scholarly journals Molecular and Cellular Biomarkers of COVID-19 Prognosis: Protocol for the Prospective Cohort TARGET Study

10.2196/24211 ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. e24211
Author(s):  
Patricia Kurizky ◽  
Otávio T Nóbrega ◽  
Alexandre Anderson De Sousa Munhoz Soares ◽  
Rodrigo Barbosa Aires ◽  
Cleandro Pires De Albuquerque ◽  
...  

Background Since the beginning of the COVID-19 pandemic, the world’s attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. Objective In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. Methods To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction–confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. Results The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase. Conclusions This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008). Trial Registration Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk International Registered Report Identifier (IRRID) DERR1-10.2196/24211


2020 ◽  
Author(s):  
Patricia Kurizky ◽  
Otávio Toledo Nóbrega ◽  
Alexandre Anderson Sousa Munhoz Soares ◽  
Rodrigo Barbosa Aires ◽  
Cleandro Pires de Albuquerque ◽  
...  

BACKGROUND Since the beginning of the COVID-19 pandemic, the world’s attention has been focused on better understanding the relations between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. Objective: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation and haemostasis, comparing mild and severe forms of COVID-19. OBJECTIVE : In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation and haemostasis, comparing mild and severe forms of COVID-19. METHODS To accomplish these aims, we will analyse demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile and neutrophil function (ROS and NET production, phagocytosis, migration, gene expression and proteomics). Two hundred RT-PCR confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. RESULTS No data collection. CONCLUSIONS We believe that this information will provide more knowledge for ensuing studies that will provide more robust and useful clinical information that may allow for better decisions at the frontlines of health assistance. CLINICALTRIAL RBR-62zdkk



1994 ◽  
Vol 14 (3) ◽  
pp. 1553-1565 ◽  
Author(s):  
K E Conrad ◽  
J M Oberwetter ◽  
R Vaillancourt ◽  
G L Johnson ◽  
A Gutierrez-Hartmann

Ras, a small GTP-binding protein, is required for functional receptor tyrosine kinase signaling. Ultimately, Ras alters the activity of specific nuclear transcription factors and regulates novel patterns of gene expression. Using a rat prolactin promoter construct in transient transfection experiments, we show that both oncogenic Ras and activated forms of Raf-1 kinase selectively stimulated the cellular rat prolactin promoter in GH4 rat pituitary cells. We also show that the Ras signal is completely blocked by an expression vector encoding a dominant-negative Raf kinase. Additionally, using a molecular genetic approach, we determined that inhibitory forms of p42 mitogen-activated protein kinase and an Ets-2 transcription factor interfere with both the Ras and the Raf activation of the rat prolactin promoter. These findings define a functional requirement for these signaling constituents in the activation of the prolactin gene, a cell-specific gene which marks the lactotroph pituitary cell type. Further, this analysis allowed us to order the components in the Ras signaling pathway as it impinges on regulation of prolactin gene transcription as Ras-->Raf kinase-->mitogen-activated protein kinase-->Ets. In contrast, we show that intact c-Jun expression inhibited the Ras-induced activation of the prolactin promoter, defining it as a negative regulator of this pathway, whereas c-Jun was able to enhance the Ras activation of an AP-1-driven promoter in GH4 cells. These data show that c-Jun is not the nuclear mediator of the Ras signal for the highly specialized, pituitary cell-specific prolactin cellular promoter. Thus, we have defined a model system which provides an ideal paradigm for studying Ras/Raf signaling pathways and their effects on neuroendocrine cell-specific gene regulation.



1990 ◽  
Vol 265 (27) ◽  
pp. 16373-16379
Author(s):  
J J Enyeart ◽  
B A Biagi ◽  
R N Day ◽  
S S Sheu ◽  
R A Maurer


1996 ◽  
Vol 16 (1) ◽  
pp. 27-37 ◽  
Author(s):  
L Gabou ◽  
M Boisnard ◽  
I Gourdou ◽  
H Jammes ◽  
J-P Dulor ◽  
...  

ABSTRACT cDNA clones coding for rabbit prolactin were isolated from a pituitary library using a rat prolactin RNA probe. One cDNA contained 873 bases including the entire coding sequence of rabbit prolactin, its signal peptide and the 5′ and 3′ untranslated regions of 44 and 145 nucleotides respectively. The deduced amino acid sequence of the cloned prolactin cDNA presented a 93–78% identity with mink, porcine and human prolactins. The prolactin gene transcription was investigated by RT-PCR analysis in several organs of midlactating New Zealand White rabbits. The ectopic transcription of the prolactin gene was examined in more detail in the mammary gland. A strong PCR signal was detected in the mammary gland of virgin does and was also observed during pregnancy and at the beginning of lactation. This PCR signal was very weak in mid-lactating and absent in post-weaning mammary gland.



2003 ◽  
Vol 79 (1) ◽  
pp. 182-185 ◽  
Author(s):  
John Y. Phelps ◽  
Elizabeth M. Bugg ◽  
Michael J. Shamblott ◽  
Nikos P. Vlahos ◽  
Joe Whelan ◽  
...  


Endocrinology ◽  
1987 ◽  
Vol 121 (4) ◽  
pp. 1251-1255 ◽  
Author(s):  
MARK D. CREW ◽  
STEPHEN R. SPINDLER ◽  
ROY L. WALFORD ◽  
AKIO KOIZUMI


2003 ◽  
Vol 173 (4) ◽  
pp. 333-337 ◽  
Author(s):  
M. Ando ◽  
T. Sakamoto ◽  
T. Agustsson ◽  
S. Moriyama ◽  
T. Itoh ◽  
...  


Cell ◽  
1988 ◽  
Vol 52 (5) ◽  
pp. 685-695 ◽  
Author(s):  
Stuart Adler ◽  
Marian L. Waterman ◽  
Xi He ◽  
Michael G. Rosenfeld


Author(s):  
Mara E. Lieberman ◽  
Richard A. Maurer ◽  
Philippa Claude ◽  
Julie Wiklund ◽  
Nancy Wertz ◽  
...  


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