PReD-Bench/PRed-Bench huggingface dataset:
Glucosyltransferases of Viridans Group Streptococci Modulate Interleukin-6 and Adhesion Molecule Expression in Endothelial Cells and Augment Monocytic Cell Adherence
Authors: Jean-San Chia
Chiou-Yueh Yeh
Jen-Yang Chen
Journal: Infection and Immunity (2006)
Discipline: IMMUNOLOGY
Keywords: Recruitment; Monocytes; Vegetation formation; Endocardial inflammation; Infective endocarditis
Affiliations: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, National Health Research Institute, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan, Republic of China

Abstract:  Recruitment of monocytes plays important roles during vegetation formation and endocardial inflammation in the pathogenesis of infective endocarditis (IE). Bacterial antigens or modulins can activate endothelial cells through the expression of cytokines or adhesion molecules and modulate the recruitment of leukocytes. We hypothesized that glucosyltransferases (GTFs), modulins of viridans group streptococci, may act directly to up-regulate the expression of adhesion molecules and also interleukin-6 (IL-6) to augment monocyte attachment to endothelial cells. Using primary cultured human umbilical vein endothelial cells (HUVECs) as an in vitro model, we demonstrated that GTFs (in the cell-bound or free form) could specifically modulate the expression of IL-6, and also adhesion molecules, in a dose- and time-dependent manner. Results of inhibition assays suggested that enhanced expression of adhesion molecules was dependent on the activation of nuclear factor kappaB (NF-kappaB) and extracellular signal-regulated kinase and that p38 mitogen-activated protein kinase pathways also contributed to the release of IL-6. Streptococcus-infected HUVECs or treatment with purified IL-6 plus soluble IL-6 receptor alpha enhanced the expression of ICAM-1 and the adherence of the monocytic cell line U937. These results suggest that streptococcal GTFs might play an important role in recruiting monocytic cells during inflammation in IE through induction of adhesion molecules and IL-6, a cytokine involved in transition from neutrophil to monocyte recruitment. 

Retracted: No

PubPeer comments:
 Could the authors please check an unexpected similarity between the  GS-5 GAPDH lanes in Figure 2D and the  rGTFC GAPDH lanes in Figure 3A? Marked here with red boxes. ![file] ,
1, 25(OH)2 D3 Induces Reactivation and Death of Kaposi’s Sarcoma-Associated Herpesvirus of Primary Effusion Lymphoma cells
Authors: Sushil Kumar Sahu
Amit Kumar
Suchitra Mohanty
Piyanki Das
Shanmugam Rajasubramaniam
Tathagata Choudhuri
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Kaposi's sarcoma associated herpesvirus; KSHV; 1, 25(OH)2 D3; PEL cells; apoptosis

Abstract:  Kaposi's sarcoma associated herpesvirus (KSHV) a gammaherpesvirus establishes perennial latency in the host with periodic reactivation. Occasionally change in the physiological condition like hypoxia, host cell differentiation can trigger the lytic switch and reactivation of the virus. The biologically active form of 1, 25(OH)2 D3 plays a critical role in the regulation of various physiological processes (e.g. regulation of mineral homeostasis and control of bone metabolism). Apart from its role in host physiology, 1, 25(OH)2 D3 has been implicated as a potential agent for the prevention and/or treatment of many a tumors. Here we show that 1, 25(OH)2 D3 induces both death of Kaposi sarcoma associated herpesvirus infected PEL cells and KSHV replication. 1, 25(OH)2 D3 mediated inhibition of proliferation was associated with apoptosis of the PEL cells, and virus reactivation. In addition, p38 signalling is required for KSHV reactivation. Furthermore, treatment of PEL cells with p38 inhibitor abrogated the expression of ORF57, thus blocking lytic switch. Furthermore, silencing of VDR resulted in reduced ORF57 expression compared to the control cells, signifying the potential role of 1, 25(OH)2 D3 in KSHV reactivation. Thus, our studies have revealed a novel role of 1, 25(OH)2 D3 in the regulation of KSHV reactivation and PEL cell death. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than you would expect. https: imgur.com QDyklw2 ,
The effect of reiki on pain: A meta-analysis
Authors: Melike Demir Doğan
Journal: Complementary Therapies in Clinical Practice (2018)
Discipline: CLINICAL MEDICINE
Keywords: Meta-analysis; Pain; Reiki.
Affiliations: Gümüşhane University, Faculty of Health Sciences, Gümüşhane, Bağlarbaşı Mahallesi 29100, Turkey. Electronic address: .

Abstract:  Objective: Pain is one of the most common symptoms and may lead to important psychological, mental, and physiological problems in individuals. According to data by The Center for Reiki Research, Reiki is an effective approach to decrease the levels of pain, depression, and anxiety. Therefore, the aim of this meta-analysis was to investigate the effect of Reiki on pain level. Methods: Randomized controlled clinical trials in databases of Pubmed, ISI Web of Sciences, and Google Scholar were investigated. 4 randomized controlled studies involving 212 participants were included in the meta-analysis. Results: The result obtained after the final Reiki application was evaluated in VAS pain score. When Reiki (n = 104) group was compared with control group (n = 108), standardized mean difference was observed to be -0.927 (95% CI: -1.867 to 0.0124). Reiki was observed to cause a statistically significant decrease in VAS score. Conclusion: Consequently, this meta-analysis revealed that Reiki was an effective approach in relieving the pain. 

Retracted: No

PubPeer comments:
 1.  Our use of plasmids instead of adeno-associated viruses [37] (AAV) may have further limited the efficiency of genetic correction. 2.  While there were no adverse effects, clear benefits were not seen ... AAV would improve efficiency, but it [integrates significantly] . Unfortunately so would the [Cas9 TALEN ZFN] - even if one uses plasmid as they have done here. Unfortunately, they have not done sequencing. How would one get past this delivery issue? It is unacceptable to have humans expressing Cas9. ,
Distributed coding of choice, action and engagement across the mouse brain
Authors: Kenneth D Harris
Nicholas A Steinmetz
Peter Zatka-Haas
Matteo Carandini
Journal: Nature (2019)
Discipline: Multidisciplinary
Keywords: Neuronal activity; Brain regions; Neuropixels probes; Visual discrimination task; Neocortex
Affiliations: Institute of Ophthalmology, University College London, London, UK. ., Department of Biological Structure, University of Washington, Seattle, WA, USA. ., Institute of Neurology, University College London, London, UK., Institute of Ophthalmology, University College London, London, UK.

Abstract:  Vision, choice, action and behavioural engagement arise from neuronal activity that may be distributed across brain regions. Here we delineate the spatial distribution of neurons underlying these processes. We used Neuropixels probes1,2 to record from approximately 30,000 neurons in 42 brain regions of mice performing a visual discrimination task3. Neurons in nearly all regions responded non-specifically when the mouse initiated an action. By contrast, neurons encoding visual stimuli and upcoming choices occupied restricted regions in the neocortex, basal ganglia and midbrain. Choice signals were rare and emerged with indistinguishable timing across regions. Midbrain neurons were activated before contralateral choices and were suppressed before ipsilateral choices, whereas forebrain neurons could prefer either side. Brain-wide pre-stimulus activity predicted engagement in individual trials and in the overall task, with enhanced subcortical but suppressed neocortical activity during engagement. These results reveal organizing principles for the distribution of neurons encoding behaviourally relevant variables across the mouse brain. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar and different than expected. ![file] , 
 Figure 3 continued. Much more similar and different. ![file] ,
MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation
Authors: Bing Lim
Yvonne Tay
Isidore Rigoutsos
Jinqiu Zhang
Andrew M Thomson
Journal: Nature (2008)
Discipline: Multidisciplinary
Keywords: MicroRNAs; mRNA degradation; mRNA translation; Nanog; Oct4

Abstract:  MicroRNAs (miRNAs) are short RNAs that direct messenger RNA degradation or disrupt mRNA translation in a sequence-dependent manner. For more than a decade, attempts to study the interaction of miRNAs with their targets were confined to the 3' untranslated regions of mRNAs, fuelling an underlying assumption that these regions are the principal recipients of miRNA activity. Here we focus on the mouse Nanog, Oct4 (also known as Pou5f1) and Sox2 genes and demonstrate the existence of many naturally occurring miRNA targets in their amino acid coding sequence (CDS). Some of the mouse targets analysed do not contain the miRNA seed, whereas others span exon-exon junctions or are not conserved in the human and rhesus genomes. miR-134, miR-296 and miR-470, upregulated on retinoic-acid-induced differentiation of mouse embryonic stem cells, target the CDS of each transcription factor in various combinations, leading to transcriptional and morphological changes characteristic of differentiating mouse embryonic stem cells, and resulting in a new phenotype. Silent mutations at the predicted targets abolish miRNA activity, prevent the downregulation of the corresponding genes and delay the induced phenotype. Our findings demonstrate the abundance of CDS-located miRNA targets, some of which can be species-specific, and support an augmented model whereby animal miRNAs exercise their control on mRNAs through targets that can reside beyond the 3' untranslated region. 

Retracted: No

PubPeer comments:
 2009 Corrigendum for an error in Figure 3A: https: www.nature.com articles nature07880.pdf  In this Letter, an incorrect micrograph was inadvertently used in the panel entitled u2018Nanog-WT 1 Scru2019 in row 1 of Fig. 3a: the used micrograph was from a different field of view from the u2018EV 1 Scru2019 experiment. A representative micrograph from the u2018Nanog-WT 1 Scru2019 experiment is presented below. This oversight affects neither the data nor the conclusions of the work presented in the manuscript. Here is the original Figure 3A, with the duplication marked in blue. ![file] , 
 A reader was wondering about similar Western blot panels between Figure 1 and 2. I have marked them here with boxes of the same color. It looks as if in most cases the experiments might have been the same, but the reader was not sure. Could the authors please clarify? The experiments were performed in triplicate, so there should have been other sets of Western blots. ![file] ,
Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon
Authors: Awesh K Yadav
Govind P Agrawal
Narendra K Jain
Gopal Rai
Journal: Drug Delivery (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Colon cancer; dextran microspheres; dextranase; organ distribution; pH-sensitive polymers.
Affiliations: a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , Madhya Pradesh , India.

Abstract:  Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes. 

Retracted: No

PubPeer comments:
 Figure 1.  Scanning electron photomicrographs of crosslinked dextran microspheres. ![file] Figure 1 from [Sudheesh et al (2011)] .  SEM image showing spherical morphology of TT loaded AGNPs. ![file] How to explain the common elements, while also explaining the differences? There are no authors in common between the two papers, although the institution is the same. ,
Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFβ-Induced EMT in Ovarian Cancer
Authors: Fangfang Tao
Wenhong Liu
Minhe Shen
Libin Wang
Shanming Ruan
Yang Xiong
Journal: PLoS ONE (2016)
Discipline: Multidisciplinary
Keywords: fuling granule; ovarian cancer; microarray analysis; cell cycle; epithelial-mesenchymal transition (EMT)
Affiliations: Department of Immunology and Microbiology, Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China., Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China., Institute of Stem Cell Research, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China., School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Abstract:  The compound fuling granule (CFG) is a traditional Chinese drug which has been used to treat ovarian cancer in China for over twenty years. Nevertheless, the underlying molecular mechanism of its anti-cancer effect remains unclear. In this study, microarray data analysis was performed to search differentially expressed genes in CFG-treated ovarian cancer cells. Several cell cycle and epithelial-mesenchymal transition (EMT) related genes were identified. The microarray analyses also revealed that CFG potentially regulates EMT in ovarian cancer. We also found that, functionally, CFG significantly suppresses ovarian cancer cell proliferation by cell cycle arrest, apoptosis and senescence and the AKT/GSK-3β pathway is possibly involved. Additionally, the invasion and migration ability of ovarian cancer induced by TGFβ is significantly suppressed by CFG. In conclusion, our results demonstrated that CFG suppresses ovarian cancer cell proliferation as well as TGFβ1-induced EMT in vitro. Finally, we discovered that CFG suppresses tumor growth and distant metastasis in vivo. Overall, these findings provide helpful clues to design novel clinical treatments against cancer. 

Retracted: No

PubPeer comments:
 Figure 6 appears to have a repeated image. *** ![file] ,
Hyperoxia and interferon-γ-induced injury in developing lungs occur via cyclooxygenase-2 and the endoplasmic reticulum stress-dependent pathway
Authors: Cecilia Janér
Mansoor A Syed
Gloria Pryhuber
Robert J Homer
Vineet Bhandari
Rayman Choo-Wing
Brianne Bowen
Sture Andersson
Anantha Harijith
Journal: American Journal of Respiratory Cell and Molecular Biology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cox2; ER stress pathway; hyperoxia; IFN-γ; alveolarization
Affiliations: Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract:  We noted a marked increase in cyclooxygenase-2 (Cox2) and the activation of the endoplasmic reticulum (ER) stress pathway in newborn murine lung on exposure to hyperoxia and IFN-γ. We sought to evaluate Cox2-mediated ER stress pathway activation in hyperoxia-induced and IFN-γ-mediated injury in developing lungs. We applied in vivo genetic gain-of-function and genetic/chemical inhibition, as well as in vitro loss-of-function genetic strategies. Hyperoxia-induced and IFN-γ-mediated impaired alveolarization was rescued by Cox2 inhibition, using celecoxib. The use of small interfering RNA against the ER stress pathway mediator, the C/EBP homologous protein (CHOP; also known as growth arrest and DNA damage-inducible gene 153/GADD153), alleviated cell death in alveolar epithelial cells as well as in hyperoxia-induced and IFN-γ-mediated murine models of bronchopulmonary dysplasia (BPD). In addition, CHOP siRNA also restored alveolarization in the in vivo models. Furthermore, as evidence of clinical relevance, we show increased concentrations of Cox2 and ER stress pathway mediators in human lungs with BPD. Cox2, via CHOP, may significantly contribute to the final common pathway of hyperoxia-induced and IFN-γ-mediated injury in developing lungs and human BPD. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than expected. https: imgur.com j7VnZYC , 
 Figure 4C. Much more similar than expected. https: imgur.com oMXG1fF ,
Geldanamycin inhibits tyrosine phosphorylation-dependent NF-kappaB activation
Authors: Julie Crèvecoeur
Geoffrey Gloire
Marie-Paule Merville
Jacques Piette
Journal: Biochemical Pharmacology (2008)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Hsp90; NF-kappaB pathway; geldanamycin; IKK complex; IkappaBalpha phosphorylation
Affiliations: GIGA-Research, University of Liège, B-4000 Liège, Belgium.

Abstract:  Hsp90 is a protein chaperone regulating the stability and activity of many signalling molecules. The requirement of Hsp90 activity in the NF-kappaB pathway has been recently reported by several authors using the Hsp90 ATPase inhibitor geldanamycin (GA), an anti-tumor drug. Hsp90 inhibition blocks the synthesis and activation of the IKK complex, the major kinases complex responsible for IkappaBalpha phosphorylation on serine 32 and 36, a key step for its degradation and the nuclear translocation of NF-kappaB. However, the effect of GA on other IkappaBalpha kinases, including tyrosine kinases, is unknown. In the present study, we investigated the effect of GA on NF-kappaB activation induced by sodium pervanadate (PV), a tyrosine phosphatase inhibitor triggering c-Src-mediated tyrosine phosphorylation of IkappaBalpha. We report for the first time that GA inhibits PV-induced IkappaBalpha tyrosine phosphorylation and degradation. Using an in vitro kinase assay, we demonstrated that GA inhibits the activity of c-Src as an IkappaBalpha tyrosine kinase, but not its cellular expression. As a result, GA blocked PV-induced NF-kappaB DNA-binding activity on an exogenous kappaB element and on the endogenous ikappabalpha promoter, thereby inhibiting ikappabalpha transcription. Finally, we demonstrated that, despite NF-kappaB inhibition, pre-treatment with GA does not potentiate PV-induced apoptosis. We conclude that c-Src requires Hsp90 for its tyrosine kinase activity, and its inhibition by GA blocks c-Src-dependent signalling pathways, such as NF-kappaB activation induced by sodium pervanadate. The effect of GA on PV-induced apoptosis is discussed in the light of recent publications in the literature. 

Retracted: No

PubPeer comments:
 Figures 4(A) and 4(C). Much more similar than expected (different cell types). Much more similar after 180 degree rotation. https: imgur.com 9pHFptj ,
The efficacy of trans-esophageal echocardiography in treatment of nonvalvular atrial fibrillation with left atrial appendage occlusion
Authors: S-C Qin
X-L Wang
K Chen
R-F Zhang
Z-M Jiang
Y Liuang
X Fu
Y Liu
Y Song
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: transesophageal echocardiography; nonvalvular atrial fibrillation; left atrial appendage occlusion; 2D-TEE; 3D-TEE
Affiliations: Departments of Ultrasonography, Cardiology and Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China. Zhangruifang999@hotmail.

Abstract:  Objective: To investigate the efficacy of transesophageal echocardiography (TEE) in the treatment of nonvalvular atrial fibrillation with left atrial appendage (LAA) occlusion. Patients and methods: Forty-nine patients with nonvalvular atrial fibrillation were selected from January 2015 to December 2015 to serve as control group, and 49 patients with nonvalvular atrial fibrillation were selected from January 2016 to December 2016 to serve as observation group. Patients in both groups were treated with LAA occlusion. After surgery, patients in control group received 2D-transesophageal echocardiography (2D-TEE), while patients in observation group received 3D-TEE. LAA diameter, maximum depth, postoperative parameters, and postoperative complications were compared between two groups. Results: The maximum LAA diameter can be measured from different angles in control group, and maximum depth cannot be measured in control group. No significant differences in maximum LAA diameter and maximum depth were found between two groups from different angles (p&lt;0.05). No significant difference in left ventricular end diastolic diameter (LVEDd), left atrial diameter (LA-d), left ventricular ejection fraction (LVEF), mitral regurgitation volume (MV Reg V), E peak and pulmonary vein diastolic flow velocity (PVd) were found between those two groups (p&lt;0.05). The overall occurrence of postoperative complications in observation group and control group were 0.00% and 12.24%, respectively, significant difference was found between those two groups (p&lt;0.05). Conclusions: Compared with 2D-TEE, the application of 3D-TEE in treatment of nonvalvular atrial fibrillation with left atrial appendage occlusion is more conducive to the selection of the size of the reservoir, and can reduce the occurrence of postoperative complications. 

Retracted: Yes

PubPeer comments:
 This August 2018 article has been withdrawn in December 2018. The original paper PDF has been removed from the journal s website. ,
Oxytocin increases trust in humans
Authors: Urs Fischbacher
Ernst Fehr
Markus Heinrichs
Paul J Zak
Michael Kosfeld
Journal: Nature (2005)
Discipline: Multidisciplinary
Keywords: Trust; Oxytocin; Social interactions; Neuropeptide; Prosocial behavior
Affiliations: University of Zurich, Institute for Empirical Research in Economics, Blumlisalpstrasse 10, CH-8006 Zurich, Switzerland.

Abstract:  Trust pervades human societies. Trust is indispensable in friendship, love, families and organizations, and plays a key role in economic exchange and politics. In the absence of trust among trading partners, market transactions break down. In the absence of trust in a country's institutions and leaders, political legitimacy breaks down. Much recent evidence indicates that trust contributes to economic, political and social success. Little is known, however, about the biological basis of trust among humans. Here we show that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions. We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks. On the contrary, oxytocin specifically affects an individual's willingness to accept social risks arising through interpersonal interactions. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour. 

Retracted: No

PubPeer comments:
 Readers should become aware of a Replication Study recently published in Nature Human Behaviour entitled  A registered replication study on oxytocin and trust From the Abstract:  In an influential paper, Kosfeld et al. (2005) showed that intranasal administration of oxytocin (OT) increases the transfers made by investors in the trust gameu2014suggesting that OT increases trust in strangers. Subsequent studies investigating the role of OT in the trust game found inconclusive effects on the trusting behaviour of investors but these studies deviated from the Kosfeld et al. study in an important wayu2014they did not implement minimal social contact (MSC) between the investors and the trustees in the trust game. **Here, we performed a large double-blind and placebo-controlled replication study of the effects of OT on trusting behaviour that yields a power of more than 95% and implements an MSC condition as well as a no-social-contact (NoC) condition. We find no effect of OT on trusting behaviour in the MSC condition. Exploratory post hoc analyses suggest that OT may increase trust in individuals with a low disposition to trust in the NoC condition, but this finding requires confirmation in future research.** , 
 There was a good overview of how the 2005 Kosfeld paper has not stood up to replication over time and the challenge of getting that information out from the [ Statistical Modeling, Causal Inference, and Social Science blog] . A challenge that perhaps services like PubPeer will help rectify. ,
First flight of ion-drive aircraft
Journal: Nature (2018)
Discipline: Multidisciplinary
Keywords: Technology.

Abstract: A remarkable machine propelled by ionic wind could signal a future with cleaner aeroplanes. A remarkable machine propelled by ionic wind could signal a future with cleaner aeroplanes.

Retracted: No

PubPeer comments:
 This is *not* the first flight of an ion-drive aircraft. Seversky was patenting and flying ionocraft [in the 1960s] , hobbyists have been building them for decades under the name  lifter , and a self-contained device that carries its own power supply was developed by Ethan Krauss in 2006. MIT s device may be the first ionocraft *to use wings for lift*, however. The previous devices behaved more like helicopters than airplanes, and did not need wings to stay aloft. ,
Retracted : Ras‐PI3K‐AKT signaling promotes the occurrence and development of uveal melanoma by downregulating H3K56ac expression
Authors: Dajun Sun
Weixuan Sun
Yaping Li
Dexin Yin
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: GCN5; H3K56ac; MDM2; Ras-PI3K-AKT; SIRT1
Affiliations: Department of Ophthalmology The Second Hospital of Jilin University Changchun Jilin China, Department of Vascular Surgery China–Japan Union Hospital of Jilin University Changchun Jilin China, Department of Gastrointestinal Colorectal and Anal Surgery China–Japan Union Hospital of Jilin University Changchun Jilin China

Abstract:  Background: Uveal melanoma (UM) is an intraocular malignant tumor characterized by rapid progression and recurrence. The current conventional treatments are unsatisfactory. Histone acetylation at H3 lysine 56 (H3K56ac) has been reported to be a tumor suppressor in breast cancer. However, whether H3K56ac prevents the occurrence and development of UM remains uninvestigated. The study aimed to explore the regulatory effect of H3K56ac on Ras-PI3K-AKT induced UM cells proliferation and migration. Methods: The vectors of pEGFP-RasWT , pEGFP-K-Ras G12V/Y40C , and pEGFP-N1 were transfected into MP46 cells, and protein levels of phosphorylated AKT Ser473 and H3K56ac were examined using western blot analysis. The effect of H3K56ac on cell proliferation and migration were studied using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, colony formation, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and chromatin immunoprecipitation assays were performed to determine the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) downstream genes. Further, the regulatory effects of silent mating type information regulation 2 homolog-1 (SIRT1), general control nonderepressible 5 (GCN5), and mouse double minute 2 homolog (MDM2) on Ras-PI3K-AKT affected H3K56ac expression were also investigated. Results: H3K56ac expression was specifically downregulated by Ras-PI3K-AKT activation pathway. H3K56ac inhibited the tumorigenic effect of Ras-PI3K-AKT on MP46 cells viability, colony formation, and migration, as well as participated in regulating the transcription of PI3K/AKT downstream genes. SIRT1 silence recovered H3K56ac expression, and reversed the tumorigenic effect of Ras-PI3K-AKT activation on MP46 cells. Downregulation of H3K56ac induced by Ras-PI3K-AKT activation was found to be associated with MDM2-mediated the degradation of GCN5. Conclusions: The results demonstrated that Ras-PI3K-AKT signaling promoted UM cells proliferation and migration via downregulation of H3K56ac expression, which might be related to MDM2-mediated the degradation of GCN5. 

Retracted: Yes

PubPeer comments:
 This paper uses the MDA-MB-435 cell line as a model of metastatic breast cancer. But it has long been shown that it is a melanoma cell line as it is derives through contamination from the M14 cell line. See: * [The relevant Cellosaurus entry] * [The paper that provides definitive proof of the contamination] ,
Overexpression of pyruvate dehydrogenase kinase 1 in retinoblastoma: A potential therapeutic opportunity for targeting vitreous seeds and hypoxic regions
Authors: Mamatha M Reddy
Swatishree Sradhanjali
Suryasnata Rath
Ruchi Mittal
Devjyoti Tripathy
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Pyruvate dehydrogenase kinase 1; PDK1; retinoblastoma; cell growth; migration
Affiliations: The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Bhubaneswar, India., School of Biotechnology, KIIT University, Bhubaneswar, India., Ophthalmic Plastics, Orbit and Ocular Oncology Services, L V Prasad Eye Institute, Bhubaneswar, India., Dalmia Ophthalmic Pathology Services, LV Prasad Eye Institute, Bhubaneswar, India.

Abstract:  Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic reprogramming of tumors, is induced in several tumors including glioblastoma, breast cancer and melanoma. However, the role played by PDK1 is not studied in retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in RB clinical samples, and studied its inhibition as a strategy to decrease cell growth and migration. We show that PDK1 is specifically overexpressed in RB patient samples especially in vitreous seeds and hypoxic regions and cell lines compared to control retina using immunohistochemistry and real-time PCR. Our results further demonstrate that inhibition of PDK1 using small molecule inhibitors dichloroacetic acid (DCA) and dichloroacetophenone (DAP) resulted in reduced cell growth and increased apoptosis. We also confirm that combination treatment of DCA with chemotherapeutic agent carboplatin further enhanced the therapeutic efficacy compared to single drug treatment. In addition, we observed changes in glucose uptake, lactate and reactive oxygen species (ROS) levels as well as decreased cell migration in response to PDK1 inhibition. Additionally, we show that DCA treatment led to inhibition of PI3K/Akt pathway and reduction in PDK1 protein levels. Overall, our data suggest that targeting PDK1 could be a novel therapeutic strategy for RB. 

Retracted: No

PubPeer comments:
 The scratch assay images in Figure 4 feature multiple image duplications. ![file] Orange, green and pink boxes would all seem to be different croppings of the same image. However, the right hand side and middle of the scratch changes between the pink and the orange boxes. ![file] Do the authors have an explanation as to what might have gone wrong here? , 
 I noticed another duplication as I was uploading. ![file] , 
 Thank you for pointing this out. We acknowledge it. This is an oversight. We should have avoided. The error crept in while naming the cropped images of the panels. Two overlapping images from the same treatment were labeled as two different treatments. We looked at the original images and prepared a corrected figure. The correction in the figure does not alter inferences from the figure nor the overall conclusions of the study. Corrected figure is below.![file] ,
Type I Interferon Regulates the Survival and Functionality of B Cells in Rainbow Trout
Authors: Christopher J Secombes
Ottavia Benedicenti
Tiehui Wang
Irene Soleto
Esther Morel
Carolina Tafalla
Patricia Díaz-Rosales
Journal: Frontiers in Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: B cells; IgM; interferon (IFN); phagocytosis; teleost fish.
Affiliations: Animal Health Research Center (CISA-INIA), Madrid, Spain., Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom.

Abstract:  Interferons (IFNs) orchestrate antiviral responses in jawed vertebrates and can be classified into three types based on different aspects of their genomic organization, structure and receptors through which they signal and function. Generally, type I and type III IFNs include cytokines that directly induce an antiviral response, whereas type II IFNs are well-known for their immunomodulatory role during viral infections. In mammals, type I IFNs have been shown to also regulate many aspects of B cell development and differentiation. Yet, these functions have been only faintly investigated for teleost IFNs. Thus, in the current study, we have examined the effects of a model type I rainbow trout IFN molecule (IFNa) on blood naïve (IgM+IgD+) B cells, comparing them to those exerted by type II IFN (IFNγ). Our results demonstrate that IFNa increases the survival of naïve rainbow trout B cells, in the absence of lymphoproliferative effects, by rescuing them from spontaneous apoptosis. Additionally, IFNa increased the phagocytic capacity of blood IgM+IgD+ B cells and augmented the number of IgM-secreting cells in blood leukocyte cultures. IFNγ, on the other hand, had only minor effects up-regulating IgM secretion, whereas it increased the phagocytic capacity of IgM- cells in the cultures. Finally, given the recent identification of 9 mx genes in rainbow trout, we have also established which of these genes were transcriptionally regulated in blood naïve B cells in response to IFNa. This study points to a previously undescribed role for teleost type I IFNs in the regulation of B cell responses. 

Retracted: No

PubPeer comments:
 Let $$mu_1=(0.8, 0.2, 0)$$ $$mu_2=(0, 1, 0)$$ According to Definition 2, $$mu_1cup mu_2 = (0.8, 0.2, 0)$$ $$mu_1cap mu_2 = (0, 0.2, 0)$$ Consequently, **eq(5) in Theorem 1 does not hold according to Definition 7.** The proof presented in this paper is nonsensical. ![file] ![file] ![file] , 
 Provide complete calculation of your statement? verify it by giving detail calculation. , 
 #2 Enough information has been provided. The calculation is simple for the provided example because most terms in eq(6) will cancel out to reach the invalidity of (5) in Theorem 1. Are you willing to defend your theory by demonstrating the details? ,
A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine lung tumors
Authors: Elisabeth Brambilla
Galina Merdzhanova
Beatrice Eymin
Sylvie Gazzeri
Valerie Edmond
Stephanie Gout
Journal: Cell Cycle (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AKT; E2F1; SRSF2; cellular proliferation; neuroendocrine lung tumors
Affiliations: INSERM, U823, Equipe 2 Bases Moléculaires de la Progression des Cancers du Poumon, Grenoble, France.

Abstract:  The transcription factor E2F1 belongs to the E2F family and plays a crucial role during cell cycle progression and apoptosis. Ser/Arg-Rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. We previously identified the SR protein SRSF2 as a new transcriptional target of E2F1 and demonstrated that both proteins cooperate to induce apoptosis in non-small cell lung carcinoma. In this study, we postulated that SRSF2 is also involved in the proliferative functions of E2F1. Using IHC, we first demonstrate that SRSF2 and its phosphorylated form (P-SRSF2) are overexpressed in neuroendocrine lung tumors that are highly proliferative tumors expressing high levels of E2F1. Importantly, we show a direct correlation between cyclin E, an E2F1-target gene controlling S phase, and P-SRSF2 proteins levels (p = 0.0083), suggesting a role of SRSF2 in E2F1-mediated cellular proliferation. Accordingly, using neuroendocrine lung carcinoma cell lines, we demonstrate that SRSF2 is a cell cycle-regulated protein involved in entry and progression into S phase. We also provide evidence that SRSF2 interacts with E2F1 and stimulates its transcriptional control of cell cycle target genes such as cyclin E. Finally, we show that inhibition of AKT signaling pathway prevents SRSF2 phosphorylation and activity toward E2F1 transcriptional function. Taken together, these results identify a new role of SRSF2 in the control of cell cycle progression and reinforce the functional link between SRSF2 and E2F1 proteins. 

Retracted: No

PubPeer comments:
 Figure 4C. Lower 2 panels. https: imgur.com 58s1BwE ,
PUMA Cooperates with p21 to Regulate Mammary Epithelial Morphogenesis and Epithelial-To-Mesenchymal Transition
Authors: Xinbin Chen
Yong Sam Jung
Wensheng Yan
Yanhong Zhang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Lumen formation; mammary morphogenesis; p53; p73; PUMA
Affiliations: Comparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California Davis, Davis, California, United State of America.

Abstract:  Lumen formation is essential for mammary morphogenesis and requires proliferative suppression and apoptotic clearance of the inner cells within developing acini. Previously, we showed that knockdown of p53 or p73 leads to aberrant mammary acinus formation accompanied with decreased expression of p53 family targets PUMA and p21, suggesting that PUMA, an inducer of apoptosis, and p21, an inducer of cell cycle arrest, directly regulate mammary morphogenesis. To address this, we generated multiple MCF10A cell lines in which PUMA, p21, or both were stably knocked down. We found that morphogenesis of MCF10A cells was altered modestly by knockdown of either PUMA or p21 alone but markedly by knockdown of both PUMA and p21. Moreover, we found that knockdown of PUMA and p21 leads to loss of E-cadherin expression along with increased expression of epithelial-to-mesenchymal transition (EMT) markers. Interestingly, we found that knockdown of ΔNp73, which antagonizes the ability of wide-type p53 and TA isoform of p73 to regulate PUMA and p21, mitigates the abnormal morphogenesis and EMT induced by knockdown of PUMA or p21. Together, our data suggest that PUMA cooperates with p21 to regulate normal acinus formation and EMT. 

Retracted: No

PubPeer comments:
 Figure 6 - could the authors please check? * Red boxes: The Delta-Np73 panels in Figure 6B and 6E appear to look similar. ![file] , 
 Dear Dr. Bik, Thank you very much for alerting us about the Figures in our PLoS ONE paper. We have been aware of this issue for some time and a correction had been sent to PLoS ONE Senior Publications Assistant to solve this issue. Best regards, , 
 Dear Dr. Bik, A correction was published last week by PLOS ONE . Thank you very much for alerting us about the figure. Warm regards, , 
 Thank you Dr. Chen, for correcting the paper. Much appreciated. ,
Evaluation of the toxicity of iron-ion irradiation in murine bone marrow dendritic cells via increasing the expression of indoleamine 2,3-dioxygenase 1
Authors: Yan-Shan Zhang
Hong Zhang
Yan-Cheng Ye
Hong-Yan Li
Jing-Yi Ma
Jun-Fang Yan
Yi Xie
Journal: Toxicology Research (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: High linear energy transfer radiation; toxicity; immunosuppression; irradiation; dendritic cells
Affiliations: Institute of Modern Physics, School of Pharmaceutical Sciences, Gansu Wuwei Tumor Hospital

Abstract:  High linear energy transfer radiation is known to deposit higher energy in tissues and cause greater toxicity compared to low-LET irradiation. Local immunosuppression is frequently observed after irradiation (IR). Dendritic cells (DCs) play important roles in the initiation and maintenance of the immune response. The dysfunction of DCs contributes to tumor evasion and growth. However, molecular mechanisms underlying the establishment of immune tolerance induced by heavy ion IR through this DC population are poorly understood. Therefore, here we report our findings on the dysfunction of bone marrow-derived dendritic cells (BMDCs) induced by 1 Gy iron ion radiation and promotions of expressions of JNK1/2/3, indoleamine 2,3-dioxygenase 1 (IDO1), p-ERK1/2 and p38/MAPK; and decrease of IDO2, MHC class II, CD40, CD80 expressions and IFN-γ and TNF-α secretion after total-body IR in mice. JNK+IDO1+ BMDCs showed up-expression of p-ERK1/2 and p-p38/MAPK, reduced expression of MHC class II and CD80, and were not able to effectively stimulate allogeneic spleen T cells. The inhibition of IDO1 expressions could partly restore the function of BMDCs. In all, our study shows that elevated JNK and IDO1 expression induced by Fe ion IR could result in dysfunction of BMDCs via p-p38/MAPK and p-ERK1/2 signal pathway, and it may represent a new mechanism in radiation-induced immune tolerance. 

Retracted: No

PubPeer comments:
 ![file] Can you explain why the figures are similar in fig5c? ,
Transcription regulation of HYPK by Heat Shock Factor 1
Authors: Nitai Pada Bhattacharyya
Srijit Das
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: HYPK; Huntingtin; chaperone-like activity; aggregate formation; toxicity
Affiliations: Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India.

Abstract:  HYPK (Huntingtin Yeast Partner K) was originally identified by yeast two-hybrid assay as an interactor of Huntingtin, the protein mutated in Huntington's disease. HYPK was characterized earlier as an intrinsically unstructured protein having chaperone-like activity in vitro and in vivo. HYPK has the ability of reducing rate of aggregate formation and subsequent toxicity caused by mutant Huntingtin. Further investigation revealed that HYPK is involved in diverse cellular processes and required for normal functioning of cells. In this study we observed that hyperthermia increases HYPK expression in human and mouse cells in culture. Expression of exogenous Heat Shock Factor 1 (HSF1), upon heat treatment could induce HYPK expression, whereas HSF1 knockdown reduced endogenous as well as heat-induced HYPK expression. Putative HSF1-binding site present in the promoter of human HYPK gene was identified and validated by reporter assay. Chromatin immunoprecipitation revealed in vivo interaction of HSF1 and RNA polymerase II with HYPK promoter sequence. Additionally, acetylation of histone H4, a known epigenetic marker of inducible HSF1 binding, was observed in response to heat shock in HYPK gene promoter. Overexpression of HYPK inhibited cells from lethal heat-induced death whereas knockdown of HYPK made the cells susceptible to lethal heat shock-induced death. Apart from elevated temperature, HYPK was also upregulated by hypoxia and proteasome inhibition, two other forms of cellular stress. We concluded that chaperone-like protein HYPK is induced by cellular stress and under transcriptional regulation of HSF1. 

Retracted: No

PubPeer comments:
 Concern about Figure 2, reported to the journal in October 2015. * Red boxes: The left and right AcH4 panels look very similar. Could the authors please clarify if these were two different sets of samples? ![file] ,
CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation
Authors: Stéphane Romano
Estelle Escudier
Joëlle Roume
Sylvie Odent
Marion Gérard
Férechté Encha-Razavi
Soumaya Mougou-Zerelli
Emmanuelle Szenker
Nathalie Boddaert
Sophie Saunier
Ali Saad
Jeanne Amiel
Marie Gonzales
Tania Attié-Bitach
Enza Maria Valente
Bruno Leheup
Sophie Audollent
Suonavy Khung
Chantal Esculpavit
Marie-Pierre Cordier
Anne-Lise Delezoide
Michel Vekemans
Sophie Thomas
Sophie Patrier
Arnold Munnich
Nadia Elkhartoufi
Raymonde Bouvier
Rémi Salomon
Jéléna Martinovic
Marie-Claire Gubler
Candice Babarit
Philippe Loget
Journal: Human Mutation (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Meckel-Gruber syndrome; Joubert syndrome; ciliopathies; autosomal recessive; TMEM67
Affiliations: INSERM U-781, Hôpital Necker-Enfants Malades, Paris, France.

Abstract:  Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, a brain malformation that is usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert syndrome (JBS) is a viable neurological disorder with a characteristic "molar tooth sign" (MTS) on axial images reflecting cerebellar vermian hypoplasia/dysplasia. Both conditions are classified as ciliopathies with an autosomal recessive mode of inheritance. Allelism of MKS and JBS has been reported for TMEM67/MKS3, CEP290/MKS4, and RPGRIP1L/MKS5. Recently, one homozygous splice mutation with a founder effect was reported in the CC2D2A gene in Finnish fetuses with MKS, defining the 6th locus for MKS. Shortly thereafter, CC2D2A mutations were also reported in JBS. The analysis of the CC2D2A gene in our series of MKS fetuses, identified 14 novel truncating mutations in 11 cases. These results confirm the involvement of CC2D2A in MKS and reveal a major contribution of CC2D2A to the disease. We also identified three missense CC2D2A mutations in two JBS cases. Therefore, and in accordance with the data reported regarding RPGRIP1L, our results indicate phenotype-genotype correlations, as missense and presumably hypomorphic mutations lead to JBS while all null alleles lead to MKS. 

Retracted: No

PubPeer comments:
 ![file] ,
The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid
Authors: Angelo F Borghetti
Marina M Morganti
Maria Cristina Baroni
Antonello A Romani
Paolo Soliani
Silvia Desenzani
Journal: Cancer Chemotherapy and Pharmacology (2011)
Discipline: CLINICAL MEDICINE
Keywords: cholangiocarcinoma; zoledronic acid; apoptosis; BH3-mimetic; ABT-737
Affiliations: Dipartimento di Scienze Chirurgiche, Sezione di Clinica Chirurgica e dei Trapianti d'Organo, Università degli Studi di Parma, Parma, Italy.

Abstract:  Purpose: In TFK-1 and EGI-1 cholangiocarcinoma cell lines, zoledronic acid (ZOL) determines an S-phase block without apoptosis. Here, we investigated the occurrence of apoptosis stigmata when ZOL is associated to the BH3-mimetic ABT-737. Methods: In EGI-1 and TFK-1 cholangiocarcinoma cell lines untreated or treated with ABT-737 alone or in combination with ZOL, the pro-survival protein's pattern (BCL-2, BCL-XL, MCL-1, HSP72, HSP27) was investigated by biochemical criteria along with the occurrence of mitochondrial damage evaluated by cytofluorimetric analysis using a cationic dye. Results: ABT-737 induced growth inhibition and significantly affected the colony-forming ability of both EGI-1 and TFK-1 cells. However, activated PARP-1 or/and caspase-3 cleavage (apoptosis markers) were detected only at the highest ABT-737 concentrations used. Combined treatment showed synergistic effect by converting the predominant cytostatic effect of ZOL into a cytotoxic one as shown by striking increment of mitochondrial harmed cells along with PARP-1 activation and caspase-3 cleavage. Conclusion: The lack of apoptosis following ZOL treatment in these cholangiocarcinoma cell lines appears to be multifactorial and could be ascribed to the large constitutive expression of pro-survival proteins. The efficacy of ZOL treatment requires a concomitant unleashing of apoptosis using a selective BH3-mimetic as ABT-737. The rational targeting of specific components of the apoptotic pathway may appear a useful approach to improve the treatment of refractory or relapsed cholangiocarcinoma. Combined treatment could be further explored in in vivo tumor model of cholangiocarcinoma. 

Retracted: No

PubPeer comments:
 Figure 1. * Red boxes: Two lanes in the actin panels in a) and b) appear to look more similar than expected. ![file] Reported to the journal together with 28 other papers in the summer of 2015, with a friendly reminder in April 2017, but no answer. With the exception of one paper, the journal did not correct or retract a single paper from this set. Could the authors please clarify if the journal contacted them back in 2015? ,