Evidence map›Paper›PMID 35841265›Full record

ArticleJournal of pineal research2022

Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.

Michael D Weiss, Silvia Carloni, Tania Vanzolini, Sofia Coppari, Walter Balduini, Giuseppe Buonocore, Mariangela Longini, Serafina Perrone, Livia Sura, Atefeh Mohammadi and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of pineal research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 2 countries.

Michael D WeissDepartment of Pediatrics, University of Florida, Gainesville, Florida, USA.ORCID https://orcid.org/0000-0002-4567-9286
Silvia CarloniDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.ORCID https://orcid.org/0000-0003-3634-3454
Tania VanzoliniDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Sofia CoppariDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Walter BalduiniDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.ORCID http://orcid.org/0000-0001-8438-9559
Giuseppe BuonocoreDepartment of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
Mariangela LonginiDepartment of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
Serafina PerroneNeonatal Unit, University Medical Center of Parma (AOUP) and University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0001-5478-5657
Livia SuraDepartment of Pediatrics, University of Florida, Gainesville, Florida, USA.
Atefeh MohammadiDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Marco Bruno Luigi RocchiDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Massimo NegriniDepartment of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Davide MelandriO. U. Burns Center, Dermatology and Emilia Romagna Regional Skin Bank, "M. Bufalini" Hospital, Cesena, Italy.
Maria Cristina AlbertiniDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.ORCID http://orcid.org/0000-0003-4549-1475
University of Urbino · ITUniversity of Florida · USUniversity of Siena · ITOspedale “M. Bufalini” di Cesena · ITUniversity of Ferrara · ITUniversity of Parma · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neonatal encephalopathy (NE) is a pathological condition affecting long-term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic-ischemic (HI) brain injury. However, unlike animal models that enable the study of the brain and the pathophysiologic cascade, only blood is available from human subjects. Therefore, due to the unavailability of neonatal brain tissue, assumptions about the pathophysiology in pathways and cascades are made in human subjects with NE. We analyzed animal and human specimens to improve our understanding of the pathophysiology in human neonates. A neonate with NE who underwent hypothermia and enrolled in a melatonin pharmacokinetic study was compared to HI rats treated/untreated with melatonin. MicroRNA (miRNA) analyses provided profiles of the neonate's plasma, rat plasma, and rat brain cortexes. We compared these profiles through a bioinformatics tool, identifying Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways common to HI brain injury and melatonin treatment. After evaluating the resulting pathways and the literature, to validate the method, the key proteins expressed in HI brain injury were investigated using cerebral cortexes. The upregulated miRNAs in human neonate and rat plasma helped identify two KEGG pathways, glioma and long-term potentiation, common to HI injury and melatonin treatment. A unified neonatal cerebral melatonin-sensitive HI pathway was designed and validated by assessing the expression of protein kinase Cα (PKCα), phospho (p)-Akt, and p-ERK proteins in rat brain cortexes. PKCα increased in HI-injured rats and further increased with melatonin. p-Akt and p-ERK returned phosphorylated to their basal level with melatonin treatment after HI injury. The bioinformatics analyses validated by key protein expression identified pathways common to HI brain injury and melatonin treatment. This approach helped complete pathways in neonates with NE by integrating information from animal models of HI brain injury.

Indexed as

Brain InjuriesHypothermiaHypoxia-Ischemia, BrainMelatoninMicroRNAsAnimalsAnimals, NewbornHumansProtein Kinase C-alphaProto-Oncogene Proteins c-aktRatsMelatoninMicroRNAsProtein Kinase C-alphaProto-Oncogene Proteins c-akthypothermiahypoxic-ischemiamelatoninmiRNAneonatal brain injuryneonatal encephalopathy

Identifiers

PMID35841265
PMCPMC9540681
OpenAlexW4285588806

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.