Evidence map›Paper›PMID 41254428›Full record

ArticleMolecular neurobiology2025

Pharmacological Inhibition of JAK/STAT-IL2 Axis Alleviated Cisplatin-Induced Ototoxicity.

Shimei Zheng, Chang Liu, Jiahuan Li, Hongbo Yu, Siyu Qiu, Wen Li, Liping Zhao, Xiangli Zeng, Bing Chen, Yingzi He

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Shimei Zheng *ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.
Chang Liu *Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China.
Jiahuan Li *ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.
Hongbo YuShanghai Medical College, Fudan University, Shanghai, 200031, China.
Siyu QiuENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.
Wen LiENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.
Liping ZhaoENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.
Xiangli ZengDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China. zxiangl@mail.sysu.edu.cn.
Bing ChenENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China. bingchen@fudan.edu.cn.
Yingzi HeENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China. yingzihe09611@126.com.ORCID http://orcid.org/0000-0002-2248-2237

Funding

National Natural Science Foundation of China 82271158National Natural Science Foundation of China 82301312Science and Technology Commission of Shanghai Municipality 23Y11909700
6 · The paper itself

Abstract

Sensorineural hearing loss (SNHL) is recognized as one of the most common sensory disorders and is characterized by irreversible damage to cochlear hair cells (HCs). Our research, which utilized the HEI-OC1 cell line for drug screening, revealed that inhibiting the JAK/STAT signaling pathway protects HEI-OC1 cells from cisplatin-induced ototoxicity. Further studies with cochlear explants showed that ifidancitinib, an inhibitor of both JAK1 and JAK3, offered superior protection compared with other JAK inhibitors. Additionally, in vivo studies with adult mice demonstrated that mice treated with ifidancitinib had lower auditory brainstem response (ABR) thresholds than those treated with cisplatin alone, along with improved morphology in HCs, nerve fibers, and pre- and postsynaptic structures. Western blot and MitoSOX Red assays demonstrated that the JAK/STAT signaling pathway promoted intracellular ROS accumulation and cell apoptosis. Furthermore, ELISA showed that ifidancitinib significantly decreased the levels of proinflammatory markers such as TNF-α, CD38, IL-6, and IL-1β. STRING analysis revealed that ifidancitinib's protective effects on hearing were mediated through regulation of the JAK/STAT5-IL2 axis, which was further confirmed using an interleukin 2 (IL-2) inhibitor and animal-free IL-2 protein. This study underscores the importance of the JAK/STAT signaling pathway in HC survival, highlighting its potential as a therapeutic target for the prevention and treatment of SNHL.

Indexed as

CisplatinJanus KinasesOtotoxicitySignal TransductionSTAT Transcription FactorsAnimalsApoptosisCell LineEvoked Potentials, Auditory, Brain StemHair Cells, AuditoryMaleMiceMice, Inbred C57BLCisplatinJanus KinasesSTAT Transcription FactorsApoptosisHearing lossIL-2Inflammatory reactionJAK inhibitors

Identifiers

PMID41254428

What Socratic holds

Textmetadata
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.