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1دورية أكاديمية
المؤلفون: Laura Thümmler, Nadine Beckmann, Carolin Sehl, Matthias Soddemann, Peer Braß, Maren Bormann, Leonie Brochhagen, Carina Elsner, Nicolas Hoertel, Céline Cougoule, Sandra Ciesek, Marek Widera, Ulf Dittmer, Monika Lindemann, Peter A. Horn, Oliver Witzke, Stephanie Kadow, Markus Kamler, Erich Gulbins, Katrin Anne Becker, Adalbert Krawczyk
المصدر: Viruses, Vol 16, Iss 4, p 545 (2024)
مصطلحات موضوعية: SARS-CoV-2, antidepressants, COVID-19, Microbiology, QR1-502
الوصف: The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus-like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Maren Bormann, Leonie Brochhagen, Mira Alt, Mona Otte, Laura Thümmler, Lukas van de Sand, Ivana Kraiselburd, Alexander Thomas, Jule Gosch, Peer Braß, Sandra Ciesek, Marek Widera, Sebastian Dolff, Ulf Dittmer, Oliver Witzke, Folker Meyer, Monika Lindemann, Andreas Schönfeld, Hana Rohn, Adalbert Krawczyk
المصدر: Frontiers in Immunology, Vol 14 (2023)
مصطلحات موضوعية: SARS-CoV-2, breakthrough infections, Omicron, Delta, COVID-19, Immunologic diseases. Allergy, RC581-607
الوصف: BackgroundBreakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, are poorly understood. We investigated the humoral and cellular immune responses of hospitalized COVID-19 patients during Delta and Omicron infection waves.MethodsThe corresponding SARS-CoV-2 variant of the respective patients were identified by whole genome sequencing. Humoral immune responses were analyzed by ELISA and a cell culture-based neutralization assay against SARS-CoV-2 D614G isolate (wildtype), Alpha, Delta (AY.43) and Omicron (BA.1 and BA.5). Cellular immunity was evaluated with an IFN-γ ELISpot assay.ResultsOn a cellular level, patients showed a minor IFN-γ response after stimulating PBMCs with mutated regions of SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced. Double-vaccinated patients with Delta breakthrough infection showed a significantly increased neutralizing antibody response against Delta compared to double-vaccinated uninfected controls (median complete neutralization titer (NT100) 640 versus 80, p
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1150667/fullTest; https://doaj.org/toc/1664-3224Test
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3دورية أكاديمية
المؤلفون: Jon-Ruben van Rhijn, Yan Shi, Maren Bormann, Britt Mossink, Monica Frega, Hatice Recaioglu, Marina Hakobjan, Teun Klein Gunnewiek, Chantal Schoenmaker, Elizabeth Palmer, Laurence Faivre, Sarah Kittel-Schneider, Dirk Schubert, Han Brunner, Barbara Franke, Nael Nadif Kasri
المصدر: Neurobiology of Disease, Vol 163, Iss , Pp 105587- (2022)
مصطلحات موضوعية: Brunner syndrome, MAOA, Human iPSC, Dopaminergic neuron, NMDA receptor, Microelectrode array, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
الوصف: Monoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Among these, Monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linked MAOA gene have been associated with Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function, specifically in dopaminergic (DA) neurons. Here we generated human induced pluripotent stem cell (hiPSC)-derived DA neurons from three individuals with Brunner syndrome carrying different mutations and characterized neuronal properties at the single cell and neuronal network level in vitro. DA neurons of Brunner syndrome patients showed reduced synaptic density but exhibited hyperactive network activity. Intrinsic functional properties and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission were not affected in DA neurons of individuals with Brunner syndrome. Instead, we show that the neuronal network hyperactivity is mediated by upregulation of the GRIN2A and GRIN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), resulting in increased NMDAR-mediated currents. By correcting a MAOA missense mutation with CRISPR/Cas9 genome editing we normalized GRIN2A and GRIN2B expression, NMDAR function and neuronal population activity to control levels. Our data suggest that MAOA mutations in Brunner syndrome increase the activity of dopaminergic neurons through upregulation of NMDAR function, which may contribute to the etiology of Brunner syndrome associated phenotypes.
وصف الملف: electronic resource
العلاقة: http://www.sciencedirect.com/science/article/pii/S0969996121003363Test; https://doaj.org/toc/1095-953XTest
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4دورية أكاديمية
المؤلفون: Laura Thümmler, Anja Gäckler, Maren Bormann, Sandra Ciesek, Marek Widera, Hana Rohn, Neslinur Fisenkci, Mona Otte, Mira Alt, Ulf Dittmer, Peter A. Horn, Oliver Witzke, Adalbert Krawczyk, Monika Lindemann
المصدر: Vaccines, Vol 10, Iss 8, p 1348 (2022)
مصطلحات موضوعية: ELISpot, T cells, vaccination, Medicine
الوصف: In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. Cellular responses were analyzed by interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpot assays. Neutralizing antibody titers were assessed against SARS-CoV-2 D614G (wild type) and the variants alpha, delta, and omicron by a cell culture-based neutralization assay. Humoral immunity was also determined by a competitive fluorescence assay, using 11 different variants of SARS-CoV-2. Antibody ratios were measured by ELISA. KTX patients showed significantly lower SARS-CoV-2-specific IFN-γ responses after booster vaccination than healthy controls. However, SARS-CoV-2-specific IL-2 responses were comparable to the T cell responses of healthy controls. Cell culture-based neutralizing antibody titers were 1.3-fold higher in healthy controls for D614G, alpha, and delta, and 7.8-fold higher for omicron (p < 0.01). Healthy controls had approximately 2-fold higher concentrations of potential neutralizing antibodies against all 11 variants than KTX patients. However, more than 60% of the KTX patients displayed antibodies to variants of SARS-CoV-2. Thus, KTX patients should be partly protected, due to neutralizing antibodies to variants of SARS-CoV-2 or by cross-reactive T cells, especially those producing IL-2.
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Maren Bormann, Mira Alt, Leonie Schipper, Lukas van de Sand, Vu Thuy Khanh Le-Trilling, Lydia Rink, Natalie Heinen, Rabea Julia Madel, Mona Otte, Korbinian Wuensch, Christiane Silke Heilingloh, Thorsten Mueller, Ulf Dittmer, Carina Elsner, Stephanie Pfaender, Mirko Trilling, Oliver Witzke, Adalbert Krawczyk
المصدر: Viruses, Vol 13, Iss 10, p 1914 (2021)
مصطلحات موضوعية: SARS-CoV-2, COVID-19, herbal medicine, antiviral, Curcuma longa, turmeric root, Microbiology, QR1-502
الوصف: Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited. Traditional herbal medicines elicit antiviral activity against various viruses and might therefore represent a promising option for the complementary treatment of COVID-19 patients. The application of turmeric root in herbal medicine has a very long history. Its bioactive ingredient curcumin shows a broad-spectrum antimicrobial activity. In the present study, we investigated the antiviral activity of aqueous turmeric root extract, the dissolved content of a curcumin-containing nutritional supplement capsule, and pure curcumin against SARS-CoV-2. Turmeric root extract, dissolved turmeric capsule content, and pure curcumin effectively neutralized SARS-CoV-2 at subtoxic concentrations in Vero E6 and human Calu-3 cells. Furthermore, curcumin treatment significantly reduced SARS-CoV-2 RNA levels in cell culture supernatants. Our data uncover curcumin as a promising compound for complementary COVID-19 treatment. Curcumin concentrations contained in turmeric root or capsules used as nutritional supplements completely neutralized SARS-CoV-2 in vitro. Our data argue in favor of appropriate and carefully monitored clinical studies that vigorously test the effectiveness of complementary treatment of COVID-19 patients with curcumin-containing products.
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Lukas van de Sand, Maren Bormann, Yasmin Schmitz, Christiane Silke Heilingloh, Oliver Witzke, Adalbert Krawczyk
المصدر: Viruses, Vol 13, Iss 7, p 1386 (2021)
مصطلحات موضوعية: herpes simplex viruses, natural products, antiherpetic drugs, resistance, Microbiology, QR1-502
الوصف: Herpes simplex viruses (HSV) are ubiquitously distributed with a seroprevalence ranging up to 95% in the adult population. Refractory viral infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent a major global health issue. In particular, the increasing occurrence of resistance to conventional antiviral drugs make the therapy of such infections even more challenging. For instance, the frequent and long-term use of acyclovir and other nucleoside analogues targeting the viral DNA-polymerase enhance the development of resistant viruses. Particularly, the incidental increase of those strains in immunocompromised patients is alarming and represent a major health concern. Alternative treatment concepts are clearly needed. Natural products such as herbal medicines showed antiherpetic activity in vitro and in vivo and proved to be an excellent source for the discovery and isolation of novel antivirals. By this means, numerous plant-derived compounds with antiviral or antimicrobial activity could be isolated. Natural medicines and their ingredients are well-tolerated and could be a good alternative for treating herpes simplex virus infections. This review provides an overview of the recent status of natural sources such as plants, bacteria, fungi, and their ingredients with antiviral activity against herpes simplex viruses. Furthermore, we highlight the most potent herbal medicines and ingredients as promising candidates for clinical investigation and give an overview about the most important drug classes along with their potential antiviral mechanisms. The content of this review is based on articles that were published between 1996 and 2021.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: Lukas van de Sand, Maren Bormann, Mira Alt, Leonie Schipper, Christiane Silke Heilingloh, Eike Steinmann, Daniel Todt, Ulf Dittmer, Carina Elsner, Oliver Witzke, Adalbert Krawczyk
المصدر: Viruses, Vol 13, Iss 4, p 609 (2021)
مصطلحات موضوعية: SARS-CoV-2, glycyrrhizin, main protease, Microbiology, QR1-502
الوصف: The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are still urgently needed. Complementary medicine is used along with standard medical treatment and accessible to a vast majority of people worldwide. Natural products with antiviral activity may contribute to improve the overall condition of SARS-CoV-2 infected individuals. In the present study, we investigated the antiviral activity of glycyrrhizin, the primary active ingredient of the licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits SARS-CoV-2 replication in vitro. Furthermore, we uncovered the underlying mechanism and showed that glycyrrhizin blocks the viral replication by inhibiting the viral main protease Mpro that is essential for viral replication. Our data indicate that the consumption of glycyrrhizin-containing products such as licorice root tea of black licorice may be of great benefit for SARS-CoV-2 infected people. Furthermore, glycyrrhizin is a good candidate for further investigation for clinical use to treat COVID-19 patients.
وصف الملف: electronic resource
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8دورية أكاديمية
المؤلفون: Maren Bormann, Mira Alt, Leonie Schipper, Lukas van de Sand, Mona Otte, Toni Luise Meister, Ulf Dittmer, Oliver Witzke, Eike Steinmann, Adalbert Krawczyk
المصدر: Viruses, Vol 13, Iss 4, p 598 (2021)
مصطلحات موضوعية: SARS-CoV-2, UVC-box, ultraviolet light, Microbiology, QR1-502
الوصف: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted from person to person by close contact, small aerosol respiratory droplets, and potentially via contact with contaminated surfaces. Herein, we investigated the effectiveness of commercial UVC-LED disinfection boxes in inactivating SARS-CoV-2-contaminated surfaces of personal items. We contaminated glass, metal, and plastic samples representing the surfaces of personal items such as smartphones, coins, or credit cards with SARS-CoV-2 formulated in an organic matrix mimicking human respiratory secretions. For disinfection, the samples were placed at different distances from UVC emitting LEDs inside commercial UVC-LED disinfection boxes and irradiated for different time periods (up to 10 min). High viral loads of SARS-CoV-2 were effectively inactivated on all surfaces after 3 min of irradiation. Even 10 s of UVC-exposure strongly reduced viral loads. Thus, UVC-LED boxes proved to be an effective method for disinfecting SARS-CoV-2-contaminated surfaces that are typically found on personal items.
وصف الملف: electronic resource
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المؤلفون: Moritz Negwer, Bram Bosch, Maren Bormann, Rick Hesen, Lukas Lütje, Lynn Aarts, Carleen Rossing, Nael Nadif Kasri, Dirk Schubert
المصدر: GigaScience. 12
مصطلحات موضوعية: Health Informatics, Computer Science Applications
الوصف: Background Tissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratory’s use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2’s CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment. We also provide detailed tutorials for each step of the pipeline. Findings For more precise alignment, we add a landmark-based atlas registration to ClearMap’s functions as well as include young mouse reference atlases for developmental studies. We provide an alternative cell segmentation method besides ClearMap’s threshold-based approach: Ilastik’s Pixel Classification, importing segmentations from commercial image analysis packages and even manual annotations. Finally, we integrate BrainRender, a recently released visualization tool for advanced 3-dimensional visualization of the annotated cells. Conclusions As a proof of principle, we use FriendlyClearMap to quantify the distribution of the 3 main GABAergic interneuron subclasses (parvalbumin+ [PV+], somatostatin+, and vasoactive intestinal peptide+) in the mouse forebrain and midbrain. For PV+ neurons, we provide an additional dataset with adolescent vs. adult PV+ neuron density, showcasing the use for developmental studies. When combined with the analysis pipeline outlined above, our toolkit improves on the state-of-the-art packages by extending their function and making them easier to deploy at scale.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ce7e9d0b84dfcb2c5855565c59b96edTest
https://doi.org/10.1093/gigascience/giad035Test -
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المؤلفون: Maren Bormann, Lukas van de Sand, Adalbert Krawczyk, Oliver Witzke
المصدر: Klinische Monatsblätter für Augenheilkunde. 238:569-578
مصطلحات موضوعية: medicine.medical_specialty, COVID-19 Vaccines, Population, Disease, Antiviral Agents, ChAdOx1 nCoV-19, Internal medicine, Pandemic, Humans, media_common.cataloged_instance, Medicine, European union, education, COVID-19 Serotherapy, media_common, education.field_of_study, Nucleoside analogue, SARS-CoV-2, business.industry, Vaccination, Immunization, Passive, COVID-19, Vector vaccine, Clinical trial, Ophthalmology, business, 2019-nCoV Vaccine mRNA-1273, medicine.drug
الوصف: Since the end of 2019, the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been spreading worldwide and has caused severe health and economic issues on a global scale. By the end of February 2021, more than 100 million SARS-CoV-2 cases had been reported worldwide. SARS-CoV-2 causes the coronavirus disease 2019 (COVID-19) that can be divided into three phases: An early phase with fever and cough (phase I), a pulmonary vascular disease (phase II) and a hyperinflammatory syndrome (phase III). Since viral replication plays a particularly important role in the early stage of the disease and the patient's immune system in the later course of infection, different therapeutic options arise depending on the stage of the disease. The antiviral nucleoside analogue remdesivir is the only antiviral compound with conditional approval in the European Union. Treatment with remdesivir should be initiated early (within the first seven days of symptom onset) in patients receiving supplemental oxygen without invasive ventilation. In turn, the anti-inflammatory corticosteroid dexamethasone should be administered later in the course of disease in patients receiving oxygen therapy. Since autopsies indicate an increased frequency of thromboembolic events due to COVID-19, additional treatment with anticoagulants is recommended. Since the development of novel antivirals may take years, the application of convalescent plasma from patients who recovered from a SARS-CoV-2 infection for the treatment of COVID-19 is reasonable. However, large-scale studies indicated low efficacy of convalescent plasma. Furthermore, vaccination of the population is essential to control the pandemic. Currently, the mRNA vaccine Tozinameran from BioNTech and Pfizer, the mRNA-1273 vaccine from Moderna as well as the vector vaccine AZD1222 from AstraZeneca are licensed in the European Union. All three vaccines have demonstrated high efficacy in large clinical trials. In addition to these licensed vaccines, many others are being tested in clinical trials. In the present article, an overview of therapeutic options for COVID-19 as well as vaccines for protection against SARS-CoV-2 is provided.Das sich seit Ende 2019 weltweit verbreitende neuartige Coronavirus SARS-CoV-2 („severe acute respiratory syndrome coronavirus type 2“) führte auf globaler Ebene zu schweren gesundheitlichen und volkswirtschaftlichen Problemen. Bis Ende Februar 2021 wurden weltweit mehr als 100 Mio. SARS-CoV-2-Fälle gemeldet. Die durch SARS-CoV-2 ausgelöste Erkrankung COVID-19 („Coronavirus-Disease-2019“) lässt sich in 3 Phasen einteilen: eine frühe Phase mit Fieber und Husten (Phase I), die pneumovaskuläre Erkrankung (Phase II) und die hyperinflammatorische Erkrankung (Phase III). Da im frühen Krankheitsstadium besonders die Virusreplikation eine wichtige Rolle spielt und im späteren Verlauf das Immunsystem der Patienten, ergeben sich, je nach Krankheitsstadium, verschiedene Therapiemöglichkeiten. Das antivirale Nukleosidanalogon Remdesivir ist das einzige therapeutische Medikament mit einer bedingten Zulassung in der Europäischen Union. Eine Behandlung mit Remdesivir sollte bei Patienten, die zusätzlichen Sauerstoff ohne invasive Beatmung erhalten, möglichst frühzeitig nach Symptombeginn eingeleitet werden. Das entzündungshemmende Kortikosteroid Dexamethason sollte wiederum erst später im Krankheitsverlauf bei Patienten mit Sauerstofftherapie verabreicht werden. Da Autopsien auf ein verstärktes Auftreten von thromboembolischen Ereignissen durch COVID-19 hindeuten, wird eine zusätzliche Behandlung mit gerinnungshemmenden Medikamenten empfohlen. Die Entwicklung von Medikamenten ist sehr zeitaufwendig, weshalb es naheliegend ist, schnell verfügbare Rekonvaleszenzplasmen von Patienten nach überstandener SARS-CoV-2-Infektion für die Behandlung von COVID-19 zu testen. Groß angelegte Studien deuten jedoch auf eine geringe Effektivität dieser Rekonvaleszenzplasmen hin. Um die Ausbreitung von SARS-CoV-2 einzudämmen, ist die Entwicklung von Impfstoffen von essenzieller Bedeutung. Derzeit sind in der Europäischen Union die mRNA-Impfstoffe Tozinameran der Unternehmen BioNTech und Pfizer sowie mRNA-1273 der Firma Moderna und der Vektorimpfstoff AZD1222 des Konzerns AstraZeneca zugelassen. Alle 3 Impfstoffe konnten in großen klinischen Studien eine hohe Effektivität ausweisen. Neben diesen zugelassenen Impfstoffen werden noch viele weitere in klinischen Studien erprobt. In dem vorliegenden Artikel wird eine Übersicht über Therapiemöglichkeiten von COVID-19 sowie über Impfstoffe zum Schutz vor SARS-CoV-2 gegeben.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f4971bc7b97dbfef8ca4fd039c2919bTest
https://doi.org/10.1055/a-1423-8961Test
النص الكامل