82063-5
ISSN	1096-9098 ; 0022-4790
ISSN (online)	1096-9098
ISSN	0022-4790
DOI	10.1002/jso.25798
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Article ; Online: Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy: A European multicenter cohort study.

Gkekas, Ioannis / Jan, Novotny / Kaprio, Tuomas / Beilmann-Lehtonen, Ines / Fabian, Pavel / Tavelin, Björn / Böckelman, Camilla / Edin, Sofia / Strigård, Karin / Svoboda, Tomas / Hagström, Jaana / Barsova, Lucie / Jirasek, Tomas / Haglund, Caj / Palmqvist, Richard / Gunnarsson, Ulf

Journal of surgical oncology

2024

Abstract: Background and objectives: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal ... ...

Abstract	Background and objectives: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status. Methods: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAF Results: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60-75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89-3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67-3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28-2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72-3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05-2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63-3.42, p = 0.005), respectively. Conclusion: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	82063-5
ISSN	1096-9098 ; 0022-4790
ISSN (online)	1096-9098
ISSN	0022-4790
DOI	10.1002/jso.27619
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Article: Biocompatibility of α-Al

Asimakopoulou, Akrivi / Gkekas, Ioannis / Kastrinaki, Georgia / Prigione, Alessandro / Zaspalis, Vasileios T / Petrakis, Spyros

Journal of functional biomaterials

2020 Volume 11, Issue 3

Abstract: Background: Biocompatible materials-topography could be used for the construction of scaffolds allowing the three-dimensional (3D) organization of human stem cells into functional tissue-like structures with a defined architecture.: Methods: ... ...

Abstract	Background: Biocompatible materials-topography could be used for the construction of scaffolds allowing the three-dimensional (3D) organization of human stem cells into functional tissue-like structures with a defined architecture. Methods: Structural characterization of an alumina-based substrate was performed through XRD, Brunauer-Emmett-Teller (BET) analysis, scanning electron microscopy (SEM), and wettability measurements. Biocompatibility of the substrate was assessed by measuring the proliferation and differentiation of human neural precursor stem cells (NPCs). Results: α-Al Conclusions: Our work indicates the potential use of alumina for the construction of 3D engineered biosystems utilizing human neurons. Such systems may be useful for diagnostic purposes, drug testing, or biotechnological applications.
Language	English
Publishing date	2020-09-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2648525-4
ISSN	2079-4983
ISSN	2079-4983
DOI	10.3390/jfb11030065
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