keyword
https://read.qxmd.com/read/38498600/angiotensin-1-7-treatment-early-in-life-prevents-cardiac-hypertrophy-in-adult-hypertensive-rats
#21
JOURNAL ARTICLE
Carolina Nobre Ribeiro Pontes, Amanda de Sá Martins de Bessa, Larissa Matuda Macedo, Marcos Divino Ferreira-Junior, Keilah Valéria Naves Cavalcante, Hericles Mesquita Campos, Vanessa Rafaela Milhomem Cruz-Leite, Ângela Ribeiro Neves, Rodrigo Mello Gomes, Paulo César Ghedini, Manoel Francisco Biancardi, Elizabeth Pereira Mendes, Clayton Luiz Borges, Gustavo Rodrigues Pedrino, Carlos Henrique Castro
Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Pre-puberty has been considered as a later susceptible window of development and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the pre-puberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHR). SHR were treated with Ang-(1-7) (24 μg/Kg/h) from 4 to 7 weeks of age...
March 12, 2024: Journal of Cardiovascular Pharmacology
https://read.qxmd.com/read/38498345/candesartan-upregulates-angiotensin-converting-enzyme-2-in-kidneys-of-male-animals-by-decreased-ubiquitination
#22
JOURNAL ARTICLE
Ping Wang, Zhiyun Ren, Weiwan Wang, Mingda Liu, Yutao Jia, Mingzhuo Zhang, Ying Xue, Chenyang Zhang, Jianteng Xu, Cheng Wang, Xiaoyan Wang
Candesartan is a common angiotensin-II receptor-1 blocker used for patients with cardiovascular and renal diseases. Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of blood pressure (BP), and also a major receptor for coronaviruses. To determine whether and how candesartan upregulates ACE2, we examined BP and ACE2 in multi-organs from male and female C57BL/6J mice treated with candesartan (1 mg/kg, i.p.) for 7 days. Relative to the vehicle, candesartan lowered BP more in males than females; ACE2 protein abundances were increased in kidneys, not lungs, hearts, aorta, liver, spleen, brain, or serum, only from males...
March 31, 2024: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/38496880/untargeted-metabolomics-uncovers-metabolic-dysregulation-and-tissue-sensitivity-in-ace2-knockout-mice
#23
JOURNAL ARTICLE
Lili Zhao, Weili Yang, Wenyi Ji, Qiuyue Pan, Jinkui Yang, Xi Cao
Angiotensin-converting enzyme 2 (ACE2) polymorphisms are associated with increased risk of type 2 diabetes mellitus (T2DM), obesity and dyslipidemia, which have been determined in various populations. Consistently, ACE2 knockout (ACE2 KO) mice display damaged energy metabolism in multiple tissues, especially the key metabolic tissues such as liver, skeletal muscle and epididymal white adipose tissue (eWAT) and show even more severe phenotype under high-fat diet (HFD) induced metabolic stress. However, the effects of ACE2 on global metabolomics profiling and the tissue sensitivity remain unclear...
March 30, 2024: Heliyon
https://read.qxmd.com/read/38496411/physics-driven-structural-docking-and-protein-language-models-accelerate-antibody-screening-and-design-for-broad-spectrum-antiviral-therapy
#24
Hannah Faisal Almubarak, Wuwei Tan, Andrew D Hoffmann, Juncheng Wei, Lamiaa El-Shennawy, Joshua R Squires, Yuanfei Sun, Nurmaa K Dashzeveg, Brooke Simonton, Yuzhi Jia, Radhika Iyer, Yanan Xu, Vlad Nicolaescu, Derek Elli, Glenn C Randall, Matthew J Schipma, Suchitra Swaminathan, Michael G Ison, Huiping Liu, Deyu Fang, Yang Shen
Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains...
March 4, 2024: bioRxiv
https://read.qxmd.com/read/38496410/rapid-degradation-of-the-human-ace2-receptor-upon-binding-and-internalization-of-sars-cov-2-spike-rbd-protein
#25
Paul Feinstein
It is widely accepted that the SARS-CoV-2 betacoronavirus infects humans through binding the human Angiotensin Receptor 2 (ACE2) that lines the nasal cavity and lungs, followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) cofactor. ACE2 binding is mediated by an approximately 200-residue portion of the SARS-CoV-2 extracellular spike protein, the receptor binding domain (RBD). Robust interactions are shown using a novel cell-based assay between an RBD membrane tethered-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein...
March 8, 2024: bioRxiv
https://read.qxmd.com/read/38496407/coronavirus-spike-rbd-variants-differentially-bind-to-the-human-ace2-receptor
#26
Paul Feinstein
The SARS-CoV-2 betacoronavirus infects people through binding the human Angiotensin Receptor 2 (ACE2), followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) and Furin cofactors. Analysis of the SARS-CoV-2 extracellular spike protein has suggested critical amino acids necessary for binding within a 197-residue portion, the receptor binding domain (RBD). A cell-based assay between a membrane tethered RBD-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein allowed for mutational intersection of both RBD and ACE2 proteins...
March 8, 2024: bioRxiv
https://read.qxmd.com/read/38496296/soluble-ace2-correlates-with-severe-covid-19-and-can-impair-antibody-responses
#27
JOURNAL ARTICLE
Mikhail Lebedin, Christoph Ratswohl, Amar Garg, Marta Schips, Clara Vázquez García, Lisa Spatt, Charlotte Thibeault, Benedikt Obermayer, January Weiner, Ilais Moreno Velásquez, Cathrin Gerhard, Paula Stubbemann, Leif-Gunnar Hanitsch, Tobias Pischon, Martin Witzenrath, Leif Erik Sander, Florian Kurth, Michael Meyer-Hermann, Kathrin de la Rosa
Identifying immune modulators that impact neutralizing antibody responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is of great relevance. We postulated that high serum concentrations of soluble angiotensin-converting enzyme 2 (sACE2) might mask the spike and interfere with antibody maturation toward the SARS-CoV-2-receptor-binding motif (RBM). We tested 717 longitudinal samples from 295 COVID-19 patients and showed a 2- to 10-fold increase of enzymatically active sACE2 (a-sACE2), with up to 1 μg/mL total sACE2 in moderate and severe patients...
March 15, 2024: IScience
https://read.qxmd.com/read/38495173/unraveling-the-binding-mechanisms-of-sars-cov-2-variants-through-molecular-simulations
#28
JOURNAL ARTICLE
Shin-Pon Ju, Yung-Cheng Yang, Hsing-Yin Chen
The emergence of SARS-CoV-2 variants like Delta (AY.29) and Omicron (EG.5) poses continued challenges for vaccines and therapeutics. Mutations in the viral spike protein are key in altering infectivity and immune evasion. This study uses computational modeling to investigate the molecular binding mechanisms between spike protein variants and the ACE2 host receptor. Using the MARTNI force field, coarse-grained molecular dynamics (CGMD) simulations and nudged elastic band (NEB) calculations explore spike-ACE2 interactions for the wild type, Delta variant, and Omicron variant...
March 15, 2024: Heliyon
https://read.qxmd.com/read/38494528/human-bronchial-epithelial-cell-transcriptome-changes-in-response-to-serum-from-patients-with-different-status-of-inflammation
#29
JOURNAL ARTICLE
Kokilavani Sivaraman, Bin Liu, Beatriz Martinez-Delgado, Julia Held, Manuela Büttner, Thomas Illig, Sonja Volland, Gema Gomez-Mariano, Nils Jedicke, Tetyana Yevsa, Tobias Welte, David S DeLuca, Sabine Wrenger, Beata Olejnicka, Sabina Janciauskiene
PURPOSE: To investigate the transcriptome of human bronchial epithelial cells (HBEC) in response to serum from patients with different degrees of inflammation. METHODS: Serum from 19 COVID-19 patients obtained from the Hannover Unified Biobank was used. At the time of sampling, 5 patients had a WHO Clinical Progression Scale (WHO-CPS) score of 9 (severe illness). The remaining 14 patients had a WHO-CPS of below 9 (range 1-7), and lower illness. Multiplex immunoassay was used to assess serum inflammatory markers...
March 17, 2024: Lung
https://read.qxmd.com/read/38493838/nasal-delivery-of-encapsulated-recombinant-ace2-as-a-prophylactic-drug-for-sars-cov-2
#30
JOURNAL ARTICLE
Alberto Baldelli, Chun Yuen Jerry Wong, Hale Oguzlu, Hanieh Gholizadeh, Yigong Guo, Hui Xin Ong, Anika Singh, Daniela Traini, Anubhav Pratap-Singh
Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml...
March 15, 2024: International Journal of Pharmaceutics
https://read.qxmd.com/read/38492859/structural-impact-of-a-new-spike-y170w-mutation-detected-in-early-emerging-sars-cov-2-omicron-variants-in-france
#31
REVIEW
Marie Glenet, Anne-Laure Lebreil, Yohan N'Guyen, Ittah Meyer, Stephanie Baud, Laurent Andreoletti
To assess the genetic characteristics of the early emerging SARS-CoV-2 Omicron variant strains, we retrospectively analyzed a collection of 150 nasopharyngeal samples taken from a series of outpatient cases tested positive by a referenced qRT-PCR assay during the reported period of Omicron variant emergence in December 2021, in northeastern region of France. Next Generation Sequencing (NGS) analysis of SARS-CoV-2 spike sequences revealed that only 3 (2%) of these detected strains were Omicron variants, while 147 (98%) were identified as previously described delta variants...
March 14, 2024: Virus Research
https://read.qxmd.com/read/38492437/novel-nitric-oxide-donors-are-coronary-vasodilators-that-also-bind-to-the-papain-like-protease-of-sars-cov-2
#32
JOURNAL ARTICLE
John F Schmedtje, Fred Ciske, Kendall M Muzzarelli, Zahra Assar
Several investigational nitric oxide donors were originally created to correct vascular endothelial dysfunction in cardiovascular diseases. These 48 compounds contain an urea-like moiety attached to the well-known NO donors isosorbide 2- and 5-mononitrate. CR-0305 and CR-0202 were synthesized and found to be nontoxic in the cell lines HMEC-1, A549/hACE2 and VeroE6. CR-0305 induced vasodilation in human coronary arteries ex vivo. Since NO can also have antiviral properties, a study of drug-protein interactions with SARS-CoV-2 was undertaken using in silico modeling...
March 15, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38491326/autoantibodies-to-ace2-and-immune-molecules-are-associated-with-covid-19-disease-severity
#33
JOURNAL ARTICLE
Eric S Geanes, Rebecca McLennan, Cas LeMaster, Todd Bradley
BACKGROUND: Increased inflammation caused by SARS-CoV-2 infection can lead to severe coronavirus disease 2019 (COVID-19) and long-term disease manifestations. The mechanisms of this variable long-term immune activation are poorly defined. One feature of this increased inflammation is elevated levels of proinflammatory cytokines and chemokines. Autoantibodies targeting immune factors such as cytokines, as well as the viral host cell receptor, angiotensin-converting enzyme 2 (ACE2), have been observed after SARS-CoV-2 infection...
March 15, 2024: Commun Med (Lond)
https://read.qxmd.com/read/38491227/characterization-of-omicron-ba-4-6-xbb-and-bq-1-1-subvariants-in-hamsters
#34
JOURNAL ARTICLE
Peter J Halfmann, Kiyoko Iwatsuki-Horimoto, Makoto Kuroda, Yuichiro Hirata, Seiya Yamayoshi, Shun Iida, Ryuta Uraki, Mutsumi Ito, Hiroshi Ueki, Yuri Furusawa, Yuko Sakai-Tagawa, Maki Kiso, Tammy Armbrust, Sam Spyra, Ken Maeda, Zhongde Wang, Masaki Imai, Tadaki Suzuki, Yoshihiro Kawaoka
During the Omicron wave, previous variants such as BA.2, BA.4, and BA.5 were replaced by newer variants with additional mutations in the spike protein. These variants, BA.4.6, BQ.1.1, and XBB, have spread in different countries with different degrees of success. Here, we evaluated the replicative ability and pathogenicity of BA.4.6, BQ1.1, and XBB clinical isolates in male Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with these Omicron subvariants, the replicative ability of BQ...
March 15, 2024: Communications Biology
https://read.qxmd.com/read/38489333/pathological-changes-in-oral-epithelium-and-the-expression-of-sars-cov-2-entry-receptors-ace2-and-furin
#35
JOURNAL ARTICLE
Osnat Grinstein-Koren, Michal Lusthaus, Hilla Tabibian-Keissar, Ilana Kaplan, Amos Buchner, Ron Ilatov, Marilena Vered, Ayelet Zlotogorski-Hurvitz
BACKGROUND: Expression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection. METHODS: Study included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51)...
2024: PloS One
https://read.qxmd.com/read/38488938/generation-of-a-humanized-mace2-and-a-conditional-hace2-mouse-models-permissive-to-sars-cov-2-infection
#36
JOURNAL ARTICLE
I-Wen Song, Megan Washington, Carolina Leynes, Jason Hsu, Kempaiah Rayavara, Yangjin Bae, Nele Haelterman, Yuqing Chen, Ming-Ming Jiang, Aleksandra Drelich, Vivian Tat, Denise G Lanza, Isabel Lorenzo, Jason D Heaney, Chien-Te Kent Tseng, Brendan Lee, Ronit Marom
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2F83Y,H353K mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26hACE2 )...
March 15, 2024: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/38486021/antibody-independent-protection-against-heterologous-sars-cov-2-challenge-conferred-by-prior-infection-or-vaccination
#37
JOURNAL ARTICLE
Valeria Fumagalli, Micol Ravà, Davide Marotta, Pietro Di Lucia, Elisa B Bono, Leonardo Giustini, Federica De Leo, Maura Casalgrandi, Emanuele Monteleone, Violette Mouro, Chiara Malpighi, Chiara Perucchini, Marta Grillo, Sara De Palma, Lorena Donnici, Silvia Marchese, Matteo Conti, Hiromi Muramatsu, Stanley Perlman, Norbert Pardi, Mirela Kuka, Raffaele De Francesco, Marco E Bianchi, Luca G Guidotti, Matteo Iannacone
Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under the presumption that it is the primary defense mechanism following vaccination or infection. This perspective, however, can overlook the role of T cells, particularly when antibody levels are low or absent. Here we show, through studies in mouse models lacking antibodies but maintaining functional B cells and lymphoid organs, that immunity conferred by prior infection or mRNA vaccination can protect against SARS-CoV-2 challenge independently of antibodies...
March 14, 2024: Nature Immunology
https://read.qxmd.com/read/38484369/a-comprehensive-investigation-on-the-receptor-bsg-expression-reveals-the-potential-risk-of-healthy-individuals-and-cancer-patients-to-2019-ncov-infection
#38
JOURNAL ARTICLE
Yongbiao Huang, Haiting Zhou, Yuan Wang, Lingyan Xiao, Wan Qin, Long Li
BACKGROUND: Coronavirus disease-2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly emerging coronavirus. BSG (basigin) is involved in the tumorigenesis of multiple tumors and recently emerged as a novel viral entry receptor for SARS-CoV-2. However, its expression profile in normal individuals and cancer patients are still unclear. METHODS: We performed a comprehensive analysis of the expression and distribution of BSG in normal tissues, tumor tissues, and cell lines via bioinformatics analysis and experimental verification...
March 13, 2024: Aging
https://read.qxmd.com/read/38483537/evolution-of-nasal-and-olfactory-infection-characteristics-of-sars-cov-2-variants
#39
JOURNAL ARTICLE
Mengfei Chen, Andrew Pekosz, Jason S Villano, Wenjuan Shen, Ruifeng Zhou, Heather Kulaga, Zhexuan Li, Amy Smith, Asiana Gurung, Sarah E Beck, Kenneth W Witwer, Joseph L Mankowski, Murugappan Ramanathan, Nicholas R Rowan, Andrew P Lane
SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium...
March 14, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38481677/neutralization-of-sars-cov-2-and-intranasal-protection-of-mice-with-a-nanoclamp-antibody-mimetic
#40
JOURNAL ARTICLE
Quentin Pagneux, Nathalie Garnier, Manon Fabregue, Sarah Sharkaoui, Sophie Mazzoli, Ilka Engelmann, Rabah Boukherroub, Mary Strecker, Eric Cruz, Peter Ducos, Sabine Szunerits, Ana Zarubica, Richard Suderman
Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B...
March 8, 2024: ACS Pharmacology & Translational Science
keyword
keyword
82467
2
3
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.