PReD-Bench/PRed-Bench huggingface dataset:
Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity
Authors: Karen A Pauwelyn
Alexei A Sharov
Aernout Luttun
Catherine M Verfaillie
Minoru S H Ko
Yulan Piao
Martine Geraerts
Benjamin L Kidder
Fernando Ulloa-Montoya
Wei-Shou Hu
Lucas G Chase
Annelies Crabbe
Journal: Genome biology (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: postnatal stem cells; multipotent adult progenitor cells (MAPCs); transcriptome; pluripotent embryonic stem cells (ESCs); lineage-restricted mesenchymal stem cells (MSCs)
Affiliations: Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. 

Abstract:  Background: Recently, several populations of postnatal stem cells, such as multipotent adult progenitor cells (MAPCs), have been described that have broader differentiation ability than classical adult stem cells. Here we compare the transcriptome of pluripotent embryonic stem cells (ESCs), MAPCs, and lineage-restricted mesenchymal stem cells (MSCs) to determine their relationship. Results: Applying principal component analysis, non-negative matrix factorization and k-means clustering algorithms to the gene-expression data, we identified a unique gene-expression profile for MAPCs. Apart from the ESC-specific transcription factor Oct4 and other ESC transcripts, some of them associated with maintaining ESC pluripotency, MAPCs also express transcripts characteristic of early endoderm and mesoderm. MAPCs do not, however, express Nanog or Sox2, two other key transcription factors involved in maintaining ESC properties. This unique molecular signature was seen irrespective of the microarray platform used and was very similar for both mouse and rat MAPCs. As MSC-like cells isolated under MAPC conditions are virtually identical to MSCs, and MSCs cultured in MAPC conditions do not upregulate MAPC-expressed transcripts, the MAPC signature is cell-type specific and not merely the result of differing culture conditions. Conclusion: Multivariate analysis techniques clustered stem cells on the basis of their expressed gene profile, and the genes determining this clustering reflected the stem cells' differentiation potential in vitro. This comparative transcriptome analysis should significantly aid the isolation and culture of MAPCs and MAPC-like cells, and form the basis for studies to gain insights into genes that confer on these cells their greater developmental potency. 

Retracted: No

PubPeer comments:
 It is possible this article received a silent correction. The version deposited [at NCBI PubMed] shows a duplication in Figure 2A, highlighted: ![file] However, on [BMC website] the plot for mClone-3 CD44 is different. ,
MicroRNA-192 inhibits the proliferation, migration and invasion of osteosarcoma cells and promotes apoptosis by targeting matrix metalloproteinase-11
Authors: Guanghui Wang
Yadong Wang
Yingwu Mei
Guoqiang Zhao
Yuebai Li
Yisheng Wang
Xinjie Li
Yang Mi
Guowei Shang
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; invasion; matrix metalloproteinase-11; miR-192; migration
Affiliations: Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China

Abstract:  MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation and differentiation. miRNAs are also involved in the development and progression of a number of cancer types, including osteosarcoma (OS). miR-192 is significantly downregulated in various tumors, including lung, bladder and rectal cancer. miR-192 expression is associated with the migration and invasion of OS cells. However, the expression of miR-192 and its effects on the development of OS have not been reported. In the present study, the involvement of miR-192 and its molecular mechanisms in the development of OS was investigated. The results indicate that miR-192 expression was significantly downregulated in OS tissues compared with non-tumor tissues (P&lt;0.05). Next, a miR-192 agomir was transfected into the OS cell line MG-63 to upregulate miR-192. The effects of miR-192 overexpression were then investigated by examining cell proliferation, apoptosis, migration and invasion. Matrix metalloproteinase (MMP)-11 belongs to a family of nine or more highly homologous Zn2+-endopeptidases. It was demonstrated that the mRNA and protein expression of MMP-11 were upregulated in OS tissues compared with non-tumor tissues (P&lt;0.05). MMP-11 was predicted by TargetScan and miRanda as a miR-192 target, which was confirmed by western blotting and dual-luciferase assays. Finally, it was demonstrated that the overexpression of miR-192 was able to downregulate MMP-11 expression and reduce proliferation, migration and invasion, and promote apoptosis in OS cells. Together, these data indicate that miR-192 may be a tumor suppressor that inhibits the progression and invasion of OS by targeting MMP-11. Therefore, miR-192 may be useful for the diagnosis and treatment of OS. 

Retracted: No

PubPeer comments:
 Figure 4B (below bottom) in this paper appears to share images from Figure 2C (below top) from DOI: 10.3892 etm.2018.6068, also posted here: https: pubpeer.com publications A66A292B578141FB94E04A75A0ACF5. They are described differently in the 2 papers. Could the authors explain? *** ![file] , 
 #1 Not to forget the 3rd appearance in [Zhao et al. (2019)] ! ![] , 
 [Perhaps a systemic problem] . Journals and readers may wish to proceed with caution. ,
The tumor suppressor protein PML controls apoptosis induced by the HIV-1 envelope
Authors: M Piacentini
F Subra
M Bourouba
D M Ojcius
R Nardacci
G Kroemer
C Séror
G Manic
M-L Gougeon
A Amendola
L Gros
H de Thé
J-L Perfettini
C Auclair
F Rosselli
P Masdehors
Journal: Cell death and differentiation (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Promyelomonocytic leukemia; PML; HIV-1; syncytia; apoptosis
Affiliations: INSERM U848, Institut Gustave Roussy, Université Paris Sud, Paris 11, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.

Abstract:  Promyelomonocytic leukemia (PML) is a prominent oncosuppressor whose inactivation is involved in the pathogenesis of hematological and epithelial cancers. Here, we report that PML aggregated in nuclear bodies in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. PML aggregation occurred after the fusion of nuclei (karyogamy) within syncytia but before the apoptotic program was activated. The aggregation of PML was detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Using a range of specific inhibitors of PML (the oncogenic PML/RARalpha fusion product or specific small interfering RNAs), we demonstrated that, in Env-elicited syncytia, PML was required for activating phosphorylation of ataxia telangiectasia mutated (ATM), which colocalized with PML in nuclear bodies, in a molecular complex that also involved topoisomerase IIbeta-binding protein 1. PML knockdown thus inhibited the ATM-dependent DNA damage response that culminates in the activation of p53, p53-dependent transcription of pro-apoptotic genes and cell death. Infection of CD4-expressing cells with HIV-1 also induced syncytial apoptosis, which could be suppressed by inhibiting PML. Altogether, these data indicate that PML activation is a critical early event that participates in the apoptotic demise of HIV-1-elicited syncytia. 

Retracted: No

PubPeer comments:
 Supplemental Fig. S5 - GAPDH bands are more similar than expected, and should represent different experimental conditions. Could authors check it please? ![file] ,
MicroRNA hsa-miR-125a-3p activates p53 and induces apoptosis in lung cancer cells
Authors: Lili Jiang
Xueshan Qiu
Limei Sun
Qingfu Zhang
Jihong Chang
Journal: Cancer Investigation (2013)
Discipline: CLINICAL MEDICINE
Keywords: hsa-miR-125a-3p; apoptosis; p53 pathway; proliferation; lung cancer
Affiliations: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University , Shenyang, Liaoning , China,1.

Abstract:  The mature microRNA hsa-miR-125a-3p is derived from the 3' end of pre-miR-125a. Here, we reported that hsa-miR-125a-3p suppressed proliferation and induced apoptosis in A549 cells. In addition, wild-type p53 mRNA and protein expression was increased by hsa-miR-125a-3p over-expression. Moreover, blocking wild-type p53 attenuated the effect of hsa-miR-125a-3p on apoptosis but could not restore completely. In p53-deficient cell line H1299, hsa-miR-125a-3p still induced apoptosis. Taken together, these data suggest that hsa-miR-125a-3p induces apoptosis not only via the p53 pathway in human lung cancer cells. These results provide new insight into the roles of the miR-125a family in lung cancer. 

Retracted: No

PubPeer comments:
 Figure 3. * Red boxes: Lanes 1-2 of the p53 panel look similar to lanes 2 and 3 of the b-actin panel. Note that the lanes on the right do not look the same. ![file] Reported to the journal in October 2015, but no action as of today. ,
Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2
Authors: Milan Obradovic
Esma R Isenovic
Katarina Smiljanic
Danimir Jevremovic
Pierre Marche
Jelena Djordjevic
Aleksandra Jovanovic
Branislava Dobutovic
Journal: Molecular and Cellular Biochemistry (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EGFR; ERK1/2; HB-EGF; metalloproteinases; MMP-2
Affiliations: Department of Biochemistry, Faculty of Chemistry, University of Belgrade, Studentski trg 16, 11000, Belgrade, Serbia, .

Abstract:  In this study, the role of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK1/2), heparin-binding EGF-like growth factor (HB-EGF), general metalloproteinases, matrix metalloproteinases-2 (MMP-2) in mediating the mitogenic action of thrombin in rat vascular smooth muscle cells (VSMC) was investigated. The incubation of rat VSMC with thrombin (1 U/ml) for 5 min resulted in significant (p &lt; 0.001) increase of ERK1/2 phosphorylation by 8.7 ± 0.9-fold, EGFR phosphorylation by 8.5 ± 1.3-fold (p &lt; 0.001) and DNA synthesis by 3.6 ± 0.4-fold (p &lt; 0.001). Separate 30-min pretreatments with EGFR tyrosine kinase irreversible inhibitor, 10 µM PD169540 (PD), and 20 µM anti-HB-EGF antibody significantly reduced thrombin-stimulated EGFR and ERK1/2 phosphorylation by 81, 72 % and by 48 and 61 %, respectively. Furthermore, the same pretreatments with PD or anti-HB-EGF antibody reduced thrombin-induced VSMC proliferation by 44 and 45 %, respectively. In addition, 30-min pretreatments with 10 µM specific MMP-2 inhibitor significantly reduced thrombin-stimulated phosphorylation of both EGFR and ERK1/2 by 25 %. Moreover, the same pretreatment with MMP-2 inhibitor reduced thrombin-induced VSMC proliferation by 45 %. These results show that the thrombin-induced DNA synthesis correlates with the level of ERK1/2 activation rather than EGFR activation. These results further suggest that thrombin acts through EGFR and ERK 1/2 signaling pathways involving MMP-2 to upregulate proliferation of VSMC. 

Retracted: No

PubPeer comments:
 Figures 2, 3, 5, and 7. * Red and blue boxes highlight panels that look remarkably similar but that appear to show different experiments. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ![file] ,
Cytoplasmic translocation of polypyrimidine tract-binding protein and its binding to viral RNA during Japanese encephalitis virus infection inhibits virus replication
Authors: Richa Jalodia
Sudhanshu Vrati
Manjula Kalia
Deepika Bhullar
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Japanese encephalitis virus; RNA genome; polypyrimidine tract-binding protein; RNA replicase complex; virus replication
Affiliations: National Institute of Immunology, New Delhi, India., Vaccine and Infectious Disease Research Centre, Translational Health Science & Technology Institute, Gurgaon, India., National Institute of Immunology, New Delhi, India; Vaccine and Infectious Disease Research Centre, Translational Health Science & Technology Institute, Gurgaon, India.

Abstract:  Japanese encephalitis virus (JEV) has a single-stranded, positive-sense RNA genome containing a single open reading frame flanked by the 5'- and 3'-non-coding regions (NCRs). The virus genome replicates via a negative-sense RNA intermediate. The NCRs and their complementary sequences in the negative-sense RNA are the sites for assembly of the RNA replicase complex thereby regulating the RNA synthesis and virus replication. In this study, we show that the 55-kDa polypyrimidine tract-binding protein (PTB) interacts in vitro with both the 5'-NCR of the positive-sense genomic RNA--5NCR(+), and its complementary sequence in the negative-sense replication intermediate RNA--3NCR(-). The interaction of viral RNA with PTB was validated in infected cells by JEV RNA co-immunoprecipitation and JEV RNA-PTB colocalization experiments. Interestingly, we observed phosphorylation-coupled translocation of nuclear PTB to cytoplasmic foci that co-localized with JEV RNA early during JEV infection. Our studies employing the PTB silencing and over-expression in cultured cells established an inhibitory role of PTB in JEV replication. Using RNA-protein binding assay we show that PTB competitively inhibits association of JEV 3NCR(-) RNA with viral RNA-dependent RNA polymerase (NS5 protein), an event required for the synthesis of the plus-sense genomic RNA. cAMP is known to promote the Protein kinase A (PKA)-mediated PTB phosphorylation. We show that cells treated with a cAMP analogue had an enhanced level of phosphorylated PTB in the cytoplasm and a significantly suppressed JEV replication. Data presented here show a novel, cAMP-induced, PTB-mediated, innate host response that could effectively suppress JEV replication in mammalian cells. 

Retracted: No

PubPeer comments:
 ![file] ,
Preclinical assessment of carboplatin treatment efficacy in lung cancer by 18F-ICMT-11-positron emission tomography
Authors: R Fortt
Eric O Aboagye
Timothy H Witney
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Tumour response; therapy monitoring; non-invasive imaging techniques; (18)F-ICMT-11 positron emission tomography; caspase 3/7 activation
Affiliations: Department of Surgery and Cancer, Imperial College London, London, United Kingdom.

Abstract:  Tumour response to therapy is assessed primarily in the clinic by monitoring reductions in tumour size. However, this approach lacks sensitivity since in many cases several weeks may elapse before there is evidence of tumour shrinkage. There is therefore a need to develop non-invasive imaging techniques for monitoring tumour treatment response in the clinic. Here, we assessed the pre-clinical utility of (18)F-ICMT-11 positron emission tomography--a method for detecting caspase 3/7 activation--in non-small cell lung cancer (NSCLC). (18)F-ICMT-11 uptake was compared to molecular biochemical measures of cell death in PC9 and A549 NSCLC cells following treatment with carboplatin in vitro and in vivo. Carboplatin-induced apoptosis in the ERCC1 low/mutant EGFR PC9 cells was characterised by time and dose-related increased caspase-3/7 activation, poly-ADP-ribose polymerase cleavage and Annexin V staining. 18F-ICMT-11 uptake was consequently increased up to 14-fold at 200 µM carboplatin compared to vehicle treated cells (P&lt;0.01). In contrast, necrosis was the predominant death mechanism in ERCC1 high/wt EGFR A549 cells and no change in (18)F-ICMT-11 uptake was detected. In vivo, histological analysis of PC9 tumour xenografts indicated high pre-therapy necrosis. A 4.6-fold increase in cleaved caspase-3/7 was measured in non-necrotic regions of PC9 tumours at 48 h post carboplatin therapy. Average PET-derived tumour (18)F-ICMT-11 uptake was insensitive to changes in apoptosis in the presence of substantial pre-existing necrosis. PET-based voxel intensity sorting however, identified intra-tumoural regions of high (18)F-ICMT-11 uptake, enabling accurate assessment of apoptosis and therefore therapy response. In A549 tumours that lacked high pre-therapy necrosis, carboplatin induced growth inhibition that was only minimally associated with apoptosis and thus not detectable by (18)F-ICMT-11 PET. 

Retracted: No

PubPeer comments:
 Two corrections. The June 2014 correction can be found here: https: journals.plos.org plosone article?id=10.1371 journal.pone.0100020 It corrects an author name and Figure 1. A second correction was issued in July 2020: https: journals.plos.org plosone article?id=10.1371 journal.pone.0235804 This second addendum corrects a duplicated panel in Figure 3B(ii), which I reported in October 2015. Shown here in red boxes: ![file] , 
 Thanks for first identifying this honest but embarrassing mistake Elisabeth. A worrying aspect of this was that the mistake was brought up by myself with the PLOSone editors right after your notification and it took them this length of time and many many emails to action the correction. ,
Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy
Authors: Yan Zhou
Shuaiyao Lu
Maosheng Sun
Zhanlong He
Wenju Wang
Wanpu Wang
Min Yan
Hongjun Li
Journal: Cytotherapy (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Adipose mesenchymal stromal cells; Gene therapy; Neurodegenerative disorders; Parkinson disease; LIM homeobox transcription factor 1, alpha (LMX1A)
Affiliations: Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Science, Kunming, China.

Abstract:  Background aims: The use of adipose mesenchymal stromal cells (ASCs) in cellular and genic therapy has attracted considerable attention as a possible treatment for neurodegenerative disorders, including Parkinson disease. However, the effects of gene therapy combined with intracerebral cell transplantation have not been well defined. Recent studies have demonstrated the respective roles of LIM homeobox transcription factor 1, alpha (LMX1A) and Neurturin (NTN) in the commitment of embryonic stem cells (ESCs) to a midbrain dopaminergic neuronal fate and the commitment of mesenchymal stromal cells to cells supporting the nutrition and protection of neurons. Methods: We investigated a novel in vitro neuronal differentiation strategy with the use of LMX1A and Neurturin. We were able to elicit a neural phenotype regarding cell morphology, specific gene/protein expression and physiological function. Neuronal-primed ASCs derived from rhesus monkey (rASCs) combined with adenovirus containing NTN and tyrosine hydroxylase (TH) (Ad-NTN-TH) were implanted into the striatum and substantia nigra of methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored with the use of behavioral tests and health measures until the fourth month after implantation. Results: The differentiated cells transcribed and expressed a variety of dopaminergic neuron-specific genes involved in the SHH/LMX1A pathway. Single-photon emission computed tomography analysis and postmortem analysis revealed that the grafting of rASCs combined with Ad-NTN-TH had neuroprotective effects compared with Ad-NTN-TH or rASCs alone. Behavioral measures demonstrated autograft survival and symptom amelioration. Conclusions: These findings may lead to cellular sources for autologous transplantation of Parkinson disease. Combined transplantation of Ad-NTN-TH and induced rASCs expressing LMX1A and NTN may be a better therapy candidate for the treatment of Parkinson disease. 

Retracted: No

PubPeer comments:
 Figure 9. * Green boxes: Panels A and B appear to show an overlap * Blue boxes: Panels C and D appear to show an overlap ![file] ,
Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway
Authors: Tom K Hei
Sally A Amundson
Charles R Geard
David J Brenner
Hongning Zhou
Joseph Gillespie
Zengliang Yu
Vladimir N Ivanov
Howard B Lieberman
Journal: Proceedings of the National Academy of Sciences of the United States of America (2005)
Discipline: Multidisciplinary
Keywords: radiation-induced bystander effect; biological effects; charged particle; gap junction communication; soluble mediator
Affiliations: Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Abstract:  The radiation-induced bystander effect is defined as "the induction of biological effects in cells that are not directly traversed by a charged particle but are in close proximity to cells that are." Although these bystander effects have been demonstrated with a variety of biological endpoints in both human and rodent cell lines (as well as in 3D tissue samples), the mechanism of the phenomenon is not known. Although gap junction communication and the presence of soluble mediator(s) are both known to play important roles in the bystander response, the precise signaling molecules have yet to be identified. By using the Columbia University charged particle beam in conjunction with a strip dish design, we show here that the cyclooxygenase-2 (COX-2, also known as prostaglandin endoperoxide synthase-2) signaling cascade plays an essential role in the bystander process. Treatment of bystander cells with NS-398, which suppresses COX-2 activity, significantly reduced the bystander effect. Because the critical event of the COX-2 signaling is the activation of the mitogen-activated protein kinase pathways, our finding that inhibition of the extracellular signal-related kinase phosphorylation suppressed bystander response further confirmed the important role of mitogen-activated protein kinase signaling cascade in the bystander process. These results provide evidence that the COX-2-related pathway, which is essential in mediating cellular inflammatory response, is the critical signaling link for the bystander phenomenon. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than expected. ![file] ,
Site-specific group selection drives locally adapted group compositions
Authors: Jonathan N Pruitt
Charles J Goodnight
Journal: Nature (2014)
Discipline: Multidisciplinary
Keywords: Group selection; Anelosimus studiosus; behavioural polymorphism; docile; aggressive
Affiliations: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA., Department of Biology, University of Vermont, Burlington, Vermont 05405, USA.

Abstract:  Group selection may be defined as selection caused by the differential extinction or proliferation of groups. The socially polymorphic spider Anelosimus studiosus exhibits a behavioural polymorphism in which females exhibit either a 'docile' or 'aggressive' behavioural phenotype. Natural colonies are composed of a mixture of related docile and aggressive individuals, and populations differ in colonies' characteristic docile:aggressive ratios. Using experimentally constructed colonies of known composition, here we demonstrate that population-level divergence in docile:aggressive ratios is driven by site-specific selection at the group level--certain ratios yield high survivorship at some sites but not others. Our data also indicate that colonies responded to the risk of extinction: perturbed colonies tended to adjust their composition over two generations to match the ratio characteristic of their native site, thus promoting their long-term survival in their natal habitat. However, colonies of displaced individuals continued to shift their compositions towards mixtures that would have promoted their survival had they remained at their home sites, regardless of their contemporary environment. Thus, the regulatory mechanisms that colonies use to adjust their composition appear to be locally adapted. Our data provide experimental evidence of group selection driving collective traits in wild populations. 

Retracted: No

PubPeer comments:
 Editorial note https: www.nature.com articles nature13811#citeas 26 February 2021 Editor s Note: Readers are alerted that the reliability of some of the data presented in this Article is currently in question and is being investigated by the editors. A further editorial response will follow when the issues are resolved. , 
 https: www.legacy.com obituaries burlingtonfreepress obituary.aspx?n=charles-j-goodnight pid=196909137 fhid=23408 Last author may be deceased. ,
The HIF-pathway inhibitor NSC-134754 induces metabolic changes and anti-tumour activity while maintaining vascular function
Authors: Y-L Chung
L C J Baker
M Ashcroft
Y Jamin
J K R Boult
S Walker-Samuel
S P Robinson
Journal: British Journal of Cancer (2012)
Discipline: CLINICAL MEDICINE
Keywords: Hypoxia-inducible factor-1; NSC-134754; tumour progression; survival; prostate cancer cells

Abstract:  Background: Hypoxia-inducible factor-1 (HIF-1) mediates the transcriptional response to hypoxic stress, promoting tumour progression and survival. This study investigated the acute effects of the small-molecule HIF-pathway inhibitor NSC-134754. Methods: Human PC-3LN5 prostate cancer cells were treated with NSC-134754 for 24 h in hypoxia. Orthotopic prostate tumour-bearing mice were treated with a single dose of NSC-134754 for 6, 24 or 48 h. Treatment response was measured using magnetic resonance spectroscopy and imaging. Ex-vivo histological validation of imaging findings was also sought. Results: In vitro, NSC-134754 significantly reduced lactate production and glucose uptake (P&lt;0.05), while significantly increasing intracellular glucose (P&lt;0.01) and glutamine uptake/metabolism (P&lt;0.05). Increased glutamine metabolism was independent of c-Myc, a factor also downregulated by NSC-134754. In vivo, a significantly higher tumour apparent diffusion coefficient was determined 24 h post-treatment (P&lt;0.05), with significantly higher tumour necrosis after 48 h (P&lt;0.05). NSC-134754-treated tumours revealed lower expression of HIF-1α and glucose transporter-1, at 6 and 24 h respectively, while a transient increase in tumour hypoxia was observed after 24 h. Vessel perfusion/flow and vascular endothelial growth factor levels were unchanged with treatment. Conclusion: NSC-134754 induces metabolic alterations in vitro and early anti-tumour activity in vivo, independent of changes in vascular function. Our data support the further evaluation of NSC-134754 as an anti-cancer agent. 

Retracted: No

PubPeer comments:
 Figure 1A highly composite. Figure 1B. Marks suggestive of splicing in the beta-actin panel, but not in the GLUT-1 panel. ![file] ,
Transforming Growth Factor β<sub>1</sub>Selectively Inhibits the Cyclic AMP-dependent Proliferation of Primary Thyroid Epithelial Cells by Preventing the Association of Cyclin D3–cdk4 with Nuclear p27<sup>kip1</sup>
Authors: J E Dumont
F Depoortere
P P Roger
I Pirson
J Bartek
Journal: Molecular Biology of the Cell (2000)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Dog thyroid epithelial cells; cAMP; TSH; cyclin D3; cdk4
Affiliations: Institute of Interdisciplinary Research, Université Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium., Institute of Interdisciplinary Research, Université Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium; and, Division of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark

Abstract:  Dog thyroid epithelial cells in primary culture constitute a physiologically relevant model of positive control of DNA synthesis initiation and G0-S prereplicative phase progression by cAMP as a second messenger for thyrotropin (thyroid-stimulating hormone [TSH]). As previously shown in this system, the cAMP-dependent mitogenic pathway differs from growth factor cascades as it stimulates the accumulation of p27(kip1) but not cyclins D. Nevertheless, TSH induces the nuclear translocations and assembly of cyclin D3 and cdk4, which are essential in cAMP-dependent mitogenesis. Here we demonstrate that transforming growth factor beta(1) (TGFbeta(1)) selectively inhibits the cAMP-dependent cell cycle in mid-G1 and various cell cycle regulatory events, but it weakly affects the stimulation of DNA synthesis by epidermal growth factor (EGF), hepatocyte growth factor, serum, and phorbol esters. EGF+serum and TSH did not interfere importantly with TGFbeta receptor signaling, because they did not affect the TGFbeta-induced nuclear translocation of Smad 2 and 3. TGFbeta inhibited the phosphorylation of Rb, p107, and p130 induced by TSH, but it weakly affected the phosphorylation state of Rb-related proteins in EGF+serum-treated cells. TGFbeta did not inhibit c-myc expression. In TSH-stimulated cells, TGFbeta did not affect the expression of cyclin D3, cdk4, and p27(kip1), nor the induced formation of cyclin D3-cdk4 complexes, but it prevented the TSH-induced relocalization of p27(kip1) from cdk2 to cyclin D3-cdk4. It prevented the nuclear translocations of cdk4 and cyclin D3 without altering the assembly of cyclin D3-cdk4 complexes probably formed in the cytoplasm, where they were prevented from sequestering nuclear p27(kip1) away from cdk2. This study dissociates the assembly of cyclin D3-cdk4 complexes from their nuclear localization and association with p27(kip1). It provides a new mechanism of regulation of proliferation by TGFbeta, which points out the subcellular location of cyclin D-cdk4 complexes as a crucial factor integrating mitogenic and antimitogenic regulations in an epithelial cell in primary culture. 

Retracted: No

PubPeer comments:
 Figure 8. Vertical changes in background in 4 panels. ![file] ,
Effect of Mutant p53 Proteins on Glycolysis and Mitochondrial Metabolism
Authors: Amanda Tomie Ouchida
Gorbatchev Ambroise
Matilda Eriksson
Marcin P Iwanicki
Patricia A Muller
Andre Lima Queiroz
Helin Vakifahmetoglu-Norberg
Erik Norberg
Dominique Smith
Alfredo Gimenez-Cassina
Journal: Molecular and Cellular Biology (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EMT; OxPhos; cancer; glycolysis; metabolism
Affiliations: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Departamento de Biología Molecular, Universidad Autónoma de Madrid, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA., MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom., Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden  .

Abstract:  TP53 is one of the most commonly mutated genes in human cancers. Unlike other tumor suppressors that are frequently deleted or acquire loss-of-function mutations, the majority of TP53 mutations in tumors are missense substitutions, which lead to the expression of full-length mutant proteins that accumulate in cancer cells and may confer unique gain-of-function (GOF) activities to promote tumorigenic events. Recently, mutant p53 proteins have been shown to mediate metabolic changes as a novel GOF to promote tumor development. There is a strong rationale that the GOF activities, including alterations in cellular metabolism, might vary between the different p53 mutants. Accordingly, the effect of different mutant p53 proteins on cancer cell metabolism is largely unknown. In this study, we have metabolically profiled several individual frequently occurring p53 mutants in cancers, focusing on glycolytic and mitochondrial oxidative phosphorylation pathways. Our investigation highlights the diversity of different p53 mutants in terms of their effect on metabolism, which might provide a foundation for the development of more effective targeted pharmacological approaches toward variants of mutant p53. 

Retracted: No

PubPeer comments:
 I believe there is a mixup with the figures regarding the OCR and ECAR data. In Figure 2E, ATP-coupled respiration is at similar higher levels when compared with basal respiration, which seems to be odd regarding the Seahorse system data. Figure 3E, Basal respiration panel is same as the ATP-coupled respiration data panel. Figure 5E, glycolysis and glycolytic capacity panels are same. Figure 5F, it should be OCR measurement in the graph, basal respiration and ATP-coupled respiration panels are same. ![file] ![file] ![file] ,
Upregulation of the expression of Wnt5a promotes the proliferation of pancreatic cancer cells in vitro and in a nude mouse model
Authors: Jing Zhang
Haiji Bo
Ying Chen
Minghua Zhu
Li Gao
Journal: Molecular Medicine Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Wnt proteins; cell fate; pattern formation; embryogenesis; Wnt5a
Affiliations: Department of Pathology, No. 455 Hospital of PLA, Shanghai 200052, P.R. China., Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.

Abstract:  Wnt proteins are a group of secreted signaling proteins, which function to regulate cell fate and pattern formation during embryogenesis. Altered expression of Wnt5a has been implicated in human carcinogenesis and tumor progression. A previous study identified that Wnt5a is overexpressed in human pancreatic cancer tissues, and that upregulated expression of Wnt5a promotes tumor cell migration and invasion. The present study investigated the role of Wnt5a in pancreatic cancer cell proliferation in vitro and in an orthotopic nude mouse model. Wnt5a cDNA or small interfering RNA were stably transfected into pancreatic cancer cells to assess cell proliferation-associated behaviors, including cell viability, colony formation and apoptosis in vitro, as well as tumor cell growth in an orthotopic nude mouse model. Western blot analysis was used to analyze the expression of Wnt signaling molecules. The data showed that upregulation of the expression of Wnt5a significantly promoted proliferation of the human pancreatic cells, but inhibited tumor cell apoptosis in vitro and promoted tumor growth in an orthotopic nude mouse model. By contrast, knockdown of the expression of Wnt5a inhibited cell growth and promoted apoptosis of the pancreatic cancer cells. The data also revealed that β-catenin mediated the effects of Wnt5a on the regulation of pancreatic cancer cell apoptosis in vitro. These results suggested that Wnt5a is involved in the modulation of pancreatic cancer cell proliferation, and that Wnt5a may be a potential target for pancreatic cancer therapy. 

Retracted: No

PubPeer comments:
 Figure 2A appears to have a repeated image. *** Closeup ![file] *** Full figure ![file] ,
Kaposi sarcoma herpesvirus (KSHV) vFLIP oncoprotein induces B cell transdifferentiation and tumorigenesis in mice
Authors: Kang Chen
Ethel Cesarman
Gianna Ballon
Wayne Tam
Rocio Perez
Journal: Journal of Clinical Investigation (2011)
Discipline: CLINICAL MEDICINE
Keywords: Kaposi sarcoma herpesvirus; Kaposi sarcoma; primary effusion lymphoma; multicentric Castleman disease; viral FLICE-inhibitory protein
Affiliations: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10065, USA. 

Abstract:  Kaposi sarcoma herpesvirus (KSHV) is specifically associated with Kaposi sarcoma (KS) and 2 B cell lymphoproliferative diseases, namely primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KS, PEL, and MCD are largely incurable and poorly understood diseases most common in HIV-infected individuals. Here, we have revealed the role of viral FLICE-inhibitory protein (vFLIP) in the initiation of PEL and MCD by specifically expressing vFLIP at different stages of B cell differentiation in vivo. Mice showed MCD-like abnormalities and immunological defects including lack of germinal centers (GCs), impaired Ig class switching, and affinity maturation. In addition, they showed increased numbers of cells expressing cytoplasmic IgM-λ, a thus far enigmatic feature of the KSHV-infected cells in MCD. B cell-derived tumors arose at high incidence and displayed Ig gene rearrangement with downregulated expression of B cell-associated antigens, which are features of PEL. Interestingly, these tumors exhibited characteristics of transdifferentiation and acquired expression of histiocytic/dendritic cell markers. These results define immunological functions for vFLIP in vivo and reveal what we believe to be a novel viral-mediated tumorigenic mechanism involving B cell reprogramming. Additionally, the robust recapitulation of KSHV-associated diseases in mice provides a model to test inhibitors of vFLIP as potential anticancer agents. 

Retracted: No

PubPeer comments:
 Figure 4c. Much more similar than expected (post-switch and germline). ![file] , 
 I agree with Sceptonia nigra. They are identical. ![file] ,
Propofol suppresses proliferation, migration and invasion of gastric cancer cells via regulating miR-29/MMP-2 axis
Authors: Y-J Ni
J Lu
H-M Zhou
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Propofol; proliferation; migration; invasion; gastric cancer cells
Affiliations: Department of Anesthesiology, The Second Affiliated Hospital of Jiaxing College, Zhejiang, Jiaxing, China.

Abstract:  The article "Propofol suppresses proliferation, migration and invasion of gastric cancer cells via regulating miR-29/MMP-2 axis" by Y.-J. Ni, J. Lu, H.-M. Zhou, published in Eur Rev Med Pharmacol Sci 2019; 23(19): 8606-8615 has been withdrawn. 

Retracted: No

PubPeer comments:
 Figure 3.  Cell apoptosis in Metformin treatment groups (10, 20 and 40 mM) and Control group detected by a flow cytometer. ![file] All the panels contain unexpected repeating constellations of points, and variations in the width of the axes between quadrants, as if they had been re-drawn. Here, 20 and 40 mM panels. ![file] , 
 Dear Hoya Camphorifolia Thank you for pointing out the problem of pictures in our manuscript. We are very sorry about our mistake and we confess that we wrougly used the figures unintentionally. We will check our data and contact the Journal as soon as possible. We deeply apologize to the readership for any incovenience caused. ,
Wound healing activity of the ethanol root extract and polyphenolic rich fraction from Potentilla fulgens
Authors: Damiki Laloo
Anindita Kundu
Narendra K Singh
Ankit Seth
Siva Hemalatha
Gireesh K Singh
Arka Ghosh
Santosh K Maurya
Journal: Pharmaceutical biology (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Antioxidant; HPTLC; collagen; excision wounds; re-pithelialization.
Affiliations: a Ayurvedic Pharmacy Research Laboratory , Rajiv Gandhi South Campus, Banaras Hindu University , Mirzapur , India., b Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.

Abstract:  Context: Potentilla fulgens Wall. ex Hook (Rosaceae) is a potent medicinal plant of the Western Himalayas, where its roots are traditionally used by the local people of Uttaranchal (India) to treat wounds and tiger bites. Objective: The present study scientifically evaluates the wound healing activity of P. fulgens ethanol root extract (EPF) and its ethyl acetate fraction (PFEA) on experimental rats. Materials and methods: Wounds were inflicted on animals by using both excision and incision models. The wounded animals were treated for 16 days with EPF (oral: 200-400 mg/kg and topical: 5-10% w/w) and PFEA (oral: 75 mg/kg; topical: 1.75% w/w). Various physical (wound contraction, epithelialization rate, tensile strength) and biochemical parameters (hydroxyproline, hexosamine, proteins, DNA) were examined during the study. Oxidant product (lipidperoxidase), antioxidant enzymes (catalase, superoxide-dismutase) and reduced glutathione were determined. Morphological and histopathological studies of the skin tissues were monitored. Results: A significant (p &lt; 0.05) wound healing property was observed when the animals were treated topically with EPF (10% w/w) and PFEA (1.75% w/w). A significantly (p &lt; 0.05) increased in the levels of hydroxyproline, hexosamine, protein and DNA up to 59.22, 70.42, 61.01 and 60.00% was observed, respectively. This effect was further demonstrated by the morphological and histopathological representation, thus showing significant (p &lt; 0.05) re-epethelialization on the healing area. EPF and PFEA also showed significant (p &lt; 0.05) antioxidant activity. Conclusions: The present study provided the scientific evidence, where P. fulgens rich in polyphenolic components possess remarkable wound healing activities, thereby supporting the traditional claims. 

Retracted: No

PubPeer comments:
 Figure 3.  Histological section of the skin tissue obtained from the 16th day excision wound model. ... (C) group treated with CMC 0.5% w v, p.o.; (D) group treated with an ointment base (topical) . Please compare the lower sections of (C) and horizontally-flipped (D). ![file] , 
 Meanwhile the upper sections of (C) and (D) are related **without** the horizontal flip. ![file] It is also instructive to compare Figs 3(C) and horizontally-flipped (D) with *[below]* 4(A):  Histological section of the skin tissue obtained from oral treated groups on 16th day excision wound model. (A) Group treated with VTC 200u2009mg kg, p.o. . ![] ,
p65/RelA Modulates BECN1 Transcription and Autophagy
Authors: Francesca Demarchi
Emiliano Dalla
Cosetta Bertoli
Tamara Copetti
Claudio Schneider
Journal: Molecular and Cellular Biology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: autophagy; T-cell homeostasis; NF-kappaB; BECN1; p65/RelA
Affiliations: Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy, Dipartimento di Scienze e Tecnologie Biomediche, Universita’ degli Studi di Udine, p.le Kolbe 4, 33100 Udine, Italy

Abstract:  Recently, autophagy has emerged as a critical process in the control of T-cell homeostasis. Given the pivotal role of NF-kappaB in the signaling events of T cells, we have analyzed and unveiled a conserved NF-kappaB binding site in the promoter of the murine and human BECN1 autophagic gene (Atg6). Accordingly, we demonstrate that the NF-kappaB family member p65/RelA upregulates BECN1 mRNA and protein levels in different cellular systems. Moreover, p65-mediated upregulation of BECN1 is coupled to increased autophagy. The newly identified kappaB site in the BECN1 promoter specifically interacts with p65 both in vitro and in living Jurkat cells upon phorbol myristate acetate (PMA)-ionomycin stimulation, where p65 induction is coupled to BECN1 upregulation and autophagy induction. Finally, anti-CD3- and PMA-ionomycin-mediated activation of T-cell receptor signaling in peripheral T cells from lymph nodes of healthy mice results in an upregulation of BECN1 expression that can be blocked by the NF-kappaB inhibitor BAY 11-7082. Altogether, these data suggest that autophagy could represent a novel route modulated by p65 to regulate cell survival and control T-cell homeostasis. 

Retracted: No

PubPeer comments:
 July 2017 Correction found here: https: mcb.asm.org content 37 16 e00270-17 article-info From the notice:  *Fig. 2B, right: The published actin blot was taken from a different experiment and inserted by mistake. The corrected blot should appear as shown below. This change does not alter the results or conclusions of the study.* Here is how the figure originally appeared. Duplication marked with red boxes and reported to the journal in September 2016. ![file] I thank the authors for correcting this error. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
The Ccr4-not complex and yTAF1 (yTaf(II)130p/yTaf(II)145p) show physical and functional interactions
Authors: Marc Lemaire
Grégory Theiler
Miguel Molinete
Nicole Paquet
Nicole James
Martine A Collart
Cécile Deluen
Laurent Maillet
Journal: Molecular and Cellular Biology (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Saccharomyces cerevisiae; Ccr4-Not complex; transcription regulation; TATA binding protein; Not1p
Affiliations: Département de Biochimie Médicale, CMU, 1211 Geneva 4, Switzerland.

Abstract:  The Saccharomyces cerevisiae Ccr4-Not complex is a global regulator of transcription that is thought to regulate TATA binding protein (TBP) function at certain promoters specifically. In this paper, we show interactions between the essential domain of Not1p, which interacts with Not4p and Not5p, and the N-terminal domain of yTAF1. We isolated a temperature-sensitive nonsense allele of TAF1, taf1-4, which is synthetically lethal at the permissive temperature when combined with not4 and not5 mutants and which produces high levels of a C-terminally truncated yTAF1 derivative. Overexpression of C-terminally truncated yTAF1 is toxic in not4 or not5 mutants, whereas overexpression of full-length yTAF1 suppresses not4. Furthermore, mutations in the autoinhibitory N-terminal TAND domain of yTAF1 suppress not5, and the overexpression of similar mutants does not suppress not4. We find that, like Not5p, yTAF1 acts as a repressor of stress response element-dependent transcription. Finally, we have evidence for stress-regulated occupancy of promoter DNA by Not5p and for Not5p-dependent regulation of yTAF1 association with promoter DNA. Taken together with our finding that Not1p copurifies with glutathione S-transferase-yTaf1 in large complexes, these results provide the first molecular evidence that the Ccr4-Not complex might interact with yTAF1 to regulate its association at promoters, a function that might in turn regulate the autoinhibitory N-terminal domain of yTAF1. 

Retracted: No

PubPeer comments:
 Figure 1A (contrast adjusted). * Red arrows: In the bottom yTAF1 panel, lanes 1 and 3 look very similar * Sharp vertical background transitions are visible between lanes in all four panels. ![file] ,