PReD-Bench/PRed-Bench huggingface dataset:
Cross-hemispheric gamma synchrony between prefrontal parvalbumin interneurons supports behavioral adaptation during rule shift learning
Authors: Kathleen K A Cho
Jesse D Marshall
Vikaas S Sohal
Mark J Schnitzer
Guy Bouvier
Thomas J Davidson
Journal: Nature Neuroscience (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Organisms; adapt; changing environments; neurons; synchronization
Affiliations: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA., Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA., Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA, USA., Department of Physiology, University of California, San Francisco, San Francisco, CA, USA., Howard Hughes Medical Institute, San Francisco, CA, USA., Department of Organismic & Evolutionary Biology, Harvard University, Cambridge, MA, USA., Departments of Biology and Applied Physics, Stanford University, Stanford, CA, USA., Howard Hughes Medical Institute, Stanford, CA, USA., Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA. ., Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA. ., Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA, USA. .

Abstract:  Organisms must learn new strategies to adapt to changing environments. Activity in different neurons often exhibits synchronization that can dynamically enhance their communication and might create flexible brain states that facilitate changes in behavior. We studied the role of gamma-frequency (~40 Hz) synchrony between prefrontal parvalbumin (PV) interneurons in mice learning multiple new cue-reward associations. Voltage indicators revealed cell-type-specific increases of cross-hemispheric gamma synchrony between PV interneurons when mice received feedback that previously learned associations were no longer valid. Disrupting this synchronization by delivering out-of-phase optogenetic stimulation caused mice to perseverate on outdated associations, an effect not reproduced by in-phase stimulation or out-of-phase stimulation at other frequencies. Gamma synchrony was specifically required when new associations used familiar cues that were previously irrelevant to behavioral outcomes, not when associations involved new cues or for reversing previously learned associations. Thus, gamma synchrony is indispensable for reappraising the behavioral salience of external cues. 

Retracted: No

PubPeer comments:
 Very interesting paper. Can the authors please confirm if the PV- neurons photometry data in the following figures (1, 3, and 5) represent the same group of rats (n=8)? Thanks ![file] ,
The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition
Authors: Xiefu Zhang
Chaohui Ding
Zhen Yang
Chunlin Zhao
Junfeng Sun
Jiaxiang Wang
Tao Liu
Journal: Journal of Translational Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: lncRNAs; TUG1; colorectal cancer; gene expression regulation; metastasis
Affiliations: Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East, Zhengzhou, 450052, China. ., Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East, Zhengzhou, 450052, China. .

Abstract:  Background: Long intergenic non-coding RNAs (lncRNAs) are a class of non-coding RNAs that are involved in gene expression regulation. Taurine up-regulated gene 1 (TUG1) is a cancer progression related lncRNA in some tumor oncogenesis; however, its role in colorectal cancer (CRC) remains unclear. In this study, we determined the expression patterns of TUG1 in CRC patients and explored its effect on CRC cell metastasis using cultured representative CRC cell lines. Methods: The expression levels of TUG1 in 120 CRC patients and CRC cells were determined using quantitative real-time PCR. HDACs and epithelial-mesenchymal transition (EMT)-related gene expression were determined using western blot. CRC cell metastasis was assessed by colony formation, migration assay and invasion assay. Results: Our data showed that the levels of TUG1 were upregulated in both CRC cell lines and primary CRC clinical samples. TUG1 upregulation was closely correlated with the survival time of CRC patients. Overexpression of TUG1 in CRC cells increased their colony formation, migration, and invasion in vitro and promoted their metastatic potential in vivo, whereas knockdown of TUG1 inhibited the colony formation, migration, and invasion of CRC cells in vitro. It is also worth pointing out that TUG1 activated EMT-related gene expression. Conclusion: Our data suggest that tumor expression of lncRNA TUG1 plays a critical role in CRC metastasis. TUG1 may have potential roles as a biomarker and/or a therapeutic target in colorectal cancer. 

Retracted: No

PubPeer comments:
 Some apparent duplications in figures 3 and 4 ![file] ![file] , 
 Figs 3 and 4 together: ![file] , 
 *Astonishing that the journal published this as a correction.* Published: 22 December 2020 Correction to: The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition The Original Article was published on 08 February 2016 Correction to: J Transl Med (2016) 14:42 https: doi.org 10.1186 s12967-016-0786-z The authors (sic) found an error in the Figs. 3cu2013d and 4cu2013d of the original publication [1]. During the combination of the images of Figs. 3 and 4, the migration and invasion images were mixed up. The incorrect and correct figures are published in this correction article. The original article has been updated. ![file] ![file] ,
RETRACTED: Differential effects of valproic acid on growth, proliferation and metastasis in HTB5 and HTB9 bladder cancer cell lines
Authors: Binod Kumar
Shandra Wilson
Seok-Soo Byun
Fernando J Kim
Hari K Koul
Sweaty Koul
Lakshmipathi Khandrika
Journal: Cancer Letters (2009)
Discipline: CLINICAL MEDICINE
Keywords: bladder cancer; valproic acid; cell proliferation; cell cycle arrest; invasion
Affiliations: Department of Surgery, University of Colorado at Denver and Health Sciences Center, Aurora, 80045, USA.

Abstract:  High grade invasive bladder cancer is a leading cause of cancer deaths and treatment options are limited for this type of cancer. Recent studies have reported anticancer effects of valproic acid in many cancers and also in superficial bladder cancer. Acute valproic acid administration suppressed cell proliferation in a time- and dose-dependent manner in two muscle-invasive human bladder cancer cell lines (HTB5 and HTB9), with accompanying G1 phase cell cycle arrest. A significant decrease in colony formation ability and invasiveness was seen with valproic acid treatment though the effectiveness varied with cell type. Our results suggest a role for valproic acid in inhibiting growth and invasion of muscle-invasive bladder cancer. 

Retracted: Yes

PubPeer comments:
 It is worth noting that although published in 2019, the data contained within this paper is more than 15 years old. u201cFollowing provision of information about the study, 120 (17.8%) participants were asked to agree to remain in the study for its duration and to sign the Institutional informed consent document. Data were collected from 2000 to 2003.u201d It also appears that the institution (Fleming Heart Health Institute) with which the first author was affiliated 20 years ago no longer exists. Given these facts, it seems forgivable to ask the authors if they can make the original data files available for statistical analysis by an independent statistician. If yes, those files can be shared publicly via GitHub or Dropbox. Original data files might reassure readers as to the accuracy of results such as this: u201dOne hundred percent participant retention, that is, zero attrition, was maintained throughout this study, obviating any need for the pre-planned intent-to-treat analyses.u201d This is a remarkable result given the 16-month life of the study, the challenging diet regimens that were randomly assigned, and given that the entire study group was obese. In fact, the authors point out the normally high attrition rate with diet studies. (A similar diet+counseling randomly-assigned diet study showed 80% participants completed the trial, although this was for 24 months: N Engl J Med. 2009 February 26; 360(9): 859u2013873. doi:10.1056 NEJMoa0804748). Given remarkable results the original data is respectfully requested. ,
Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels
Authors: Fan Yang
Qian Zhong
Malin Gou
Tao Yi
Hongxin Deng
Xia Zhao
Yuquan Wei
Journal: Oncology Reports (2012)
Discipline: CLINICAL MEDICINE
Keywords: IP-10; ovarian cancer; polymeric nanoparticles; gene delivery; antitumor activity
Affiliations: Department of Gynecology and Obstetrics, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu 610041, Sichuan, PR China.

Abstract:  Currently, great interest is focused on the anti-neoplastic effects of CXC chemokine ligand 10 (IP-10/CXCL10). IP-10 has shown significant antitumor and anti-metastatic properties via immunological, antiangiogenic and anti-neoplastic mechanisms. However, very few studies on the antitumor activity of IP-10 in human ovarian cancer have been reported. The use of polymeric nanoparticles to deliver functional genes intraperitoneally holds much promise as an effective therapy for ovarian cancer. In our study, a recombinant plasmid expressing IP-10 (pVITRO-IP-10) was constructed, and biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels were prepared to deliver pVITRO-IP-10 into SKOV3 human ovarian cancer cells. Transfection efficiency was detected by expression profiling of green fluorescent protein. The expression of IP-10 was determined using RT-PCR and western blot analysis. In vitro, cell proliferation was evaluated by MTT assay. Apoptosis was examined by Hoechst33258/PI staining and flow cytometry assays. The effect on the inhibition of angiogenesis was evaluated by tube formation assay using human umbilical vein endothelial cells (HUVECs). Moreover, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the antitumor activity of HPEI+pVITRO-IP-10 complexes in nude mice. Tumor weights were evaluated during the treatment course. Cell proliferation and apoptosis were evaluated by Ki-67 immunochemical staining and TUNEL assay, and the antiangiogenic effect of pVITRO-IP-10 was assessed by CD31 immunochemical staining and alginate-encapsulated tumor cell assay. pVITRO-IP-10 was efficiently transfected into SKOV3 cells by HPEI nanogels. Intraperitoneal administration of HPEI+pVITRO-IP-10 complexes led to effective growth inhibition of ovarian cancer, in which tumor weight decreased by ~69.92% in the treatment group compared with that in the empty vector control group. Meanwhile, decreased cell proliferation, increased tumor cell apoptosis and reduction in angiogenesis were observed in the HPEI+pVITRO-IP-10 group compared with those in the control groups. These results indicated that HPEI nanogel delivery of pVITRO-IP-10 may be of value in the treatment against human ovarian cancer. 

Retracted: No

PubPeer comments:
 Fig 1D has overlap, please make comments. Thanks! ![file] ,
IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload
Authors: Alessandro Bertero
Giuseppe Cifelli
Mauro Sbroggiò
Giada Mascio
Mara Brancaccio
Guido Tarone
Emilia Turco
Emanuele De Blasio
Emilio Hirsch
Wadie F Bahou
Daniela Carnevale
Giuseppe Lembo
Lorenzo Silengo
Journal: Cardiovascular Research (2011)
Discipline: CLINICAL MEDICINE
Keywords: Raf-MEK1/2-ERK1/2 signalling cascade; IQ motif-containing GTPase-activating protein 1 (IQGAP1); heart function; remodelling; pressure overload
Affiliations: Dipartimento di Genetica, Biologia e Biochimica, Molecular Biotechnology Center, Università di Torino, via Nizza 52, Turin, Italy.

Abstract:  Aims: The Raf-MEK1/2-ERK1/2 (ERK1/2-extracellular signal-regulated kinases 1/2) signalling cascade is crucial in triggering cardiac responses to different stress stimuli. Scaffold proteins are key elements in coordinating signalling molecules for their appropriate spatiotemporal activation. Here, we investigated the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1), a scaffold for the ERK1/2 cascade, in heart function and remodelling in response to pressure overload. Methods and results: IQGAP1-null mice have unaltered basal heart function. When subjected to pressure overload, IQGAP1-null mice initially develop a compensatory hypertrophy indistinguishable from that of wild-type (WT) mice. However, upon a prolonged stimulus, the hypertrophic response develops towards a thinning of left ventricular walls, chamber dilation, and a decrease in contractility, in an accelerated fashion compared with WT mice. This unfavourable cardiac remodelling is characterized by blunted reactivation of the foetal gene programme, impaired cardiomyocyte hypertrophy, and increased cardiomyocyte apoptosis. Analysis of signalling pathways revealed two temporally distinct waves of both ERK1/2 and AKT phosphorylation peaking, respectively, at 10 min and 4 days after aortic banding in WT hearts. IQGAP1-null mice show strongly impaired phosphorylation of MEK1/2-ERK1/2 and AKT following 4 days of pressure overload, but normal activation of these kinases after 10 min. Pull-down experiments indicated that IQGAP1 is able to bind the three components of the ERK cascade, namely c-Raf, MEK1/2, and ERK1/2, as well as AKT in the heart. Conclusion: These data demonstrate, for the first time, a key role for the scaffold protein IQGAP1 in integrating hypertrophy and survival signals in the heart and regulating long-term left ventricle remodelling upon pressure overload. 

Retracted: No

PubPeer comments:
null, 
 ![file] Fig S4: also not superimposable ,
Theaflavins retard human breast cancer cell migration by inhibiting NF-kappaB via p53-ROS cross-talk
Authors: Tanya Das
Suchismita Mohanty
Lakshmishri Lahiry
Samik Chakraborty
Dewan Md Sakib Hossain
Arghya Adhikary
Journal: FEBS Letters (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: theaflavins; p53; metastasis; breast cancer cells; reactive oxygen species
Affiliations: Division of Molecular Medicine, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata, India.

Abstract:  The present study demonstrates that theaflavins exploit p53 to impede metastasis in human breast cancer cells. Our data suggest that p53-dependent reactive oxygen species (ROS) induce p53-phosphorylation via p38MAPK in a feedback loop to inhibit IkappaBalpha-phosphorylation and NF-kappaB/p65 nuclear translocation, thereby down-regulating the metastatic proteins metalloproteinase (MMP)-2 and MMP-9. When wild-type p53-expressing MCF-7 cells are transfected with p53 short-interfering RNA, or treated with a pharmacological inhibitor of ROS, theaflavins fail to inhibit NF-kappaB-mediated cell migration. On the other hand, NF-kappaB over-expression bestows MCF-7 cells with resistance to the anti-migratory effect of theaflavins. These results indicate that inhibition of NF-kappaB via p53-ROS crosstalk is a pre-requisite for theaflavins to accomplish the anti-migratory effect in breast cancer cells. 

Retracted: No

PubPeer comments:
 ![file] , 
 **YIANNIS ANDREOPOULOS** is the common co-author! ![file] , 
 **YIANNIS ANDREOPOULOS** is the common co-author! ![file] ,
Long non‐coding RNA deleted in lymphocytic leukaemia 1 promotes hepatocellular carcinoma progression by sponging miR‐133a to regulate IGF‐1R expression
Authors: Kai Liu
Wei Zhang
Yahui Liu
Songyang Liu
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DLEU1; IGF-1R; LncRNAs; PI3K/AKT; hepatocellular carcinoma
Affiliations: Department of Hepatopancreatobiliary Surgery, The First Hospital of Jilin University, Changchun, P.R. China.

Abstract:  Long non-coding RNA (lncRNA) deleted in lymphocytic leukaemia 1 (DLEU1) was reported to be involved in the occurrence and development of multiple cancers. However, the exact expression, biological function and underlying mechanism of DLEU1 in hepatocellular carcinoma (HCC) remain unclear. In this study, real-time quantitative polymerase chain reaction (qRT-PCR) in HCC tissues and cell lines revealed that DLEU1 expression was up-regulated, and the increased DLEU1 was closely associated with advanced tumour-node-metastasis stage, vascular metastasis and poor overall survival. Function experiments showed that knockdown of DLEU1 significantly inhibited HCC cell proliferation, colony formation, migration and invasion, and suppressed epithelial to mesenchymal transition (EMT) process via increasing the expression of E-cadherin and decreasing the expression of N-cadherin and Vimentin. Luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay demonstrated that DLEU1 could sponge miR-133a. Moreover, miR-133a inhibition significantly reversed the suppression effects of DLEU1 knockdown on HCC cells. Besides, we found that silenced DLEU1 significantly decreased insulin-like growth factor 1 receptor (IGF-1R) expression (a target of miR-133a) and its downstream signal PI3K/AKT pathway in HCC cells, while miR-133a inhibitor partially reversed this trend. Furthermore, DLEU1 knockdown impaired tumour growth in vivo by regulating miR-133a/IGF-1R axis. Collectively, these findings indicate that DLEU1 promoted HCC progression by sponging miR-133a to regulate IGF-1R expression. Deleted in lymphocytic leukaemia 1/miR-133a/IGF-1R axis may be a novel target for treatment of HCC. 

Retracted: No

PubPeer comments:
 Clinico-radiological data are surprising. ![file] ![file] Clearly, the problem involves several parts of the corpus callosum: body, isthmus and splenium ![file] Furthermore, the authors describe this malformation as corpus callosum agenesis ![file] This pattern seems to be hypoplasia and not agenesis (see Barkovich and Raybaud, Pediatric Neuroimaging for example). This distinction is important since pathophysiology should be different. Furthermore, another case is described in the same family: ![file] Unfortunately, the authors did not illustrate this case. Why? At last, the authors describe a cell migrational defect. But I don t understand the relevance of this *in vitro* finding with the clinico-radilogical description. I would be very interested to have additional data from the authors. ,
The major chemical-detoxifying system of UDP-glucuronosyltransferases requires regulated phosphorylation supported by protein kinase C
Authors: Partha S Mitra
Labanyamoy Kole
Ida S Owens
Kushal Chakraborty
Nikhil K Basu
Mousumi Basu
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: UGT; phosphorylation; PKC; curcumin; LS180 cells
Affiliations: Heritable Disorders Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-1830, USA.

Abstract:  Finding rapid, reversible down-regulation of human UDP-glucuronosyltransferases (UGTs) in LS180 cells following curcumin treatment led to the discovery that UGTs require phosphorylation. UGTs, distributed primarily in liver, kidney, and gastrointestinal tract, inactivate aromatic-like metabolites and a vast number of dietary and environmental chemicals, which reduces the risk of toxicities, mutagenesis, and carcinogenesis. Our aim here is to determine relevant kinases and mechanism(s) regulating phosphorylation of constitutive UGTs in LS180 cells and 10 different human UGT cDNA-transfected COS-1 systems. Time- and concentration-dependent inhibition of immunodetectable [(33)P]orthophosphate in UGTs and protein kinase Cepsilon (PKCepsilon), following treatment of LS180 cells with curcumin or the PKC inhibitor calphostin-C, suggested UGT phosphorylation is supported by active PKC(s). Immunofluorescent and co-immunoprecipitation studies with UGT-transfected cells showed co-localization of UGT1A7His and PKCepsilon and of UGT1A10His and PKCalpha or PKCdelta. Inhibition of UGT activity by PKCepsilon-specific antagonist peptide or by PKCepsilon-targeted destruction with PKCepsilon-specific small interference RNA and activation of curcumin-down-regulated UGTs with typical PKC agonists verified a central PKC role in glucuronidation. Moreover, in vitro phosphorylation of nascent UGT1A7His by PKCepsilon confirms it is a bona fide PKC substrate. Finally, catalase or herbimycin-A inhibition of constitutive or hydrogen peroxide-activated-UGTs demonstrated that reactive oxygen species-related oxidants act as second messengers in maintaining constitutive PKC-dependent signaling evidently sustaining UGT phosphorylation and activity. Because cells use signal transduction collectively to detect and respond appropriately to environmental changes, this report, combined with our earlier demonstration that specific phospho-groups in UGT1A7 determined substrate selections, suggests regulated phosphorylation allows adaptations regarding differential phosphate utilization by UGTs to function efficiently. 

Retracted: No

PubPeer comments:
 There are several undeclared splicing sites in Fig. 5C. ![file] ,
Melatonin suppresses Ti-particle-induced inflammatory osteolysis via activation of the Nrf2/Catalase signaling pathway
Authors: Jun Lin
Yazhong Zhang
Xu Zhu
Huilin Yang
Fan He
Journal: International Immunopharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Melatonin; Nrf2; Osteoclasts; Osteolysis; Ti particles.
Affiliations: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou 215007, China., Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou 215007, China. Electronic address: ., Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: .

Abstract:  Aseptic loosening induced by osteolysis is recognized as a late complication of joint replacement. Osteoclasts stimulated by Titanium (Ti) nanoparticles play a critical role in periprosthetic osteolysis. Emerging evidence indicates that melatonin, a hormone primarily synthesized by the pineal gland, has been shown an inhibitory effect on osteoclast formation. However, it is unclear whether melatonin could suppress Ti-particle-induced osteoclastogenesis and what the underlying mechanisms were involved in. Herein, we aimed to investigate the effect of melatonin on osteoclast differentiation and osteolysis stimulated by Ti particles. Our results showed that the in vitro osteoclastogenesis of mouse bone marrow monocytes (BMMs) stimulated by Ti particles was suppressed by melatonin treatments in a dose-dependent manner. Further experiments revealed that melatonin up-regulated the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and catalase (CAT) at both the mRNA and protein levels. The role of the Nrf2/CAT signaling pathway was confirmed by the fact that silencing the expression of NRF2 by small interfering RNA (siRNA) counteracted the anti-osteolysis effects of melatonin. Furthermore, in vivo intraperitoneal injection of melatonin successfully attenuated periprosthetic osteolysis induced by Ti particles in a murine calvarial model. Our findings demonstrate that melatonin is a promising therapeutic agent for treating periprosthetic osteolysis by inhibiting the Ti-particle-stimulated osteoclastogenesis via activation of the Nrf2/Catalase signaling pathway. 

Retracted: No

PubPeer comments:
 One of the micrographs in 2A has been duplicated, rotated and presented as something else in Figure 3A. ![file] ,
microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest
Authors: Alexander Pertsemlidis
Monica Li
Xiuye Ma
Tzu-Hung Hsiao
Liqin Du
Yidong Chen
Zhenze Zhao
Adam Kosti
Derek Sung
Gregory Lin
Journal: RNA Biology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: 13-cis retinoic acid; Bio-control; Bio-miR-449a; CASP2; CCNE2
Affiliations: a Greehey Children's Cancer Research Institute; The University of Texas Health Science Center at San Antonio ; San Antonio , TX USA.

Abstract:  microRNA-449a (miR-449a) has been identified to function as a tumor suppressor in several types of cancers. However, the role of miR-449a in neuroblastoma has not been intensively investigated. We recently found that the overexpression of miR-449a significantly induces neuroblastoma cell differentiation, suggesting its potential tumor suppressor function in neuroblastoma. In this study, we further investigated the mechanisms underlying the tumor suppressive function of miR-449a in neuroblastoma. We observed that miR-449a inhibits neuroblastoma cell survival and growth through 2 mechanisms--inducing cell differentiation and cell cycle arrest. Our comprehensive investigations on the dissection of the target genes of miR-449a revealed that 3 novel targets- MFAP4, PKP4 and TSEN15 -play important roles in mediating its differentiation-inducing function. In addition, we further found that its function in inducing cell cycle arrest involves down-regulating its direct targets CDK6 and LEF1. To determine the clinical significance of the miR-449a-mediated tumor suppressive mechanism, we examined the correlation between the expression of these 5 target genes in neuroblastoma tumor specimens and the survival of neuroblastoma patients. Remarkably, we noted that high tumor expression levels of all the 3 miR-449a target genes involved in regulating cell differentiation, but not the target genes involved in regulating cell cycle, are significantly correlated with poor survival of neuroblastoma patients. These results suggest the critical role of the differentiation-inducing function of miR-449a in determining neuroblastoma progression. Overall, our study provides the first comprehensive characterization of the tumor-suppressive function of miR-449a in neuroblastoma, and reveals the potential clinical significance of the miR-449a-mediated tumor suppressive pathway in neuroblastoma prognosis. 

Retracted: No

PubPeer comments:
 Figure 4: * Red boxes: The RA BE(2)-C panels in Figure 4D appear to look similar to the RA SKNBE panels in Figure 4E, albeit rotated 180 degrees. I have only marked the DAPI panels, but the similarities are also visible in the BrdU and Merge panels. Could the authors please check? ![file] ,
ARR19 (androgen receptor corepressor of 19 kDa), an antisteroidogenic factor, is regulated by GATA-1 in testicular Leydig cells
Authors: Hyun Joo Lee
Keesook Lee
Imteyaz Qamar
Eun-Yeung Gong
Eunsook Park
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ARR19; Leydig cells; steroidogenesis; GATA-1; cAMP
Affiliations: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.

Abstract:  ARR19 (androgen receptor corepressor of 19 kDa), which encodes for a leucine-rich protein, is expressed abundantly in the testis. Further analyses revealed that ARR19 was expressed in Leydig cells, and its expression was differentially regulated during Leydig cell development. Adenovirus-mediated overexpression of ARR19 in Leydig cells inhibited testicular steroidogenesis, down-regulating the expression of steroidogenic enzymes, which suggests that ARR19 is an antisteroidogenic factor. Interestingly, cAMP/luteinizing hormone attenuated ARR19 expression in a fashion similar to that of GATA-1, which was previously reported to be down-regulated by cAMP. Sequence analysis of the Arr19 promoter revealed the presence of two putative GATA-1 binding motifs. Further analyses with 5' deletion and point mutants of putative GATA-1 binding motifs showed that these GATA-1 binding sites were critical for high promoter activity. CREB-binding protein coactivated GATA-1 and markedly increased the activity of the Arr19 promoter. Both GATA-1 and CREB-binding proteins occupied the GATA-1 motifs within the Arr19 promoter, which was repressed by cAMP treatment. Altogether, these findings demonstrate that ARR19 is the target gene of GATA-1 and suggest that ARR19 gene expression in testicular Leydig cells is regulated by luteinizing hormone/cAMP signaling via the control of GATA-1 expression, resulting in the control of testicular steroidogenesis. 

Retracted: No

PubPeer comments:
 ![file] ,
The role of N-acetyltransferase 8 in mesenchymal stem cell-based therapy for liver ischemia/reperfusion injury in rats
Authors: Huan Liu
Jinqiu Fu
Yong Zhuang
Qing Shi
Dong Li
Xiuli Ju
Haiyan Zhang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Mesenchymal stem cells; MSCs; hepatic I/R injury; N-acetyltransferase 8; NAT8
Affiliations: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, P.R. China.

Abstract:  Objective: To evaluate the impact of mesenchymal stem cells (MSCs) against hepatic I/R injury and explore the role of N-acetyltransferase 8 (NAT8) in the process. Methods: We investigated the potential of injected MSCs systemically via the tail vein in healing injuried liver of the SD rat model of 70% hepatic I/R injury by measuring the biochemical and pathologic alterations. Subsequently, we evaluated the expression levels of NAT8 by western blotting in vivo. Concurrently, hydrogen peroxide (H2O2)-induced apoptosis in the human normal liver cell line L02 was performed in vitro to evaluate the protective effects of MSC conditioned medium (MSC-CM) on L02 cells. In addition, we downregulated and upregulated NAT8 expression in L02 cells and induced apoptosis by using H2O2 to study the protective role of NAT8. Results: MSCs implantation led to a significant reduced liver enzyme levels, an advanced protection in the histopathological findings of the acutely injured liver and a significantly lower percentage of TUNEL-positive cells, which were increased after I/R injury. In vitro assays, MSC-CM inhibited hepatocyte apoptosis induced by H2O2. Moreover, overexpression or downregulation of NAT8 prevented or aggravated hepatocyte apoptosis induced by H2O2, respectively. Conclusions: MSC transplantation provides support to the I/R-injured liver by inhibiting hepatocellular apoptosis and stimulating NAT8 regeneration. 

Retracted: No

PubPeer comments:
 Figure 5A. * Red boxes: In the Sham column, the 6h and 24h panels appear to show an overlap. ![file] , 
 #1 I have been recently made aware of this issue. It is true that the 6h and 24h panels are overlaped in the sham column. When TUNEL staining liver tissue sections were made, all the sham group sections were taken together for photos. The same section was taken from different angles during taking the photos, and the author made mistakes in marking. Now the figure is corrected after examination of the original images.u00a0The completeness of the whole research did not been affected and conclusions did not been changed.u00a0We have informed PLOS ONE and are waiting for a reply from the journal , 
 Dear Dr. Li, Thank you for checking and correcting this figure. I appreciate your reply here. ,
Cytokine-like 1 Knock-out Mice (Cytl1−/−) Show Normal Cartilage and Bone Development but Exhibit Augmented Osteoarthritic Cartilage Destruction
Authors: Jimin Jeon
Jin-Hong Kim
Jinseol Rhee
Kyung-Hwun Chung
Churl-Hong Chun
Woo-Keun Song
Je-Hwang Ryu
Gyusuk Lee
Hwanhee Oh
Jang-Soo Chun
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cytl1; chondrogenesis; cartilage development; osteoarthritis; mouse model
Affiliations: Cell Dynamics Research Center and School of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.

Abstract:  We have shown that cytokine-like 1 (Cytl1) is a novel autocrine regulatory factor that regulates chondrogenesis of mouse mesenchymal cells (Kim, J. S., Ryoo, Z. Y., and Chun, J. S. (2007) J. Biol. Chem. 282, 29359-29367). In this previous work, we found that Cytl1 expression was very low in mesenchymal cells, increased dramatically during chondrogenesis, and decreased during hypertrophic maturation, both in vivo and in vitro. Moreover, exogenous addition or ectopic expression of Cytl1 caused chondrogenic differentiation of mouse limb bud mesenchymal cells. In the current study, we generated a Cytl1 knock-out (Cytl1(-/-)) mouse to investigate the in vivo role of Cytl1. Deletion of the Cytl1 gene did not affect chondrogenesis or cartilage development. Cytl1(-/-) mice also showed normal endochondral ossification and long bone development. Additionally, ultrastructural features of articular cartilage, such as matrix organization and chondrocyte morphology, were similar in wild-type and Cytl1(-/-) mice. However, Cytl1(-/-) mice were more sensitive to osteoarthritic (OA) cartilage destruction. Compared with wild-type littermates, Cytl1(-/-) mice showed more severe OA cartilage destruction upon destabilization of the medial meniscus of mouse knee joints. In addition, expression levels of Cytl1 were markedly decreased in OA cartilage of humans and experimental mice. Taken together, our results suggest that, rather than regulating cartilage and bone development, Cytl1 is required for the maintenance of cartilage homeostasis, and loss of Cytl1 function is associated with experimental OA cartilage destruction in mice. 

Retracted: No

PubPeer comments:
 Figure 3D. * Red boxes: In the right column the WT and KO images appear to look very similar, with a slight rotation. ![file] ,
Forkhead factor FOXQ1 promotes TGF-β1 expression and induces epithelial–mesenchymal transition
Authors: Peng-Wei Qi
Ya-Wei Chen
Xiao-Shan Feng
Dong-Mei Fan
Journal: Molecular and Cellular Biochemistry (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Epithelial-mesenchymal transition (EMT); tumor invasion; metastasis; genetic program; forkhead box Q1 (FOXQ1)
Affiliations: Department of Gynecology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, Henan, People's Republic of China.

Abstract:  Epithelial-mesenchymal transition (EMT) promotes tumor invasion and metastasis, but the coordination and integration mechanisms of these processes are still not fully understood. In this study, we used a cross-species expression profiling strategy of Hela cells to determine an important genetic program transfers. In particular, we have discovered a new transfer function, which is not previously known about transcription factor forkhead box Q1 (FOXQ1). The shRNA anti-FOXQ1 gene was synthesized and transfected into the Hela and EpRas cells. RT-PCR assay was performed to detect the mRNA levels in cells. Cell adhesion and separation assay were used to examine the cell-cell adhesion and separation among cells. Wound healing assay was utilized to examine cell migration and invasion ability. Chromatin immunoprecipitation assay was used to investigate the interaction between E-cadherin and N-cadherin and FOXQ1 promoter region. The results indicated that ectopic expression of FOXQ1 increased cell migration and invasion in vitro, enhanced mammary epithelial cells in vivo lung metastasis, and triggered significant EMT. In contrast, the opposite effects in vitro and in vivo of FOXQ1 knockdown phenotypes were caused by these mechanisms. Notably, FOXQ1 repressed core EMT regulation of the expression of TGF-β1. FOXQ1 protein directly interacts with E-cadherin and N-cadherin promoter region. And surveys show that FOXQ1 expression regulation by TGF-β1 and blockade induced EMT both morphological and molecular levels. Our findings emphasize the feasibility of cross-species expression profiles, as a strategy to identify metastasis-related genes. The induction of EMT by FOXQ1 defines a new transfer function in promoting cancer behind possible mechanisms. 

Retracted: No

PubPeer comments:
 Figure 2. Unexpected similarities between the top and bottom panels. I marked some areas that look similar to each other without trying to mark them all. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ![file] , 
 Not part of the 2015 report, but something I just noticed (maybe because of 5 more years of experience?) is that all four panels in Figure 4C appear to contain repetitive elements. ![file] ,
BTG3 upregulation induces cell apoptosis and suppresses invasion in esophageal adenocarcinoma
Authors: Xiaonan Chen
Wenqiao Zang
Min Li
Yuanyuan Wang
Guoqiang Zhao
Pingping Liu
Yuwen Du
Journal: Molecular and Cellular Biochemistry (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BTG3; tumor suppressor; esophageal adenocarcinoma; cell proliferation; migration
Affiliations: College of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou, 450001, China.

Abstract:  B cell translocation gene 3 (BTG3) is a tumor suppressor by inhibiting cell proliferation, migration, and regulating cell cycle progression in several tumors. However, its role in esophageal adenocarcinoma (EAC) remains unknown. Here, we detected the expression of BTG3 in EAC tissues and subsequent progression. BTG3 expression was significant decreased in EAC tissues and cell lines detected by real-time RT-PCR and Western blot. Relationships of BTG3 with EAC clinicopathology were analyzed statistically. The decrease expression of BTG3 is associated with lymph node metastases. In vitro assay demonstrated that overexpression of BTG3 significantly suppressed colony formation and proliferation of EAC cells. The suppressed migration and invasion abilities found in BTG3-overexpressing EAC cells. Our findings suggested that BTG3 is suppressor in the progression of EAC. 

Retracted: No

PubPeer comments:
 [Top]:  Fig. 2 ... f, g Cells were stained with Giemsa after transfection with BTG3 expression construct in OE-33 and OE-19 cells . [Bottom]:  Figure 3 ... D. miR-663 transfection of PANC-1 reduced growth of colonies. Colony formation in soft agar after 14 days using PANC-1 exposed to miR-663. From  miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer [(Zang et al. 2015)] . ![file] Could the authors clarify whether the colonies involve esophageal or pancreatic carcinoma cell lines? , 
 Left: Fig 2 F, G again. At right:  Figure 2 c, d Number of EC9706 and KYSE30 colonies in the miR-494 group was significantly reduced compared with that in the Scramble and Blank groups... from  Upregulation of miR-494 Inhibits Cell Growth and Invasion and Induces Cell Apoptosis by Targeting Cleft Lip and Palate Transmembrane 1-Like in Esophageal Squamous Cell Carcinoma [(Zhang et al. 2015)] . ![file] Could the authors clarify the identities of the cell lines in these images? Could they comment on the appearance of a few colonies in one of the versions in each matched pair, or alternatively, the disappearance of colonies from the other version? , 
 [Bottom]:  Fig. 5 ... (c OE-33 cells, d OE-19 cells). Cell invasion was measured using the Transwell invasion assay. [Top]:  Fig. 3 Trans-well assays were used to assess the invasive ability of EC cells after transfection. a...b From [Zhang et al 2015] . ![file] Images overlap, as shown, after diagonal flips. , 
 [Perhaps a systemic problem] . Journals and readers may wish to proceed with caution. ,
Long non-coding RNA XIST promotes hepatocellular carcinoma progression by sponging miR-200b-3p
Authors: Q Xu
W-G Liu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA XIST; hepatocellular carcinoma; RT-qPCR; CCK-8 assay; colony formation assay
Affiliations: Department of General Surgery, Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing, China. .

Abstract:  Objective: Recent studies have proved that long noncoding RNAs (lncRNAs) act as an important role in many diseases. In this research, lncRNA XIST was explored to identify how it functions in the development of hepatocellular carcinoma (HCC). Patients and methods: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect XIST expression in HCC patients. Then, we conducted Cell Counting Kit-8 (CCK-8) assay and colony formation assays in vitro. Furthermore, mechanism assays and the interaction between XIST and miR-200b-3p were conducted. Results: By comparing with XIST expression in adjacent tissues, the XIST expression level was significantly higher in HCC samples. Moreover, functional assays showed that the cell growth ability of HCC cells was inhibited after XIST was silenced in vitro, and tumor formation was inhibited after XIST was silenced in vivo. Further experiments showed that miR-200b-3p was directly targeted by XIST. Conclusions: Above results suggest that XIST could enhance the cell growth ability of HCC by targeting miR-200b-3p, which suggest that XIST may be a potential therapeutic target in HCC. 

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. ,
Vulnerability to Meningococcal Disease in Immunodeficiency Due to a Novel Pathogenic Missense Variant in NFKB1
Authors: Gunnar Schmidt
Torsten Witte
Reinhold Ernst Schmidt
Faranaz Atschekzei
Manfred Anim
Natalia Dubrowinskaja
Georgios Sogkas
Journal: Frontiers in Immunology (2021)
Discipline: IMMUNOLOGY
Keywords: NFKB1; Nfkb1 (p50); common variable immune deficiency (CVID); hypogammaglobulinemia; primary antibody deficiency (PAD).

Abstract:  NF-κB1 deficiency is suggested to be the most common cause of common variable immunodeficiency (CVID). NFKB1 encodes for the p105 precursor protein of NF-κB1, which is converted into the active transcriptional subunit p50 through proteasomal processing of its C-terminal half upon stimulation and is implicated in the canonical NF-kB pathway. Rare monoallelic NFKB1 variants have been shown to cause (haplo) insufficiency. Our report describes a novel NFKB1 missense variant (c.691C&gt;T, p.R230C; allele frequency 0.00004953) in a family vulnerable to meningitis, sepsis, and late-onset hypogammaglobulinemia. We investigated the pathogenic relevance of this variant by lymphocyte stimulation, immunophenotyping, overexpression study and immunoblotting. The ectopic expression of p50 for c.691 C&gt;T restricted transcriptionally active p50 in the cytoplasm, and immunoblotting revealed reduced p105/50 expression. This study shows that the deleterious missense variant in NFKB1 adversely affects the transcriptional and translational activity of NFκB1, impairing its function. Patients immunological parameters show a progressive course of hypogammaglobulinemia, which may partially account for the incomplete disease penetrance and suggest the need for closer immunological monitoring of those mutation carriers. 

Retracted: No

PubPeer comments:
 Dear authors, Could you please check Fig. 1 and E: the actin loading control appears to be identical in D and E, although PBMCs in D were unstimulated whereas PBMCs in E were PMA stimulated. ![file] ,
Circ-PRMT5 promotes gastric cancer progression by sponging miR-145 and miR-1304 to upregulate MYC
Authors: Xiaomin Guo
Wenbo Du
Ding Li
Junhui Tong
Lihua Kuang
Ping Li
Xin Li
Daoming Liang
Shuping Tong
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gastric cancer; MYC; circ-PRMT5; invasion; miR-1304
Affiliations: Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, China;, Department of General Surgery, Nantong Tumor Hospital, Nantong, Jiangsu, China;, School of Mongol Medicine, Chuxiong Medical College, Chuxiong, Yunnan, China;, Academic Office, Hainan Medical University, Haikou, Hainan, China;, School of Mongol Medicine, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, China;, Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, China;, Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China;, Department of Internal Medicine, Shenzhen Pingle Orthopaedic Hospital, Pingshan New District, Shenzhen, China;, Department of Gastrointestinal Surgery, Kunming Medical University Second Hospital, Kunming, Yunnan, China

Abstract:  Background: Gastric cancer (GC) is a global leading source of cancer-associated deaths. Circular RNAs (circRNAs) are a new type of non-coding RNA and promising biomarkers for diagnosis of multiple diseases such as cancer.Methods: Circ-PRMT5 expression was validated in 90 GC patient tissues and 6 different GC cells by qRT-PCR. Sublocalization of circ-PRMT5 in GC cells was determined in isolated nuclear and cytoplasmic RNAs. CircInteractome and miRanda were used to predict binding sites between circ-PRMT5 with micRNAs, and micRNAs with target mRNA. The correlation between genes was determined by the Pearson correlation analysis. The molecular mechanism was demonstrated by RNA in vivo precipitation, point mutation, luciferase activity and rescue experiments.Results: Circ-PRMT5 expression was significantly higher in GC than in adjacent normal tissues, and GC patients with circ-PRMT5 high expression had shorter survival times. Functionally, circ-PRMT5 silence inhibited GC cell growth and invasion. Mechanism analysis showed that circ-PRMT5 sponged miR-145/miR-1304 to upregulate MYC expression and GC development.Conclusion: Our findings demonstrated that circ-PRMT5 function as an oncogene in GC patients by targeting miR-145/miR-1304/MYC axis. High circ-PRMT5 expression may provide a poor prognostic indicator of survival in GC patients and targeting circ-PRMT5/miR-145/miR-1304/MYC axis may be a novel therapeutic strategy for GC. 

Retracted: No

PubPeer comments:
 Figure 2 and 5 appear to show two sets of overlapping panels, shown here in red and yellow boxes. ![file] ,