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Article ; Online: High altitude is associated with pTau deposition, neuroinflammation, and myelin loss.

Iacono, Diego / Murphy, Erin K / Sherman, Paul M / Chapapas, Holly / Cerqueira, Bianca / Christensen, Christine / Perl, Daniel P / Sladky, John

Scientific reports

2022 Volume 12, Issue 1, Page(s) 6839

Abstract: Mammals are able to adapt to high altitude (HA) if appropriate acclimation occurs. However, specific occupations (professional climbers, pilots, astronauts and other) can be exposed to HA without acclimation and be at a higher risk of brain consequences. ...

Abstract	Mammals are able to adapt to high altitude (HA) if appropriate acclimation occurs. However, specific occupations (professional climbers, pilots, astronauts and other) can be exposed to HA without acclimation and be at a higher risk of brain consequences. In particular, US Air Force U2-pilots have been shown to develop white matter hyperintensities (WMH) on MRI. Whether WMH are due to hypoxia or hypobaria effects is not understood. We compared swine brains exposed to 5000 feet (1524 m) above sea level (SL) with 21% fraction inspired O
MeSH term(s)	Altitude ; Animals ; Brain/diagnostic imaging ; Brain/pathology ; Magnetic Resonance Imaging ; Mammals ; Myelin Sheath ; Neuroinflammatory Diseases ; Swine
Language	English
Publishing date	2022-04-27
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-10881-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Chronic oral methylene blue treatment in a rat model of focal cerebral ischemia/reperfusion.

Huang, Lei / Lu, Jianfei / Cerqueira, Bianca / Liu, Yichu / Jiang, Zhao / Duong, Timothy Q

Brain research

2018 Volume 1678, Page(s) 322–329

Abstract: A single acute low-dose methylene blue (MB), an FDA-grandfathered drug, has been shown to ameliorate behavioral deficits and reduces MRI-defined infarct volume in experimental ischemic stroke when administered intravenously or intraperitoneally. The ... ...

Abstract	A single acute low-dose methylene blue (MB), an FDA-grandfathered drug, has been shown to ameliorate behavioral deficits and reduces MRI-defined infarct volume in experimental ischemic stroke when administered intravenously or intraperitoneally. The efficacy of chronic MB treatment in ischemic stroke remains unknown. In a randomized, double-blinded and vehicle-controlled design, we investigated the efficacy of chronic oral MB administration in ischemic stroke longitudinally up to 60 days post injury using MRI and behavioral tests, with end-point histology. The major findings were chronic oral MB treatment, compared to vehicle, i) improves functional behavioral outcomes starting on day 7 and up to 60 days, ii) reduces MRI-defined total lesion volumes from day 14 and up to 60 days where some initial abnormal MRI-defined core and perfusion-diffusion mismatch were salvaged, iii) reduces white-matter damage, iv) gray matter and white matter damages are consistent with Nissl stains and Black Gold stain histology. These findings provide further evidence that long-term oral administration of low-dose MB is safe and has positive therapeutic effects in chronic ischemic stroke.
MeSH term(s)	Administration, Oral ; Analysis of Variance ; Animals ; Disease Models, Animal ; Double-Blind Method ; Image Processing, Computer-Assisted ; Infarction, Middle Cerebral Artery/diagnostic imaging ; Infarction, Middle Cerebral Artery/drug therapy ; Infarction, Middle Cerebral Artery/physiopathology ; Magnetic Resonance Imaging ; Male ; Methylene Blue/administration & dosage ; Neuroprotective Agents/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Sensory Gating/drug effects ; Sensory Gating/physiology ; Silver Staining ; Spin Labels
Chemical Substances	Neuroprotective Agents ; Spin Labels ; Methylene Blue (T42P99266K)
Language	English
Publishing date	2018-01-01
Publishing country	Netherlands
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2017.10.033
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Article ; Online: Intraarterial transplantation of human umbilical cord blood mononuclear cells in hyperacute stroke improves vascular function.

Huang, Lei / Liu, Yichu / Lu, Jianfei / Cerqueira, Bianca / Misra, Vivek / Duong, Timothy Q

Stem cell research & therapy

2017 Volume 8, Issue 1, Page(s) 74

Abstract: Background: Human umbilical cord blood (hUCB) cell therapy is a promising treatment for ischemic stroke. The effects of hyperacute stem cell transplantation on cerebrovascular function in ischemic stroke are, however, not well understood. This study ... ...

Abstract	Background: Human umbilical cord blood (hUCB) cell therapy is a promising treatment for ischemic stroke. The effects of hyperacute stem cell transplantation on cerebrovascular function in ischemic stroke are, however, not well understood. This study evaluated the effects of hyperacute intraarterial transplantation of hUCB mononuclear cells (MNCs) on cerebrovascular function in stroke rats using serial magnetic resonance imaging (MRI). Methods: HUCB MNCs or vehicle were administered to stroke rats via the internal carotid artery immediately after reperfusion at 60 min following ischemia onset. Lesion volumes were longitudinally evaluated by MRI on days 0, 2, 14, and 28 after stroke, accompanied by behavioral tests. Cerebral blood flow (CBF) and cerebrovascular reactivity were measured by perfusion MRI and CO Results: We found that CBF to the stroke-affected region at 28 days was improved (normalized CBF value: 1.41 ± 0.30 versus 0.49 ± 0.07) by intraarterial transplantation of hUCB MNCs in the hyperacute stroke phase, compared to vehicle control. Cerebrovascular reactivity within the stroke-affected area, measured by CBF fMRI, was also increased (35.2 ± 3.5% versus 12.8 ± 4.3%), as well as the corresponding cerebrovascular density. Some engrafted cells appeared with microvascular-like morphology and stained positive for von Willebrand Factor (an endothelial cell marker), suggesting they differentiated into endothelial cells. Some engrafted cells also connected to host endothelial cells, suggesting they interacted with the host vasculature. Compared to the vehicle group, infarct volume at 28 days in the stem cell treated group was significantly smaller (160.9 ± 15.7 versus 231.2 ± 16.0 mm Conclusions: Intraarterial hUCB MNC transplantation during the hyperacute phase of ischemic stroke improved cerebrovascular function and reduced behavioral deficits and infarct volume.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Blood Flow Velocity ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Brain Ischemia/therapy ; Carotid Artery, Internal ; Cell Differentiation ; Cell Separation ; Cerebrovascular Circulation ; Disease Models, Animal ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Fetal Blood/cytology ; Fetal Blood/metabolism ; Gene Expression ; Humans ; Injections, Intra-Arterial ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/transplantation ; Male ; Postural Balance/physiology ; Rats ; Rats, Sprague-Dawley ; Stroke/metabolism ; Stroke/pathology ; Stroke/therapy ; Transplantation, Heterologous ; von Willebrand Factor/genetics ; von Willebrand Factor/metabolism
Chemical Substances	Biomarkers ; von Willebrand Factor
Language	English
Publishing date	2017-03-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-017-0529-y
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Article ; Online: Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats.

Tiwari, Yash V / Lu, Jianfei / Shen, Qiang / Cerqueira, Bianca / Duong, Timothy Q

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2016 Volume 37, Issue 8, Page(s) 2706–2715

Abstract: Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange ( ... ...

Abstract	Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (K
MeSH term(s)	Animals ; Blood-Brain Barrier/diagnostic imaging ; Blood-Brain Barrier/physiopathology ; Capillary Permeability/physiology ; Contrast Media ; Diffusion Magnetic Resonance Imaging/methods ; Disease Models, Animal ; Evans Blue ; Ischemic Attack, Transient/diagnostic imaging ; Ischemic Attack, Transient/physiopathology ; Male ; Perfusion ; Rats, Sprague-Dawley ; Spin Labels
Chemical Substances	Contrast Media ; Spin Labels ; Evans Blue (45PG892GO1)
Language	English
Publishing date	2016-01-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1177/0271678X16673385
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Zs.A 1663: Show issues

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McDonald, J Tyson / Enguita, Francisco Javier / Taylor, Deanne / Griffin, Robert J / Priebe, Waldemar / Emmett, Mark R / Sajadi, Mohammad M / Harris, Anthony D / Clement, Jean / Dybas, Joseph M / Aykin-Burns, Nukhet / Guarnieri, Joseph W / Singh, Larry N / Grabham, Peter / Baylin, Stephen B / Yousey, Aliza / Pearson, Andrea N / Corry, Peter M / Saravia-Butler, Amanda /

Aunins, Thomas R / Sharma, Sadhana / Nagpal, Prashant / Meydan, Cem / Foox, Jonathan / Mozsary, Christopher / Cerqueira, Bianca / Zaksas, Viktorija / Singh, Urminder / Wurtele, Eve Syrkin / Costes, Sylvain V / Davanzo, Gustavo Gastão / Galeano, Diego / Paccanaro, Alberto / Meinig, Suzanne L / Hagan, Robert S / Bowman, Natalie M / Wolfgang, Matthew C / Altinok, Selin / Sapoval, Nicolae / Treangen, Todd J / Moraes-Vieira, Pedro M / Vanderburg, Charles / Wallace, Douglas C / Schisler, Jonathan / Mason, Christopher E / Chatterjee, Anushree / Meller, Robert / Beheshti, Afshin

bioRxiv : the preprint server for biology

2021

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a ...

Abstract	MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 positive patients, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.04.23.441024
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Article ; Online: Role of miR-2392 in driving SARS-CoV-2 infection.

McDonald, J Tyson / Enguita, Francisco J / Taylor, Deanne / Griffin, Robert J / Priebe, Waldemar / Emmett, Mark R / Sajadi, Mohammad M / Harris, Anthony D / Clement, Jean / Dybas, Joseph M / Aykin-Burns, Nukhet / Guarnieri, Joseph W / Singh, Larry N / Grabham, Peter / Baylin, Stephen B / Yousey, Aliza / Pearson, Andrea N / Corry, Peter M / Saravia-Butler, Amanda /

Aunins, Thomas R / Sharma, Sadhana / Nagpal, Prashant / Meydan, Cem / Foox, Jonathan / Mozsary, Christopher / Cerqueira, Bianca / Zaksas, Viktorija / Singh, Urminder / Wurtele, Eve Syrkin / Costes, Sylvain V / Davanzo, Gustavo Gastão / Galeano, Diego / Paccanaro, Alberto / Meinig, Suzanne L / Hagan, Robert S / Bowman, Natalie M / Wolfgang, Matthew C / Altinok, Selin / Sapoval, Nicolae / Treangen, Todd J / Moraes-Vieira, Pedro M / Vanderburg, Charles / Wallace, Douglas C / Schisler, Jonathan C / Mason, Christopher E / Chatterjee, Anushree / Meller, Robert / Beheshti, Afshin

Cell reports

2021 Volume 37, Issue 3, Page(s) 109839

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a ... ...

Abstract	MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Animals ; Antiviral Agents/pharmacology ; Biomarkers/metabolism ; COVID-19/genetics ; COVID-19/immunology ; Cricetinae ; Female ; Ferrets ; Gene Expression Regulation ; Glycolysis ; Healthy Volunteers ; Humans ; Hypoxia ; Inflammation ; Male ; Mice ; MicroRNAs/genetics ; Middle Aged ; Proteomics/methods ; ROC Curve ; Rats ; SARS-CoV-2/genetics ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Biomarkers ; MIRN2392 microRNA, human ; MicroRNAs
Language	English
Publishing date	2021-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109839
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McDonald, J. Tyson / Enguita, Francisco Javier / Taylor, Deanne / Bowen, Richard A / Griffin, Robert J / Priebe, Waldemar / Emmett, Mark R / McGrath, Marisa / Sajadi, Mohammad / Harris, Anthony D / Clement, Jean / Dybas, Joseph M / Aykin-Burns, Nukhet / Guarnieri, Joseph W / Singh, Larry N / Grabham, Peter / Baylin, Stephen / Yousey, Aliza / Pearson, Andrea N /

Corry, Peter M / Saravia-Butler, Amanda / Aunins, Thomas R / Nagpal, Prashant / Meydan, Cem / Foox, Jonathan / Mozsary, Christopher / Cerqueira, Bianca / Zaksas, Viktorija / Singh, Urminder / Wurtele, Eve Syrkin / Costes, Sylvain V / Galeano, Diego / Paccanaro, Alberto / Meinig, Suzanne L / Hagan, Robert S / Bowman, Natalie M / UNC COVID-19 Pathobiology Consortium / Wolfgang, Matthew C / Altinok, Selin / Sapoval, Nicolae / Treangen, Todd J / Frieman, Matthew / Vanderburg, Charles / Schisler, Jonathan C / Mason, Christopher / Chatterjee, Anushree / Meller, Robert / Beheshti, Afshin

bioRxiv

Abstract	MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we found that miR-2392 was key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 patients tested, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using both in vitro human and in vivo hamster models, we have developed a novel miRNA-based antiviral therapeutic targeting miR-2392 that significantly reduces SARS-CoV-2 viability and may potentially inhibit a COVID-19 disease state in the host.
Keywords	covid19
Language	English
Publishing date	2021-04-23
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.04.23.441024
Database	COVID19

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Article ; Online: The Great Deceiver: miR-2392’s Hidden Role in Driving SARS-CoV-2 Infection

McDonald, J. Tyson / Enguita, Francisco Javier / Taylor, Deanne / Bowen, Richard A. / Griffin, Robert J. / Priebe, Waldemar / Emmett, Mark R. / McGrath, Marisa / Sajadi, Mohammad M. / Harris, Anthony D. / Clement, Jean / Dybas, Joseph M. / Aykin-Burns, Nukhet / Guarnieri, Joseph W. / Singh, Larry N. / Grabham, Peter / Baylin, Stephen B. / Yousey, Aliza / Pearson, Andrea N. /

Corry, Peter M. / Saravia-Butler, Amanda / Aunins, Thomas R. / Nagpal, Prashant / Meydan, Cem / Foox, Jonathan / Mozsary, Christopher / Cerqueira, Bianca / Zaksas, Viktorija / Singh, Urminder / Wurtele, Eve Syrkin / Costes, Sylvain V. / Galeano, Diego / Paccanaro, Alberto / Meinig, Suzanne L. / Hagan, Robert S. / Bowman, Natalie M / UNC COVID-19 Pathobiology Consortium / Wolfgang, Matthew C. / Altinok, Selin / Sapoval, Nicolae / Treangen, Todd J. / Frieman, Matthew / Vanderburg, Charles / Wallace, Douglas C. / Schisler, Jonathan / Mason, Christopher E. / Chatterjee, Anushree / Meller, Robert / Beheshti, Afshin

bioRxiv

Abstract	MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we found that miR-2392 was key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 patients tested, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using both in vitro human and in vivo hamster models, we have developed a novel miRNA-based antiviral therapeutic targeting miR-2392 that significantly reduces SARS-CoV-2 viability and may potentially inhibit a COVID-19 disease state in the host.
Keywords	covid19
Language	English
Publishing date	2021-04-23
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.04.23.441024
Database	COVID19

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Article ; Online: High altitude is associated with pTau deposition, neuroinflammation, and myelin loss.

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Article ; Online: Chronic oral methylene blue treatment in a rat model of focal cerebral ischemia/reperfusion.

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Article ; Online: Intraarterial transplantation of human umbilical cord blood mononuclear cells in hyperacute stroke improves vascular function.

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Article ; Online: Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats.

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Article ; Online: Role of miR-2392 in driving SARS-CoV-2 infection.

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Article ; Online: The Great Deceiver: miR-2392’s Hidden Role in Driving SARS-CoV-2 Infection

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