PReD-Bench/PRed-Bench huggingface dataset:
Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head
Authors: Changqing Zhang
Yong Feng
Hongyi Zhu
Yanchun Gao
Qiyang Wang
Journal: International Journal of Biological Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PERK signaling; apoptosis; endoplasmic-reticulum stress; endotheliocyte; glucocorticoid
Affiliations: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Abstract:  Vascular injury is considered an important pathological process during glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). In this study, we tried to investigate whether the endoplasmic reticulum (ER) stress is triggered in the GC-induced endotheliocyte (EC) apoptosis and ONFH. The results showed that a GC upregulated the expression of ER stress-related proteins, and PERK-CHOP signaling played an important role and induced EC apoptosis. The inhibition of PERK by GSK2656157 significantly decreased the GC-induced EC apoptosis in vitro and in vivo, thus protecting a rat model from vascular injury and significantly preventing GC-induced ONFH. 

Retracted: No

PubPeer comments:
 Figure 2A was brought to my attention by a reader. * Red boxes: Lanes in the XBP-1 panels in A and B appear to look more similar than expected. ![file] , 
 Figure 1C and 3D. * The 0h control panel in Figure 1C looks more similar to the Dex+GSK2656157 panel in Figure 3D than expected. Boxes of the same color highlight areas that look similar. ![file] , 
 Although the journal agreed to accept one of the articles with an erratum, however, the western blot images have some unexpected similarities to another article from a different study.The boxes in the same color are shown below https: pubpeer.com publications 5821BEDBCF741AF18F00078B569399#5 ![file] , 
 March 2021 Erratum found here: https: www.ijbs.com v17p1101.htm  In our paper [1], there were two errors due to the mishandling of Western Blot picture and Flow Cytometry data during the final preparation of manuscript. We regret that we did not detect these errors before publication. Here we showed the corrected Figure 2A.B and Figure 3D with side by side comparison of the previous figures. The data analyses and conclusion remain unchanged. This is an erratum for a type III duplication. In this case, at least one of the flow cytometry panels in Figures 2 and 3 appears to have been manipulated, as show in comment #1. The Erratum speaks of  Two errors but at least 3 panels have been quietly replaced in the first figure of the erratum, and perhaps all 11 panels in the second part of the erratum (although it is very low resolution). I have marked the replaced panels from the erratum here with pink boxes: ![file] ![file] ,
Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins
Authors: Josie I Johnson
Xia Xuan Hu
Heiko Bugger
Sandra Sena
Xiaoming Sheng
Jordan J Wright
Salwa Aziz
Heather Theobald
Vlad G Zaha
E Dale Abel
Sihem Boudina
Journal: Diabetes (2007)
Discipline: CLINICAL MEDICINE
Keywords: obesity; diabetes; myocardial fatty acid utilization; myocardial oxygen consumption; cardiac efficiency
Affiliations: Division of Endocrinology, Metabolism, and Diabetes, Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.

Abstract:  Objective: In obesity and diabetes, myocardial fatty acid utilization and myocardial oxygen consumption (MVo(2)) are increased, and cardiac efficiency is reduced. Mitochondrial uncoupling has been proposed to contribute to these metabolic abnormalities but has not been directly demonstrated. Research design and methods: Oxygen consumption and cardiac function were determined in db/db hearts perfused with glucose or glucose and palmitate. Mitochondrial function was determined in saponin-permeabilized fibers and proton leak kinetics and H(2)O(2) generation determined in isolated mitochondria. Results: db/db hearts exhibited reduced cardiac function and increased MVo(2). Mitochondrial reactive oxygen species (ROS) generation and lipid and protein peroxidation products were increased. Mitochondrial proliferation was increased in db/db hearts, oxidative phosphorylation capacity was impaired, but H(2)O(2) production was increased. Mitochondria from db/db mice exhibited fatty acid-induced mitochondrial uncoupling that is inhibitable by GDP, suggesting that these changes are mediated by uncoupling proteins (UCPs). Mitochondrial uncoupling was not associated with an increase in UCP content, but fatty acid oxidation genes and expression of electron transfer flavoproteins were increased, whereas the content of the F1 alpha-subunit of ATP synthase was reduced. Conclusions: These data demonstrate that mitochondrial uncoupling in the heart in obesity and diabetes is mediated by activation of UCPs independently of changes in expression levels. This likely occurs on the basis of increased delivery of reducing equivalents from beta-oxidation to the electron transport chain, which coupled with decreased oxidative phosphorylation capacity increases ROS production and lipid peroxidation. 

Retracted: No

PubPeer comments:
 ![file] , 
 https: pubpeer.com publications 616A48B4001ED082802189C565A709 ,
RETRACTED: Autoimmunity as a Consequence of Retrovirus-Mediated Expression of C-FLIP in Lymphocytes
Authors: Y Refaeli
A K Abbas
D Baltimore
L Van Parijs
Journal: Immunity (1999)
Discipline: IMMUNOLOGY
Keywords: apoptosis; death receptors; FLICE inhibitory proteins (FLIPs); lymphocytes; c-FLIP
Affiliations: Department of Biology, California Institute of Technology, Pasadena 91125, USA.

Abstract:  The induction of apoptosis by death receptors serves to regulate immune responses by eliminating unwanted and harmful cells. Mature lymphocytes express FLICE inhibitory proteins (FLIPs) that block death receptor-induced cell death. Here, we show that both B and T cells downregulate c-FLIP upon activation in vitro. Retrovirus-mediated expression of c-FLIP blocks Fas-induced apoptosis of activated lymphocytes but does not affect cell death resulting from cytokine withdrawal. In vivo, c-FLIP expression results in defective superantigen-mediated elimination of T cells, the accumulation of activated B cells, the production of autoantibodies, and the development of autoimmune disease. No effect was seen on negative selection of thyomocytes. These results suggest that activation-dependent downregulation of c-FLIP renders mature lymphocytes sensitive to death receptor-mediated apoptosis and is required to maintain self-tolerance. 

Retracted: Yes

PubPeer comments:
 https: doi.org 10.1016 j.immuni.2009.04.003 The authors have agreed to retract this paper because of duplication of the flow cytometry dot plots in Figure 5 [labeled as u201cInfected (GFP+)u201d and u201cNot infected (GFPu2212)u201d; lower panels] by the first author. This figure shows the IgM expression on B cells from mice with and without FLIP expression. These panels are important for showing that cells not expressing FLIP are not affected by the FLIP-expressing cells in the same mice. This matter was investigated by the California Institute of Technology and the Office of Research Integrity at the United States Department of Human Services, which found the first author to be responsible for the scientific misconduct pertaining to the issue described here. The authors stand by the validity of the other figures and sincerely apologize for the inconvenience caused by this retraction. ,
EGFR inhibition in glioblastoma cells induces G2/M arrest and is independent of p53
Authors: Gurpreet S Kapoor
Donald M O&#x27;Rourke
Antoire Christie
Journal: Cancer biology & therapy (2007)
Discipline: CLINICAL MEDICINE
Keywords: TP53 gene; glioblastomas; EGFR/erbB2 complexes; mutant erbB2; oncogenic transformation
Affiliations: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Abstract:  Mutations involving the TP53 gene are frequently identified in up to 50% of all human tumors, including glioblastomas. Analysis of expression patterns of TP53 in glioblastomas shows that it is mainly mutated in secondary glioblastomas and is less common in primary GBMs. However, the prognostic significance of TP53 loss of function in astrocytomas has always been controversial. In contrast, EGFR/erbB2 complexes have been implicated in the poor prognosis of several cancers, including glioblastomas. Our previous work showed that transforming phenotypes could be inhibited by interfering with active EGFR/erbB2 complex using mutant erbB2 proteins in wild-type p53 GBM cells. To assess the dependence of EGFR inhibited phenotype on p53, we used three mutant p53 glioblastoma cell lines in the present study and showed that mutant erbB2 can be exploited to inhibit EGFR-mediated oncogenic transformation irrespective of p53 status. Ectopic expression of a mutant erbB2 receptor (T691S) in mutant p53 GBM cells resulted in slower growth rate than empty vector controls. T691S-expressing clones exhibited a more flattened and nontransformed morphology. Consistently, T691S inhibited transformation in soft agar assays and tumor formation in nude mice independent of p53 status. Biochemical analysis showed reduced Akt and GSK-3 alpha/beta, but not p42/44MAPK phosphorylation, in T691S-expressing cells, when compared to parental controls, suggesting the P13-K pathway may be more relevant than MAPK for glial cell transformation. Cell cycle analysis showed reduced cyclin D1 and CDK6 and increased phospho-Cdc-2 (Tyr15) and p15INK4B in erbB2-inhibited cells, suggesting that nonfunctional EGFR/erbB2 complexes exert their inhibitory effects at various stages of the cell cycle to block the progression of cells through G2/M via Akt/GSK-3/Cdc2 pathway. Collectively, these observations provide a basis for receptor-based therapies that disable erbB receptors and inhibit proliferative signals in erbB-expressing human cancers including glioblastomas, regardless of their TP53 status. 

Retracted: No

PubPeer comments:
 Figure 3A. Much more similar than expected. https: imgur.com jT1LKDw , 
 Figure 3D. Much more similar than expected. https: imgur.com gEmNLXT , 
 Figure 4C. Much more similar than expected. https: imgur.com TiisqQf ,
Retinoblastoma promotes definitive erythropoiesis by repressing Id2 in fetal liver macrophages
Authors: Emerson R King
Gustavo Leone
Xu-Ming Dai
Antonio Iavarone
Anna Lasorella
E Richard Stanley
Journal: Nature (2004)
Discipline: Multidisciplinary
Keywords: fetal liver; erythropoiesis; erythroblastic island; retinoblastoma; Rb
Affiliations: Institute for Cancer Genetics, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. 

Abstract:  In mammals, the fetal liver is the first site of definitive erythropoiesis-the generation of mature, enucleated red cells. The functional unit for definitive erythropoiesis is the erythroblastic island, a multicellular structure composed of a central macrophage surrounded by erythroblasts at various stages of differentiation. Targeted disruption of the retinoblastoma (Rb) tumour suppressor gene in the mouse leads to embryonic death caused by failure of erythroblasts to enucleate. The erythroid defect has been attributed to loss of Rb in cells that support erythropoiesis, but the identity of these cells is unknown. Here we show that Rb-deficient embryos carry profound abnormalities of fetal liver macrophages that prevent physical interactions with erythroblasts. In contrast, wild-type macrophages bind Rb-deficient erythroblasts and lead them to terminal differentiation and enucleation. Loss of Id2, a helix-loop-helix protein that mediates the lethality of Rb-deficient embryos, rescues the defects of Rb-deficient fetal liver macrophages. Rb promotes differentiation of macrophages by opposing the inhibitory functions of Id2 on the transcription factor PU.1, a master regulator of macrophage differentiation. Thus, Rb has a cell autonomous function in fetal liver macrophages, and restrains Id2 in these cells in order to implement definitive erythropoiesis. 

Retracted: No

PubPeer comments:
 Figure 2e. https: imgur.com v4J4S8l ,
Negative regulation of JNK signaling by the tumor suppressor CYLD
Authors: Minying Zhang
William Reiley
Shao-Cong Sun
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CYLD; tumor suppressor; familial cylindromatosis; deubiquitinating enzyme; NF-kappaB
Affiliations: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

Abstract:  CYLD is a tumor suppressor that is mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple tumors of the skin appendages. Recent studies suggest that transfected CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. However, the role of endogenous CYLD in regulating cell signaling remains poorly defined. Here we report a critical role for CYLD in negatively regulating the c-Jun NH(2)-terminal kinase (JNK). CYLD knockdown by RNA interference results in hyper-activation of JNK by diverse immune stimuli, including tumor necrosis factor-alpha, interleukin-1, lipopolysaccharide, and an agonistic anti-CD40 antibody. The JNK-inhibitory function of CYLD appears to be specific for immune receptors because the CYLD knockdown has no significant effect on stress-induced JNK activation. Consistently, CYLD negatively regulates the activation of MKK7, an upstream kinase known to mediate JNK activation by immune stimuli. We further demonstrate that CYLD also negatively regulates IkappaB kinase, although this function of CYLD is seen in a receptor-dependent manner. These findings identify the JNK signaling pathway as a major downstream target of CYLD and suggest a receptor-dependent role of CYLD in regulating the IkappaB kinase pathway. 

Retracted: No

PubPeer comments:
 Parts of this paper are written in an unusual language. See examples below, highlighted are words passages that are very typical to texts transformed by a paraphrasing tool. Note that **least vitality** (*minimum energy*) is a *tortured phrase*. So is **Jahn teller impact** (*Jahn-Teller effect*). ![file] ![file] ,
The influence of Sam-Chil-Geun (Panax notoginseng) on the serum lipid levels and inflammations of rats with hyperlipidemia induced by poloxamer-407
Authors: Jae Hwan Ryu
Han Jin Oh
Il Woo Joo
Journal: Yonsei Medical Journal (2010)
Discipline: CLINICAL MEDICINE
Keywords: Atherosclerosis; hyperlipidemic mice model; P. notoginseng; atorvastatin; lipid lowering
Affiliations: Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Gangneung 210-701, Korea., East-West Medicine, Kyung Hee University, Seoul, Korea., Department of Family Medicine, College of Medicine, Kwandong University, Gangneung, Korea.

Abstract:  Purpose: Atherosclerosis is characterized by the progressive deposition of lipids and inflammatory process. We attempted to develop a chemically-induced hyperlipidemic mice model, using poloxamer-407 and evaluated the lipid lowering and anti-inflammatory effect of P. notoginseng compared with that of atorvastatin, an antihyperlipidemic drug. Materials and methods: Male Wistar rats were randomly divided into 5 groups: control group without any intervention (normal), poloxamer 500 mg/kg i.p. (P), poloxamer plus atorvastatin 1.34 mg/kg p.o. (P + ST), poloxamer plus P. notogin-seng 40 mg/kg p.o. (P + NG40), and poloxamer plus P. notoginseng 100 mg/kg p.o. (P + NG100). After 3 weeks, we measured serum total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, interleukin (IL)-1, tumor necrosis factor (TNF)-alpha levels, and reports of cyclo-oxygenase (COX)-2 and intercellular adhesion molecule (ICAM) appearances in each group. Results: After 3 weeks, serum cholesterol levels significantly decreased in P + ST and P + NG40 groups. Significant decrease of LDL level was only noted in the P + ST group. P + ST, P + NG40, and P + NG100 also had decreased serum triglyceride levels; however, P + ST and P + NG40 showed no statistical difference of the triglyceride lowering effect. The results of IL-1 and TNF-alpha and the appearance of COX-2 and ICAM were statistically not different in each group. Conclusion: P. notoginseng 40 mg/kg showed significantly lowering effects on serum total cholesterol and triglyceride levels. We suggest a well-designed study showing the effects of regulating blood lipids with combined administration of P. notoginseng and statin-drug. 

Retracted: No

PubPeer comments:
 image duplications ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 #1 ![file] ,
STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus
Authors: Mark H Kaplan
Hua-Chen Chang
Qing Yu
Audrey O&#x27;Sullivan
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: STAT4; interleukin-12; immune responses; gene induction; chromatin remodeling

Abstract:  Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)-stimulated inflammatory immune responses. Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor alpha chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. Thus, these results provide a model for STAT4-dependent gene induction and a mechanism for cytokine-induced expression of the CD25 gene. 

Retracted: No

PubPeer comments:
 Undeclared splicing site. ![file] ,
Lnc RNA ‐ PAGBC acts as a micro RNA sponge and promotes gallbladder tumorigenesis
Authors: Wei Gong
Lin Jiang
Xiang-Song Wu
Yi-Chi Zhang
Mao-Lan Li
Zheng Wang
Yi-Jun Shu
Run-Fa Bao
Lei Zheng
Xu-An Wang
Yang Cao
Yun-Peng Jin
Huai-Feng Li
Fei Zhang
Ying-Bin Liu
Hai-Bin Liang
Yi-Jian Zhang
Wei Lu
Shu-Han Sun
Hao Weng
Fang Wang
Yun-Ping Hu
Wen-Guang Wu
Journal: EMBO reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PAGBC; ceRNA; gallbladder cancer; lncRNA; prognosis.
Affiliations: Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Shanghai Research Center of Biliary Tract Disease, Shanghai, China., Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Medical Genetics, Second Military Medical University, Shanghai, China., Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA   ., Department of Medical Genetics, Second Military Medical University, Shanghai, China   ., Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China   .

Abstract:  Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC. 

Retracted: No

PubPeer comments:
 ![file] ,
Silencing MEG3 protects PC12 cells from hypoxic injury by targeting miR-21
Authors: Dan Deng
Hui Liang
Journal: Artificial Cells Nanomedicine and Biotechnology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hypoxic-ischaemic brain damage (HIBD); NF-κB pathway; PI3K/AKT pathway; neuron damage.
Affiliations: Department of Neurology, Daqing Oilfield General Hospital, Daqing, China., Department of Neurology, Hainan General Hospital, Haikou, China.

Abstract:  Increasing number of literatures highlighted lncRNA maternally expressed gene 3 (MEG3) as an emerging target for hypoxic-ischaemic brain damage (HIBD). This study attempted to assess the role of MEG3 in a cell model of HIBD. Expression of MEG3 in PC12 cells was suppressed by siRNA-mediated transfection, after which the cells were subjected to hypoxia. Cell viability, apoptosis, migration and the expression of related proteins were assessed. Furthermore, the downstream gene of MEG3 and its downstream signalling pathways were explored. We found that, down-regulation of MEG3 prevented hypoxic injury in PC12 cells, as hypoxia induced viability loss, apoptosis and migration repression were attenuated by transfection with MEG3 siRNA. Meanwhile, MEG3 acted as a miR-21 sponge. The neuroprotective functions of MEG3 silence were flattened when miR-21 was suppressed. Moreover, the deactivation of PI3K/AKT pathway and the activation of NF-κB pathway induced by hypoxia were attenuated by MEG3 silence. As expected, the effects of MEG3 silence on these two signalling were via miR-21. In conclusion, the neuroprotective effects of MEG3 silence on PC12 cells injured by hypoxia were observed in this study. Mechanistically, the neuroprotective effects of MEG3 silence on PC12 cells were via sponging miR-21 and thus regulating PI3K/AKT and NF-κB pathways.HIGHLIGHTSMEG3 is highly expressed in PC12 cells following hypoxic injury;Silence of MEG3 prevents hypoxia-induced cell damage in PC12 cells;MEG3 acts as a miR-21 sponge;MEG3 sponges miR-21 to regulate PI3K/AKT and NF-κB pathways. 

Retracted: No

PubPeer comments:
 The Western Blots in this paper all display the curious, stylised form, like tadpoles or performing sardines, familiar from products of the celebrated  Tadpole Papermill. Here, Fig 6. ![file] Is it possible for the authors to upload or link to scans of the original gels? ,
Direct Identification of α-Bisabolol Enantiomers in an Essential Oil Using a Combined Ion Mobility-Mass Spectrometry/Quantum Chemistry Approach
Authors: Alain Muselli
Erik Laurini
Aura Tintaru
Stéphane Andreani
Sabrina Pricl
Journal: Journal of natural products (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Enantiomer-specific; chiral molecules; natural extracts; analytical techniques; ion mobility-mass spectrometry
Affiliations: Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS), DEA, University of Trieste, 34127 Trieste, Italy, Université de Corse, UMR CNRS 6134 SPE, Laboratoire Chimie des Produits Naturels (CPN), Campus Grimaldi, BP 52, 20250 Corte, France, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, Poland, Aix Marseille Univ, CNRS, Institut de Chimie Radicalaire, UMR7273, 13397 Marseille, France

Abstract:  Enantiomer-specific identification of chiral molecules in natural extracts is a challenging task, as many routine analytical techniques fail to provide selectivity in multicomponent mixtures. Here we describe an alternative approach, based on the combination of ion mobility-mass spectrometry (IM-MS) and quantum chemistry (QM), for the direct enantiomers differentiation in crude essential oils. The identification of α-bisabolol enantiomers contained in the raw essential oil (EO) from the Corsican Xanthium italicum fruits is reported as a proof-of-concept. Accordingly, IM-MS experiments performed in Ag+-doped methanol revealed the presence of both (+)- and (-)-α-bisabolol in the EO, while molecular simulations provided the structures of the two α-bisabolol enantiomer silver(I) adducts. 

Retracted: No

PubPeer comments:
  Accordingly, IM-MS experiments performed in Ag+-doped methanol revealed the presence of both (+)- and (u2212)-u03b1-bisabolol in the EO So they use a non chiral method and are able to distinguish enantiomers. This would be a really strong violation of parity of the weak nuclear force. We know it exist,but it is a phenomenon 10^-11 smaller than what the report and that would have no impact with the technique they used. , 
 Can the authors clarify this point? Bearing in mind that the silver ion is not chiral and, according to the definition, the energy of each enantiomer is the same (in a non polarized space), how can we explain the huge difference in internal energy for the two adducts (3.67 kcal mol) ? What about the Ag-O bond length? why such a huge difference? What would be the calculated energy of the [(+)-u03b1-bisabolol + Ag]+ using as cartesian coordinates the X,Y,Z times(-1) of [(-)-u03b1-bisabolol + Ag]+? , 
 This article seems to cite: https: doi.org 10.1002 jms.3085 as a reference for that work. Same questions apply to this earlier article. ,
Long non-coding RNA AK027294 promotes tumor growth by upregulating PCNA in gastric cancer
Authors: X-Y He
J-X Ma
M-M Jin
Y-L Yang
Z-Q Yang
D Yan
X-M Pan
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; AK027294; gastric cancer; RT-qPCR; cell proliferation
Affiliations: Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China. .

Abstract:  Objective: Recent researches have proved that long non-coding RNAs (lncRNAs) has an important role in many diseases. In this research, lncRNA AK027294 was explored to identify how it functions in the development of gastric cancer (GC). Patients and methods: Real Time-quantitative-Polymerase Chain Reaction (RT-qPCR) was utilized to detect AK027294 expression in GC patients. Then, MTT assay, colony formation assay, and EdU incorporation assay were performed to identify its function in GC cells. Furthermore, the potential mechanism was also explored using mechanism assays. Results: AK027294 expression level was significantly higher in GC tissue samples and cell lines. Results of MTT assay, colony formation assay, and EdU incorporation assay showed that cell proliferation was inhibited through the silence of AK027294 in GC cells, while cell proliferation was promoted through overexpression of AK027294 in GC cells. Furthermore, the expression of PCNA was downregulated via silence of AK027294 in GC cells, while the expression of PCNA was upregulated via overexpression of AK027294 in GC cells. The correlation analysis showed that PCNA expression was positively correlated with AK027294 expression in GC tissues. Conclusions: Our results suggest that AK027294 could enhance cell proliferation of GC cells by upregulating PCNA and might be applied as a novel target for therapy of GC. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
Androgen receptor-interacting protein 3 and other PIAS proteins cooperate with glucocorticoid receptor-interacting protein 1 in steroid receptor-dependent signaling
Authors: Marianne Vihinen
Olli A Jänne
Noora Kotaja
Jorma J Palvimo
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Androgen receptor; ARIP3; PIASxalpha; coregulator; transcriptional activity
Affiliations: Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki and Helsinki University Central Hospital, Helsinki FIN-00014, Finland.

Abstract:  Androgen receptor (AR)-interacting protein 3 (ARIP3/PIASxalpha) is a coregulator capable of modulating transcriptional activity of various steroid receptors. We have characterized functional regions of ARIP3 and studied its interaction with the glucocorticoid receptor (GR)-interacting protein 1 (GRIP1). We find that the potential zinc-binding domain is critical for ARIP3 to function as a coactivator; the deletion of amino acids 347-418 or the mutation of the conserved cysteines 385 and 388 to serines converts ARIP3 to a transcriptional repressor from AR-dependent minimal promoters and abolishes its ability to activate GR. By contrast, mutations in the two LXXLL motifs of ARIP3 have relatively minor effects on its ability to regulate AR or GR function. ARIP3 is able to interact with different regions of GRIP1, but the strongest interaction is detected with the C-terminal region (amino acids 1122-1462) of GRIP1. The interaction of ARIP3 with the latter GRIP1 domain or full-length GRIP1 and the ability of ARIP3 to cooperate with GRIP1 in the regulation of AR- or GR-dependent transcription are dependent on the ARIP3 zinc-binding region. We also find a strong synergism between GRIP1 and two other PIAS family members, Miz1 and PIAS1. Taken together, our results suggest that PIAS proteins and GRIP1 interact functionally in transcriptional regulation. 

Retracted: No

PubPeer comments:
 In FIG 2E, several bands with splicing margin. ![file] ,
Site specific chemical delivery of NSAIDs to inflamed joints: synthesis, biological activity and gamma-imaging studies of quaternary ammonium salts of tropinol esters of some NSAIDs or their active metabolites
Authors: Rajani Giridhar
Anil K Mishra
Vijay P Pawar
Parmeshwari K Halen
Sejal M Marvaniya
Mange Ram Yadav
Journal: Bioorganic & Medicinal Chemistry (2008)
Discipline: CHEMISTRY
Keywords: Quaternized tropinol ester derivatives; non-steroidal anti-inflammatory drugs; chronic inflammation; tissue tropism; 99mTechnetium
Affiliations: Pharmacy Department, Faculty of Technology & Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara 390001, India. 

Abstract:  Quaternized tropinol ester derivatives of some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) or their active metabolites, were prepared and studied for their anti-inflammatory activity in a chronic inflammation model and for inflamed tissue tropism. The quaternized esters were radiolabeled with 99mTechnetium (99mTc) and their selective localization in the inflamed tissue was traced using scintigraphy. In the chronic arthritis rodent model, most of the quaternized esters exhibited anti-inflammatory effect comparable to their respective parent drugs. In the gamma-imaging studies only the quaternary derivatives exhibited selective accumulation into the inflamed tissue unlike the parent NSAIDs or the unquaternized tropinol esters. This work is a step ahead in the direction of use of quaternary ammonium ester derivatives for site specific chemical delivery of commonly used NSAIDs to the inflamed tissues to minimize their GIT side effect or other systemic toxicities. 

Retracted: No

PubPeer comments:
 Figure-1: strange similarity of gamma images for different compounds ? ![file] ![file] ![file] , 
 I agree with comment #1. Some additional panels that are remarkably similar are shown below highlighted with pink and blue boxes: ![file] ,
miR-133 involves in lung adenocarcinoma cell metastasis by targeting FLOT2
Authors: Jie Yan
Yahuan Xu
Tao Peng
Guangxia Wei
Journal: Artificial Cells Nanomedicine and Biotechnology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Akt signalling pathway; FLOT2; Lung adenocarcinoma; metastasis; miR-133.
Affiliations: a Department of Cardiothoracic Surgery , Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group , Huangshi , Hubei Province , China.

Abstract:  Background: Dysregulated microRNAs (miRNAs) reported to involve into the oncogenesis and progression in various human cancers. However, the roles and mechanism of miR-133 in lung adenocarcinoma remain largely unclear. Methods: In this study, qPCR assay and western blot were used to detect the expression levels of miR-133, Akt and FLOT2. Luciferase reporter assay was used to identify the target role of miR-133 on FLOT2. The cell invasion and the migration capability were performed using the transwell invasion assay and wound healing assay. Results: We found that miR-133 expression levels were downregulated in human lung adenocarcinoma specimens and cell lines compared with the adjacent normal tissues and normal human bronchial epithelial cell. miR-133 significantly suppressed metastasis of lung adenocarcinoma cells in vitro. Furthermore, FLOT2 (flotillin-2) identified as a direct target of miR-133, and FLOT2 expression levels were inversely correlated with miR-133 expression levels in human lung adenocarcinoma specimens. And the restoration studies suggested FGF2 as a downstream effector of miR-133 which acted through Akt signalling pathway. Conclusions: Our study revealed the mechanism that miR-133 suppresses lung adenocarcinoma metastasis by targeting FLOT2 via Akt signalling pathway, implicating a potential prognostic biomarker and therapeutic target for lung adenocarcinoma treatment. 

Retracted: No

PubPeer comments:
 In this article, you used human PC cell lines, BxPC-3, Panc-1, Miapaca-2, to establish CDX on C57BL 6 (B6) immunocompetent mice? Please provide comprehensive methods and evidence for the establishment of a human xenograft model in immunocompetent mice. We would love to discuss this important new discovery with the journal, which seems even more valuable than this article itself. ![file] ,
Up‐regulation of ZFAS1 indicates dismal prognosis for cholangiocarcinoma and promotes proliferation and metastasis by modulating USF1 via miR‐296‐5p
Authors: Kaiming Leng
Lining Huang
Yi Xu
Yunfu Cui
Xingming Jiang
Jinglin Li
Daolin Ji
Zhenglong Li
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: USF1; cholangiocarcinoma; lncRNA ZFAS1; metastasis; proliferation.
Affiliations: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract:  LncRNAs has been demonstrated to modulate neoplastic development by modulating downstream miRNAs and functional genes. In this study, we aimed to detect the interaction among lncRNA ZFAS1 miR-296-5p and USF1. We explored the proliferation, migration and invasion of cholangiocarcinoma. The differentially expressed ZFAS1 was discovered in both tissues and cell lines by qRT-PCR. The targeting relationship between miR-296-5p and ZFAS1 or USF1 was validated by dual-luciferase assay. The impact of ZFAS1 on CCA cell proliferation was observed by CCK-8 assay. The protein expression of USF1 was determined by Western blot. The effects of ZFAS1, miR-296-5p and USF1 on tumour growth were further confirmed using xenograft model. LncRNA ZFAS1 expression was relatively up-regulated in tumour tissues and cells while miR-296-5p was significantly down-regulated. Knockdown of ZFAS1 significantly suppressed tumour proliferation, migration, invasion and USF1 expression. Overexpressed miR-296-5p suppressed cell proliferation and metastasis. Knockdown of USF1 inhibited cell proliferation and metastasis and xenograft tumour growth. In conclusion, ZFAS1 might promote cholangiocarcinoma proliferation and metastasis by modulating USF1 via miR-296-5p. 

Retracted: No

PubPeer comments:
 Figure 2F * Green boxes: In the CCLP-1 row, the si-ZFAS1-1 and si-ZFAS1-2 panels appear to show an area of overlap. ![file] , 
 Figure 3B * Red boxes: In the CCLP-1 Invasion row, the si-ZFAS1-1 and si-ZFAS1-2 panels appear to show an area of overlap. ![file] , 
 More similarities between Figure 3B and 5C can be observed. Boxes of the same color depict areas in panels that look unexpectedly similar. The area marked in dark green might be representing the same experiment and cell line, but the other colors appear to be showing similarities between panels that represent different experiments. ![file] , 
 The method for measuring miR-296-5p would not work as described. A standard reverse transcription kit will not prepare mature miRNAs for amplification. Instead, a microRNA-specific RT strategy would be needed, specifically in this case a stem-loop RT primer strategy, as reflected in the  forward primer described in the methods section. However, the  forward and  reverse primers appear to have been switched in the primer table, a feature shared with numerous other articles claiming to amplify mature miR-296-5p. ,
AMPA receptor-mediated regulation of a Gi-protein in cortical neurons
Authors: Y Wang
D B Stanimirovic
P Morley
D L Small
J P Durkin
Journal: Nature (1997)
Discipline: Multidisciplinary
Keywords: Excitatory synaptic transmission; glutamate; NMDA receptor; AMPA receptor; intracellular signals
Affiliations: Cellular Neurobiology Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario. 

Abstract:  Excitatory synaptic transmission in the central nervous system is mediated primarily by the release of glutamate from presynaptic terminals onto postsynaptic channels gated by N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. The myriad intracellular responses arising from the activation of the NMDA and AMPA receptors have previously been attributed to the flow of Ca2+ and/or Na+ through these ion channels. Here we report that the binding of the agonist AMPA to its receptor can generate intracellular signals that are independent of Ca2+ and Na+ in rat cortical neurons. In the absence of intracellular Ca2+ and Na+, AMPA, but not NMDA, brought about changes in a guanine-nucleotide-binding protein (Galpha[il]) that inhibited pertussis toxin-mediated ADP-ribosylation of the protein in an in vitro assay. This effect was observed in intact neurons treated with AMPA as well as in isolated membranes exposed to AMPA, and was also found in MIN6 cells, which express functional AMPA receptors but have no metabotropic glutamate receptors. AMPA also inhibited forskolin-stimulated activity of adenylate cyclase in neurons, demonstrating that Gi proteins were activated. Moreover, both Gbetagamma blockage and co-precipitation experiments demonstrated that the modulation of the Gi protein arose from the association of Galpha(il) with the glutamate receptor-1 (GluR1) subunit. These results suggest that, as well as acting as an ion channel, the AMPA receptor can exhibit metabotropic activity. 

Retracted: No

PubPeer comments:
 A December 2017 correction for an issue reported in May 2015. The text of the correction reads: * It has come to our attention that Fig. 4 in this Letter presented three events of data duplication. In Fig. 4a the panels in row 1, columns 1 and 7 were the same, in Fig. 4a the panels in row 3, columns 5 and 7 were the same, and in Fig. 4c and e, the panels in columns 1u20133 were the same. Given the time elapsed since publication, we could not locate the original raw data. The main conclusion illustrated by Fig. 4, however, of dose-dependent (Fig. 4d) and Gu03b2u03b3-sensitive (Fig. 4f) activation of Gu03b1i1 by AMPA in MIN6 cells, which do not express GluR6 (Fig. 4b), remains unaffected. Authors J.P.D. and P.M., now both retired, could not be reached. The original Letter has not been corrected online. Correspondence should be addressed to Y.W. (yzwang@ion.ac.cn).* Here are the original concerns about Figure 4. Of note, this is an admitted case of image duplication (Category 3 duplication) that got addressed with a correction. ![file] ,
Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN-55,212-2
Authors: Song Zhao
Lin Chen
Tian-Hong Nie
Gui-Bin Bi
Chang-Yan Xu
Hui Sha
Feng Niu
Long Ye
Ping Gong
Journal: Oncology Letters (2015)
Discipline: CLINICAL MEDICINE
Keywords: WIN-55,212-2; adriamycin; cannabinoid; combination; osteosarcoma.
Affiliations: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China., Department of Medical Records, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract:  Osteosarcoma is the most frequent primary malignant bone tumor that occurs in children and adolescents. The present study aimed to identify novel therapeutic strategies for osteosarcoma, by assessing the antitumor activity of the cannabinoid WIN-55,212-2 and its combined effect with adriamycin (ADM) against the MG-63 human osteosarcoma cell line. To evaluate the antiproliferative action of these molecules, a Cell Counting kit-8 (CCK-8) assay was used. The ability of cannabinoid to inhibit the migration, invasion and angiogenic activity of MG-63 cells were assessed by scratch, Transwell® chamber and angiogenesis assays, respectively, in vitro. To examine the alterations in expression of targeted genes, quantitative polymerase chain reaction and western blot analysis were used. The administration of cannabinoid combined with ADM was demonstrated to inhibit the growth of MG-63 cells, resulting in a cell viability of 32.12±3.13%, which was significantly lower (P&lt;0.05) compared with the cell viability following treatment with cannabinoid (70.86±7.55%) and ADM (62.87±5.98%) alone. Greater antimetastasis and antiangiogenic activities were also observed following the coadministration of the two agents compared with individual treatments and controls. In addition, the expression levels of Notch-1, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in MG-63 cells were downregulated following the treatments with cannabinoid alone or in combination with ADM. In conclusion, the present findings demonstrated that cannabinoid WIN-55,212-2 may significantly potentiate the antiproliferative, antimetastasis and antiangiogenic effects of ADM against MG-63 cells via the downregulation of Notch-1, MMP-2 and VEGF. These findings may offer a novel strategy for the treatment of osteosarcoma. 

Retracted: No

PubPeer comments:
 This paper was found during a systematic search of papers in this journal with possible duplicated images. Fifteen papers in this journal (n=98 examined) were found to contain inappropriately duplicated images. These papers have all been reported to the journal publisher in 2017. The editors promised to  investigate promptly but no action has been taken as of today. Figure 2. Several regions within or between panels appear to look similar. Boxes of the same color highlight areas that look similar to each other. ![file] , 
 Those are some impressively straight vertical edges! ,
Long non-coding RNA H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in gallbladder cancer
Authors: Xiao-Cai Wu
Zhao-Hui Tang
Shou-Hua Wang
Jian-Dong Wang
Zhi-Wei Quan
Qiang Cai
Ming-Di Zhang
Di Zhou
Ming-Zhe Weng
Fei Ma
Journal: Journal of Experimental & Clinical Cancer Research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Competing endogenous RNA; FOXM1; Gallbladder cancer; H19; miR-342-3p.
Affiliations: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China., Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao tong University School of Medicine, Shanghai, 200092, China., Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China. .

Abstract:  Background: Long non-coding RNA (lncRNA) H19 has been reported to involve in many kinds of human cancers and functions as an oncogene. Our previous study found that H19 was over-expressed in gallbladder cancer (GBC) and was shown to promote tumor development in GBC. However, the competing endogenous RNA (ceRNA) regulatory network involving H19 in GBC progression has not been fully elucidated. We aim to detect the role of H19 as a ceRNA in GBC. Methods and results: In this study, the expression of H19 and miR-342-3p were analyzed in 35 GBC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR). We demonstrated H19 was overexpressed and negatively correlated with miR-342-3p in GBC. By dual-luciferase reporter assays, RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays, we verified that H19 was identified as a direct target of miR-342-3p. QRT-PCR and Western-blotting assays demonstrated that H19 silencing down-regulated, whereas over-expression enhanced the expression of miR-342-3p targeting FOXM1 through competitively 'sponging' miR-342-3p. Furthermore, transwell invasion assays and cell cycle assays indicated that H19 knockdown inhibited both cells invasion and proliferation, but this effects was attenuated by co-transfection of siRNA-H19 and miR-342-3p inhibitor in GBC cells. In vivo, tumor volumes were decreased significantly in H19 silenced group compared to the control group, but was attenuated by co-transfection of shRNA-H19 and miR-342-3p inhibitor, which were stablely constructed through lenti-virus vector. Conclusion: Our results suggest a potential ceRNA regulatory network involving H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in GBC. This mechanism may contribute to a better understanding of GBC pathogenesis and provides potential therapeutic strategy for GBC. 

Retracted: No

PubPeer comments:
 Figure 5 appears to have a duplication, with the brightness of the image adjusted. ![file] ,