PReD-Bench/PRed-Bench huggingface dataset:
Quercetin improve ischemia/reperfusion‐induced cardiomyocyte apoptosis in vitro and in vivo study via SIRT1/PGC‐1α signaling
Authors: Lifang Yang
Jun Ren
Jipeng Ma
Shiqiang Yu
Yang Liu
Hong Guo
Linhe Lu
Lanlan Li
Jian Yang
Jiayou Tang
Heping Bai
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cell apoptosis; peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α); quercetin (QU); silent information regulatory factor 1 (SIRT1).
Affiliations: Department of Cardiovascular Surgery Xijing Hospital, Fourth Military Medical University Xi'an China, Department of Anesthesiology Xi'an Children's Hospital Xi'an China, College of Health Sciences, University of Wyoming Laramie Wyoming, Department of Thoracic and Cardiovascular Surgery The Second Hospital of Yulin  Shaanxi China

Abstract:  Aim: To evaluate the effects of quercetin to improve ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro and in vivo study. Methods: The cells were divided into five groups: model control (MC) group was ischemia/reperfusion (I/R) model group; DL group was treated with 25 mL/L quercetin based on MC group; DM group was treated with 50 ml/L quercetin based on MC group; DH group was treated with 100 mL/L quercetin based on MC group; Meto group was treated with metoprolol based on MC group. In the in vivo study, the rats were divided into five groups: MC group was I/R model group; DL group was treated with 25 mg/kg quercetin; DM group was treated with 50 mg/kg quercetin; DM group was treated with 100 mg/kg quercetin; Meto group was treated with Meto as positive drug. Results: The cell apoptosis rates of quercetin treated groups (DL, DM, and DH groups) were significantly suppressed compared with the MC group. The silent information regulatory factor 1 (SIRT1), peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), and Bcl-2 proteins expression of quercetin treated were significantly upregulation compared with MC group (P &lt; 0.05, respectively), and Bax protein expression of quercetin treated group was significantly downregulation compared with MC group ( P &lt; 0.05, respectively). In the vivo study, the myocardial pathological morphology of quercetin treated groups was improved. The cell apoptosis number of quercetin treated group were significantly suppressed compared with MC group by terminal deoxynucleotidyl transferase dUTP nick end labeling assay ( P &lt; 0.05, respectively). SIRT1, PGC-1a, Bcl-2, and Bax proteins expressions of quercetin treated groups were significant differences compared with MC group in myocardial tissue ( P &lt; 0.05, respectively). Conclusion: Quercetin had improved the myocardial ischemia/reperfusion-induced cardiomyocyte apoptosis via SIRT1/PGC-1α signaling. 

Retracted: No

PubPeer comments:
 Fig 4.  The pathological of difference groups by HE staining . Panels MC and DM are supposed to represent different rats, receiving different treatment. ![file] ,
Enhancement of antitumor immunity by CTLA-4 blockade
Authors: M F Krummel
D R Leach
J P Allison
Journal: Science (1996)
Discipline: Multidisciplinary
Keywords: tumors; immunogenicity; CD28; costimulation; T cells
Affiliations: Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.

Abstract:  One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells. 

Retracted: No

PubPeer comments:
 As a young scholar, I personally respect the achievements of JP Allison, who is the 2018 Nobel Prize winner, so I read the original article. But I unexpectedly found that some tumors were suspected of exceeding the ethical regulations. Generally, the diameter of the tumor cannot exceed 15 mm, so if calculated according to the square area, the maximum area cannot exceed 15*15=225 (if calculated according to the circle area, the maximum area cannot exceed 176). However, the upper limit of the standard deviation of the data in figure 4 obviously exceeds the ethical regulations.![file] , 
 #1 Did you find a source for the regulatory guidelines that were applicable in 1996, when this paper was published? ,
Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health
Authors: Dharma N Bhatta
Stanton A Glantz
Journal: Journal of the American Heart Association (2019)
Discipline: CLINICAL MEDICINE
Keywords: epidemiology; e‐cigarettes; myocardial infarction; smoking.
Affiliations: 1 Center for Tobacco Control Research and Education University of California, San Francisco San Francisco CA., 2 Helen Diller Family Comprehensive Cancer Center University of California, San Francisco San Francisco CA., 3 Department of Medicine (Cardiology) Cardiovascular Research Institute, and Philip R Lee Institute for Health Policy Studies University of California, San Francisco San Francisco CA.

Abstract:  Background E-cigarettes are popular for smoking cessation and as an alternative to combustible cigarettes. We assess the association between e-cigarette use and having had a myocardial infarction ( MI ) and whether reverse causality can explain the observed cross-sectional association between e-cigarette use and MI . Methods and Results Cross-sectional analysis of the Population Assessment of Tobacco and Health Wave 1 for association between e-cigarette use and having had and MI . Longitudinal analysis of Population Assessment of Tobacco and Health Waves 1 and 2 for reverse causality analysis. Logistic regression was performed to determine the associations between e-cigarette initiation and MI , adjusting for cigarette smoking, demographic and clinical variables. Every-day (adjusted odds ratio, 2.25, 95% CI : 1.23-4.11) and some-day (1.99, 95% CI : 1.11-3.58) e-cigarette use were independently associated with increased odds of having had an MI with a significant dose-response ( P&lt;0.0005). Odds ratio for daily dual use of both products was 6.64 compared with a never cigarette smoker who never used e-cigarettes. Having had a myocardial infarction at Wave 1 did not predict e-cigarette use at Wave 2 ( P&gt;0.62), suggesting that reverse causality cannot explain the cross-sectional association between e-cigarette use and MI observed at Wave 1. Conclusions Some-day and every-day e-cigarette use are associated with increased risk of having had a myocardial infarction, adjusted for combustible cigarette smoking. Effect of e-cigarettes are similar as conventional cigarette and dual use of e-cigarettes and conventional cigarettes at the same time is risker than using either product alone. 

Retracted: No

PubPeer comments:
 In Figure 2i and 5f, two images have been duplicated, modified (flipped horizontally) and presented as something else. ![file] , 
 Another concern that has not been addressed for the many problematic papers published in Cell Cycle. This indicates that there is one papermill producer involved, which has a silencing strategy against whistleblowers. ,
Stimulating the ventrolateral prefrontal cortex (VLPFC) modulates frustration-induced aggression: A tDCS experiment
Authors: Paolo Riva
Alessia Gallucci
Brad J Bushman
Leonor J Romero Lauro
Journal: Brain stimulation (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Aggression; Frustration; Transcranial direct current stimulation (tDCS); Ventrolateral prefrontal cortex (VLPFC).
Affiliations: University of Milano-Bicocca, Milan, Italy. Electronic address: ., The Ohio State University, Columbus, OH, USA. Electronic address: .

Abstract:  Background: The prefrontal cortex is crucial for top-down regulation of aggression, but the neural underpinnings of aggression are still poorly understood. Past research showed the transcranial direct current stimulation (tDCS) over the ventrolateral prefrontal cortex (VLPFC) modulates aggression following exposure to risk factors for aggression (e.g., social exclusion, violent media). Although frustration is a key risk factor for aggression, no study to date has examined the modulatory role of tDCS on frustration-induced aggression. Objectives: By exploring the VLPFC involvement in frustration-aggression link, we tested the hypothesis that the anodal tDCS over right and left VLPFC modulates frustration-induced aggression. We also explored whether tDCS interacts with gender to influence frustration-induced aggression. Methods: 90 healthy participants (45 men) were randomly assigned to receive anodal or sham tDCS over the right or left VLPFC before being frustrated by an accomplice. To increase reliability, several tasks were used to measure aggression. Results: We found that anodal tDCS over the left VLPFC, compared to sham stimulation, increased aggression. Unexpectedly, no main effect was found following tDCS of right VLPFC. However, we also found a significant interaction between gender and tDCS, showing that males were more aggressive than females following sham stimulation, but females became as aggressive as males following active tDCS. Conclusion: Overall, these results shed light on the neural basis of frustration-induced aggression, providing further evidence for the involvement of VLPFC in modulating aggressive responses, and on gender differences in aggression. Future research should further investigate the role of stimulating the VLPFC on frustration-induced aggression. 

Retracted: No

PubPeer comments:
 The effect sizes reported are of very large magnitude (d = 1, 2, 3, and even 4.6). I think that this is just a calculation error, and perhaps the authors have calculated d as (m1 - m2) SE when it should be calculated as (m1 - m2) SD. It might be nice to have the correct effect sizes reported, especially in case some meta-analyst is going to use these effect sizes. , 
 #1 Thank you a lot for your message. Yes, we actually used standard error for our statistics. This is a very full period for me, thus as soon as possibile I will contact the Editor to add a supplementary material with the correct effect sizes. Thank you again. , 
 #2 I don t see any correction issue in the two years since this message. Have the authors contacted the journal yet? ,
REGγ regulates ERα degradation via ubiquitin–proteasome pathway in breast cancer
Authors: Yan Liang
Jiong Bi
Fan Chai
Youhong Cui
Li Chen
Jun Jiang
Fan Zhang
Journal: Biochemical and Biophysical Research Communications (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Breast cancer; Degradation; ERα; Proteasome; REGγ
Affiliations: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China., Laboratory of General Surgery, First Affiliated Hospital, Sun Yet-sen University, Guangzhou 510080, China., Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China., Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: .

Abstract:  REGγ is a proteasome coactivator which regulates proteolytic activity in eukaryotic cells. Abundant lines of evidence have showed that REGγ is over expressed in a number of human carcinomas. However, its precise role in the pathogenesis of cancer is still unclear. In this study, by examining 200 human breast cancer specimens, we demonstrated that REGγ was highly expressed in breast cancers, and the expression of REGγ was positively correlated with breast cancer patient estrogen receptor alpha (ERα) status. Moreover, the expression of REGγ was found positively associated with poor clinical features and low survival rates in ERα positive breast cancer patients. Further cell culture studies using MCF7 and BT474 breast cancer cell lines showed that cell proliferation, motility, and invasion capacities were decreased significantly by REGγ knockdown. Lastly, we demonstrated that REGγ indirectly regulates the degradation of ERα protein via ubiquitin-proteasome pathway. In conclusion, our findings provide the evidence that REGγ expression was positively correlated with ERα status and poor clinical prognosis in ERα positive breast cancer patients. As well, we disclose a new connection between the two molecules that are both highly expressed in most breast cancer cases. 

Retracted: No

PubPeer comments:
 Figure 2. Three panels visible in E (MCF7 cells) appear similar to panels visible in F (BT474 cells). ![file] ,
Precise excitation-inhibition balance controls gain and timing in the hippocampus
Authors: Aanchal Bhatia
Sahil Moza
Upinder Singh Bhalla
Journal: eLife (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: EI balance; channelrhodopsin; hippocampus; inhibition; mouse
Affiliations: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.

Abstract:  Excitation-inhibition (EI) balance controls excitability, dynamic range, and input gating in many brain circuits. Subsets of synaptic input can be selected or 'gated' by precise modulation of finely tuned EI balance, but assessing the granularity of EI balance requires combinatorial analysis of excitatory and inhibitory inputs. Using patterned optogenetic stimulation of mouse hippocampal CA3 neurons, we show that hundreds of unique CA3 input combinations recruit excitation and inhibition with a nearly identical ratio, demonstrating precise EI balance at the hippocampus. Crucially, the delay between excitation and inhibition decreases as excitatory input increases from a few synapses to tens of synapses. This creates a dynamic millisecond-range window for postsynaptic excitation, controlling membrane depolarization amplitude and timing via subthreshold divisive normalization. We suggest that this combination of precise EI balance and dynamic EI delays forms a general mechanism for millisecond-range input gating and subthreshold gain control in feedforward networks. 

Retracted: No

PubPeer comments:
 This paper make uses of the following cell line  Human GC cell line SGC-7901 (American Type Culture Collection, ATCC, Manassas, VA, USA) . There are two problems: 1) ATCC has never distributed SGC-7901, si this statement is incorrect. 2) SGC-7901 is not a gastric carcinoma cell line, but is a HeLa contaminated cell line. Thus many of the conclusions of this paper when relevant to experiments carried out on SGC-7901 are unfortunatly not relevant. See the relevant [Cellosaurus entry] ,
The small GTPase Arf6 is essential for the Tram/Trif pathway in TLR4 signaling
Authors: Tim Van Acker
Frank Peelman
Celia Bovijn
Lieselotte Vande Walle
Marc Goethals
Sven Eyckerman
Jan Tavernier
Mohamed Lamkanfi
Sarah Gerlo
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Arf6; Cytokines/Interferon; Endocytosis; Innate Immunity; Lipopolysaccharide (LPS)
Affiliations: From the Department of Medical Protein Research, Cytokine Receptor Lab, VIB, Ghent B-9000, Belgium.

Abstract:  Recognition of lipopolysaccharides (LPS) by Toll-like receptor 4 (TLR4) at the plasma membrane triggers NF-κB activation through recruitment of the adaptor proteins Mal and MyD88. Endocytosis of the activated TLR4 allows recruitment of the adaptors Tram and Trif, leading to activation of the transcription factor IRF3 and interferon production. The small GTPase ADP-ribosylation factor 6 (Arf6) was shown to regulate the plasma membrane association of Mal. Here we demonstrate that inhibition of Arf6 also markedly reduced LPS-induced cytokine production in Mal(-/-) mouse macrophages. In this article, we focus on a novel role for Arf6 in the MyD88-independent TLR4 pathway. MyD88-independent IRF3 activation and IRF3-dependent gene transcription were strictly dependent on Arf6. Arf6 was involved in transport of Tram to the endocytic recycling compartment and internalization of LPS, possibly explaining its requirement for LPS-induced IRF3 activation. Together, these results show a critical role for Arf6 in regulating Tram/Trif-dependent TLR4 signaling. 

Retracted: No

PubPeer comments:
 The cell morphology of different groups in red boxes appear to look similar in Fig 6A and Fig6c. ![file] ,
Regulation of miR-33b on endometriosis and expression of related factors
Authors: L Jiang
Q Wang
W-W Yang
L Hong
J-L Huang
X-X Xu
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Endometriosis; miRNA; miR-33b; cell proliferation; apoptosis
Affiliations: Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. .

Abstract:  Objective: Endometriosis is a common benign disease in gynecology, and can cause chronic pelvic pain, dysmenorrhea and even infertility. Its pathogenesis mechanism has not been fully illustrated. miRNA (miR) participates in various biological activities including cell growth, proliferation, apoptosis, organ formation, inflammation and tumor. Its role in endometriosis has not been reported. MiR-33b is involved in cell metabolism, proliferation and invasion, but with its function and mechanism in endometriosis unknown. Patients and methods: Real-time PCR was used to test miR-33b expression in ectopic endometrial and normal tissues. In vitro cultured endometrial cells were transfected with miR-33b mimic or inhibitor, followed by Real-time PCR for miR-33b expression. MTT method detected endometrial cell proliferation. Caspase 3 activity was quantified by test kit. Real-time PCR and Western blot measured effect of miR-33b on vascular endothelial growth factor (VEGF) and matrix metalloprotein 9 (MMP-9). Results: MiR-33b was down-regulated in ectopic endometrial tissues (p &lt; 0.05 compared to normal tissues). Transfection of miR-33b inhibitor facilitated endometrial proliferation, decreased Caspase 3 activity, increased VEGF and MMP-9 mRNA or protein expression (p &lt; 0.05 compared to control group). MiR-33b mimic suppressed endometrial proliferation, elevated Caspase 3 activity, and decreased VEGF or MMP-9 expression (p &lt; 0.05 compared to control group). Conclusions: MiR-33b can mediate cell apoptosis, alter VEGF and MMP-9 expression and affect proliferation and apoptosis of uterus endometrial cells, thus participating endometriosis formation. 

Retracted: Yes

PubPeer comments:
 Figure 2D and 4C. Several flow cytometry panels appear to show similar groupings of dots. Boxes of the same color show some of those groups. ![file] ![file] ,
Expression of human cardiac-specific homeobox protein in Escherichia coli
Authors: Z Xu
J H Zhao
Z C Hua
Journal: Protein expression and purification (2000)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Human cardiac-specific homeobox protein; cDNA; Escherichia coli; thioredoxin; fusion protein
Affiliations: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, People's Republic of China.

Abstract:  Human cardiac-specific homeobox protein cDNA (hCsx) was cloned into expression plasmid pET32a and fused with Escherichia coli thioredoxin (Trx). The Trx-Csx fusion protein was under the control of bacteriophage T7 promoter. When expressed in E. coli BL21(DE3), about half of the recombinant Trx-Csx products existed in the form of insoluble inclusion bodies. When coexpressed with human protein disulfide isomerase, more than 90% of Trx-Csx products accumulated in the soluble form in the cell lysate. The recombinant Csx fusion protein was purified by one-step metal-chelating affinity chromatography. 

Retracted: No

PubPeer comments:
 This is another duplicated self-plagiarism publication from Hua s lab. Contents were copied pasted between international and domestic journals. Both articles are not long, and I will paste both to the bottom. ----- The first page of this article ![file] The first page of the one in a Chinese journal ![file] ------ The second page of this article ![file] Part of the 1st and 2nd pages of the Chinese one ![file] ![file] ----- The third page of this article ![file] part of the 2nd and 3rd pages of the Chinese one ![file] ![file] ----- The 4th page of this article ![file] and the 3th page of the Chinese one ![file] ----- **I paste the 2 articles here.** ----- ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ,
Crocetin exploits p53-induced death domain (PIDD) and FAS-associated death domain (FADD) proteins to induce apoptosis in colorectal cancer
Authors: Pallab Ray
Samik Chakraborty
Deblina Guha
Gaurisankar Sa
Tanya Das
Shuvomoy Banerjee
Juni Chakraborty
Arghya Adhikary
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Tumor suppressor p53; colon cancer; crocetin; apoptosis; p53 status
Affiliations: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, India.

Abstract:  Tumor suppressor p53 preserves the genomic integrity by restricting anomaly at the gene level. The hotspots for mutation in half of all colon cancers reside in p53. Hence, in a p53-mutated cellular milieu targeting cancer cells may be achievable by targeting the paralogue(s) of p53. Here we have shown the effectiveness of crocetin, a dietary component, in inducing apoptosis of colon cancer cells with varying p53 status. In wild-type p53-expressing cancer cells, p53 in one hand transactivates BAX and in parallel up-regulates p53-induced death domain protein (PIDD) that in turn cleaves and activates BID through caspase-2. Both BAX and t-BID converge at mitochondria to alter the transmembrane potential thereby leading to caspase-9 and caspase-3-mediated apoptosis. In contrast, in functional p53-impaired cells, this phytochemical exploits p53-paralogue p73, which up-regulates FAS to cleave BID through FAS-FADD-caspase-8-pathway. These findings not only underline the phenomenon of functional switch-over from p53 to p73 in p53-impaired condition, but also validate p73 as a promising and potential target for cancer therapy in absence of functional p53. 

Retracted: No

PubPeer comments:
 Fig 3d (using HCT116 cells) ![file] Fig 5a (using HT29 cells) ![file] The Actin is duplicated because both figures were made from two different cell lines. The only difference is the size of the figure. Furthermore, the caspase 3 seems to be duplicated with intensity enhancement in Fig 3d. Can author please clarify? ,
An Anopheles aquasalis GATA factor Serpent is required for immunity against Plasmodium and bacteria
Authors: Yara M Traub-Csekö
Cláudia M Ríos-Velásquez
Caroline M Gonçalves
Ana C Bahia
Ana Beatriz Barletta
Leonardo B Koerich
Marina S Kubota
Paulo F P Pimenta
Helena R C Araújo
Jayme A Souza-Neto
Journal: PLoS neglected tropical diseases (2018)
Discipline: IMMUNOLOGY
Keywords: Innate immunity; Anopheles mosquitoes; immune genes; GATA transcription factor; P. vivax infection
Affiliations: Laboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil., Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Laboratório de Fisiologia de Insetos Hematófagos, Instituto de Biologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Laboratório de Bioquímica de Artrópodes Hematófagos, Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Laboratório de Entomologia Médica, Instituto René Rachou, Fiocruz, Belo Horizonte, MG, Brazil., Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas & Maria Deane, Fiocruz, Manaus, AM, Brazil., Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil., Laboratório de Biodiversidade em Saúde, Centro de Pesquisa Leônidas & Maria Deane, Fiocruz, Manaus, AM, Brazil.

Abstract:  Innate immunity is an ancient and conserved defense system that provides an early effective response against invaders. Many immune genes of Anopheles mosquitoes have been implicated in defense against a variety of pathogens, including plasmodia. Nevertheless, only recent work identified some immune genes of Anopheles aquasalis mosquitoes upon P. vivax infection. Among these was a GATA transcription factor gene, which is described here. This is an ortholog of GATA factor Serpent genes described in Drosophila melanogaster and Anopheles gambiae. Gene expression analyses showed an increase of GATA-Serpent mRNA in P. vivax-infected A. aquasalis and functional RNAi experiments identified this transcription factor as an important immune gene of A. aquasalis against both bacteria and P. vivax. Besides, we were able to identify an effect of GATA-Serpent knockdown on A. aquasalis hemocyte proliferation and differentiation. These findings expand our understanding of the poorly studied A. aquasalis-P. vivax interactions and uncover GATA-Serpent as a key player of the mosquito innate immune response. 

Retracted: No

PubPeer comments:
 The same image is used for a patient with constipation and megacolon (2011) and a patient with Chagas disease (2007). ![file] ,
Phosphorylation of p62 by cdk1 controls the timely transit of cells through mitosis and tumor cell proliferation
Authors: Juan F Linares
Maria T Diaz-Meco
Kenneth Greis
Jorge Moscat
Ramars Amanchy
Journal: Molecular and Cellular Biology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p62; signaling regulator; cancer; TRAF6/NF-κB signaling cascade; cdk1 phosphorylation
Affiliations: Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Vontz Center for Molecular Studies, 3125 Eden Avenue, Cincinnati, OH 45267, USA.

Abstract:  The protein scaffold and signaling regulator p62 is important in critical cellular functions, including bone homeostasis, obesity, and cancer, because of its interactions with various signaling intermediaries. p62 is overexpressed in human cancers and is induced during cell transformation. Its genetic ablation inhibits lung tumorigenesis in vivo and cell proliferation in culture by regulating the TRAF6/NF-κB signaling cascade to control reactive oxygen species (ROS) production and apoptosis. Here we show that cdk1 phosphorylates p62 in vitro and in vivo at T269 and S272, which is necessary for the maintenance of appropriate cyclin B1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis. The lack of cdk1-mediated phosphorylation of p62 leads to a faster exit from mitosis, which translates into enhanced cell proliferation and tumorigenesis in response to Ras-induced transformation. Therefore, p62 emerges as a node for the control of not only cell survival but also cell transit through mitosis. 

Retracted: No

PubPeer comments:
 This article has three corrections, as per: https: mcb.asm.org content 31 1 105 * Correction 1, January 2011.  *Page 116, column 2, last line: u201cWostonu201d should read u201cWooten.u201d* * Correction 2, April 2011.  *Page 105: The article byline should read as given above.* * Correction 3, July 2017.  *Fig. 11B, top: The actin blot was an inadvertent duplication of the actin blot in the bottom panel. The corrected image, obtained from original data, should appear as shown below. This change does not affect the interpretation of the data and conclusion of the study.* Here is the original Figure 11B, marked for a potential duplication with red boxes, and reported to the journal in September 2016. ![file] I thank the authors for correcting this error. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
Molecularly Engineering Triptolide with Aptamers for High Specificity and Cytotoxicity for Triple-Negative Breast Cancer
Authors: Lili Ai
Yongbo Peng
Xue-Qiang Wang
Jiaxuan He
Weihong Tan
Tianhuan Peng
Zhengyu Deng
Journal: Journal of the American Chemical Society (2020)
Discipline: CHEMISTRY
Keywords: Triple-negative breast cancer; TNBC; targeted therapy; aptamer-drug conjugate; AS1411-triptolide conjugate
Affiliations: Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, People’s Republic of China, Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, and The Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China, Foundation for Applied Molecular Evolution, 13709 Progress Boulevard, Alachua, Florida 32615, United States

Abstract:  Triple-negative breast cancer (TNBC) lacks three important receptors, ER, PR, and HER2. It is more aggressive and more likely to relapse after treatment, thus has been identified as one of the most malignant breast cancer types. The development of efficient targeted TNBC therapy is an important research topic in TNBC treatment. We report the development of a new aptamer-drug conjugate (ApDC), AS1411-triptolide conjugate (ATC), as targeted therapy for the treatment of TNBC with high efficacy. The conjugate possesses excellent specificity and high cytotoxicity against the MDA-MB-231 cell line. The advantages of our newly invented ATC are further highlighted by its excellent in vivo anti-TNBC efficacy and negligible side effects toward healthy organs. 

Retracted: No

PubPeer comments:
 partial duplication - could the authors please check? ![file] ,
Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells
Authors: Claire B Pollock
Amardeep S Dhillon
Senji Shirasawa
Takehiko Sasazuki
Walter Kolch
Journal: Cancer research (2005)
Discipline: CLINICAL MEDICINE
Keywords: RAS oncogenes; tumorigenesis; K-RAS; cytoskeletal disruption; cell adhesion
Affiliations: The Beatson Institute for Cancer Research, Garscube Estate, Bearsden, United Kingdom.

Abstract:  RAS oncogenes are thought to play a role at multiple stages of tumorigenesis. The role and mechanisms by which RAS oncogenes maintain the transformed state of human cancer cells are poorly understood. Here, we have studied the role of oncogenic K-RAS in maintaining cytoskeletal disruption, cell adhesion and motility in metastatic colon carcinoma cells. Targeted deletion of K-RAS(G13D) from HCT116 colon carcinoma cells restored their ability to assemble stress fibers and focal adhesions/complexes, accompanied by increased cell-matrix adhesion and reduced motility. We further show that oncogenic K-Ras induces high Rho activity, but uncouples Rho from stress fiber formation. This uncoupling required the maintenance of high levels of the activator protein-1 family member, Fra-1, via a mitogen-activated protein/extracellular signal-regulated kinase-dependent pathway. We also show that PI3-kinase signaling is required for the motility of HCT116 cells downstream of oncogenic K-Ras. Our findings suggest that mutated K-RAS oncogenes are essential for maintenance of the transformed and invasive phenotype of human colon cancer cells. 

Retracted: No

PubPeer comments:
 Figure 5C. Much more similar than you would expect. https: imgur.com 2gUY7aG ,
Selective cytotoxicity against human osteosarcoma cells by a novel synthetic C-1 analogue of 7-deoxypancratistatin is potentiated by curcumin
Authors: Siyaram Pandey
Phillip Tremblay
Dennis Ma
Kevinjeet Mahngar
Tomas Hudlicky
Jonathan Collins
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: pancratistatin; apoptosis; synthetic analogues; osteosarcoma; mitochondrial targeting
Affiliations: Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.

Abstract:  The natural compound pancratistatin (PST) is a non-genotoxic inducer of apoptosis in a variety of cancers. It exhibits cancer selectivity as non-cancerous cells are markedly less sensitive to PST. Nonetheless, PST is not readily synthesized and is present in very low quantities in its natural source to be applied clinically. We have previously synthesized and evaluated several synthetic analogues of 7-deoxypancratistatin, and found that JC-TH-acetate-4 (JCTH-4), a C-1 acetoxymethyl analogue, possessed similar apoptosis inducing activity compared to PST. In this study, notoriously chemoresistant osteosarcoma (OS) cells (Saos-2, U-2 OS) were substantially susceptible to JCTH-4-induced apoptosis through mitochondrial targeting; JCTH-4 induced collapse of mitochondrial membrane potential (MMP), increased reactive oxygen species (ROS) production in isolated mitochondria, and caused release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from isolated mitochondria. Furthermore, JCTH-4 selectively induced autophagy in OS cells. Additionally, we investigated the combinatory effect of JCTH-4 with the natural compound curcumin (CC), a compound found in turmeric spice, previously shown to possess antiproliferative properties. CC alone had no observable effect on Saos-2 and U-2 OS cells. However, when present with JCTH-4, CC was able to enhance the cytotoxicity of JCTH-4 selectively in OS cells. Such cytotoxicity by JCTH-4 alone and in combination with CC was not observed in normal human osteoblasts (HOb) and normal human fetal fibroblasts (NFF). Therefore, this report illustrates a new window in combination therapy, utilizing a novel synthetic analogue of PST with the natural compound CC, for the treatment of OS. 

Retracted: No

PubPeer comments:
 Two images in Figure 6c of Investigational New Drugs (2012) - doi: 10.1007 s10637-011-9668-7 also seem to appear in Figure 7B of PLoS ONE (2011) - doi: 10.1371 journal.pone.0028780, but are described differently. Could the authors please check? *** Original ![file] ![file] *** Brightness enhanced ![file] ![file] ,
Suppression of epileptogenesis-associated changes in response to seizures in FGF22-deficient mice
Authors: Hisashi Umemori
Clara H Lee
Journal: Frontiers in Cellular Neuroscience (2013)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: fibroblast growth factor 22; hilar cell death; hilar ectopic dentate granule cells; mossy fiber sprouting; neurogenesis
Affiliations: Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School Ann Arbor, MI, USA.

Abstract:  In the developing hippocampus, fibroblast growth factor (FGF) 22 promotes the formation of excitatory presynaptic terminals. Remarkably, FGF22 knockout (KO) mice show resistance to generalized seizures in adults as assessed by chemical kindling, a model that is widely used to study epileptogenesis (Terauchi et al., 2010). Repeated injections of low dose pentylenetetrazol (PTZ) induce generalized seizures ("kindled") in wild type (WT) mice. With additional PTZ injections, FGF22KO mice do show moderate seizures, but they do not kindle. Thus, analyses of how FGF22 impacts seizure susceptibility will contribute to the better understanding of the molecular and cellular mechanisms of epileptogenesis. To decipher the roles of FGF22 in the seizure phenotype, we examine four pathophysiological changes in the hippocampus associated with epileptogenesis: enhancement of dentate neurogenesis, hilar ectopic dentate granule cells (DGCs), increase in hilar cell death, and formation of mossy fiber sprouting (MFS). Dentate neurogenesis is enhanced, hilar ectopic DGCs appeared, and hilar cell death is increased in PTZ-kindled WT mice relative to PBS-injected WT mice. Even in WT mice with fewer PTZ injections, which showed only mild seizures (so were not kindled), neurogenesis, hilar ectopic DGCs, and hilar cell death are increased, suggesting that mild seizures are enough to induce these changes in WT mice. In contrast, PTZ-injected FGF22KO mice do not show these changes despite having moderate seizures: neurogenesis is rather suppressed, hilar ectopic DGCs do not appear, and hilar cell death is unchanged in PTZ-injected FGF22KO mice relative to PBS-injected FGF22KO mice. These results indicate that FGF22 plays important roles in controlling neurogenesis, ectopic migration of DGCs, and hilar cell death after seizures, which may contribute to the generalized seizure-resistant phenotype of FGF22KO mice and suggests a possibility that inhibition of FGF22 may alleviate epileptogenesis. 

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. ,
Timing requirements for insulin/IGF-1 signaling in C. elegans
Authors: Cynthia Kenyon
Douglas K Crawford
Andrew Dillin
Journal: Science (2002)
Discipline: Multidisciplinary
Keywords: insulin/IGF-1 signaling pathway; longevity; reproduction; diapause; Caenorhabditis elegans
Affiliations: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-0448, USA.

Abstract:  The insulin/IGF-1 (where IGF-1 is insulin-like growth factor-1) signaling pathway influences longevity, reproduction, and diapause in many organisms. Because of the fundamental importance of this system in animal physiology, we asked when during the animal's life it is required to regulate these different processes. We find that in Caenorhabditis elegans, the pathway acts during adulthood, to relatively advanced ages, to influence aging. In contrast, it regulates diapause during development. In addition, the pathway controls longevity and reproduction independently of one another. Together our findings show that life-span regulation can be dissociated temporally from phenotypes that might seem to decrease the quality of life. 

Retracted: No

PubPeer comments:
 Fig. 3D, Fig. 3E - More similar than expected. Could authors check please? ![file] , 
 #1 To clarify, the BLUE curves are supposed to be identical in all of these panels (including panels A-N); they represent the untreated control, repeated to provide a reference. (The blue bars in the bar charts are also all identical.) The issue here is the similarity in the RED curves between panels D and E. ,
Ku86 preserves chromatin integrity in cells adapted to high NaCl
Authors: Natalia I Dmitrieva
Maurice B Burg
André Nussenzweig
Arkady Celeste
Journal: Proceedings of the National Academy of Sciences of the United States of America (2005)
Discipline: Multidisciplinary
Keywords: DNA breaks; Ku86; DNA-PK; high NaCl; chromosomal integrity
Affiliations: Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, and Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 

Abstract:  Cells adapted to high NaCl have many DNA breaks both in cell culture and in the renal inner medulla in vivo; yet they survive, function, and even proliferate. Here, we show that Ku86 is important for maintaining chromosomal integrity despite the continued presence of DNA breaks. The Ku heterodimer is part of DNA-dependent PK (DNA-PK), a complex that contributes by nonhomologous end joining to repair of double-strand breaks. We demonstrate that cells deficient in Ku86, but not cells deficient in DNA-PKcs (the catalytic subunit of DNA-PK), are hypersensitive to high NaCl as manifested by profound inhibition of proliferation, aberrant mitosis, and increased chromosomal fragmentation. Lower eukaryotes, including the soil nematode Caenorhabditis elegans, lack a DNA-PKcs homologue but are able to adapt to high NaCl. We show that cells of C. elegans adapted to high NaCl have many DNA breaks, similar to the mammalian cells adapted to high NaCl. Ku86 mutant C. elegans as well as C. elegans fed with cku86 dsRNA also display hypersensitivity to high NaCl, characterized by a reduced number of progeny and prolonged generation time in high NaCl. We propose that Ku86 ameliorates the effects of high NaCl-induced DNA breaks in adapted cells by supporting alignment of the broken ends of the DNA and thus maintaining integrity of the fragmented chromatin. 

Retracted: No

PubPeer comments:
 Figure 1B. https: imgur.com oTMt8P1 ,
Decapping enzyme 1A breaks X-chromosome symmetry by controlling Tsix elongation and RNA turnover
Authors: Jeannie T Lee
Eric Aeby
Brian C Del Rosario
Wilhelm Haas
Yong-Woo Lee
Myriam Boukhali
Andrea Kriz
Hyun Jung Oh
Hun-Goo Lee
Journal: Nature Cell Biology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: allelic asymmetry; epigenetics; X-chromosome inactivation; BioRBP; RNA-proteomic method
Affiliations: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA., Department of Genetics, Harvard Medical School, Boston, MA, USA., Massachusetts General Hospital Cancer Center, Boston, MA, USA., Department of Medicine, Harvard Medical School, Boston, MA, USA., Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA. ., Department of Genetics, Harvard Medical School, Boston, MA, USA. .

Abstract:  How allelic asymmetry is generated remains a major unsolved problem in epigenetics. Here we model the problem using X-chromosome inactivation by developing "BioRBP", an enzymatic RNA-proteomic method that enables probing of low-abundance interactions and an allelic RNA-depletion and -tagging system. We identify messenger RNA-decapping enzyme 1A (DCP1A) as a key regulator of Tsix, a noncoding RNA implicated in allelic choice through X-chromosome pairing. DCP1A controls Tsix half-life and transcription elongation. Depleting DCP1A causes accumulation of X-X pairs and perturbs the transition to monoallelic Tsix expression required for Xist upregulation. While ablating DCP1A causes hyperpairing, forcing Tsix degradation resolves pairing and enables Xist upregulation. We link pairing to allelic partitioning of CCCTC-binding factor (CTCF) and show that tethering DCP1A to one Tsix allele is sufficient to drive monoallelic Xist expression. Thus, DCP1A flips a bistable switch for the mutually exclusive determination of active and inactive Xs. 

Retracted: No

PubPeer comments:
 Figure 4 has several western blot duplications ![file] , 
 We deeply appreciate your inquiry of our manuscript . Upon being notified of your inquiry, I immediately took steps to look into the serious concerns you raised with the identical figure in the Figure 4C and Figure 4E or Figure 4D and Figure 4F. We carefully checked our manuscript and raw data and lab records. I am confident about the validity and strength of the conclusion made in our manuscript. The results in Figure 4C-F were saved in the same folder although separately (named as Figure 4C-F). However, when the figures were re-arranged in the Photoshop Figure 4, we mistakenly replicated the identical figure (Figure 4C and Figure 4E or Figure 4D and Figure 4F). We have contacted the editorial office and the journal have agreed to publish a correction. ,
Baicalein inhibits mitochondrial apoptosis induced by oxidative stress in cardiomyocytes by stabilizing MARCH5 expression
Authors: Yu Wang
Yi An
Qi Li
Yufang Gao
Dandan Xiao
Zhongjie Yu
Lin Zhao
Journal: Journal of Cellular and Molecular Medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MARCH5; apoptosis; baicalein; cardioprotection; mitophagy
Affiliations: Department of Emergency medicine, The Affiliated Hospital of Qingdao University, Qingdao, China., School of Medicine, Qingdao University, Qingdao, China., Institute for Translational Medicine, Qingdao University, Qingdao, China., School of Basic Medicine, Qingdao University, Qingdao, China., Nursing Department Office, The Affiliated Hospital of Qingdao University, Qingdao, China., Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Abstract:  Abnormal mitochondrial fission and mitophagy participate in the pathogenesis of many cardiovascular diseases. Baicalein is a key active component in the roots of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. It has been reported that baicalein can resist cardiotoxicity induced by several stress, but the mechanisms of baicalein operate in the protection of cardiomyocytes need to be researched further. Here we report that baicalein can promote cell survival under oxidative stress by up-regulating the expression level of MARCH5 in cardiomyocytes. Pre-treatment cells or mice with baicalein can stabilize the expression of MARCH5, which plays a crucial role in the regulation of mitochondrial network and mitophagy. Overexpressed MARCH5 is able to against H2 O2 and ischaemia/reperfusion (I/R) stress by suppressing mitochondrial fission and enhancing mitophagy, and then attenuate cells apoptosis. Altogether, our present study investigated that baicalein exerts a protective effect through regulating KLF4-MARCH5-Drp1 pathway, our research also provided a novel theoretical basis for the clinical application of baicalein. 

Retracted: No

PubPeer comments:
 A panel of micrographs has been duplicated and presented as something else (Figure 1E vs Figure 2F). ![file] ,
Fibroblast growth factor 21 (FGF21) inhibits chondrocyte function and growth hormone action directly at the growth plate
Authors: Alexei Kharitonenkov
Shufang Wu
Francesco De Luca
Amy Levenson
Journal: Journal of Biological Chemistry (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FGF21; growth plate; chondrocytes; GH; bone growth
Affiliations: Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania 19134, USA.

Abstract:  Fibroblast growth factor 21 (FGF21) modulates glucose and lipid metabolism during fasting. In addition, previous evidence indicates that increased expression of FGF21 during chronic food restriction is associated with reduced bone growth and growth hormone (GH) insensitivity. In light of the inhibitory effects on growth plate chondrogenesis mediated by other FGFs, we hypothesized that FGF21 causes growth inhibition by acting directly at the long bones' growth plate. We first demonstrated the expression of FGF21, FGFR1 and FGFR3 (two receptors known to be activated by FGF21) and β-klotho (a co-receptor required for the FGF21-mediated receptor binding and activation) in fetal and 3-week-old mouse growth plate chondrocytes. We then cultured mouse growth plate chondrocytes in the presence of graded concentrations of rhFGF21 (0.01-10 μg/ml). Higher concentrations of FGF21 (5 and 10 μg/ml) inhibited chondrocyte thymidine incorporation and collagen X mRNA expression. 10 ng/ml GH stimulated chondrocyte thymidine incorporation and collagen X mRNA expression, with both effects prevented by the addition in the culture medium of FGF21 in a concentration-dependent manner. In addition, FGF21 reduced GH binding in cultured chondrocytes. In cells transfected with FGFR1 siRNA or ERK 1 siRNA, the antagonistic effects of FGF21 on GH action were all prevented, supporting a specific effect of this growth factor in chondrocytes. Our findings suggest that increased expression of FGF21 during food restriction causes growth attenuation by antagonizing the GH stimulatory effects on chondrogenesis directly at the growth plate. In addition, high concentrations of FGF21 may directly suppress growth plate chondrocyte proliferation and differentiation. 

Retracted: No

PubPeer comments:
 In Figure 2. JamaEDX spectra of two different compounds (a) nanou2010Fe3O4@SiO2u2010NH2 and (b) nanou2010Fe3O4@SiO2u2010NH2@GA., there are fragments that seem to be very very similar!! The more troubling thing is that it seems that the numbers are trying to hide something! *** ![file] *** , 
 Figure 3 in this paper (DOI: 10.1002 aoc.4810) for (nanou2010Fe3O4@SiO2u2010NH2@GA), looks very similar to Figure 3 in another paper (DOI: 10.1016 j.poly.2019.04.015) that represents (Fe3O4@SiO2-NH-GA) and they both look very similar to Figure 5 in a 2020 paper (DOI: 10.1016 j.solidstatesciences.2020.106284) that is for (Fe3O4@tannic acid-Cu). *** ![file] *** ,