MicroRNA-140-5p elevates cerebral protection of dexmedetomidine against hypoxic-ischaemic brain damage via the Wnt/β-catenin signalling pathway
Authors: Yong-Jian Wang
Dong-Mei Wu
Xin-Rui Han
Bin Hu
Chun-Hui Sun
Xin Wen
Min Shen
Liang Wang
Meng-Qiu Li
Jun Lu
Shan Wang
Shao-Hua Fan
Qun Shan
Zi-Feng Zhang
Yuan-Lin Zheng
Journal: Journal of Cellular and Molecular Medicine (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Wnt/β-catenin signalling pathway; Wnt1; cerebral protection; dexmedetomidine; hypoxic-ischaemic brain damage
Affiliations: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu Province, China., College of Health Sciences, Jiangsu Normal University, Xuzhou, Jiangsu Province, China.

Abstract:  Hypoxia-ischaemia (HI) remains a major cause of foetal brain damage presented a scarcity of effective therapeutic approaches. Dexmedetomidine (DEX) and microRNA-140-5p (miR-140-5p) have been highlighted due to its potentially significant role in the treatment of cerebral ischaemia. This study was to investigate the role by which miR-140-5p provides cerebral protection using DEX to treat hypoxic-ischaemic brain damage (HIBD) in neonatal rats via the Wnt/β-catenin signalling pathway. The HIBD rat models were established and allocated into various groups with different treatment plans, and eight SD rats into sham group. The learning and memory ability of the rats was assessed. Apoptosis and pathological changes in the hippocampus CA1 region and expressions of the related genes of the Wnt/β-catenin signalling pathway as well as the genes responsible of apoptosis were detected. Compared with the sham group, the parameters of weight, length growth, weight ratio between hemispheres, the rate of reaching standard, as well as Bcl-2 expressions, were all increased. Furthermore, observations of increased levels of cerebral infarction volume, total mortality rate, response times, total response duration, expressions of Wnt1, β-catenin, TCF-4, E-cadherin, apoptosis rate of neurons, and Bax expression were elevated. Following DEX treatment, the symptoms exhibited by HIBD rats were ameliorated. miR-140-5p and si-Wnt1 were noted to attenuate the progression of HIBD. Our study demonstrates that miR-140-5p promotes the cerebral protective effects of DEX against HIBD in neonatal rats by targeting the Wnt1 gene through via the negative regulation of the Wnt/β-catenin signalling pathway. 

Retracted: No

PubPeer comments:
 Fig 3A:  The combined action of miRu2010140u20105p and DEX protects neurons of hippocampal CA 1 region in the left hemisphere observed by HE staining and Nissl staining. Notes: A, HE staining of pyramid neurons in the hippocampal CA 1 region of the left hemisphere . ![file] Compare with Fig 2(a) from [Wen et al (2018)] ,  Pathological changes of hippocampal CA1 region were found in the model group. Note: (a) hippocampal CA1 region in the two groups using HE staining . ![file]  Sham or  Normal ? Could the authors clarify? , 
 Fig 3A again. Overlap with Fig. 1 of [Sun et al (2018)] .  HE staining of hippocampal tissues in the normal and HIBD groups *[below]*. ![file] No authors in common. , 
 #2 Fig 3A again, again. ![] 5A from [Zhang et al (2018)] , after a 180-deg flip, ![] , 
 Fig 4A,  Results of TUNEL staining among groups . ![] Fig 8b from [Liu, Han Xiong (2019)] : ![file] Fig 1D of [Liu et al (2020)] ,  Measurement of neuronal apoptosis in normal and rats exposed to 2% sevoflurane detected by TUNEL assay . ![] -------------------------------- Retracted, [Jan 4 2021] .  The above article from Journal of Cellular and Molecular Medicine, published online on 13 March 2018 on Wiley Online Library (wileyonlinelibrary.com) in Volume 22, pp. 3167-3182, has been retracted by agreement between the authors, the journal Editor-in-Chief and John Wiley Sons Ltd. The retraction has been agreed following an investigation based on allegations raised by a third party. The authors asked to retract this manuscript as raw experimental data were not accessible anymore and thus the validity of the overall results could not be confirmed. , 
 #4 More thorough annotations to Fig 4A. ![] , 
 Assessed here, as part of the first of 10 broad investigations: https: www.nsfc.gov.cn publish portal0 tab442 info85495.htm **Decisions on handling scientific research misconduct cases investigated and dealt with in 2022 (first batch)** Date 2022-05-13 Source: u3000 Author: u3000 u3010 Large, Middle and Small u3011 u3010Printu3011 u3010Closeu3011 u3000u3000The National Natural Science Foundation of China resolutely implements the spirit of the  Several Opinions on Further Strengthening the Construction of Scientific Research Integrity and  Opinions on Further Promoting the Spirit of Scientists and Strengthening the Construction of Style and Study Style by the General Office of the Central Committee of the Communist Party of China and the General Office of the State Council. Horizontal science and technology are self-reliant and self-reliant, continue to carry out scientific research integrity construction, and seriously investigate and deal with scientific research misconduct involving the National Natural Science Foundation of China. The Supervision Committee of the National Natural Science Foundation of China conducts investigations, verifications and comprehensive judgments on the accepted scientific research integrity cases, in accordance with the Regulations of the National Natural Science Foundation of ) and  Measures for Investigation and Handling of Scientific Research Misconduct in National Natural Science Foundation of China and other regulations and systems to propose handling suggestions. After deliberation at the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to deal with the relevant parties involved. The 10 handling decisions (online release version) that have been criticized and criticized are hereby announced. -------------------------------- About the existence of papers published on Wu Dongmei, Zheng Yuanlin, Lu Jun, etc. - Falsification of pictures or data, fabrication of research process, use of others signatures without consent, and false information in project final reports - processing decision - National Science and Technology Financial Supervisory Office [2022] No. 1 u3000u3000The Supervision Committee of the National Natural Science Foundation of China launched an investigation into several papers of Jiangsu Normal University, including Wu Dongmei, Zheng Yuanlin, and Jun Jun, for suspected academic misconduct. The papers involved are as follows: ... Paper 13:  Xin-Rui Han # , Xin Wen # , Yong-Jian Wang # , Shan Wang, Min Shen, Zi-Feng Zhang, Shao-Hua Fan, Qun Shan, Liang Wang, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Dong-Mei Wu*, Jun Lu*, Yuan-Lin Zheng*. **MicroRNA-140-5p elevates cerebral protection of dexmedetomidine against hypoxic-ischaemic brain damage via the Wnt u03b2-cateninsignalling pathway**. Journal of Cellular and Molecular Medicine, 2018, 22:3167-3182.u201d (with fund numbers 81271225, 81171012, 30950031, 81571055, 81400902, 81570531, 81672731) ... u3000u3000According to the investigation of the supporting unit, the above 35 papers involved all have the problem of improper use of pictures or data fraud, and the pictures or data in question are all provided by third-party companies. Among the 35 papers involved, 34 (except paper 21) still have the problem of using others signatures without consent, and papers 4, 5, 9, 12, 30, and 34 also have the problem of fabricating the research process. Wu Dongmei is the author of the above 35 papers involved, of which 12 papers (papers 2, 8, 9, 10, 11, 12, 14, 15, 25, 26, 30, 35) are the first author and 22 papers (Paper 1, 4, 5, 6, 7, 13, 16, 17, 18, 19, 20, 21, 22, 23, 24, 27, 28, 29, 31, 32, 33, 34) Corresponding author, They should be primarily responsible for the objective results of falsifying pictures or data, using others signatures without consent, and fabricating research processes; Zheng Yuanlin and Lu Jun, as the co-corresponding authors of the 35 papers involved, were negligent in reviewing and took secondary responsibility. In addition, Wu Dongmei included 4 papers involved (papers 21, 24, 28, 29) in the final report of the National Natural Science Foundation of China (Grant No. 81400902), and Zheng Yuanlin included 9 papers involved (papers 6, 8, 10, 13, 21, 24, 26, 28, 29) included in the final report of the National Natural Science Foundation of China (Grant No. 81571055), and should be responsible for the objective results of false information in the final report. u3000u3000After deliberation at the 12th meeting of the Fifth Supervision Committee of the National Natural Science Foundation of China (Life Medicine Professional Committee) and the approval of the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to follow the thirty-fifth National Natural Science Foundation of China Regulations. Article 4, Article 17, Items 3, 4, and 9 of  Measures for Handling Misconduct in Science Fund Work by the Supervision Committee of the National Natural Science Foundation of China (for Trial Implementation) , revocation of Wu Dongmei s National Natural Science Foundation of Molecular mechanism of TRPV4-mediated domoic acid treatment-induced cognitive deficits in mice (Grant No. 81400902), recovering the allocated funds, permanently disqualifying Wu Dongmei from the National Natural Science Foundation of China (since January 18, 2022), Give Wu Dongmei a circular of criticism; decide to follow Article 35, item 4 of the  National Natural Science Foundation of China Regulations , and refer to  The National Natural Science Foundation of China Supervision Committee s Handling of Misconduct in Science Fund Work (Trial) Tenth Items 3 and 4 of seven articles, the Zheng Yuanlin National Natural Science Foundation of China project  The Mechanism of HDAC6 Activating HMGB1 RAGE Signaling Axis to Mediate Cognitive Defects in Type 2 Diabetic Mice (Approval No. 81571055), recover the allocated funds, cancel Zheng Yuanlin will be eligible to apply for the National Natural Science Foundation of China for 5 years (January 18, 2022 to January 17, 2027), and will give Zheng Yuanlin a notice of criticism; it is decided to refer to the  National Natural Science Foundation of China Supervision Committee on misconduct in the work of the National Natural Science Foundation of China. Items 3 and 4 of Article 17 of the Measures (for Trial Implementation), the Army s National Natural Science Foundation of China project application qualification will be cancelled for 5 years (January 18, 2022 to January 17, 2027), and the Army will be criticized in a circular. - National Natural Science Foundation of China - March 30, 2022 ,