Evidence map›Paper›PMID 39890804›Full record

ArticleNature communications2025

Methylcobalamin protects against liver failure via engaging gasdermin E.

Wanfeng Xu, Yun Wang, Shuang Cui, Qiuling Zheng, Yanghao Lin, Qingqing Cui, Yuxin Xie, Yuming Zeng, Chuan Zhang, Yujie Li and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
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

15 authors.

Wanfeng Xu *State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Yun Wang *State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Shuang Cui *State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.ORCID http://orcid.org/0000-0002-0859-3141
Qiuling Zheng *State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Yanghao LinState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Qingqing CuiState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Yuxin XieState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Yuming ZengState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Chuan ZhangState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Yujie LiState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Xin JinState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Minna QinState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Huiyong SunState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China. huiyongsun@cpu.edu.cn.ORCID http://orcid.org/0000-0002-7107-7481
Haiping HaoState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China. haipinghao@cpu.edu.cn.ORCID http://orcid.org/0000-0003-2522-7546
Lijuan CaoState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R. China. caolijuan0702@cpu.edu.cn.ORCID http://orcid.org/0000-0002-3834-5018

Funding

Medical Science and Technology Foundation of Guangdong Province (Science and Technology Foundation of Guangdong Province) A2023228National Natural Science Foundation of China (National Science Foundation of China) 81930109, 82321005National Natural Science Foundation of China (National Science Foundation of China) 82173886, 82373886National Natural Science Foundation of China (National Science Foundation of China) 82204512National Natural Science Foundation of China (National Science Foundation of China) 82304590Shenzhen Science and Technology Innovation Commission JCYJ20220530151415034
6 · The paper itself

Abstract

Gasdermin E (GSDME) is a pyroptotic cell death effector and a promising target for pyroptotic tissue injury. Here we perform high-throughput screening and demonstrate that methylcobalamin (MeCbl), an endogenous coenzyme form of vitamin B12, is a specific GSDME inhibitor and highly effective against cholestatic liver failure. MeCbl specifically blocks GSDME cleavage by directly binding with GSDME. In cholestasis-, cisplatin- or concanavalin A (Con A)-induced male mouse models, MeCbl significantly suppresses liver transaminase activities and inflammation, alleviates hepatocyte death, and reduces mortality of mice by blocking GSDME cleavage. The conserved Cys180 residue in GSDME is essential for caspase-3/GzmB recognition. MeCbl in base-off conformation coordinates to Cys180 to prevent caspase-3/GzmB-GSDME interactions and thereby GSDME-mediated pyroptosis. In summary, our study discovers MeCbl as a specific GSDME inhibitor that is promisingly to be developed as an effective drug against cholestatic liver failure, and other GSDME triggered sterile inflammation and/or organ failure.

Indexed as

Liver FailureVitamin B 12AnimalsCaspase 3CholestasisCisplatinConcanavalin ADisease Models, AnimalGasderminsHepatocytesHumansLiverMaleMiceMice, Inbred C57BLPyroptosisCaspase 3CisplatinConcanavalin AGasderminsGsdme protein, mouseVitamin B 12

Identifiers

PMID39890804
PMCPMC11785938

What Socratic 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 Socratic graph.