Skullcapflavone I protects cardiomyocytes from hypoxia-caused injury through up-regulation of lincRNA-ROR
Authors: Hui Li
Xiaotian Zhang
Jianshuai He
Yuehua Chen
Mingyang Liu
Zhenxiao Zhang
Journal: International Journal of Immunopathology and Pharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MEK/ERK pathway; Skullcapflavone I; flavonoids; lincRNA-ROR; myocardial infarction.
Affiliations: 1 Department of Emergency, The Affiliated Hospital of Qingdao University, Qingdao, China., 2 Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, China., 3 Department of Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, China.

Abstract:  Myocardial infarction (MI) is a serious heart disease in which cardiomyocytes are damaged, caused by hypoxia. This study explored the possible protective activity of Skullcapflavone I (SF I), a flavonoid isolated from the root of Scutellaria baicalensis Georgi, on hypoxia-stimulated cardiomyocytes cell injury in vitro. Viability and apoptosis of H9c2 cells and primary cardiomyocytes were tested using cell counting kit-8 (CCK-8) assay and Guava Nexin Reagent, respectively. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the long non-coding RNA regulator of reprogramming (lincRNA-ROR) expression. si-ROR was transfected to knockdown lincRNA-ROR. Western blotting was conducted to assess the protein levels of key molecules related to cell proliferation, apoptosis, and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. We discovered that hypoxia stimulation obviously reduced H9c2 cell and primary cardiomyocytes' viability and proliferation, but promoted cell apoptosis. SF I treatment mitigated the cell viability and proliferation inhibition, as well as cell apoptosis caused by hypoxia. Moreover, SF I promoted the hypoxia-caused up-regulation of lincRNA-ROR in H9c2 cells and primary cardiomyocytes. Knockdown of lincRNA-ROR reversed the influence of SF I on hypoxia-stimulated H9c2 cells and primary cardiomyocytes. Besides, SF I activated MEK/ERK pathway in H9c2 cells and primary cardiomyocytes via up-regulating lincRNA-ROR. To sum up, our research verified the beneficial activity of SF I on hypoxia-caused cardiomyocytes injury. SF I protected cardiomyocytes from hypoxia-caused injury through up-regulation of lincRNA-ROR and activation of MEK/ERK pathway. 

Retracted: No

PubPeer comments:
 The Western blots and other figures in this paper have an interesting layout that appears to be shared with many other papers, as discussed in a January 2020 post on Leonid Schneider s blog: https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing In almost all papers, Western blot panels within the same figure, and across figures and papers, appear to share the same background, while the bands are regularly spaced, all have similar rounded edges without the usual smudges and specks, and with some bands showing a recognizable  jumping sardine shape. Also in almost all papers, bar graphs show a characteristic layout with bars in solid shades of grey, and the left-most bar in black, as well as double-edged error bars. Many papers have  cell viability and  apoptotic cells graphs. To illustrate the recognizable layout of the graphs in this paper, here is Figure 2. ![file] , 
 February 2021 Expression of Concern found here: https: journals.sagepub.com doi full 10.1177 20587384211000846 From the Notice:  *It has been brought to SAGEu2019s attention that this article may have been written (and possibly submitted) by a third-party agency, and that the contents of the article may be partially or wholly fabricated. SAGE is currently conducting a thorough investigation into this to establish the most appropriate way forward.* , 
 Retracted [2 September 2021] . H t [RetractionWatch] . ------------------------- At the request of the Journal Editor(s) the following article has been retracted. Zhang Z, Li H, Liu M, He J, Zhang X, Chen Y (2019) Skullcapflavone I protects cardiomyocytes from hypoxia-caused injury through up-regulation of lincRNA-ROR. International Journal of Immunopathology and Pharmacology 33: 1-11. DOI: 10.1177 2058738419857537. Significant similarities between this paper and a number of other papers have been identified, as well as indication of image and data manipulation suggestive of the use of a u201cpaper millu201d. These papers share common structures and wording yet do not share any common authors. The authors did not provide a sufficient response or evidence to refute these claims. As a result, the scientific accuracy of this paper is not reliable. Adhering to the international guidelines established by the Committee on Publication Ethics, the Journal has determined these are grounds for retraction. ,