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Article ; Online: To what extent can mastication functionality be restored following mandibular reconstruction surgery? A computer modeling approach.

Aftabi, Hamidreza / Sagl, Benedikt / Lloyd, John E / Prisman, Eitan / Hodgson, Antony / Fels, Sidney

Computer methods and programs in biomedicine

2024 Volume 250, Page(s) 108174

Abstract: Statement of problem: Advanced cases of head and neck cancer involving the mandible often require surgical removal of diseased sections and subsequent replacement with donor bone. During the procedure, the surgeon must make decisions regarding which ... ...

Abstract	Statement of problem: Advanced cases of head and neck cancer involving the mandible often require surgical removal of diseased sections and subsequent replacement with donor bone. During the procedure, the surgeon must make decisions regarding which bones or tissues to resect. This requires balancing tradeoffs related to issues such as surgical access and post-operative function; however, the latter is often difficult to predict, especially given that long-term functionality also depends on the impact of post-operative rehabilitation programs. Purpose: To assist in surgical decision-making, we present an approach for estimating the effects of reconstruction on key aspects of post-operative mandible function. Material and methods: We develop dynamic biomechanical models of the reconstructed mandible considering different defect types and validate them using literature data. We use these models to estimate the degree of functionality that might be achieved following post-operative rehabilitation. Results: We find significant potential for restoring mandibular functionality, even in cases involving large defects. This entails an average trajectory error below 2 mm, bite force comparable to a healthy individual, improved condyle mobility, and a muscle activation change capped at a maximum of 20%. Conclusion: These results suggest significant potential for adaptability in the masticatory system and improved post-operative rehabilitation, leading to greater restoration of jaw function.
Language	English
Publishing date	2024-04-17
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632564-6
ISSN	1872-7565 ; 0169-2607
ISSN (online)	1872-7565
ISSN	0169-2607
DOI	10.1016/j.cmpb.2024.108174
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Article ; Online: It takes more than two to tango: mechanosignaling of the endothelial surface.

Fels, Benedikt / Kusche-Vihrog, Kristina

Pflugers Archiv : European journal of physiology

2020 Volume 472, Issue 4, Page(s) 419–433

Abstract: The endothelial surface is a highly flexible signaling hub which is able to sense the hemodynamic forces of the streaming blood. The subsequent mechanosignaling is basically mediated by specific structures, like the endothelial glycocalyx building the ... ...

Abstract	The endothelial surface is a highly flexible signaling hub which is able to sense the hemodynamic forces of the streaming blood. The subsequent mechanosignaling is basically mediated by specific structures, like the endothelial glycocalyx building the top surface layer of endothelial cells as well as mechanosensitive ion channels within the endothelial plasma membrane. The mechanical properties of the endothelial cell surface are characterized by the dynamics of cytoskeletal proteins and play a key role in the process of signal transmission from the outside (lumen of the blood vessel) to the interior of the cell. Thus, the cell mechanics directly interact with the function of mechanosensitive structures and ion channels. To precisely maintain the vascular tone, a coordinated functional interdependency between endothelial cells and vascular smooth muscle cells is necessary. This is given by the fact that mechanosensitive ion channels are expressed in both cell types and that signals are transmitted via autocrine/paracrine mechanisms from layer to layer. Thus, the outer layer of the endothelial cells can be seen as important functional mechanosensitive and reactive cellular compartment. This review aims to describe the known mechanosensitive structures of the vessel building a bridge between the important role of physiological mechanosignaling and the proper vascular function. Since mutations and dysfunction of mechanosensitive proteins are linked to vascular pathologies such as hypertension, they play a potent role in the field of channelopathies and mechanomedicine.
MeSH term(s)	Animals ; Endothelial Cells/metabolism ; Glycocalyx/metabolism ; Humans ; Ion Channels/metabolism ; Mechanotransduction, Cellular/physiology ; Myocytes, Smooth Muscle/metabolism ; Stress, Mechanical
Chemical Substances	Ion Channels
Language	English
Publishing date	2020-04-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-020-02369-2
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Article: Prolonged Door-to-Balloon Time Leads to Endothelial Glycocalyx Damage and Endothelial Dysfunction in Patients with ST-Elevation Myocardial Infarction.

Vahldieck, Carl / Fels, Benedikt / Löning, Samuel / Nickel, Laura / Weil, Joachim / Kusche-Vihrog, Kristina

Biomedicines

2023 Volume 11, Issue 11

Abstract: Damage to the endothelial glycocalyx (eGC) has been reported during acute ischemic events like ST-elevation myocardial infarction (STEMI). In STEMI, a door-to-balloon time (D2B) of <60 min was shown to reduce mortality and nonfatal complications. Here, ... ...

Abstract	Damage to the endothelial glycocalyx (eGC) has been reported during acute ischemic events like ST-elevation myocardial infarction (STEMI). In STEMI, a door-to-balloon time (D2B) of <60 min was shown to reduce mortality and nonfatal complications. Here, we hypothesize that eGC condition is associated with D2B duration and endothelial function during STEMI. One hundred and twenty-six individuals were analyzed in this study (STEMI patients vs. age-/sex-matched healthy volunteers). After stimulating endothelial cells with patient/control sera, the eGC's nanomechanical properties (i.e., height/stiffness) were analyzed using the atomic force microscopy-based nanoindentation technique. eGC components were determined via ELISA, and measurements of nitric oxide levels (NO) were based on chemiluminescence. eGC height/stiffness (both
Language	English
Publishing date	2023-10-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11112924
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Article ; Online: Nanomechanics of the Endothelial Glycocalyx: From Structure to Function.

Cosgun, Zülfü Cem / Fels, Benedikt / Kusche-Vihrog, Kristina

The American journal of pathology

2020 Volume 190, Issue 4, Page(s) 732–741

Abstract: The negatively charged, brush-like glycocalyx covers the surface layer of endothelial cells. This layer of membrane-bound, carbohydrate-rich molecules covers the luminal surface of the endothelium along the entire vascular tree, mostly comprising ... ...

Abstract	The negatively charged, brush-like glycocalyx covers the surface layer of endothelial cells. This layer of membrane-bound, carbohydrate-rich molecules covers the luminal surface of the endothelium along the entire vascular tree, mostly comprising glycoproteins and proteoglycans. Together with the underlying actin-rich endothelial cortex, 50 to 150 nm beneath the plasma membrane, the endothelial glycocalyx (eGC) is recognized as a vasoprotective nanobarrier and responsive hub. Importantly, both the eGC and cortex are highly dynamic and can adapt their nanomechanical properties (ie, stiffness and height) to changes in the environment. The constant change between a soft and a stiff endothelial surface is imperative for proper functioning of the endothelium. This review defines the nanomechanical properties of the eGC and stresses the underlying mechanisms and factors leading to a disturbed structure-function relationship. Specifically, under inflammatory conditions, the eGC is damaged, resulting in enhanced vascular permeability, tissue edema, augmented leukocyte adhesion, platelet aggregation, and dysregulated vasodilation. An integrated knowledge of the relationship between the nanomechanical properties, structure, and function of the eGC might be key in understanding vascular function and dysfunction. In this context, the clinical aspects for preservation and restoration of proper eGC nanomechanics are discussed, considering the eGC as a potentially promising diagnostic marker and therapeutic target in the near future.
MeSH term(s)	Animals ; Biomechanical Phenomena ; Capillary Permeability ; Cell Adhesion ; Endothelium, Vascular/metabolism ; Glycocalyx/chemistry ; Glycocalyx/physiology ; Humans
Language	English
Publishing date	2020-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2019.07.021
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Article ; Online: Analysis of mold and mycotoxins in naturally infested indoor building materials.

Lindemann, Viktoria / Schleiner, Tim / Maier, Ulrich / Fels, Hubert / Cramer, Benedikt / Humpf, Hans-Ulrich

Mycotoxin research

2022 Volume 38, Issue 3, Page(s) 205–220

Abstract: Health issues of residents of mold-infested housing are reported on a regular basis, and reasons for the arising impairments can be manifold. One possible cause are the toxic secondary metabolite produced by indoor microfungi (mycotoxins). To enable a ... ...

Abstract	Health issues of residents of mold-infested housing are reported on a regular basis, and reasons for the arising impairments can be manifold. One possible cause are the toxic secondary metabolite produced by indoor microfungi (mycotoxins). To enable a more thorough characterization of the exposure to mycotoxins in indoor environments, data on occurrence and quantities of mycotoxins is essential. In the presented study, 51 naturally mold-infested building material samples were analyzed applying a previously developed method based on ultra-high performance liquid chromatography (UHPLC) separation in combination with triple-quadrupole mass spectrometry (TQMS) detection. A total of 38 secondary metabolites derived from different indoor mold genera like Aspergillus, Fusarium, Penicillium, and Stachybotrys were analyzed, of which 16 were detectable in 28 samples. As both the spectrum of target analytes and the investigated sample matrices showed high chemical varieties, an alternative calibration approach was applied complementary to identify potentially emerging matrix effects during ionization and mass spectrometric detection. Overall, strong alterations of analyte signals were rare, and compensation of considerable matrix suppression/enhancement only had to be performed for certain samples. Besides mycotoxin determination and quantification, the presence of 18 different mold species was confirmed applying microbiological approaches in combination with macro- and microscopic identification according to DIN ISO 16000-17:2010-06. These results additionally highlight the diversity of mycotoxins potentially arising in indoor environments and leads to the assumption that indoor mycotoxin exposure stays an emerging topic of research, which has only just commenced.
MeSH term(s)	Air Pollution, Indoor/analysis ; Chromatography, High Pressure Liquid ; Construction Materials/analysis ; Construction Materials/microbiology ; Mycotoxins/analysis ; Stachybotrys/chemistry
Chemical Substances	Mycotoxins
Language	English
Publishing date	2022-07-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	14500-2
ISSN	1867-1632 ; 0178-7888
ISSN (online)	1867-1632
ISSN	0178-7888
DOI	10.1007/s12550-022-00461-3
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Article: Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.

Budde, Ilka / Schlichting, André / Ing, David / Schimmelpfennig, Sandra / Kuntze, Anna / Fels, Benedikt / Romac, Joelle M-J / Swain, Sandip M / Liddle, Rodger A / Stevens, Angela / Schwab, Albrecht / Pethő, Zoltán

bioRxiv : the preprint server for biology

2024

Abstract: Pancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces ... ...

Abstract	Pancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces durotaxis, a form of directional cell migration driven by differential stiffness. The molecular sensors behind durotaxis are still unclear. To investigate the role of mechanosensitive ion channels in PSC durotaxis, we established a two-dimensional stiffness gradient mimicking PDAC. Using pharmacological and genetic methods, we investigated the role of the ion channels Piezo1, TRPC1, and TRPV4 in PSC durotaxis. We found that PSC migration towards a stiffer substrate is diminished by altering Piezo1 activity. Moreover, disrupting TRPC1 along with TRPV4 abolishes PSC durotaxis even when Piezo1 is functional. Hence, PSC durotaxis is optimal with an intermediary level of mechanosensitive channel activity, which we simulated using a numerically discretized mathematical model. Our findings suggest that mechanosensitive ion channels, particularly Piezo1, detect the mechanical microenvironment to guide PSC migration.
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.22.572956
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Article: The Role of TRP Channels in the Metastatic Cascade.

Fels, Benedikt / Bulk, Etmar / Pethő, Zoltán / Schwab, Albrecht

Pharmaceuticals (Basel, Switzerland)

2018 Volume 11, Issue 2

Abstract: A dysregulated cellular ... ...

Abstract	A dysregulated cellular Ca
Language	English
Publishing date	2018-05-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph11020048
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Article: Analysis of mold and mycotoxins in naturally infested indoor building materials

Lindemann, Viktoria / Schleiner, Tim / Maier, Ulrich / Fels, Hubert / Cramer, Benedikt / Humpf, Hans-Ulrich

Mycotoxin research. 2022 Aug., v. 38, no. 3

2022

Abstract	Health issues of residents of mold-infested housing are reported on a regular basis, and reasons for the arising impairments can be manifold. One possible cause are the toxic secondary metabolite produced by indoor microfungi (mycotoxins). To enable a more thorough characterization of the exposure to mycotoxins in indoor environments, data on occurrence and quantities of mycotoxins is essential. In the presented study, 51 naturally mold-infested building material samples were analyzed applying a previously developed method based on ultra-high performance liquid chromatography (UHPLC) separation in combination with triple-quadrupole mass spectrometry (TQMS) detection. A total of 38 secondary metabolites derived from different indoor mold genera like Aspergillus, Fusarium, Penicillium, and Stachybotrys were analyzed, of which 16 were detectable in 28 samples. As both the spectrum of target analytes and the investigated sample matrices showed high chemical varieties, an alternative calibration approach was applied complementary to identify potentially emerging matrix effects during ionization and mass spectrometric detection. Overall, strong alterations of analyte signals were rare, and compensation of considerable matrix suppression/enhancement only had to be performed for certain samples. Besides mycotoxin determination and quantification, the presence of 18 different mold species was confirmed applying microbiological approaches in combination with macro- and microscopic identification according to DIN ISO 16000–17:2010–06. These results additionally highlight the diversity of mycotoxins potentially arising in indoor environments and leads to the assumption that indoor mycotoxin exposure stays an emerging topic of research, which has only just commenced.
Keywords	Aspergillus ; Fusarium ; Penicillium ; Stachybotrys ; calibration ; chemical species ; fungi ; ionization ; mass spectrometry ; mycotoxins ; research ; secondary metabolites ; toxicity ; ultra-performance liquid chromatography
Language	English
Dates of publication	2022-08
Size	p. 205-220.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	14500-2
ISSN	1867-1632 ; 0178-7888
ISSN (online)	1867-1632
ISSN	0178-7888
DOI	10.1007/s12550-022-00461-3
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Mineralocorticoid receptor-antagonism prevents COVID-19-dependent glycocalyx damage.

Fels, Benedikt / Acharya, Sovon / Vahldieck, Carl / Graf, Tobias / Käding, Nadja / Rupp, Jan / Kusche-Vihrog, Kristina

Pflugers Archiv : European journal of physiology

2022 Volume 474, Issue 10, Page(s) 1069–1076

Abstract: Proinflammatory cytokines target vascular endothelial cells during COVID-19 infections. In particular, the endothelial glycocalyx (eGC), a proteoglycan-rich layer on top of endothelial cells, was identified as a vulnerable, vasoprotective structure ... ...

Abstract	Proinflammatory cytokines target vascular endothelial cells during COVID-19 infections. In particular, the endothelial glycocalyx (eGC), a proteoglycan-rich layer on top of endothelial cells, was identified as a vulnerable, vasoprotective structure during infections. Thus, eGC damage can be seen as a hallmark in the development of endothelial dysfunction and inflammatory processes. Using sera derived from patients suffering from COVID-19, we could demonstrate that the eGC became progressively worse in relation to disease severity (mild vs severe course) and in correlation to IL-6 levels. This could be prevented by administering low doses of spironolactone, a well-known and highly specific aldosterone receptor antagonist. Our results confirm that SARS-CoV-2 infections cause eGC damage and endothelial dysfunction and we outline the underlying mechanisms and suggest potential therapeutic options.
MeSH term(s)	COVID-19/blood ; COVID-19/drug therapy ; COVID-19/pathology ; Cytokines/pharmacology ; Endothelial Cells/drug effects ; Endothelial Cells/pathology ; Glycocalyx/drug effects ; Glycocalyx/pathology ; Humans ; Interleukin-6/blood ; Mineralocorticoid Receptor Antagonists/pharmacology ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Proteoglycans/analysis ; Proteoglycans/blood ; SARS-CoV-2 ; Spironolactone/pharmacology ; Spironolactone/therapeutic use
Chemical Substances	Cytokines ; Interleukin-6 ; Mineralocorticoid Receptor Antagonists ; Proteoglycans ; Spironolactone (27O7W4T232)
Language	English
Publishing date	2022-07-22
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-022-02726-3
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Article ; Online: Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta.

Pacia, Marta Z / Chorazy, Natalia / Sternak, Magdalena / Fels, Benedikt / Pacia, Michal / Kepczynski, Mariusz / Kusche-Vihrog, Kristina / Chlopicki, Stefan

Cellular and molecular life sciences : CMLS

2022 Volume 79, Issue 6, Page(s) 317

Abstract: Endothelial inflammation is recognized as a critical condition in the development of cardiovascular diseases. TNF-induced inflammation of endothelial cells is linked to the formation of lipid droplets, augmented cortical stiffness, and nanostructural ... ...

Abstract	Endothelial inflammation is recognized as a critical condition in the development of cardiovascular diseases. TNF-induced inflammation of endothelial cells is linked to the formation of lipid droplets, augmented cortical stiffness, and nanostructural endothelial plasma membrane remodelling, but the insight into the mechanism linking these responses is missing. In the present work, we determined the formation of lipid droplets (LDs), nanomechanical, and nanostructural responses in the model of TNF-activated vascular inflammation in the isolated murine aorta using Raman spectroscopy, fluorescence imaging, atomic force microscopy (AFM), and scanning electron microscopy (SEM). We analysed the possible role of Rac1, a major regulator of cytoskeletal organization, in TNF-induced vascular inflammation. We demonstrated that the formation of LDs, polymerization of F-actin, alterations in cortical stiffness, and nanostructural protuberances in endothelial plasma membrane were mediated by the Rac1. In particular, we revealed a significant role for Rac1 in the regulation of the formation of highly unsaturated LDs formed in response to TNF. Inhibition of Rac1 also downregulated the overexpression of ICAM-1 induced by TNF, supporting the role of Rac1 in vascular inflammation. Altogether, our results demonstrate that LDs formation, an integral component of vascular inflammation, is activated by Rac1 that also regulates nanomechanical and nanostructural alterations linked to vascular inflammation.
MeSH term(s)	Animals ; Aorta ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Inflammation/metabolism ; Lipid Droplets/metabolism ; Mice
Language	English
Publishing date	2022-05-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04362-7
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