PReD-Bench/PRed-Bench huggingface dataset:
Association of CNK1 with Rho guanine nucleotide exchange factors controls signaling specificity downstream of Rho
Authors: Alan Hall
Anja Schmidt
Aron B Jaffe
Journal: Current Biology (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Rho; GTPase; signal transduction pathways; Rho target proteins; scaffold proteins
Affiliations: Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom.

Abstract:  Background: Rho is a small GTPase that controls signal transduction pathways in response to a large number of extracellular stimuli. With over 15 potential Rho target proteins identified to date, however, it is not clear how distinct signaling outputs can be generated downstream of a particular stimulus. Results: Several of the known Rho targets are structurally reminiscent of scaffold proteins, which are generally thought to play an important role in controlling signaling specificity. Here, we show that the Rho target CNK1 is a scaffold protein that interacts with Net1 or p115RhoGEF, two Rho-specific guanine nucleotide exchange factors (GEFs), as well with MLK2 and MKK7, two of the kinase components in the JNK MAP kinase cascade. CNK1 acts cooperatively with the two GEFs to activate JNK MAP kinase, but not other Rho-mediated pathways. In HeLa cells, serum or sphingosine-1-phosphate stimulate Rho-dependent activation of the JNK MAP kinase cascade, and this requires endogenous CNK1. Conclusions: We conclude that CNK1 couples a subset of Rho exchange factors to activation of the JNK MAP kinase pathway and that signaling specificity is achieved through complexes containing both upstream activators and downstream targets of Rho. 

Retracted: No

PubPeer comments:
 Figure 2. Splicing in some panels, but not apparent in others. ![file] , 
 Figure 5. Splicing in some panels, but not apparent in others. ![file] ,
Withdrawn: COVID-19 is ageist, sexist, ruthless, dispassionate and opportunistic – Protecting our vulnerable
Authors: Victor Grech
Sarah Cuschieri
Journal: Early Human Development (2020)
Discipline: CLINICAL MEDICINE
Keywords: Article withdrawal; Author; Editor; Publisher; Elsevier Policy
Affiliations: Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta. Electronic address: ., Mater Dei Hospital, Malta. Electronic address: .

Abstract:  This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal. 

Retracted: No

PubPeer comments:
 **Retracted** in March 2021: https: doi.org 10.1016 j.earlhumdev.2020.105214  *This article has been withdrawn at the request of the author(s) and or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https: www.elsevier.com about our-business policies article-withdrawal* The background for this and other retractions of the same authors has been covered by Retraction Watch: https: retractionwatch.com 2021 03 31 beam-us-up-elsevier-pulls-26-covid-19-papers-by-researcher-with-a-penchant-for-star-trek ,
Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway
Authors: Yarui Li
Yun Wang
Dan Guo
Yan Zhao
Guifang Lu
Juan Zhang
Chen Mi
Mudan Ren
Xinlan Lu
Shuixiang He
Journal: Cell death & disease (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: lncRNA; SNHG5; hepatocellular carcinoma; progression; apoptosis
Affiliations: Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China., Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China. .

Abstract:  Accumulating evidence have suggested that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers. The present study aimed to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in hepatocellular carcinoma (HCC) progression using human tissues and cell lines. The quantitative real-time PCR results showed that SNHG5 was up-regulated in both HCC tissues and hepatoma cell lines and was closely associated with tumor size, hepatitis B virus infection, histologic grade, TNM stage, and portal vein tumor thrombus (PVTT) in HCC patients. Knockdown of SNHG5 induced apoptosis and repressed cell cycle progression, cell growth, and metastasis in hepatoma cell lines, whereas overexpression of SNHG5 had the opposite effects. In vivo functional assay, xenograft tumors grown from SNHG5-knockdown cells had smaller mean volumes than the tumors grown from negative control cells. Further investigations showed that SNHG5 may act as a competing endogenous RNA by competitively binding miR-26a-5p and thereby modulating the derepression of downstream target GSK3β, which were further confirmed by luciferase reporter assay. Functionally, SNHG5 promotes tumor growth and metastasis by activating Wnt/β-catenin pathway and inducing epithelial to mesenchymal transition (EMT). Taken together, SNHG5 promotes HCC progression by competitively binding miR-26a-5p and regulating GSK3β and Wnt/β-catenin signal pathway. 

Retracted: No

PubPeer comments:
 Figure 2G. Some panels appear to show an overlap. In one set of images that look similar (marked in three shades of blue) the left and right  shores are similar, while the middle (scratch) area appears to be different. ![file] , 
 Figure 2I. * Blue boxes: Two panels appear to show an overlap. ![file] , 
 Figure 3H. * Yellow boxes: Two panels appear to show an overlap. ![file] , 
 Two assays in Figure 6B also appear unexpectedly similar, after 90-degree rotation and recoloring. *** ![file] ,
Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype
Authors: Annarita Miccio
Luis C Fernandez-Diaz
Licia Selleri
Francesco Blasi
Elena Longobardi
Giuliana Ferrari
Patrizia Di Rosa
Roberta Mazzieri
Nicola Micali
Elisabetta Ferretti
J Carlos Villaescusa
Journal: Molecular and Cellular Biology (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Prep1; Pbx homeodomain transcription factors; embryonic development; hypoplasia; anemia
Affiliations: Laboratory of Molecular Genetics, DIBIT, via Olgettina 58, 20132 Milano, Italy.

Abstract:  The interaction of Prep1 and Pbx homeodomain transcription factors regulates their activity, nuclear localization, and likely, function in development. To understand the in vivo role of Prep1, we have analyzed an embryonic lethal hypomorphic mutant mouse (Prep1(i/i)). Prep1(i/i) embryos die at embryonic day 17.5 (E17.5) to birth with an overall organ hypoplasia, severe anemia, impaired angiogenesis, and eye anomalies, particularly in the lens and retina. The anemia correlates with delayed differentiation of erythroid progenitors and may be, at least in part, responsible for intrauterine death. At E14.5, Prep1 is present in fetal liver (FL) cMyb-positive cells, whose deficiency causes a marked hematopoietic phenotype. Prep1 is also localized to FL endothelial progenitors, consistent with the observed angiogenic phenotype. Likewise, at the same gestational day, Prep1 is present in the eye cells that bear Pax6, implicated in eye development. The levels of cMyb and Pax6 in FL and in the retina, respectively, are significantly decreased in Prep1(i/i) embryos, consistent with the hematopoietic and eye phenotypes. Concomitantly, Prep1 deficiency results in the overall decrease of protein levels of its related family member Meis1 and its partners Pbx1 and Pbx2. As both Prep1 and Meis interact with Pbx, the overall Prep1/Meis-Pbx DNA-binding activity is strongly reduced in whole Prep1(i/i) embryos and their organs. Our data indicate that Prep1 is an essential gene that acts upstream of and within a Pbx-Meis network that regulates multiple aspects of embryonic development. 

Retracted: No

PubPeer comments:
null, 
 Figure 7B. Much more similar than expected. https: imgur.com nWh4eew ,
An ortho-Iminoquinone Compound Reacts with Lysine Inhibiting Aggregation while Remodeling Mature Amyloid Fibrils
Authors: Luciana Romão
Fernando L Palhano
Debora Foguel
Neil P Grimster
Marcela C de Moraes
Jeffery W Kelly
Fernanda S Sagrillo
Luiza Fernandes
Nathalia Moraes
Augusto V Magalhães
Journal: ACS chemical neuroscience (2017)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Alzheimer’s disease; Imine; Parkinson’s disease; alpha-synuclein; amyloid aggregation
Affiliations: Instituto de Bioquímica Médica Leopoldo de Meis, Programa de Biologia Estrutural, Universidade Federal do Rio de Janeiro , Rio de Janeiro 21941-590, Brazil., Department of Organic Chemistry, Chemistry Institute, Fluminense Federal University , Niteroi, Rio de Janeiro 24020-141, Brazil., Universidade Federal do Rio de Janeiro , Pólo de Xerém, Duque de Caxias, Rio de Janeiro 25245-390, Brazil., Departments of Chemistry and Molecular Medicine and the Skaggs Institute for Chemical Biology, The Scripps Research Institute , 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.

Abstract:  Protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. It has been shown that lysine residues play a key role in the formation of these aggregates. Thus, the ability to disrupt aggregate formation by covalently modifying lysine residues could lead to the discovery of therapeutically relevant antiamyloidogenesis compounds. Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit amyloid aggregation. Using alpha-synuclein and Aβ1-40 as model amyloidogenic proteins, we observed that IQ was able to react with lysine residues and reduce amyloid aggregation. We also observed that IQ reacted with free amines within the amyloid fibrils preventing their dissociation and seeding capacity. 

Retracted: No

PubPeer comments:
 Figures 6B and 7B are surprisingly similar. Could authors check if a mistake occurred during the arrangement of these photos? ![file] ,
Daidzin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents LPS‐induced bone loss in vivo
Authors: Chengming Wei
Gejin Wei
Tihong Liang
Xiaolian Nong
Jinmin Zhao
Qiteng Lu
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: daidzin; osteoclast; osteoclastogenesis; osteolytic diseases.
Affiliations: Guangxi Medical University Postdoctoral Research Station, Guangxi Medical University, Guangxi, China., Department of Orthopedics, No.303 hospital of PLA, Guangxi, China., Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Abstract:  Osteoclasts are multinuclear giant cells responsible for bone resorption in bone loss diseases, including rheumatoid arthritis, periodontitis, and the aseptic loosening of orthopedic implants. Because of injurious side effects with currently available drugs, it is necessary to continue research novel bone-protective therapies. Daidzin, a naturally occurring isoflavone found in leguminous plants, has numerous beneficial pharmacologic effects, including anti-cancer, anti-cholesterol, and anti-angiocardiopathy, promoting osteoblasts differentiation, and even anti-osteoporosis. However, the effect of daidzin on the regulation of osteoclast activity has not yet been investigated. In this study, our study showed that daidzin significantly inhibited receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages and the hydroxyapatite-resorbing activity of mature osteoclasts by inhibiting RANKL-induced NF-kB signaling pathway. In addition, daidzin could inhibit the expression of osteoclast marker genes, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene fos (c-Fos), tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK). Consistent with in vitro results, daidzin inhibited lipopolysaccharide-induced bone loss by suppressing the osteoclast differentiation. Together our data demonstrated that daidzin inhibits RANKL-induced osteoclastogenesis through suppressing NF-ĸB signaling pathway and that daidzin is a promising agent in the treatment of osteolytic diseases. 

Retracted: Yes

PubPeer comments:
 I wanted to make the authors aware of the findings on this website https: covid19.scienceofscience.org doi 10.1101 2020.04.19.048710 ![file] Disclaimer: THE SITE DO NOT SHOW OR IMPLY ANY TYPE OF RESEARCH MISCONDUCT, INCLUDING PLAGIARISM, FABRICATION, OR FALSIFICATION, EITHER DIRECTLY OR INDIRECTLY. THE SITE DOES NOT WARRANT THAT ANY RESULTS OR ANALYSES ARE COMPLETE OR ACCURATE. The site and all information available through the site are provided  as is , with all faults, and  as available . ,
DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells
Authors: Yoshiyuki Suzuki
Ryota Sekine
Takashi Nakano
Sangeeta Kakoti
Mayu Isono
Kiyoshi Miyagawa
Takaaki Yasuhara
Takahiro Oike
Endang Nuryadi
Atsushi Shibata
Koji Kono
Atsuko Niimi
Kathryn D Held
Yoshihiko Hagiwara
Hiro Sato
Tiara Bunga Mayang Permata
Yuya Yoshimoto
Journal: Nature communications (2017)
Discipline: Multidisciplinary
Keywords: PD-L1 upregulation; DNA double-strand break (DSB); genotoxic stress; ATM; ATR
Affiliations: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan., Research Program for Heavy Ion Therapy, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma, 371-8511, Japan., Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan., Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma, 371-8511, Japan., Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02114, USA., International Open Laboratory, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma, 371-8511, Japan., Department of Radiation Oncology, Fukushima Medical University, Fukushima, 960-1295, Japan., Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, 960-1295, Japan., Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma, 371-8511, Japan. ., Education and Research Support Center, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan. .

Abstract:  Accumulating evidence suggests that exogenous cellular stress induces PD-L1 upregulation in cancer. A DNA double-strand break (DSB) is the most critical type of genotoxic stress, but the involvement of DSB repair in PD-L1 expression has not been investigated. Here we show that PD-L1 expression in cancer cells is upregulated in response to DSBs. This upregulation requires ATM/ATR/Chk1 kinases. Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP inhibition. In addition, we show that Ku70/80 depletion substantially enhances PD-L1 upregulation after X-rays. The upregulation by Ku80 depletion requires Chk1 activation following DNA end-resection by Exonuclease 1. DSBs activate STAT1 and STAT3 signalling, and IRF1 is required for DSB-dependent PD-L1 upregulation. Thus, our findings reveal the involvement of DSB repair in PD-L1 expression and provide mechanistic insight into how PD-L1 expression is regulated after DSBs. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar than you would expect. https: imgur.com rpe426U ,
CRISPR/Cas9-mediated deletion of miR-146a enhances antiviral response in HIV-1 infected cells
Authors: Shuliang Chen
Ting Yu
Yan Zeng
Yan Teng
Lang Chen
Linlin Xie
Hairong Xiong
Wei Hou
Fan Luo
Yong Feng
Qiuling Huang
Yuanyuan Liu
Mingqi Luo
Journal: Genes and Immunity (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HIV-1; miR-146a; CRISPR/Cas9; cytokines; immune response

Abstract:  The human immunodeficiency virus type 1 (HIV-1) causes persistent infection in human and induces miR-146a expression in infected cells. miR-146a represses the innate immune response by inhibiting the expression of TRAF6 and IRAK1 genes, thus negatively controls the NF-κB-related cytokines and interferon stimulated genes. Here we reported that lentiviral CRISPR/Cas9 system was highly efficient in introducing mutations in the precursor miR-146a genomic sequences, resulting in a loss of miR-146a expression and function. miR-146a ablation led to increasing cytokines production in LPS-stimulated A549 cells. Moreover, miR-146a knockout in HIV-1 infected MT2 cells markedly increased the expression of cytokines and HIV-1 restriction factors and reversed T cell exhaustion markers expression, thus influencing HIV-1 replication. Our study indicates that lentiviral CRISPR/Cas9-mediated gene editing is an effective approach to abrogate miR-146a expression, which consequently inhibits HIV-1 replication as well as proviral reactivation by enhancing the expression of cytokines and HIV-1 restriction factors. 

Retracted: No

PubPeer comments:
 One of the bands in Figure 2 is duplicated (pay close attention to the uneven outer edge of the band - how every dent is identical in the two bands), suggesting not only that the blot has been spliced, but spliced wrong. ![file] Do the authors have an explanation? ,
COX-2 inhibitors suppress integrin alpha5 expression in human lung carcinoma cells through activation of Erk: involvement of Sp1 and AP-1 sites
Authors: ShouWei Han
Jesse Roman
Journal: International Journal of Cancer (2005)
Discipline: CLINICAL MEDICINE
Keywords: COX-2; inhibitors; integrin alpha5beta1; NSCLC; Erk
Affiliations: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. 

Abstract:  Tumor cell expression of COX-2 has been implicated in the progression of murine and human lung cancer. Inhibition of COX-2 by nonsteroidal antiinflammatory drugs reduces the risk of cancer development in humans and suppresses tumor growth in animal models. However, the underlying mechanisms for this beneficial effect are not fully understood. Here we explore the potential link between the anticancer effects of COX-2 inhibitors and the expression of the integrin alpha5beta1. Expression of this integrin in carcinoma cells is associated with invasiveness and malignant progression. This, together with our studies showing that fibronectin, the ligand of alpha5beta1, stimulates the growth of human lung carcinoma cells, and that this effect is mediated through alpha5beta1-dependent signals, has prompted us to examine the effects of COX-2 inhibitors on alpha5beta1 expression in human non small cell lung carcinoma (NSCLC) cells. We found that the selective COX-2 inhibitors NS398 and Nimesulide decreased mRNA expression and protein production of the integrin alpha5 subunit. This effect was associated with inhibition of NSCLC cell adhesion to fibronectin. The COX-2 inhibitors triggered the phosphorylation of extracellular signal-regulated kinase (Erk) in a time-dependent manner, and the inhibitor of Mek-1/Erk PD98095 prevented their inhibitory effects on integrin alpha5 expression. Transient transfection assays showed that the COX-2 inhibitors affected integrin alpha5 gene transcription by acting between -92 to -41 bp of the human integrin alpha5 gene promoter. Gel mobility shift assays showed that the COX-2 inhibitors increased Sp1 DNA binding, but decreased that of AP-1. These effects were accompanied by an increase in Sp1 protein and a decrease in c-Jun protein expression, as well as inhibition of SAPK/JNK phosphorylation. The Sp1 inhibitor, Mithramycin A, also blocked the inhibitory effect of the COX-2 inhibitors on alpha5 expression and promoter activity. Overall, these findings suggest that COX-2 inhibitors suppress alpha5beta1 integrin expression in NSCLC through effects on integrin alpha5 gene transcription mediated by Erk activation, increased Sp1, decreased AP-1 DNA binding and inactivation of SAPK/JNK signals. Our observations unveil a new mechanism of action against NSCLC for COX-2 inhibitors that relates to regulation of integrin alpha5 gene expression and, consequently, recognition of extracellular matrices (i.e., fibronectin) by tumor cells. (c) 2005 Wiley-Liss, Inc. 

Retracted: Yes

PubPeer comments:
null, 
 https: retractionwatch.com 2015 08 11 eighth-retraction-published-for-former-physiology-researcher ,
LncRNA SNHG16 promotes tumor growth of pancreatic cancer by targeting miR-218-5p
Authors: Kai Liu
Wei Zhang
Yahui Liu
Songyang Liu
Journal: Biomedicine & Pharmacotherapy (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Invasion; Pancreatic cancer; Proliferation; SNHG16; lncRNA
Affiliations: Department of Hepatopancreatobiliary Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, PR China., Department of Hepatopancreatobiliary Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, PR China. Electronic address: .

Abstract:  Small Nucleolar RNA Host Gene (SNHG16) is a novel cancer-related long noncoding RNA (lncRNA) and functions as an oncogene in a variety of cancers. Nonetheless, the expression patterns, biological function, and potential mechanisms in SNHG16 in pancreatic cancer (PC) remain rarely known. An increase in expression of SNHG16 in PC samples against adjacent normal tissues was shown here. Increased SNHG16 was linked intimately to the tumor-node-metastasis (TNM) stage, distant metastasis, tumor differentiation, and poor overall survival. Loss-of-function experiments revealed that SNHG16 knockdown suppressed the proliferation, formation of colonies, ability to migrate and invade in vitro, along with a lowered growth of the tumor in a mouse model. Mechanistically, SNHG16 might serve as a sponge competitive endogenous RNA (ceRNA) for miR-218-5p, thereby playing a role in regulating the expression of high mobility group box 1 (HMGB1) expression, a known direct miR-218-5p target in PC cells. These results provide novel insight into PC tumorigenesis and suggest that SNHG16 could serve as a likely therapeutic intervention in PC. 

Retracted: No

PubPeer comments:
 Fig 2D.  Photographs of xenograft tumors . ![file] Colored shapes mark similarities with Fig 7C from [Chen et al (2017)] .  Photographs of xenograft tumors isolated from miR-25 mimic and miR-Ctrl injected mice . ![file] And with Fig 6B from [Li et al (2017),  Photographs of xenograft tumors. ![file] Fig 6B from [Li et al (2018a)] . ![file] Other manifestations are linked in those threads. UPDATE: Fig 6B from [Li et al (2018b)] .  Tumor tissues were imaged after tumors were harvested on day 30 . ![] ,
MiR-302e attenuates allergic inflammation in vitro model by targeting RelA
Authors: Li Jiang
Qi Hu
Yuru Li
Lifeng Xiao
Journal: Bioscience reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RelA; allergic inflammation; cytokines; mast cells; microRNA-302e.
Affiliations: Department of Otolaryngology Head and Neck surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China., Department of Otolaryngology Head and Neck surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China .

Abstract:  Allergic inflammation is the foundation of allergic rhinitis and asthma. Although microRNAs are implicated in the pathogenesis of various diseases, information regarding the functional role of microRNAs in allergic diseases is limited. Herein, we reported that microRNA-302e (miR-302e) serves as an important regulator of allergic inflammation in human mast cell line, HMC-1 cells. Our results showed that miR-302e is the dominant member of miR-302 family expressed in HMC-1 cells. Moreover, the expression of miR-302e was significantly decreased in response to phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 or ovalbumin (OVA) stimulation. Overexpression of miR-302e blocked PMA/A23187 or OVA induced the increase in inflammatory cytokines levels, such as IL-1β, IL-6, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin, while miR-302 inhibition further promoted the release of these cytokines. Mechanistically, we found that miR-302e is a novel miRNA that targets RelA, a gene known to be involved in regulating inflammation, through binding to the 3'-UTR of RelA mRNA. Ectopic miR-302e remarkably suppressed the luciferase activity and expression of RelA, whereas down-regulation of miR-302e increased RelA luciferase activity and expression. Pharmacological inhibition of NF-κB reversed the augmented effect of miR-302e down-regulation on inflammatory cytokines level. Taken together, the present study demonstrates miR-302e limits allergic inflammation through inhibition of NF-κB activation, suggesting miR-302e may play an anti-inflammatory role in allergic diseases and function as a novel therapeutic target for the treatment of these diseases. 

Retracted: No

PubPeer comments:
 2 images in Figure 5G appear to have been placed in the wrong row. Perhaps not worthy of a correction. *** ![file] *** ![file] ,
Transcriptional regulation of signal regulatory protein alpha1 inhibitory receptors by epidermal growth factor receptor signaling
Authors: Dmitri Kapitonov
Gurpreet S Kapoor
Donald M O&#x27;Rourke
Journal: Cancer Research (2004)
Discipline: CLINICAL MEDICINE
Keywords: Signal regulatory protein; SIRPalpha1; EGFR signaling; Glioblastoma cells; Cancer therapy
Affiliations: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Abstract:  Signal regulatory protein (SIRP) alpha1 is a membrane glycoprotein and a member of the SIRP receptor family. These transmembrane receptors have been shown to exert negative effects on signal transduction by receptor tyrosine kinases via immunoreceptor tyrosine-based inhibitory motifs in the carboxyl domain. Previous work has demonstrated that SIRPs negatively regulate many signaling pathways leading to reduction in tumor migration, survival, and cell transformation. Thus, modulation of SIRP expression levels or activity could be of great significance in the field of cancer therapy. The aim of the present study was to determine the factors that regulate levels of SIRPalpha1 in human glioblastoma cells that frequently overexpress the epidermal growth factor receptor (EGFR) because SIRPs have been shown to negatively regulate EGFR signaling. Northern blot analysis and immunoprecipitation assays showed variable expression levels of endogenous SIRPalpha transcripts in nine well-characterized glioblastoma cell lines. We examined SIRPalpha1 regulation in U87MG and U373MG cells in comparison with clonal derivatives that express a truncated form of erbB2, which negatively regulates EGFR signaling by inducing the formation of nonfunctional heterodimeric complexes. Mutant erbB2-expressing cells contained more SIRPalpha1 mRNA when compared with the parental cells in presence or absence of serum. Similarly, immunoprecipitation assays showed increased SIRPalpha1 protein levels in erbB-inhibited cells when compared with parental cells. Messenger RNA stability assays revealed that the increased mRNA levels in EGFR-inhibited cells were due to an induction of transcription. Consistent with this finding, expression of the erbB2 mutant receptor up-regulated SIRPalpha1 promoter activity in all cell lines tested. Interestingly, pharmacological inhibition of the kinase activities of EGFR, erbB2, and src and activation of mitogen-activated protein kinase, but not phosphatidylinositol 3'-kinase, significantly up-regulated SIRPalpha1 promoter activity. Based on these observations, we hypothesize that down-modulation of EGFR signaling leads to transcriptional up-regulation of the inhibitory SIRPalpha1 gene. These data may be important in the application of erbB-inhibitory strategies and for design of therapies for the treatment of glial tumors and other epithelial malignancies. 

Retracted: No

PubPeer comments:
 Figure 2B. Much more similar than expected. https: imgur.com 1eCRYj8 , 
 #1 Figure 2B. Much more similar after vertical stretch than expected. ![file] ,
Decreased cell proliferation in the dentate gyrus does not associate with development of anhedonic-like symptoms in rats
Authors: M N Jayatissa
K Henningsen
Ove Wiborg
M J West
Journal: Brain Research (2009)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Depressive disorders; hippocampal neurogenesis; rodent models; chronic mild stress; MAM
Affiliations: Centre for Psychiatric Research, Aarhus University Hospital, Skovagervej 2, 8240 Risskov, Aarhus, Denmark.

Abstract:  Depressive disorders have been proposed to be caused by stress-induced down-regulation of hippocampal neurogenesis. Nevertheless, several reports have recently pointed out that, in rodent models of depression, suppression of generation of new hippocampal neurons is not by itself sufficient to induce the development of depression-related symptoms. In the present study, we used the cell proliferation blocker methylazoxymethanol (MAM) and the rat chronic mild stress (CMS) model of depression to challenge the neurogenic theory of depression. In order to achieve a comparable reduction in hippocampal cytogenesis, rats were either chronically treated with MAM for 2 weeks, or subjected to an 8 week regime of chronic mild stress. Consumption of a palatable sucrose solution was monitored once a week to assess the development of anhedonic behavior. Prior to terminal perfusion, the animals were injected with bromodeoxyuridine, a marker of proliferating cells. The number of proliferating cells and total cell number and volume were estimated for the granule cell layer of the ventral hippocampal formation. Unlike CMS, chronic injections with MAM did not induce anhedonia-like symptoms in rats. Both MAM-treated and CMS-exposed groups of rats showed a comparable significant reduction in cell proliferation in the granular cell layer of the ventral hippocampal formation. However, the total cell number was reduced for CMS-exposed rats only while the granule cell layer volume was conserved for both groups. Our results show that suppression of cell proliferation in the hippocampal formation is not an absolute factor for induction of an anhedonia-like state in rats. However, it may still represent an important causal factor for vulnerable subjects. 

Retracted: No

PubPeer comments:
 The images in Figure 3 are highly problematic, since the authors have used these same images in another report purporting them to be from other animals undergoing different treatments. Refer to separate post here: https: pubpeer.com publications A71A48873C134C832DF656F6743E4E Side-by-side of images. ![file] Note also that the magnified inset in Figure 3C does not actually match the region it supposedly depicts. Until the authors can provide a good explanation, I would urge caution in how the results of this study are to be interpreted. ,
HIF-1α activation by intermittent hypoxia requires NADPH oxidase stimulation by xanthine oxidase
Authors: Nanduri R Prabhakar
Damodara Reddy Vaddi
Shakil A Khan
Gregg L Semenza
Vladislav Makarenko
Ning Wang
Jayasri Nanduri
Journal: PLoS ONE (2015)
Discipline: Multidisciplinary
Keywords: Hypoxia-inducible factor 1; intermittent hypoxia; Nox2; xanthine oxidase; ROS
Affiliations: Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, Chicago, Illinois, United States of America., Vascular Program, Institute for Cell Engineering; Department of Pediatrics, Medicine, Oncology, Radiation Oncology and Biological Chemistry; and Mckusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Abstract:  Hypoxia-inducible factor 1 (HIF-1) mediates many of the systemic and cellular responses to intermittent hypoxia (IH), which is an experimental model that simulates O2 saturation profiles occurring with recurrent apnea. IH-evoked HIF-1α synthesis and stability are due to increased reactive oxygen species (ROS) generated by NADPH oxidases, especially Nox2. However, the mechanisms by which IH activates Nox2 are not known. We recently reported that IH activates xanthine oxidase (XO) and the resulting increase in ROS elevates intracellular calcium levels. Since Nox2 activation requires increased intracellular calcium levels, we hypothesized XO-mediated calcium signaling contributes to Nox activation by IH. We tested this possibility in rat pheochromocytoma PC12 cells subjected to IH consisting alternating cycles of hypoxia (1.5% O2 for 30 sec) and normoxia (21% O2 for 5 min). Kinetic analysis revealed that IH-induced XO preceded Nox activation. Inhibition of XO activity either by allopurinol or by siRNA prevented IH-induced Nox activation, translocation of the cytosolic subunits p47phox and p67phox to the plasma membrane and their interaction with gp91phox. ROS generated by XO also contribute to IH-evoked Nox activation via calcium-dependent protein kinase C stimulation. More importantly, silencing XO blocked IH-induced upregulation of HIF-1α demonstrating that HIF-1α activation by IH requires Nox2 activation by XO. 

Retracted: No

PubPeer comments:
 One band in Figure 4A appears to have a sharp transition in the background, after adjusting the contrast. Could the authors please post original uncropped scans to reassure readers? *** Inverse image ![file] *** Original ![file] *** Full figure ![file] , 
 Another possible splice in Fig 5: ![file] ![file] , 
 https: pubpeer.com search?q=Gregg+Semenza Some corrected, many not. ,
A ride through the epigenetic landscape: aging reversal by reprogramming
Authors: Lucas Paulo de Lima Camillo
Robert B A Quinlan
Journal: GeroScience (2021)
Discipline: CLINICAL MEDICINE
Keywords: Aging; Epigenetics; Rejuvenation; Reprogramming.
Affiliations: Department of Chemistry, Brown University, Providence, RI, USA. ., Nuffield Department of Medicine, University of Oxford, Oxford, UK. .

Abstract:  Aging has become one of the fastest-growing research topics in biology. However, exactly how the aging process occurs remains unknown. Epigenetics plays a significant role, and several epigenetic interventions can modulate lifespan. This review will explore the interplay between epigenetics and aging, and how epigenetic reprogramming can be harnessed for age reversal. In vivo partial reprogramming holds great promise as a possible therapy, but several limitations remain. Rejuvenation by reprogramming is a young but rapidly expanding subfield in the biology of aging. 

Retracted: No

PubPeer comments:
 From  Table 1 Studies of partial epigenetic reprogramming it seems like the results of partial-reprogramming are temporary. I think the article should focus more about this problem and explain the reasons for why the rejuvenation effect doesn t last long or even suggesting potential ways for dealing with that problem and make the rejuvenation effect to endure like  regular young cells. , 
 It has been a long time since I read a paper so lacking in intellectual content. They simply say  epigenetic in every sentence as if it is a talisman of some kind. The title of Figure 1 is  Drawing of the original epigenetic landscape proposed by Waddignton - that s right, they did not even spellcheck the text. Then we have Figure 3: ![file] The legend says:  Transition of the epigenetic landscape during reprogramming. The peaks become grooves, pulling the marble towards the center No idea where or what the  marble is, but I m glad old CHW is not around to see this. I have seen much better undergraduate essays. , 
 #2 1. This is entirely vacuous without examples as to why the use of the word  epigenetic is inadequate. 2. Gasp! What a sin! Now the entire content of the paper is rendered just because the authors misplaced 1 (one) singular letter in a name that is not trivial for non-native English speakers to spell and is usually not picked up by checkers due to being a name. Sorry, but How is this Pubpeer worthy? Is the underlying science affected by this typo? Did it impact your understanding of the content? Here, i ll tyep am entierly rong centence adn im soore u wil stiu understood mi point. 3. The two figures above figure 3 show the marble and its position. Figure 2 is basically the left-side panel of Figure 3 with the marble IN CLEAR SIGHT. How did you miss that? Surely an undergraduate student would have picked it up. I suggest that in your next reply you offer more specific (and thus more constructive) criticism instead of vitriol and snark, then maybe we can get somewhere. , 
 This study was done in two  cohorts of size seven and three, respectively, to a total of 10 (ten) subjects. The study was not randomized and every subject s dose was adjusted. ,
<p>Long Non-Coding RNA-NEAT1 Promotes Cell Migration and Invasion via Regulating miR-124/NF-κB Pathway in Cervical Cancer</p>
Authors: Wei Zhao
Yumei Zhang
Bin Liang
Xiaofang Shen
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: cervical cancer; invasion; lncRNA-NEAT1; miR-124/NF-κB pathway; migration.
Affiliations: Department of Obstetrics-Gynecology, Dongying City People's Hospital, Dongying City, Shandong Province 257091, People's Republic of China., Department of Obstetrics-Gynecology, Dongying City Dongying District People's Hospital, Dongying City, Shandong Province 257000, People's Republic of China.

Abstract:  Background: This study aimed to investigate the regulatory role of lncRNA-NEAT1 on cervical cancer (CC) and the underlying molecular mechanisms. Methods: The expression of lncRNA-NEAT1 and miR-124 was detected in CC tissues and cells (HeLa and SiHa cells) by qRT-RCR. The relation between lncRNA-NEAT1 expression and clinical parameters of CC patients was explored. The cell migration and invasion were detected by wound healing assay and transwell assay. The cell proliferation was detected by CCK-8 and anchorage-independent colony assay. The targeting relation between miR-124 and lncRNA-NEAT1 was predicted by TargetScan and identified by dual luciferase reporter gene and RNA pull-down assay. The expression of metastasis- (MMP-2 and MMP), EMT- (E-cadherin, N-cadherin and Vimentin), and NF-κB pathway-related factors (NF-κB p65, p-NF-κB p65 and IκBα) was detected by Western blot. Results: The expression of lncRNA-NEAT1 was upregulated in CC tissues and cells and positively correlated with TNM stage and lymph node metastasis. Overexpression of lncRNA-NEAT1 promoted the proliferation, migration and invasion, influenced the expression of EMT markers, and activated NF-κB pathway in HeLa and SiHa cells. Silencing of lncRNA-NEAT1 exhibited opposite effects on HeLa and SiHa cells. LncRNA-NEAT1 could negatively regulate its target miR-124. MiR-124 reversed the effects of lncRNA-NEAT1 on the migration, invasion, EMT and NF-κB pathway of HeLa cells. Conclusion: LncRNA-NEAT1 promoted the migration and invasion of CC cells via regulating miR-124/NF-κB pathway. 

Retracted: No

PubPeer comments:
 I have found what I believe to be numerous image duplications in this paper. The images are small, so the duplications are difficult to see without enlarging them. Sometimes the duplications were stacked on top of each other, but sometimes they were turned upside down and pasted into another image (circled in red). For example, you can see the duplication circled in red in both figures 2 and 7. Here are the last two rows of figure 7A: ![file] And here are 2C and 2D: ![file] , 
 #1 Very well caught. I will just add that similar collaging techniques seem to have gone into the scratch assays as well. ![file] Colored boxes are not identical, but near-identical. ![file] More examples from the next set of images. ,
Role of human herpesvirus 8 interleukin-6-activated gp130 signal transducer in primary effusion lymphoma cell growth and viability
Authors: John Nicholas
Emily Cousins
Journal: Journal of Virology (2013)
Discipline: MICROBIOLOGY
Keywords: Human herpesvirus 8; HHV-8; Kaposi's sarcoma; primary effusion lymphoma; multicentric Castleman's disease
Affiliations: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract:  Human herpesvirus 8 (HHV-8) infection is associated with Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. HHV-8-encoded viral interleukin-6 (vIL-6) is believed to contribute to pathogenesis via proproliferative, antiapoptotic, and proangiogenic activities. In PEL cells, vIL-6 is produced in functional amounts during viral latency and promotes the growth of these cells, mediating its activity from the endoplasmic reticulum (ER), where it is predominantly localized. This vIL-6 activity is dependent, in part, on its interaction with a splice variant of vitamin K epoxide reductase complex subunit 1 (VKORC1), termed VKORC1 variant 2 (VKORC1v2). Here we report that the IL-6 signal transducer, gp130, which can support vIL-6 signaling from the ER, is also required for optimal PEL cell growth and viability. Levels of activated extracellular regulated kinases (ERKs) 1 and 2 and signal transducer and activator of transcription 1 (STAT1) and STAT3, phosphorylated following gp130 stimulation, were reduced in gp130-depleted BCBL-1 and BC-1 cells. Diminished STAT activation was also detected in JSC-1 and BC-3 cells. Effects of gp130 depletion on growth could be mimicked by short hairpin RNA targeting of ERKs 1 and 2 or by depletion of STAT3. Finally, inhibition of vIL-6-gp130 association specifically within the ER compartment suppressed cell proliferation and viability, mirroring the effects of gp130 depletion. Combined, these data demonstrate that gp130, in addition to VKORC1v2, is essential for normal PEL cell growth and survival and that ER-localized vIL-6-gp130 interactions are critical for these activities. Targeting of intracellular vIL-6-gp130 interactions could potentially provide a means of PEL therapy. 

Retracted: No

PubPeer comments:
 November 2017 correction found here: https: jvi.asm.org content 91 24 e01567-17 It reads: *Fig. 3A: The STAT3 immunoblot image for JSC-1 cells was inadvertently duplicated from the corresponding BCBL-1 cell data.* Here is the original Figure 3A as reported to the journal in December 2014, with the duplication marked with red boxes. I thank the authors and journal for correcting this error. ![file] ,
Endocannabinoids are expressed in bone marrow stromal niches and play a role in interactions of hematopoietic stem and progenitor cells with the bone marrow microenvironment
Authors: Hava Karsenty Avraham
Jodi Anne T Wood
Jerome E Groopman
Alexandros Makriyannis
Shalom Avraham
Naheed Banu
Radoslaw Zagozdzon
John S Williams
Meritxell Alberich Jorda
Yigong Fu
Kalindi Parmar
Shuxian Jiang
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Endocannabinoids; CB(1) receptors; hematopoietic stem cells; HSPCs; BM niches
Affiliations: Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Northeastern University, Boston, Massachusetts 02215, USA.

Abstract:  Endocannabinoids are lipid signaling molecules that act via G-coupled receptors, CB(1) and CB(2). The endocannabinoid system is capable of activation of distinct signaling pathways on demand in response to pathogenic events or stimuli, hereby enhancing cell survival and promoting tissue repair. However, the role of endocannabinoids in hematopoietic stem and progenitor cells (HSPCs) and their interaction with hematopoietic stem cells (HSC) niches is not known. HSPCs are maintained in the quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signaling. We report that HSPCs express the CB(1) receptors and that BM stromal cells secrete endocannabinoids, anandamide (AEA) (35 pg/10(7) cells), and 2-AG (75.2 ng/10(7) cells). In response to the endotoxin lipopolysaccharide (LPS), elevated levels of AEA (75.6 pg/10(7) cells) and 2-AG (98.8 ng/10(7) cells) were secreted from BM stromal cells, resulting in migration and trafficking of HSPCs from the BM niches to the peripheral blood. Furthermore, administration of exogenous cannabinoid CB(1) agonists in vivo induced chemotaxis, migration, and mobilization of human and murine HSPCs. Cannabinoid receptor knock-out mice Cnr1(-/-) showed a decrease in side population (SP) cells, whereas fatty acid amide hydrolase (FAAH)(-/-) mice, which have elevated levels of AEA, yielded increased colony formation as compared with WT mice. In addition, G-CSF-induced mobilization in vivo was modulated by endocannabinoids and was inhibited by specific cannabinoid antagonists as well as impaired in cannabinoid receptor knock-out mice Cnr1(-/-), as compared with WT mice. Thus, we propose a novel function of the endocannabinoid system, as a regulator of HSPC interactions with their BM niches, where endocannabinoids are expressed in HSC niches and under stress conditions, endocannabinoid expression levels are enhanced to induce HSPC migration for proper hematopoiesis. 

Retracted: Yes

PubPeer comments:
 2011 retraction. http: www.jbc.org content 286 27 24534 This article has been withdrawn by the authors. https: retractionwatch.com 2011 07 06 second-retraction-by-harvard-group-studying-cannabinoids-this-one-in-jbc ,