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Article: The Role of NOX2-Derived Reactive Oxygen Species in the Induction of Endothelin-Converting Enzyme-1 by Angiotensin II.

Adu-Gyamfi, Michael / Goettsch, Claudia / Kamhieh-Milz, Julian / Chen, Lei / Pfefferkorn, Anna Maria / Hofmann, Anja / Brunssen, Coy / Müller, Gregor / Walther, Thomas / Ashraf, Muhammad Imtiaz / Morawietz, Henning / Witowski, Janusz / Catar, Rusan

Antioxidants (Basel, Switzerland)

2024 Volume 13, Issue 4

Abstract: Endothelin-1 is a key regulator of vascular tone and blood pressure in health and disease. We have recently found that ET-1 production in human microvascular endothelial cells (HMECs) can be promoted by angiotensin II (Ang II) through a novel mechanism ... ...

Abstract	Endothelin-1 is a key regulator of vascular tone and blood pressure in health and disease. We have recently found that ET-1 production in human microvascular endothelial cells (HMECs) can be promoted by angiotensin II (Ang II) through a novel mechanism involving octamer-binding transcription factor-1 (Oct-1), NADPH oxidase-2 (NOX2), and superoxide anions. As the formation of bioactive ET-1 also depends on endothelin-converting enzyme-1 (ECE-1), we investigated the transcriptional regulation of the
Language	English
Publishing date	2024-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox13040500
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Article ; Online: A 17-year analysis of pregnancies termination ≥14 weeks of gestation in a German level 1 perinatal center.

Kiver, Verena I I / Altmann, Judith / Kamhieh-Milz, Julian / Weichert, Alexander

Journal of perinatal medicine

2019 Volume 47, Issue 8, Page(s) 847–856

Abstract: Background When discussing termination of pregnancy (TOP) after the first trimester, the main foci are the ethics and psychological reasoning/consequences. In daily clinical practice, physicians are often faced with affected women querying the frequency ... ...

Abstract	Background When discussing termination of pregnancy (TOP) after the first trimester, the main foci are the ethics and psychological reasoning/consequences. In daily clinical practice, physicians are often faced with affected women querying the frequency of their condition(s) and decisions made by women in similar situations. The present study aimed to provide an overview of a representable number of such cases. Methods Cases of TOP beyond 14 + 0 weeks of gestation were collected between January 2000 and December 2017 in the Department of Obstetrics. Fetal and/or maternal medical causes leading to TOP were extracted and presented. Results A total of 1746 TOPs ≥14 + 0 weeks were performed. Reasons leading to TOP were subcategorized into 23 groups. The main medical diagnoses were trisomy 21 (15.5%), neurological malformations (11.0%), and cardiac and major vessel malformations (7.9%). There was no statistical difference concerning maternal age or gravida/para between the groups. The average gestational age (GA) was 21.0 weeks, varying between 16.2 and 24.2 weeks in the 23 subgroups, with an average of 23.6% per year of TOPs after viability. Conclusion An overview of the various causes of TOP and their frequency within a large dataset are shown here. According to data provided by the German Federal Statistical Office, the overall number of TOPs has declined over the past two decades; however, the number and percentage of TOPs beyond viability have increased continuously in Germany. Only early detection of maternal and fetal constitution can prevent a portion of TOP after viability.
MeSH term(s)	Abortion, Induced/statistics & numerical data ; Congenital Abnormalities/epidemiology ; Female ; Germany/epidemiology ; Humans ; Pregnancy ; Pregnancy Trimester, Second
Language	English
Publishing date	2019-09-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	123512-6
ISSN	1619-3997 ; 0300-5577 ; 0936-174X
ISSN (online)	1619-3997
ISSN	0300-5577 ; 0936-174X
DOI	10.1515/jpm-2019-0072
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Article ; Online: MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy.

Moll, Guido / Drzeniek, Norman / Kamhieh-Milz, Julian / Geissler, Sven / Volk, Hans-Dieter / Reinke, Petra

Frontiers in immunology

2020 Volume 11, Page(s) 1091

Abstract: Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for ... ...

Abstract	Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for COVID-19, but MSC therapies have shown first promise in the treatment of acute respiratory distress syndrome (ARDS) pneumonia, inflammation, and sepsis, which are among the leading causes of mortality in COVID-19 patients. Many of the critically ill COVID-19 patients are in a hypercoagulable procoagulant state and at high risk for disseminated intravascular coagulation, thromboembolism, and thrombotic multi-organ failure, another cause of high fatality. It is not yet clear whether IV infusion is a safe and effective route of MSC delivery in COVID-19, since MSC-based products express variable levels of highly procoagulant tissue factor (TF/CD142), compromising the cells' hemocompatibility and safety profile. Of concern, IV infusions of poorly characterized MSC products with unchecked (high) TF/CD142 expression could trigger blood clotting in COVID-19 and other vulnerable patient populations and further promote the risk for thromboembolism. In contrast, well-characterized products with robust manufacturing procedures and optimized modes of clinical delivery hold great promise for ameliorating COVID-19 by exerting their beneficial immunomodulatory effects, inducing tissue repair and organ protection. While the need for MSC therapy in COVID-19 is apparent, integrating both innate and adaptive immune compatibility testing into the current guidelines for cell, tissue, and organ transplantation is critical for safe and effective therapies. It is paramount to only use well-characterized, safe MSCs even in the most urgent and experimental treatments. We here propose three steps to mitigate the risk for these vulnerable patients: (1) updated clinical guidelines for cell and tissue transplantation, (2) updated minimal criteria for characterization of cellular therapeutics, and (3) updated cell therapy routines reflecting specific patient needs.
MeSH term(s)	Administration, Intravenous ; Blood Coagulation Disorders/etiology ; COVID-19 ; Cell- and Tissue-Based Therapy/methods ; Coronavirus Infections/complications ; Coronavirus Infections/immunology ; Coronavirus Infections/therapy ; Guidelines as Topic ; Humans ; Injections, Intramuscular ; Mesenchymal Stem Cell Transplantation/adverse effects ; Mesenchymal Stem Cell Transplantation/methods ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/immunology ; Pneumonia, Viral/therapy ; Transplantation Immunology
Keywords	covid19
Language	English
Publishing date	2020-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01091
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Article ; Online: Addressing multiple gastroenterological aspects of coronavirus disease 2019.

Eder, Piotr / Łodyga, Michał / Dobrowolska, Agnieszka / Rydzewska, Grażyna / Kamhieh-Milz, Julian

Polish archives of internal medicine

2020 Volume 130, Issue 5, Page(s) 420–430

Abstract: The outbreak of the coronavirus disease 2019 (COVID‑19) pandemic has become the biggest challenge for the whole human community since many years. It seems that the proper identification of all people infected with severe acute respiratory syndrome ... ...

Abstract	The outbreak of the coronavirus disease 2019 (COVID‑19) pandemic has become the biggest challenge for the whole human community since many years. It seems that the proper identification of all people infected with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the best strategy to limit the transmission. However, in a significant proportion of patients, there are no clinical manifestations of the disease, and symptoms may be very mild or atypical. There is a growing body of evidence that digestive manifestations of COVID‑19 are frequently reported and may precede typical respiratory symptoms. Moreover, SARS‑CoV‑2 particles were found in the gastrointestinal epithelial cells, and viral RNA was detected in the feces of patients with COVID‑19. These data suggest that gastrointestinal symptoms in COVID‑19 are not accidental findings and they may result from direct digestive involvement. Patients with new‑onset diarrhea, abdominal pain, nausea, and vomiting without any other evident etiological factors should be tested for SARS‑CoV‑2 infection. Gastroenterologists and members of other medical specialties should also remember that the current epidemiological situation has changed diagnostic and therapeutic algorithms in the management of several gastrointestinal and liver disorders. This review article summarizes the currently available data on multiple gastroenterological aspects of COVID‑19 and provides information on practical recommendations and position statements of the most prominent associations in the field of gastroenterology, which appeared in response to the emergence of the pandemic.
MeSH term(s)	Betacoronavirus/metabolism ; Coronavirus/metabolism ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Coronavirus Infections/drug therapy ; Coronavirus Infections/therapy ; Digestive System/metabolism ; Digestive System/virology ; Digestive System Diseases/virology ; Humans ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/therapy
Keywords	covid19
Language	English
Publishing date	2020-05-01
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.15332
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Article ; Online: Oxidative stress is predominant in female but not in male patients with autoimmune thrombocytopenia.

Kamhieh-Milz, Julian / Salama, Abdulgabar

Oxidative medicine and cellular longevity

2014 Volume 2014, Page(s) 720347

Abstract: As the involvement of oxidative stress (OS) in autoimmune thrombocytopenia (AITP) has been reported, a fast and rapid test for the reliable measurement of OS and antioxidant capacities (AOCs) might be a useful tool in extending current diagnostic ... ...

Abstract	As the involvement of oxidative stress (OS) in autoimmune thrombocytopenia (AITP) has been reported, a fast and rapid test for the reliable measurement of OS and antioxidant capacities (AOCs) might be a useful tool in extending current diagnostic possibilities. The free oxygen radical test (FORT) and free oxygen radical defence (FORD) assay (Callegari, Italy) are easy to perform and reliable, with results available within 15 minutes. Thirty-seven AITP patients and 37 matched healthy individuals were included in this study. All participants responded to a standard questionnaire provided by these assays. Female patients with AITP were observed to demonstrate significantly higher OS in comparison to female controls (P = 0.0027) and male AITP patients (P = 0.0018). The AOCs were not reduced in patients with AITP (P = 0.7648). Correlation of OS with platelet count identified a weak positive correlation (P = 0.0327, Spearman R = 0.4672). The questionnaire revealed that ITP patients in comparison to healthy controls are more stressed, feel exhausted and fatigued, and eat a healthier diet. In conclusion, OS is predominant in female but not in male patients with AITP suggesting gender-specific differences in the pathomechanisms of AITP. Identification of patients with high levels of OS might be beneficial in the management of AITP.
MeSH term(s)	Adult ; Antioxidants/metabolism ; Case-Control Studies ; Demography ; Female ; Humans ; Male ; Oxidative Stress ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic/blood ; Purpura, Thrombocytopenic, Idiopathic/pathology ; Surveys and Questionnaires
Chemical Substances	Antioxidants
Language	English
Publishing date	2014-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2455981-7
ISSN	1942-0994 ; 1942-0994
ISSN (online)	1942-0994
ISSN	1942-0994
DOI	10.1155/2014/720347
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Article ; Online: Editorial comment: variables affecting the presence of mesenchymal stromal cells in the peripheral blood and their relationship with apheresis product.

Moll, Guido / Drzeniek, Norman / Kamhieh-Milz, Julian / Geissler, Sven / Reinke, Petra

British journal of haematology

2020 Volume 189, Issue 4, Page(s) 593–596

MeSH term(s)	Blood Component Removal ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cell Mobilization ; Humans ; Mesenchymal Stem Cells
Chemical Substances	Granulocyte Colony-Stimulating Factor (143011-72-7)
Language	English
Publishing date	2020-02-10
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.16389
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Article ; Online: Ang II Promotes ET-1 Production by Regulating NOX2 Activity Through Transcription Factor Oct-1.

Kamhieh-Milz, Julian / Chen, Lei / Goettsch, Claudia / Pfefferkorn, Anna Maria / Hofmann, Anja / Brunssen, Coy / Müller, Gregor M / Walther, Thomas / Ashraf, Muhammad Imtiaz / Moll, Guido / Morawietz, Henning / Witowski, Janusz / Catar, Rusan

Arteriosclerosis, thrombosis, and vascular biology

2023 Volume 43, Issue 8, Page(s) 1429–1440

Abstract: Background: Increasing evidence suggests that superoxide ions produced by NOX (nicotinamide adenine dinucleotide phosphate oxidases) mediate vascular effects of Ang II (angiotensin II) evoked by atherogenic diets. Here, we analyzed the mechanism by ... ...

Abstract	Background: Increasing evidence suggests that superoxide ions produced by NOX (nicotinamide adenine dinucleotide phosphate oxidases) mediate vascular effects of Ang II (angiotensin II) evoked by atherogenic diets. Here, we analyzed the mechanism by which NOX2 contributes to Ang II-induced ET-1 (endothelin 1) production in human microvascular endothelial cells. Methods: The effects of high-fat diet were compared between WT (wild type) and Results: Feeding mice high-fat diet for 10 weeks increased cardiac expression and plasma levels of Ang II and ET-1 in WT but not in Conclusions: Ang II may promote ET-1 production in the endothelium in response to atherogenic diets through a mechanism that involves the transcription factor Oct-1 and the increased formation of superoxide anions by NOX2.
MeSH term(s)	Mice ; Animals ; Humans ; Superoxides/metabolism ; Endothelial Cells/metabolism ; Octamer Transcription Factor-1 ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Angiotensin II/pharmacology ; Angiotensin II/metabolism ; Reactive Oxygen Species/metabolism
Chemical Substances	Superoxides (11062-77-4) ; Octamer Transcription Factor-1 ; NADPH Oxidases (EC 1.6.3.-) ; Angiotensin II (11128-99-7) ; Reactive Oxygen Species
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.122.318764
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Article ; Online: Autoimmune activation and hypersensitization of the AT1 and ETA receptors contributes to vascular injury in scleroderma renal crisis.

Hegner, Björn / Kretzschmar, Tobias / Zhu, Nan / Kleinau, Gunnar / Zhao, Hongfan / Kamhieh-Milz, Julian / Hilger, Julia / Schindler, Ralf / Scheerer, Patrick / Riemekasten, Gabriela / Philippe, Aurélie / Catar, Rusan

Rheumatology (Oxford, England)

2023 Volume 62, Issue 6, Page(s) 2284–2293

Abstract: Objectives: Scleroderma renal crisis (SRC) is a rare vascular complication of systemic sclerosis with substantial risks for end-stage renal disease and premature death. Activating autoantibodies (Abs) targeting the angiotensin II type 1 (AT1R) and the ... ...

Abstract	Objectives: Scleroderma renal crisis (SRC) is a rare vascular complication of systemic sclerosis with substantial risks for end-stage renal disease and premature death. Activating autoantibodies (Abs) targeting the angiotensin II type 1 (AT1R) and the endothelin-1 type A receptor (ETAR) have been identified as predictors for SRC. Here, we sought to determine their pathogenic significance for acute renal vascular injury potentially triggering kidney failure and malignant hypertension. Methods: IgG from patients with SRC was studied for AT1R and ETAR dependent biologic effects on isolated rat renal interlobar arteries and vascular cells including contraction, signalling and mechanisms of receptor activation. Results: In myography experiments, patient IgG exerted vasoconstriction sensitive to inhibition of AT1R and ETAR. This relied on MEK-ERK signalling indicating functional relevance of anti-AT1R and anti-ETAR Abs. The contractile response to angiotensin II and endothelin-1 was amplified by patient IgG containing anti-AT1R and anti-ETAR Abs with substantial crosstalk between both receptors implicating autoimmune receptor hypersensitization. Co-immunoprecipitation experiments indicated heterodimerization between both receptor types which may enable the observed functional interrelation by direct structural interactions. Conclusion: We provide experimental evidence that agonistic Abs may contribute to SRC. This effect is presumably related to direct receptor stimulation and additional allosteric effects, at least in heterodimeric receptor constellations. Novel therapies targeted at autoimmune hyperactivation of AT1R and ETAR might improve outcomes in severe cases of SRC.
MeSH term(s)	Rats ; Animals ; Angiotensin II ; Vascular System Injuries ; Endothelin-1 ; Autoantibodies ; Receptor, Endothelin A ; Scleroderma, Localized ; Acute Kidney Injury ; Immunoglobulin G
Chemical Substances	Angiotensin II (11128-99-7) ; Endothelin-1 ; Autoantibodies ; Receptor, Endothelin A ; Immunoglobulin G
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keac594
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Article: The Role of Adipose Tissue in the Pathogenesis and Therapeutic Outcomes of Inflammatory Bowel Disease.

Eder, Piotr / Adler, Maciej / Dobrowolska, Agnieszka / Kamhieh-Milz, Julian / Witowski, Janusz

Cells

2019 Volume 8, Issue 6

Abstract: Though historically regarded as an inert energy store, adipose tissue is a complex endocrine organ, which is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Accumulating evidence points to visceral adipose tissue and ... ...

Abstract	Though historically regarded as an inert energy store, adipose tissue is a complex endocrine organ, which is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Accumulating evidence points to visceral adipose tissue and specifically to its mesenteric component, or "creeping fat" as impacting on the disease course through its immunomodulatory properties. On the one hand, mesenteric fat acts as a physical barrier to inflammation and is involved in controlling host immune response to translocation of gut bacteria. On the other hand, however, there exists a strong link between visceral fat and complicated course of the disease with unfavorable therapeutic outcomes. Furthermore, "creeping fat" appears to play different roles in different IBD phenotypes, with the greatest pathogenetic contribution probably to an ileal form of Crohn's disease. In this review, we summarize and discuss the existing literature on the subject and identify high-priority areas for future research. It may be that a better understanding of the role of mesenteric fat in IBD will determine new therapeutic targets and translate into improved clinical outcomes.
MeSH term(s)	Adipokines/metabolism ; Adipose Tissue/pathology ; Animals ; Disease Progression ; Humans ; Inflammatory Bowel Diseases/etiology ; Inflammatory Bowel Diseases/therapy ; Phenotype ; Treatment Outcome
Chemical Substances	Adipokines
Language	English
Publishing date	2019-06-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409
ISSN	2073-4409
DOI	10.3390/cells8060628
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Article ; Online: Donating blood on a regular basis reduces blood pressure (in hypertensives): appearances are not deceiving.

Kamhieh-Milz, Julian / Tauchmann, Yvonne / Kamhieh-Milz, Sundrela / Pruss, Axel / Doerffel, Yvonne / Michalsen, Andreas

Transfusion

2019 Volume 59, Issue 4, Page(s) 1405–1406

MeSH term(s)	Blood Donors ; Blood Pressure ; Humans ; Hypertension
Language	English
Publishing date	2019-04-05
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.15131
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