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Article: NADPH Oxidase 3: Beyond the Inner Ear.

Herb, Marc

2024 Volume 13, Issue 2

Abstract: Reactive oxygen species (ROS) were formerly known as mere byproducts of metabolism with damaging effects on cellular structures. The discovery and description of NADPH oxidases (Nox) as a whole enzyme family that only produce this harmful group of ... ...

Abstract	Reactive oxygen species (ROS) were formerly known as mere byproducts of metabolism with damaging effects on cellular structures. The discovery and description of NADPH oxidases (Nox) as a whole enzyme family that only produce this harmful group of molecules was surprising. After intensive research, seven Nox isoforms were discovered, described and extensively studied. Among them, the NADPH oxidase 3 is the perhaps most underrated Nox isoform, since it was firstly discovered in the inner ear. This stigma of Nox3 as "being only expressed in the inner ear" was also used by me several times. Therefore, the question arose whether this sentence is still valid or even usable. To this end, this review solely focuses on Nox3 and summarizes its discovery, the structural components, the activating and regulating factors, the expression in cells, tissues and organs, as well as the beneficial and detrimental effects of Nox3-mediated ROS production on body functions. Furthermore, the involvement of Nox3-derived ROS in diseases progression and, accordingly, as a potential target for disease treatment, will be discussed.
Language	English
Publishing date	2024-02-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox13020219
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Functions of ROS in Macrophages and Antimicrobial Immunity.

Herb, Marc / Schramm, Michael

Antioxidants (Basel, Switzerland)

2021 Volume 10, Issue 2

Abstract: Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. ... ...

Abstract	Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors.
Language	English
Publishing date	2021-02-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10020313
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Article ; Online: Encapsulation of propolis extracted with methylal in the chitosan nanoparticles and its antibacterial and cell cytotoxicity studies.

Vaseghi, Akbar / Parchin, Reza Ashrafi / Chamanie, Kosar Rezaee / Herb, Marc / Maleki, Hajar / Sadeghizadeh, Majid

BMC complementary medicine and therapies

2024 Volume 24, Issue 1, Page(s) 165

Abstract: In this study we develop novel type of antibacterial chitosan-propolis NPs to improve theantimicrobial activity against various pathogens. To this aim, we primarily extracted propolis with methylal and ethanol as green solvents and its encapsulation with ...

Abstract	In this study we develop novel type of antibacterial chitosan-propolis NPs to improve theantimicrobial activity against various pathogens. To this aim, we primarily extracted propolis with methylal and ethanol as green solvents and its encapsulation with chitosan NPs. The developed propolis loaded chitosan NPs indicated antimicrobial and anti-biofilm properties against various gram positive and negative. FTIR revealed the successful encapsulation of the propolis extract with Ethanol (PE) and Methylal (PM) into the chitosan nano career matrix. HPLC and GC-MASS also confirmed the presence of flavonoids and phenols compounds of propolis extracted with both solvents. In addition, we confirmed the total phenolic and flavonoid compounds in propolis by calorimetric method of Folin-Ciocalteu and aluminum trichloride complex formation assays, respectively. PE-CH and PM-CH were optimized regarding physicochemical properties such as particle size, zeta potential, and poly dispersity index (PDI) index. DLS and SEM micrographs confirmed a spherical morphology in a range of 360-420 nm with Z potential values of 30-48 mV and PDI of 0.105-0.166 for PE-CH and PM-CH, respectively. The encapsulation efficiency was evaluated using colorimetric analysis, with median values ranging from 90 to 92%. The MIC values within the range of 2 to 230 µg/ml and MBC values between 3 to 346 μg/ml against both gram-positive and negative bacteria. While both PE and PM showed a significant reduction in the number of E. coli, S. aureus, and S. epidermidis, the use of PE-CH and PM-CH led to a statistically significant and greater reduction in number of E. coli, S. aureus, and S. epidermidis strains on the biofilm, pre-formed biofilm and planktonic phases. Besides, the DPPH assay showed significant antioxidant activity for these NPs within the range of 36 to 92%. MTT assay for MHFB-1, HFF, L929, MDF, and MCF-7 cells exhibited statistically significant differences in each other that show the IC50 between 60-160 µg/ml for normal cells and 20 for cancer cells. Finally the present study indicated that both PM and PM-CH greater than PE and PE-CH in which contain high flavonoid and phenolic contents with a high antioxidation potential antioxidant properties, which could be beneficial for cell proliferation and antibiotic and anticancer applications.
MeSH term(s)	Propolis/pharmacology ; Chitosan/chemistry ; Escherichia coli ; Staphylococcus aureus ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/chemistry ; Solvents ; Ethanol ; Nanoparticles/chemistry ; Flavonoids ; Methyl Ethers
Chemical Substances	Propolis (9009-62-5) ; Chitosan (9012-76-4) ; dimethoxymethane (7H1M4G2NUE) ; Anti-Bacterial Agents ; Solvents ; Ethanol (3K9958V90M) ; Flavonoids ; Methyl Ethers
Language	English
Publishing date	2024-04-19
Publishing country	England
Document type	Journal Article
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-024-04472-8
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Article: Functions of ROS in Macrophages and Antimicrobial Immunity

Herb, Marc / Schramm, Michael

Antioxidants. 2021 Feb. 19, v. 10, no. 2

2021

Abstract	Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors.
Keywords	antimicrobial properties ; immune response ; inflammasomes ; macrophages ; oxygen ; reactive oxygen species
Language	English
Dates of publication	2021-0219
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10020313
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA).

Herb, Marc / Gluschko, Alexander / Farid, Alina / Krönke, Martin

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 834321

Abstract: Macrophages remove bacteria from the extracellular ... ...

Abstract	Macrophages remove bacteria from the extracellular milieu
MeSH term(s)	Autophagy/physiology ; Host-Pathogen Interactions ; Microtubule-Associated Proteins/metabolism ; Phagocytosis/physiology ; Phagosomes/microbiology
Chemical Substances	Microtubule-Associated Proteins
Language	English
Publishing date	2022-03-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.834321
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Article: Reactive Oxygen Species: Not Omnipresent but Important in Many Locations.

Herb, Marc / Gluschko, Alexander / Schramm, Michael

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 716406

Abstract: Reactive oxygen species (ROS), such as the superoxide anion or hydrogen peroxide, have been established over decades of research as, on the one hand, important and versatile molecules involved in a plethora of homeostatic processes and, on the other hand, ...

Abstract	Reactive oxygen species (ROS), such as the superoxide anion or hydrogen peroxide, have been established over decades of research as, on the one hand, important and versatile molecules involved in a plethora of homeostatic processes and, on the other hand, as inducers of damage, pathologies and diseases. Which effects ROS induce, strongly depends on the cell type and the source, amount, duration and location of ROS production. Similar to cellular pH and calcium levels, which are both strictly regulated and only altered by the cell when necessary, the redox balance of the cell is also tightly regulated, not only on the level of the whole cell but in every cellular compartment. However, a still widespread view present in the scientific community is that the location of ROS production is of no major importance and that ROS randomly diffuse from their cellular source of production throughout the whole cell and hit their redox-sensitive targets when passing by. Yet, evidence is growing that cells regulate ROS production and therefore their redox balance by strictly controlling ROS source activation as well as localization, amount and duration of ROS production. Hopefully, future studies in the field of redox biology will consider these factors and analyze cellular ROS more specifically in order to revise the view of ROS as freely flowing through the cell.
Language	English
Publishing date	2021-09-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.716406
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Article ; Online: The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye.

Wolf, Anne / Herb, Marc / Schramm, Michael / Langmann, Thomas

Nature communications

2020 Volume 11, Issue 1, Page(s) 2709

Abstract: Aberrant immune responses including reactive phagocytes are implicated in the etiology of age-related macular degeneration (AMD), a major cause of blindness in the elderly. The translocator protein (18 kDa) (TSPO) is described as a biomarker for reactive ...

Abstract	Aberrant immune responses including reactive phagocytes are implicated in the etiology of age-related macular degeneration (AMD), a major cause of blindness in the elderly. The translocator protein (18 kDa) (TSPO) is described as a biomarker for reactive gliosis, but its biological functions in retinal diseases remain elusive. Here, we report that tamoxifen-induced conditional deletion of TSPO in resident microglia using Cx3cr1
MeSH term(s)	Animals ; Cell Line ; Gene Expression Regulation/drug effects ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Microglia/drug effects ; Microglia/metabolism ; NADPH Oxidase 1/genetics ; NADPH Oxidase 1/metabolism ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism ; Phagocytes/drug effects ; Phagocytes/metabolism ; Purines/pharmacology ; Reactive Oxygen Species/metabolism ; Receptors, GABA/genetics ; Receptors, GABA/metabolism ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Wet Macular Degeneration/genetics ; Wet Macular Degeneration/metabolism
Chemical Substances	Bzrp protein, mouse ; N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide ; Purines ; Reactive Oxygen Species ; Receptors, GABA ; NADPH Oxidase 1 (EC 1.6.3.-) ; NOX1 protein, mouse (EC 1.6.3.-)
Language	English
Publishing date	2020-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-16400-8
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Article ; Online: LC3-associated phagocytosis - The highway to hell for phagocytosed microbes.

Herb, Marc / Gluschko, Alexander / Schramm, Michael

Seminars in cell & developmental biology

2019 Volume 101, Page(s) 68–76

Abstract: Phagocytes ingest, kill and degrade invading microbes in a process called phagocytosis. LC3-associated phagocytosis (LAP) combines the molecular machinery of phagocytosis with that of autophagy, the cellular pathway for ingestion of cytoplasmic ... ...

Abstract	Phagocytes ingest, kill and degrade invading microbes in a process called phagocytosis. LC3-associated phagocytosis (LAP) combines the molecular machinery of phagocytosis with that of autophagy, the cellular pathway for ingestion of cytoplasmic components, resulting in the eponymous association of 'microtubule-associated proteins 1 A/1B light chain 3' (LC3) with the phagosomal membrane. The LC3-decorated phagosomes, or LAPosomes, show enhanced fusion with lysosomes resulting in enhanced killing and degradation of contained pathogens. Thus, LAP is a particularly microbicidal pathway. In this review, we discuss the molecular mechanisms involved in induction and execution of LAP and its crucial role in antimicrobial immunity against bacteria, fungi and parasites. As LAP has only recently been defined, we also point out the key open questions that remain to be answered.
MeSH term(s)	Animals ; Humans ; Lysosomes/immunology ; Microtubule-Associated Proteins/immunology ; Phagocytosis/immunology ; Phagosomes/immunology ; Phagosomes/microbiology
Chemical Substances	Microtubule-Associated Proteins
Language	English
Publishing date	2019-04-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2019.04.016
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Article ; Online: Co-inhibition of PGF and VEGF blocks their expression in mononuclear phagocytes and limits neovascularization and leakage in the murine retina.

Balser, Carsten / Wolf, Anne / Herb, Marc / Langmann, Thomas

Journal of neuroinflammation

2019 Volume 16, Issue 1, Page(s) 26

Abstract: Background: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly. The neovascular (wet) form of AMD can be treated with intravitreal injections of different anti-vascular endothelial growth factor (VEGF) agents. ... ...

Abstract	Background: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly. The neovascular (wet) form of AMD can be treated with intravitreal injections of different anti-vascular endothelial growth factor (VEGF) agents. Placental growth factor (PGF) is another member of the VEGF family of cytokines with pro-angiogenic and pro-inflammatory effects. Here, we aimed to compare single and combined inhibition of VEGF-A and PGF in the laser-induced mouse model of choroidal neovascularization (CNV) with a focus on the effects on retinal mononuclear phagocytes. Methods: CNV was induced in C57BL/6J mice using a YAG-Laser. Immediately after laser damage antibodies against VEGF-A (aVEGF), anti-PGF (aPGF), aVEGF combined with aPGF, aflibercept, or IgG control were injected intravitreally in both eyes. Three and 7 days after laser damage, the vascular leakage was determined by fluorescence angiography. Lectin staining of retinal and RPE/choroidal flat mounts was used to monitor CNV. In situ mRNA co-expression of Iba1, VEGF and PGF were quantified using in situ hybridization. Retinal and RPE/choroidal protein levels of VEGF and PGF as well as the pro-inflammatory cytokines IL-6, IL1-beta, and TNF were determined by ELISA. Results: Early (day 3) and intermediate (day 7) vascular leakage and CNV were significantly inhibited by PGF and VEGF-A co-inhibition, most effectively with the trap molecule aflibercept. While VEGF-A blockage alone had no effects, trapping PGF especially with aflibercept prevented the accumulation of reactive microglia and macrophages in laser lesions. The lesion-related mRNA expression and secretion of VEGF-A and PGF by mononuclear phagocytes were potently suppressed by PGF and partially by VEGF-A inhibition. Protein levels of IL-6 and IL1-beta were strongly reduced in all treatment groups. Conclusions: Retinal inhibition of PGF in combination with VEGF-A prevents vascular leakage and CNV possibly via modulating their own expression in mononuclear phagocytes. PGF-related, optimized strategies to target inflammation-mediated angiogenesis may help to increase efficacy and reduce non-responders in the treatment of wet AMD patients.
MeSH term(s)	Animals ; Choroid Plexus/pathology ; Cytokines/metabolism ; Female ; Interleukin-1/antagonists & inhibitors ; Interleukin-1/biosynthesis ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/biosynthesis ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes/drug effects ; Monocytes/metabolism ; Neovascularization, Pathologic/pathology ; Neovascularization, Pathologic/prevention & control ; Placenta Growth Factor/antagonists & inhibitors ; Placenta Growth Factor/biosynthesis ; RNA, Messenger/biosynthesis ; Retina/pathology ; Retinal Diseases/pathology ; Retinal Diseases/prevention & control ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/biosynthesis
Chemical Substances	Cytokines ; Interleukin-1 ; Interleukin-6 ; Pgf protein, mouse ; RNA, Messenger ; Vascular Endothelial Growth Factor A ; interleukin-6, mouse ; vascular endothelial growth factor A, mouse ; Placenta Growth Factor (144589-93-5)
Language	English
Publishing date	2019-02-07
Publishing country	England
Document type	Journal Article
ISSN	1742-2094
ISSN (online)	1742-2094
DOI	10.1186/s12974-019-1419-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties.

Abie, Nahal / Ünlü, Ceyda / Pinho, Ana Rita / Gomes, Maria C / Remmler, Torsten / Herb, Marc / Grumme, Daniela / Tabesh, Ehsan / Shahbazi, Mohammad-Ali / Mathur, Sanjay / Mano, João F / Maleki, Hajar

ACS applied materials & interfaces

2024

Abstract: Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating ... ...

Abstract	Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating self-assembled silk fibroin (SF), tannic acids (TA), and electrospun bioactive glass nanofibers 70SiO
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.4c00065
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