PReD-Bench/PRed-Bench huggingface dataset:
The expression and function of miRNA-451 in osteosarcoma
Authors: Yangbo Liu
Junzhe Lang
Lei Chen
Kai Zhou
Cailong Liu
Jiandong Yuan
Journal: Medical Oncology (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-451; down-regulated; malignancies; tumor progression; osteosarcoma
Affiliations: Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, China.

Abstract:  MicroRNA-451 has been proven down-regulated in many human malignancies and correlated with tumor progression. However, its expression and clinical significance in osteosarcoma is still unclear. Thus, the aim of this study was to explore the effects of miR-451 in osteosarcoma tumorigenesis and development. The expression level of miR-451 was quantified by quantitative real-time reverse-transcriptase-polymerase chain reaction in primary osteosarcoma tissues and osteosarcoma cell lines. MTT, flow cytometric, and scratch migration assay were used to test the proliferation, apoptosis, and migration of miR-451 transfection osteosarcoma cells, and a mouse model was used to investigate tumorigenesis. The expression levels of miR-451 in osteosarcoma tissues were significantly lower than those in corresponding noncancerous bone tissues (P &lt; 0.001). In addition, miR-451 down-regulation more frequently occurred in osteosarcoma specimens with advanced clinical stage (P &lt; 0.001), positive distant metastasis (P = 0.015), and poor response to neoadjuvant chemotherapy (P &lt; 0.001). Univariate and multivariate analysis identified low miR-451 expression as an unfavorable prognostic factor for both overall and disease-free survival. After miR-451 transfection, cell proliferation, migration, and tumorigenesis in the osteosarcoma cells were significantly inhibited and cell apoptosis was increased. These findings indicate that miR-451 may act not only as a novel diagnostic and prognostic marker, but also as a potential target for molecular therapy of osteosarcoma. 

Retracted: No

PubPeer comments:
 Fig 3.  Effects of miR-451 mimic transfection on cell proliferation, apoptosis, and migration of MG63 and U2OS cells ![file] For comparison, Fig 2 of [Hou et al (2015)] : ![] Fig 3 from [Zhu et al (2014)] : ![] ---------------------------------------- A broader context is available from [a Chinese science-integrity enthusiast] , blogging in 2016 and citing work by the now-vanished site PlagiarismWatch, to reconstruct a network of multiple mutually-plagiarised papers, not including this one. All presumably the work of a papermill. Some of this series of retractions was [covered by RetractionWatch] . ![] ![file] ![file] ,
Enterovirus 71 protease 2Apro targets MAVS to inhibit anti-viral type I interferon responses
Authors: Xiaoyan Zhang
Zhendong Zhao
Sheng Cui
Xiaobo Lei
Xueyan Xi
Jianwei Wang
Qi Jin
Bei Wang
Journal: PLoS Pathogens (2013)
Discipline: MICROBIOLOGY
Keywords: Enterovirus 71; EV71; hand, foot, and mouth disease; HFMD; innate immune evasion
Affiliations: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.

Abstract:  Enterovirus 71 (EV71) is the major causative pathogen of hand, foot, and mouth disease (HFMD). Its pathogenicity is not fully understood, but innate immune evasion is likely a key factor. Strategies to circumvent the initiation and effector phases of anti-viral innate immunity are well known; less well known is whether EV71 evades the signal transduction phase regulated by a sophisticated interplay of cellular and viral proteins. Here, we show that EV71 inhibits anti-viral type I interferon (IFN) responses by targeting the mitochondrial anti-viral signaling (MAVS) protein--a unique adaptor molecule activated upon retinoic acid induced gene-I (RIG-I) and melanoma differentiation associated gene (MDA-5) viral recognition receptor signaling--upstream of type I interferon production. MAVS was cleaved and released from mitochondria during EV71 infection. An in vitro cleavage assay demonstrated that the viral 2A protease (2A(pro)), but not the mutant 2A(pro) (2A(pro)-110) containing an inactivated catalytic site, cleaved MAVS. The Protease-Glo assay revealed that MAVS was cleaved at 3 residues between the proline-rich and transmembrane domains, and the resulting fragmentation effectively inactivated downstream signaling. In addition to MAVS cleavage, we found that EV71 infection also induced morphologic and functional changes to the mitochondria. The EV71 structural protein VP1 was detected on purified mitochondria, suggesting not only a novel role for mitochondria in the EV71 replication cycle but also an explanation of how EV71-derived 2A(pro) could approach MAVS. Taken together, our findings reveal a novel strategy employed by EV71 to escape host anti-viral innate immunity that complements the known EV71-mediated immune-evasion mechanisms. 

Retracted: No

PubPeer comments:
 Correction, March 2017: https: journals.plos.org plospathogens article?id=10.1371 journal.ppat.1006243  The authors would like to correct Fig 5A, as an error was introduced in the preparation of this figure for publication. In Fig 5A, the u201cmocku201d graph was duplicated and also appears as the u201c4hu201d graph. The authors have replaced the duplicated graph with the correct u201c4hu201d graph. Here is the original Figure 5A, with blue boxes marking the duplicated panels, as reported to the journal in September 2014. ![file] I thank the authors and journal for correcting this error. 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. ,
Phosphorylation of PDE4A5 by MAPKAPK2 attenuates fibrin degradation via p75 signalling
Authors: B A Fertig
F Christian
J Ling
M D Houslay
J E Findlay
K F Houslay
G S Baillie
A J Tibbo
Journal: Journal of biochemistry (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PDE4A; cyclic-AMP; extracellular matrix; p75-NTR; phosphodiesterase.
Affiliations: Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Granta Park, Cambridge, UK., Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK., Institute of Cancer Studies and Pharmaceutical Science, King's College, 150 Stamford Street, London, UK.

Abstract:  Phosphodiesterases (PDEs) shape local cAMP gradients to underpin the specificity of receptor function. Key to this process is the highly defined nature of the intra-cellular location of PDEs in the cell. PDE4A5 is a PDE isoform that specifically degrades cAMP and is known to associate with the p75 neurotrophin receptor (p75NTR) where it modulates cAMP signalling cascades that regulate extracellular matrix remodelling in the lungs. Here we map and validate novel protein-protein interaction sites that are important for formation of the PDE4A5-p75NTR complex and show, for the first time, that phosphorylation of PDE4A5 by MAPKAPK2 enhances PDE4A5 interaction with p75NTR and that this, in turn, serves to attenuate fibrin degradation. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than you would expect. https: imgur.com KKA3FIF , 
 Figure 3 (f) shows reuse of the same original image, with cropping, rotating and stretching, to represent  4A KO MEFs + PDE4A5 (S147A) Untreated condition and Aniso + SB condition. ![file] See imgur image at https: i.imgur.com m6msI7H.jpg for better clarity , 
 Figure 3 (h) shows reuse of the same original image, with cropping, flipping and stretching, to represent  Wild-type MEFs Untreated condition and  PDE4B -KO MEFs Anisomycin condition. ![file] , 
 Figure 2. Much more similar and different than expected. ![file] , 
 Figure 2. Much more similar after vertical stretch than expected. ![file] , 
 Figure 2. Much more similar and different than expected. ![file] , 
 https: retractionwatch.com 2021 11 11 exclusive-university-of-glasgow-seeking-retraction-of-multiple-papers-after-findings-of-image-manipulation , 
 14 October 2022 retraction https: academic.oup.com jb advance-article doi 10.1093 jb mvac074 6761197 J. Biochem. 2021. doi:10.1093 jb mvz016 This is a retraction to: K F Houslay, B A Fertig, F Christian, A J Tibbo, J Ling, J E Findlay, M D Houslay, G S Baillie. Phosphorylation of PDE4A5 by MAPKAPK2 attenuates fibrin degradation via p75 signalling, The Journal of Biochemistry, Volume 166, Issue 1, July 2019, Pages 97u2013106, https: doi.org 10.1093 jb mvz016 The corresponding author is retracting this article following an institutional investigation into the authenticity of the figures in the paper. The institution ultimately determined Figure 3 was not authentic and the scientific integrity of the article had been compromised. ,
Labeling efficacy of superparamagnetic iron oxide nanoparticles to human neural stem cells: comparison of ferumoxides, monocrystalline iron oxide, cross-linked iron oxide (CLIO)-NH2 and tat-CLIO
Authors: Dongyeol Lim
Byung-Woo Yoon
Miyeoun Song
Yunhee Kim
In-Chan Song
Woo Kyung Moon
Journal: Korean Journal of Radiology (2007)
Discipline: CLINICAL MEDICINE
Keywords: human neural stem cell; superparamagnetic iron oxide nanoparticles; labeling efficacy; ferumoxides; MION
Affiliations: Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul National University, Seoul 110-744, Korea., Department of Diagnostic Radiology, Seoul National University Hospital, and the Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul 110-744, Korea., Department of Applied Chemistry, Sejong University, Seoul 143-747, Korea.

Abstract:  Objective: We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH(2) and tat-CLIO. Materials and methods: The hNSCs (5 x 10(5) HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 microg/ml of ferumoxides, MION or CLIO-NH(2), and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. Results: The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15+/-0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH(2), respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH(2) into the hNSCs was comparable to that of tat-CLIO. Conclusion: For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH(2) and the transfection agent PLL. 

Retracted: No

PubPeer comments:
 Figure 5 appears to have a set of repeated images. Marked here in green. Additionally, if I understand correctly, the caption seems to refer to three sets of cells for 5C, but only two sets are pictured. Apologies if I am misunderstanding something. The previous correction for this paper concerned another matter: u201cErratum: KJR 2007;8:365-371 Author s Correction. Page 366, first sentence of Material and Methods should read,  A human immortalized neural stem cell (NSC) line, HB1.F3, was used for our study. The tactics used for the isolation, propagation, characterization, and cloning of these cells, were as described previously (26, 27). This was kindly provided by Dr. Seung U. Kim (Ajou University, Suwon, Korea).u201d http: dx.doi.org 10.3348 kjr.2008.9.1.94 *** Figure 5 and caption ![file] , 
 Figure 2 as well ![file] ,
MicroRNA-217 inhibits cell proliferation and invasion by targeting Runx2 in human glioma
Authors: Yonggang Zhu
Li Feng
Hongguang Zhao
Songbai Xu
Journal: American journal of translational research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glioma; Runx2; invasion; miR-217; proliferation.
Affiliations: Department of Radiotherapy, China-Japan Union Hospital of Jilin University Changchun130033, P.R. China., Department of Nuclear Medicine, The First Hospital of Jilin University Changchun 130021, P.R. China., Department of Neurosurgery, The First Hospital of Jilin University Changchun 130021, P.R. China.

Abstract:  MircroRNA-217 (miR-217) has been showed to involve in the initiation and development of human cancers, and is recognize as a tumor suppressor miRNA in several tumors. However, the clinical significance and its underlying role in human glioma remain unclear. Herein, we found that the expression of miR-217 was significantly down-regulated in glioma tissues as compared with adjacent normal brain tissues. Clinical association analysis disclosed that low-expression of miR-217 was evidently negative associated with advanced tumor stage (grade III + IV) in glioma. Further function assays showed that miR-217 inhibited proliferation, colony formation, invasion and migration of glioma cells. Notably, runt-related transcription factors 2 (Runx2) was identified as a functional target of miR-217 in glioma. Furthermore, an inverse correlation between miR-217 and Runx2 expression was observed in glioma tissues. Downregulation of Runx2 has similar with inhibition effect of overexpression of miR-217, and upregulation of Runx2 reversed the effects of overexpressing of miR-217. Taken together, these results suggest a critical role of miR-217 in suppressing proliferation, migration, and invasion of glioma by targeting Runx2. 

Retracted: No

PubPeer comments:
 *[right]* Fig 5B.  Runx22 expression on ... protein level were measured in U87 cells transfected with si-Runx2 or si-NC by ... western blot . *[left]* Fig 3D from [Zhu et al (2017)] .  The PIK3R3 ... protein expression levels were determined in U87 cells transfected with miR-365 mimic or miR-NC by ... western blotting . ![file] The only difference seems to be in focus. UPDATE: A third sighting of the Runx22 PIK3R3 band! Fig 4D from [De et al (2019)] .  SOX12 expression on ... protein levels was examined in MCF-7 cells transfected with miR-326 mimics or miR-NC . ![file] , 
 Corrected [15 November 2021] . --------------- In this article, we found that there are some mistakes in Figures 3, u200b,5,5, u200b,6,6, and the correct pictures are shown below. We would like to publish this Erratum to reflect changes. The authors express regrets for these mistakes. Fig 3: ![file] Fig 5: ![file] Fig 6: ![] ,
Effect of adiponectin on kidney crystal formation in metabolic syndrome model mice via inhibition of inflammation and apoptosis
Authors: Yasuhiro Fujii
Shuzo Hamamoto
Yasue Kubota
Masahito Hirose
Yutaro Hayashi
Atsushi Okada
Takahiro Yasui
Keiichi Tozawa
Kenjiro Kohri
Kazuhiro Niimi
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: kidney crystal formation; metabolic syndrome; adiponectin treatment; genome-wide expression analyses; genetic environmental changes
Affiliations: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Abstract:  The aims of the present study were to elucidate a possible mechanism of kidney crystal formation by using a metabolic syndrome (MetS) mouse model and to assess the effectiveness of adiponectin treatment for the prevention of kidney crystals. Further, we performed genome-wide expression analyses for investigating novel genetic environmental changes. Wild-type (+/+) mice showed no kidney crystal formation, whereas ob/ob mice showed crystal depositions in their renal tubules. However, this deposition was remarkably reduced by adiponectin. Expression analysis of genes associated with MetS-related kidney crystal formation identified 259 genes that were &gt;2.0-fold up-regulated and 243 genes that were &lt;0.5-fold down-regulated. Gene Ontology (GO) analyses revealed that the up-regulated genes belonged to the categories of immunoreaction, inflammation, and adhesion molecules and that the down-regulated genes belonged to the categories of oxidative stress and lipid metabolism. Expression analysis of adiponectin-induced genes related to crystal prevention revealed that the numbers of up- and down-regulated genes were 154 and 190, respectively. GO analyses indicated that the up-regulated genes belonged to the categories of cellular and mitochondrial repair, whereas the down-regulated genes belonged to the categories of immune and inflammatory reactions and apoptosis. The results of this study provide compelling evidence that the mechanism of kidney crystal formation in the MetS environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. This is the first report to prove the preventive effect of adiponectin treatment for kidney crystal formation by renoprotective activities and inhibition of inflammation and apoptosis. 

Retracted: No

PubPeer comments:
 Figure 6. * Blue arrows: sharp vertical background transitions are visible between some lanes. * Some bands in the LYZ1 and STAT3 panels appear to look similar, although sometimes rotated or shown at a different exposures. Boxes and arrows of the same color show bands that look similar, as well as their respective orientation. ![file] This was reported to the journal in 2015, with a friendly reminder in 2016, but no response so far. ,
Down-regulation of Treg by interference of enhances the killing effect of CIK on leukemia cell HL-60
Authors: X-X Xing
Y-C Dong
X-Y Zhao
Journal: European Review for Medical and Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cytokine-induced killer cells; Regulatory T cells; Foxp3; Leukemia; HL-60 cells
Affiliations: Department of Cardiovascular, Gaotang County People's Hospital of Shandong Province, LiaoCheng, Shandong, China. .

Abstract:  Objective: Cytokine-induced killer cells (CIK) is a type of immune cell with antitumor activity induced by a variety of cytokines. Regulatory T cells (Treg) is a T cell subgroup featured as immunosuppressive function. Existing CIK cultivation system may inevitably induce Treg. Forkhead box protein 3 (Foxp3) is an essential transcription factor for Treg function. This study aimed to investigate the effects of CIK on the leukemia cell HL-60. Materials and methods: This work silenced Foxp3 expression on the basis of CIK induction, aiming to investigate its killing effect on HL-60 cells. Peripheral blood mononuclear cells were separated and differentiated to CIK in vitro. CD3+CD56+ and CD4+CD25+Foxp3+ Treg cells were detected by flow cytometry. CIK cells were co-cultured with HL-60 cells under the effector-target ratio at 20:1, 10:1, and 5:1, respectively. The killing activity of CIK on HL-60 cells was determined by CCK-8 assay. Results: The ratio of CD3+, CD3+CD8+, and CD3+CD56+ cells gradually increased during CIK induction. Foxp3 interference significantly reduced Treg cell ratio on the 7th day (p &lt; 0.05). Treg cell ratio was significantly lower in Foxp3 interference group at 1.62% ± 0.07% compared with control (p &lt; 0.05). The killing activity of CIK on HL-60 cells enhanced following the increase of effector-target ratio. Interference of Foxp3 significantly elevated the killing activity of CIK on HL-60 cells with effector-target ratio dependence (p &lt; 0.05). CIK can effectively suppress HL-60 cell growth. Treg significantly inhibited the anti-tumor effect of CIK. Conclusions: Interference of Foxp3 expression significantly declined Treg level and attenuated its suppression impact on CIK, thus enhancing the killing effect of CIK on HL-60 cells. 

Retracted: No

PubPeer comments:
 Somewhere along the process of composition, the words  FOXP3 expression appear to have been dropped from the title. Inquiring minds are wondering whether this happened before or after the peer-reviewing. This paper has features suggestive of [what has elsewhere been labeled as  Papermill #2 ] , characterised by stylised geometrical WBs that are reduced to black blobs on a featureless grey background, reminiscent of a Miro painting: ![file] In the present case, the flow-cytometry scatterplots depart from the template preferred by that papermill, though I am not completely convinced that they arose from separate records of separate conditions. ![file] Other examples are listed in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit?usp=sharing ,
CaCO3 blowing agent mixing method for biomass composites improved buffer packaging performance
Authors: Jian-Feng Li
Zi-Yu Guo
Mao-Cheng Ji
Kai-Qiang Sun
Chuan-Wei Zhang
Jian-Yong Li
Fang-Yi Li
Journal: RSC Advances (2021)
Discipline: CHEMISTRY
Keywords: Biodegradable composites; open-cell structure; CaCO3; nucleating agent; porous composites
Affiliations: Key Laboratory of High Efficiency and Clean Mechanical Manufacture, Ministry of Education, School of Mechanical Engineering, Shandong University, Jinan 250061

Abstract:  Biodegradable composites with an open-cell structure were developed to replace petroleum-based buffer packaging materials. To overcome the problem of uneven and insufficient foam in the composites, CaCO3 was used as a nucleating agent to prepare porous composites. At 5 wt% CaCO3, more uniform and dense composite cells with better cushioning performance were obtained. A further increase in the CaCO3 content caused the density of the cells and the cushioning properties of the composites to decrease. The addition of CaCO3 improved the thermal stability and water barrier properties. The moisture absorption was reduced by 15%. X-ray diffraction analysis indicated that the addition of CaCO3 destroyed the crystalline structure of the starch and produced a new crystalline peak, resulting in a significant reduction in the crystallinity. The decrease in the crystallinity of the starch resulted in the formation of a homogeneous slurry that produced a uniform foam in the composites. 

Retracted: No

PubPeer comments:
 Figure 6 Blue and red XRD patterns identical for different samples ![file] ,
Kaposi's sarcoma-associated herpesvirus induces rapid release of angiopoietin-2 from endothelial cells
Authors: Fu-Chun Zhou
Feng-Chun Ye
Stanley Nithianantham
Bala Chandran
Xiao-Lan Yu
Shou-Jiang Gao
Aaron Weinberg
Journal: Journal of Virology (2013)
Discipline: MICROBIOLOGY
Keywords: Kaposi sarcoma-associated herpesvirus; KSHV; angiopoietin-2; Ang-2; endothelial cells
Affiliations: Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio, USA. 

Abstract:  Kaposi sarcoma-associated herpesvirus (KSHV) stimulates proliferation, angiogenesis, and inflammation to promote Kaposi sarcoma (KS) tumor growth, which involves various growth factors and cytokines. Previously, we found that KSHV infection of human umbilical vein endothelial cells (HUVECs) induces a transcriptional induction of the proangiogenic and proinflammatory cytokine angiopoietin-2 (Ang-2). Here, we report that KSHV induces rapid release of Ang-2 that is presynthesized and stored in the Weibel-Palade bodies (WPB) of endothelial cells upon binding to its integrin receptors. Blocking viral binding to integrins inhibits Ang-2 release. KSHV binding activates the integrin tyrosine kinase receptor signaling pathways, leading to tyrosine phosphorylation of focal adhesion kinase (FAK), the tyrosine kinase Src, and the Calα2 subunit of the l-type calcium channel to trigger rapid calcium (Ca(2+)) influx. Pretreatment of endothelial cells with specific inhibitors of protein tyrosine kinases inhibits KSHV-induced Ca(2+) influx and Ang-2 release. Inhibition of Ca(2+) mobilization with calcium channel blockers also inhibits Ang-2 release. Thus, the interaction between KSHV and its integrin receptors plays a key role in regulating rapid Ang-2 release from endothelial cells. This finding highlights a novel mechanism of viral induction of angiogenesis and inflammation, which might play important roles in the early event of KS tumor development. 

Retracted: No

PubPeer comments:
 Figure 4. * Marked in red: The first three lanes of the Ang-2 panel in FIgure 4A appear to look similar to the Ang-2 panel in Figure 4C, albeit with a different height-width ratio. This has been reported to the journal in December 2014. ![file] , 
 #1 Appreciations and sincere apology! Indeed the same Ang-2 bands shown in Fig. 4A were accidently re-loaded in Fig. 4C. We are in the process of submitting an Author Correction to address this issue. Attached are the corrected Fig. 4 and the original Western blot for Fig. 4A and C. ![file] ![file] , 
 Thank you, dr. Ye, for posting the correct blots here. Are you planning to issue a correction to the journal as well? , 
 Yes, we made the correction by submitting an Author Correction, which has been accepted for publication. ,
Targeting the mTOR Complex by Everolimus in NRAS Mutant Neuroblastoma
Authors: Gerhard Rogler
Derek A Oldrige
Alessandra Curioni-Fontecedro
Panagiotis Samaras
John M Maris
Adriano Aguzzi
Michael K Kiessling
Michael Scharl
Silvia Lang
Journal: PloS one (2016)
Discipline: Multidisciplinary
Keywords: High-risk neuroblastoma; NRAS mutant; MEK inhibitors; cell growth; PI3K pathway
Affiliations: Department of Gastroenterology and Hepatology, UniversityHospital Zurich, Zurich, Switzerland., Department of Oncology, University Hospital Zurich, Zurich, Switzerland., Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland., Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States of America.

Abstract:  High-risk neuroblastoma remains lethal in about 50% of patients despite multimodal treatment. Recent attempts to identify molecular targets for specific therapies have shown that Neuroblastoma RAS (NRAS) is significantly mutated in a small number of patients. However, few inhibitors for the potential treatment for NRAS mutant neuroblastoma have been investigated so far. In this in-vitro study, we show that MEK inhibitors AZD6244, MEK162 and PD0325901 block cell growth in NRAS mutant neuroblastoma cell lines but not in NRAS wild-type cell lines. Several studies show that mutant NRAS leads to PI3K pathway activation and combined inhibitors of PI3K/mTOR effectively block cell growth. However, we observed the combination of MEK inhibitors with PI3K or AKT inhibitors did not show synergestic effects on cell growth. Thus, we tested single mTOR inhibitors Everolimus and AZD8055. Interestingly, Everolimus and AZD8055 alone were sufficient to block cell growth in NRAS mutant cell lines but not in wild-type cell lines. We found that Everolimus alone induced apoptosis in NRAS mutant neuroblastoma. Furthermore, the combination of mTOR and MEK inhibitors resulted in synergistic growth inhibition. Taken together, our results show that NRAS mutant neuroblastoma can be targeted by clinically available Everolimus alone or in combination with MEK inhibitors which could impact future clinical studies. 

Retracted: No

PubPeer comments:
 Figure 3: More similar than expected. Could authors check it please? ![file] , 
 According to Plos One policies:  PLOS does not permit references to u201cdata not shown.u201d Authors should deposit relevant data in a public data repository or provide the data in the manuscript. However, in this paper authors have at least two data not shown:  To assure that the BKM120 would be generally functional in this setting, we used the multiple myeloma cell line L-363 as a positive control. In previous screening experiments in our lab, L-363 was one of the very few cell lines that showed a relevant IC50 towards BKM120 (data not shown).   However, we could not observe a synergism of AKT inhibitor MK2206 and MEK inhibitors AZD6244 and MEK162 in NRAS mutant neuroblastoma cell lines (data not shown). This might be explained by different downstream signaling of the different RAS family members. Could authors kindly provide these data to follow Plos One policies? ,
12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction
Authors: Nikhlesh K Singh
James A Mobley
Gadiparthi N Rao
Sivareddy Kotla
Alexander Tinnikov
Rima Chattopadhyay
Elena Dyukova
Journal: Journal of Lipid Research (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: 15(S)-hydroxyeicosatetraenoic acid; 15-lipoxygenase 1; reactive oxygen species; tight junction; xanthine oxidase.
Affiliations: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38138., Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35291., Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38138. Electronic address: .

Abstract:  To understand the mechanisms of 15(S)-HETE-induced endothelial cell (EC) barrier dysfunction, we examined the role of xanthine oxidase (XO). 15(S)-HETE induced junction adhesion molecule A (JamA) phosphorylation on Y164, Y218, and Y280 involving XO-mediated reactive oxygen species production and Src and Pyk2 activation, resulting in its dissociation from occludin, thereby causing tight junction (TJ) disruption, increased vascular permeability, and enhanced leukocyte and monocyte transmigration in vitro using EC monolayer and ex vivo using arteries as models. The phosphorylation of JamA on Y164, Y218, and Y280 appears to be critical for its role in 15(S)-HETE-induced EC barrier dysfunction, as mutation of any one of these amino acid residues prevented its dissociation from occludin and restored TJ integrity and barrier function. In response to high-fat diet (HFD) feeding, WT, but not 12/15-lipoxygenase (LO)(-/-), mice showed enhanced XO expression and its activity in the artery, which was correlated with increased aortic TJ disruption and barrier permeability with enhanced leukocyte adhesion and these responses were inhibited by allopurinol. These observations provide novel insights on the role of XO in 12/15-LO-induced JamA tyrosine phosphorylation and TJ disruption leading to increased vascular permeability in response to HFD. 

Retracted: Yes

PubPeer comments:
 2019 retraction. http: www.jlr.org content 60 4 909 This article has been withdrawn by Elena Dyukova, Nikhlesh K. Singh, Sivareddy Kotla, James A. Mobley, and Gadiparthi N. Rao. In Fig. 2D, the images for the Ad-dnPyk2 from control and Ad-dnSrc from 15(S)-HETE were derived from the same slide. In Fig. 2F, the Ad-dnSrc + 15(S)-HETE and Ad-dnPyk2 + 15(S)-HETE panels are duplicated images. In Fig. 3E, the rJamA (Y107F) and rJamA (Y164F) from control panels were derived from the same slide, as were the rJamA (Y218F) and rJamA (Y280F) from control panels. Due to these image duplications, the above-named authors have withdrawn this article. , 
 Here is an illustration of the duplications and overlaps mentioned in the Retraction Notice: ![file] ,
Facile Peptide Bond Formation: Effective Interplay between Isothiazolone Rings and Silanol Groups at Silver/Iron Oxide Nanocomposite Surfaces
Authors: Mahya Soroushnejad
Zoleikha Hajizadeh
Jamal Rahimi
Ali Maleki
Reza Taheri-Ledari
Journal: ACS Omega (2019)
Discipline: CHEMISTRY
Keywords: protein-drug conjugations; peptide coupling reagents; heterogeneous nanoscale reagent; silver; silica-coated iron oxide nanoparticles
Affiliations: Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran.

Abstract:  Proportional to considerable progress in protein-drug conjugations, attention to the efficient peptide coupling reagents is being increased. Hence, in this study, a versatile heterogeneous nanoscale reagent is presented for chemical, biological, and medical purposes. A combination of silver and silica-coated iron oxide nanoparticles (Ag/Fe3O4) has been well functionalized with isothiazolone rings via a silver-modified Heck mechanism. An appropriate condition is provided for peptide bond formation through the surface interplay between silanol groups and the loaded isothiazolone rings. A logical mechanism including a series of successive covalent bonds onto the surface of Ag/Fe3O4 nanocomposites is suggested for this catalyzed peptide bond formation. Accurate comparisons have been made to obtain the optimum value of the nanocatalyst and suitable conditions. As an additional application, the biological activity of the desired product has also been investigated through antibacterial assay tests. The results showed that our desired product could also be used as an effective heterogeneous nanoscale antibacterial agent for different purposes. In this regard, all of the essential structural and practical analyses have been carried out and precisely interpreted. 

Retracted: No

PubPeer comments:
 Figure 4a of this paper appears to show an overlap with Figure 4C from another paper by the same group, i.e. Reza Taheri-Ledari et al., Ultrasonics - Sonochemistry 59 (2019) 104737, DOI: 10.1016 j.ultsonch.2019.104737 - https: pubpeer.com publications 20A9999AC61F9C5A22D56A05A894EB Shown with pink boxes. The photos appear to be showing different nanocomposites: * Ali Maleki 2019 10.1021 acsomega.9b00986: Fe3O4@SiO2@vinyl * Reza Taheri-Ledari 2019, 10.1016 j.ultsonch.2019.104737: Fe2O4 SiO2.PDA USW Irradiation Could the authors please clarify if these were the same samples? ![file] , 
 Both of mentioned figures in #1, also look strikingly similar to Fig 6. (A) Fe3O4@SiO2 NP in another paper by the same group (DOI: 10.1002 slct.201803001). *** ![file] *** ,
Effect of exosomes derived from mir-126-modified mesenchymal stem cells on the repair process of spinal cord injury in rats
Authors: X-D He
Y-Q Dong
S Pan
W-W Zhang
B Yuan
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-126; mesenchymal stem cell; exosomes; spinal cord injury; rats
Affiliations: Department of Spine Surgery, Xinchang Hospital Affiliated to Wenzhou Medical University, Shaoxing, China. .

Abstract:  Objective: To investigate the effect of the micro ribonucleic acid (miR)-126-modified mesenchymal stem cell (MSC)-derived exosomes (MSC-exos) on the repair process of spinal cord injury (SCI) in rats. Materials and methods: MiR-126-modified MSCs were cultured, the exosomes were extracted, and a rat model of SCI was established. The Quantitative Polymerase Chain Reaction (qPCR) was carried out to detect the expression of miR-126 in the injured spinal cord, and the Western blotting (WB) was adopted to detect the expressions of the exosome-related molecules. Subsequently, the motor function recovery of rats was examined via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The effects of miR-126 exosomes on the injury volume and NeuN retention following SCI were evaluated via immunohistochemistry. Results: MSCs were able to package miR-126 into exosomes secreted. After SCI, the recovery of the hind limb function of rats was remarkably improved by miR-126-modified MSC-exos relative to the control group. Treatment with miR-126-modified MSC-exos remarkably decreased the injury volume, retained the neuronal cells, and triggered the axon regeneration following SCI. Besides, the expression of Ras homolog gene family member A (RhoA), identified as the downstream gene of miR-126, was downregulated in the group with miR-126-modified MSC-exos. Moreover, miR-126-modified MSC-exos activated the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. Conclusions: MiR-126-modified MSC-exos protect neurons of rats with SCI, stimulates axon regeneration, and improves the recovery of limb motor function after SCI. 

Retracted: No

PubPeer comments:
 This article has been withdrawn. The journal does not provide any details beyond  This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause. The original article has been removed. ,
Exposure to Cigarette Smoke Enhances the Stemness of Alveolar Type 2 Cells
Authors: Minako Sato
Mamoru Sasaki
Tomoko Betsuyaku
Naofumi Kameyama
Makoto Ishii
Hidehiro Irie
Mari Ozaki
Akihiro Tsutsumi
Koichi Fukunaga
Ahmed E Hegab
Shotaro Chubachi
Journal: American Journal of Respiratory Cell and Molecular Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: alveolar type 2 cell; cigarette smoke; colony-forming assay; emphysema; lung stem cell.
Affiliations: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Abstract:  Chronic exposure to cigarette smoke (CS) causes chronic inflammation, oxidative stress, and apoptosis of epithelial cells, which results in destruction of the lung matrix. However, the mechanism by which the lung fails to repair the CS-induced damage, thereby succumbing to emphysema, remains unclear. Alveolar type 2 (AT2) cells comprise the stem cells of the alveolar compartments and are responsible for repairing and maintaining lung tissues. In this study, we examined the effect of chronic CS on AT2 stem cells. Adult mice expressing GFP in their AT2 cells were exposed to CS for &gt; 3 months. Histological assessment showed that CS not only induced emphysematous changes but also increased the number of AT2 cells compared with that of air-exposed lungs. Assessment of sorted GFP+/AT2 cells via the stem cell three-dimensional organoid/colony-forming assay revealed that the number and size of the colonies formed by the CS-exposed AT2 stem cells were significantly higher than those of air-exposed control AT2 cells. Although CS-exposed lungs had more apoptotic cells, examination of the surviving AT2 stem cells in two-dimensional in vitro culture revealed that they developed a higher ability to resist apoptosis. Microarray analysis of CS-exposed AT2 stem cells revealed the upregulation of genes related to circadian rhythm and inflammatory pathways. In conclusion, we provide evidence that AT2 stem cells respond to chronic CS exposure by activating their stem cell function, thereby proliferating and differentiating faster and becoming more resistant to apoptosis. Disturbances in expression levels of several circadian rhythm-related genes might be involved in these changes. 

Retracted: No

PubPeer comments:
 Fig 4 with duplications which may occur in serial photographs of the same object area. Control 0h and Control 4h seem to be more different, however, than Smoke 0h and Smoke 4h. According to methods, near confluent 2D cell monolayer on fixed membrane with minimal proliferation while Smoke4h, Smoke8h and Smoke16h show only small identical areas. Are there more serial photographs available? ![file] ,
DHA supplemented in peptamen diet offers no advantage in pathways to amyloidosis: is it time to evaluate composite lipid diet?
Authors: David Westaway
Lin Wang
Mary Keet
Zareen Amtul
Peter Merrifield
Richard F Rozmahel
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: DHA; beta-amyloid; Alzheimer's disease; plaque pathogenesis; dietary nutrients
Affiliations: Department of Biochemistry, University of Western Ontario, London, Ontario, Canada. 

Abstract:  Numerous reports have documented the beneficial effects of dietary docosahexaenoic acid (DHA) on beta-amyloid production and Alzheimer's disease (AD). However, none of these studies have examined and compared DHA, in combination with other dietary nutrients, for its effects on plaque pathogenesis. Potential interactions of DHA with other dietary nutrients and fatty acids are conventionally ignored. Here we investigated DHA with two dietary regimes; peptamen (pep+DHA) and low fat diet (low fat+DHA). Peptamen base liquid diet is a standard sole-source nutrition for patients with gastrointestinal dysfunction. Here we demonstrate that a robust AD transgenic mouse model shows an increased tendency to produce beta-amyloid peptides and amyloid plaques when fed a pep+DHA diet. The increase in beta-amyloid peptides was due to an elevated trend in the levels of beta-secretase amyloid precursor protein (APP) cleaving enzyme (BACE), the proteolytic C-terminal fragment beta of APP and reduced levels of insulin degrading enzyme that endoproteolyse beta-amyloid. On the contrary, TgCRND8 mice on low fat+DHA diet (based on an approximately 18% reduction of fat intake) ameliorate the production of abeta peptides and consequently amyloid plaques. Our work not only demonstrates that DHA when taken with peptamen may have a tendency to confer a detrimental affect on the amyloid plaque build up but also reinforces the importance of studying composite lipids or nutrients rather than single lipids or nutrients for their effects on pathways important to plaque development. 

Retracted: No

PubPeer comments:
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 #4 Identified by another reader, another illustration of concerns for Figure 4, apparently unaddressed in 2017 correction. Journal notified. *** ![file] , 
 Response from the institution s ethics office:  Thank you for contacting the Research Ethics Office. I can confirm that this issue has already been addressed. ,
Mechanisms of oxidative stress effects of the NADPH oxidase-ROS-NF-κB transduction pathway and VPO1 on patients with chronic obstructive pulmonary disease combined with pulmonary hypertension
Authors: X Zhao
B Zhuan
P Li
Z Yang
Y Yu
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: NADPH oxidase; ROS; NF-κB; VPO1; oxidative stress
Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Northwest University for Nationalities, Yinchuan, Ningxia Province, China. .

Abstract:  Objective: This study explored the oxidative stress effects of the NADPH oxidase-ROS-NF-κB transduction pathway and vascular peroxidase 1 (VPO1) on patients with chronic obstructive pulmonary disease (COPD) combined with pulmonary hypertension (PH). Patients and methods: 30 patients with pure COPD and 30 patients with stable COPD combined with PH, who were admitted to our hospital from January 2015 to December 2015, were enrolled as the control group and the observation group, respectively. NADPH oxidase activity in mononuclear cells, reactive oxygen species (ROS), NF-κB, VPO1 levels in serum, and further oxidative stress-related indices were compared and analyzed. Results: Systolic pulmonary pressure (SPAP) (63.65±9.47 mmHg) of the observation group was higher than SPAP (53.13±7.52 mmHg) of the control group (p&lt;0.05); malondialdehyde (MDA) (7.81±2.24 nmol/l) of the observation group was lower than MDA (9.54±3.38 nmol/l) of the control group (p&lt;0.05); superoxide dismutase (SOD) (406.73±147.35 U/ml) of the observation group was higher than SOD (295.16±106.73 U/ml) of the control group (p&lt;0.05). NADPH oxidase activity, ROS and NF-κB levels of the observation group were higher than those of the control group (p&lt;0.05). The average level of serum VPO1 in the observation group (236.71±42.35) ng/L was significantly higher than that of the control group (122.56±34.62) ng/L (p&lt;0.05). In the observation group, the level of SPAP was positively correlated with the concentration of VPO1 (r=0.615, p&lt;0.05), the serum levels VPO1 were negatively correlated with MDA levels (r=-0.537, p&lt;0.05), MDA and ROS levels were negatively correlated (r=-0.482, p&lt;0.05), and the levels of SOD were positively correlated with NF-κB (r=0.427, p&lt;0.05). Conclusions: The NADPH oxidase-ROS-NF-κB transduction pathway, VPO1, oxidative stress and their complicated interactions are implicated in the occurrence and development of COPD combined with PH. 

Retracted: No

PubPeer comments:
 Figures 2 to 5. Is there any special meaning in the varying symbols in these scatterplots? - sometimes circles in Figs 4 and 5 and sometimes semicircles or smaller fragments; sometimes compressed rhombs in 2 and 3, sometimes broken fragments. ![file] ![file] VPO1 ranges around 150-250 ng ul in the horizontal axis of Fig 2, and from 1 to 12 ng ul in the horizontal axis of Fig 3. Another factor of 12 distinguishes the MDA measurements plotted on the horizontal axes of Figs 3 and 4. Am I missing something? ,
Angiotensin II induces the exocytosis of galectin-3 via integrin αv/AKT/NF-κB signaling pathway
Authors: Z-L Li
D Coletti
L Tian
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: integrin αv; Angiotensin II; exocytosis; endocytosis; galectin-3
Affiliations: Sorbonne Universités, UPMC Univ Paris 06, INSERM ERL U1164, Institut Biologie Paris-Seine, Paris, CNRS, France. .

Abstract:  Objective: To explore the role of integrin αv in Angiotensin II (Ang II)-induced exocytosis and endocytosis of galectin-3 (gal-3) in vascular smooth muscle cells (VSMCs). Materials and methods: A primary culture of mouse VSMCs was established by the enzymatic digestion of aorta. Adeno-Cre was used to specifically knockdown integrin αv. VSMCs were treated with Ang II, LY294002 (inhibitor of AKT signaling pathway), and Bay11-7082 (inhibitor of nuclear factor-kappa B, NF-κB), respectively. Endocytosis of His-tagged gal-3 was analyzed by immunofluorescence. The Western blot was performed to detect the protein level in cell supernatant and lysate. Results: Ang II increased the exocytosis of gal-3 and activated AKT and NF-κB signaling pathways. The knockdown integrin αv effectively decreased the activation of AKT and NF-κB signals and the exocytosis of gal-3 induced by Ang II, but it had a little effect on the endocytosis of gal-3. Ang II increased the phosphorylation of AKT and NF-κB through integrin αv. AKT is the upstream signal of the NF-κB signaling pathway. LY294002 or Bay11-7082 could decrease Ang II-induced exocytosis of gal-3 in VSMCs. Conclusions: Ang II, depending on integrin αv/AKT/NF-κB signaling pathway, induced the exocytosis of gal-3. 

Retracted: No

PubPeer comments:
 Can the authors please indicate which individual or organisation provided the exception for review by the institutional review board? , 
 This paper does not appear have a conflict of interest statement, which is unusual for a medical journal. ,