PReD-Bench/PRed-Bench huggingface dataset:
A novel transcript for DNA repair gene Ercc1 in mouse skin
Authors: J Selfridge
D W Melton
A G Winter
L Song
Journal: Transgenic Research (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: nucleotide excision repair pathway; UV-induced DNA damage; skin; Ercc1 gene; XPF
Affiliations: Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Western General Hospital, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.

Abstract:  The nucleotide excision repair pathway deals with UV-induced DNA damage. The tissue that receives by far the greatest exposure to UV is the skin and we have investigated the possibility that expression of the nucleotide excision repair gene, Ercc1, may display different properties in the skin to deal with a more demanding role in that tissue. ERCC1, in a complex with XPF, is the structure--specific endonuclease responsible for incising 5' to the UV-induced lesion. We identified a novel Ercc1 mRNA in mouse skin that originates from an alternative upstream promoter. Levels of this skin-specific transcript were low in embryonic skin and increased rapidly after birth, but there was no induction by UV, either in adult skin, or in a cultured keratinocyte model. Levels of the skin-specific Ercc1 transcript were higher in albino than pigmented mouse strains, but there was no difference in ERCC1 protein levels and the expression of the skin-specific transcript was found to be determined by the Ercc1 gene sequence rather than by coat pigmentation. Using an Ercc1 transgene the promoter for the skin-specific transcript was mapped to a region around 400 bp upstream of the normal promoter, where a transposable element with known promoter activity was found in albino but not in pigmented strains. 

Retracted: No

PubPeer comments:
 Data in Transgenic Res . 2011 Feb;20(1):109-22. doi: 10.1007 s11248-010-9396-3. Epub 2010 Apr 21. are very similar to data in Nucleic Acids Res. 2001 Nov 15; 29(22): 4541u20134550. The figure 1 legend Transgenic Res . 2011 Feb;20(1):109-22 does not state that the data have appeared earlier. Transgenic Res . 2011 Feb;20(1):109-22 claims to be an ORIGINAL PAPER. The text of Transgenic Res . 2011 Feb;20(1):109-22 does mention Selfridge et al. 2001 in the text, but does not state that the data are the same.  A panel of tissues from a wild-type BALB c adult male mouse was analysed by Northern blotting using an Ercc1 cDNA probe (Probe a in Selfridge et al. 2001). ![file] , 
 Mre data in Transgenic Res . 2011 Feb;20(1):109-22. doi: 10.1007 s11248-010-9396-3. Epub 2010 Apr 21. are very similar to data in Nucleic Acids Res. 2001 Nov 15; 29(22): 4541u20134550. ![file] ,
Antigen-specific regulatory T cells develop via the ICOS–ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity
Authors: Dale T Umetsu
Everett H Meyer
Gordon J Freeman
Rosemarie H DeKruyff
Tammy T Chang
Edward A Greenfield
Gerald Berry
Omid Akbari
Arlene H Sharpe
Journal: Nature Medicine (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Asthma; T-helper cell 2; Th2; immune responses; T-cell tolerance
Affiliations: Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, Stanford University, Stanford, California, USA.

Abstract:  Asthma is caused by T-helper cell 2 (Th2)-driven immune responses, but the immunological mechanisms that protect against asthma development are poorly understood. T-cell tolerance, induced by respiratory exposure to allergen, can inhibit the development of airway hyperreactivity (AHR), a cardinal feature of asthma, and we show here that regulatory T (T(R)) cells can mediate this protective effect. Mature pulmonary dendritic cells in the bronchial lymph nodes of mice exposed to respiratory allergen induced the development of T(R) cells, in a process that required T-cell costimulation via the inducible costimulator (ICOS-ICOS-ligand pathway. The T(R) cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice, T(R) cells blocked the development of AHR. Both the development and the inhibitory function of regulatory cells were dependent on the presence of IL-10 and on ICOS-ICOS-ligand interactions. These studies demonstrate that T(R) cells and the ICOS-ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma. 

Retracted: No

PubPeer comments:
 Figure 2. Some groups of events (dots) are more similar to each other than expected. ![file] , 
 Figure 1 also might have an occurrence of the group of events marked above in pink. Of course, the authors could take away any concern by providing the original higher resolution graphs, although this might be hard after so many years. ![file] , 
 Figure 3, panels c through f appear to have some repetitive features at the bottom of each photo. Is this some artifact created during slicing the tissue? They appear to look more similar than I would expect if they were adjacent tissue slice, but maybe there is a good explanation for this. ![file] , 
 Figure 3G appears to show some repetitive features. Note several of these are the pink group of dots that appear to be visible in Figures 1 and 2 as well. ![file] , 
 Figure 4. Some areas in different panels as well as areas within the same panel appear to look similar. Most of the events in the narrow gates appear to look similar to each other, albeit different cut-outs. ![file] , 
 Then Figure 5C, which appears to have been made with parts of all previous figures, with re-appearances of pink, blue, and red areas, but not necessarily in the same order. ![file] ,
Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflammation While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Mediates PTGS2, CDK5 and FOXQ1 in Alzheimer's Disease
Authors: Peizhi Ma
Mingzhou Liu
Lingfang Dong
Wei Zhang
Fengqin Fang
Jun Sun
Yuanlong Li
Kun Li
Journal: Current Alzheimer research (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Alzheimer's disease; Lnc-MALAT1; Neuroinflammation; Neuron apoptosis; miR-125b
Affiliations: Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China

Abstract:  Background: This study aimed to investigate the effect of long noncoding ribonucleic acids (RNAs) metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) on regulating neuron apoptosis, neurite outgrowth and inflammation, and further explore its molecule mechanism in Alzheimer's disease (AD). Methods: Control overexpression, lnc-MALAT1 overexpression, control shRNA, and lnc-MALAT1 shRNA were transfected into NGF-stimulated PC12 cellular AD model and cellular AD model from primary cerebral cortex neurons of rat embryo, which were established by Aβ1-42 insult. Rescue experiments were performed by transferring lnc-MALAT1 overexpression and lnc-MALAT1 overexpression &amp; miR-125b overexpression plasmids. Neuron apoptosis, neurite outgrowth and inflammation were detected by Hoechst-PI/apoptosis marker expressions, and observations were made using microscope and RT-qPCR/Western blot assays. PTGS2, CDK5 and FOXQ1 expressions in rescue experiments were also determined. Results: In two AD models, lnc-MALAT1 overexpression inhibited neuron apoptosis, promoted neurite outgrowth, reduced IL-6 and TNF-α levels, and increased IL-10 level compared to control overexpression, while lnc-MALAT1 knockdown promoted neuron apoptosis, repressed neurite outgrowth, elevated IL-6 and TNF-α levels, but reduced IL-10 level compared to control shRNA. Additionally, lnc- MALAT1 reversely regulated miR-125b expression, while miR-125b did not influence the lnc- MALAT1 expression. Subsequently, rescue experiments revealed that miR-125b induced neuron apoptosis, inhibited neurite outgrowth and promoted inflammation, also increased PTGS2 and CDK5 expressions but decreased FOXQ1 expression in lnc-MALAT1 overexpression treated AD models. Conclusion: Lnc-MALAT1 might interact with miR-125b to inhibit neuron apoptosis and inflammation while promote neurite outgrowth in AD. 

Retracted: No

PubPeer comments:
 The Western Blots in this paper are unusual in that the background textures on which they are drawn (repeated among bands) are sufficiently coarse that they can be seen, and recognised, even without contrast enhancement. Here, Fig 5D. ![file] ,
PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A
Authors: Soner Altiok
Min Xu
Bruce M. Spiegelman
Journal: Genes & Development (1997)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PPARγ; adipocyte differentiation; growth arrest; fibroblasts; SV40 large T-antigen

Abstract: PPARγ is an adipose-selective nuclear hormone receptor that plays a key role in the control of adipocyte differentiation. Previous studies indicated that activation of ectopically expressed PPARγ induces differentiation when cells have ceased growth because of confluence. We show here that ligand activation of PPARγ is sufficient to induce growth arrest in fibroblasts and SV40 large T-antigen transformed, adipogenic HIB1B cells. Cell cycle withdrawal is accompanied by a decrease in the DNA-binding and transcriptional activity of the E2F/DP complex, which is attributable to an increase in the phosphorylation of these proteins, especially DP-1. This effect is a consequence of decreased expression of the catalytic subunit of the serine–threonine phosphatase PP2A. These data suggest an important role for PP2A in the control of E2F/DP activity and a new mode of cell cycle control in differentiation. 

Retracted: No

PubPeer comments:
 ![file] ,
Verbascoside inhibits progression of glioblastoma cells by promoting Let‐7g‐5p and down‐regulating HMGA2 via Wnt/beta‐catenin signalling blockade
Authors: Wei-Qiang Jia
Ru-Xiang Xu
Cheng-Yong Yang
Jun Ma
Tian-You Pu
Ming-Ming Zou
Jian-Wei Zhu
Guo-Qiang Han
Journal: Journal of Cellular and Molecular Medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Wnt/β-catenin signalling pathway; autophagy; glioblastoma; invasion; let-7g-5p
Affiliations: Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China., Department of Neurosurgery, Guizhou Provincial People's Hospital, Guiyang, China., Department of Neurosurgery, The Seventh Medical Center of PLA General Hospital, Beijing, China.

Abstract:  Glioblastoma (GBM) continues to show a poor prognosis despite advances in diagnostic and therapeutic approaches. The discovery of reliable prognostic indicators may significantly improve treatment outcome of GBM. In this study, we aimed to explore the function of verbascoside (VB) in GBM and its effects on GBM cell biological processes via let-7g-5p and HMGA2. Differentially expressed GBM-related microRNAs (miRNAs) were initially screened. Different concentrations of VB were applied to U87 and U251 GBM cells, and 50 µmol/L of VB was selected for subsequent experiments. Cells were transfected with let-7g-5p inhibitor or mimic, and overexpression of HMGA2 or siRNA against HMGA2 was induced, followed by treatment with VB. The regulatory relationships between VB, let-7g-5p, HMGA2 and Wnt/β-catenin signalling pathway were determined. The results showed that HMGA2 was a direct target gene of let-7g-5p. VB treatment or let-7g-5p overexpression inhibited HMGA2 expression and the activation of Wnt/β-catenin signalling pathway, which further inhibited cell viability, invasion, migration, tumour growth and promoted GBM cell apoptosis and autophagy. On the contrary, HMGA2 overexpression promoted cell viability, invasion, migration, tumour growth while inhibiting GBM cell apoptosis and autophagy. We demonstrated that VB inhibits cell viability and promotes cell autophagy in GBM cells by up-regulating let-7g-5p and down-regulating HMGA2 via Wnt/β-catenin signalling blockade. 

Retracted: No

PubPeer comments:
 Fig 9 in this paper appears to have been duplicated and manipulated from a previous publication. The accompanying text also appears to have been duplicated. See image below. ![file] ,
<p>Linc00511 Indicates A Poor Prognosis Of Liver Hepatocellular Carcinoma</p>
Authors: Siqiao Li
Ting Lei
Fuxin Jia
Huxiao Cui
Pingan Hu
Erhui Mai
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: LIHC; linc00511; miRNA-29c; migration; proliferation.
Affiliations: Department of Hepatobiliary Surgery, Luoyang Center Hospital, Luoyang, People's Republic of China., Department of Hepatobiliary Surgery, Xuchang Central Hospital, Xuchang, People's Republic of China.

Abstract:  Objective: To uncover the specific function of linc00511 in the progression of liver hepatocellular carcinoma (LIHC) and the underlying mechanism. Patients and methods: GEPIA dataset containing 9736 LIHC samples and 857 normal samples were downloaded from TCGA. Expression pattern and prognostic potential of linc00511 in LIHC were analyzed. Subsequently, expression level of linc00511 in LIHC tissues collected in our hospital and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Differential expressions of linc00511 in LIHC with different tumor grades and metastatic status were compared. After transfection of si-linc00511, proliferative and migratory changes in Huh7 and Hep3B cells were assessed by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assay. Lastly, Pearson correlation analysis and qRT-PCR were conducted to investigate the interaction between linc00511 and miR-29c. Results: Linc00511 was upregulated in LIHC tissues and cell lines. Its level was positively correlated to TNM staging, lymphatic metastasis and poor prognosis in LIHC patients. Knockdown of linc00511 attenuated proliferative and migratory abilities in Huh7 and Hep3B cells. In addition, miR-29c was downregulated in LIHC and negatively linked to linc00511 level. A negative interaction between linc00511 and miR-29c could be a regulatory feedback influencing the progression of LIHC. Conclusion: Linc00511 accelerates the proliferation and migration in LIHC, thus aggravating tumor progression. Meanwhile, linc00511 could be utilized as a hallmark predicting poor prognosis in LIHC patients. 

Retracted: No

PubPeer comments:
 This study describes  exosomes (likely a broader population of extracellular vesicles, EVs) that carry a specific lncRNA. However, at least according to the supplementary methods, the cell lines were grown in media containing 10% fetal bovine serum (FBS). FBS is rich in EVs to the point that conditioned culture media with 10% FBS often contain more bovine EVs than cell culture-derived EVs. Exogenous EVs likely contributed to the findings, making interpretation difficult. ,
Expression of alpha V integrin is modulated by Epstein–Barr virus nuclear antigen 3C and the metastasis suppressor Nm23-H1 through interaction with the GATA-1 and Sp1 transcription factors
Authors: Erle S Robertson
Subhash C Verma
Ke Lan
Tathagata Choudhuri
Journal: Virology (2006)
Discipline: MICROBIOLOGY
Keywords: Epstein-Barr virus; EBV; lymphotrophic herpesvirus; human lymphoid tumors; epithelial tumors
Affiliations: Department of Microbiology, The Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract:  Epstein-Barr virus (EBV) is a lymphotrophic herpesvirus infecting most of the world's population. It is associated with a number of human lymphoid and epithelial tumors and lymphoproliferative diseases in immunocompromised patients. A subset of latent EBV antigens is required for immortalization of primary B-lymphocytes. The metastatic suppressor Nm23-H1 which is downregulated in human invasive breast carcinoma reduces the migration and metastatic activity of breast carcinoma cells when expressed from a heterologous promoter. Interestingly, the EBV nuclear antigen 3C (EBNA3C) reverses these activities of Nm23-H1. The alpha V integrins recognize a variety of ligands for signaling and are involved in cell migration and proliferation and also serve as major receptors for extracellular-matrix-mediated cell adhesion and migration. The goal of this study was to determine if Nm23-H1 and EBNA3C can modulate alpha V integrin expression and downstream activities. The results of our studies indicate that Nm23-H1 downregulates alpha V intregrin expression in a dose responsive manner. In contrast, EBNA3C can upregulate alpha V integrin expression. Furthermore, the study showed that the association of the Sp1 and GATA transcription factors with Nm23-H1 is required for modulation of the alpha V integrin activity. Thus, these results suggest a direct correlation between the alpha V integrin expression and the interaction of Nm23-H1 with EBNA3C. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar than you would expect. https: imgur.com az9UQiS , 
 Figure 5. Much more similar than you would expect. https: imgur.com PZ4JoLq , 
 Last author appears to be on the editorial board of this journal: https: www.sciencedirect.com journal virology about editorial-board , 
 Figures 3C and 3D. Much more similar than expected. https: imgur.com hr3YWKk ,
Expression patterns of AMP-deaminase isozymes in human hepatocellular carcinoma (HCC)
Authors: Magdalena Szydłowska
Anna Roszkowska
Journal: Molecular and Cellular Biochemistry (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AMP-deaminase; nucleotide breakdown; energetic metabolism; mammalian cells; AMPD1
Affiliations: Department of Biochemistry and Clinical Physiology, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland. 

Abstract:  Background: AMP-deaminase (EC 3.5.4.6) is an enzyme of nucleotide breakdown involved in regulation of energetic metabolism in mammalian cells. The enzyme is coded by a family of three independent genes (AMPD1, AMPD2 and AMPD3), synthesizing three different isozymes. In mammalian liver, the reaction catalyzed by AMP-deaminase constitutes a rate-limiting step in adenine nucleotide catabolism. In neoplastic liver, adenine nucleotide catabolism is a subject of many modifications, which influence the expression of genes synthesizing enzymes regulating this pathway. Aims: The experimental studies presented here illustrate the expression of AMPD genes in human liver neoplasm tumor (HCC, hepatocellular carcinoma). Methods: RT-PCR and Western blotting methods were used for determining of the goal mentioned above. Results and conclusion: Expression level of AMPD gene family in the tumorous fragment (HCC tumor) of neoplastic liver did not differ substantially from that found in the nontumorous (cirrhotic) fragment of the organ. In this case the expression of AMPD2 gene was prevailing. AMPD2 was the main isoform of AMP-deaminase identified in two liver fragments compared. This is a first report evidencing the pattern of AMPD genes expression in neoplastic human liver. 

Retracted: No

PubPeer comments:
 * Figure 2: Possible cuts visible between lanes * Figure 3: Possible cuts visible between lanes in top panel; the two bands in the bottom actin panel look very similar to each other albeit stretched differently Reported to the journal in October 2015, but no response as of today. ![file] ,
Upregulated lncRNA CASC2 May Inhibit Malignant Melanoma Development Through Regulating miR-18a-5p/RUNX1
Authors: Feng Feng
Yankun Zhang
Qian Cao
Jufeng Fan
Ying Hou
Wei Qian
Luyang Zhang
Yanqi Li
Journal: Oncology research (2019)
Discipline: CLINICAL MEDICINE
Keywords: lncRNA CASC2; malignant melanoma; miR-18a-5p; cell proliferation; migration
Affiliations: Department of Plastic and Reconstructive Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P.R. China, Department of Operating Room, Sanfine International Hospital, Beijing, P.R. China

Abstract:  This study aimed to investigate the effect and underlying mechanism of lncRNA CASC2 in malignant melanoma (MM). Expression of CASC2 in MM tissues and cells was detected. A375 cells were transfected with pc-CASC2, si-CASC2, miR-18a-5p inhibitor, or corresponding controls, and then cell proliferation, migration, and invasion were detected using MTT assay, colony formation assay, and Transwell analysis, respectively. The relationship of miR-18a-5p and CASC2 or RUNX1 was detected by luciferase reporter assay. The levels of CASC2 and RUNX1 were significantly reduced in MM tissues compared with normal skin tissues or cells, while the miR-18a-5p level was obviously increased (all p &lt; 0.01). Cell viability, colony number, migration, and invasion were significantly decreased in cells with pc-CASC2 compared with cells transfected with pcDNA3.1 (all p &lt; 0.05). These effects were consistent with the cells transfected with miR-18a-5p inhibitor. The luciferase reporter assay revealed that CASC2 acted as a molecular sponge for miR-18a-5p, and RUNX1 was a target gene of miR-18a-5p. Moreover, CASC2 overexpression promoted the expression of RUNX1, while upregulated miR-18a-5p significantly reversed the effect of CASC2 on the RUNX1 level (all p &lt; 0.05). Upregulated CASC2 may inhibit cell proliferation, migration, and invasion through regulating miR-18a-5p and its target gene RUNX1 in MM. 

Retracted: No

PubPeer comments:
 Fig 1  (F) The migratory cell number in A375 cells with pc-CASC2, pcDNA3.1 (blank), si-CASC2, or si-control using Transwell analysis. (G) The invasive cell number in A375 cells with pc-CASC2, pcDNA3.1 (blank), si-CASC2, or si-control using Transwell analysis. ![file] Fig 2  (G) The migratory cell number of A375 cells with miR-18a-5p inhibitor or inhibitor control using Transwell analysis. (H) The invasive cell number of A375 cells with miR-18a-5p inhibitor or inhibitor control using Transwell analysis.  ![file] Fig 4.  (C) The migratory cell number of A375 cells with pc-RUNX1 or pcDNA3.1 (blank) using Transwell analysis. (D) The invasive cell number of A375 cells with pc-RUNX1 or pcDNA3.1 using Transwell analysis. ![file] There are an implausible number of graphic elements repeated across these independent cell-count images. I have left the panels of Fig 4 as an exercise for the reader. ,
Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells
Authors: Werner Müller-Esterl
Ivan Dikic
Robert Elez
Manfred P Lutz
Bernd Kronenberger
Albrecht Piiper
Henning Cramer
Stefan Zeuzem
Jürgen Leser
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PC12 cells; cAMP; intracellular; survival; neurite outgrowth
Affiliations: Department of Internal Medicine and Institute for Biochemistry II, Johann Wolfgang Goethe-University, D-60590 Frankfurt, Germany. 

Abstract:  In PC12 cells, a well studied model for neuronal differentiation, an elevation in the intracellular cAMP level increases cell survival, stimulates neurite outgrowth, and causes activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). Here we show that an increase in the intracellular cAMP concentration induces tyrosine phosphorylation of two receptor tyrosine kinases, i.e. the epidermal growth factor (EGF) receptor and the high affinity receptor for nerve growth factor (NGF), also termed Trk(A). cAMP-induced tyrosine phosphorylation of the EGF receptor is rapid and correlates with ERK1/2 activation. It occurs also in Panc-1, but not in human mesangial cells. cAMP-induced tyrosine phosphorylation of the NGF receptor is slower and correlates with Akt activation. Inhibition of EGF receptor tyrosine phosphorylation, but not of the NGF receptor, reduces cAMP-induced neurite outgrowth. Expression of dominant-negative Akt does not abolish cAMP-induced survival in serum-free media, but increases cAMP-induced ERK1/2 activation and neurite outgrowth. Together, our results demonstrate that cAMP induces dual signaling in PC12 cells: transactivation of the EGF receptor triggering the ERK1/2 pathway and neurite outgrowth; and transactivation of the NGF receptor promoting Akt activation and thereby modulating ERK1/2 activation and neurite outgrowth. 

Retracted: No

PubPeer comments:
 Figure 1B u2013 More similar than expected, although it should represent different experimental conditions. Could authors clarify this issue please? ![file] , 
 2020 correction. https: www.jbc.org content 295 43 14792.short VOLUME 277 (2002) PAGES 43623u201343630 In Fig. 1B, in the lane marked EGF, the result of a similar experiment on the EGF-induced tyrosine phosphorylation of EGFR in the presence of H-89 was shown, which was published elsewhere (Piiper et al. (2003) Biochem. Biophys. Res. Commun. 301, 848u2013854; Fig. 1A, lane H89+EGF). The revised Fig. 1B shows the correct lane of the EGF-induced phosphorylation of EGFR in the absence of H-89 that was taken from the same original blot as the 8-Br-cAMPu2013induced EGFR phosphorylation after 0, 3, and 5 min, respectively. This error does not affect the validity of the results and the conclusions of our study; the authors apologize for any inconvenience this might have caused for the readers. ,
Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding
Authors: Valerie Grum-Tokars
Adrian Saldanha
Peter Hodder
J Scott Daniels
Eric Dawson
Shaun R Stauffer
Andrew D Mesecar
Aspen Chun
Peter Chase
Sakshi Tomar
Mark Turlington
Craig W Lindsley
Jon Jacobs
Yahira M Baez-Santos
Aimee Eggler
Journal: Bioorganic & Medicinal Chemistry Letters (2013)
Discipline: CHEMISTRY
Keywords: 3CLpro; Coronavirus; MERS; SARS; Severe acute respiratory syndrome.
Affiliations: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN 37232, USA.

Abstract:  Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond. 

Retracted: No

PubPeer comments:
 The chemical structure of molecule 7 shown in Fig. 2 does not match that in the crystal structure, PDB 4mds. I checked the crystallographic maps of 4mds, and the ligand structure looks correct to me. The error is in the pyrrole. The crystal structure, as shown in Fig. 3A, has the pyrrole nitrogen ortho to the peptide Cbeta. However, Fig. 2 shows the pyrrole nitrogen meta to the peptide Cbeta. ,
Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers
Authors: Masaki Inoue
Noriyuki Yatabe
Taro Kanaya
Yoshiko Maida
Satoru Kyo
Mitsuhiro Nakamura
Masaaki Tanaka
Journal: Oncogene (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MLH1 gene; promoter hypermethylation; microsatellite instability; endometrial cancers; CpG methylation
Affiliations: Department of Obstetrics and Gynecology, Kanazawa university School of Medicine, Kanazawa, Ishikawa 920-8641, Japan.

Abstract:  Silencing of the MLH1 gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of MLH1 promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study investigates the region 700 bp upstream of MLH1 covering 48 CpG sites using bisulfite sequencing. Methylation status was classified as full (over 80% of CpGs are methylated), partial (10-80%) or nonmethylation (less than 10%). Of 56 endometrioid endometrial cancers, 16 (29%) were fully methylated, 14 (25%) were partially methylated and 26 (46%) were not methylated. Analyses of MLH1 by immunohistochemical means and of MSI revealed that the degree, rather than region-specific methylation of CpG islands is critical for decreased MLH1 expression and the MSI phenotype. Among 12 patients with methylated cancers, five (42%) patients contained methylated promoters in their normal endometria with profiles similar to those of cancer lesions, and these were associated with the MSI phenotype. In contrast, only one of 31 (3%) normal endometria from patients without endometrial malignancies harbored methylated promoters. These findings suggest that hypermethylation of the MLH1 promoter is frequent in the histologically normal endometrium adjacent to cancers, supporting the notion that hypermethylation of mismatch repair genes is the initial step that triggers various genetic events in endometrial carcinogenesis. 

Retracted: No

PubPeer comments:
 Figure 4B. Very similar, but low resolution. ![file] Could the authors post higher resolution images here? ,
Enhanced Aβ(1-40) production in endothelial cells stimulated with fibrillar Aβ(1-42)
Authors: Francis J Chrest
Jayakumar Rajadas
John W Kusiak
Aaron Tan
Wanli Wei Smith
Hai Li
Valeria de Mello Coelho
Joseph M Rifkind
Joseph C Wu
Dennis Taub
Damiano Cereghetti
Wenchao Sun
Mohammed Inayathullah
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Amyloid accumulation; Alzheimer's patients; amyloid β protein; amyloid precursor protein; Aβ
Affiliations: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, California, United States of America. 

Abstract:  Amyloid accumulation in the brain of Alzheimer's patients results from altered processing of the 39- to 43-amino acid amyloid β protein (Aβ). The mechanisms for the elevated amyloid (Aβ(1-42)) are considered to be over-expression of the amyloid precursor protein (APP), enhanced cleavage of APP to Aβ, and decreased clearance of Aβ from the central nervous system (CNS). We report herein studies of Aβ stimulated effects on endothelial cells. We observe an interesting and as yet unprecedented feedback effect involving Aβ(1-42) fibril-induced synthesis of APP by Western blot analysis in the endothelial cell line Hep-1. We further observe an increase in the expression of Aβ(1-40) by flow cytometry and fluorescence microscopy. This phenomenon is reproducible for cultures grown both in the presence and absence of serum. In the former case, flow cytometry reveals that Aβ(1-40) accumulation is less pronounced than under serum-free conditions. Immunofluorescence staining further corroborates these observations. Cellular responses to fibrillar Aβ(1-42) treatment involving eNOS upregulation and increased autophagy are also reported. 

Retracted: No

PubPeer comments:
 Figure 5. * Red boxes: Panels A and B appear to look very similar. ![file] ,
Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head
Authors: Rui Su
Ping Zhang
Bo Yuan
Ling Li
Yun Liao
Journal: Journal of Orthopaedic Surgery and Research (2017)
Discipline: CLINICAL MEDICINE
Keywords: Avascular necrosis of the femoral head; Cortisol; HIF; mTOR.

Abstract:  Background: ANFH is a major health problem, to which long lasting and definitive treatments are lacking. The aim of this study is to study RNA alterations attributed to cortisol-induced ANFH. Methods: Rat models were stratified into three groups: in vitro group (n = 20) for molecular biological assays, control group (n = 3), and ANFH group induced using lipopolysaccharide and dexamethasone (n = 3). Bone marrow-derived endothelial progenitor cells (BM-EPCs) were extracted from the rats. An RNA expression array was performed on BM-EPCs, and enriched genes were subject to pathway analysis. In vitro studies following findings of array results were also performed using the isolated BM-EPCs. Results: Significant alterations in mammalian target of rapamycin (mTOR) and HIF signaling pathways were identified in BM-EPCs of ANFH. By applying cortisol and dexamethasone to BM-EPCs, significant changes in mTOR and HIF elements were identified. The alteration of HIF pathways appeared to be downstream of mTOR signaling. Glucocorticoid receptor (GR) expression was related to glucocorticoid-dependent mRNA expression of mTOR/HIF genes. mTOR-dependent angiogenesis but not anabolism was the target of GR in ANFH. Inhibition of mTOR signaling also induced apoptosis of BM-EPCs via CHOP-dependent DR5 induction in response to GR stimulation. Conclusion: Decreased mTOR signaling in response to GR stimulation leading to downregulated HIF pathway as well as increased apoptosis could be the pathophysiology. 

Retracted: No

PubPeer comments:
 Figure 2a appears to include at least one repeated image. COR and DEX appear to be the same for the p-S6K bands. When overlaid, the images match exactly (pictured with DEX at 50% transparency). The same may be true for the S6K bands, but I did not perform the same analysis. Could the authors post the original uncropped scans here? *** Close-up ![file] *** ![file] , 
 Fig 4(a):  Application of COR (1.0 u03bcM), DEX (1.0 u03bcM), and rapamycin (RAPA, 10 u03bcM) inducing apoptosis . Surprisingly many points have identical locations in the COR and DEX panels. ![file] Here dramatised by overlaying the DEX panel on COR, black-white reversed and 50% transparency. At left, with slight offset so shared points stand out with a pseudo-3D effect. Suggested by a colleague. ![file] ,
Ubiquitination and degradation of ribonucleotide reductase M1 by the polycomb group proteins RNF2 and Bmi1 and cellular response to gemcitabine
Authors: Gerold Bepler
Xin Li
Zhengming Chen
Yingtao Zhang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Ribonucleotide reductase M1; gemcitabine; ubiquitination; proteasome-mediated degradation; Bmi1
Affiliations: Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, Michigan, United States of America.

Abstract:  Ribonucleotide reductase M1 (RRM1) is required for mammalian deoxyribonucleotide (dNTP) metabolism. It is the primary target of the antimetabolite drug gemcitabine, which is among the most efficacious and most widely used cancer therapeutics. Gemcitabine directly binds to RRM1 and irreversibly inactivates ribonucleotide reductase. Intra-tumoral RRM1 levels are predictive of gemcitabine's therapeutic efficacy. The mechanisms that regulate intracellular RRM1 levels are largely unknown. Here, we identified the E3 ubiquitin-protein ligases RNF2 and Bmi1 to associate with RRM1 with subsequent poly-ubiquitination at either position 48 or 63 of ubiquitin. The lysine residues 224 and 548 of RRM1 were identified as major ubiquitination sites. We show that ubiquitinated RRM1 undergoes proteasome-mediated degradation and that targeted post-transcriptional silencing of RNF2 and Bmi1 results in increased RRM1 levels and resistance to gemcitabine. Immunohistochemical analyses of 187 early-stage lung cancer tumor specimens revealed a statistically significant co-expression of RRM1 and Bmi1. We were unable to identify suitable reagents for in situ quantification of RNF2. Our findings suggest that Bmi1 and possibly RNF2 may be attractive biomarkers of gemcitabine resistance in the context of RRM1 expression. They also provide novel information for the rational design of gemcitabine-proteasome inhibitor combination therapies, which so far have been unsuccessful if given to patients without taking the molecular context into account. 

Retracted: No

PubPeer comments:
 Figure 3B. * Cyan arrows focus attention on lanes 1 and 2, which look remarkably similar. * Red arrows: Vertical discontinuities visible, suggesting splices Reported to the journal in October 2015, but no action taken as of today. ![file] ,
Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis
Authors: David Pajuelo Reguera
Massimo Zeviani
Ian M Fearnley
Marek Vrbacký
Josef Houštěk
Kristýna Čunátová
Tomáš Mráček
Erika Fernández-Vizarra
Petr Pecina
Shujing Ding
Journal: Cells (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: COX; COX4; OXPHOS; biogenesis interdependency; cI
Affiliations: Laboratory of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, 142 00 Prague, Czech Republic., Department of Cell Biology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic., MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, CB2 0XY, UK.

Abstract:  The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependency of individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) deficiencies affect the level of fully assembled NADH dehydrogenase (cI) in monomeric as well as supercomplex forms. It was hypothesized that cI is affected at the level of enzyme assembly as well as at the level of cI stability and maintenance. However, the true nature of interdependency between cI and cIV is not fully understood yet. We used a HEK293 cellular model where the COX4 subunit was completely knocked out, serving as an ideal system to study interdependency of cI and cIV, as early phases of cIV assembly process were disrupted. Total absence of cIV was accompanied by profound deficiency of cI, documented by decrease in the levels of cI subunits and significantly reduced amount of assembled cI. Supercomplexes assembled from cI, cIII, and cIV were missing in COX4I1 knock-out (KO) due to loss of cIV and decrease in cI amount. Pulse-chase metabolic labeling of mitochondrial DNA (mtDNA)-encoded proteins uncovered a decrease in the translation of cIV and cI subunits. Moreover, partial impairment of mitochondrial protein synthesis correlated with decreased content of mitochondrial ribosomal proteins. In addition, complexome profiling revealed accumulation of cI assembly intermediates, indicating that cI biogenesis, rather than stability, was affected. We propose that attenuation of mitochondrial protein synthesis caused by cIV deficiency represents one of the mechanisms, which may impair biogenesis of cI. 

Retracted: No

PubPeer comments:
 A very interesting article. Unfortunately, I couldn t find the loading controls for Fiures 1C, 3, 5A and Supplemental Figure 3A. ,
Disruption of DNA-methylation-dependent long gene repression in Rett syndrome
Authors: Hume Stroud
Caitlin S Gilbert
Martin Hemberg
Daniel H Ebert
Benyam Kinde
David A Harmin
Nathaniel R Kastan
Michael E Greenberg
Harrison W Gabel
Journal: Nature (2015)
Discipline: Multidisciplinary
Keywords: MECP2 gene; Rett syndrome; autism; methyl-DNA-binding protein; transcriptional repressor
Affiliations: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA., Department of Ophthalmology, Children's Hospital Boston, Center for Brain Science and Swartz Center for Theoretical Neuroscience, Harvard University, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.

Abstract:  Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that has been proposed to function as a transcriptional repressor, but despite numerous mouse studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 protein regulates transcription. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 Figure 1 and Figure 2 appear to have an image which overlaps. Could the authors please confirm that this is intentional? *** Figure 1 ![file] *** Figure 2 ![file] ,
<i>Retracted</i> : Paeoniflorin promotes angiogenesis and tissue regeneration in a full‐thickness cutaneous wound model through the PI3K/AKT pathway
Authors: Cong Mao
Zhenjiang Xu
Zili He
Xiaoyu Dong
Guangheng Xiang
Yongzeng Feng
Leyi Cai
Journal: Journal of Cellular Physiology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K/AKT pathway; angiogenesis; paeoniflorin; wound healing.
Affiliations: Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China., Key Laboratory of Orthopedics of Zhejiang Province, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract:  The treatment of wounds remains a clinical challenge because of poor angiogenesis under the wound bed, and increasingly, the patients' need for functional and aesthetically pleasing scars. For the wound healing process, new blood vessels which can deliver nutrients and oxygen to the wound area are necessary. In this study, we investigated the pro-angiogenesis ability and mechanism in wound healing of paeoniflorin (PF), which is a traditional Chinese medicine. In our in vitro results, the ability for proliferation, migration and in vitro angiogenesis in human umbilical vein endothelial cells was promoted by coculturing with PF (1.25-5 μM). Meanwhile, molecular docking studies revealed that PF has excellent binding abilities to phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT), and consistent with our western blot results, that PF suppressed PI3K and AKT phosphorylation. Furthermore, to investigate the healing effect of PF in vivo, we constructed a full-thickness cutaneous wound model in rats. PF stimulated the cellular proliferation status, collagen matrix deposition and remodeling processes in vitro and new blood vessel formation at the wound bed resulting in efficient wound healing after intragastric administration of 10 mg·kg-1 ·day-1 in vivo. Overall, PF performed the pro-angiogenetic effect in vitro and accelerating wound healing in vivo. In summary, the capacity for angiogenesis in endothelial cells could be enhanced by PF treatment via the PI3K/AKT pathway in vitro and could accelerate the wound healing process in vivo through collagen deposition and angiogenesis in regenerated tissue. This study provides evidence that application of PF represents a novel therapeutic approach for the treatment of cutaneous wounds. 

Retracted: Yes

PubPeer comments:
 Data from this paper has not yet been deposited on GEO as stated in the paper: https: www.ncbi.nlm.nih.gov geo query acc.cgi?acc=GSE139088 ,
Brefeldin A Acts to Stabilize an Abortive ARF–GDP–Sec7 Domain Protein Complex
Authors: J Cherfils
C L Jackson
A Peyroche
B Antonny
J Acker
S Robineau
Journal: Molecular cell (1999)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: brefeldin A; Sec7 domain; ARF exchange factors; budding yeast; Gea1p

Abstract:  We demonstrate that the major in vivo targets of brefeldin A (BFA) in the secretory pathway of budding yeast are the three members of the Sec7 domain family of ARF exchange factors: Gea1p and Gea2p (functionally interchangeable) and Sec7p. Specific residues within the Sec7 domain are important for BFA inhibition of ARF exchange activity, since mutations in these residues of Gea1p (sensitive to BFA) and of ARNO (resistant to BFA) reverse the sensitivity of each to BFA in vivo and in vitro. We show that the target of BFA inhibition of ARF exchange activity is an ARF-GDP-Sec7 domain protein complex, and that BFA acts to stabilize this complex to a greater extent for a BFA-sensitive Sec7 domain than for a resistant one. 

Retracted: No

PubPeer comments:
 The lanes highlighted in red and green are duplicates. ![file] ,
Kaempferol promotes proliferation, migration and differentiation of MC3T3-E1 cells via up-regulation of microRNA-101
Authors: Hanyang Zhang
Hongyu Chen
Yang Wang
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Fracture healing; Kaempferol; Wnt/β-catenin pathway; microRNA-101; osteoblast.
Affiliations: Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, China;, Department of Orthopaedics, Qingdao West Coast New Area Central Hospital, Qingdao, China;, Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, China

Abstract:  Osteoblast has been found to exert indispensable functions during fracture healing. This study aimed to investigate the effects of kaempferol, a natural flavonoid compound, on osteoblast proliferation, migration and differentiation, as well as possible molecular mechanisms. qRT-PCR was performed to measure the expression level of microRNA-101 (miR-101). Cell viability and migration were respectively assessed using cell counting kit-8 (CCK-8) assay and two-chamber migration assay. Relative alkaline phosphatase (ALP) activity was evaluated using p-nitrophenyl phosphate (pNPP) as substrate. Western blotting was used to detect the protein expression levels of key molecules involved in cell proliferation, migration, differentiation, and Wnt/β-catenin pathway. Kaempferol treatment significantly promoted MC3T3-E1 cell proliferation, migration, and differentiation. Mechanistically, kaempferol notably enhanced the expression level of miR-101 in MC3T3-E1 cells. Knockdown of miR-101 obviously weakened the promoting effects of kaempferol on MC3T3-E1 cell proliferation, migration, and differentiation. In addition, kaempferol remarkably activated Wnt/β-catenin pathway in MC3T3-E1 cells via up-regulating miR-101. This research further confirmed the promoting effects of kaempferol on osteoblast proliferation, migration, and differentiation. The up-regulation of miR-101 and activation of Wnt/β-catenin pathway caused by kaempferol play critical roles in the promoting effects of kaempferol on osteoblast proliferation, migration, and differentiation. 

Retracted: No

PubPeer comments:
 Although this study uses RT-PCR, the precise protocol or kit used cannot be clearly identified. Could the authors kindly offer details. ,