Evidence map›Paper›PMID 33686952›Full record

ArticleAging2021

Transcriptome profiling reveals target in primary myelofibrosis together with structural biology study on novel natural inhibitors regarding JAK2.

Weihang Li, Bin Yuan, Yingjing Zhao, Tianxing Lu, Shilei Zhang, Ziyi Ding, Dong Wang, Sheng Zhong, Guangxun Gao, Ming Yan

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

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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

10 authors at 5 institutions in 2 countries.

Weihang LiDepartment of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Bin YuanDepartment of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Yingjing ZhaoCollege of Clinical Medicine, Jilin University, Changchun, China.
Tianxing LuHou Zonglian Medical Experimental Class, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Shilei ZhangDepartment of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Ziyi DingDepartment of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Dong WangDepartment of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Sheng ZhongDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Guangxun GaoDepartment of Hematology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Ming YanDepartment of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Xijing Hospital · CNAir Force Medical University · CNDana-Farber Cancer Institute · USJilin University · CNXi'an Jiaotong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study aimed to identify effective targets for carcinogenesis of primary myelofibrosis (PMF), as well as to screen ideal lead compounds with potential inhibition effect on Janus kinase 2 to contribute to the medication design and development. Gene expression profiles of GSE26049, GSE53482, GSE61629 were obtained from the Gene Expression Omnibus database. The differentially expressed genes were identified, and functional enrichment analyses such as Gene Ontology, protein-protein interaction network etc., were performed step by step. Subsequently, highly-precise computational techniques were conducted to identify potential inhibitors of JAK2. A series of structural biology methods including virtual screening, ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction, molecule docking, molecular dynamics simulation etc., were implemented to discover novel natural compounds. Results elucidated that PMF patients had abnormal LCN2, JAK2, MMP8, CAMP, DEFA4, LTF, MPO, HBD, STAT4, EBF1 mRNA expression compared to normal patients. Functional enrichment analysis revealed that these genes were mainly enriched in erythrocyte differentiation, neutrophil degranulation and killing cells of other organisms. Two novel natural compounds, ZINC000013513540 and ZINC000004099068 were found binding to JAK2 with favorable interaction energy together with high binding affinity. They were predicted with non-Ames mutagenicity, low-rodent carcinogenicity, less developmental toxicity potential as well as non-toxicity with liver. Molecular dynamics simulation demonstrated that these two complexes: ZINC000013513540-JAK2 and ZINC000004099068-JAK2 could exist stably under natural circumstances. In conclusion, this study revealed hub genes in the carcinogenesis of PMF. ZINC000013513540 and ZINC000004099068 were promising drugs in dealing with PMF. This study may also accelerate exploration of new drugs.

Indexed as

Drug DiscoveryDrug Evaluation, PreclinicalEnzyme InhibitorsGene Expression ProfilingHumansJanus Kinase 2Primary MyelofibrosisEnzyme InhibitorsJAK2 protein, humanJanus Kinase 2bioinformaticsdiscovery studioinhibitorJanus Kinase 2virtual screening

Identifiers

PMID33686952
PMCPMC8034969
OpenAlexW3134246173

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.