PReD-Bench/PRed-Bench huggingface dataset:
miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1
Authors: Honglei Chen
Bin Zhu
Zhixu Zhang
Junzhi Wang
Li Zhang
Minghui Zhang
Journal: Brazilian Journal of Medical and Biological Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; heart valve disease; inflammation; miR-27a; TNF-α
Affiliations: Department of Cardiology, Chengyang People's Hospital, Qingdao, Shandong, China., Teaching and Research Office of Immunology, Qingdao University, Qingdao, Shandong, China., Department of Imaging, Eastern District of Linyi People's Hospital, Linyi, Shandong, China.

Abstract:  MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways. 

Retracted: No

PubPeer comments:
 Figure 7B - similar background between lanes ![file] , 
 #1 This paper conforms to a style identified by [Dr Elisabeth Bik] and [Dr Jana Christopher] , among others. ,
Rare variants in the CYP27B1 gene are associated with multiple sclerosis
Authors: M Zameel Cader
George C Ebers
Antonio J Berlanga-Taylor
Katie M Morrison
Giulio Disanto
Pierre Lepage
Julia M Morahan
Alexandre Montpetit
Gabriele C De Luca
Adam Handel
Sreeram V Ramagopalan
A Dessa Sadovnick
David A Dyment
Journal: Annals of neurology (2011)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Multiple sclerosis; genetic linkage analysis; whole exome sequencing; rare variants; CYP27B1 gene
Affiliations: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Abstract:  Objective: Multiple sclerosis (MS) is a complex neurological disease. Genetic linkage analysis and genotyping of candidate genes in families with 4 or more affected individuals more heavily loaded for susceptibility genes has not fully explained familial disease clustering. Methods: We performed whole exome sequencing to further understand the heightened prevalence of MS in these families. Results: Forty-three individuals with MS (1 from each family) were sequenced to find rare variants in candidate MS susceptibility genes. On average, &gt;58,000 variants were identified in each individual. A rare variant in the CYP27B1 gene causing complete loss of gene function was identified in 1 individual. Homozygosity for this mutation results in vitamin D-dependent rickets I (VDDR1), whereas heterozygosity results in lower calcitriol levels. This variant showed significant heterozygous association in 3,046 parent-affected child trios (p = 1 × 10(-5)). Further genotyping in &gt;12,500 individuals showed that other rare loss of function CYP27B1 variants also conferred significant risk of MS, Peto odds ratio = 4.7 (95% confidence interval, 2.3-9.4; p = 5 × 10(-7)). Four known VDDR1 mutations were identified, all overtransmitted. Heterozygous parents transmitted these alleles to MS offspring 35 of 35× (p = 3 × 10(-9)). Interpretation: A causative role for CYP27B1 in MS is supported; the mutations identified are known to alter function having been shown in vivo to result in rickets when 2 copies are present. CYP27B1 encodes the vitamin D-activating 1-alpha hydroxylase enzyme, and thus a role for vitamin D in MS pathogenesis is strongly implicated. 

Retracted: No

PubPeer comments:
 According to the press news, this research was funded by  the National Multiple Sclerosis Society, The Wellcome Trust and the support of science investor, Jeffrey Epstein and The Jeffrey Epstein VI Foundation. https: www.prnewswire.com news-releases a-genetic-cause-for-multiple-sclerosis-is-identified-and-funded-by-science-patron-jeffrey-epstein-159172275.html Could authors clarify why part of this information was omitted in the acknowledgments section? ![file] ,
Cell transformation by the E5/E8 protein of bovine papillomavirus type 4. p27(Kip1), Elevated through increased protein synthesis is sequestered by cyclin D1-CDK4 complexes
Authors: G J Grindlay
M S Campo
V O&#x27;Brien
Journal: Journal of Biological Chemistry (2001)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: BPV-4; E5/E8; transformation; NIH-3T3 cells; cyclin A
Affiliations: Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Glasgow G61 1BD, Scotland, United Kingdom. 

Abstract:  The E5/E8 hydrophobic protein of BPV-4 is, at only 42 residues, the smallest transforming protein identified to date. Transformation of NIH-3T3 cells by E5/E8 correlates with up-regulation of both cyclin A-associated kinase activity and, unusually, p27(Kip1) (p27) but does not rely on changes in cyclin E or cyclin E-CDK2 activity. Here we have examined how p27 is prevented from functioning efficiently as a CDK2 inhibitor, and we investigated the mechanisms used to achieve elevated p27 expression in E5/E8 cells. Our results show that normal subcellular targeting of p27 is not subverted in E5/E8 cells, and p27 retains its ability to inhibit both cyclin E-CDK2 and cyclin A-CDK activities upon release from heat-labile complexes. E5/E8 cells also have elevated levels of cyclins D1 and D3, and high levels of nuclear p27 are tolerated because the inhibitor is sequestered within an elevated pool of cyclin D1-CDK4 complexes, a significant portion of which retain kinase activity. In agreement with this, pRB is constitutively hyperphosphorylated in E5/E8 cells in vivo. The increased steady-state level of p27 is achieved largely through an increased rate of protein synthesis and does not rely on changes in p27 mRNA levels or protein half-life. This is the first report of enhanced p27 synthesis as the main mechanism for increasing protein levels in continuously cycling cells. Our results are consistent with a model in which E5/E8 promotes a coordinated elevation of cyclin D1-CDK4 and p27, as well as cyclin A-associated kinase activity, which act in concert to allow continued proliferation in the absence of mitogens. 

Retracted: No

PubPeer comments:
 Figure 1. Much more similar than expected. https: imgur.com IFMvY0P ,
LIM and SH3 protein 1 regulates cell growth and chemosensitivity of human glioblastoma via the PI3K/AKT pathway
Authors: Xiaobo Yang
Xiangguo Xia
Bei Tao
Ligang Chen
Yitian Chen
Tangming Peng
Lilei Peng
Chuanhong Zhong
Journal: BMC cancer (2018)
Discipline: CLINICAL MEDICINE
Keywords: Glioblastoma; LIM and SH3 protein 1; PI3K/AKT pathway; Temozolomide.
Affiliations: Neurosurgery Department, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China., Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China., Rheumatism Department, Affiliated Hospital of Southwest Medical University, Luzhou, China., Neurosurgery Department, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China. .

Abstract:  Background: LIM and SH3 protein 1 (LASP1) is upregulated in several types of human cancer and implicated in cancer progression. However, the expression and intrinsic function of LASP1 in glioblastoma (GBM) remains unclear. Method: Oncomine and The Cancer Genome Atlas (TCGA) database was analyzed for the expression and clinical significance of LASP1 in GBM. LASP1 mRNA and protein level were measured by qRT-PCR and western blotting. The effect of LASP1 on GBM proliferation was examined by MTT assay and colony formation assay, the effect of LASP1 on sensitivity of Temozolomide was measured by flow cytometry and subcutaneous tumor model. The association between LASP1 and PI3K/AKT signaling was assessed by western blotting. Results: Oncomine GBM dataset analysis indicated LASP1 is significantly upregulated in GBM tissues compared to normal tissues. GBM dataset from The Cancer Genome Atlas (TCGA) revealed that high LASP1 expression is related to poor overall survival. LASP1 mRNA and protein in clinical specimens and tumor cell lines are frequently overexpressed. LASP1 knockdown dramatically suppressed U87 and U251 cell proliferation. Silencing LASP1 potentiated cell chemosensitivity to temozolomide in vitro, LASP1 knockdown inhibited tumor growth and enhanced the therapeutic effect of temozolomide in vivo. TCGA dataset analysis indicated LASP1 was correlated with PI3K/AKT signaling pathway, and LASP1 deletion inhibited this pathway. Combination treatment with PI3K/AKT pathway inhibitor LY294002 dramatically accelerated the suppression effect of temozolomide. Conclusion: LASP1 may function as an oncogene in GBM and regulate cell proliferation and chemosensitivity in a PI3K/AKT-dependent mechanism. Thus, the LASP1/PI3K/AKT axis is a promising target and therapeutic strategy for GBM treatment. 

Retracted: No

PubPeer comments:
 Figure 3B: * Blue boxes: The NC PBS and siRNA1 PBS panels look remarkably similar to each other. ![file] ,
Biomimetic nanoscale metal–organic framework harnesses hypoxia for effective cancer radiotherapy and immunotherapy
Authors: Wenbin Lin
Ziyang Hao
Kaiyuan Ni
Guangxu Lan
Yang Song
Journal: Chemical Science (2020)
Discipline: CHEMISTRY
Keywords: Tumor hypoxia; nanoscale metal-organic-framework; catalase-like activity; H2O2; oxygen
Affiliations: Department of Chemistry, The University of Chicago, Chicago, USA, Department of Radiation and Cellular Oncology

Abstract:  Tumor hypoxia presents a major impediment to effective cancer therapy with ionizing radiation and immune checkpoint inhibitors. Here we report the design of a biomimetic nanoscale metal-organic-framework (nMOF), Hf-DBP-Fe, with catalase-like activity to decompose elevated levels of H2O2 in hypoxic tumors to generate oxygen and hydroxyl radical. The generated oxygen attenuates hypoxia to enable radiodynamic therapy upon X-ray irradiation and fixes DNA damage while hydroxyl radical inflicts direct damage to tumor cells to afford chemodynamic therapy. Hf-DBP-Fe thus mediates effective local therapy of hypoxic cancer with low-dose X-ray irradiation, leading to highly immunogenic tumor microenvironments for synergistic combination with anti-PD-L1 immune checkpoint blockade. This combination treatment not only eradicates primary tumors but also rejects distant tumors through systemic anti-tumor immunity. We have thus advanced an nMOF-based strategy to harness hypoxic tumor microenvironments for highly effective cancer therapy using a synergistic combination of low dose radiation and immune checkpoint blockade. 

Retracted: No

PubPeer comments:
 In Figure S18, duplicated images for PBS and H2DBP-Fe under Hypoxia(-) conditions, H2DBP under Normoxia(+) conditions and Hf-DBP-Fe under Normoxia(-) conditions.![file] ,
Astaxanthin protecting myocardial cells from hypoxia/reoxygenation injury by regulating miR-138/HIF-1α axis
Authors: Y-S Gai
H-N Liu
Y Gao
Y-H Ren
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: astaxanthin; myocardial cells; hypoxia/reoxygenation injury; miR-138; HIF-1α
Affiliations: Department of Cardiology, Yantaishan Hospital, Shandong, P.R. China. .

Abstract:  Objective: To investigate astaxanthin (AST) protecting myocardial cells from hypoxia/reoxygenation (H/R) injury by regulating miR-138/HIF-1α axis. Materials and methods: Myocardial cells were collected and divided into a control group, a H/R group, and a H/R+AST group. The H/R injury model was established, and cells in the H/R+AST group were given AST before modeling. The cell survival rate, contents of myocardial enzymes, and apoptosis were detected. Results: The survival rate in the H/R group reduced and was lower than that in the H/R+AST group (p&lt;0.05). Compared with the control group, activities of myocardial enzymes significantly increased in the H/R group but those were inhibited in the H/R+AST group (p&lt;0.05). The apoptotic rate in the H/R group significantly increased compared with the control group but that significantly decreased compared with the H/R+AST group (p&lt;0.05). The expression of cleaved caspase-9 and caspase-3 increased in the H/R group (p&lt;0.05), and was higher than that in the H/R+AST group (p&lt;0.05). The expression levels of miR-138 and HIF-1α were detected. MiR-138 level significantly decreased in the H/R group but increased in the H/R+AST group (p&lt;0.05). Compared with the control group, HIF-1α content significantly increased in the H/R group but that was significantly inhibited in the H/R+AST group (p&lt;0.05). The Luciferase reporter gene assay confirmed that HIF-1α was the target gene of miR-138. After miR-138 mimics and HIF-1α siRNA were transfected into myocardial cells, the cell survival rate significantly increased, and activities of myocardial enzymes were significantly inhibited in the H/R+AST+miR-138 mimics and H/R+AST+HIF-1α siRNA groups (p&lt;0.05). The apoptotic rate significantly decreased, and contents of cleaved caspase-9 and caspase-3 were significantly inhibited in the miR-138 mimics and HIF-1α siRNA groups (p&lt;0.05). Conclusions: AST can exert a protective function in myocardial cells via regulating the expression of miR-138/HIF-1α axis. 

Retracted: No

PubPeer comments:
 Figure 3C, 4D and 5H: Patterns in the background of the immuno blots are duplicated. This is a typical papermill product and Eur Review Med Pharm Sci is now retracting a large number of falsified papers. , 
 ![file] ,
Regulatory effect of LncRNA DRAIC/miR-149-5p/NFIB molecular network on autophagy of esophageal cancer cells and its biological behavior
Authors: Xinghua Zhou
Ming Chen
Furong Li
Wei Fan
Journal: Experimental and Molecular Pathology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Autophagy; Esophageal cancer; LncRNA DRAIC; NFIB; miR-149-5p.
Affiliations: Department of Laboratory medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China; Department of Immunology, Zunyi Medical University, Zunyi 563099, Guizhou, , China., Department of Laboratory medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China., Department of laboratory medicine, Huaian Tumor Hospital, No.14 Yue miao East Street, Huaian 223200, Jiangsu Province, China. Electronic address: .

Abstract:  Objective: This experiment will explore the effect of LncRNA DRAIC/miR-149-5p/NFIB molecular network on esophageal cancer (EC) cells' biological behavior and autophagy. Methods: We bought human EC cells and normal esophageal epithelial cells HEEC. DRAIC, miR-149-5p and NFIB protein expression were tested. The low expression plasmid of DRAIC and empty vector of DRAIC, miR-149-5p miR-mimics, miR-149-5p inhibitors and negative control groups, NFIB high expression plasmid, NFIB low expression plasmid and empty vector were transfected into EC cells (Eca-109 and EC9706) to detect changes in cell biological behavior and autophagy protein expression. The targeted relationship between DRAIC/miR-149-5p/NFIB was verified through dual-luciferase report and pull-down experiment. Results: DRAIC and NFIB showed high expression in EC cells, while miR-149-5p showed low expression. Down-regulating DRAIC, NFIB and over-expressing miR-149-5p can inhibit EC cells' proliferation and invasion, and improve apoptosis and autophagy. Dual-luciferase report and pull-down experiment confirmed that DRAIC targeted miR-149-5p regulation, and down-regulating DRAIC could reverse miR-149-5p inhibitor's effect on the biological behavior of EC cells. However, dual-luciferase report revealed that miR-149-5p directly targeted NFIB, and miR-149-5p inhibitor could weaken the effect of down-regulating NFIB on apoptosis and autophagy of EC cells. Moreover, DRAIC has an effect on the autophagy of EC cells through miR-149-5p/NFIB. Conclusion: LncRNA DRAIC is relevant to cell biology and autophagy of EC. In the future, DRAIC may be developed as a key gene for EC diagnosis and treatment. 

Retracted: No

PubPeer comments:
 Can I ask the authors to please provide the raw FCS files for the Flow cytometry data and raw data for the Western immunoblot presented in this article? Files for Figure 1 alone would help a lot. The flow cytometry dot plots and the Western immunoblots show a very unusal pattern. All Western immunoblots show the same dotted pattern. Description of the Flow cytometry method is very limited and unclear. E.g. you use  5 u00b5l Annexin-V-FITC and 5 u00b5l PI . Concentration? Furthermore you  assessed the apoptosis via flow cytometry . Type of flow cytometer? Examples from Figure 1 are shown. ![file] ![file] ,
Icariside II attenuates cardiac remodeling via AMPKα2/mTORC1 in vivo and in vitro
Authors: Qi-Zhu Tang
Wen-Jing Li
Hai-Han Liao
Xiao-Yu Liu
Nan Zhang
Hong Feng
Jing-Jing Yang
Si Chen
Wei Deng
Journal: Journal of Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AMPK/mTORC; Cardiac remodeling; Cardiomyocyte; Icariside II.
Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute of Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China., Department of Gerontology, Renmin Hospital of Wuhan University, Wuhan, 430060, China., Cardiovascular Research Institute of Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China., Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute of Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China; Department of Cardiology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi Xinjiang, 830001, China. Electronic address: ., Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute of Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China. Electronic address: .

Abstract:  Icariside II (ICA II), a flavonoid derived from Epimediumbrevicormum Maxin in, has multiple biological activities in Chinese traditional medicine. Our study aimed to investigate the potential activity of ICA II against cardiac remodeling and the underlying mechanism. Mice received aorta banding (AB) or sham surgery, and then were randomly divided into ICA II or vehicle (veh) group for 6 weeks. After echocardiography and pressure-volume loop examination, hearts were harvested for histopathological analysis and molecular mechanism investigation. Additionally, neonatal rat cardiomyocytes (NRCM) were used for in vitro experiments. ICA II attenuated the systolic and diastolic cardiac dysfunction, and protected mouse heart from hypertrophy and fibrosis. The underlying mechanism might involve in the regulation of Akt, AMPKα and mTORC. In in vitro experiment, ICA II prevented phenylephrine (PE) induced NRCM hypertrophy by regulating AMPKα/mTORC pathway. This protective effect was disappeared after treatment with Compound C (CpC), an AMPKα inhibitor. Moreover, ICA II activated AMPK at baseline. ICAII was superior to resveratrol in activating AMPKα and similar to AICAR. ICA II protected against cardiac remodeling and NRCM hypertrophy by regulating AMPK/mTORC pathway. ICA II may be a candidate for the treatment of malignant cardiac remodeling. 

Retracted: No

PubPeer comments:
 Could the authors provide the correct sequences of these primers? As these are at the moment, the **Figures** referring to expressions of TGFu03b2 and CTGF are completely **invalid**. ![file] **Only the GAPDH primers are correct.** ![file] ,
MicroRNA-218–5p inhibit the migration and proliferation of pterygium epithelial cells by targeting EGFR via PI3K/Akt/mTOR signaling pathway
Authors: Shuang Han
Ying Chen
Bei Sun
Yanlin Gao
Yichun Kong
Journal: Experimental Eye Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: EGFR; MiR-218–5p; Pterygium; hPECs.
Affiliations: Department of General Ophthalmology, Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, 300020, China; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, 300020, China; Ji Ning No.1 People's Hospital, Jining, 272100, China., Department of General Ophthalmology, Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, 300020, China., Tianjin Key Laboratory of Metabolic Diseases, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300020, China. Electronic address: ., Department of General Ophthalmology, Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, 300020, China. Electronic address: .

Abstract:  Pterygium is a common ocular surface disease which could result in various ocular surface symptoms. MicroRNAs play an important role in the development of various eye diseases. However, the role of microRNAs in the pathogenesis of pterygium is rarely reported. Our research aims to analyze the relationship between miR-218-5p and Epidermal Growth Factor Receptor (EGFR) in human pterygium tissues and cultured Human Pterygium Epithelial Cells (hPECs). Furthermore, the EGFR/PI3K/Akt/mTOR signaling pathway was firstly verified in pterygium. Pterygium tissues and normal bulbar conjunctival tissues were obtained from surgery, and primary hPECs were cultured in vitro. Cell transfection, Quantitative real-time PCR (qRT-PCR), Western blotting, Luciferase reporter assay and Scratch Wound Healing Assay were performed. Our data demonstrated that miR-218-5p was decreased and EGFR was increased in pterygium tissues than normal conjunctival tissues. In transfected hPECs, our results indicated that upregulated miR-218-5p significantly suppressed the expression level of EGFR via PI3K/Akt/mTOR pathway. In addition, the migration and proliferation of hPECs was promoted by miR-218-5p inhibitor and retarded by miR-218-5p mimics. And knockdown of EGFR significantly inhibit hPECs migration. Taken together, miR-218-5p downregulated the expression of EGFR via PI3K/Akt/mTOR pathway in pterygium tissues and hPECs and inhibited hPECs migration and proliferation. The microRNA-218-5p-EGFR-PI3K/Akt/mTOR axis should be further investigated for the potential treatment of pterygium. 

Retracted: No

PubPeer comments:
 Figures 4 and 5 appear to have some images which overlap. *** ![file] *** ![file] ,
Ppm1b Negatively Regulates 3-Bromopyruvate Induced Necroptosis in Breast Cancer Cells
Authors: Surong Zhao
Hao Liu
Linyan Ma
Yiming Sun
Qiong Pan
Chao Chen
Journal: Frontiers in Oncology (2021)
Discipline: CLINICAL MEDICINE
Keywords: 3-bromopyruvate; breast cancer cells; dephosphorylation; necroptosis; protein phosphatase 1b.
Affiliations: Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China., School of Pharmacy, Bengbu Medical College, Bengbu, China.

Abstract:  Up to 30% of breast cancer mortality is caused by cancer relapse despite primary clinical treatments due to distant metastases. Further research focusing on breast cancer mechanisms are needed for deeper understanding of disease prognosis. 3-bromopyruvate (3-BP), a glycolysis inhibitor, has been studied as one of the antitumor agents in recent years. In this report, we want to investigate the form of cell death induced by 3-BP and demonstrate the inhibitory effect of 3-BP on breast cancer cell proliferation and its mechanism in vivo and in vitro. We found that 3-BP could inhibit MDA-MB-231 and MCF-7 breast cancer cell proliferation, through energy metabolism inhibition. Further, necroptosis characters in MDA-MB-231 cells after 3-BP treatment were observed, which could be negatively regulated through Ppm1b by dephosphorylation of RIP3. In addition, 3-BP treatment in an MDA-MB-231 cell-transplanted mouse model showed a significant antitumor effect, which correlated with necroptosis-related protein Ppm1b. The findings demonstrate the potential for 3-BP in the treatment of breast cancer, providing impetus for further clinical studies. 

Retracted: Yes

PubPeer comments:
 Figure 2F contains multiple images which appear to overlap with brightness adjustment. ![file] , 
 Dear Lecithocera Eumenopis, We appreciate your correction in our work, we have carefully re-checked the raw data and confirmed the error in Figure 2F, and it mistakenly displays the images. We are contacting the editorial office to address this and will update Figure 2F in the article, We will also upload the updated data here. I am also deeply sorry for any negligence in our work and any inconvenience that may have been caused. , 
 **RETRACTED** https: www.frontiersin.org articles 10.3389 fonc.2021.757083 full The Journal and Authors retract the 14 January 2021 article cited above for the following reasons provided by the Authors: Following publication, concerns were raised regarding the integrity of the images in the published figures. The authors failed to provide a satisfactory explanation during the investigation, which was conducted in accordance with Frontiersu2019 policies. This retraction was approved by the Chief Editors of Frontiers in Oncology and the Chief Executive Editor of Frontiers. The authors agree to this retraction. ,
Small interfering RNA effectively inhibits protein expression and negative strand RNA synthesis from a full-length hepatitis C virus clone
Authors: Erik Flemington
Ramesh Prabhu
Padmaja Vittal
Qinyan Yin
Srikanta Dash
William H Robichaux
Robert Garry
Journal: Journal of Medical Virology (2005)
Discipline: MICROBIOLOGY
Keywords: Hepatitis C virus; RNA interference; siRNAs; antiviral strategy; HCV infection
Affiliations: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.

Abstract:  Hepatitis C virus (HCV) infection is usually treated with the combination of interferon and ribavirin, but only a small fraction of patients develop a sustained remission. There is need for the development of specific molecular approaches for the treatment of chronic HCV infection. We propose that RNA interference is highly effective antiviral strategy that offers great potential for the treatment of HCV infection. Three plasmid constructs expressing small interfering RNAs (siRNAs) targeted to sequences encoding the structural gene (E2) and non-structural genes (NS3, NS5B) of HCV1a genome were prepared. Antiviral properties of siRNAs against the HCV1a strain were studied in a transient replication model that involved the use of a transcription plasmid containing the full-length HCV genome and an adenovirus expressing T7 RNA polymerase. We found that siRNAs targeted to the E2, NS3 and NS5B regions of the HCV genome efficiently inhibited expression of the HCV core and NS5A protein measured by Western blot analysis and immunocytochemical staining. Intracytoplasmic immunization of siRNAs in HCV-transfected cells efficiently degraded genomic positive strand HCV RNA, as shown by ribonuclease protection assay (RPA). All three siRNAs efficiently inhibited synthesis of replicative negative strand HCV RNA in the transfected cells. A control siRNA plasmid against a Epstein--Barr virus latency gene did not inhibit protein expression and negative strand HCV RNA. These results suggest that RNAi is an effective and alternative approach that can be used to inhibit HCV expression and replication. 

Retracted: No

PubPeer comments:
 Figure 3. * Red boxes: The bottom Mock and EBNA1 panels appear to show an overlap, with a slightly different stretch. * Dark blue boxes: The bottom E2 and NS5B panels appear to show an overlap, with a different stretch. * Light blue boxes: The bottom E2 and NS3 panels appear to show an overlap, with a different stretch. ![file]  This work was supported by NIH grant CA89121 and partial support from the Tulane Cancer Center. ,
Antithrombin III prevents progression of chronic kidney disease following experimental ischaemic-reperfusion injury
Authors: Zeyuan Lu
Jianyong Yin
Guangyuan Zhang
Niansong Wang
Yiwei Kong
Feng Wang
Mingyu Liang
Rui Wu
Ling Wang
Journal: Journal of Cellular and Molecular Medicine (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: acute kidney injury; antithrombin III; chronic kidney disease.
Affiliations: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China., Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA., Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA., Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China., Department of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract:  Acute kidney disease (AKI) leads to increased risk of progression to chronic kidney disease (CKD). Antithrombin III (ATIII) is a potent anticoagulant with anti-inflammatory properties, and we previously reported that insufficiencies of ATIII exacerbated renal ischaemia-reperfusion injury (IRI) in rats. In this study, we examined the characteristic of AKI-CKD transition in rats with two distinct AKI models. Based on our observation, left IRI plus right nephrectomy (NX-IRI) was used to determine whether ATIII had therapeutic effects in preventing CKD progression after AKI. It was observed that NX-IRI resulted in significant functional and histological damage at 5 weeks after NX-IRI compared with sham rats, which was mitigated by ATIII administration. Besides, we noticed that ATIII administration significantly reduced NX-IRI-induced interstitial fibrosis. Consistently, renal expression of collagen-1, α-smooth muscle actin and fibronectin were substantial diminished in ATIII-administered rats compared with un-treated NX-IRI rats. Furthermore, the beneficial effects of ATIII were accompanied with decreased M1-like macrophage recruitment and down-regulation of M1-like macrophage-dependent pro-inflammatory cytokines such as tumour necrosis factor α, inducible nitric oxide synthase and interleukin-1β, indicating that ATIII prevented AKI-CKD transition via inhibiting inflammation. Overall, ATIII shows potential as a therapeutic strategy for the prevention of CKD progression after AKI. 

Retracted: No

PubPeer comments:
 An image in Figure 1C and Figure 4A appear to overlap. Additionally, there s a small typo in the legend of 1C (there are 2 descriptions for 1B, but none for 1C). *** ![file] *** Pink highlight should be labeled (C), not (B). ![file] ,
SLPI promotes the gastric cancer growth and metastasis by regulating the expression of P53, Bcl-2 and Caspase-8
Authors: X-Y Du
X Liu
Y-Y Wang
Z-J Wang
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Gastric cancer; Secretory leukocyte protease inhibitor (SLPI); Metastasis; Expression level; Mechanism
Affiliations: Department of Pathology, Jinzhou Medical University, Jinzhou, China. .

Abstract:  Objective: The incidence of gastric cancer is very high all over the world, but the mechanism of the occurrence and development of gastric cancer is unclear. Secretory leukocyte protease inhibitor (SLPI) is overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. In this research, we mainly explored the expression level and possible mechanism of SLPI in gastric cancer. Patients and methods: The expression and clinical significance of SLPI in 68 cases of gastric cancer tissues and adjacent tissues were detected by qRT-PCR. Cell Counting Kit-8 (CCK8) assay was used to detect the proliferation ability of gastric cancer cell lines. In addition, we used Western blot to clarify the relationship between SLPI and metastasis. Results: Compared with the adjacent tissues, we found that SLPI was highly expressed in gastric cancer tissues. We also found that the expression of SLPI was in significant correlation with the survival time, clinical classification and size of the tumor. What's more, SLPI could promote the proliferation and metastasis of gastric cancer by regulating P53, Bcl-2 and Caspase-8 expression through apoptosis signaling pathway. Conclusions: We concluded that SLPI was closely related with to invasion and metastasis of gastric cancer. Perhaps we can hopefully find new targets for the treatment of gastric cancer. 

Retracted: No

PubPeer comments:
 Figure 5. * Red boxes: Panels GI (Control) and GII-Selenite + IR3G appear to show the same lens, but in mirror image. ![file] , 
 All three panels (or should I say two?) in Figure 5 look remarkably similar to panels in Figure 6 in another paper by the same group, where they represent the wonderful preventive effect of luteolin isolated from Vitex negundo on oxidative stress. Here is a comparison between the two figures, with diagonal stripes indication the variable orientations, and red and cyan boxes the panels that look similar. ![file] ,
Long non-coding RNA Linc00518 promotes paclitaxel resistance of the human prostate cancer by sequestering miR-216b-5p
Authors: Sujian Tian
Junhui He
Huaizhen Geng
Mingchong Sun
Journal: Biology of the Cell (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: GATA6; Linc00518; Paclitaxel resistance; Prostate cancer; miR-216b-5p.
Affiliations: Department of Urology Surgery, Heze Municipal Hospital, Heze, 274000, China.

Abstract:  Background information: To characterise Linc00518 expression in prostate cancer and elucidate the potential mechanistic involvement in paclitaxel resistance, the relative expression of Linc00518 and miR-216b-5p was determined by real-time PCR. The regulatory effect of miR-216b-5p on either Linc00518 or GATA6 was interrogated with luciferase reporter assay. The endogenous GATA6 protein was analysed by Western blotting. The cell viability was measured by MTT assay and IC50 of paclitaxel was calculated through cell counting. Results: Linc00518 was highly expressed in prostate tumour both in vivo and in vitro. High level of Linc00518 transcripts associated with paclitaxel resistance. Linc00518 competitively inhibited miR-216b-5p through sponging mechanism. Linc00518 deficiency compromised the paclitaxel resistance in the acquired resistance cell lines. Conclusions and significance: We demonstrated that overexpression of Linc00518 contributed to the paclitaxel resistance in prostate cancer via sequestering miR-216b-5p. 

Retracted: No

PubPeer comments:
 The authors seem to have uploaded the same loading control twice in Figure 3. I suggest to contact the journal about replacing the incorrect blot. There is also some heavy post-processing on the blots giving them an  airbrushed look. I suggest using unprocessed scans. ![file] ,
miR‐145 promotes miR‐133b expression through c‐myc and DNMT3A‐mediated methylation in ovarian cancer cells
Authors: Jie Li
Lei Wu
Meili Pei
Yuliang Zou
Yu Jiang
Songlin Zhang
Journal: Journal of Cellular Physiology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DNMT3A; Warburg effect; c-myc; miR-133b; miR-145
Affiliations: Department of PathologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an China, Department of Structural Heart DiseaseThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an China, Department of Gynecology and ObstetricsThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an China

Abstract:  Ovarian cancer presents as malignant tumors in the female reproductive system with high mortality. MicroRNAs are involved in the progression of ovarian cancer; however, the regulatory relationship among miRs remains unclear. In our study, we verified that both miR-145 and miR-133b messenger RNA (mRNA) levels in ovarian cancer tissues were lower than in normal ovarian tissues, and their mRNA level in serum of patients with ovarian cancer was reduced. We demonstrated miR-145 targeted c-myc, and c-myc interacted physically with DNMT3A in ovarian cancer cells. We confirmed that c-myc recruited DNMT3A to the miR-133b promoter. miR-133b overexpression also inhibited target gene PKM2 expression along with the Warburg effect. Our results indicate that miR-145 inhibited the Warburg effect through miR-133b/PKM2 pathways, which may improve approaches to ovarian cancer diagnosis and treatment. 

Retracted: No

PubPeer comments:
null, 
 Figure 1B. Much more similar than you would expect. ![file] ,
Parkin Regulates the Activity of Pyruvate Kinase M2
Authors: Yingming Zhao
Haichao Han
Yue Chen
Fanzhou Li
Kun Liu
Wei Gu
Wenhui Zhao
Jianyuan Luo
Zebin Mao
Bin Zheng
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Parkinson disease; glycolysis; parkin; pyruvate kinase; pyruvate kinase M2
Affiliations: From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China., Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois 60637., Department of Genetics, Peking University Health Science Center, Beijing 100191, China., Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, and., Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032., From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China, .

Abstract:  Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease. 

Retracted: No

PubPeer comments:
 ![file] ,
Chondroitin sulphate decorated nanoparticulate carriers of 5-fluorouracil: development and in vitro characterization
Authors: Anil K Mishra
Abhinav Agarwal
Gopal Rai
Govind P Agrawal
Hirnanshu Agrawal
Awesh K Yadav
Sanyog Jain
Hemant Bid
Journal: Journal of biomedical nanotechnology (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Tailored nanoparticles; therapeutic efficacy; anti-cancer drug; 5-FU; Condritin Sulphate
Affiliations: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University Sagar (M.P.) 470003, India.

Abstract:  The present study investigates prospective of tailored nanoparticles as vectors to provide improved therapeutic efficacy of encapsulated anti-cancer drug 5-FU. Condritin Sulphate (CS) conjugated PLGA nanoparticles were prepared using PEG-bis-amine and adipic dihydrazide as spacers and loaded with an anti-cancer drug 5-FU (CS-PEG-PLGA-FU and CS-ADH-PLGA-FU). The formulations were then compared with non CS-anchored monomethoxy(polyethylene glycol) (MPEG-PLGA-FU) nanoparticles. Nanoparticlulate systems were further characterized by FTIR, NMR, TEM studies and particle size/polydispersity index (PDI) analysis. DSC and XRD were also performed to assess the nature of 5-FU inside the nanoparticles. The nanoparticles prepared using amphiphilic block copolymer CS-PEG-PLGA were able to sustain the release of 5-FU up to 48 h whereas those of CS-ADH-PLGA and MPEG-PLGA released the drug up to 24 h. The CS-PEG-PLGA-FU nanoparticles were found to be least haemolytic when compared to free drug, CS-ADH-PLGA-FU and MPEG-PLGA-FU nanoparticles. Cytotoxicity studies were performed on MCF-7/MDA-MD 231 breast cancer cells. PLGA nanoparticles exhibited more potent cytotoxic effect on MCF-7/MDA-MD 231 cells than free doxorubicin. Further, enhanced cytotoxicity and lower hemolytic potential of CS-PEG-PLGA-FU nanoparticles suggest a potential application in cancer chemotherapy. 

Retracted: No

PubPeer comments:
  Fig. 4. XRD of (A) 5-Fluorouracil, (B) CS-PEG-PLGA nanoparticles, (C) CS-PEG-PLGA-FU nanoparticles, (D) CS-ADH-PLGA nanoparticles, (E) CS-ADH-PLGA-FU nanoparticles, (F) MPEG-PLGA nanoparticles, (G) MPEG-PLGA-FU nanoparticles. ![file] Diffractograms (B), (D) and (E) are indistinguishable (at the resolution of the printer scanner) for most of their ranges, apart from additional peaks. (F) and (G) are also indistinguishable across most of their ranges. (B), (D) and (E) superimposed. ![file] (F) and (G) superimposed. ![file] ,
Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats
Authors: Ji-Min Deng
Chang-Liang Xu
Xiu-Min Li
Jie Lu
Lu-Fan Li
Shi-Ping Ma
Rong Qu
Journal: Phytotherapy Research (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Magnolol; Antidepressant-like effect; Mechanisms; Unpredictable chronic mild stress; HPLC-ECD
Affiliations: Department of Pharmacology of Chinese Materia Medica; China Pharmaceutical University; Nanjing 210009 PR China, Department of Pharmacology of Traditional Chinese Medical Formulae; Nanjing University of Traditional Chinese Medicine; Nanjing 210029 PR China

Abstract:  Magnolol is the main constituent identified in the barks of Magnolia officinalis, which has been used for the treatment of mental disorders including depression in China. In this study, we investigated the antidepressant-like effect of magnolol, and its possible mechanisms in rats subjected to unpredictable chronic mild stress (UCMS). High performance liquid chromatography with electrochemical detection (HPLC-ECD) and immunohistochemical staining analysis were applied to explore the mechanisms underlying the antidepressant-like effect of magnolol. Magnolol (20, 40 mg/kg) significantly reversed UCMS-induced reduction in sucrose consumption and deficiency in locomotor activity. In addition, it was observed that administration of magnolol (20, 40 mg/kg) restored brain-derived neurotrophic factor (BDNF) expression, and normalized the serotonergic system changes in the UCMS-treated rats. These results confirmed the antidepressant-like effect of magnolol, which might be based primarily on its ability to increase the BDNF expression and enhance the activity of the serotonergic system in rat brains. 

Retracted: No

PubPeer comments:
 The histology images in Figure 4 feature a number of duplications. It is most easily demonstrated by comparing panels A and E. We rotate E 180u00b0: ![file] The red boxes are identical, except the structures in green have been magically vanished. We can similarly compare panels H and J. But here more work has been done. Blue boxes are clearly the same (once we mirror J), except, again, the structures in green have been altered. ![file] I do not see how this could be an inoccuous accident. , 
 #1 Similarity between H and (horizontally-flipped) J is greatest in the lower-right and the upper-left of the area of overlap. ![file] , 
 There s a lot going on in panel J. Here with H, vertically flipped for ease of comparison. ![file] , 
 #3 With so much work put into it, it is perhaps understandable that the authors saw fit to recycle this panel in another publication. ![file] https: pubpeer.com publications E7346E642629CD9808DE2589F30E2D ,
SOST silencing promotes proliferation and invasion and reduces apoptosis of retinoblastoma cells by activating Wnt/β-catenin signaling pathway
Authors: D-R Tang
F-Y Sun
L-N Wang
T Wu
Journal: Gene Therapy (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: SOST; Wnt/β-catenin signaling pathway; proliferation; migration; invasion
Affiliations: Department of Oculoplastic and Orbital Diseases, Tianjin Medical University Eye Hospital, Tianjin, China., Department of Ophthalmology, Tianjin First Center Hospital, Tianjin, China.

Abstract:  This study aimed to investigate the effects of SOST and the Wnt/β-catenin signaling pathway on the proliferation, migration, invasion, and apoptosis of human retinoblastoma cells. Fifty-five retinoblastoma and 21 normal retinal tissue samples were collected as the case group and control group, respectively. HXO-RB44 and SO-RB50 cells were selected and assigned into blank, negative control (NC), siRNA 1, siRNA 2, siRNA 3, IWR-1-endo 1, IWR-1-endo 2 and IWR-1-endo 3 groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of SOST, Wnt-1, and β-catenin in the collected tissue samples. MTT assay, flow cytometry, transwell assay and the starch test were employed to determine the cell proliferation, cell cycle, apoptosis, invasion and migration after transfection. The qRT-PCR and western blotting were also used to detect the mRNA and protein expressions of SOST, Wnt-1, β-catenin, C-myc, Cyclin D1, MMP-2 and MMP-9. The tumor formation in nude mice was conducted to evaluate the effects of SOST on the growth of a transplanted tumor. Compared with normal retinal tissues, the retinoblastoma tissues exhibited a downregulation of SOST but an upregulation of Wnt-1 and β-catenin. The proliferation, invasion and migration of HXO-RB44 and SO-RB50 cells in the SOST-siRNA group were significantly higher than the cells in the blank and NC groups. The expressions of Wnt-1, β-catenin, C-myc, Cyclin D1, MMP-2 and MMP-9 in the three SOST-siRNA groups were elevated, but the SOST decreased when compared with the blank and NC groups. SOST silencing promoted the growth of transplanted tumors in nude mice. These findings indicate that SOST silencing promotes the proliferation, invasion and migration, and decreases the apoptosis of human retinoblastoma cells by activating the Wnt/β-catenin signaling pathway. 

Retracted: No

PubPeer comments:
 https: twitter.com GaetanBurgio status 1250395808450506752 ,