PReD-Bench/PRed-Bench huggingface dataset:
Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium
Authors: Sarah Navina
Jenny Karlsson
Krutika Patel
Sohail Z Husain
Ram Narayan Trivedi
Chandra Durgampudi
Chathur Acharya
Vivek Mishra
Catherine J Baty
Rachel Cline
Lidiya Orlichenko
Pawan Noel
Vijay P Singh
Donna B Stolz
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: acute pancreatitis; acinar injury; inflammatory mediators; signaling pathways; non-receptor tyrosine kinases
Affiliations: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Abstract:  Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. 

Retracted: No

PubPeer comments:
 Figure 1. * Red boxes: Two lanes in the SC-18 panel in Figure 1A look similar to two lanes in Figure 1B. Reported to the journal in October 2015. ![file] ,
RNA-interference components are dispensable for transcriptional silencing of the drosophila bithorax-complex
Authors: A Maxwell Burroughs
Achim Breiling
Valerio Orlando
Chiara Lanzuolo
Axel Imhof
Filippo M Cernilogar
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Dicer-2; Argonaute-2; RNA interference; epigenetic regulation; centromeric heterochromatin
Affiliations: Epigenetics and Genome Reprogramming Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy. 

Abstract:  Background: Beyond their role in post-transcriptional gene silencing, Dicer and Argonaute, two components of the RNA interference (RNAi) machinery, were shown to be involved in epigenetic regulation of centromeric heterochromatin and transcriptional gene silencing. In particular, RNAi mechanisms appear to play a role in repeat induced silencing and some aspects of Polycomb-mediated gene silencing. However, the functional interplay of RNAi mechanisms and Polycomb group (PcG) pathways at endogenous loci remains to be elucidated. Principal findings: Here we show that the endogenous Dicer-2/Argonaute-2 RNAi pathway is dispensable for the PcG mediated silencing of the homeotic Bithorax Complex (BX-C). Although Dicer-2 depletion triggers mild transcriptional activation at Polycomb Response Elements (PREs), this does not induce transcriptional changes at PcG-repressed genes. Moreover, Dicer-2 is not needed to maintain global levels of methylation of lysine 27 of histone H3 and does not affect PRE-mediated higher order chromatin structures within the BX-C. Finally bioinformatic analysis, comparing published data sets of PcG targets with Argonaute-2-bound small RNAs reveals no enrichment of these small RNAs at promoter regions associated with PcG proteins. Conclusions: We conclude that the Dicer-2/Argonaute-2 RNAi pathway, despite its role in pairing sensitive gene silencing of transgenes, does not have a role in PcG dependent silencing of major homeotic gene cluster loci in Drosophila. 

Retracted: No

PubPeer comments:
 Figure 2C. * Red boxes: The two -RT panels appear to look unexpectedly similar. Reported to the journal in October 2015, but not addressed as of today. ![file] ,
Systems approaches identify the consequences of monosomy in somatic human cells
Authors: Paul Menges
Jan O Korbel
Markus Raeschle
Vincent Leon Gotsmann
Maik Kschischo
Angela Wieland
Zuzana Storchova
Christopher Buccitelli
Xiaoxiao Zhang
Balca R Mardin
Narendra Kumar Chunduri
Felix Willmund
Journal: Nature Communications (2021)
Discipline: Multidisciplinary
Keywords: Chromosome loss; Monosomy; Proliferation; Genomic stability; Transcriptome
Affiliations: Department of Molecular Genetics, TU Kaiserslautern, Kaiserslautern, Germany., University of Applied Sciences Koblenz, Remagen, Germany., Group Genetics of Eukaryotes, TU Kaiserslautern, Kaiserslautern, Germany., Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany., Department of Molecular Genetics, TU Kaiserslautern, Kaiserslautern, Germany. .

Abstract:  Chromosome loss that results in monosomy is detrimental to viability, yet it is frequently observed in cancers. How cancers survive with monosomy is unknown. Using p53-deficient monosomic cell lines, we find that chromosome loss impairs proliferation and genomic stability. Transcriptome and proteome analysis demonstrates reduced expression of genes encoded on the monosomes, which is partially compensated in some cases. Monosomy also induces global changes in gene expression. Pathway enrichment analysis reveals that genes involved in ribosome biogenesis and translation are downregulated in all monosomic cells analyzed. Consistently, monosomies display defects in protein synthesis and ribosome assembly. We further show that monosomies are incompatible with p53 expression, likely due to defects in ribosome biogenesis. Accordingly, impaired ribosome biogenesis and p53 inactivation are associated with monosomy in cancer. Our systematic study of monosomy in human cells explains why monosomy is so detrimental and reveals the importance of p53 for monosomy occurrence in cancer. 

Retracted: No

PubPeer comments:
 Can authors check the source image 5c and clarify why there are different numbers of lines on western blot and ponceau loading control ![file] , 
 Are ponceau loading control and immunoblot from the same gel? If yes, why are there the different numbers of lines? And why do authors do not show loading controls for phosphoproteins and total proteins? Immunoblots for phosphorylated and total proteins are different and seem to be performed on other membranes. ,
Combining Single Strand Oligodeoxynucleotides and CRISPR/Cas9 to Correct Gene Mutations in β-Thalassemia-induced Pluripotent Stem Cells
Authors: Zhanhui Ou
Xiaohua Niu
Yong Fan
Bing Song
Xiaofang Sun
Wenyin He
Di Fan
Yuchang Chen
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CRISPR/Cas; cell therapy; genetic disease; hemoglobin; induced pluripotent stem cell (iPS cell) (iPSC).
Affiliations: From the Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China., From the Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China .

Abstract:  β-Thalassemia (β-Thal) is one of the most common genetic diseases in the world. The generation of patient-specific β-Thal-induced pluripotent stem cells (iPSCs), correction of the disease-causing mutations in those cells, and then differentiation into hematopoietic stem cells offers a new therapeutic strategy for this disease. Here, we designed a CRISPR/Cas9 to specifically target the Homo sapiens hemoglobin β (HBB) gene CD41/42(-CTTT) mutation. We demonstrated that the combination of single strand oligodeoxynucleotides with CRISPR/Cas9 was capable of correcting the HBB gene CD41/42 mutation in β-Thal iPSCs. After applying a correction-specific PCR assay to purify the corrected clones followed by sequencing to confirm mutation correction, we verified that the purified clones retained full pluripotency and exhibited normal karyotyping. Additionally, whole-exome sequencing showed that the mutation load to the exomes was minimal after CRISPR/Cas9 targeting. Furthermore, the corrected iPSCs were selected for erythroblast differentiation and restored the expression of HBB protein compared with the parental iPSCs. This method provides an efficient and safe strategy to correct the HBB gene mutation in β-Thal iPSCs. 

Retracted: No

PubPeer comments:
 There appear to be regions of unexpectedly high similarity in Figure 6B ![image] , 
 Fig 1C ![file] , 
 #2 The top panels of gRNA3 and gRNA4 also look unusually similar in this figure ,
Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo
Authors: Kai Liu
Songyang Liu
Yingchao Wang
Wei Zhang
Bai Ji
Yahui Liu
Journal: Oncology Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: Sorafenib; VEGFR inhibitor; liver cancer; drug resistance; ADAM10
Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract:  Sorafenib (SOR), a vascular endothelial growth factor receptor (VEGFR) inhibitor, is in wide clinical use for the treatment and prevention of liver cancer. However, extended SOR administration for hepatocellular carcinoma (HCC) induces drug resistance thereby limiting its efficacy and highlighting the need for improved therapeutic strategies. It has previously been demonstrated that knockout of a disintegrin and metalloproteinase 10 (ADAM10) via siRNA induced cancer apoptosis and decreased chemotherapy drug resistance. However, whether knockout of ADAM10 is able to decrease SOR resistance remains to be determined. Therefore, in the present study, the effect of siRNA-ADAM10 in combination with SOR was analyzed in HCC cell lines (HepG2) by inhibiting tumor growth and simultaneously reducing doses of SOR. Cell proliferation, apoptosis, migration, invasion and involvement in receptor signaling were determined after siRNA-ADAM10 was applied in combination with SOR treatment. Tumor growth ability in nude mice was also detected. The results showed that siRNA-ADAM10 in combination with SOR treatment in HCC cancer cells significantly suppressed proliferation, migration and invasion, and induced tumor apoptosis in vitro, and suppressed tumor growth in vivo. In addition, the results showed that knockout of ADAM10 by siRNA inhibited the constitutive phosphorylation of PI3K and AKT, which may contribute to the reduction of SOR resistance. Collectively, our experimental results indicate that knockout of ADAM10 by siRNA increased the SOR antitumor activity of liver cancer in vitro and in vivo, and that this additive combination is a promising drug candidate for treatment of HCC. 

Retracted: No

PubPeer comments:
 Figs 4C, 5D. ![file] There seems to have been some error during figure composition. Could the authors check? For comparison: Figs 2C *[left]* and 5 *[right]* from [Liu et al (2014)] . ![file] For further comparison: Figs 3C, 7 from [Liu et al (2014)] . ![] , 
 #1 Figs 4C, 5D again... ![] and Figs 3C and 7 from [Liu et al (2014)] ... ![] ...this time for comparison with the bands of Fig 5C, [Li et al (2014)] . ![] UPDATE: Another sighting! Fig 4 of [Li et al (2015)] . ![] , 
 Fig 7A.  Tumor weight in treated and untreated mice for 21 days. ![file] The first manifestation of *[left]* Fig 6A from [Qu et al (2015)] .  Images of tumor tissue with different plasmid treatments collected after sacrifice at day 21. *[right]* Fig 6A from [Liu et al (2015)] .  Graphs of the tumor tissue from the different groups . ![file] Fig 5A from [Yang et al (2015)] .  Images of tumor tissue from different treatments collected after sacrifice at day 22. ![file] And many other appearances. ,
Zymogen activation and subcellular activity of subtilisin kexin isozyme 1/site 1 protease
Authors: Marco Salamina
Laura Cendron
Antonella Pasquato
Joël Oppliger
Patrizia Polverino de Laureto
Nabil Georges Seidah
Dominique Julien Burri
Joel Ramos da Palma
Stefan Kunz
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bioluminescence; Biosensor; Enzyme Mechanism; Enzyme Processing; Serine Protease.
Affiliations: From the Institute of Microbiology, University Hospital Center and University of Lausanne, 1011 Lausanne, Switzerland., the Department of Biology and., the Department of Pharmaceutical Sciences, Centro Ricerche Interdipartimentale Biotecnologie Innovative, University of Padua, 35121 Padua, Italy, and., the Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec H2W 1R7, Canada., From the Institute of Microbiology, University Hospital Center and University of Lausanne, 1011 Lausanne, Switzerland, .

Abstract:  The proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) plays crucial roles in cellular homeostatic functions and is hijacked by pathogenic viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P involves sequential autocatalytic processing of its N-terminal prodomain at sites B'/B followed by the herein newly identified C'/C sites. We found that SKI-1/S1P autoprocessing results in intermediates whose catalytic domain remains associated with prodomain fragments of different lengths. In contrast to other zymogen proprotein convertases, all incompletely matured intermediates of SKI-1/S1P showed full catalytic activity toward cellular substrates, whereas optimal cleavage of viral glycoproteins depended on B'/B processing. Incompletely matured forms of SKI-1/S1P further process cellular and viral substrates in distinct subcellular compartments. Using a cell-based sensor for SKI-1/S1P activity, we found that 9 amino acid residues at the cleavage site (P1-P8) and P1' are necessary and sufficient to define the subcellular location of processing and to determine to what extent processing of a substrate depends on SKI-1/S1P maturation. In sum, our study reveals novel and unexpected features of SKI-1/S1P zymogen activation and subcellular specificity of activity toward cellular and pathogen-derived substrates. 

Retracted: No

PubPeer comments:
 Visible white splice line in Fig.4A. ![file] ![file] ,
Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies
Authors: Tony Hunter
Zhiyong Wang
O Jameel Shah
Journal: Current Biology (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Tuberous sclerosis; tumor suppressor; TSC1; TSC2; Rheb
Affiliations: Molecular and Cellular Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract:  Tuberous sclerosis is a largely benign tumor syndrome derived from the acquisition of somatic lesions in genes encoding the tumor suppressor products, TSC1 or TSC2. Loss of function of the TSC1-TSC2 complex, which acts as a Rheb GAP, yields constitutive, unrestrained signaling from the cell growth machinery comprised of Rheb, mTOR, and S6K. We demonstrate herein that constitutive activation of the Rheb/mTOR/S6K cassette, whether by genetic deletion of TSC1 or TSC2 or by ectopic expression of Rheb, is sufficient to induce insulin resistance. This is the result of downregulation of the insulin receptor substrates, IRS1 and IRS2, which become limiting for signal transmission from the insulin receptor to PI3K. Downstream of PI3K, the survival kinase, Akt, is completely refractory to activation by IRS-dependent growth factor pathways such as insulin or IGF-I in TSC1- or TSC2-deficient cells but not to activation by IRS-independent pathways such as those utilized by PDGF. The antiapoptotic program induced by IGF-I but not PDGF is severely compromised in TSC2 null cells. Our results suggest that inappropriate activation of the Rheb/mTOR/S6K pathway imposes a negative feedback program to attenuate IRS-dependent processes such as cell survival. 

Retracted: No

PubPeer comments:
 ![file] , 
 An additional concern in Fig. 1E: ![file] , 
 #1 Figure 1E. Images are relatviely high resolution. The background is very light, but many of the spots in the backround appear at very similar positions. https: imgur.com SEDWgqs , 
 Figure 1C. Much more similar than you would expect despite different genotype. https: imgur.com PUa6BY8 ,
Induction of Macrophage M2b/c Polarization by Adipose Tissue-Derived Mesenchymal Stem Cells
Authors: Chongchu Huang
Zhenxu Zhou
Meng Sun
Linxiao Sun
Bi-Cheng Chen
Journal: Journal of Immunology Research (2019)
Discipline: IMMUNOLOGY
Keywords: Adipose-derived mesenchymal stem cells; ADMSCs; healing; inflammation; immune response
Affiliations: Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract:  Background: Adipose-derived mesenchymal stem cells (ADMSCs) can promote healing and inhibit inflammation/immune response in local tissues, while the detailed mechanism remains unknown. Results: ADMSCs and peritoneal macrophages were collected from C57BL/6 mice. The culture medium (CM) from ADMSCs (24 hours cultured) was collected. The CM was added to the Mφ culture system with lipopolysaccharide (LPS) or IL-4/IL-13 or blank. And those Mφ cultures without adding CM were used as controls. A series of classification markers and signaling pathways for Mφ polarization were detected by using flow cytometry, RT-PCR, and western blotting. Furthermore, the cell viability of all the groups was detected by CCK8 assay. After CM induction in different groups, M1-Mφ markers and M2a-Mφ were decreased; however, M2b/c-Mφ markers increased. STAT3/SOCS3 and STAT6/IRF4 were suppressed in all 3 CM-treated groups. Moreover, the cell viability of all 3 groups which were induced by CM significantly increased as compared to that of the control groups without adding CM. Conclusion: ADMSCs can induce nonactivated macrophage and M1-Mφ into M2b/c-Mφ. Downregulation of the STAT3 and STAT6 pathway may involve in this process. This data shows that the anti-inflammatory role of ADMSC in local tissues may be partly due to their effect on Mφ to M2b/c-Mφ. 

Retracted: No

PubPeer comments:
 The title complex, [(Ph3P)2Cu(mu-S)2Cu(PPh3)], is almost certainly [(Ph3P)2Cu(mu-Cl)2Cu(PPh3)] (whose structure can be found at https: doi.org 10.1016 j.ica.2009.11.037). A comparison of their metrical parameters reveals identical Cu-Cl bond lengths, which is unexpected considering the charge difference between Cl- and S2-. The Cu-P bond lengths are also identical, which is also unexpected considering the change in copper oxidation state. ,
The stability of the ternary interferon-receptor complex rather than the affinity to the individual subunits dictates differential biological activities
Authors: Eyal Kalie
Yulia Podoplelova
Gideon Schreiber
Diego A Jaitin
Jacob Piehler
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Type I interferons; IFNAR1; IFNAR2; antiproliferative activity; binding affinity
Affiliations: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.

Abstract:  Type I interferons (IFNs) signal for their diverse biological effects by binding a common receptor on target cells, composed of the two transmembrane IFNAR1 and IFNAR2 proteins. We have previously differentially enhanced the antiproliferative activity of IFN by increasing the weak binding affinity of IFN to IFNAR1. In this study, we further explored the affinity interdependencies between the two receptor subunits and the role of IFNAR1 in differential IFN activity. For this purpose, we generated a panel of mutations targeting the IFNAR2 binding site on the background of the IFNalpha2 YNS mutant, which increases the affinity to IFNAR1 by 60-fold, resulting in IFNAR2-to-IFNAR1 binding affinity ratios ranging from 1000:1 to 1:1000. Both the antiproliferative and antiviral potencies of the interferon mutants clearly correlated to the in situ binding IC(50) values, independently of the relative contributions of the individual receptors, thus relating to the integral lifetime of the complex. However, the antiproliferative potency correlated throughout the entire range of affinities, as well as with prolonged IFNAR1 receptor down-regulation, whereas the antiviral potency reached a maximum at binding affinities equivalent to that of wild-type IFNalpha2. Our data suggest that (i) the specific activity of interferon is related to the ternary complex binding affinity and not to affinity toward individual receptor components and (ii) although the antiviral pathway is strongly dependent on pSTAT1 activity, the cytostatic effect requires additional mechanisms that may involve IFNAR1 down-regulation. This differential interferon response is ultimately mediated through distinct gene expression profiling. 

Retracted: No

PubPeer comments:
 Fig 2  (C) Transwell assay . Someone was not paying attention during the selection of representative images. ![file] , 
 Figs 2C, 4C. ![file] As well as the overlap within 2C, the green, orange, light blue, dark blue rectangles mark overlaps with Figures 3D, 4D, 5B, 5F from [Dang et al (2017)] - with a 180-deg rotation in two cases. ![file] No authors in common. ,
Akt1/Akt2 and mammalian target of rapamycin/Bim play critical roles in osteoclast differentiation and survival, respectively, whereas Akt is dispensable for cell survival in isolated osteoclast precursors
Authors: Keith A Hruska
Toshifumi Sugatani
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Akt; protein kinase B; osteoclast differentiation; mTOR; Bim
Affiliations: Department of Pediatrics, Cell and Molecular Biology Unit, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Abstract:  Akt, also known as protein kinase B, is a serine/threonine protein kinase with antiapoptotic activities; also, it is a downstream target of phosphatidylinositol 3-kinase. Here we show that Akt1/Akt2 play a critical role in osteoclast differentiation but not cell survival and that mammalian target of rapamycin (mTOR) and Bim, a pro-apoptotic Bcl-2 family member, are required for cell survival in isolated osteoclast precursors. To investigate the function of Akt1, Akt2, mTOR, and Bim, we employed a retroviral system for delivery of small interfering RNA into cells. Loss of Akt1 and/or Akt2 protein inhibited osteoclast differentiation due to down-regulation of IkappaB-kinase (IKK) alpha/beta activity, phosphorylation of IkappaB-alpha, nuclear translocation of nuclear factor-kappaB (NFkappaB) p50, and NFkappaB p50 DNA-binding activity. Surprisingly, deletion of Akt1 and/or Akt2 protein did not stimulate cleaved caspase-3 activity and failed to promote apoptosis. Conversely, loss of mTOR protein induced apoptosis due to up-regulation of cleaved caspase-3 activity. In addition, we found that mTOR is downstream of phosphatidylinositol 3-kinase (but not Akt) and that macrophage colony-stimulating factor regulates Bim expression through mTOR activation for cell survival. These results demonstrate that Akt1/Akt2 are key elements in osteoclast differentiation and that the macrophage colony-stimulating factor stimulation of mTOR leading to Bim inhibition is essential for cell survival in isolated osteoclast precursors. 

Retracted: No

PubPeer comments:
 Fig. 4: Akt1 siRNA and Akt2 siRNA shares same field ![file] Fig. 1A and 1B u2013 more similar than expected ![file] ,
circRNA_0084043 promote malignant melanoma progression via miR-153-3p/Snail axis
Authors: Yan Shi
Jinlong Wang
Zhou Zhou
Wenkang Luan
Yun Xia
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Circular RNA; Melanoma; Snail; circRNA_0084043; miR-153-3p.
Affiliations: Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China. Electronic address: ., Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Department of Neurosurgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China., Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

Abstract:  Circular RNAs (circRNAs) has been found to play an important role in the regulation of multiple diseases, and participate in cancer development. However, the role of circRNA in malignant melanoma has not been reported. In this study, human circRNA microarray was used to screen the dysregulated circRNA in melanoma. We found that circRNA_0084043 was significantly up-regulated in melanoma tissue, and the result was replicated in a larger sample size. High circRNA_0084043 expression was an independent risk factor of overall survival in melanoma patients. circRNA_0084043 promotes melanoma cell proliferation, invasion and migration. Bioinformatics and luciferase reporter assays confirmed that circRNA_0084043 directly binds to miR-153-3p, and Snail is directly targeted by miR-153-3p. We also demonstrated that circRNA_0084043 may act as the sponge of miR-153-3p to up-regulate Snail expression, and consequently function as an oncogene in melanoma. Overall, this result elucidates a new mechanism for circRNA_0084043 in melanoma development and provides a potential therapeutic target for melanoma patients. 

Retracted: No

PubPeer comments:
null, 
null, 
 #2 Figure 6. Likely mismatch. ![file] , 
 #1 Figure 2C Anticancer Res. 2012 Aug;32(8):3015-27 much more similar to figure 1A Clin Cancer Res. 2008 Feb 15;14(4):1172-81, even though beta-actin and beta-tubulin are different proteins. ![file] , 
 September 2021 retraction. https: ar.iiarjournals.org content 41 9 4661.long The article entitled u201cTargeting PI3KC2u03b2 impairs proliferation and survival in acute leukemia, brain tumours and neuroendocrine tumoursu201d by Boller et al. published in Anticancer Research 32(8): 3015-3027, 2012 is retracted due to the similarity of Figure 2C with Figure 1A of the article published in Clinical Cancer Research 14(4): 1172-1181, 2008. Efforts of the Editorial Office of Anticancer Research to communicate with the Authors were unsuccessful. ,
Targeted silencing of genes related to acute monocytic leukaemia by CpG(B)-MLAA-34 siRNA conjugates
Authors: Yun Yang
Pengyu Zhang
Bingqiao Huang
Xiaorong Ma
Jin Wang
Jianli Wang
Aili He
Wanggang Zhang
Journal: Journal of drug targeting (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Acute monocytic leukaemia; CpG(B) oligonucleotides; JAK2; MLAA-34; STAT3
Affiliations: Department of Haematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract:  Acute monocytic leukaemia (AML-M5) associated antigen-34 (MLAA-34) is a novel antigen overexpressed in patients with acute monocytic leukaemia. RNA interference is a promising therapy in oncology, especially for refractory acute leukaemia. In this study, we delivered MLAA-34 siRNA into AML-M5 THP-1 cells using CpG(B)-MLAA-34 siRNA conjugates, in the absence of any other transfection reagent. The uptake efficiency and the rate of apoptosis were measured by using flow cytometry. The level of relevant mRNAs was measured by quantitative PCR. THP-1 cell invasion was assessed by transwell assay. Protein expression was analysed by western blotting. The spleen and liver of AML-M5 nude mice were measured and weighted after euthanisation. Spleen sections were analysed by immunohistochemistry. We found that MLAA-34 siRNA was successfully delivered into THP-1 cells and induced MLAA-34 gene silencing via the blockade of JAK2/STAT3 and Wnt/-catenin signalling pathways. In addition, CpG(B)-MLAA-34 siRNA upregulated Gsk3β protein expression, resulting in retraining of the JAK2/STAT3 and Wnt/β-catenin signalling pathways. Importantly, CpG(B)-MLAA-34 siRNA reduced the survival and invasiveness of THP-1 cells. We further demonstrated that CAB39L was effectively downregulated by CpG(B)-MLAA-34 siRNA in vivo. These findings suggested CpG(B)-MLAA-34 siRNA conjugates may provide a novel therapeutic strategy for acute monocytic leukaemia. 

Retracted: No

PubPeer comments:
 Figure 4. The top two panels appear to look more similar to each other than expected. Red boxes show the areas that appear to look similar, with rounded colored boxes added to draw attention to groups of cells that look similar. The images are not identical, and the position of the groups of cells is slightly different, indicating perhaps two different exposures or timepoints. Could the authors please clarify? ![file] , 
 Figure 7. * Blue boxes: In the  Spleen (CAB39L) row, the  Untreated and  AG 490 panels appear to show an area of overlap. ![file] ,
P53 dependent and independent apoptosis induced by lidamycin in human colorectal cancer cells
Authors: Chunlei Cheng
Lihui Chen
Jianming Jiang
Qiyang He
Zhen Wang
Ajing Yang
Diandong Li
Journal: Cancer Biology & Therapy (2007)
Discipline: CLINICAL MEDICINE
Keywords: Enediyne compound; antibiotics; anti-cancer activity; p53 signaling pathway; apoptosis induction
Affiliations: Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.

Abstract:  Enediyne compound is one class of antibiotics with very potent anti-cancer activity. However, the role of p53 in enediyne antibiotic-induced cell killing remains elusive. Here we reported the involvement of p53 signaling pathway in apoptosis induction by lidamycin (LDM), a member of the enediyne antibiotic family. We found that LDM at low drug concentration of 10 nmol/L induces apoptotic cell death much more effectively in human colorectal cancer cells with wild type p53 than those with mutant or deleted p53. p53 is functionally activated as an early event in response to low dose LDM that precedes the significant apoptosis induction. The primarily activation of mitochondria as well as the activation of p53 transcriptional targets such as Puma, Bad and Bax in HCT116 p53 wild type cells further demonstrates the key role of p53 in mediating the compound-induced apoptosis. This is further supported by the observation that the absence of Bax or Puma decreases apoptosis dramatically while Bcl-2 overexpression confers partially resistance after drug treatment. Activation of p53 signaling pathway leads to activation of caspases and caspases inhibitor VAD-fmk completely blocks low dose LDM induced apoptosis through the inhibition of mitochondria pathway. In contrast, LDM at higher concentration causes rapid apoptosis through more direct DNA damaging mechanism that is independent of activation of p53 and caspases and cannot be blocked by caspase inhibitor. Taken together, LDM induces apoptosis in a p53-dependent manner when given at low doses, but in a p53-independent manner when given at high doses. This dosage-dependent regimen can be applied to cancer clinic based upon the p53 status of cancer patients. 

Retracted: No

PubPeer comments:
 Figure 3B appears to contain two images which overlap with obvious manipulation. ![file] ,
Dose- and time-dependent apoptosis induced by avian H9N2 influenza virus in human cells
Authors: Shahla Shahsavandi
Mohammad Majid Ebrahimi
Kaveh Sadeghi
Seyedeh Zahra Mosavi
Ashraf Mohammadi
Journal: BioMed Research International (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: avian H9N2 influenza; viral infection; A549; HepG2; HeLa cells
Affiliations: Razi Vaccine & Serum Research Institute, P.O. Box 31975-148, Karaj 3197619751, Iran., Razi Vaccine & Serum Research Institute, P.O. Box 31975-148, Karaj 3197619751, Iran

Abstract:  To understand human response to avian H9N2 influenza, we investigated the effects of the viral infection on A549, HepG2, and HeLa cells at low and high MOIs. To identify virus-host interplay, expression of Mx and NP genes was measured in the cells supernatants. Cell viability and apoptosis were evaluated by MTT assay, DNA fragmentation, and florescent staining. The virus titration and NP gene transcript levels indicate lower susceptibility of HeLa cell to H9N2 replication than other cells. Although H9N2 did produce a faster CPE in HepG2, high dose of the virus induced apoptosis within early stage of A549 infection. The DNA laddering was enhanced in the cell correlated with increase in virus transcripts. The undetectable to different regulation levels of Mx gene were observed in response to H9N2 infection suggesting that an insufficient antiviral defense in the noncompetent-IFN HepG2 cell promotes efficient viral replication. These results showed that the permissivity of HepG2 for H9N2 is comparable with A549; however, liver cells are not target tissue respond to the infection. These data revealed that the H9N2 virus induced apoptosis signaling via mitochondrial pathway in human alveolar epithelial cells, indicating that the induction may be associated with a dose-dependent manner. 

Retracted: No

PubPeer comments:
 image duplication, just 180 deg rotated ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Propofol Alleviates Apoptosis Induced by Chronic High Glucose Exposure via Regulation of HIF-1α in H9c2 Cells
Authors: Ming Yin
Dandan Zhou
Lidong Zhao
Jinjun Pu
Shun Zhu
Zejian Wang
Jiang Hong
Journal: Oxidative Medicine and Cellular Longevity (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: propofol; cardioprotective; hyperglycemia; myocardial hypertrophy; cell apoptosis
Affiliations: Department of Internal and Emergency Medicine, Shanghai General Hospital (Originally Named Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Emergency Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China., School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.

Abstract:  Background: The sedative anesthetic, propofol, is a cardioprotective agent for hyperglycemia-induced myocardial hypertrophy and dysfunction in rats. However, the specific protective mechanism has not been clarified. Methods and results: In this experiment, we used H9c2 cells subjected to 22 mM glucose lasting for 72 hours as an in vitro model of cardiomyocyte injury by hyperglycemia and investigated the potential mechanism of propofol against hyperglycemic stress in cells. Propofol (5, 10, or 20 μM) was added to the cell cultures before and during the high glucose culture phases. Cell viability and levels of ROS were measured. The levels of proinflammatory cytokines were tested by ELISA. The levels of SIRT3, SOD2, PHD2, HIF-1α, Bcl-2, P53, and cleaved caspase-3 proteins were detected by western blotting. Our data showed that propofol attenuated high glucose-induced cell apoptosis accompanied by a decrease in the level of reactive oxygen species (ROS) and proinflammatory cytokines. Meanwhile, propofol decreased the apoptosis of H9c2 cells via increasing the expression of Bcl-2, SIRT3, SOD2, and PHD2 proteins and decreasing the expression of cleaved caspase-3, P53, and HIF-1α. Real-time PCR analysis showed that propofol did not significantly change the HIF-1α but increase PHD2 at mRNA level. HIF-1α silence significantly decreased apoptosis and inflammation in H9c2 cell during high glucose stress. Pretreatment of IOX2 (the inhibitor of PHD2) inhibited cell viability until the concentration reached 200 μM during high glucose stress. However, 50 μM TYP (the inhibitor of SIRT3) significantly inhibited cell viability during high glucose stress. Delayed IOX2 treatment for 6 hours significantly inhibited cell viability during high glucose stress. Conclusions: Propofol might alleviate cell apoptosis via SIRT3-HIF-1α axis during high glucose stress. 

Retracted: No

PubPeer comments:
 In Figure 7, a Western immunoblot has been duplicated, modified and presented as something else. ![file] ,
Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes
Authors: Martina Malatesta
Anton Wutz
Kristian Helin
Julie Skotte
Julian Walfridsson
Diego Pasini
Anton Willer
Ole Nørregaard Jensen
Hye Ryung Jung
Bo Porse
Linda Olsson
Journal: Nucleic Acids Research (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Polycomb group proteins; transcriptional repression; PRC2; histone modifications; Suz12
Affiliations: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.

Abstract:  Polycomb group (PcG) proteins are transcriptional repressors, which regulate proliferation and cell fate decisions during development, and their deregulated expression is a frequent event in human tumours. The Polycomb repressive complex 2 (PRC2) catalyzes trimethylation (me3) of histone H3 lysine 27 (K27), and it is believed that this activity mediates transcriptional repression. Despite the recent progress in understanding PcG function, the molecular mechanisms by which the PcG proteins repress transcription, as well as the mechanisms that lead to the activation of PcG target genes are poorly understood. To gain insight into these mechanisms, we have determined the global changes in histone modifications in embryonic stem (ES) cells lacking the PcG protein Suz12 that is essential for PRC2 activity. We show that loss of PRC2 activity results in a global increase in H3K27 acetylation. The methylation to acetylation switch correlates with the transcriptional activation of PcG target genes, both during ES cell differentiation and in MLL-AF9-transduced hematopoietic stem cells. Moreover, we provide evidence that the acetylation of H3K27 is catalyzed by the acetyltransferases p300 and CBP. Based on these data, we propose that the PcG proteins in part repress transcription by preventing the binding of acetyltransferases to PcG target genes. 

Retracted: No

PubPeer comments:
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 Figure 5B. H3K27Ac and H3 panels do not look like they come from the same blot. How to quantify? ![image] , 
 2021 correction. https: academic.oup.com nar article 49 15 9000 6332815 In Figure 5 of article (1), the authors have inadvertently duplicated the Vinculin blot in panel C. REFERENCES 1.tPasini D., Malatesta M., Jung H.R., Walfridsson J., Willer A., Olsson L., Skotte J., Wutz A., Porse B., Jensen O.N. et al. . Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res. 2010; 38:4958u20134969. ,
LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes
Authors: Alexandre Reymond
Martine A Collart
Didier Picard
Hamid Mehenni
Nathalie Lin-Marq
Karine Buchet-Poyau
Stylianos E Antonarakis
Journal: Human Molecular Genetics (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Germline mutations; LKB1; PTEN; tumor suppressor; Peutz-Jeghers syndrome
Affiliations: Département de Biologie Cellulaire, Université de Genève, 1211 Genève 4, Switzerland.

Abstract:  Germline mutations of the LKB1 (STK11) tumor suppressor gene lead to Peutz-Jeghers syndrome (PJS) and predisposition to cancer. LKB1 encodes a serine/threonine kinase generally inactivated in PJS patients. We identified the dual phosphatase and tumor suppressor protein PTEN as an LKB1-interacting protein. Several LKB1 point mutations associated with PJS disrupt the interaction with PTEN suggesting that the loss of this interaction might contribute to PJS. Although PTEN and LKB1 are predominantly cytoplasmic and nuclear, respectively, their interaction leads to a cytoplasmic relocalization of LKB1. In addition, we show that PTEN is a substrate of the kinase LKB1 in vitro. As PTEN is a dual phosphatase mutated in autosomal inherited disorders with phenotypes similar to those of PJS (Bannayan-Riley-Ruvalcaba syndrome and Cowden disease), our study suggests a functional link between the proteins involved in different hamartomatous polyposis syndromes and emphasizes the central role played by LKB1 as a tumor suppressor in the small intestine. 

Retracted: No

PubPeer comments:
 Figure 5B * Red arrows: Lanes 1-3 of the left anti-LKB1 panel look similar to lanes 2-4 of the right anti-LKB1 panel ![file] ,
Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity
Authors: Davide Bernareggi
Hanna Julie Hoel
Zhengming Wu
Karl-Johan Malmberg
Chengsheng Wu
Zhipeng Meng
Eivind Heggernes Ask
Robert H Blum
Huang Zhu
Kun-Liang Guan
Dan S Kaufman
Journal: Cell stem cell (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CISH; IL-15; JAK-STAT; acute myelogenous leukemia; cell therapy
Affiliations: Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA., Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA., Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: .

Abstract:  Cytokine-inducible SH2-containing protein (CIS; encoded by the gene CISH) is a key negative regulator of interleukin-15 (IL-15) signaling in natural killer (NK) cells. Here, we develop human CISH-knockout (CISH-/-) NK cells using an induced pluripotent stem cell-derived NK cell (iPSC-NK cell) platform. CISH-/- iPSC-NK cells demonstrate increased IL-15-mediated JAK-STAT signaling activity. Consequently, CISH-/- iPSC-NK cells exhibit improved expansion and increased cytotoxic activity against multiple tumor cell lines when maintained at low cytokine concentrations. CISH-/- iPSC-NK cells display significantly increased in vivo persistence and inhibition of tumor progression in a leukemia xenograft model. Mechanistically, CISH-/- iPSC-NK cells display improved metabolic fitness characterized by increased basal glycolysis, glycolytic capacity, maximal mitochondrial respiration, ATP-linked respiration, and spare respiration capacity mediated by mammalian target of rapamycin (mTOR) signaling that directly contributes to enhanced NK cell function. Together, these studies demonstrate that CIS plays a key role to regulate human NK cell metabolic activity and thereby modulate anti-tumor activity. 

Retracted: No

PubPeer comments:
 Figs 5B, 6.  Cell migration analysis was performed using A375 cells transfected with versican plasmid or versican siRNA ;  A cell migration assay was performed using A375 cells transfected with miR-203 mimics, or cotransfected with miR-203 mimics and a versican plasmid . ![file] For comparison, Figs 3B, 7B of [Xiao et al (2018)] . ![file] Fig 5A of [Long et al (2016)] .  A Transwell assay was performed to determine the invasion capacity of T24 cells following 24 or 48 h of transfection with miR-101 mimics, c-FOS siRNA, or co-transfected with miR-101 mimics and c-FOS plasmid. (A) Representative images of lower sides of the Transwell membranes with invaded cells stained with crystal violet. ![] Figs 2D, 4C of [Ma et al (2017)] . ![] Other manifestations are linked in those threads. ,
Raloxifene suppresses experimental autoimmune encephalomyelitis and NF-κB-dependent CCL20 expression in reactive astrocytes
Authors: Wen Xu
Aimin Wu
Xueqiang Hu
Ying Chen
Yaqing Shu
Yongqiang Dai
Rui Li
Jian Bao
Zhengqi Lu
Wei Qiu
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: sexual steroids; therapeutic tools; multiple sclerosis; estrogen receptor modulators; neuroprotective effects
Affiliations: Multiple Sclerosis Center, Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China.

Abstract:  Recent clinical data have led to the consideration of sexual steroids as new potential therapeutic tools for multiple sclerosis. Selective estrogen receptor modulators can exhibit neuroprotective effects like estrogen, with fewer systemic estrogen side effects than estrogen, offering a more promising therapeutic modality for multiple sclerosis. The important role of astrocytes in a proinflammatory effect mediated by CCL20 signaling on inflammatory cells has been documented. Their potential contribution to selective estrogen receptor modulator-mediated protection is still unknown. Using a mouse model of chronic neuroinflammation, we report that raloxifene, a selective estrogen receptor modulator, alleviated experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and decreased astrocytic production of CCL20. Enzyme-linked immunosorbent assay, immunohistochemistry imaging and transwell migration assays revealed that reactive astrocytes express CCL20, which promotes Th17 cell migration. In cultured rodent astrocytes, raloxifene inhibited IL-1β-induced CCL20 expression and chemotaxis ability for Th17 migration, whereas the estrogen receptor antagonist ICI 182,780 blocked this effect. Western blotting further indicated that raloxifene suppresses IL-1β-induced NF-κB activation (phosphorylation of p65) and translocation but does not affect phosphorylation of IκB. In conclusion, these data demonstrate that raloxifene provides robust neuroprotection against experimental autoimmune encephalomyelitis, partially via an inhibitory action on CCL20 expression and NF-κB pathways in reactive astrocytes. Our results contribute to a better understanding of the critical roles of raloxifene in treating experimental autoimmune encephalomyelitis and uncover reactive astrocytes as a new target for the inhibitory action of estrogen receptors on chemokine CCL20 expression. 

Retracted: No

PubPeer comments:
 Figure 2E * Green boxes: The EAE+S+V and EAE+O+R panels appear to show an area of overlap, if one of the two panels is rotated. Reported to the journal in April 2014, but no action taken as of today. ![file] ,