PReD-Bench/PRed-Bench huggingface dataset:
Reciprocal regulation of miR‐206 and IL‐6/STAT3 pathway mediates IL6‐induced gefitinib resistance in EGFR‐mutant lung cancer cells
Authors: Hong Chang
Tingguo Zhang
Yanhua Yang
Xinjuan Yu
Zenglei Han
Wei Wang
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: IL-6; STAT3; gefitinib; miR-206.
Affiliations: Department of Pathology, Qilu Hospital, Shandong University, Jinan, China., Department of Pathology, Qingdao Municipal Hospital, Qingdao, China., Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China., Department of Pathology, The Third People's Hospital of Qingdao, Qingdao, China., Center Laboratory, Qingdao Municipal Hospital, Qingdao, China., Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China.

Abstract:  Persistently activated IL-6/STAT3 pathway promotes acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC) treatment. miR-206 has been verified to be dysregulated and plays as a negative regulator in lung cancer. However, whether miR-206 may overcome IL6-induced gefitinib resistance in EGFR-mutant lung cancer remains elusive. In this study, we investigated the role of miR-206 in IL6-induced gefitinib-resistant EGFR-mutated lung cancer cell lines. We showed that forced miR-206 expression restored gefitinib sensitivity in IL6-induced gefitinib-resistant EGFR-mutant lung cancer cells by inhibiting IL6/JAK1/STAT3 pathway. Specifically, mechanistic investigations revealed that miR-206 blocked IL-6/STAT3 signalling via directly targeting the 3'-UTR of intracellular IL-6 messenger RNA. Moreover, IL-6 induced miR-206 down-regulation by reducing the cropping process of primary miR-206 (pri-miR-206) into the Drosha/DGCR8 complex. Taken together, our findings reveal a direct role of miR-206 in regulating IL-6/STAT3 pathway and contrarily activated IL-6/STAT3 signalling mediates the miR-206 maturation process in gefitinib-resistant EGFR-mutant lung cancer cells. 

Retracted: No

PubPeer comments:
 The western blots in this paper look to have gone through some post-processing in places. I wonder if the authors could show the raw scans? In particular, for the loading controls in Figure 3, the right hand bands are a *perfect* mirror of the left hand side for the lower panel (I have entered guidelines and highlighted two artifacts that also align perfectly). ![file] For the upper panel, there again seems to be a mirrored band among the loading controls. ![file] ,
Japonicone A antagonizes the activity of TNF-α by directly targeting this cytokine and selectively disrupting its interaction with TNF receptor-1
Authors: Lei Shan
Yaping Hua
Huahua Zhang
Junping Zhang
Jiangjiang Qin
Weidong Zhang
Dan Wang
Huizi Jin
Zhenlin Hu
Jieping Ding
Journal: Biochemical Pharmacology (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Anti-TNF biologics; TNF receptor-1 (TNFR1); TNFR2 signaling; Japonicone A (Jap A); TNF-α antagonist
Affiliations: School of Pharmacy, Second Military Medical University, Shanghai, China. 

Abstract:  Anti-TNF biologics are effective therapies for various inflammatory diseases. Unfortunately, their clinical use is associated with an increased risk of infections. Selectively inhibiting TNF receptor-1 (TNFR1)-mediated signaling while preserving TNFR2 signaling may reduce inflammation yet maintain host immune response to pathogens. However, few small molecules that selectively target the TNF/TNFR system have been discovered. In the present study, we identified Japonicone A (Jap A), a nature compound derived from Inula japonica Thunb, as a novel TNF-α antagonist, as it reduced the TNF-α-mediated cytotoxicity on L929 cells and inhibited the binding of (125)I-labeled TNF-α to L929 cell surface. Furthermore, Jap A could directly bind to TNF-α rather than TNFR1 as determined by surface plasmon resonance. More importantly, Jap A could effectively inhibit the binding of TNF-α to TNFR1, while displaying only marginal inhibitory effects on that to TNFR2. Jap A also could block TNFR1-mediated signaling as it inhibited TNF-α-induced NF-κB activation in 293 cells. In addition, Jap A suppressed TNF-α-induced expressions of adhesion molecules (ICAM-1, VCAM-1) and chemokine (MCP-1) in the endothelial cells by blocking TNF-α-triggered multiple signaling pathways. Data from in vivo experiments demonstrated that Jap A protected mice from acute hepatitis induced by TNF-α/d-galactosamine, but did not compromise host antiviral immunity in adenovirus-infected mice. These results indicate that Jap A can directly target TNF-α, selectively disrupt its interaction with TNFR1, and antagonize its pro-inflammatory activities without compromising host defense against virus, thus emphasizing the potential of Jap A as an interesting lead compound for development of new anti-inflammatory drugs. 

Retracted: No

PubPeer comments:
null, 
 Figure 7B: P38 blot seems cut from other pictures as the border looks very strange. ![file] ,
STAT1 interaction with E3-14.7K in monocytes affects the efficacy of oncolytic adenovirus
Authors: Baisui Feng
Ann Tollefson
Pengju Wang
William Wold
Yaohe Wang
Dongling Gao
Fengyu Cao
Rathi Gangeswaran
Nicholas R Lemoine
Emma Spurrell
Journal: Journal of Virology (2014)
Discipline: MICROBIOLOGY
Keywords: Oncolytic viruses; adenovirus type 5; therapeutic agents; cancers; virotherapy
Affiliations: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

Abstract:  Oncolytic viruses based on adenovirus type 5 (Ad5) have been developed as a new class of therapeutic agents for cancers that are resistant to conventional therapies. Clinical experience shows that these agents are safe, but virotherapy alone has not achieved long-term cure in cancer patients. The vast majority of oncolytic adenoviruses used in clinical trials to date have deletion of the E3B genes. It has been demonstrated that the antitumor potency of the E3B-deleted mutant (dl309) is inferior to adenovirus with E3B genes intact. Tumors treated with dl309 show markedly greater macrophage infiltration than E3B-intact adenovirus. However, the functional mechanisms for this were not previously known. Here, we demonstrate that deletion of E3B genes increases production of chemokines by monocytes after adenovirus infection and increases monocyte migration. The E3B 14,700-Da protein (E3B-14.7K) inhibits STAT1 function by preventing its phosphorylation and nuclear translocation. The STAT1 inhibitor, fludarabine, rescues the effect of E3B-14.7K deletion by downregulating target chemokine expression in human and murine monocytes and results in an enhanced antitumor efficacy with dl309 in vivo. These findings have important implications for clinical use of E3B-deleted oncolytic adenovirus and other E3B-deleted adenovirus vector-based therapy. 

Retracted: No

PubPeer comments:
null, 
null, 
 2017 correction. https: jvi.asm.org content 91 20 e00670-17 Corrected figures 2B and 3B. https: pubpeer.com publications 9AAD091A9132F595902971B9EA1E4C#1 ,
Clinical use of current polygenic risk scores may exacerbate health disparities
Authors: Alicia R Martin
Yoichiro Kamatani
Mark J Daly
Benjamin M Neale
Masahiro Kanai
Yukinori Okada
Journal: Nature Genetics (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Polygenic risk scores; precision medicine; biomedical outcomes; ethical challenges; scientific challenges
Affiliations: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. ., Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. ., Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. ., Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA., Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Kyoto-McGill International Collaborative School in Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan., Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan., Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan., Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

Abstract:  Polygenic risk scores (PRS) are poised to improve biomedical outcomes via precision medicine. However, the major ethical and scientific challenge surrounding clinical implementation of PRS is that those available today are several times more accurate in individuals of European ancestry than other ancestries. This disparity is an inescapable consequence of Eurocentric biases in genome-wide association studies, thus highlighting that-unlike clinical biomarkers and prescription drugs, which may individually work better in some populations but do not ubiquitously perform far better in European populations-clinical uses of PRS today would systematically afford greater improvement for European-descent populations. Early diversifying efforts show promise in leveling this vast imbalance, even when non-European sample sizes are considerably smaller than the largest studies to date. To realize the full and equitable potential of PRS, greater diversity must be prioritized in genetic studies, and summary statistics must be publically disseminated to ensure that health disparities are not increased for those individuals already most underserved. 

Retracted: No

PubPeer comments:
 ![file] ![file] Repetitive band patterns which are most likely  copy and paste . It is almost impossible to obtain such similarity from E. coli strains particularly from ESBL producing ones isolated from different human patients. Some part of the banding patter is also similar to that published by Gu00fcldemir et al. 2015. Gu00fcldemir et al. (2015) Turk Hij Den Biyol Drg: 2015: 72(1):1-10. ,
The Wnt inhibitor, Dickkopf 4, is induced by canonical Wnt signaling during ectodermal appendage morphogenesis
Authors: Gavin D Richardson
Colin A B Jahoda
Katherine A Fantauzzo
Angela M Christiano
Hisham Bazzi
Journal: Developmental Biology (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ectodermal appendage morphogenesis; epithelial-mesenchymal cross-talk; Canonical Wnt signaling; hair follicles; primary HF morphogenesis
Affiliations: Department of Genetics and Development, Columbia University, New York, NY, USA.

Abstract:  Ectodermal appendage morphogenesis requires continuous epithelial-mesenchymal cross-talk during development. Canonical Wnt signaling has been shown to be pivotal during this process and its inhibition leads to the absence of any morphological or molecular signs of appendage formation, including hair follicles (HFs). In the mouse, primary HFs arise in utero starting just before E14.5, when the first morphological signs of a placode are discernible. In this study, our goal was to identify novel factors expressed during primary HF morphogenesis. We performed transcriptional profiling of the developing epidermis at 12 h intervals between E12.5 and E15.5. One of the significantly differentially expressed genes was the Wnt inhibitor Dickkopf 4, Dkk4. We show that Dkk4 mRNA increases sharply in the dorso-lateral epidermis around E14 and then decreases until E15.5. Using whole mount in situ hybridization, we show that Dkk4 mRNA is localized to the pre-placodes at sites of presumptive epithelial-mesenchymal interactions during appendage morphogenesis, including the dental lamina, mammary gland, eccrine gland, and primary and secondary HFs. In silico analysis, reporter gene assays as well as in vitro transfections of LEF1 and beta-catenin show that Dkk4 is a potential downstream target of canonical Wnt signaling. In addition, we demonstrate a direct physical interaction between LEF1/beta-catenin complex and the Dkk4 promoter using ChIP. We propose that Dkk4 acts in a negative feedback loop to attenuate canonical Wnt signaling, and may facilitate a switch to the non-canonical Wnt planar cell polarity (PCP) pathway that is involved in cell movements during morphogenesis. 

Retracted: No

PubPeer comments:
 Possible band duplication between different works. Not mentioned in the legends or in the references ![file] ,
VASN promotes proliferation of prostate cancer through the YAP/TAZ axis
Authors: Z-P Xu
A-N Mahmud
J-P Hu
Z-Y Wang
F-L Cui
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: VASN; YAP; TAZ; prostate cancer; proliferation
Affiliations: Department of Urology Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China. .

Abstract:  Objective: The purpose of this study was to uncover the role of VASN in regulating proliferative ability of prostate cancer (PCa) cells through the yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) axis, thus influencing the progression of PCa. Patients and methods: VASN, YAP, and TAZ levels in PCa tissues or in the serum were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The diagnostic value of VASN in PCa was assessed by introducing receiver operating characteristic (ROC) curves. Besides, the regulatory effects of VASN on viability, clonality, and expression levels of YAP/TAZ were evaluated by cell counting kit-8 (CCK-8), colony formation, and Western blot, respectively. Finally, rescue experiments were conducted to uncover the involvement of YAP in VASN-regulated proliferation of PCa. Results: Results manifested that VASN, YA, and TAZ were upregulated in PCa patients, and VASN presented a certain diagnostic value. Knockdown of VASN in LNCaP and C4-2 cells suppressed viability and clonality, and downregulated protein levels of YAP and TAZ. Notably, overexpression of YAP abolished the attenuated viability and clonality in PCa cells with VASN knockdown. Conclusions: VASN promotes proliferative ability in PCa via regulating the YAP/TAZ axis, thus aggravating the progression of the disease. 

Retracted: No

PubPeer comments:
 Figure 2D has a duplicated figure panel with a slight shift (top right and bottom right): ![file] This becomes more apparent when equalization is applied to panels side by side: ![file] ,
Erratum: Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis
Authors: Shu-Jue Lan
Wenli Zhang
Xuesong Yang
Shan Chi
Wei-Jie Zhou
Zhen H Geng
Li Ma
Xiao-Feng Niu
Li-Jing Wang
Yan-Qing Ding
Jian-Guo Geng
Journal: Cell Research (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Correction; Cell Research; Figure 1G; Misplacement; Apologize

Abstract: Correction to: Cell Research (2011) 21:609–626. doi:10.1038/cr.2011.17; published online 1 February 2011 The authors apologize for the misplacement of the upper right panel of Figure 1G. The correct panel of Figure 1G is as follows.

Retracted: No

PubPeer comments:
 Erratum Published: 02 June 2011 u201cCorrection to: Cell Research (2011) 21:609u2013626. doi:10.1038 cr.2011.17; published online 1 February 2011 The authors apologize for the misplacement of the upper right panel of Figure 1G. The correct panel of Figure 1G is as follows.u201d The original figure is below. *** ![file] , 
 Someone appears to have taken artistic liberties with an image in Figure 2. *** Closeup ![file] *** Showing location ![file] , 
 Two flow cytometry plots in Figure 6 appear unexpectedly similar. Just noticed the other two do also. *** ![file] , 
 #2 This accused figure does not exist in the above paper , 
 #4 I agree, and apologize. Could the moderators please remove entries 2-4? ,
Pyrrolidinedithiocarbamate Induces Apoptosis in Human Acute Myelogenous Leukemic Cells Affecting NF-κB Activity
Authors: Angelo Messina
Lucia Malaguarnera
Livia Manzella
Rosanna Dimarco
Giuseppe Palumbo
Maria Rosaria Pilastro
Luisa Vicari
Journal: Cancer Investigation (2005)
Discipline: CLINICAL MEDICINE
Keywords: PDTC; metal chelator; redox sensitive transcription factors; pro-oxidant properties; NF-kappaB

Abstract:  Pyrrolidindithiocarbamate (PDTC), is a metal chelator widely used to study the activation of redox sensitive transcription factors. Recently it has been demonstrated that it manifests pro-oxidant properties. The nuclear factor-Kappa B (NF-kappaB) transcription factor can both promote cell survival and induce apoptosis depending on cell type and context in response to genotoxic stress. In our previous study we reported that in acute myelogenous leukemia CD34+ cells PDTC stimulates apoptosis, whereas in CD34+ cells of healthy volunteers PDTC was ineffective. This cytotoxicity was dependent on the generation of superoxide anion and oxidized glutathione. In this article we have shown that the pro-oxidant effect of PDTC in AML cells induces NF-kappaB activity. These findings imply a role for NF-kappaB in the survival of normal cells with respect to leukemic cells, suggesting that NF-kappaB activity and function differs according to tumor cell phenotype. 

Retracted: No

PubPeer comments:
 Figure 4: * Red boxes: Two bands appear to look very similar ![file] Figure 6B: * Teal and yellow boxes: Some lanes show remarkable similarities ![file] This paper was found during a systematic screen of biomedical papers for image duplications, as published in Bik et al., mBio (2016), doi: 10.1128 mBio.00809-16, https: journals.asm.org doi 10.1128 mBio.00809-16. These issues were reported to the journal in October 2015, but it has not yet been addressed by the journal, more than six years later. ,
Antimicrobial photodynamic activity of rose bengal conjugated multi walled carbon nanotubes against planktonic cells and biofilm of Escherichia coli
Authors: Parasuraman Paramanantham
Anju Vt
Syed Asad
Marzouq H Alsaedi
Siddhardha Busi
Alok Sharan
Sruthil Lal Sb
Turki M S Dawoud
Journal: Photodiagnosis and Photodynamic Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: Antimicrobial photodynamic inactivation; Carbon nanotubes; Escherichia coli; RBCNT; Reactive oxygen species
Affiliations: Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, 605 014, India., Department of Physics, School of Physical, Chemical & Applied Sciences, Pondicherry University, Puducherry, 605014, India., Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia., Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, 605 014, India. Electronic address: .

Abstract:  Background: The global threat of antimicrobial resistance especially due to the bacterial biofilms has engaged researchers in the search of new treatment modalities. Antimicrobial photodynamic inactivation (aPDI) is one of the alternative treatment modalities which kills bacteria by generating endogenous reactive oxygen species (ROS). In this work authors evaluated the antibacterial and antibiofilm efficacy of rose Bengal (RB) conjugated to CNT against E. coli. Methods: The interaction of anionic dye to the CNT was studied using UV-vis spectroscopy, HRTEM, FTIR and spectrofluorometry. Phototoxicity of RBCNT conjugate against E. coli was studied using a green light of 50 mW and radiant exposure of 1674.7 J/ cm2 for 10 min. The antibiofilm activity and mechanism of action of RBCNT conjugate in presence of light was evaluated. Results: The loading and encapsulation was found to be 15.46 ± 1.05 and 61.85 ± 4.23% respectively. The photodynamic inactivation of planktonic cells of E. coli was found to 5.46 and 3.56 log10 CFU/ml reduction on treatment with RBCNT and RB respectively. The conjugate also exhibited efficient and enhanced antibiofilm activity against E. coli. The study of mechanism of action has confirmed cell membrane and DNA damage were the two main targets of aPDI. Conclusion: This report has concluded the efficient photodynamic inactivation occurred in Gram negative bacteria E. coli due to the increased production of ROS inside the bacterial cells. Hence, the newly synthesized RBCNT conjugate can be efficiently utilized to control infections caused by E. coli. 

Retracted: No

PubPeer comments:
 In Figure 6, a micrograph has been duplicated and presented as something else. ![file] , 
 Dear Pubpeer Team, Thank you for the valuable comment. We analyzed the original CLSM data. The mistake happened in the original article as an inadvertent mistake during the arrangement of Figure 6 image panels. We apologize for this error. A Corrigendum was published: https: doi.org 10.1016 j.pdpdt.2021.102363 ,
miR-139-mediated NOTCH1 regulation is crucial for the inhibition of osteosarcoma progression caused by resveratrol
Authors: Xinghua Xiao
Weinan Pan
Yanqin Zhang
Feng Chen
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; NOTCH1; Osteosarcoma; Resveratrol; miR-139-5p.

Abstract:  Aims: Osteosarcoma (OS) has the highest incidence among primary malignancies. It is characterized by high tumor heterogeneity, poor prognosis and high lung metastases. Here, we aimed to investigate the role of resveratrol on an OS cell line and its mechanism. Materials and methods: Cell apoptosis and proliferation were analyzed by MTT and flow cytometry analysis respectively. In U2OS cells miR-139-5p overexpression or knock-down and NOTCH1 knock-down cell models were constructed. Quantitative real-time PCR were used to determine the expression of miR-139-5p. Western bot was used to detect levels of NOTCH1, caspase3 and cleaved-caspase-3. Dual luciferase activity assay was used to assess the target of miR-139-5p. Key findings: The apoptosis of U20S and MG63 cell were induced by resveratrol, and lower levels of miR-139-5p in both U2OS and MG63 cells than in osteoblast cells. Alteration of miR-139-5p had an outstanding effect on apoptosis of U2OS cell. The expression of miR-139-5p in U2OS and MG63 cells can be induced by resveratrol. Bioinformatic analysis indicated that the 3'UTR of NOTCH1 contained the motif for microRNA-139-5p binding. Co-transfection with the luciferase reporter contained the wild-type, but not the mutant, of 3'UTR of NOTCH1, together with miR-139-5p decreased the luciferase activity in U2OS cells. NOTCH1 gene knockout altered the apoptosis of U2OS cell. Significance: Collectively, these findings indicate that resveratrol induces the apoptosis of OS cells via the miR-139-5p/NOTCH1 signaling pathway, and provides an experimental and theoretical basis for the development of natural plant-derived compounds that can effectively prevent and treat OS. 

Retracted: No

PubPeer comments:
 Figure 4. Parts of two panels from Figure 4A appear to look similar to parts in panels in Figure 4B. Boxes of the same color highlight areas that look similar to each other. ![file] , 
 Figure 5G. Two panels appear to look similar each other. Boxes of the same color highlight areas that look similar to each other. ![file] ,
Cancer gene therapy by NF-κB-activated cancer cell-specific expression of CRISPR/Cas9 targeting telomeres
Authors: Jian Wu
Wei Dai
Danyang Wang
Jinke Wang
Journal: Gene Therapy (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: NF-κB; cancer therapy; gene therapy; Nage; cancer cells
Affiliations: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China., State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China. .

Abstract:  The transcription factor NF-κB is an attractive target for cancer therapy due to its over-activation in all tumours; however, NF-κB inhibitors developed in the past decades rarely became drugs due to undesirable side effects. In this study, we developed a gene therapy strategy named NF-κB-activated gene expression (Nage), which could induce the death of cancer cells in vitro and in vivo by utilising NF-κB over-activity in cancer cells, but had no effects on normal cells. Nage was consisted of an NF-κB-specific promoter formed by fusing an NF-κB decoy sequence with a minimal promoter, which could be bound by the intracellular over-activated NF-κB and thus activated the expression of downstream effector genes in an NF-κB-specific manner. In this study, we first confirmed the cancer cell-specific over-activation of NF-κB and then tested the cancer cell specificity of the Nage vector by expressing the reporter gene ZsGreen in various in vitro cultivated cells. We next demonstrated that the Nage vector could be used to express CRISPR/Cas9 protein only in cancer cells. The Cas9 protein was then guided by a sgRNA targeting telomeric DNA and induced cancer cell death. The Nage vector expressing Cas9/sgRNA could be packaged into adeno-associated virus (AAV) and intravenously injected to inhibit tumour growth in mice without visible side effects and toxicity. 

Retracted: No

PubPeer comments:
 Supplementary Figure 1A:  Representative images of cells that were only transfected with lipofectin as blank control. As far as I can tell, all the black squares are entirely  perfect black, i.e. Hex code  000000 . If this is a genuine fluorescence microscope image of cells (even cells not expressing GFP) I think one would typically expect to see a few bright spots in the image, or at least a green glow on the image, it s not **only** GFP that will fluoresce, after all. See for example [this paper] which has a non-transduced control (Figure 1A). Perhaps the instrument was set up in such a way that it only captured perfectly black images, in which case I don t think the settings were correct. I wonder if the authors could comment on this. ![file] ,
Effect of Spp1 on nerve degeneration and regeneration after rat sciatic nerve injury
Authors: Meiyuan Li
Dengbing Yao
Yuting Li
Xingyu Liu
Shusen Cui
Ying Yuan
Yuhua Sun
Huaiqin Li
Journal: BMC Neuroscience (2017)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Nerve regeneration; Rat; Schwann cells; Sciatic nerve injury; Secreted phosphoprotein 1 (Spp1)
Affiliations: China-Japan Union Hospital of Jilin University, 126 Xiantai Road, Changchun, 130033, Jilin, People's Republic of China., School of Life Sciences, Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nnatong, 226001, Jiangsu, People's Republic of China., Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China., China-Japan Union Hospital of Jilin University, 126 Xiantai Road, Changchun, 130033, Jilin, People's Republic of China. ., School of Life Sciences, Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nnatong, 226001, Jiangsu, People's Republic of China. .

Abstract:  Background: Wallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. In our previous studies, we reported some key factors that are differentially expressed to activate nerve degeneration and regeneration during WD. Here, we determined the effects of secreted phosphoprotein 1 (Spp1) on WD after rat sciatic nerve injury. Results: Spp1 was upregulated from 6 h to 14 days after sciatic nerve injury. Altered expression of Spp1 in Schwann cells (SC) resulted in altered mRNA and protein expression levels for cytokines, c-Fos, PKCα and phospho-ERK/ERK and affected SC apoptosis in vitro. Silencing of Spp1 expression in SCs using siRNA technology reduced proliferation and promoted migration of SCs in vitro. By contrast, overexpression of Spp1 promoted proliferation and reduced migration in SCs in vitro. Differential expression of Spp1 after sciatic nerve injury in vivo altered the expression of cytokines, c-Fos, PKCα, and the p-ERK/ERK pathway. Conclusions: Spp1 is a key regulatory factor that affects nerve degeneration and regeneration through c-Fos, PKCα and p-ERK/ERK pathways after rat sciatic nerve injury. These results shed new light on the role of Spp1 in nerve degeneration and regeneration during WD. 

Retracted: No

PubPeer comments:
 As we know, Erk protein should be two bands. But, the Erk protein has only one band in this paper! ![file] ,
Genetic Modification of Mesenchymal Stem Cells Overexpressing Angiotensin II Type 2 Receptor Increases Cell Migration to Injured Lung in LPS-Induced Acute Lung Injury Mice
Authors: Song-Qiao Liu
Jing-Yuan Xu
Ai-Ran Liu
Li-Li Huang
Xiu-Ping Xu
Hai-Bo Qiu
Hong-Li He
Feng-Mei Guo
Ling Liu
Shu-Ling Hu
Jian-Feng Xie
Yi Yang
Ji-Bin Han
Ying-Zi Huang
Journal: Stem Cells Translational Medicine (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AT2R; Acute lung injury; Lentiviral vector; Mesenchymal stem cells; Migration.
Affiliations: Department of Critical Care Medicine, Nanjing Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China., Department of Critical Care Medicine, Affiliated Hospital of University of Electronic Science and Technology of China & Sichuan Provincial People's Hospital, Chengdu, People's Republic of China.

Abstract:  Although mesenchymal stem cells (MSCs) transplantation has been shown to promote the lung respiration in acute lung injury (ALI) in vivo, its overall restorative capacity appears to be restricted mainly because of low retention in the injured lung. Angiotensin II (Ang II) are upregulated in the injured lung. Our previous study showed that Ang II increased MSCs migration via Ang II type 2 receptor (AT2R). To determine the effect of AT2R in MSCs on their cell migration after systemic injection in ALI mice, a human AT2R expressing lentiviral vector and a lentivirus vector carrying AT2R shRNA were constructed and introduced into human bone marrow MSCs. A mouse model of lipopolysaccharide-induced ALI was used to investigate the migration of AT2R-regulated MSCs and the therapeutic potential in vivo. Overexpression of AT2R dramatically increased Ang II-enhanced human bone marrow MSC migration in vitro. Moreover, MSC-AT2R accumulated in the damaged lung tissue at significantly higher levels than control MSCs 24 and 72 hours after systematic MSC transplantation in ALI mice. Furthermore, MSC-AT2R-injected ALI mice exhibited a significant reduction of pulmonary vascular permeability and improved the lung histopathology and had additional anti-inflammatory effects. In contrast, there were less lung retention in MSC-ShAT2R-injected ALI mice compared with MSC-Shcontrol after transplantation. Thus, MSC-ShAT2R-injected group exhibited a significant increase of pulmonary vascular permeability and resulted in a deteriorative lung inflammation. Our results demonstrate that overexpression of AT2R enhance the migration of MSCs in ALI mice and may provide a new therapeutic strategy for ALI. Stem Cells Translational Medicine 2018;7:721-730. 

Retracted: No

PubPeer comments:
 An image may be misplaced in Figure 3B. There are similarities between the two marked in red. *** ![file] , 
 Figure 4 appears to a set of images which overlap (green boxes). *** ![file] ,
SIRPalpha1 receptors interfere with the EGFRvIII signalosome to inhibit glioblastoma cell transformation and migration
Authors: G S Kapoor
D M O&#x27;Rourke
Journal: Oncogene (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EGFRvIII; SIRPalpha1; SHP-2; migration; transformation
Affiliations: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract:  EGFRvIII, a frequent genetic alteration of the epidermal growth factor receptor (EGFR), has been shown to increase the migratory potential of tumor cells and normal fibroblasts. Previously, we showed that signal regulatory protein alpha1 (SIRPalpha1) receptors interact with SHP-2 to inhibit wild-type (wt) EGFR-mediated tumor migration, survival and cell transformation. However, the effects of SIRPalpha1 inhibitory receptors on EGFRvIII-mediated phenotypes are unclear. The aim of this study was to investigate the effect of SIRPalpha1 receptor on the EGFRvIII signalosome and phenotypes. Overexpression of SIRPalpha1 in U87MG.EGFRvIII cells inhibited transformation and migration in a MAPK-dependent manner, and is independent of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. We observed reduced EGFRvIII/SHP-2/Gab1/Grb2/Sos-1 interaction and enhanced SIRP/SHP-2 association in U87MG.EGFRvIII/SIRPalpha1 cells when compared with empty vector control cells. Interestingly, SIRPalpha1 overexpression differentially modulated SHP-2 phosphorylation at tyrosyl 542 and 580 residues, which may regulate Erk1/2 activity and the EGFRvIII phenotype. In addition, SIRPalpha1-expressing cells exhibited reduced focal adhesion kinase (FAK) phosphorylation and its recruitment to the EGFRvIII/Grb2/Sos-1/Gab1/SHP-2 complex. Collectively, our data indicate that SIRPalpha1 specifically affects the SHP-2/FAK/Grb2/Sos-1/MAPK activation loop to downmodulate EGFRvIII-mediated migration and transformation. Further understanding of the molecular interactions between the SIRPalpha1 inhibitory receptor and the EGFRvIII signalosome may facilitate the identification of novel targets to inhibit the EGFRvIII glioblastoma phenotype. 

Retracted: No

PubPeer comments:
 Figure 9a. Much more similar than expected. ![file] ,
Downregulation of NIN/RPN12 binding protein inhibit the growth of human hepatocellular carcinoma cells
Authors: Qiyong Guo
Qingjie Lu
Aizhong Shi
Feng Xie
Zaiming Lu
Journal: Molecular Biology Reports (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Nob1; ribosome assembly factor; tumor cells growth; short hairpin RNA; human hepatocellular carcinoma
Affiliations: Department of Radiology, China Medical University Shengjing Hospital, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China.

Abstract:  The ribosome assembly factor NIN/RPN12 binding protein (Nob1) has been suggested to be essential for processing of the 20S pre-rRNA to the mature 18S rRNA, and is also reported to participate in proteasome biogenesis. However, it is unclear whether Nob1 is involved in tumor cells growth. The aim of this study was to determine whether the suppression of Nob1 by short hairpin RNA (shRNA) inhibits the growth of human hepatocellular carcinoma (HCC) cells. Recombinant lentiviral shRNA expression vector carrying Nob1 was constructed and then infected into human HCC cell line SMMC-7721. The growth properties of SMMC-7721/pGCSIL-GFP-shNC and pGCSIL-GFP-shNob1 cells were determined by MTT, BrdU incorporation assay, and flow cytometric analysis. In addition, the colony formation and tumor growth ability in nude mice were detected to define the function of Nob1 in cell transformation and tumorigenesis. Our data showed that the growth and proliferation of SMMC-7721/pGCSIL-GFP-shNob1 cells were significantly reduced compared with the SMMC-7721/pGCSIL-GFP-shNC. In addition, the colony formation was impaired after the suppression of Nob1 in SMMC-7721 cells. And in vivo, the tumor formation ability of the SMMC-7721/pGCSIL-GFP-shNob1 cells was significantly reduced compared with the control cells. Our data support that Nob1 is an important regulator of the tumorigenic properties of human HCC and could be used as a candidate therapeutic target in human HCC. 

Retracted: No

PubPeer comments:
 Copy pasted from https: link.springer.com article 10.1007 s11033-021-06320-1 :  Editorial Expression of Concern. The Editor-in-Chief would like to alert readers that this article [1] includes a problematic cell line. After further analysis, SMMC-7721 is shown to be a HeLa derivative ( https: www.ncbi.nlm.nih.gov pubmed 28807831 ). Because of this, readers are asked to interpret the results with caution. None of the authors have responded to any correspondence from the editor about this editorial expression of concern. Published: 02 April 2021. See also https: retractionwatch.com 2021 04 08 apparent-hela-cell-line-mixup-earns-a-paper-an-expression-of-concern ,
Kaposi's sarcoma-associated herpesvirus reactivation is regulated by interaction of latency-associated nuclear antigen with recombination signal sequence-binding protein Jkappa, the major downstream effector of the Notch signaling pathway
Authors: Erle S Robertson
Ke Lan
Daniel A Kuppers
Journal: Journal of Virology (2005)
Discipline: MICROBIOLOGY
Keywords: Kaposi's sarcoma-associated herpesvirus; KSHV; latency-associated nuclear antigen; LANA; RTA
Affiliations: Department of Microbiology and the Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA., Department of Microbiology and Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, Philadelphia, Pennsylvania

Abstract:  Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor contributing to development of Kaposi's sarcoma. KSHV establishes a latent infection in human B cells expressing the latency-associated nuclear antigen (LANA), a critical factor in the regulation of viral latency. LANA controls KSHV latent infection through repression of RTA, an activator of many lytic promoters. RTA activates the expression of several lytic viral genes by interacting with recombination signal sequence-binding protein Jkappa (RBP-Jkappa), a transcriptional repressor and the target of the Notch signaling pathway. The recognition that a number of KSHV lytic gene promoters, including RTA, contain RBP-Jkappa binding sites raised the possibility that RBP-Jkappa-mediated repression may be central to the establishment of latency. Here, we tested this hypothesis by examining the regulation of RTA by LANA through binding to RBP-Jkappa. This study demonstrates that LANA physically associates with RBP-Jkappa in vitro and in KSHV-infected cells, with the complex formed capable of binding to RBP-Jkappa cognate sequences. RBP-Jkappa binding sites within the RTA promoter have been found to be critical for LANA-mediated repression. Our study describes a novel mechanism through which LANA maintains KSHV latency by targeting a major downstream effector of the Notch signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 5A. Much more similar than expected. https: imgur.com ADvVvoQ , 
 I agree with the similarities noted by Cryptocephalus - and added an additional similarity between lanes 7 and 8 (marked by me in red). ![file] ,
Craniocerebral injury promotes the repair of peripheral nerve injury
Authors: Lei Na
Jingfeng Xue
Jun Gao
Pei Wang
Zhenjun Yang
Hongtao Jiang
Wei Wang
Journal: Neural Regeneration Research (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: craniocerebral injury; horseradish peroxidase tracer technique; nerve regeneration; nerve repair; neural regeneration
Affiliations: Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical College, Chengde, Hebei Province, China., Department of Postgraduate, Chengde Medical College, Chengde, Hebei Province, China., Department of Anatomy, Chengde Medical College, Chengde, Hebei Province, China.

Abstract:  The increase in neurotrophic factors after craniocerebral injury has been shown to promote fracture healing. Moreover, neurotrophic factors play a key role in the regeneration and repair of peripheral nerve. However, whether craniocerebral injury alters the repair of peripheral nerve injuries remains poorly understood. Rat injury models were established by transecting the left sciatic nerve and using a free-fall device to induce craniocerebral injury. Compared with sciatic nerve injury alone after 6-12 weeks, rats with combined sciatic and craniocerebral injuries showed decreased sciatic functional index, increased recovery of gastrocnemius muscle wet weight, recovery of sciatic nerve ganglia and corresponding spinal cord segment neuron morphologies, and increased numbers of horseradish peroxidase-labeled cells. These results indicate that craniocerebral injury promotes the repair of peripheral nerve injury. 

Retracted: No

PubPeer comments:
 Figure 1 appears to have a repeated image. *** ![file] ,
Expression of Concern: Attenuation of NDEA‐induced hepatocarcinogenesis by naringenin in rats
Authors: Duraikannu Arul
Perumal Subramanian
Journal: Cell Biochemistry and Function (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BAX; Bcl-2; caspase; hepatocarcinogenesis; naringenin.
Affiliations: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India. , Department of Biochemistry and Biotechnology, Faculty of Science Annamalai University  Tamil Nadu India

Abstract:  Chemoprevention is one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on hepatocellular carcinoma. Naringenin is one such naturally occurring flavonoid widely found in citrus fruits. In this study, we examined the molecular mechanisms by which naringenin inhibited NDEA-induced hepatocellular carcinoma in rats by analysing the expression patterns of proliferating cell nuclear antigen, Bcl-2, NF-κB, VEGF and MMP-2/9. Enhanced cell proliferation and apoptotic evasion in NDEA-induced hepatocarcinogenesis was associated with imbalance in pro-apoptotic and anti-apoptotic proteins together with upregulation of proliferating cell nuclear antigen (PCNA) and downregulation of caspase-3. Administration of pretreatment and posttreatment of naringenin decreased the expression of PCNA and Bcl-2 and increased the expression of Bax and caspase-3, indicating antiproliferative and apoptotic effects, respectively. Administration of NDEA increased the tumour expression of NF-κB, COX-2, VEGF, MMP-2 and MMP-9 that was correlated with more aggressive lesions and tumour growth. Downregulation of NF-κB, VEGF and MMPs by naringenin seen in the present study were correlated with the inhibition of liver tumour induced by NDEA. Our results suggest that naringenin could act as a legitimate agent by inhibiting cancer processes. 

Retracted: No

PubPeer comments:
 Figure 2. * The VEGF Control and Naringenin alone panels appear to show an overlap if one of the photos is rotated 90 degrees (shown in red). * The NF-kB and MMP-2 NDEA+Naringenin posttreatment panels appear to show an overlap (shown in aqua). ![file] , 
 Expression of Concern, [26 January 2021] . --------------------------------------------- This expression of concern is for the above article, published online on 21 November 2012, in Wiley Online Library , and has been published by agreement between the authors, the journal s Editoru2010inu2010Chief, Prof. Dr Martin Hewinson, and John Wiley Sons, Ltd. The expression of concern has been agreed following concerns raised regarding the appearance of Figure 2. Analysis of immunohistochemistry panels in Figure 2 presented in the manuscript suggested that some images had been duplicated. The authors were unable to provide original data confirming that the images arose from the originally reported experiments, are unmodified, and are suitable for publication. As a result, the journal is issuing this expression of concern to readers. ,
Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury
Authors: Yanzhe Wang
Zhiyi He
Shumin Deng
Journal: Drug Design Development and Therapy (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: brain ischemia; matrix metalloproteases; peroxisome proliferator-activated receptors; ursolic acid.
Affiliations: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.

Abstract:  Background: Activators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance. Methods: The middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours) was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist) was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed. Results: UA-treated (5, 10, or 20 mg/kg) rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P&lt;0.01). Both the PPARγ protein level and the percentage of PPARγ-positive cells were increased in the UA-treated groups (P&lt;0.01). Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P&lt;0.01) but an increased level of TIMP1 (P&lt;0.01). UA exerted its protective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a significant but partial neuroprotective effect. Conclusion: UA can act as a PPARγ agonist to improve the metalloprotease/anti-metalloprotease balance, possibly by inhibiting the activation of the MAPK signaling pathway, thereby attenuating cerebral ischemia and reperfusion injury. Therefore, UA may serve as a novel neuroprotective therapeutic agent. 

Retracted: No

PubPeer comments:
 Figure 4A appears to have a repeated image. *** ![file] , 
 Images in Figure 2B appear to have repeated internal features. TAM. *** ![file] ,
Withdrawn: COVID-19: A global and continental overview of the second wave and its (relatively) attenuated case fatality ratio
Authors: Victor Grech
Sarah Cuschieri
Journal: Early Human Development (2020)
Discipline: CLINICAL MEDICINE
Keywords: Article withdrawal; Author(s); Editor; Publisher; Elsevier Policy
Affiliations: Consultant Paediatrician, Mater Dei Hospital, Malta. Electronic address: ., Lecturer Anatomy Department, Faculty of Medicine and Surgery, University of Malta, 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:
 The results presented in this paper are flawed according to the commented in https: pubpeer.com publications 0DF1BF896DA8967E3BF3A79D26C5CC ![file] ![file] , 
 #1 Dear Rhipidura Albiventris, The comment in https: pubpeer.com publications 0DF1BF896DA8967E3BF3A79D26C5CC has been replied. For details, see https: pubpeer.com publications 0DF1BF896DA8967E3BF3A79D26C5CC In addition, as for the example in https: pubpeer.com publications 0DF1BF896DA8967E3BF3A79D26C5CC , we have discussed it in detail in the reply to https: pubpeer.com publications CF3471D0BE439BE323364A399498A9#4 Thank you for your comments. ,