Baicalin relieves hypoxia-aroused H9c2 cell apoptosis by activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway
Authors: Hailiang Yu
Bin Chen
Qi Ren
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Myocardial ischemia; Nrf2/HO-1 pathway; baicalin; cardiomyocytes damage; hypoxia
Affiliations: Department of Cardiology, Linyi Central Hospital , Linyi , China., Department of Cardiology, Jining No.1 People's Hospital , Jining , China.

Abstract:  Background: Myocardial ischemia is the main reason for ischemic heart disease. Baicalin is a plant-derived flavonoid with cardio-protective activity. Herein, we tested the influences of baicalin on cardiomyocytes H9c2 apoptosis aroused by hypoxia stimulation. Methods: Firstly, H9c2 cells were subjected to hypoxia and/or baicalin exposure. Cell viability and apoptosis, along with hypoxia-inducible factor 1α (HIF1α) and Bcl-2/adenovirus E1B 19-KDa interacting protein 3 (BNIP3) expressions were tested respectively. Then, si-HIF1α was transfected into H9c2 cells to probe whether up-regulation of HIF1α attended to the influences of baicalin on hypoxia-stimulated H9c2 cells. Finally, the regulatory effect of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on HIF1α expression was analyzed. Results: Hypoxia exposure aroused H9c2 cell viability reduction and apoptosis. Baicalin mitigated H9c2 cell viability reduction and apoptosis aroused by hypoxia. Moreover, HIF1α/BNIP3 pathway was further activated by baicalin in hypoxia-exposed H9c2 cells. Silencing HIF1α lowered the functions of baicalin on hypoxia-exposed H9c2 cells. Besides, baicalin enhanced hypoxia-caused activation of Nrf2/HO-1 pathway. Activation of Nrf2/HO-1 pathway was associated with the up-regulation of HIF1α and protective functions of baicalin on hypoxia-exposed H9c2 cells. Conclusion: Baicalin relieved cardiomyocytes H9c2 apoptosis aroused by hypoxia might be achieved through activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway. Highlights Baicalin mitigates H9c2 cell viability loss and apoptosis aroused by hypoxia; Baicalin activates HIF1a/BNIP3 pathway in hypoxia-exposed H9c2 cells; Silencing HIF1α weakens the influences of baicalin on hypoxia-exposed H9c2 cells; Baicalin promotes Nrf2/HO-1 pathway in hypoxia-exposed H9c2 cells; Promotion of Nrf2/HO-1 pathway is related to the up-regulation of HIF1α. 

Retracted: No

PubPeer comments:
 Figure 2.  (D) Followed by 75u2009u03bcM baicalin incubation for 24u2009h, the H9c2 cell apoptosis was tested. Followed by 75u2009u03bcM baicalin incubation for 24u2009h under hypoxia condition, (E) H9c2 cell apoptosis was tested. Annotated to highlight the similarities within the 3rd-quadrant hairball cell-clouds in these supposedly different conditions. ![file] , 
 Another examples where all the protein data is falsified. This is seen by contrast enhancement of the Western immunoblots, which show the same background pattern. Here is just some examples illustrating the problem: ![file] , 
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 , 
 Expression of Concern, [3 February 2022] . ------------------------ We, the Publisher and Editor of Artificial Cells, Nanomedicine, and Biotechnology, are issuing an Expression of Concern for the following article: After publication of this article, questions about the scientific integrity of the article content were brought to the Publisher and Editoru2019s attention. We reached out to the authors requesting that they supply information that would confirm the articleu2019s integrity. The authors provided several files in response to our queries, but they were unable to provide the original data in a format which satisfies our requirements to confirm the authenticity of some types of data. In particular, they were unable to provide full western blots, where the molecular weight markers are indicated. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. , 
 An investigation by Jining First People s Hospital (the authors institution) calls for retraction. Thx Google Translate. Can the journal editors confirm that they have received the request to depublish the paper? https: www.jnrmyy.com keyan kxyj gonggao 2021 1229 6607.html ------------------------------ 2. The paper  Baicalin relieves hypoxia-aroused H9c2 cell apoptosis by activating Nrf2 HO- is published by Ren Qi of our hospital as the corresponding author, Yu Hailiang of Linyi Central Hospital as the first author, and Chen Bin of Linyi Central Hospital as the co-first author. 1-mediated HIF1u03b1 BNIP3 pathway , after investigation, it is an academic misconduct of tampering with data. Our hospital will deal with the relevant responsible persons as follows: Ren Qi (corresponding author, combined with the other two papers): cancel the application qualifications for scientific research projects, scientific research awards, scientific and technological achievements, scientific and technological talent plans within 6 years; cancel 6 years as a nomination or Qualifications such as recommenders, nominees or recommenders, review experts, etc.; cancel their membership or membership in academic institutions such as societies, associations, etc.; recover the authoru2019s personal research awards and honorary titles; A first-level professional and technical position; 3-year postponement of promotion to a higher-level professional and technical position; instructed to contact the magazine as soon as possible to withdraw the manuscript; warning from the party. Linyi Central Hospital dealt with the relevant responsible persons as follows: Yu Hailiang (first author): Cancellation of application qualifications for scientific research projects, scientific research awards, scientific and technological achievements, scientific and technological talent plans within 5 years; Or recommenders, review experts and other qualifications; suspend their postgraduate tutor application qualifications for 5 years; require them to contact the magazine within 30 days to withdraw their manuscripts. A fine of 5,000 yuan; the scientific research integrity admonishes the conversation, and it is ordered to write a written inspection; the whole hospital circulates the criticism; cancels its participation in the 2020 annual evaluation, and the annual evaluation shall not be determined as excellent. Chen Bin (tied for the first author): speaking on the integrity of scientific research; writing a profound examination of this incident; circulating criticism in the hospital. ,