PReD-Bench/PRed-Bench huggingface dataset:
Ubiquitin B: an essential mediator of trichostatin A-induced tumor-selective killing in human cancer cells
Authors: G Xu
Y Fang
L Meng
S Wang
P Wu
D Ma
B Wang
D Wang
L Gui
Y Tian
J Zhou
G Chen
L Xi
X Ma
T Zhu
Journal: Cell death and differentiation (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Histone deacetylase inhibitors; tumor-selective killing; Ubiquitin B; trichostatin A; mitochondrial transmembrane potential
Affiliations: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

Abstract:  Although histone deacetylase inhibitors (HDACis) are emerging as a new class of anticancer agents, the mechanism of tumor-selective killing by HDACi is not well understood. We used suppression of mortality by antisense rescue technique (SMART) to screen the key genes responsible for the tumor-selective killing by trichostatin A (TSA). Twenty-four genes were identified, the most significant of which was ubiquitin B (UbB). The expression of UbB was selectively upregulated by TSA in tumor cells, but not non-malignant cells. Further observation indicated that TSA induced a substantial dissipation of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, and proteolytic cleavage of caspases-3/9 in HeLa cells, which was apparently mediated by ubiquitylation and the subsequent degradation of mitochondrial membrane proteins including BCL-2 and MCL-1. In contrast, knockdown of UbB expression inhibited the TSA-induced apoptotic cascade by abolishing TSA-induced ubiquitylation and the subsequent degradation of mitochondrial membrane proteins. Furthermore, apicidine, another HDACi, exhibited activity similar to that of TSA. Interestingly, TSA induced UbB-dependent proteasomal degradation of BCR-ABL fusion protein in K562 leukemic cells. Thus, our findings highlight the essential role of UbB and UbB-dependent proteasomal protein degradation in HDACi-induced tumor selectivity. The mechanism provides a novel starting point for dissecting the molecular mechanism underlying the tumor selectivity of HDACi. 

Retracted: No

PubPeer comments:
 Figure 2a appears to have a set of repeated images. ***  , 
 Correction Published: 30 July 2021 The original version of this article unfortunately contained a mistake. In figure 2a, the authors mistakenly used the same image in the different cell lines HeLa and MCF-7. The corrected figure can be found below. The authors apologize for the error.  , 
 It seems as if this paper has another unaddressed error. A band has been recropped and reused to represent two completely different conditions in Figure 4c and Figure 6a (red) and another seems to be repeated (green). ***  ,
MicroRNA‚Ä?38 inhibits tumor growth and enhances chemosensitivity in human cervical cancer by targeting H2AX
Authors: Min Yuan
Qianyu Wu
Rui Chen
Shuting Zhao
Guozeng Wang
Jingxin Cheng
Yachun Bie
Journal: Experimental and Therapeutic Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: H2AX; cervical cancer; chemosensitivity; microRNA-138; progression.
Affiliations: Department of Gynecology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Pudong New Area, Shanghai 200120, P.R. China

Abstract:  MicroRNA-138 (miR-138) acts as a key regulator in the modulation of carcinogenesis in numerous tumor types. Chemoresistance is common and relevant to the failure of multiple treatment strategies for cervical cancer. However, the biological role of miR-138 in the progression and chemosensitivity of cervical cancer is still unclear. The present study aimed to investigate the expression, function and mechanism of miR-138 in cervical cancer. An miR-138 mimic, inhibitor and negative control were transfected into SiHa and C33A cells. The expression of miR-138 and its target were assessed by reverse transcription-PCR, western blotting and immunohistochemistry. The functional significance of miR-138 in tumor progression and chemosensitivity to cisplatin in vitro was examined by Cell Counting Kit-8, flow cytometry, wound healing and Transwell assays. A tumor xenograft model was used to validate the effects in vivo. These results demonstrated that miR-138 was significantly downregulated in cervical cancer cells. Overexpression of miR-138 suppressed cervical cancer cell proliferation, invasion, increased apoptosis and enhanced chemotherapy sensitivity in vivo and in vitro. Furthermore, bioinformatics analysis and dual luciferase reporter assays demonstrated that H2AX served as a target for miR-138, and the rescue experiment revealed that H2AX was a functional target of miR-138. The protective effects of miR-138 overexpression were dependent on H2AX. This study provides evidence that miR-138/H2AX may be a novel therapeutic target in cervical cancer. 

Retracted: No

PubPeer comments:
 Figure 6B appears to include 2 images which overlap. ***  , 
 Figure 3A and Figure 6B appear to have an image which overlaps. Area of overlap roughly shown. ***   ,
Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease
Authors: T T MacDonald
G Monteleone
H W Steer
N M Croft
A Kumberova
C McKenzie
Journal: Journal of Clinical Investigation (2001)
Discipline: CLINICAL MEDICINE
Keywords: TGF-beta1; Smad7; inflammatory bowel disease; signaling; immune responses
Affiliations: Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, United Kingdom.

Abstract:  TGF-beta1 functions as a negative regulator of T cell immune responses, signaling to target cells using the Smad family of proteins. We show here that Smad7, an inhibitor of TGF-beta1 signaling, is overexpressed in inflammatory bowel disease (IBD) mucosa and purified mucosal T cells. Both whole tissue and isolated cells exhibit defective signaling through this pathway, as measured by phospho-Smad3 immunoreactivity. Specific antisense oligonucleotides for Smad7 reduce Smad7 protein expression in cells isolated from patients with IBD, permitting the cells to respond to exogenous TGF-beta1. TGF-beta1 cannot inhibit proinflammatory cytokine production in isolated lamina propria mononuclear cells from patients with Crohn disease (CD), but inhibition of Smad7 restores TGF-beta1 signaling and enables TGF-beta1 to inhibit cytokine production. In inflamed mucosal tissue explants from patients with CD, inhibition of Smad7 also restores p-Smad3 and decreases proinflammatory cytokine production, an effect that is partially blocked by anti-TGF-beta1. These results show that Smad7 blockade of TGF-beta1 signaling helps maintain the chronic production of proinflammatory cytokines that drives the inflammatory process in IBD and that inhibition of Smad7 enables endogenous TGF-beta to downregulate this response. 

Retracted: No

PubPeer comments:
 After flipping the order of treatments is different. , 
null, 
 Crohn s disease and Ulcerative Colitis are thought to be different diseases. ,
p300 modulates ATF4 stability and transcriptional activity independently of its acetyltransferase domain
Authors: Emilie Estrabaud
Irina Lassot
Richard Benarous
Stephane Emiliani
Monsef Benkirane
Florence Margottin-Goguet
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ATF4; stress response; ubiquitination; p300; acetylation
Affiliations: Institut Cochin, Department of Maladies Infectieuses, INSERM U567, CNRS UMR8104, University Rene Descartes Paris V, Bat G. Roussy, 27 Rue du Faubourg Saint Jacques, 75014 Paris, France.

Abstract:  ATF4 plays a crucial role in the cellular response to stress and multiple stress responses pathways converge to the translational up-regulation of ATF4. ATF4 is a substrate of the SCF(betaTrCP) ubiquitin ligase that binds to betaTrCP through phosphorylation on a DSGXXXS motif. We show here that ATF4 stability is also modulated by the histone acetyltransferase p300, which induces ATF4 stabilization by inhibiting its ubiquitination. Despite p300 acetylates ATF4, we found that p300-mediated ATF4 stabilization is independent of p300 catalytic activity, using either the inactive form of p300 or the acetylation mutant ATF4-K311R. ATF4 deleted of its p300 binding domain is no more stabilized by p300 nor recruited into nuclear speckles. In consequence of ATF4 stabilization, both p300 and the catalytically inactive enzyme increase ATF4 transcriptional activity. 

Retracted: No

PubPeer comments:
 Fig.1B There is visible splice line. Could the authors explain?  , 
 There is indeed a visible line that we wanted to be seen. This line separates 2 parts from one unique polyacrylamide gel. The other line drawn on the left separates samples coming from the same experiment but present on 2 different gels. ,
Visual bias of unseen hand position with a mirror: spatial and temporal factors
Authors: Charles Spence
Nicholas P Holmes
Journal: Experimental Brain Research (2005)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: visual information; proprioceptive information; integration; mirror; hand location
Affiliations: Department of Experimental Psychology, Oxford University, Oxford, OX1 3UD, UK. 

Abstract:  Two experiments examined the integration of visual and proprioceptive information concerning the location of an unseen hand, using a mirror positioned along the midsagittal plane. In experiment 1, participants tapped the fingers of both hands in synchrony, while viewing the mirror-reflection of their left hand. After 6 s, participants made reaching movements to a target with their unseen right hand behind the mirror. Reaches were accurate when visually and proprioceptively specified hand positions were congruent prior to the reach, but significantly biased by vision when the visual location conflicted with the real location. This effect was independent of the target location and depended strongly upon the relative position of the mirror-reflected hand. In experiment 2, participants made reaching movements following 4, 8, or 12 s active visuomotor or passive visual exposure to the mirror, or following passive exposure without the mirror. Reaching was biased more by the visual location following active visuomotor compared to passive visual exposure, and this bias increased with the duration of visual exposure. These results suggest that the felt position of the hand depends upon an integrated, weighted sum of visual and proprioceptive information. Visual information is weighted more strongly under active visuomotor than passive visual exposure, and with increasing exposure duration to the mirror reflected hand. 

Retracted: No

PubPeer comments:
 This paper has a published response by our research group: Bandini, E., Reeves, J.S., Snyder, W.D., Tennie, C.. 2021. Clarifying Misconceptions of the Zone of Latent Solutions Hypothesis: A Response to Haidle and Schlaudt. Biol Theory. https: doi.org 10.1007 s13752-021-00374-x ,
MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins
Authors: Sveva Sanzone
Angela Strambi
Carlo Iavarone
David Colecchia
Mario Chiariello
Arturo Verrotti di Pianella
Matteo Rossi
Federica Piccioni
Claudia Dall&#x27;Armi
Journal: Autophagy (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Autophagy; MAPK15; ATG8-like proteins; MAP kinase; signaling networks
Affiliations: Istituto Toscano Tumori-Core Research Laboratory, Signal Transduction Unit, AOU Senese, Siena, Italy.

Abstract:  Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved catabolic process necessary for normal recycling of cellular constituents and for appropriate response to cellular stress. Although several genes belonging to the core molecular machinery involved in autophagosome formation have been discovered, relatively little is known about the nature of signaling networks controlling autophagy upon intracellular or extracellular stimuli. We discovered ATG8-like proteins (MAP1LC3B, GABARAP and GABARAPL1) as novel interactors of MAPK15/ERK8, a MAP kinase involved in cell proliferation and transformation. Based on the role of these proteins in the autophagic process, we demonstrated that MAPK15 is indeed localized to autophagic compartments and increased, in a kinase-dependent fashion, ATG8-like proteins lipidation, autophagosome formation and SQSTM1 degradation, while decreasing LC3B inhibitory phosphorylation. Interestingly, we also identified a conserved LC3-interacting region (LIR) in MAPK15 responsible for its interaction with ATG8-like proteins, for its localization to autophagic structures and, consequently, for stimulation of the formation of these compartments. Furthermore, we reveal that MAPK15 activity was induced in response to serum and amino-acid starvation and that this stimulus, in turn, required endogenous MAPK15 expression to induce the autophagic process. Altogether, these results suggested a new function for MAPK15 as a regulator of autophagy, acting through interaction with ATG8 family proteins. Also, based on the key role of this process in several human diseases, these results supported the use of this MAP kinase as a potential novel therapeutic target. 

Retracted: No

PubPeer comments:
 Fig 2C.  Autophagy induced by L-OHP protects CNE1 and CNE2 cells from the cytotoxicity of L-OHP. .. (C) Representative fluorescence microscope images of drug-resistant cells and parental cells stably expressing GFP-LC3, with serum starvation as a positive control . Fig 3B.  Txr1 promotes autophagy and oxaliplatin resistance in CNE1 and CNE2 cells. ... (B) Representative fluorescence microscope images of Txr1-overexpression cells stably expressing GFP-LC3, with serum starvation as a positive control. A panel is repeated (with a vertical flip), representing two different conditions.  , 
 Retracted [25 March 2021] .  An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. ,
G1/S Cyclins interact with regulatory subunit of PKA via A-kinase anchoring protein, AKAP95
Authors: Pierre P Roger
Chantal Degraef
Tatjana Arsenijevic
Jacques E Dumont
Isabelle Pirson
Journal: Cell Cycle (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cyclins; cell cycle progression; AKAP95; CDKs; G(1)/S
Affiliations: Institute of Interdisciplinary Research (IRIBHM), and Laboratoire de Chimie Biologique et de la Nutrition, School of Medicine, Free University of Brussels, Campus Erasme, Brussels, Belgium. 

Abstract:  The mechanisms by which cyclins promote mammalian cell cycle progression have been a topic of intense investigation over the last decade. We previously described an interaction between D-type cyclins and A-kinase anchoring protein, AKAP95. Here, we demonstrate that AKAP95 can also bind cyclin E1. Association between AKAP95 and cyclins is displaced by CDKs. We show that these G(1)/S cyclins can interact with RII subunit of PKAalpha through AKAP95. The presence of alternate complexes cyclin-CDK and cyclin D/E-AKAP95-PKA.RIIalpha suggest different roles of G(1)/S cyclins and a wider biological importance of these interactions in cells. 

Retracted: No

PubPeer comments:
 Figure 1. WCE Cyclin E panel. Vertical change signal right end band lane 3.  , 
 Figure 2A. WCE Cyclin D3 panel. Vertical change signal right end band lane 3.  ,
Complement in the pathogenesis of Alzheimer‚Äôs disease
Authors: B Paul Morgan
Journal: Seminars in Immunopathology (2018)
Discipline: IMMUNOLOGY
Keywords: Alzheimer‚Äôs disease; Complement; Neurodegeneration.
Affiliations: Systems Immunity Research Institute and Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK. .

Abstract:  The emergence of complement as an important player in normal brain development and pathological remodelling has come as a major surprise to most scientists working in neuroscience and almost all those working in complement. That a system, evolved to protect the host against infection, should have these unanticipated roles has forced a rethink about what complement might be doing in the brain in health and disease, where it is coming from, and whether we can, or indeed should, manipulate complement in the brain to improve function or restore homeostasis. Complement has been implicated in diverse neurological and neuropsychiatric diseases well reviewed elsewhere, from depression through epilepsy to demyelination and dementia, in most complement drives inflammation to exacerbate the disease. Here, I will focus on just one disease, the most common cause of dementia, Alzheimer's disease. I will briefly review the current understanding of what complement does in the normal brain, noting, in particular, the many gaps in understanding, then describe how complement may influence the genesis and progression of pathology in Alzheimer's disease. Finally, I will discuss the problems and pitfalls of therapeutic inhibition of complement in the Alzheimer brain. 

Retracted: No

PubPeer comments:
 The presentation of Fig. 2 was incorrect. The correct version of Fig. 2 is given below.  ,
Isoalantolactone inhibits the migration and invasion of human breast cancer MDA-MB-231 cells via suppression of the p38 MAPK/NF-Œ∫B signaling pathway
Authors: Jie Song
Dan Liu
Liang Feng
Li Cui
Zhenhai Zhang
Jing Wang
Xiaobin Jia
Journal: Oncology reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Isoalantolactone; MDA-MB-231 cells; anti-migratory; anti-invasive activities; MMP-2
Affiliations: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.

Abstract:  Isoalantolactone is a bioactive sesquiterpene lactone isolated from the flowering plant Inula helenium L. This study was conducted to assess the anti-migratory and anti-invasive activities of isoalantolactone in MDA-MB-231 cells, and to explore the underlying mechanisms. Wound-healing and Transwell chambers assays demonstrated that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells. The activity and expression of MMP-2 and MMP-9 were downregulated by isoalantolactone in a dose-dependent manner. Additionally, isoalantolactone markedly decreased the p-p38 MAPK level, whereas no significant change in p-ERK1/2 and p-JNK1/2 was noted. The downregulation of MMP-2 and MMP-9 protein expression and suppression of in vitro invasion might be associated with the blockade of p38 MAPK activation. Furthermore, isoalantolactone blocked the translocation of NF-Œ∫B p65 from the cytoplasm into the nucleus. These results revealed that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells via suppression of the p38 MAPK/NF-Œ∫B signaling pathway, and isoalantolactone might be an alternative treatment for breast cancer. 

Retracted: No

PubPeer comments:
 Two images in figure 2D (a and e) appear to overlap, although they have a slightly different dimensions, and have been flipped horizontally and vertically, and rotated slightly (not shown). Difficult to see how these alterations could occur if this was simply an error made during figure assembly. ***  ***  ,
Pervanadate-induced nuclear factor-kappaB activation requires tyrosine phosphorylation and degradation of IkappaBalpha. Comparison with tumor necrosis factor-alpha
Authors: B B Aggarwal
A Mukhopadhyay
S K Manna
Journal: Journal of Biological Chemistry (2000)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Tumor necrosis factor; NF-kappaB; IkappaBalpha; phosphorylation; degradation
Affiliations: Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract:  Tumor necrosis factor activates nuclear transcription factor kappaB (NF-kappaB) by inducing serine phosphorylation of the inhibitory subunit of NF-kappaB (IkappaBalpha), which leads to its ubiquitination and degradation. In contrast, pervanadate (PV) activates NF-kappaB and induces tyrosine phosphorylation of IkappaBalpha (Singh, S., Darney, B. G., and Aggarwal, B. B. (1996) J. Biol. Chem. 271, 31049-31054; Imbert, V., Rupec, R. A., Antonia, L., Pahl, H. L., Traenckner, E. B.-M., Mueller-Dieckmann, C., Farahifar, D., Rossi, B., Auderger, P., Baeuerle, P. A., and Peyron, J.-F. (1996) Cell 86, 787-798). Whether PV also induces IkappaBalpha degradation and whether degradation is required for NF-kappaB activation are not understood. We investigated the effect of PV-induced tyrosine phosphorylation on IkappaBalpha degradation and NF-kappaB activation. PV activated NF-kappaB, as determined by DNA binding, NF-kappaB-dependent reporter gene expression, and phosphorylation and degradation of IkappaBalpha. Maximum degradation of IkappaBalpha occurred at 180 min, followed by NF-kappaB-dependent IkappaBalpha resynthesis. N-Acetylleucylleucylnorlucinal, a proteasome inhibitor, blocked both IkappaBalpha degradation and NF-kappaB activation, suggesting that the IkappaBalpha degradation is required for NF-kappaB activation. PV did not induce serine phosphorylation of IkappaBalpha but induced phosphorylation at tyrosine residue 42. Unlike tumor necrosis factor (TNF), PV did not induce ubiquitination of IkappaBalpha. Like TNF, however, PV induced phosphorylation and degradation of IkappaBalpha, and subsequent NF-kappaB activation, which could be blocked by N-tosyl-L-phenylalanine chloromethyl ketone, calpeptin, and pyrrolidine dithiocarbomate, suggesting a close link between PV-induced NF-kappaB activation and IkappaBalpha degradation. Overall, our studies demonstrate that PV activates NF-kappaB, which, unlike TNF, requires tyrosine phosphorylation of IkappaBalpha and its degradation. 

Retracted: No

PubPeer comments:
 Identified by another reader. ***  ,
Empathy and pro-social behavior in rats
Authors: Jean Decety
Peggy Mason
Inbal Ben-Ami Bartal
Journal: Science (2011)
Discipline: Multidisciplinary
Keywords: pro-social behavior; empathic concern; rodents; restrainer; cagemate
Affiliations: Department of Psychology, University of Chicago, Chicago, IL, USA.

Abstract:  Whereas human pro-social behavior is often driven by empathic concern for another, it is unclear whether nonprimate mammals experience a similar motivational state. To test for empathically motivated pro-social behavior in rodents, we placed a free rat in an arena with a cagemate trapped in a restrainer. After several sessions, the free rat learned to intentionally and quickly open the restrainer and free the cagemate. Rats did not open empty or object-containing restrainers. They freed cagemates even when social contact was prevented. When liberating a cagemate was pitted against chocolate contained within a second restrainer, rats opened both restrainers and typically shared the chocolate. Thus, rats behave pro-socially in response to a conspecific's distress, providing strong evidence for biological roots of empathically motivated helping behavior. 

Retracted: No

PubPeer comments:
 The authors developed a very complicated multi-criteria decision making method for location selection of seawater pumped hydro storage station. However, the proposed method itself is very confusing. For example, in **Step 2**, the authors presented a normalization procedure in eq.(7) for a decision making matrix concerning the benefit and cost criteria. After such a step, the larger the value is, the better the alternative under consideration with a certain criterion no matter it is benefit- or cost-related. In **Step 3**, the authors determined **the positive ideal solution** and **the negative ideal solution** using eq.(8) and eq.(9). However, **eq.(8) and eq.(9) treat the benefit and cost criteria separately and are not consistent with the normalization procedure in Step 2.** Besides, the terms in eq.(8) and eq.(9) are also confusing. The authors used $C_{ij}$ to denote a criterion. This means that the subscript $i$ and $j$ denote jointly a particular criterion. Under such a setting, the maximization and minimization in eq.(8) and eq.(9) cannot be performed over the index $i$. The meaning of $i=1,2,ldots, m$ in eq.(8) and eq.(9) is also not clear because the value $m$ is not explained in the context. Could the authors address these issues?    ,
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination
Authors: Jessica Tollkuhn
Lorin E Olson
Claudio Scafoglio
Kenneth A Ohgi
Anna Krones
Michael G Rosenfeld
Wei Wu
Jie Zhang
Makoto M Taketo
Rolf Kemler
Rudolf Grosschedl
Dave Rose
Xue Li
Journal: Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Wnt/beta-catenin signaling; cell-lineage determination; transcriptional programs; beta-catenin; Prop1
Affiliations: Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

Abstract:  While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-dependent regulation of cell-lineage determination based on interactions between beta-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. beta-catenin acts as a binary switch to simultaneously activate expression of the critical lineage-determining transcription factor, Pit1, and to repress the gene encoding the lineage-inhibiting transcription factor, Hesx1, acting via TLE/Reptin/HDAC1 corepressor complexes. The strategy of functionally distinct actions of a homeodomain factor in response to Wnt signaling is suggested to be prototypic of a widely used mechanism for generating diverse cell types from pluripotent precursor cells in response to common signaling pathways during organogenesis. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A32 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene
Authors: Thierry Maudelonde
Fran√ßoise Vignon
Aur√©lie Bardin
Pascal Pujol
Carine Chavey
Anne Licznar
Nad√®ge Servant
Vincent Cavailles
Jacques Teyssier
Jean-S√©bastien Annicotte
Lluis Fajas
Gwendal Lazennec
Eric Badia
Journal: Oncogene (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LRH-1; nuclear receptor; cholesterol homeostasis; tumor progression; breast cancer
Affiliations: Inserm Equipe Avenir, U540, 60 rue de Navacelles, Montpellier, France.

Abstract:  Liver receptor homolog-1 (LRH-1) is a nuclear receptor previously known to have distinct functions during mouse development and essential roles in cholesterol homeostasis. Recently, a new role for LRH-1 has been discovered in tumor progression, giving LRH-1 potential transforming functions. In order to identify critical factors stimulating LRH-1 expression leading to deregulated cellular proliferation, we studied its expression and its regulation in several breast cancer cell lines. We observed that LRH-1 expression was increased in estrogen receptor (ER) alpha expressing cell lines, whereas weak-to-no expression was found in nonexpressing ERalpha cell lines. In MCF7, LRH-1 expression was highly induced after treatment with 17beta-estradiol (E2). This transcriptional regulation was the result of a direct binding of the ER to the LRH-1 promoter, as demonstrated by gelshift and chromatin immunoprecipitation assays. Interestingly, siRNA-mediated inactivation of LRH-1 decreased the E2-dependent proliferation of MCF7 cells. Finally, LRH-1 protein expression was detected by immunohistochemistry in tumor cells of human mammary ductal carcinomas. Altogether, these data demonstrate that LRH-1 is transcriptionally regulated by the ER alpha and reinforce the hypothesis that LRH-1 could exert potential oncogenic effects during breast cancer formation. 

Retracted: No

PubPeer comments:
null, 
 Good afternoon, This is Lluis Fajas, the last author of this paper. First of all, I am sorry for the delayed reply. Second, I feel very uncomfortable not knowing with whom I am discussing. Concerning the issue that you raised, here it is my response. I have flipped the image 180 degrees, and as you suggested, I enhanced the contrast. If you now amplify the image, you will realize that the shape of the bands (please take the left band as an example) is very different. Moreover, even the pattern of the luminosity of the edges of the band (which is probably the reason why you thought that are duplicates) is also different. I hope that I properly addressed the question. Have a nice day  ,
Low dose IL‚Ä? suppress osteoclastogenesis in collagen‚Äêinduced arthritis via JNK dependent pathway
Authors: Yimin Wang
Yunjie Lu
Kun Wang
Yong Zhao
Jian Dong
Xiaoliang Sun
Li Zhu
Jie Zhao
Huan Li
Han Sun
Journal: Immunity Inflammation and Disease (2020)
Discipline: IMMUNOLOGY
Keywords: NF-Œ∫B; c-Jun N-terminal kinase; collagen-induced arthritis; interleukin-2; rheumatoid arthritis.
Affiliations: The Third Affiliated Hospital of Soochow University, Changzhou, China., Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China., Department of Hepatobiliary Surgery, The people's hospital of Jinsha County, China.

Abstract:  Background: Rheumatoid arthritis (RA) is one of the most common chronic immune joint diseases, mainly involving blood vessels and small joints. The complex pathogenesis of RA greatly increases the difficulty of treatment. At present, the common hormone and immunosuppressive therapy are not effective, while low-dose interleukin-2 (IL-2) recently has been found to possess some advantages for immunotherapy. However, its related signal pathway remains to be elucidated. Methods: We fabricated the model of arthritis in mice, and then low-dose IL-2 was injected at a fixed time point to observe the changes of related vascular and organ pathology, inflammatory factors, and signal pathway proteins, which were verified by statistical analysis. Results: Low dose IL-2 can reduce the severity of vascular and bone lesions in collagen-induced arthritis immune model, and inhibit osteoclast formation in vitro by phosphorylation of nuclear factor-Œ∫B (NF-Œ∫B), which inhibits the receptor activator of NF-Œ∫B ligand effect through c-Jun N-terminal kinase (JNK) pathway, and its immunotherapeutic effect depends on the activation of JNK. Conclusion: It is the first time for us to prove that low dose IL-2 can inhibit osteoclast formation in collagen-induced arthritis through the JNK dependent pathway, which will provide the angle and theoretical basis for future immunotherapy of IL-2. 

Retracted: No

PubPeer comments:
 Concern about Figure 1A: * Two figure panels in Figure 1A have a tiny overlap with each other, and both overlap with the Fibroblast panel in Figure 3A of another paper by some of the same authors, i.e. Qing Chang et al., Scandinavian Journal of Immunology (2020), doi: 10.1111 sji.12877 - https: pubpeer.com publications 71662B027149B7D15F8B57D91B5CD2 The animal models appear to be different.   , 
 The animal models were different but they were the same batches that treated in different conditions. So the images were collected in the same hard drive and some of their images was named mistakenly (the overlapped images were actually from the Model group but named mistakenly ). We had noticed this issue before and the original data has been provided to the editor for a corrigendum, which has been approved. Thank you! ,
Sch9 is a major target of TORC1 in Saccharomyces cerevisiae
Authors: Alexandre Soulard
Olivier Deloche
Robbie Loewith
Debdyuti Mukhopadhyay
Michael N Hall
Dorothea Anrather
Howard Riezman
Soyeon Lippman
Gustav Ammerer
Claudio De Virgilio
J√∂rg Urban
Alexandre Huber
Valeria Wanke
James R Broach
Journal: Molecular Cell (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Target of Rapamycin; TOR; TORC1; TORC2; AGC kinase Sch9
Affiliations: Department of Molecular Biology, University of Geneva, Geneva, CH-1211, Switzerland.

Abstract:  The Target of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intracellular and extracellular cues. Here we report that the AGC kinase Sch9 is a substrate of yeast TORC1. Six amino acids in the C terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin treatment as well as carbon or nitrogen starvation and transiently reduced following application of osmotic, oxidative, or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity, and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1 independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation, and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt. 

Retracted: No

PubPeer comments:
 Figure 6D: PCA analysis suggests that these images are more similar than expected   , 
 #1 I don t find this post to be the least bit compelling. It is obvious (from the high-res figure at the journal) that these images are not identical. The commenter makes a vague and obscure claim to have conducted some sort of  analysis , without elaboration or any explanation. The commenter provides no basis for what level of similarity is  expected , and no evidence of having understood or considered the relevant experimental technique. Overall, in its current form this post does not warrant any further serious consideration. ,
Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells
Authors: Chang Han
George K Michalopoulos
Tong Wu
Journal: Journal of Cellular Physiology (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: COX-2; EGFR; hepatocarcinogenesis; HCC cells; PGE(2)
Affiliations: Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.

Abstract:  Recent evidence indicates that cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are involved in hepatocarcinogenesis. This study was designed to evaluate the possible interaction between the COX-2 and EGFR signaling pathways in human hepatocellular carcinoma (HCC) cells. Immunohistochemical analysis using serial sections of human HCC tissues revealed positive correlation between COX-2 and EGFR in HCC cells (P &lt; 0.01). Overexpression of COX-2 in cultured HCC cells (Hep3B) or treatment with PGE(2) or the selective EP(1) receptor agonist, ONO-DI-004, increased EGFR phosphorylation and tumor cell invasion. The PGE(2)-induced EGFR phosphorylation and cell invasiveness were blocked by the EP(1) receptor siRNA or antagonist ONO-8711 and by two EGFR tyrosine kinase inhibitors, AG1478 and PD153035. The EP(1)-induced EGFR transactivation and cell invasion involves c-Src, in light of the presence of native binding complex of EP(1)/Src/EGFR and the inhibition of PGE(2)-induced EGFR phosphorylation and cell invasion by the Src siRNA and the Src inhibitor, PP2. Further, overexpression of COX-2 or treatment with PGE(2) also induced phosphorylation of c-Met, another receptor tyrosine kinase critical for HCC cell invasion. Moreover, activation of EGFR by EGF increased COX-2 promoter activity and protein expression in Hep3B and Huh-7 cells, whereas blocking PGE(2) synthesis or EP(1) attenuated EGFR phosphorylation induced by EGF, suggesting that the COX-2/PGE(2)/EP(1) pathway also modulate the activation of EGFR by its cognate ligand. These findings disclose a cross-talk between the COX-2/PGE(2)/EP(1) and EGFR/c-Met signaling pathways that coordinately regulate human HCC cell invasion. 

Retracted: Yes

PubPeer comments:
 March 2016 correction, which reads:  The authors would like to correct Fig 2, as errors were introduced in the preparation of this figure for publication. The GAPDH panel shown in Fig 2C (Anterior Cortex) is incorrectly duplicated in the GADPH panel shown in Fig 2D (Striatum). The authors have provided a corrected Fig 2D here. The authors confirm that these changes do not alter their findings. The raw blot images are provided as a Supporting Information file. Here is the original Figure 2, marked for a duplication of the GAPDH panels. Note that one blot is flipped. Reported to the journal in April 2014. I thank the authors for correcting the duplication.  ,
<p>Targeting PIK3CG in Combination with Paclitaxel as a Potential Therapeutic Regimen in Claudin-Low Breast Cancer</p>
Authors: Zhijian Li
Shubing Zhang
Yiwen Pan
Jun Chang
Wenrui Ye
Yaozhong Liu
Hao Yang
Keli Xu
Ling Hong
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: PIK3CG; combined drugs; paclitaxel; targeted therapy; Ôªøclaudin-low breast cancer.

Abstract:  Purpose: Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo. Patients and methods: The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo. Results: We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX. Conclusion: We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer. 

Retracted: No

PubPeer comments:
 Figure 2E may have a repeated image. ***  ,
MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin in osteosarcoma by targeting mTOR
Authors: L-L Yao
K Jiang
N Li
N Zhang
Z Yu
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: mTOR; MiR-100; osteosarcoma; autophagy; cisplatin
Affiliations: Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. .

Abstract:  Objective: Mammalian target of rapamycin (mTOR) can negatively regulate cell autophagy, while its expression and activity are associated with the pathogenesis of osteosarcoma. MicroRNA 100 (MiR-100) down-regulation is associated with the pathogenesis and chemo-sensitivity of osteosarcoma. Bioinformatics analysis revealed the targeted relationship between miR-100 and the 3'-UTR of mTOR. We investigate the role of miR-100 in affecting mTOR expression, osteosarcoma cell autophagy, and sensitivity to cisplatin. Patients and methods: MiR-100, mTOR, and Beclin-1 expressions in osteosarcoma tissue and normal control were compared. The relationship between miR-100 and mTOR was verified by dual luciferase assay. MiR-100, mTOR, and Beclin-1 levels in MG-63 cells and MG-63/DDP cells were tested. Cell apoptosis was determined by using flow cytometry. Cell malignancy was evaluated by colony formation assay. Results: MiR-100 and Beclin-1 significantly declined, while mTOR significantly increased in osteosarcoma tissue compared with that of normal tissue (p&lt;0.05). MiR-100 targeting significantly inhibited mTOR expression compared to that of untreated (p&lt;0.05). MiR-100 expression was down-regulated and mTOR level was elevated in MG-63/DDP cells compared with MG-63 cells (p&lt;0.05). MG-63/DDP cells exhibited reduced cell autophagy and apoptosis, and enhanced colony formation induced by DDP. MiR-100 mimic and/or small interfere mTOR (si-mTOR) significantly promoted Beclin-1 expression, cell autophagy, and cell apoptosis, while attenuated colony formation. Conclusions: MiR-100 declined, while mTOR up-regulated in osteosarcoma tissue. MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin via targeted inhibiting of mTOR. 

Retracted: Yes

PubPeer comments:
 November 2016 The Editor-in-Chief and Publisher have retracted this article [1] because the scientific integrity of the content cannot be guaranteed. An investigation by the Publisher found it to be one of a group of articles we have identified as showing evidence suggestive of attempts to subvert the peer review and publication system to inappropriately obtain or allocate authorship. This article showed evidence authorship manipulation. ,
Nod1, a CARD protein, enhances pro-interleukin-1Œ≤ processing through the interaction with pro-caspase-1
Authors: Seong Gon Son
Won Sang Park
John C Reed
Jung Young Lee
Su Young Kim
Nam Jin Yoo
Sug Hyung Lee
Journal: Biochemical and Biophysical Research Communications (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: IL-1beta; caspase-1; Nod1; RIP2; pro-inflammatory cytokine

Abstract:  The production of bioactive interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, is mediated by activated caspase-1. One of the known molecular mechanisms underlying pro-caspase-1 processing and activation involves interaction between the caspase recruit domains (CARDs) of caspase-1 and a serine/threonine kinase RIP2. While the association of Nod1 with both caspase-1 and RIP2 is already known, the consequences of these interactions are poorly understood. Because Nod1 also binds to RIP2, we hypothesized that Nod1 plays a role in pro-caspase-1 activation and IL-1beta processing. We show here that Nod1 binds to both RIP2 and caspase-1 by CARD interactions. Nod1 enhances pro-caspase-1 oligomerization and pro-caspase-1 processing. Nod1 enhances caspase-1-induced IL-1beta secretion, as well as lipopolysaccharide (LPS)-induced IL-1beta secretion in transfected cells. Moreover, HT1080 cells stably transfected with Nod1 showed higher LPS-induced IL-1beta secretion than non-transfected cells, suggesting a role of Nod1 in LPS-induced responses. Our data indicate that Nod1 can regulate IL-1beta secretion, implying that Nod1 may play a role in inflammatory responses to bacterial LPS. 

Retracted: No

PubPeer comments:
 Figure 6: More similar than expected. Could authors check please?  , 
 https: www.sciencedirect.com science article pii S0306452221005455?via%3Dihub Corrigendum to u201cEmotional, Cognitive and Neurochemical Alterations in a Premotor Stage Model of Parkinsonu2019s Diseaseu201d [Neuroscience 156(4) (2008) 830u2013840] It has been brought to our attention a problem in Figure 6 of the paper entitled u201cEmotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson s diseaseu201d, by Tadaiesky et al, published in Neuroscience Volume 156, Issue 4, 28 October 2008, Pages 830u2013840 . Apparently, the image shown in panel 6B was replicated in panel 6C when it was prepared for publication. The authors were questioned about the error and have offered their sincere apologies for this unfortunate oversight, assuming full responsibility for this mistake. This issue does not affect the quantitative analysis of the data and corresponding statistics presented in panel 6D, and therefore does not affect the main findings and conclusions of the study. They would, however, like to correct this figure and propose a revised version in which the incorrect image presented is replaced by the correct image for that experimental condition. The new Figure 6 is given below:  The authors would like to apologise for any inconvenience caused. ,
Circular RNA 0001273 in exosomes derived from human umbilical cord mesenchymal stem cells (UMSCs) in myocardial infarction
Authors: Z-M Li
T Zhang
X Li
J Song
C-X Li
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: umbilical cord mesenchymal stem cells; exosomes; circ-0001273; myocardial infarction; heart repair
Affiliations: Department of Cardiology, Qingdao Central Hospital, Qingdao, China. .

Abstract:  Objective: To investigate whether human umbilical cord mesenchymal stem cells (UMSCs) derived exosomes (exosome) can repair the heart after myocardial infarction (MI) by delivering circ-0001273 and its mechanism. Materials and methods: Through the Sprague Dawley (SD) rat MI model was established, at the same time, we designed si-circ-0001273. Phosphate-buffered saline (PBS), exosome and si-circ-0001273-exosome were transplanted into ischemic hearts of rat, respectively. Through the echocardiography, hematoxylin-eosin staining (HE) method to detect the rat heart recovery. Meanwhile, H9c2 was treated with hypoxic serum-free serum to construct an in vitro apoptosis model to further explore the effect of circ-0001273 on myocardial cell apoptosis. Results: Compared with the exosome-treated group, the left ventricular ejection fraction (EF) and shortened fraction (FS) of the rat heart was remarkably reduced and the cardiac structure was more disordered in the si-circ-0001273-exosome-treated group. Meanwhile, in vitro TUNEL staining and flow cytometry detection, results showed that compared with the exosome co-culture group, the incidence of H9C2 cell apoptosis in the si-circ-0001273-exosome co-culture group was obviously increased. Conclusions: Circ-0001273 can remarkably inhibit the occurrence of myocardial cell apoptosis in ischemic environment, promote MI repair, and provide a good reference for clinical treatment. 

Retracted: No

PubPeer comments:
 The characterization of exosomes in this study is very limited. There is no characterization of ultrastructure (EM) and size. The anti-CD63 immunoblot does not have the typical smeared appearance, and is therefore questionable. In addition, the text is full of errors and unscientific expressions.  , 
 Authors issued a correction citing this thread doi : 10.26355 eurrev_202101_24308 (PMID: 33506885) ,