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2021 ◽  
Vol 25 (5) ◽  
pp. 587-590
Doyle Bosque ◽  
Sheryl Forbes ◽  
Erica Ward ◽  
Joelle Delaney ◽  
G. Tobin Meyers

2021 ◽  
Vol 11 (1) ◽  
Juliano Alves ◽  
Laurie Engel ◽  
Renata de Vasconcelos Cabral ◽  
Eduardo L. Rodrigues ◽  
Liane de Jesus Ribeiro ◽  

AbstractHere we describe a homogeneous bioluminescent immunoassay based on the interaction between Fc-tagged SARS-CoV-2 Spike RBD and human ACE2, and its detection by secondary antibodies labeled with NanoLuc luciferase fragments LgBit and SmBit. The assay utility for the discovery of novel inhibitors was demonstrated with a panel of anti-RBD antibodies, ACE2-derived miniproteins and soluble ACE2. Studying the effect of RBD mutations on ACE2 binding showed that the N501Y mutation increased RBD apparent affinity toward ACE2 tenfold that resulted in escaping inhibition by some anti-RBD antibodies. In contrast, while E484K mutation did not highly change the binding affinity, it still escaped antibody inhibition likely due to changes in the epitope recognized by the antibody. Also, neutralizing antibodies (NAbs) from COVID-19 positive samples from two distinct regions (USA and Brazil) were successfully detected and the results further suggest the persistence of NAbs for at least 6 months post symptom onset. Finally, sera from vaccinated individuals were tested for NAbs and showed varying neutralizing activity after first and second doses, suggesting the assay can be used to assess immunity of vaccinated populations. Our results demonstrate the broad utility and ease of use of this methodology both for drug discovery and clinical research applications.

2021 ◽  
Panyun Mu ◽  
Peihua Qu ◽  
Yulin Li ◽  
Jie Feng ◽  
Xu Ma ◽  

Abstract Background: it is of great significance for clinical diagnosis, prevention and treatment of osteoporosis to deeply understand the pathogenesis and development process of osteoporosis through animal models of osteoporosis. This systematic review aim to summarize the modeling methods of osteoporosis, reveal the current situation and progress of animal models of osteoporosis, and compare the advantages and disadvantages of various modeling methods, so as to provide reference for clinical research.Methods: CNKI, CBM database, VIP database, Wanfang database, PubMed database and EMBASE database were searched by computer from the database establishment to December 2020 with the key words of "animal model; osteoporosis" in Chinese and English respectively. The literatures were screened according to inclusion and exclusion criteria. The methods of osteoporosis modeling, the improvement of the methods and the advantages and disadvantages of each method are summarized.Discussion: a total of 9303 related literatures were collected, and 112 eligible literatures were included. The establishment of an appropriate animal model is the key to the etiology, pathophysiology and drug therapy of osteoporosis. As the causes and pathophysiological changes of different types of OP have their own characteristics, the modeling methods are also different. Therefore, different modeling methods and experimental animals should be selected according to different experimental requirements.Systematic review registration: No

2021 ◽  
pp. 104063872110447
Kaela E. Shaw ◽  
Alexa M. Bersenas ◽  
Shane W. Bateman ◽  
Shauna L. Blois ◽  
R. Darren Wood

Our goal was to validate a human hyaluronic acid (HA) ELISA (Hyaluronic acid plus ELISA; TECOmedical Group) for use in feline plasma. Plasma from 5 healthy cats and 5 critically ill cats was used for validation of the assay. Validation methods performed included intra- and inter-assay variability, spike-and-recovery, and dilutional linearity. All measurements were performed in duplicate. The precision study revealed good intra-assay CV of 7.4–8.9%; inter-assay CV was 3.4–4.2%. Extraction efficiency via spiking tests yielded mean recovery of 89.6%. The assay met criteria for acceptable linearity using 3 serial dilutions. Our results demonstrate that this commercial HA ELISA had acceptable analytical performance using feline plasma and could be a useful tool in the veterinary clinical research setting.

Bioanalysis ◽  
2021 ◽  
Radboud van Trigt ◽  
Jason Neat ◽  
Jan Leendert Brouwer ◽  
Amanda Hays ◽  
Hans Westerhof

The entire world was severely affected by the outbreak of the SARS-CoV-2 virus. Early phase clinical research was no exception and clinical healthy volunteer trials were halted across the globe. To enable continuation of development of new drugs, we developed a testing strategy for nonsymptomatic trial participants in an early stage of the outbreak. A point-of-care polymerase chain reaction test combined with a gold standard polymerase chain reaction test and strict social distancing and hygiene measures limited the number of infected subjects entering our clinical research units and reduced further spread for the duration of the clinical trial. Thus, proving efficacy of this strategy to allow safe and effective continuation of early phase clinical trials during the COVID-19 pandemic.

PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009772
Lingyu Zhan ◽  
Jiajin Li ◽  
Brandon Jew ◽  
Jae Hoon Sul

Late-onset Alzheimer’s disease (LOAD) is the most common type of dementia causing irreversible brain damage to the elderly and presents a major public health challenge. Clinical research and genome-wide association studies have suggested a potential contribution of the endocytic pathway to AD, with an emphasis on common loci. However, the contribution of rare variants in this pathway to AD has not been thoroughly investigated. In this study, we focused on the effect of rare variants on AD by first applying a rare-variant gene-set burden analysis using genes in the endocytic pathway on over 3,000 individuals with European ancestry from three large whole-genome sequencing (WGS) studies. We identified significant associations of rare-variant burden within the endocytic pathway with AD, which were successfully replicated in independent datasets. We further demonstrated that this endocytic rare-variant enrichment is associated with neurofibrillary tangles (NFTs) and age-related phenotypes, increasing the risk of obtaining severer brain damage, earlier age-at-onset, and earlier age-of-death. Next, by aggregating rare variants within each gene, we sought to identify single endocytic genes associated with AD and NFTs. Careful examination using NFTs revealed one significantly associated gene, ANKRD13D. To identify functional associations, we integrated bulk RNA-Seq data from over 600 brain tissues and found two endocytic expression genes (eGenes), HLA-A and SLC26A7, that displayed significant influences on their gene expressions. Differential expressions between AD patients and controls of these three identified genes were further examined by incorporating scRNA-Seq data from 48 post-mortem brain samples and demonstrated distinct expression patterns across cell types. Taken together, our results demonstrated strong rare-variant effect in the endocytic pathway on AD risk and progression and functional effect of gene expression alteration in both bulk and single-cell resolution, which may bring more insight and serve as valuable resources for future AD genetic studies, clinical research, and therapeutic targeting.

2021 ◽  
pp. 025371762110333
Damodharan Dinakaran ◽  
Vanteemar S. Sreeraj ◽  
Ganesan Venkatasubramanian

Nutraceutical agents and food supplements are commonly used as treatment adjuncts in neuropsychiatric disorders. Curcumin, a bioactive agent obtained from the rhizome of Curcuma longa, with its antioxidant and anti-inflammatory properties, has gained much research attention in the last few decades. In this narrative review, we intend to summarize the evidence available for curcumin as an add-on agent in the management of schizophrenia. We searched PubMed/EBSCO for both human and animal trials utilizing curcumin in the management of schizophrenia. We obtained ten articles (five preclinical and five clinical) from the focused literature search. Clinical research utilizing curcumin in schizophrenia is limited to negative and cognitive symptoms. Available preclinical studies suggest curcumin’s utility in ameliorating extrapyramidal and metabolic side effects when given as an adjunct with antipsychotics. Curcumin, as an add-on agent, appears promising to improve the negative and cognitive symptoms of schizophrenia. Notably, curcumin was tolerable and safe in all the randomized human clinical trials. The poor oral bioavailability is, however, a limiting factor in its widespread use.

2021 ◽  
Ani Grigoryan ◽  
Dimitra Zacharaki ◽  
Alexander Balhuizen ◽  
Christophe RM Côme ◽  
Anne-Katrine Frank ◽  

AbstractThe bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and the most frequent site of solid tumor metastasis. Pre-clinical research relies on xenograft mouse models, precluding the human-specific functional interactions of stem cells with their bone marrow microenvironment. Human mesenchymal cells can be exploited for the in vivo engineering of humanized ossicles (hOss). Those mini-bones provide a human niche conferring engraftment of human healthy and malignant blood samples, yet suffering from major reproducibility issue. Here, we report the standardized generation of hOss by developmental priming of a custom-designed human mesenchymal cell line. We demonstrate superior engraftment of cord blood hematopoietic cells and primary acute myeloid leukemia samples, but also validate our hOss as metastatic site for breast cancer cells. Finally, we report the first engraftment of neuroblastoma patient-derived xenograft cells in a humanized model, recapitulating clinically reported osteolytic lesions. Collectively, our hOss constitute a powerful standardized and malleable platform to model normal hematopoiesis, leukemia and solid tumor metastasis.

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