PReD-Bench/PRed-Bench huggingface dataset:
Cancer-associated fibroblast-derived Lumican promotes gastric cancer progression via the integrin β1-FAK signaling pathway
Authors: Chen Li
Bingya Liu
Zhenjia Yu
Min Yan
Quan Zhou
Jianfang Li
Xuehua Chen
Xiaofeng Wang
Xiongyan Wu
Liping Su
Zhenggang Zhu
Journal: International Journal of Cancer (2017)
Discipline: CLINICAL MEDICINE
Keywords: Lumican; cancer-associated fibroblasts; gastric cancer; integrin β1-FAK; tumor progression.
Affiliations: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China., Department of Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract:  Gastric cancer (GC) is one of the most frequent malignant tumors worldwide and is associated with high invasiveness, high metastasis and poor prognosis. Cancer-associated fibroblasts (CAFs), residing around tumor cells in tumor stroma, are important modifiers of tumor initiation and progression. However, the molecular mechanisms by which CAF's modulate tumor development have yet not to be characterized in GC. Here we performed tissue assay analyses identifying that Lumican, an extracellular matrix protein, is highly expressed in human gastric CAFs and its expression is positively associated with depth of invasion, lymph node metastasis, TNM stage and poor survival rate of GC. Functional studies revealed that integrin β1-FAK signaling pathways mediate the promoting effect of Lumican on GC cell proliferation, migration and invasion in vitro. In accordance with these observations, in GC cells co-cultured with CAFs in which Lumican had been knocked down, decreased gastric tumor growth and metastasis in vivo was apparent. In summary, CAF-derived Lumican contributes to tumorigenesis and metastasis of GC by activating the integrin β1-FAK signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 3G and 4K: * Two sets of panels appear to overlap. Images analyzed by ImageTwin.io. ![file] , 
 Dear Dr. Bik, Thanks for bring this issue to our attention. After carefully checking our original data and the figures on the manuscript, we found that the wrong representative images were inadvertently included when we assembled the final figure for Fig. 3g. We are sorry about this and have contacted International Journal of Cancer to make the correction. Thank you again for your valuable comments! , 
 2021 correction. https: onlinelibrary.wiley.com doi full 10.1002 ijc.33577 The image in Fig.3g, u201cMigration, MKN45+PF-228+recLumicanu201d, is partially identical to u201cInvasion, MKN45+PF-228+CAFu201d. The image in Fig.3g, u201cInvasion, MKN45+DMSO+CAFu201d, is partially identical to Fig.4k, u201cInvasion, MKN45-siNC+CAFu201d. The correct Figure 3g is shown below. ,
Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stress
Authors: Wayne Zundel
Amato Giaccia
Journal: Genes & Development (1998)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: apoptosis; ceramide; PI(3)K pathway; stress-induced; acid-sphingomyelinase

Abstract: The initiation of apoptosis often transpires in the presence of agents that regulate cell survival. This study evaluated the effects of stress-induced ceramide on the anti-apoptotic activity of the phosphoinositide-3 kinase [PI(3)K] pathway. PI(3)K activity is directly down-regulated by stress-induced ceramide in a dose-dependent manner with rapid kinetics and high specificity. Ceramide inhibition of PI(3)K is dependent on acid–sphingomyelinase. Down-regulation of PI(3)K by ceramide results in inhibition of the kinase Akt and decreased phosphorylation of the death effector Bad. Thus, ceramide levels could act as a general apoptotic rheostat controlling cell survival by regulating PI(3)K anti-apoptotic effector mechanisms. 

Retracted: No

PubPeer comments:
 Figure 5A. Much more similar than you would expect. https: imgur.com GjF8soR ,
Tanshinone IIA combined with cisplatin synergistically inhibits non‐small‐cell lung cancer in vitro and in vivo via down‐regulating the phosphatidylinositol 3‐kinase/Akt signalling pathway
Authors: Sheng Huang
Xiao-Zhong Liao
Han-Rui Chen
Ying Gao
Jia-Hui Liu
Zhuang-Zhong Chen
Li-Zhu Lin
Ling-Ling Sun
Ling Yu
Jia-Xing Zhang
Journal: Phytotherapy Research (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: A549; PC9; PI3K/Akt pathway; Tanshinone IIA; cisplatin
Affiliations: Department of OncologyThe First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou China, Department of OncologyThe First Affiliated Hospital, Sun Yat‐sen University Guangzhou China, Department of Orthopaedic SurgeryThe First Affiliated Hospital of Nanchang University Nanchang China

Abstract:  Cisplatin represents one of the first-line drugs used for non-small-cell lung cancer treatment. However, considerable side effects and the emergence of drug resistance are becoming critical limitations to its application. Combinatorial strategies may be able to extend the use of cisplatin. Both Tanshinone IIA and cisplatin inhibit non-small-cell lung cancer cell growth in a time- and dose-dependent manner. When Tanshinone IIA was combined with cisplatin at a ratio of 20:1, they were observed to exert a synergistic inhibitory effect on non-small-cell lung cancer cells. The combination treatment was shown to impair cell migration and invasion, arrest the cell cycle in the S phases, and induce apoptosis in A549 and PC9 cells in a synergistic manner. KEGG pathway analysis and molecular docking indicated that Tanshinone IIA might mainly influence the phosphatidylinositol 3-kinase-Akt signalling pathway. In all treated groups, the expression levels of Bax and cleaved Caspase-3 were up-regulated, whereas the expression levels of Bcl-2, Caspase-3, p-Akt, and p-PI3K proteins were down-regulated. Among these, the combination of Tan IIA and cisplatin exhibited the most significant difference. Tanshinone IIA may function as a novel option for combination therapy for non-small-cell lung cancer treatment. 

Retracted: No

PubPeer comments:
 Figures 3a and 3d appear to show overlapping images. This is sometimes seen in papermill papers. *** ![file] *** ![file] , 
 This paper is one of a small collection of papers which appears to include a typographical error in the spelling of an manufacturer. The company name is ACEA Biosciences headquartered in San Diego. In this paper and the others, the name is spelled ACEC. This suggests that the paper was written from a common template, although the author groups are mostly different. *** ![file] ,
Visualization of TBP oligomers binding and bending the HIV-1 and adeno promoters
Authors: L Zawel
A Makhov
D Reinberg
J D Griffith
Journal: Journal of Molecular Biology (1995)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: yTBP; TATA binding protein; HIV; adeno major late promoters; electron microscopy

Abstract:  The binding of the 28 kDa yeast TATA binding protein (yTBP) to the HIV and adeno major late promoters has been examined by electron microscopy (EM). Three different EM preparative methods were employed: direct mounting and shadowcasting of fixed samples, cryofixation and freeze-drying followed by shadowcasting, and negative staining of unfixed samples. Excellent agreement among the three methods was obtained. With ten yTBP monomers/DNA fragment, up to 25% of the DNA molecules contained easily distinguished protein particles at the TATA box and, less frequently, smaller particles were observed. Non-specific binding to DNA ends was common. The mass of the easily distinguished particles measured 63(+/- 5) kDa (cryofixation and shadowcasting) and 48(+/- 6) kDa (negative staining) indicating TBP dimerization. With 22 and 44 yTBP monomers/DNA, yTBP polymerization produced DNA-protein rods 9 nm wide and 20 to 30 nm long, frequently with two DNA strands exiting one end. Bending analysis revealed that yTBP dimers bend the DNA about the TATA box by 80 to 90 degrees. Although these protein ratios are relatively high, the structures formed demonstrate the propensity of yTBP to engage in protein-protein interactions. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: In Panel b, the same background area appears to be visible twice. ![file] ,
RETRACTED: Neurotensin contributes to pediatric intestinal failure-associated liver disease via regulating intestinal bile acids uptake
Authors: Weihui Yan
Kejun Zhou
Ying Lu
Yongtao Xiao
Wei Cai
Journal: EBioMedicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: ASBT; Cholestasis; Intestinal failure; Liver diseases; Neurotensin.
Affiliations: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute for Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China., Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China., Shanghai Institute for Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China., Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute for Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: .

Abstract:  Although the pathogenesis of intestinal failure (IF)-associated liver disease (IFALD) is uncertain, IF-associated cholestasis mediated by the combination of intestinal injury and parenteral nutrition (PN) can lead to disturbed hepatocyte bile acids (BA) homeostasis and cause liver damages. We here show that neurotensin (NT; also known as NTS) concentrations were lower compared to healthy matched controls. Patients with cholestasis [56.1 ng/L (9.7-154.7) vs. 210.4 ng/L (134-400.4), p &lt; .001] had lower serum NT concentrations than others. In patients' ileum, the levels of NT mRNA were positively correlated with the apical sodium dependent bile acid transporter (ASBT) mRNA levels. In mice and in cultured intestinal cells, NT treatments stimulated the expression of ASBT and led to increase BA uptake via NT receptors (NTR1 and NTR3; also known as NTSR1and NTSR3). In conclusion, these findings directly link NT with BA homeostasis, which provide an insight into the complex mechanisms mediating the development of liver disease in pediatric patients with IF. 

Retracted: Yes

PubPeer comments:
 Some of the images in Figure 2B appear to have internal features which have been cut and pasted; one example below. Could the authors provide high resolution images to reassure readers? *** ![file] ,
Purple acid phosphatases of Arabidopsis thaliana. Comparative analysis and differential regulation by phosphate deprivation
Authors: Georg Leggewie
Huifen Zhu
Xin Liu
Dongping Li
Daowen Wang
Michael Udvardi
Kunfan Liu
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Purple acid phosphatases; metal-ligating residues; Arabidopsis thaliana; cDNA sequences; phosphate deprivation
Affiliations: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

Abstract:  Purple acid phosphatases (PAPs) are members of the metallo-phosphoesterase family. They are characterized by the presence of seven conserved amino acid residues involved in coordinating the dimetal nuclear center in their reactive site. We compared the 29 PAPs predicted for Arabidopsis thaliana in their varieties of potential metal-ligating residues. Although 24 members possessed sets of metal-ligating residues typical of known PAPs, 1 member lacked four of the seven residues. For the remaining four members, potential metal-ligating residues were generally more similar to those in metal-dependent exonucleases and related proteins. Evidence was obtained for the expression of the majority of the 29 PAPs. To facilitate future investigations, a scheme for naming Arabidopsis PAPs and a system for classifying the 29 PAPs are proposed. The cDNA sequences and the responses to phosphate deprivation of seven Arabidopsis PAPs (AtPAP7-AtPAP13) were characterized. For some AtPAPs analyzed, there were fully processed transcripts as well as splice variants. The splice variants of AtPAP10 were found to associate with polyribosomes and may be translated into a NH(2)-terminal truncated protein. Phylogenetic investigations showed that AtPAPs 7 and 8, together with similar enzymes from other plant species, formed the low molecular weight plant PAP group. Members of this group were more closely related to PAPs from mammalian cells. AtPAPs 9-13, together with kidney bean PAP, formed the high molecular weight PAP group. In phosphate deprivation experiments, gene transcription of AtPAP11 and AtPAP12 was induced and increased, respectively, whereas that of the remaining five AtPAPs was not affected by phosphate deprivation. The present work demonstrates that structure variation and expression regulation of plant PAPs are more complex than previously described and provides a framework for comprehensive molecular genetic and biochemical studies of all Arabidopsis PAPs in the future. 

Retracted: No

PubPeer comments:
 In Fig 6, the Western bolt bands of AtPAP7 (red box) were similar to the bands of AtPAP8 (red box). ![file] ,
Prorocentroic Acid, a Neuroactive Super-Carbon-Chain Compound from the Dinoflagellate Prorocentrum hoffmannianum
Authors: David Cabrera-García
Cristina Cuadrado
José J Fernández
Antonello Novelli
M Teresa Fernández-Sánchez
Humberto J Domínguez
Antonio Hernández Daranas
Journal: Organic Letters (2021)
Discipline: CHEMISTRY
Keywords: Prorocentroic acid; dinoflagellate; NMR data; quantum mechanical calculations; murine cortical neurons
Affiliations: Instituto Universitario de Bio-Orgánica Antonio González, University of La Laguna, 38206, Tenerife, Spain, Department of Biochemistry and Molecular Biology and University Institute of Biotechnology of Asturias (IUBA), Campus “El Cristo”, University of Oviedo, 33006 Oviedo, Oviedo, Spain, Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (IPNA-CSIC), La Laguna, 38206, Tenerife, Spain, Department of Psychology and University Institute of Biotechnology of Asturias (IUBA), Campus “El Cristo”, University of Oviedo; Institute for Sanitary Research of the Princedom of Asturias (ISPA), 33006 Oviedo, Oviedo, Spain

Abstract:  Prorocentroic acid (PA) was isolated from the dinoflagellate Prorocentrum hoffmannianum. Relative configurations for its 35 asymmetric centers were determined by analysis of NMR data including heteronuclear couplings and quantum mechanical calculations. PA was tested by using murine cortical neurons grown on microelectrode arrays. Long-term exposure to subtoxic concentrations induced a significant reorganization of neuronal signaling, mainly by changes in the bursting activity. The observed effects could be due to the activation of a plasticity process. 

Retracted: No

PubPeer comments:
 Dear Authors Firstly, congratulation for your great research. I have a question and wish to meet your response. In Table S1(supplementary information), chemical shifts of carbon signals have been assigned to C-1 (176.5) and C-60 (179.1) in CD3OD, some signals appeared in Figure S5 as 169.0 and 179.2 ppm without assignment. (the same to Figure S17 CD3OD Pyridine). Can you explain more? If they are noisy peaks, is there any effect on bioactivity data? ,
Preventing the return of fear in humans using reconsolidation update mechanisms
Authors: Daniela Schiller
Joseph E Ledoux
Candace M Raio
David C Johnson
Marie-H Monfils
Elizabeth A Phelps
Journal: Nature (2010)
Discipline: Multidisciplinary
Keywords: fear memories; reconsolidation; non-invasive technique; emotional memories; pharmacological manipulations
Affiliations: Center for Neural Science, New York University, New York, New York 10003, USA.

Abstract:  Recent research on changing fears has examined targeting reconsolidation. During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. Here we introduce a non-invasive technique to target the reconsolidation of fear memories in humans. We provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear. 

Retracted: No

PubPeer comments:
 Some context for the Addendum. https: twitter.com chrisdc77 status 1027561602260918278 , 
 The results reported in this paper were found to be partly computationally irreproducible and partly down to selective reporting of data. A full report is available here: https: doi.org 10.1016 j.cortex.2020.03.031. In addition, a suitably powered Registered Replication Report failed to replicate this paper s results: https: doi.org 10.1016 j.cortex.2020.04.017. Two accompanying editorials in *Cortex* provide further background: https: doi.org 10.1016 j.cortex.2020.04.020 and https: doi.org 10.1016 j.cortex.2020.04.019. , 
 The authors of the original paper responded to the report and editorials in Cortex and demonstrate that many of the claims are biased, misleading or inaccurate. They conclude that the data, which is publicly available, fully supports the conclusions of the original paper: https: psyarxiv.com jn6uw. , 
 #3 We have now posted a reply to Schiller et al. s PsyArXiv preprint, where we clarify that they did not address (let alone rebut) the most central and critical issues we noted in our Verification Report, and rebut the arguments that they did make. Prompted by their preprint, we now also discuss the post-hoc nature of the participant exclusions that so markedly shaped their results: https: psyarxiv.com tb72e . , 
 Featured quite centrally in an article about problematic papers: https: www.the-scientist.com careers when-researchers-sound-the-alarm-on-problematic-papers-69086 ,
Valproic acid protection against the brachial plexus root avulsion-induced death of motoneurons in rats
Authors: Qiang Li
Guangzhi Wu
Xiaojuan Zhu
Shusen Cui
Dianxiu Wu
Journal: Microsurgery (2013)
Discipline: CLINICAL MEDICINE
Keywords: valproic acid; motoneuron; brachial plexus root avulsion; rats; neuroprotection
Affiliations: Department of Hand Surgery, The Third Clinical Hospital of Jilin University, Changchun, China., Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.

Abstract:  In this study, the role of valproic acid (VPA) in protecting motoneuron after brachial plexus root avulsion was investigated in adult rats. Sixty rats were used in this study, and underwent the brachial plexus root avulsion injury, which was created by using a micro-hemostat forceps to pull out brachial plexus root from the intervertebral foramen. The animals were divided into two groups, VPA group administered with VPA dissolved in drinking water (300 mg/kg) daily, and control group had drinking water every day. The spinal cords (C5-T1) were harvested at day 1, 2, 3, 7, 14, and 28 for immunohistochemistry analysis, TUNEL staining, Nissl staining, and electron microscopy, respectively. The results showed that with VPA administration, the survival of motoneurons was promoted and the cell apoptosis was inhibited. The number of c-Jun and Bcl-2 positive motoneurons was increased immediately after avulsion both in control and VPA group, however, the percent of c-Jun positive motoneurons was decreased and the percent of Bcl-2 positive motoneurons was increased by VPA treatment significantly. Our results indicated that motoneurons were protected by VPA against cell death induced by brachial plexus root avulsion through c-Jun inhibition and Bcl-2 induction. 

Retracted: No

PubPeer comments:
 https: doi.org 10.1042 CS-20070193_EOC The Editorial Board of Clinical Science would like to issue an Expression of Concern for the paper u201cNormal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or new friend?u201d (by Paterna, Gaspare, Fasullo, Sarullo and Di Pasquale). Subsequent to the publication of this paper in Clinical Science, it became evident that some data were duplicated in a paper published in the Journal of Cardiac Failure (doi 10.1016 j.cardfail.2009.06.002). While the data were first published in Clinical Science and hence is the original source the Editorial Board would like to alert readers to use the data in the paper with caution, given the duplication issue. ,
RETRACTED: A 5′ fragment of Xist can sequester RNA produced from adjacent genes on chromatin
Authors: J Mauro Calabrese
Megan D Schertzer
Jackson B Trotman
Steven R Bischoff
Rachel E Cherney
Kaoru Inoue
Dale O Cowley
David M Lee
Journal: Nucleic Acids Research (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Xist; Repeat-A; transcriptional silencing; sequestration; chromatin
Affiliations: Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA., Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA., Animal Models Core, University of North Carolina, Chapel Hill, NC 27599, USA.

Abstract:  Xist requires Repeat-A, a protein-binding module in its first two kilobases (2kb), to repress transcription. We report that when expressed as a standalone transcript in mouse embryonic stem cells (ESCs), the first 2kb of Xist (Xist-2kb) does not induce transcriptional silencing. Instead, Xist-2kb sequesters RNA produced from adjacent genes on chromatin. Sequestration does not spread beyond adjacent genes, requires the same sequence elements in Repeat-A that full-length Xist requires to repress transcription and can be induced by lncRNAs with similar sequence composition to Xist-2kb. We did not detect sequestration by full-length Xist, but we did detect it by mutant forms of Xist with attenuated transcriptional silencing capability. Xist-2kb associated with SPEN, a Repeat-A binding protein required for Xist-induced transcriptional silencing, but SPEN was not necessary for sequestration. Thus, when expressed in mouse ESCs, a 5' fragment of Xist that contains Repeat-A sequesters RNA from adjacent genes on chromatin and associates with the silencing factor SPEN, but it does not induce transcriptional silencing. Instead, Xist-induced transcriptional silencing requires synergy between Repeat-A and additional sequence elements in Xist. We propose that sequestration is mechanistically related to the Repeat-A dependent stabilization and tethering of Xist near actively transcribed regions of chromatin. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: academic.oup.com nar advance-article doi 10.1093 nar gkaa050 5716454 Nucleic Acids Research (2019) 47(13): 7049u20137062, doi:10.1093 nar gkz432 The above article has been retracted at the Authors and Editorsu2019 request. The primer identities in Figure 1D were inadvertently switched and this error affects some of the results and conclusions of the article. While the major conclusions of the article stand, the Authors now attribute the Xist-induced sequestration of nearby RNA to an indirect effect arising from a potent transcriptional anti-terminator activity associated with the Repeat A element in the 5u2032 end of Xist. The Authors have completed an additional series of experiments that address how the conclusions of change as a result of the error in Figure 1D and will soon be reporting their valid original data and new findings in a new article that will supersede the current article. The Editors commend the Authors for their openness and transparency in reporting this problem. ,
MicroRNA-101 inhibits the migration and invasion of intrahepatic cholangiocarcinoma cells via direct suppression of vascular endothelial growth factor-C
Authors: Hongbo Xu
Yinglu Teng
Gang Deng
Feizhou Huang
Lei Zhu
Wanpin Nie
Wei Huang
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-101; intrahepatic cholangiocarcinoma; ICC; metastasis
Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

Abstract:  MicroRNAs (miRs) have important roles in the pathogenesis of human malignancy. It has previously been suggested that deregulation of miR‑101 is associated with the progression of intrahepatic cholangiocarcinoma (ICC); however, the exact role of miR‑101 in the regulation of ICC metastasis remains largely unknown. The present study demonstrated that the expression levels of miR‑101 were significantly decreased in ICC tissue, as compared with matched adjacent normal tissue. Furthermore, miR‑101 was downregulated in the ICC‑9810 human ICC cell line, as compared with in the normal human intrahepatic biliary epithelial cell (HIBEC) line. Vascular endothelial growth factor (VEGF)‑C was identified as a target gene of miR‑101 in ICC‑9810 cells. The expression of VEGF‑C was negatively regulated by miR‑101 at the post‑transcriptional level in ICC‑9810 cells. Further investigation demonstrated that overexpression of miR‑101 markedly suppressed the migration and invasion of ICC‑9810 cells, and these effects were similar to those observed following VEGF‑C knockdown. Conversely, restoration of VEGF‑C reversed the inhibitory effects of miR‑101 overexpression on ICC‑9810 cell migration and invasion, thus suggesting that miR‑101 may suppress ICC‑9810 cell migration and invasion, at least partly via inhibition of VEGF‑C. It was also demonstrated that the mRNA and protein expression levels of VEGF‑C were frequently upregulated in ICC tissue and cells, and its expression level was inversely correlated with that of miR‑101 in ICC tissue. In conclusion, the present study identified important roles for miR‑101 and VEGF‑C in ICC, suggesting that miR‑101/VEGF‑C signaling may be a promising diagnostic and/or therapeutic target for ICC. 

Retracted: No

PubPeer comments:
 image duplication ![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. ,
MiR-376a-3p alleviates the development of glioma through negatively regulating KLF15
Authors: C-X Yan
S-Y Jing
L Chen
Y-K Yang
N Liu
S Han
M-Y Han
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-376a-3p; glioma; metastasis; KLF15; regulatory effects
Affiliations: Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University, Beijing, China. .

Abstract:  Objective: The purpose of this study was to uncover the role of microRNA-376a-3p (miR-376a-3p) in mediating migratory and invasive capacities of glioma, as well as the underlying mechanism. Patients and methods: MiR-376a-3p levels in 39 collected glioma tissues were detected. After collecting clinical data of included glioma patients, the relationship between miR-376a-3p level and clinical features of glioma was analyzed. Next, regulatory effects of miR-376a-3p on proliferative and metastatic capacities of U251 and T98-G cells were assessed. Downstream genes of miR-376a-3p were searched by bioinformatics approach. At last, the involvement of KLF15 in the development of glioma regulated by miR-376a-3p was explored. Results: It was found that miR-376a-3p was lowly expressed in glioma tissues. Low level of miR-376a-3p was linked to high metastasis rate and poor prognosis in glioma. Besides, overexpression of miR-376a-3p suppressed proliferative and metastatic capacities of glioma cells. KLF15, the downstream gene binding miR-376a-3p, was highly expressed in glioma, and displayed a negative correlation to miR-376a-3p. Notably, KLF15 was able to abolish the regulatory effects of miR-376a-3p on phenotypes of glioma cells. Conclusions: MiR-376a-3p is related to lymphatic metastasis and distant metastasis of glioma, and alleviates metastasis of glioma by negatively regulating KLF15. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] , 
 ![file] , 
 ![file] ,
PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA
Authors: Lari Lehtiö
Helen E Bryant
Herwig Schüler
Thomas Helleday
Olga Loseva
Ann-Sofie Jemth
Tobias Karlberg
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PARP-3; DNA repair; ADP-ribosylation; histone H1; mono-ADP-ribosylase
Affiliations: Department of Genetics, Stockholm University, S-10691 Stockholm, Sweden.

Abstract:  The PARP-3 protein is closely related to the PARP-1 and PARP-2 proteins, which are involved in DNA repair and genome maintenance. Here, we characterized the biochemical properties of human PARP-3. PARP-3 is able to ADP-ribosylate itself as well as histone H1, a previously unknown substrate for PARP-3. PARP-3 is not activated upon binding to DNA and is a mono-ADP-ribosylase, in contrast to PARP-1 and PARP-2. PARP-3 interacts with PARP-1 and activates PARP-1 in the absence of DNA, resulting in synthesis of polymers of ADP-ribose. The N-terminal WGR domain of PARP-3 is involved in this activation. The functional interaction between PARP-3 and PARP-1 suggests that it may have a role in DNA repair. However, here we report that PARP-3 small interfering RNA-depleted cells are not sensitive to the topoisomerase I poison camptothecin, inducing DNA single-strand breaks, and repair these lesions as efficiently as wild-type cells. Altogether, these results suggest that the interaction between PARP-1 and PARP-3 is unrelated to DNA single-strand break repair. 

Retracted: No

PubPeer comments:
 Figure 2B. Much more similar than expected. ![file] ,
MicroRNA-195 inhibits colorectal cancer cell proliferation, colony-formation and invasion through targeting CARMA3
Authors: Ling Wang
Liyuan Qian
Xiaorong Li
Jin Yan
Journal: Molecular Medicine Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-195; tumor suppressor; colorectal cancer; CARMA3; metastasis
Affiliations: The Second Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China., Department of Nursing, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

Abstract:  MicroRNA (miR)‑195 has been reported to be a tumor suppressor. Downregulation of miR‑195 has been shown to correlate with lymph node metastasis and poor prognosis in colorectal cancer. However, the specific regulatory role of miR‑195 in colorectal cancer cells is yet to be elucidated. In the present study, miR‑195 expression was significantly reduced in colorectal cancer tissues. Furthermore, CARMA3 was identified as a novel target of miR‑195, which was observed to be upregulated in colorectal cancer. In addition, downregulation of miR‑195 increased CARMA3 protein expression, whereas miR‑195 upregulation suppressed CARMA3 protein expression in SW480 and HT29 colorectal cancer cells. Moreover, overexpression of miR‑195 downregulated cell proliferation, colony‑formation and invasion in SW480 and HT29 cells, which was reversed upon CARMA3 overexpression. In conclusion, the findings of the present study suggest that miR‑195 has a suppressive role in colorectal cancer cells through directly targeting CARMA3. Therefore, CARMA3 may be a potential target for the treatment of colorectal cancer. 

Retracted: No

PubPeer comments:
 Fig 7.  Cell invasion assay was performed to determine the effect of miR-195 and CARMA3 on invasion in SW480 and HT29 cells following transfection with an miR-195 mimic or an miR-195 inhibitor, or co-transfected with an miR-195 mimic and CARMA3-pcDNA3.1 . ![file] For comparison: *[upper]* Figs 4 C D and 5C from [Yang et al (2016)] .  Transwell assays were conducted to examine the cell invasion capacities ofA549 cells transfected with (C) miR-133b mimics and (D) FSCN1 plasmids. Non-transfected A549 cells were used as control ....  Transwell assay were conducted to examine the cell migration and invasion in each group . *[lower]* Fig 5B from [Wang et al (2016)] .  Transwell assay to determine the invasive capacity of U2OS cells transfected with miRu2011101 mimics or cu2011FOS siRNA, or cou2011transfected with miRu2011101 mimics and cu2011FOS plasmid. Magnification, x100. Control: untransfected U2OS cells . ![file] ,
Similarities in lindane induced alterations in protein expression profiling in different brain regions with neurodegenerative diseases
Authors: Juhi Mishra
Anshuman Singh
Devendra Parmar
Lalit Pratap Chandravanshi
Sanjay Yadav
Pradhyumna Kumar Singh
Anubha Mudawal
Sanghamitra Bandyopadhyay
Manisha Mishra
Vinay K Khanna
Journal: PROTEOMICS (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Animal Proteomics; Brain regions; Lindane; Neurobehaviour; Proteomic analysis
Affiliations: Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India., Academy of Scientific & Innovative Research, CSIR-IITR Campus, Lucknow, India., Plant Molecular Biology Laboratory, CSIR-National Botanical Research Institute (CSIR-NBRI), Lucknow, India.

Abstract:  Previous studies have reported that lindane, an organochlorine pesticide induces oxidative stress in rat brain that may lead to neurodegeneration. However, as the proteins involved in lindane induced neurodegeneration are yet to be identified, the present study aims to identify the proteins that may regulate lindane induced neurotoxicity. The data showed that repeated exposure of lindane (2.5 mg/kg) for 21 days to adult rats significantly increased the reactive oxygen species and lipid peroxidation in different brain regions. Proteomic study revealed that lindane induces major dysregulation in the ubiquitin proteasome pathway. Alterations in the expression of molecular chaperones in brain regions and an increase in the expression of α-synuclein in substantia-nigra and corpus-striatum and amyloid precursor protein in hippocampus and frontal-cortex suggests the accumulation of proteins in these brain regions. Western blotting also revealed alterations in the dopaminergic and cholinergic pathways in hippocampus and substantia-nigra isolated from lindane treated rats. Neurobehavioural data indicating alterations in learning and working memory, conditioned avoidance response and motor function, supports the proteomic data. The data suggest that repeated exposure of lindane to adult rats induces alterations, which are similar to that seen in neurodegenerative diseases. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] ,
3, 3′-Diindolylmethane Exhibits Antileukemic Activity In Vitro and In Vivo through a Akt-Dependent Process
Authors: Senping Cheng
E-Hu Liu
Xianglin Shi
Ning Gao
Zailin Yang
Amit Budhraja
Deying Chen
Jia Luo
Zhuo Zhang
Jieping Chen
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: 3,3'-Diindolylmethane (DIM); apoptosis; leukemia cells; caspases activation; Mcl-1 down-regulation
Affiliations: Department of Pharmacognosy, College of Pharmacy, 3rd Military Medical University, Chongqing, China. 

Abstract:  3,3'-Diindolylmethane (DIM), one of the active products derived from Brassica plants, is a promising antitumor agent. The present study indicated that DIM significantly induced apoptosis in U937 human leukemia cells in dose- and time-dependent manners. These events were also noted in other human leukemia cells (Jurkat and HL-60) and primary human leukemia cells (AML) but not in normal bone marrow mononuclear cells. We also found that DIM-induced lethality is associated with caspases activation, myeloid cell leukemia-1 (Mcl-1) down-regulation, p21(cip1/waf1) up-regulation, and Akt inactivation accompanied by c-jun NH2-terminal kinase (JNK) activation. Enforced activation of Akt by a constitutively active Akt construct prevented DIM-mediated caspase activation, Mcl-1 down-regulation, JNK activation, and apoptosis. Conversely, DIM lethality was potentiated by the PI3K inhibitor LY294002. Interruption of the JNK pathway by pharmacologic or genetic approaches attenuated DIM-induced caspases activation, Mcl-1 down-regulation, and apoptosis. Lastly, DIM inhibits tumor growth of mouse U937 xenograft, which was related to induction of apoptosis and inactivation of Akt, as well as activation of JNK. Collectively, these findings suggest that DIM induces apoptosis in human leukemia cell lines and primary human leukemia cells, and exhibits antileukemic activity in vivo through Akt inactivation and JNK activation. 

Retracted: Yes

PubPeer comments:
 Image in Figure 4A may show signs of splicing in AR band. Contrast enhanced image below. Would the authors have an original scan that they could upload here? *** ![file] , 
 Thanks to the question raised by Actinopolyspora Biskresis. The original raw data already published together with this paper in the Science TM journal as supplementary data. please see attachment below or get in ScienceTM to read , 
 ![file] , 
 #3 Thank you for responding and providing the requested image. This addresses my concern and I apologize for not finding this in the supplemental material. ,
Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells
Authors: Jitendra Panwar
Sheik Saleem Pasha
Inamur Rahaman Laskar
Subhra Dash
R Venkataramana Dilip
Leena Fageria
Heena Saini
Vikram Pareek
Arpit Bhargava
Rajdeep Chowdhury
Journal: ACS Omega (2017)
Discipline: CHEMISTRY
Keywords: silver nanoparticles; biosynthesis; Penicillium shearii AJP05; protein-capped; anticancer activity
Affiliations: Department
of Biological Sciences and ‡Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, India

Abstract:  In recent years, the use of silver nanoparticles (AgNPs) in biomedical applications has shown an unprecedented boost along with simultaneous expansion of rapid, high-yielding, and sustainable AgNP synthesis methods that can deliver particles with well-defined characteristics. The present study demonstrates the potential of metal-tolerant soil fungal isolate Penicillium shearii AJP05 for the synthesis of protein-capped AgNPs. The particles were characterized using standard techniques, namely, UV-visible spectroscopy, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The anticancer activity of the biosynthesized AgNPs was analyzed in two different cell types with varied origin, for example, epithelial (hepatoma) and mesenchymal (osteosarcoma). The biological NPs (bAgNPs) with fungal-derived outer protein coat were found to be more cytotoxic than bare bAgNPs or chemically synthesized AgNPs (cAgNPs). Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis. Upregulation of autophagy and activation of JNK signaling were found to act as a prosurvival strategy upon bAgNP treatment, whereas ERK signaling served as a prodeath signal. Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death. Finally, bAgNPs were also found to sensitize cells with acquired resistance to cisplatin, providing valuable insights into the therapeutic potential of bAgNPs. To the best of our knowledge, this is the first study that provides a holistic idea about the molecular mechanisms behind the cytotoxic activity of protein-capped AgNPs synthesized using a metal-tolerant soil fungus. 

Retracted: No

PubPeer comments:
 ![file] ERK never has a sharp single band expression. ERK has a characteristic double band expression. , 
 ![file] Figure 7a and Figure 9d has Same picture cropped and reused and labeled differently ,
The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity
Authors: Jocelyn Widagdo
Victor Anggono
Journal: Journal of Neurochemistry (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: RNA binding proteins; RNA methylation; epitranscriptomic; m6A; post-transcriptional regulation.
Affiliations: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Qld, Australia.

Abstract:  Research over the past decade has provided strong support for the importance of various epigenetic mechanisms, including DNA and histone modifications in regulating activity-dependent gene expression in the mammalian central nervous system. More recently, the emerging field of epitranscriptomics revealed an equally important role of post-transcriptional RNA modifications in shaping the transcriptomic landscape of the brain. This review will focus on the methylation of the adenosine base at the N6 position, termed N6 methyladenosine (m6A), which is the most abundant internal modification that decorates eukaryotic messenger RNAs. Given its prevalence and dynamic regulation in the adult brain, the m6A-epitranscriptome provides an additional layer of regulation on RNA that can be controlled in a context- and stimulus-dependent manner. Conceptually, m6A serves as a molecular switch that regulates various aspects of RNA function, including splicing, stability, localization, or translational control. The versatility of m6A function is typically determined through interaction or disengagement with specific classes of m6A-interacting proteins. Here we review recent advances in the field and provide insights into the roles of m6A in regulating brain function, from development to synaptic plasticity, learning, and memory. We also discuss how aberrant m6A signaling may contribute to neurodevelopmental and neuropsychiatric disorders. 

Retracted: No

PubPeer comments:
 this has some pretty sloppy editing Despite the aforementioned reports, a recent study has questioned the role of m6A in nuclear splicing. In contrast to previous studies which reported differential regulation in splicing following METTL3 knockdown (Dominissini et al. 2012; Zhao et al. 2014; Liu et al. 2015, Ke et al. 2017) observed no detectable changes in mRNA splicing in METTL3 knockdown cells ( 90% reduction in m6A). One potential explanation for these differences is the use of different bioinformatics analyses in these studies. what study observed no detectable changes? which one? Ke et al? , 
 Thank you for your interest in the review article. The study that did not observe detectable changes in splicing after METTL3 knockdown is by Ke et al. (2017). Ke S., Pandya-Jones A., Saito Y. et al. (2017) m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes Dev. 31, 990u20131006. We apologise for the inconvenience. , 
 #2 Thanks for the clarification. Looks like the journal itself might have mangled this. ,
Inactivation of adenosine A2A receptor attenuates basal and angiotensin II-induced ROS production by Nox2 in endothelial cells
Authors: Junjie Du
Susanna Hourani
Catherine Ledent
Sapna Thakur
Jian-Mei Li
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Endothelial cells; Nox2 enzyme; reactive oxygen species; redox signaling; angiotensin II
Affiliations: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.

Abstract:  Endothelial cells (ECs) express a Nox2 enzyme, which, by generating reactive oxygen species (ROS), contributes to EC redox signaling and angiotensin II (AngII)-induced endothelial dysfunction. ECs also express abundantly an adenosine A(2A) receptor (A(2A)R), but its role in EC ROS production remains unknown. In this study, we investigated the role of A(2A)R in the regulation of Nox2 activity and signaling in ECs with or without acute AngII stimulation. In cultured ECs (SVEC4-10), AngII (100 nm, 30 min) significantly increased Nox2 membrane translocation and association with A(2A)R. These were accompanied by p47(phox), ERK1/2, p38 MAPK, and Akt phosphorylation and an increased ROS production (169 ± 0.04%). These AngII effects were inhibited back to the control levels by a specific A(2A)R antagonist (SCH58261), or adenosine deaminase, or by knockdown of A(2A)R or Nox2 using specific siRNAs. Knockdown of A(2A)R, as determined by Western blotting, decreased Nox2 and p47(phox) expression. In wild-type mouse aorta, SCH58261 significantly reduced acute AngII-induced ROS production and preserved endothelium-dependent vessel relaxation to acetylcholine. These results were further confirmed by using aortas from A(2A)R knock-out mice. In conclusion, A(2A)R is involved in the regulation of EC ROS production by Nox2. Inhibition or blockade of A(2A)R protects ECs from acute AngII-induced oxidative stress, MAPK activation, and endothelium dysfunction. 

Retracted: No

PubPeer comments:
 A possible concern about Figure 1C was pointed out to me by a reader. * Yellow boxes: The Control Vehicle panel appears to show an overlap with the +AngII SCH58261 panel. ![file] , 
 An additional finding for Figure 5A. * Green boxes: The Vehicle +SCH and AngII +SCH panels appear to show an overlap, although not all red-labeled features appear to show up at the same intensity. Some remarkable similarities are highlighted with boxes of the same shape. ![file] ,