PReD-Bench/PRed-Bench huggingface dataset:
Activity of the heat shock protein 90 inhibitor ganetespib in melanoma
Authors: F Stephen Hodi
Xinqi Wu
Melina E Marmarelis
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Heat shock protein 90; HSP90; Ganetespib; cancer therapy; signal transducing molecules
Affiliations: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.

Abstract:  Heat shock protein 90 (HSP90) is involved in the regulation of diverse biological processes such as cell signaling, proliferation and survival, and has been recently recognized as a potential target for cancer therapy. Ganetespib is a potent ATP competitive inhibitor of HSP90. Ganetespib downregulated the expression of multiple signal transducing molecules including EGFR, IGF-1R, c-Met, Akt, B-RAF and C-RAF, resulting in pronounced decrease in phosphorylation of Akt and Erk1/2 in a panel of five cutaneous melanoma cell lines including those harboring B-RAF and N-RAS mutations. Ganetespib exhibited potent antiproliferative activity on all five of these cell lines, with IC50 values between 37.5 and 84 nM. Importantly, Ganetespib is active on B-RAF mutated melanoma cells that have acquired resistance to B-RAF inhibition. Ganetespib induced apoptosis and cell cycle arrest at G1 and/or G2/M phase. Ganetespib induced cell cycle arrest was accompanied by altered expression of cyclin-dependent kinase inhibitor (CDKI) p21(Cip1) and p27(Kip1), cyclins B1, D1 and E, and/or cyclin-dependent kinases 1, 2 and 4. HSP90 is functionally important for melanoma cells and HSP90 inhibitors such as ganetespib could potentially be effective therapeutics for melanoma with various genetic mutations and acquired resistance to B-RAF inhibition. 

Retracted: No

PubPeer comments:
null, 
null, 
 An illustration of the image concerns, which have also been reported to the journal in 2015, with a friendly reminder in 2016. Figure 1B. * Red boxes: the K028 and M23 Akt panels look similar to each other.  , 
 Figure 3C. * Aqua boxes: In the Cyclin D1 row, the M23 and K033 panels look similar to each other.  ,
Striatal ŒîFosB gene suppression inhibits the development of abnormal involuntary movements induced by L-Dopa in rats
Authors: Hideki Mochizuki
Goichi Beck
Stella M Papa
Jie Zhang
M Maral Mouradian
Kayoko Fong
Journal: Gene Therapy (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: L-Dopa-induced dyskinesia; ‚àÜFosB; Parkinson's disease; gene suppression; RNAi
Affiliations: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA., RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, USA., Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan., RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, USA. ., Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA. .

Abstract:  L-Dopa-induced dyskinesia (LID) is associated with the upregulation of striatal ‚àÜFosB in animal models and patients with Parkinson's disease (PD). A mechanistic role of ‚àÜFosB is suspected because its transgenic overexpression leads to the early appearance of LID in rodents and primates. This study in rodents is aimed at exploring the therapeutic potential of striatal ‚àÜFosB gene suppression to control LID in patients with PD. To determine the effect of reducing striatal ‚àÜFosB expression, we used RNAi gene knockdown in a rat model of PD and assessed abnormal involuntary movements (AIMs) in response to L-Dopa. Rats with dopamine depletion received striatal injections of rAAV-‚àÜFosB shRNA or a control virus before exposure to chronic L-Dopa treatment. The development of AIMs during the entire L-Dopa treatment period was markedly inhibited by ‚àÜFosB gene knockdown and its associated molecular changes. The antiparkinsonian action of L-Dopa was unchanged by ‚àÜFosB gene knockdown. These results suggest a major role for ‚àÜFosB in the development of LID and support exploring strategies to reduce striatal ‚àÜFosB levels in patients with PD. 

Retracted: No

PubPeer comments:
 Figure 5: Do the authors have the uncropped images available? Some of these bands seem much more similar than expected. The scans images can be pasted below, hopefully not hard to find, since this was published last year. I ve added a difference overlay of a section to show how similar the shape of these bands are.   ,
A flow cytometric analysis of macrophage&ndash;nanoparticle interactions in vitro: induction of altered Toll-like receptor expression
Authors: Mary Ann Principato
Jeffrey J Yourick
Joyce M Njoroge
Journal: International Journal of Nanomedicine (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Toll-like receptor; flow cytometry; innate immunity; macrophage; silver nanoparticle.
Affiliations: Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708, USA, .

Abstract:  Background: Nanoparticles exhibit unique physiochemical characteristics that provide the basis for their utilization. The diversity of potential and actual applications compels a thorough understanding regarding the consequences of their containment within the cellular environment. Purpose: This paper presents a flow cytometric examination of the biologic effects associated with the internalization of citrate-buffered silver (Ag) nanoparticles (NP) by the murine macrophage cell line, RAW264.7. Materials and methods: Cells were cultured with varying concentrations of citrate-buffered Ag nanoparticle and analyzed for changes in cellular volume, fluorescence emissions, and surface receptor expression. Results: Notable changes in side scatter (SSC) signal occurred following the phagocytosis of citrate-buffered Ag NP representative of the 10 nm, 50 nm, and 100 nm particle size by cultured RAW 264.7 cells. A characteristic associated with the internalization of all the citrated Ag NP sizes tested, was the detection of emitted infra-red and near-infrared wavelength emissions. This characteristic consistently permitted the detection of 10 nm, 50 nm, and 100 nm Ag NP particles internalized within the RAW cells by flow cytometry. A functional distinction between monocyte subsets within the RAW 264.7 cell line was noted as Ag NP are taken up by the F4/80+ subset of cells within the culture. Further, the internalization of Ag NP by the cells resulted in an increased cell surface expression of the Toll-like receptor (TLR) 3, but not TLR4. Conclusion: Taken together, these results implicate the more mature macrophage in the ingestion of Ag NP; and an influence upon at least one of the Toll receptors present in macrophages following exposure to Ag NP. Further, our flow cytometric approach presents a potentially viable detection method for the identification of occult Ag NP material using an indicator cell line. 

Retracted: No

PubPeer comments:
 I am concerned about apparent similarities between 3 sets of flow cytometry plots, which are reported as being generated from cells treated with different nanoparticles. Figure 6, green boxes added by me.  ,
PPARŒ≥-dependent and PPARŒ≥-independent effects on the development of adipose cells from embryonic stem cells
Authors: R M Mortensen
C Iehl√©
N Belmonte
E Z Amri
C Dani
P E O&#x27;Donnell
C Vernochet
B Wdziekonski
B Phillips
G Ailhaud
D S Milstone
P Villageois
Journal: FEBS Letters (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PPARgamma; adipocyte formation; embryoid bodies; preadipocytes; pluripotent stem cells

Abstract:  Peroxisome proliferator-activated receptor (PPAR) gamma was shown to be required for adipocyte formation both in vivo and in vitro. However, the role of PPARgamma in the initial steps of adipose cell development was not distinguished from its role in the terminal steps. We now show that PPARgamma is expressed early in embryoid bodies (EBs) derived from embryonic stem cells and in E.8.5 mouse embryos. Addition of a specific ligand for PPARgamma in developing EBs over-expressing PPARgamma did not commit stem cells towards the adipose lineage. In differentiated PPARgamma(-/-) EBs, only markers characteristic of preadipocytes were found to be expressed. PPARdelta is present in EBs but did not compensate for the lack of PPARgamma in terminal differentiation. Taken together, these results favor a critical PPARgamma-independent phase culminating in preadipocyte formation that precedes a PPARgamma-dependent phase in the development of adipose cells from pluripotent stem cells. 

Retracted: No

PubPeer comments:
 Figure 3A: More similar than expected, could authors check please?  ,
Periostin Upregulates Wnt/Œ≤-Catenin Signaling to Promote the Osteogenesis of CTLA4-Modified Human Bone Marrow-Mesenchymal Stem Cells
Authors: Keyu Luo
Jianzhong Xu
Fei Dai
Fei Luo
Shiwu Dong
Zhigang Rong
Zhengdong Wang
Zehua Zhang
Dong Sun
Fei Zhang
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Mesenchymal stem cells; CTLA4; bone repair; demineralized bone matrix; rabbit radius defect model
Affiliations: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China., Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China.

Abstract:  The enhanced osteogenesis of mesenchymal stem cells (MSCs) modified by expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown in previous studies, but the mechanism remains unknown. Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matrix (DBM) in a rabbit radius defect model was significantly better than that observed for unmodified MSCs in DBM or DBM alone, and the periostin (POSTN) expression in CTLA4-modified MSCs was significantly higher than that in unmodified MSCs both in vivo and in vitro. In addition, we also found that treatment of CTLA4-modified MSCs with soluble POSTN could inhibit the glycogen synthase kinase-3Œ≤ activity and increase Œ≤-catenin expression through up-regulation of lipoprotein-related protein-6 phosphorylation to promote osteogenic differentiation, but blocking of integrin Œ±vŒ≤3, a receptor of POSTN, could suppress these effects. Our data demonstrated that POSTN expressed in response to CTLA4 can promote the osteogenesis of xenotransplanted MSCs through interaction with Wnt/Œ≤-catenin pathway. 

Retracted: No

PubPeer comments:
 Figure 4. * Blue boxes: The DBM POSTN and DBM b-catenin panels appear to look more similar than expected. Could the authors please check?  , 
 Correction, April 2021: https: www.nature.com articles s41598-021-89264-7  This Article contains an error in Figure 4 where the immunohistochemistry photo of POSTN for DBM group was incorrect. The correct Figure 4 appears below as Figure 1.  I thank the authors for correcting this duplication. ,
LINC00184 silencing inhibits glycolysis and restores mitochondrial oxidative phosphorylation in esophageal cancer through demethylation of PTEN
Authors: Song Zhao
Kai Huang
Zhanfeng He
Guanghui Cui
Fengbiao Wen
Weihao Li
Haizhou Guo
Journal: EBioMedicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: Esophageal cancer; Glycolysis; Long intergenic non-protein coding RNA 184; Methylation; Mitochondrial oxidative phosphorylation
Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China., Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Electronic address: .

Abstract:  Background: Total lesion glycolysis has been reported to be a satisfactory predictor of survival in patients with locally advanced esophageal cancer (EC). The aim of the present study is to investigate the function of long intergenic non-protein coding RNA 184 (LINC00184) on the EC cell glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). Methods: The expression of LINC00184 was determined to be highly expressed and PTEN was poorly expressed in EC tissues and cells by RT-qPCR. In order to evaluate the effects of LINC00184 on cellular process in vitro and in vivo, gain- and loss-of-function approaches were performed to alter the expression of LINC00184 and PTEN in EC cells. Results: Silencing of LINC00184 was observed to inhibit the proliferation, migration, invasion, colony formation, and glycolysis of EC cells and tumour growth, while the mitochondrial OXPHOS was restored. By recruiting DNMT1, LINC00184 enhanced the promoter methylation of PTEN. Inhibition of PTEN promoter methylation suppressed EC glycolysis, whereas, improved mitochondrial OXPHOS. Mechanically, LINC00184 modulated glycolysis and mitochondrial OXPHOS in EC cells through induction of the Akt phosphorylation. After blockage of Akt signaling pathway by an Akt inhibitor, LY294002, the regulatory effects of LINC00184 on the glycolysis and mitochondrial OXPHOS of EC cells were reversed. Conclusion: Taken together, the LINC00184/PTEN/Akt axis mediates glycolysis and mitochondrial OXPHOS in EC cells. This study highlighted a potential intervention target for treating EC. 

Retracted: No

PubPeer comments:
  I am intrigued by the absence of background on these WBs, and the way the bands remain perfectly linear and retain the shape of the protein blobs as they move up the gels (and between blots). Is it possible for the authors to upload scans of the original gels? Numerous other papers have Figures which display the same qualities, and sample the same limited gamut, hence my curiosity. I compiled a montage:  ,
Low-intensity pulsed ultrasound promotes proliferation and migration of HaCaT keratinocytes through the PI3K/AKT and JNK pathways
Authors: Danhui Gao
Jing Shang
Jiang Wu
Xiaoyan Leng
Journal: Brazilian Journal of Medical and Biological Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: low-intensity pulsed ultrasound; LIPUS; keratinocytes; proliferation; migration
Affiliations: Department of Ultrasound, Chengyang People's Hospital, Qingdao, China., Health Management Center, The Affiliated Hospital of Qingdao University, Qingdao, China., Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Abstract:  Although the effects of low-intensity pulsed ultrasound (LIPUS) on diverse cell types have been fully studied, the functional role of LIPUS in keratinocytes remains poorly understood. This study aimed to investigate the effects of LIPUS on proliferation and migration of HaCaT cells as well as the regulatory mechanisms associated with signaling pathways. Human HaCaT cells were exposed or not to LIPUS, and cell proliferation and migration were measured by BrdU incorporation assay and Transwell assay, respectively. Expression of proteins associated with proliferation and migration was evaluated by western blot analysis. Expression of key kinases in the PI3K/AKT and JNK pathways was also evaluated by western blot analysis. Effects of LIPUS on the PI3K/AKT and JNK pathways, and whether LIPUS affected HaCaT cells via these two pathways were finally explored. When the parameter of LIPUS (number of cycles) was set at 300, cell viability was the highest after LIPUS stimulation. We then found that the percentage of BrdU positive cells was enhanced by LIPUS, along with up-regulation of cyclinD1, CDK6, CDK4, and VEGF. LIPUS promoted migration, as well as up-regulation of MMP-2 and MMP-9. Phosphorylation levels of key kinases in the PI3K/AKT and JNK pathways were increased by LIPUS. Inhibition of either PI3K/AKT pathway or JNK pathway attenuated effects of LIPUS on HaCaT cells, and co-inhibition of these two pathways showed augmented effects. LIPUS promoted proliferation and migration of HaCaT cells through activating the PI3K/AKT and JNK pathways. 

Retracted: No

PubPeer comments:
 Increased contrast reveals similar backgrounds in bands of the putative western blots.  This paper conforms to a style identified by [Dr Elisabeth Bik] and [Dr Jana Christopher] , among others. ,
Identification of profilin 1 as the primary target for the anti-cancer activities of Furowanin A in colorectal cancer
Authors: Junhua Xu
Jing Lv
Jinxia Zhao
Journal: Pharmacological Reports (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Colorectal cancer; Furowanin A; Profilin 1.
Affiliations: The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China., The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. Electronic address: .

Abstract:  Background: Furowanin A (Fur A) is a flavonoid compound isolated from medicinal plant Millettia pachycarpa Benth. This study aims to explore the effect of Fur A on Colorectal cancer (CRC) and its molecular mechanisms. Methods: Cell proliferative capacity of CRC cells was assessed by CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell migration and invasion were detected by wound healing and Transwell assay, respectively. EMT markers, apoptosis and profilin 1(Pfn1) expression were detected by immunohistochemistry (IHC). The protein expression levels were examined by western blotting. i-TRAQ analyses were conducted to identify the differentially expressed genes in CRC cells. CRC xenograft model was also used to validate the in vivo anti-cancer activity of Fur A. Results: Fur A exhibited anti-prolifertive, blocked cell cycle progression and promoted apoptotic cell death in CRC cells. Fur A suppressed the migration, invasion and epithelial-to-mesenchymal transition (EMT) in vitro, and tumor growth and pulmonary metastasis in vivo, without causing obvious toxicity. iTRAQ analysis identified Pfn1 as a gene up-regulated by Fur A. In xenograft tumor tissue, the expression of Pfn1 was also elevated by Fur A treatment. In clinical CRC samples, high expression of Pfn1 was correlated with lower stage and longer survival. Knockdown of Pfn1 significantly dampened the pro-apoptotic and anti-metastatic activities of Fur A in CRC cells. Ectopic Pfn1 expression augmented the anti-neoplastic activities of Fur A. Conclusion: Fur A exhibited anti-cancer activities in vitro and in vivo in CRC by up-regulating Pfn1. 

Retracted: Yes

PubPeer comments:
 On Figure 1 the two top XRD spectra appear to be exactly the same.  Moreover this figure was also used as Graphical abstract. , 
 Yes, there is clear duplication of the top and middle spectra, although they supposedly belong to different materials:  ,
Oligomeric interaction of hepatitis C virus NS5B is critical for catalytic activity of RNA-dependent RNA polymerase
Authors: Naoyuki Hayashi
Weiping Qin
Tatsuya Yamashita
Seishi Murakami
Hong Luo
Takahiro Nomura
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HCV NS5B; RNA-dependent RNA polymerase; RdRP activity; catalytic enzyme; palm and fingers
Affiliations: Department Molecular Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-0924, Japan.

Abstract:  HCV NS5B is an RNA-dependent RNA polymerase (RdRP), a central catalytic enzyme for HCV replication, which has the "palm and fingers" substructure. We recently identified five novel residues critical for RdRP activity (Qin, W., Yamashita, T., Shirota, Y., Lin, Y., Wei, W., and Murakami, S. (2001) Hepatology 33, 728-737). Among them, GLU-18 and His-502, far from the catalytic center, may be involved in conformational change(s) for RdRP activity as addressed in some palm and fingers enzymes. We examined the possibility that NS5B is oligomerized, and we could detect the interaction between two different tagged NS5B proteins in vitro and transiently expressed in mammalian cells. By scanning 27 clustered and then point alanine substitutions in vivo and in vitro, Glu-18 and His-502 were found to be critical for the homomeric interaction in vivo and in vitro, strongly suggesting a close relationship between the oligomerization and RdRP activity of NS5B. All mutants with substitutions at these two residues failed to bind wild type NS5B, however E18H interacted with H502E in vitro and in vivo. Interestingly, the NS5B protein with E18H or H502E did not exhibit RdRP activity, but a mixture of the two mutant proteins did. These results clearly indicate that two residues of HCV NS5B are critical for the oligomerization that is prerequisite to RdRP activity. 

Retracted: Yes

PubPeer comments:
 Note: This article has been corrected. Please see the link below: https: www.oncotarget.com article 27256 ,
Retracted: Demethylation of miR‚Ä?95 suppresses prostate cancer cell proliferation, migration and invasion
Authors: Xiangyuan Wu
Li Wei
Zhanhong Chen
Xiaokun Ma
Liyuan Zou
Xing Li
Journal: FEBS Open Bio (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: methylation; miR-195; prostate cancer; tumor suppressor.
Affiliations: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Department of Prevention and Health Care, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Abstract:  Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of tumor-associated deaths worldwide, with increasing incidence rates over the last 10 years. Recently, miR-195 was reported to be hypermethylated at its promoter CpG island and down-regulated in hepatocellular carcinoma. However, the function of miR-195 and the underlying mechanisms in PCa remain unknown. Here, we report that a significant down-regulation of microRNA-195 (miR-195) in PCa tissues and cell lines was associated with promoter methylation status. Overexpression of miR-195 significantly suppressed cell proliferation, migration, invasion and epithelial-mesenchymal transition (increased E-cadherin and decreased N-cadherin) in PCa cells. We further demonstrated that transfection with a miR-195 inhibitor reversed the inhibitory effect of the DNA methyltransferase inhibitor 5-azacytidine on the proliferation, migration and invasion ability of PCa cells. In summary, our findings suggest that miR-195 may function as a crucial tumor suppressor in PCa. 

Retracted: No

PubPeer comments:
 Figure 2D. * Blue boxes: Three groups of data points look more similar to each other than expected.  , 
 Figure 5D. * Green boxes: Five groups of data points look more similar to each other than expected.  , 
 This article has been retracted: https: doi.org 10.1002 2211-5463.13229 ,
The lncRNA NEAT1 facilitates cell growth and invasion via the miR-211/HMGA2 axis in breast cancer
Authors: Yu Chen
Zhenzhong Li
Xiaoyu Long
Shuxia Wang
Xuerui Li
Zibai Guo
Linzhu Wen
Jian Zu
Guochun Zhang
Journal: International Journal of Biological Macromolecules (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HMGA2; NEAT1; miR-211.
Affiliations: Department of Breast Cancer, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: ., Department of Nuclear Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China., Department of Pharmacy, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China., Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China., Department of Breast Cancer, Zhongshan City People's Hospital, Zhongshan, China., Department of Breast Cancer, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China., Department of Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Abstract:  Long non-coding RNAs play a significant role in cancer metastasis. Studies have demonstrated that LncRNA NEAT1 promotes cancer progression. We aimed to explore whether NEAT1 regulated growth and invasion in breast cancer cells. We provided evidence that lncRNA NEAT1 was up-regulated in breast cancer cell lines and tissues. NEAT1 promoted invasion through inducing Epithelial-mesenchymal transition (EMT) and NEAT1 played a role in 5-fluorouracil (5-FU) resistance. In addition, we revealed a reciprocal repression between NEAT1 and miR-211. Furthermore, the EMT-inducer HMGA2 was identified as a down-stream target of miR-211. LncRNA NEAT1 induced EMT and 5-FU resistance through the miR-211/HMGA2 axis. Our findings suggest that lncRNA NEAT1 could be a new diagnostic biomarker and therapy target for breast cancer. 

Retracted: No

PubPeer comments:
 The authors claim in the Materials and Methods section to have used a primer pair to detect human NEAT1 in human MCF7 cells, as seen in Table 2.  **However, inspection of the primer for target specificity using the rna_refseq option, yields no template match to human genome or transcriptome**.  **This finding renders Results at minimum in Figs: 1-A,B,C,D, Fig 3D completely unsafe, making the core of the article to necessarily qualify for an Expression of Concern, at minimum.** It is also noteworthy that this article lacks date of submission, revision, and only shows day of online availability. Can the authors explain these findings and provide raw data for the quantification of gene expression? ,
Constitutive overexpression of Nrf2-dependent heme oxygenase-1 in A549 cells contributes to resistance to apoptosis induced by epigallocatechin 3-gallate
Authors: Mee-Hyang Kweon
Jeong-Sang Lee
Vaqar Mustafa Adhami
Hasan Mukhtar
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: EGCG; apoptosis; cancer cells; lung adenocarcinoma; A549 cells
Affiliations: Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.

Abstract:  Epigallocatechin 3-gallate (EGCG), the major polyphenol found in green tea, exerts antiproliferative and proapoptotic effects in many cancer cells. However, we found that among many cancer cells human lung adenocarcinoma A549 cells are markedly resistant to apoptosis induction by EGCG (even at 100 microm for 72 h). Heme oxygenase-1 (HO-1) induced by stress stimuli represents a prime cellular defense mechanism, but it may be associated with enhanced cell proliferation and chemoresistance in some cancer cells. Because we found that A549 cells constitutively overexpress HO-1 and its associated transcription factor Nrf2, we tested an hypothesis that EGCG resistance in these cells may be linked with Nrf2-mediated HO-1 overexpression. HO-1 inhibition with tin-protoporphyrin IX and silencing with RNA interference rendered cells more sensitive to apoptosis induction by EGCG and classical prooxidants. Interestingly, EGCG at high concentration (&gt;200 microm) induced apoptosis by suppressing expression of HO-1 protein and mRNA, and this effect correlated with a decrease in both Nrf2-ARE binding and HO-1-ARE-luciferase activity, suggesting Nrf2-driven transcriptional activation of ho-1. Because we observed notably high levels of phosphorylated protein kinase C alpha and its suppression by EGCG and deferoxamine (an iron chelator), a possible mechanism involving phosphorylated protein kinase C alpha and iron in Nrf2-HO-1 activation was further investigated. Collectively, our findings suggest that Nrf2-mediated HO-1 overexpression confers resistance to apoptosis induction by EGCG; therefore, its inactivation may be a target for overcoming the resistance to chemoprevention and chemotherapy. 

Retracted: No

PubPeer comments:
 Figure 2B. Much more similar than expected. https: imgur.com CqupzKr , 
 Figures 4A and 6A. much more similar than expected. https: imgur.com wrjwkxm ,
Changes in mRNA and protein expression in the renal cortex of male and female F344 rats treated with bromate
Authors: Richard J Bull
Brian S Cummings
Joseph A Cotruvo
Narendrababu Kolisetty
Jeff W Fisher
Srinivasa Muralidhara
Don A Delker
Journal: Archives of Toxicology (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Bromate; nephrotoxicity; Œ±-2u-globulin nephropathy; mRNA; protein expression
Affiliations: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, 30602, USA., School of Medicine, University of Utah, Salt Lake City, UT, 84132, USA., MoBull Consulting, Richland, WA, 99352, USA., Joseph Cotruvo and Associates, LLC, Washington, DC, 20016, USA., National Center for Toxicological Research, FDA, Jefferson, AR, 72079, USA., Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, 30602, USA. .

Abstract:  Bromate (BrO3(-)), a by-product of ozonation of drinking water, induces nephrotoxicity in male rats at much lower doses than in female rats. This difference appears to be related to the development of Œ±-2u-globulin nephropathy in males. To determine sex-dependent changes in mRNA and protein expression in the renal cortex attributable to Œ±-2u-globulin nephropathy, we performed microarray and immunohistochemical analyses in proximal renal tubules of male and female F344 rats treated with KBrO3 for 28 days. Particular attention was paid to molecular biomarkers of renal tubular injury. Microarray analysis of male and female rats treated with BrO3(-) at low doses (125 mg/L KBrO3) displayed marked sex-dependent changes in renal gene expression. The greatest differences were seen in genes encoding for cellular differentiation, apoptosis, ion transport, and cell proliferation. Differences by sex were especially prominent for the cell cycle checkpoint gene p21, the renal injury protein Kim-1, and the kidney injury and cancer biomarker protein osteopontin. Dose-related nephrotoxicity, assessed by hematoxylin and eosin staining, was greater in males compared to female rats, as was cellular proliferation, assessed by bromodeoxyuridine staining. The fraction of proximal renal cells with elevated 8-oxodeoxyguanosine (8-OH-dG) was only increased at the high dose and did not differ by sex. Dose-dependent increases in the expression of osteopontin were detected immunohistochemically only in male rats and were localized in proximal tubule cells. Similarly, BrO3(-) treatment increased clusterin and Kim-1 staining in the proximal tubules; however, staining for these proteins did not differ appreciably between males and females. These data demonstrate both qualitative and quantitative differences in the response of male versus female kidneys to BrO3(-)-treatment. These sex-dependent effects likely contribute to renal carcinogenesis of BrO3(-) in the male rat. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have a repeated image. ***  ,
Receptor-type protein-tyrosine phosphatase-kappa regulates epidermal growth factor receptor function
Authors: Vladimir Grachtchouk
Li-Jun Tan
John J Voorhees
Yiru Xu
Gary J Fisher
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Epidermal growth factor receptor (EGFR); protein-tyrosine phosphatase-kappa (RPTP-kappa); keratinocytes; tyrosine phosphorylation; CHO cells
Affiliations: Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109, USA.

Abstract:  Epidermal growth factor receptor (EGFR), the prototypic receptor protein tyrosine kinase, is a major regulator of growth and survival for many epithelial cell types. We report here that receptor-type protein-tyrosine phosphatase-kappa (RPTP-kappa) dephosphorylates EGFR and thereby regulates its function in human keratinocytes. Protein-tyrosine phosphatase (PTP) inhibitors induced EGFR tyrosine phosphorylation in intact primary human keratinocytes and cell-free membrane preparations. Five highly expressed RPTPs (RPTP-beta, delta, kappa, mu, and xi) were functionally analyzed in a Chinese hamster ovary (CHO) cell-based expression system. Full-length human EGFR expressed in CHO cells, which lack endogenous EGFR, displayed high basal (i.e. in the absence of ligand) tyrosine phosphorylation. Co-expression of RPTP-kappa, but not other RPTPs, specifically reduced basal EGFR tyrosine phosphorylation. RPTP-kappa also reduced epidermal growth factor-dependent EGFR tyrosine phosphorylation in CHO cells. Purified RPTP-kappa preferentially dephosphorylated EGFR tyrosines 1068 and 1173 in vitro. Overexpression of wild-type or catalytically inactive RPTP-kappa reduced or enhanced, respectively, basal and EGF-induced EGFR tyrosine phosphorylation in human keratinocytes. Furthermore, siRNA-mediated knockdown of RPTP-kappa increased basal and EGF-stimulated EGFR tyrosine phosphorylation and augmented downstream Erk activation in human keratinocytes. RPTP-kappa levels increased in keratinocytes as cells reached confluency, and overexpression of RPTP-kappa in subconfluent keratinocytes reduced keratinocyte proliferation. Taken together, the above data indicate that RPTP-kappa is a key regulator of EGFR tyrosine phosphorylation and function in human keratinocytes. 

Retracted: No

PubPeer comments:
 There are undeclared splice lines in Fig.2A,C and Fig.7.   ,
A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance
Authors: Nadia A Akawi
Lihadh Al-Gazali
Bassam R Ali
Jennifer L Silhavy
Joseph G Gleeson
Journal: Orphanet journal of rare diseases (2012)
Discipline: CLINICAL MEDICINE
Keywords: autosomal recessive syndrome; macrocephaly; multiple epiphyseal dysplasia; distinctive facial appearance; chromosome 15q26
Affiliations: Department of Pathology, Faculty of Medicine and Health Sciences, United Arab Emirates University, P,O, Box 17666, Al-Ain, United Arab Emirates.

Abstract:  Background: We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26. Methods: In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation. Results: Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia. Conclusions: We report the first missense homozygous disease-causing mutation in KIF7 and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients. 

Retracted: No

PubPeer comments:
  Several errors: complete agenesis of the corpus callosum in IV-9 and not IV-19. Cyst of the septum pellucidum: orange arrows Cyst of the cavum vergae: green arrow These cysts and hydrocephalus may be the cause of thinning of the corpus callosum. This is a secondary event and not a primary malformation. For IV-19, the posterior region of the corpus callosum (splenium) is missing. For IV-9, the anterior white commissure is missing. This should be corrected. ,
Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate
Authors: Graham M Strub
Jeremy Allegood
Kuzhuvelil B Harikumar
Tomasz Kordula
Sarah Spiegel
Ronen Marmorstein
Cheng Luo
Nitai C Hait
Sheldon Milstien
Michael Maceyka
Sandeep K Singh
Journal: Science (2009)
Discipline: Multidisciplinary
Keywords: sphingosine-1-phosphate; SphK2; histone acetylation; HDAC1; HDAC2
Affiliations: Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.

Abstract:  The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) can act intracellularly independently of its cell surface receptors through unknown mechanisms. Sphingosine kinase 2 (SphK2), one of the isoenzymes that generates S1P, was associated with histone H3 and produced S1P that regulated histone acetylation. S1P specifically bound to the histone deacetylases HDAC1 and HDAC2 and inhibited their enzymatic activity, preventing the removal of acetyl groups from lysine residues within histone tails. SphK2 associated with HDAC1 and HDAC2 in repressor complexes and was selectively enriched at the promoters of the genes encoding the cyclin-dependent kinase inhibitor p21 or the transcriptional regulator c-fos, where it enhanced local histone H3 acetylation and transcription. Thus, HDACs are direct intracellular targets of S1P and link nuclear S1P to epigenetic regulation of gene expression. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: the LaminA C panel in Figure 2A looks similar to the LaminAC panel in Figure 2C. * Blue arrow. In the Total H4 panel in B, a sharp vertical transition appears to be visible.  ,
MicroRNA-214 functions as an oncogene in human osteosarcoma by targeting TRAF3
Authors: A-L Rehei
W-B Mu
S-J Zhou
Y-X Fu
D-S Yang
A Younusi
Y Liu
L Zhang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Osteosarcoma; miR-214; TRAF3; metastasis; microRNA
Affiliations: Department of Inpatient Area 1 of Pediatric Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. .

Abstract:  Objective: Osteosarcoma is a malignant bone tumor with high incidence. The prognosis of osteosarcoma is very poor when it is diagnosed with metastasis. Numerous studies have demonstrated that aberrant expressions of microRNAs are involved in cancer initiation and development. However, the potential role of miR-214 in osteosarcoma remains largely unrevealed. The current study investigated the relationship between the miR-214 and TNF receptor-associated factor 3 (TRAF3) in osteosarcoma tissues and cell lines. We also aimed to evaluate the potential roles of miR-214 on the occurrence and metastasis in osteosarcoma and verify its effect on the regulation of TRAF3. Patients and methods: The miR-214 expression and TRAF3 expression in osteosarcoma tissue samples and cell line were measured using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Followed by transfection assays, transwell assay was conducted to detect the migration and invasion abilities of osteosarcoma cells. Subsequently, Western blotting and luciferase reporter assay were performed in osteosarcoma cells to confirm the target of miR-214. Results: The results showed that miR-214 expression levels were significantly increased not only in osteosarcoma tissues but also in osteosarcoma cell lines as compared with adjacent normal tissues and matched cell lines, respectively. On the contrary, the TRAF3 expression levels in osteosarcoma tissues and cell lines were frequently decreased compared to the control group. Moreover, TRAF3 was identified as a direct target of miR-214 and the inverse relationship between them was also observed in osteosarcoma tissues. Additionally, we found that miR-214 restoration could significantly promote osteosarcoma cell invasion and migration via targeting TRAF3. Conclusions: MicroRNA-214 functioned as an oncogene in osteosarcoma via targeting TRAF3, which may provide new insights into osteosarcoma prevention and treatment. 

Retracted: No

PubPeer comments:
 Figure 4C and 4D appear to include images which overlap. Roughly marked below with red boxes. ***  ,
Regulation of apoptosis by resveratrol through JAK/STAT and mitochondria mediated pathway in human epidermoid carcinoma A431 cells
Authors: Preeti Roy
Jasmine George
Sahdeo Prasad
Esha Madan
Yogeshwer Shukla
Journal: Biochemical and biophysical research communications (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Resveratrol; Chemopreventive; Anticancer; A431 cells; Apoptosis
Affiliations: Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow, UP 226001, India.

Abstract:  Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin present mainly in grapes, red wine and berries, is known to possess strong chemopreventive and anticancer properties. Here, we demonstrated the anti-proliferative and apoptosis-inducing activities of resveratrol in human epidermoid carcinoma A431 cells. Resveratrol has cytotoxic effects through inhibiting cellular proliferation of A431 cells, which leads to the induction of apoptosis, as evident by an increase in the fraction of cells in the sub-G(1) phase of the cell cycle and Annexin-V binding of externalized phosphatidylserine. Results revealed that inhibition of proliferation is associated with regulation of the JAK/STAT pathway, where resveratrol prevents phosphorylation of JAK, thereby inhibiting STAT1 phosphorylation. Furthermore, resveratrol treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. Consequently, an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and subsequent cleavage of PARP, thereby shifting the balance in favor of apoptosis. These observations indicate that resveratrol treatment inhibits JAK/STAT-mediated gene transcription and induce the mitochondrial cell death pathway. 

Retracted: No

PubPeer comments:
  Fig. 3. Induction of apoptosis and expression of transcription factors with resveratrol treatment in A431 cells. There were significant changes in the expression and cleavage levels of proteins, as assessed and quantified by Western-blot and densitometric analyses, respectively: **(A) Bcl-2** The control band closely resembles three of the five lanes of another band, frequently encountered in these authors work, e.g. in [Roy et al (2009)] ... though with different experimental groups.  Fig 3  (D) cleaved caspase-9, (E) cleaved caspase-3, and (F) PARP cleavage . Again, the control band is recognisably a truncated version of a 5-lane band frequently encountered in the genre, e.g. [Roy et al (2009)] .  ,
MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway
Authors: S Yang
J-H Fu
D-Q Lu
C-J Nan
C-C Zhou
S Li
H-Q Mu
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: research misconduct; MiR-182; renal cancer; proliferation; apoptosis
Affiliations: Department of Urology, Dongyang People's Hospital, Dongyang, Zhejiang, China.

Abstract:  Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway, by J.-H. Fu, S. Yang, C.-J. Nan, C.-C. Zhou, D.-Q. Lu, S. Li, H.-Q. Mu, published in Eur Rev Med Pharmacol Sci 2018; 22 (2): 351-357-DOI: 10.26355/eurrev_201801_14179-PMID: 29424922" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14179. 

Retracted: No

PubPeer comments:
 This is the 2020 retraction notice found here: https: www.europeanreview.org article 21852, retracting DOI: 10.26355 eurrev_201801_14179. See: https: pubpeer.com publications F4E783335233AAE23C3C3B258D3DCB The journal writes:  *Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, u201cMiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K AKT mTOR signaling pathway, by J.-H. Fu, S. Yang, C.-J. Nan, C.-C. Zhou, D.-Q. Lu, S. Li, H.-Q. Mu, published in Eur Rev Med Pharmacol Sci 2018; 22 (6): 351-357u2013DOI: 10.26355 eurrev_201801_14179u2013PMID: 29424922u201d has been withdrawn. *  *The Publisher apologizes for any inconvenience this may cause.* In case the PDF gets removed by the journal, it was captured by the WayBackMachine, and can be found here: https: web.archive.org web 20200208172500 https: www.europeanreview.org wp wp-content uploads 351-357.pdf This paper appears to be part of the Paper Mill #2, AKA the Paint It Black Paper Mill, described by Smut Clyde on Leonid Schneider s blog For Better Science: https: forbetterscience.com 2020 02 27 dark-satanic-papermills Here is part of Figure 4 as an illustration of the pitch black Western blots and particular shape of the flow cytometry plots.  ,
Relationship between E1A binding to cellular proteins, c-myc activation and S-phase induction
Authors: S Baluchamy
B Thimmapaya
A Navaraj
N Sankar
E Moran
Journal: Oncogene (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p300; CREB-binding protein; c-myc; S-phase induction; E1A oncoprotein
Affiliations: Department of Microbiology-Immunology Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Abstract:  We recently showed that p300/CREB-binding protein (CBP) plays an important role in maintaining cells in G0/G1 phase by keeping c-myc in a repressed state. Consistent with this, adenovirus E1A oncoprotein induces c-myc in a p300-dependent manner, and the c-myc induction is linked to S-phase induction. The induction of S phase by E1A is dependent on its binding to and inactivating several host proteins including p300/CBP. To determine whether there is a correlation between the host proteins binding to the N-terminal region of E1A, activation of c-myc and induction of S phase, we assayed the c-myc and S-phase induction in quiescent human cells by infecting them with Ad N-terminal E1A mutants with mutations that specifically affect binding to different chromatin-associated proteins including pRb, p300, p400 and p300/CBP-associated factor (PCAF). We show that the mutants that failed to bind to p300 or pRb were severely defective for c-myc and S-phase induction. The induction of c-myc and S phase was only moderately affected when E1A failed to bind to p400. Furthermore, analysis of the E1A mutants that fail to bind to p300, and both p300 and PCAF suggests that PCAF may also play a role in c-myc repression, and that the two chromatin-associated proteins may repress c-myc independently. In summary, these results suggest that c-myc deregulation by E1A through its interaction with these chromatin-associated proteins is an important step in the E1A-mediated cell cycle deregulation and possibly in cell transformation. 

Retracted: No

PubPeer comments:
 In the method section, the author explained to convert ORs to RRs, but the effect size in the figure shows ORs. So I think the results in the article are not credible.   , 
 #1 This is not the final version of our study, this is a proof. Please read the FINAL version of this study. ([ PMID ]33618187) thanks!!!! , 
 I compared the proof and final version of the figures, and found that the results between before and after proof did not change.   , 
 #2 I have read the FINAL version of this study, and then have more questions . 1.In the method section, the author only included  sleep duration as searching term, why didn t the author include  sleep time ? This will cause related research to be excluded during the literature search stage  ,