PReD-Bench/PRed-Bench huggingface dataset:
Calcium-independent phospholipase A2 localizes in and protects mitochondria during apoptotic induction by staurosporine
Authors: Konstantin Seleznev
Zhongmin Alex Ma
Keying Song
Chunying Zhao
Xu Hannah Zhang
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mitochondria; Reactive oxygen species; Cardiolipin; Phospholipase A2; iPLA2
Affiliations: Division of Experimental Diabetes and Aging, Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York 10029, USA.

Abstract:  Mitochondria-mediated production of reactive oxygen species (ROS) plays a key role in apoptosis. Mitochondrial phospholipid cardiolipin molecules are likely the main target of ROS because they are particularly rich in polyunsaturated fatty acids. They are also located in the inner mitochondrial membrane near the ROS-producing sites. Under physiological conditions mitochondria can repair peroxidative damage in part through a remodeling mechanism via the deacylation-reacylation cycle mediated by phospholipase A2 (PLA2) and acyl-coenzyme A-dependent monolysocardiolipin acyltransferase. Here we investigate whether group VIA Ca2+-independent PLA2 (iPLA2) plays a role in the protection of mitochondrial function from damage caused by mitochondrially generated ROS during apoptotic induction by staurosporine (STS). We show that iPLA2-expressing cells were relatively resistant to STS-induced apoptosis. iPLA2 localized to mitochondria even before apoptotic induction, and most iPLA2-associated mitochondria were intact in apoptotic resistant cells. Expression of iPLA2 in INS-1 cells prevented the loss of mitochondrial membrane potential, attenuated the release of cytochrome c, Smac/DIABLO, and apoptosis inducing factor from mitochondria, and reduced mitochondrial reactive oxygen species production. Inhibition of caspase 8 has little effect on STS-induced apoptosis in INS-1 cells. Finally, we found that STS down-regulated endogenous iPLA2 transcription in both INS-1 and iPLA2-expressing INS-1 cells without affecting the expression of group IV Ca2+-dependent PLA2. Together, our data indicate that iPLA2 is important for the protection of mitochondrial function from oxidative damage during apoptotic induction. Down-regulation of endogenous iPLA2 by STS may result in the loss of mitochondrial membrane repair functions and lead to mitochondrial failure and apoptosis. 

Retracted: No

PubPeer comments:
 ![file] There is a duplication in the Cytosol Cyt.c panel of the immunoblot of Figure 6A as showed in red boxes. Please check! ,
Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes
Authors: Colin Conway
Richard McCulloch
Michael L Ginger
J David Barry
Alison Browitt
Nicholas P Robinson
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Trypanosome antigenic variation; variant surface glycoprotein (VSG) genes; telomeres; DNA recombination; pathogen contingency gene systems
Affiliations: Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow, G11 6NU, Scotland, United Kingdom.

Abstract:  Trypanosome antigenic variation, involving differential expression of variant surface glycoprotein (VSG) genes, has a strong association with telomeres and with DNA recombination. All expressed VSGs are telomeric, and differential activation involves recombination into the telomeric environment or silencing/activation of subtelomeric promoters. A number of pathogen contingency gene systems associated with immune evasion involve telomeric loci, which has prompted speculation that chromosome ends provide conditions conducive for the operation of rapid gene switching mechanisms. Ku is a protein associated with eukaryotic telomeres that is directly involved in DNA recombination and in gene silencing. We have tested the hypothesis that Ku in trypanosomes is centrally involved in differential VSG expression. We show, via the generation of null mutants, that trypanosome Ku is closely involved in telomere length maintenance, more so for a transcriptionally active than an inactive telomere, but exhibits no detectable influence on DNA double strand break repair. The absence of Ku and the consequent great shortening of telomeres had no detectable influence either on the rate of VSG switching or on the silencing of the telomeric promoters of the VSG subset that is expressed in the tsetse fly. 

Retracted: No

PubPeer comments:
 Figure 7. Much more similar than you would expect. https: imgur.com HXEriT1 ,
miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway
Authors: Wenwen Li
Huicong Li
Xiaoguang Zhu
Journal: Biological research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Acute kidney injury; Dkk3; Wnt/β-catenin signaling pathway; miR-214.
Affiliations: Department of Nephrology, Huaihe Hospital of Henan University, No. 8, Baobei Road, Gulou District, Kaifeng, 475000, China. ., Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, 475000, China., Department of Nephrology, Huaihe Hospital of Henan University, No. 8, Baobei Road, Gulou District, Kaifeng, 475000, China.

Abstract:  Background: miR-214 was demonstrated to be upregulated in models of renal disease and promoted fibrosis in renal injury independent of TGF-β signaling in vivo. However, the detailed role of miR-214 in acute kidney injury (AKI) and its underlying mechanism are still largely unknown. Methods: In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell model were used to study AKI. The concentrations of kidney injury markers serum creatinine, blood urea nitrogen, and kidney injury molecule-1 were measured. The expressions of miR-214, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, were detected by RT-qPCR. The protein levels of Bcl-2, Bax, Dickkopf-related protein 3, β-catenin, c-myc, and cyclinD1 were determined by western blot. Cell apoptosis and caspase 3 activity were evaluated by flow cytometry analysis and caspase 3 activity assay, respectively. Luciferase reporter assay was used to confirm the interaction between miR-214 and Dkk3. Results: miR-214 expression was induced in ischemia-reperfusion (I/R)-induced AKI rat and hypoxic incubation of NRK-52E cells. Overexpression of miR-214 alleviated hypoxia-induced NRK-52E cell apoptosis while inhibition of miR-214 expression exerted the opposite effect. Dkk3 was identified as a target of miR-214. Anti-miR-214 abolished the inhibitory effects of DKK3 knockdown on hypoxia-induced NRK-52E cell apoptosis by inactivation of Wnt/β-catenin signaling. Moreover, miR-214 ameliorated AKI in vivo by inhibiting apoptosis and fibrosis through targeting Dkk3 and activating Wnt/β-catenin pathway. Conclusion: miR-214 ameliorates AKI by inhibiting apoptosis through targeting Dkk3 and activating Wnt/β-catenin signaling pathway, offering the possibility of miR-214 in the therapy of ischemic AKI. 

Retracted: No

PubPeer comments:
 Table 1. ![file] Expecting subgroup numbers to add up to 52 is surely not too much. ,
Approaches to therapy of prion diseases
Authors: Adriano Aguzzi
Charles Weissmann
Journal: Annual review of medicine (2005)
Discipline: CLINICAL MEDICINE
Keywords: transmissible spongiform encephalopathies; prion diseases; therapy; infectious agent; prion
Affiliations: Department of Neurodegenerative Disease/MRC Prion Unit, Institute of Neurology, Queen Square, London WC1N 3BG, UK. , Institute of Neuropathology, University Hospital, CH-8091 Zürich, Switzerland; email:

Abstract:  Devising approaches to the therapy of transmissible spongiform encephalopathies, or prion diseases, is beset by many difficulties. For one, the nature of the infectious agent, the prion, is understood only in outline, and its composition, structure, and mode of replication are still shrouded in mystery. In addition, the mechanism of pathogenesis is not well understood. Because clinical disease affects mainly the brain parenchyme, therapeutic agents must be able to traverse the brain-blood barrier (BBB) or have to be introduced directly into the cerebrospinal fluid or brain tissue. And finally, because the disease is usually recognized only after onset of severe clinical symptoms, the question arises as to whether the neurodegenerative processes can be reversed to any extent after a successful eradication of the agent. 

Retracted: No

PubPeer comments:
 https: steamtraen.blogspot.com 2020 07 how-bad-is-self-plagiarism-case-study.html ,
DNA damage invokes mismatch repair-dependent cyclin D1 attenuation and retinoblastoma signaling pathways to inhibit CDK2
Authors: Winfried Edelmann
Matthew W Strobeck
Erik S Knudsen
R Baskaran
Zhengdao Lan
Gustavo Leone
Zvjezdana Sever-Chroneos
Chi-Hyun Park
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DNA damage; cell cycle checkpoints; retinoblastoma tumor suppressor; mismatch repair complexes; RB dephosphorylation
Affiliations: Department of Cell Biology, University of Cincinnati, Cincinnati, Ohio 45267, USA.

Abstract:  DNA-damage evokes cell cycle checkpoints, which function to maintain genomic integrity. The retinoblastoma tumor suppressor (RB) and mismatch repair complexes are known to contribute to the appropriate cellular response to specific types of DNA damage. However, the signaling pathways through which these proteins impact the cell cycle machinery have not been explicitly determined. RB-deficient murine embryo fibroblasts continued a high degree of DNA replication following the induction of cisplatin damage, but were inhibited for G(2)/M progression. This damage led to RB dephosphorylation/activation and subsequent RB-dependent attenuation of cyclin A and CDK2 activity. In both Rb+/+ and Rb -/- cells, cyclin D1 expression was attenuated following DNA damage. As cyclin D1 is a critical determinant of RB phosphorylation and cell cycle progression, we probed the pathway through which cyclin D1 degradation occurs in response to DNA damage. We found that attenuation of endogenous cyclin D1 is dependent on multiple mismatch repair proteins. We demonstrate that the mismatch repair-dependent attenuation of endogenous cyclin D1 is critical for attenuation of CDK2 activity and induction of cell cycle checkpoints. Together, these studies couple the activity of the retinoblastoma and mismatch repair tumor suppressor pathways through the degradation of cyclin D1 and dual attenuation of CDK2 activity. 

Retracted: No

PubPeer comments:
 ![file] , 
 Figure 3B. https: imgur.com iwaw3A7 ,
Hsa_circ_0026134 expression promoted TRIM25- and IGF2BP3-mediated hepatocellular carcinoma cell proliferation and invasion via sponging miR-127-5p
Authors: Bo Zhou
Xudong Qu
Liang Zhu
Wei Zhang
Sheng Qian
Rong Liu
Jianhua Wang
Guowei Yang
Zhiping Yan
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: IGF2BP3; TRIM25; hepatocellular carcinoma; hsa_circ_0026134; miR-127-5p.
Affiliations: Department of Intervention Radiology, Zhongshan Hospital of Fudan University, No. 180 Fenglin Road, Xuhui, Shanghai 200032, China., Shanghai Institute of Medical Imaging, Shanghai 200032, China.

Abstract:  Increasing evidence shows that circular RNAs (circRNAs) play a regulatory role in cancer. In the present study, we aimed to investigate the characteristics and effects of hsa_circ_0026134 in hepatocellular carcinoma (HCC). We investigated hsa_circ_0026134 expression in 20 pairs of clinical tissues from HCC patients; expression of hsa_circ_0026134 in different cell lines; effect of hsa_circ_0026134 on proliferation and invasion of HCC cell lines; and the regulatory mechanisms and interactions among hsa_circ_0026134, miR-127-5p, tripartite motif-containing protein 25 (TRIM25) and insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). hsa_circ_0026134 expression was increased in HCC samples and cell lines. Down-regulation of hsa_circ_0026134 attenuated HCC cell proliferation and metastatic properties. Micro (mi)RNA (miR)-127-5p was sponged by hsa_circ_0026134. Rescue experiments indicated that inhibition of miR-127-5p expression promoted cell proliferation and invasion even after hsa_circ_0026134 silencing. TRIM25 and IGF2BP3 were targets of miR-127-5p. Overexpression of TRIM25 or IGF2BP3 promoted cell proliferation and invasion in cells overexpressing miR-127-5p. Down-regulation of hsa_circ_0026134 suppressed TRIM25- and IGF2BP3-mediated HCC cell proliferation and invasion via promotion of miR-127-5p expression, which have been confirmed by luciferase reporter assay. The present study provides a new treatment target for HCC. 

Retracted: No

PubPeer comments:
 Figure 5F appears to have 2 images which overlap, although the coloring is slightly different. *** ![file] , 
 #1 Dear Editor: There may be some typesetting problem, I have applied for replacement, thank you for pointing out.![file] , 
 Could the authors please provide an update? , 
 ![file] I have been updated the figures ,
Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation
Authors: Elias Hobeika
Emmanuel Derudder
Michael Reth
Yoshiteru Sasaki
Marc Schmidt-Supprian
Roberta Pelanda
Klaus Rajewsky
Journal: Immunity (2006)
Discipline: IMMUNOLOGY
Keywords: BAFF-R; NF-kappaB; B cells; development; survival
Affiliations: The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. 

Abstract:  The maintenance of mature B cells hinges on signals emitted from the BAFF-R cell-surface receptor, but the nature of these signals is incompletely understood. Inhibition of canonical NF-kappaB transcription factor activity through ablation of the essential scaffold protein NEMO arrests B cell development at the same stage as BAFF-R deficiency. Correspondingly, activation of this pathway by constitutively active IkappaB Kinase2 renders B cell survival independent of BAFF-R:BAFF interactions and prevents proapoptotic PKCdelta nuclear translocation. In addition, canonical NF-kappaB activity mediates differentiation and proper localization of follicular and marginal zone B cells in the absence of BAFF-R, but not CD19. By replacing BAFF-R signals, constitutive canonical NF-kappaB signaling, a hallmark of various B cell lymphomas, causes accumulation of resting B cells and promotes their proliferation and survival upon activation, but does not per se induce lymphomagenesis. Therefore, canonical NF-kappaB activity can substitute for BAFF-R signals in B cell development and pathogenesis. 

Retracted: No

PubPeer comments:
 Figure 6A. Much more similar than expected. ![file] ,
RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass
Authors: Serge Ferrari
Nicolas Bonnet
Emmanuel Biver
Lucie Bourgoin
Eleni Douni
Journal: Journal of Clinical Investigation (2019)
Discipline: CLINICAL MEDICINE
Keywords: Bone Biology; Bone disease; Muscle; Muscle Biology; Osteoporosis.
Affiliations: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland., Biomedical Sciences Research Center "Alexander Fleming," Athens, Greece., Department of Biotechnology, Agricultural University of Athens, Athens, Greece.

Abstract:  Receptor activator of Nfkb ligand (RANKL) activates, while osteoprotegerin (OPG) inhibits, osteoclastogenesis. In turn a neutralizing Ab against RANKL, denosumab improves bone strength in osteoporosis. OPG also improves muscle strength in mouse models of Duchenne's muscular dystrophy (mdx) and denervation-induce atrophy, but its role and mechanisms of action on muscle weakness in other conditions remains to be investigated. We investigated the effects of RANKL inhibitors on muscle in osteoporotic women and mice that either overexpress RANKL (HuRANKL-Tg+), or lack Pparb and concomitantly develop sarcopenia (Pparb-/-). In women, denosumab over 3 years improved appendicular lean mass and handgrip strength compared to no treatment, whereas bisphosphonate did not. HuRANKL-Tg+ mice displayed lower limb force and maximal speed, while their leg muscle mass was diminished, with a lower number of type I and II fibers. Both OPG and denosumab increased limb force proportionally to the increase in muscle mass. They markedly improved muscle insulin sensitivity and glucose uptake, and decrease anti-myogenic and inflammatory gene expression in muscle, such as myostatin and protein tyrosine phosphatase receptor-γ. Similarly, in Pparb-/-, OPG increased muscle volume and force, while also normalizing their insulin signaling and higher expression of inflammatory genes in skeletal muscle. In conclusions, RANKL deteriorates, while its inhibitor improves, muscle strength and insulin sensitivity in osteoporotic mice and humans. Hence denosumab could represent a novel therapeutic approach for sarcopenia. 

Retracted: No

PubPeer comments:
 This paper has a 2020 Corrigendum found here: https: www.jci.org articles view 138278#F1 It reads:  Following the publication of this article, errors were noted in Figure 1, B and C. The authors were able to provide the original data, and a corrected version of Figure 1 appears below. , 
 Could the authors also please take a look at Figure 6F? A concern was pointed out to me by a reader. * Red boxes: The WT and Pparb- - Opg-Fc panels appear to show an overlap. ![file] ,
The Effect of Magnesium and Vitamin E Co-Supplementation on Glycemic Control and Markers of Cardio-Metabolic Risk in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Mehri Jamilian
Niloufar Kazemi Sabzevar
Zatollah Asemi
Journal: Hormone and Metabolic Research (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: magnesium; vitamin E; co-supplementation; glycemic control; cardio-metabolic risk
Affiliations: Endocrinology and Metabolism Research Center, Arak University of Medical Sciences, Arak, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Abstract:  Data on the effects of magnesium and vitamin E co-supplementation on glycemic control and markers of cardio-metabolic risk of patients with polycystic ovary syndrome (PCOS) were collected. This investigation was conducted to evaluate the effects of magnesium and vitamin E co-supplementation on glycemic control and markers of cardio-metabolic risk in women with PCOS. This randomized, double-blind, placebo-controlled trial was carried out on 60 women with PCOS, aged 18-40 years old. Participants were randomly divided into two groups to receive 250 mg/day magnesium plus 400 mg/day vitamin E supplements or placebo (n=30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention to quantify related variables. After the 12-week intervention, compared with the placebo, magnesium and vitamin E co-supplementation led to a significant reduction in serum insulin levels (-1.1±3.0 vs. +1.6±3.7 μIU/ml, p=0.003) and homeostatic model of assessment for insulin resistance (-0.2±0.7 vs. +0.4±0.9, p=0.002), and a significant increase in the quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.009±0.02, p=0.003). Furthermore, magnesium plus vitamin E supplementation significantly decreased serum triglycerides (-15.0±24.4 vs. +6.7±22.2 mg/dl, p=0.001) and VLDL-cholesterol concentrations (-3.0±4.9 vs. +0.6±2.4 mg/dl, P=0.01) compared with the placebo. A trend toward a greater decrease in total cholesterol levels was observed in magnesium plus vitamin E group compared to placebo group (-7.0±32.6 vs. +8.1±26.6 mg/dl, p=0.05). In conclusion, magnesium and vitamin E co-supplementation for 12 weeks to PCOS women had beneficial effects on parameters of insulin metabolism and few markers of cardio-metabolic risk. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A136 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 18 publications have an expression of concern, and 6 have been retracted. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Sorting of Small RNAs into Arabidopsis Argonaute Complexes Is Directed by the 5′ Terminal Nucleotide
Authors: Emily Hodges
Huanyu Zhou
Yijun Qi
Liang Wu
Tao Cai
Yugang Hu
Yemiao Chen
Fangrui Ni
Shijun Mi
Chengzu Long
She Chen
Shan Li
Gregory J Hannon
Journal: Cell (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Argonaute proteins; small RNAs; RNAi effector complexes; Arabidopsis; AGO complexes
Affiliations: National Institute of Biological Sciences, No.7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.

Abstract:  Argonaute (AGO) proteins recruit small RNAs to form the core of RNAi effector complexes. Arabidopsis encodes ten AGO proteins and a large network of small RNAs. How these small RNAs are sorted into specific AGO complexes remains largely unknown. We have cataloged small RNAs resident in four AGO complexes. We found that AGO2 and AGO4 preferentially recruit small RNAs with a 5' terminal adenosine, whereas AGO1 harbors microRNAs (miRNAs) that favor a 5' terminal uridine. AGO5 predominantly binds small RNAs that initiate with cytosine. Changing the 5' terminal nucleotide of an miRNA predictably redirected it into a different AGO complex and alters its biological activity. These results reveal a role for small RNA sequences in assorting among AGO complexes. This suggests that specialization of AGO complexes might involve remodeling the 5' end-binding pocket to accept certain small RNA sequences, perhaps explaining the evolutionary drive for miRNAs to initiate with uridine. 

Retracted: No

PubPeer comments:
 Figure 2B u2013 the sum of percentages is bigger than 100% in some cases. For example, in Total group 28+17+8+44+9+8 = 114%. AGO2 group 38+10+25+11+20+6=110% Could authors check it please? ![file] , 
 Hi Grammodes, As the authors have indicated in the legend of Figure 2B,  Some small RNAs can match more than one category of the sequences listed, so the sum of the numbers may be bigger than the input total number. ,
Paeoniflorin inhibits proliferation and induces apoptosis of human glioma cells via microRNA-16 upregulation and matrix metalloproteinase-9 downregulation
Authors: Zhonghua Qi
Zhenqing Wei
Weihua Li
Yongshun Zhao
Siwei Liu
Yanwei Chen
Pin Wang
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Paeoniflorin; MicroRNA-16; MMP-9; Glioma; Apoptosis
Affiliations: Department of Neurosurgery, 1st Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China., Academic Affairs Office, Dalian Medical University, Dalian, Liaoning 116044, P.R. China., Department of Pharmacy, 1st Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.

Abstract:  Paeoniflorin is one of the active ingredients of the commonly used herbal medicine derived from Paeonia, which exhibits anticancer properties. MicroRNA-16 (miR-16) is upregulated in CD133(-) cells, but downregulated in CD133(+) cells from glioma tissue. Matrix metalloproteinase-9 (MMP-9) expression in glioma tissue samples is significantly higher than that in healthy brain tissue samples. Therefore, miR-16 and MMP-9 expression may be associated with glioma pathogenesis. In the present study, the effects of paeoniflorin on glioma were analyzed. U87 cells were treated with paeoniflorin at 0, 5, 10 and 20 μΜ concentrations. The results suggested that paeoniflorin inhibited U87 cell proliferation and accelerated cell apoptosis. In the present study paeoniflorin treatment increased miR-16 expression and reduced MMP-9 protein expression in U87 cells. Additionally, the results of the present study suggested that miR-16 may regulate MMP-9 expression in miR-16-transfected U87 cells. Furthermore, anti-miR-16 antibodies were used in order to investigate the apoptotic effects of paeoniflorin on U87 cells. The results demonstrated that paeoniflorin inhibits proliferation and induces apoptosis of human glial cells, via miR-16 upregulation and MMP-9 downregulation. 

Retracted: No

PubPeer comments:
 Figure 3 -  Flow cytometric analysis of cell apoptosis. (A) U87 cell apoptosis increased following paeoniflorin treatment for 24 h in a dose-dependent manner, according to Annexin V-fluorescein isothiocyanate PI . Just the first two panels here, to highlight the unexpected regions of dots. ![file] , 
 Fig 4B.  MMP-9 protein expression . With, *[above]*. Fig 7A from [Xiao et al (2015)] .  MMP-9 agonist suppresses the effect of mangiferin on U87 glioma cells. (A and B) Representative gelatin zymography analysis of MMP-9 expression . Unexpected similarities. ![file] ,
Post-translational modifications of cardiac tubulin during chronic heart failure in the rat
Authors: Christian Poüs
Pierre-François Méry
Renée Ventura-Clapier
Rodolphe Fischmeister
Souad Belmadani
Journal: Molecular and Cellular Biochemistry (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cytoskeletal reorganization; cellular remodeling; mechanical function; pressure overload hypertrophy; post-translational modifications
Affiliations: INSERM U-446, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.

Abstract:  Cytoskeletal reorganization has been shown to participate in cellular remodeling and in the alterations of mechanical function of isolated cardiomyocytes during pressure overload hypertrophy. Post-translational modifications of tubulin towards stabilization of microtubules have also been described in animal models of compensatory hypertrophy, but the status of the microtubules network in end stage heart failure is not clearly established. Using a rat model of congestive heart failure (CHF) induced by aortic banding, we studied the expression of alpha- and beta-tubulin, as well as their post-translational modification and distribution in the soluble and polymerized fraction by immunoblotting. We found an accumulation of alpha- and beta-tubulin protein content specifically in the soluble fraction with no change in the polymerized fraction. Amongst the several variants of alpha-tubulin examined, only detyrosinated Glu-tubulin and deglutamylated delta2-tubulin levels were selectively increased during heart failure. Glu-tubulin accumulated in the polymerized fraction while delta2-tubulin levels were increased in the soluble fraction in CHF hearts. These results show that a profound remodeling of the microtubule network occurs in heart failure. This remodeling suggests an increase in the stability of the microtubule network which is discussed in terms of possible functional consequences. 

Retracted: No

PubPeer comments:
 ![file] ,
Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites
Authors: Huiying Lv
Jinlan Jiang
Yingnan Cui
Bai Yang
Xiuying Li
Liya Wu
Hua Yao
Zhenhong Wei
Jing Li
Hao Zhang
Journal: International Journal of Nanomedicine (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Fe3O4 nanoparticles; mesenchymal stem cells; migration; polydopamine.
Affiliations: Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China, ., State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, People's Republic of China.

Abstract:  Background: Developing new methods to deliver cells to the injured tissue is a critical factor in translating cell therapeutics research into clinical use; therefore, there is a need for improved cell homing capabilities. Materials and methods: In this study, we demonstrated the effects of labeling rat bone marrow-derived mesenchymal stem cells (MSCs) with fabricated polydopamine (PDA)-capped Fe3O4 (Fe3O4@PDA) superparticles employing preassembled Fe3O4 nanoparticles as the cores. Results: We found that the Fe3O4@PDA composite superparticles exhibited no adverse effects on MSC characteristics. Moreover, iron oxide nanoparticles increased the number of MSCs in the S-phase, their proliferation index and migration ability, and their secretion of vascular endothelial growth factor relative to unlabeled MSCs. Interestingly, nanoparticles not only promoted the expression of C-X-C chemokine receptor 4 but also increased the expression of the migration-related proteins c-Met and C-C motif chemokine receptor 1, which has not been reported previously. Furthermore, the MSC-loaded nanoparticles exhibited improved homing and anti-inflammatory abilities in the absence of external magnetic fields in vivo. Conclusion: These results indicated that iron oxide nanoparticles rendered MSCs more favorable for use in injury treatment with no negative effects on MSC properties, suggesting their potential clinical efficacy. 

Retracted: No

PubPeer comments:
 Figure 2C appears to have two images which overlap, when one is rotated approximately 24u00b0. *** ![file] *** Full figure ![file] , 
 Figure 7A and 7C appear to have two images which overlap; red boxes roughly identify area of overlap. If I understand the caption correctly, these should have been treated differently. *** Close up ![file] *** Figure figure ![file] , 
 Also Figure 6A. *** ![file] , 
 And an additional probable overlap in Figure 7. *** ![file] ,
TATDN1 promotes the development and progression of breast cancer by targeting microRNA-140-3p
Authors: X-Y Yu
H-R Tan
J-R Tian
D Yang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA TATDN1; microRNA-140-3p; breast cancer; proliferation; cell cycle progression
Affiliations: Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China. .

Abstract:  Objective: To explore whether long non-coding RNA (lncRNA) TATDN1 can promote the proliferation and cell cycle progression of breast cancer cells by adsorbing microRNA-140-3p, thus participating in the development of breast cancer (BCa). Patients and methods: Expressions of TATDN1 and microRNA-140-3p in BCa tissues and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, TATDN1 expression in BCa cell lines was detected as well. Regulatory effects of TATDN1 and microRNA-140-3p on proliferation and cell cycle progression of BCa cells were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. The binding relationship of microRNA-140-3p to NOVA1 and TATDN1 was examined by dual-luciferase reporter gene assay. Finally, rescue experiments were conducted to explore whether TATDN1 can regulate NOVA1 expression by adsorbing microRNA-140-3p to exert its biological function in BCa. Results: TATDN1 was highly expressed in BCa tissues and cell lines. Upregulation of TATDN1 promoted the proliferative potential and cell cycle progression of MCF-7 and MDA-MB-231 cells. Dual-luciferase reporter gene assay indicated that TATDN1 could bind to microRNA-140-3p, which was lowly expressed in BCa. Overexpression of microRNA-140-3p inhibited the proliferative potential and cell cycle progression of MCF-7 and MDA-MB-231 cells. Moreover, microRNA-140-3p partially inhibited the role of TATDN1 in regulating cellular behaviors of BCa cells. NOVA1 was predicted to be the target gene of microRNA-140-3p. Overexpression of NOVA1 partially abolished the inhibitory effects of microRNA-140-3p on proliferation and cell cycle progression of MCF-7 and MDA-MB-231 cells. Conclusions: TATDN1 promotes the proliferative potential and cell cycle progression of BCa cells through adsorbing microRNA-140-3p to upregulate NOVA1 expression. 

Retracted: No

PubPeer comments:
 Fig 1D.  Survival curve plotted based on follow-up data of enrolled BCa patients indicated the diagnostic potential of TATDN1 in BCa (AUC=0.8567, cut-off value=1.324). ![file] This is not a survival curve. What a ROC curve is doing here, and how it was derived, is anyone s guess. ,
Inhibition of glioblastoma growth and angiogenesis by gambogic acid: an in vitro and in vivo study
Authors: Xiao-Tang Wang
Lan Yang
Li Zhao
Lei Qiang
Qing-Long Guo
Fei-Fei Nie
Wei Liu
Yan-Jun Ma
Hong-Yan Gu
Qi-Dong You
Yong Yang
Qi Qi
Na Lu
Journal: Biochemical Pharmacology (2008)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Gambogic acid; Anticancer activity; Glioblastoma; Blood-brain barrier; Mitochondrial pathway
Affiliations: Department of Physiology, Jiangsu Key Laboratory of Carcinogenesis and intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.

Abstract:  Gambogic acid (GA) is the major active ingredient of gamboge, a brownish to orange resin exuded from Garcinia hanburryi tree in Southeast Asia. The present study aims to demonstrate that gambogic acid (GA) has potent anticancer activity for glioblastoma by in vitro and in vivo study. Rat brain microvascular endothelial cells (rBMEC) were used as an in vitro model of the blood-brain barrier (BBB). To reveal an involvement of the intrinsic mitochondrial pathway of apoptosis, the mitochondrial membrane potential and the western blot evaluation of Bax, Bcl-2, Caspase-3, caspase-9 and cytochrome c released from mitochondria were performed. Angiogenesis was detected by CD31 immunochemical study. The results showed that the uptake of GA by rBMEC was time-dependent, which indicated that it could pass BBB and represent a possible new target in glioma therapy. GA could cause apoptosis of rat C6 glioma cells in vitro in a concentration-dependent manner by triggering the intrinsic mitochondrial pathway of apoptosis. In vivo study also revealed that i.v. injection of GA once a day for two weeks could significantly reduce tumor volumes by antiangiogenesis and apoptotic induction of glioma cells. Collectively, the current data indicated that GA may be of potential use in treatment of glioblastoma by apoptotic induction and antiangiogenic effects. 

Retracted: No

PubPeer comments:
 Fig. 6B ![file] ![file] ,
Activation of IRS-2-mediated signal transduction by IGF-1, but not TGF-alpha or EGF, augments pancreatic beta-cell proliferation
Authors: Daniel R Twardzik
Christopher J Rhodes
Sigrun R Hugl
Melissa K Lingohr
Lorna M Dickson
Jill F McCuaig
Journal: Diabetes (2002)
Discipline: CLINICAL MEDICINE
Keywords: Transforming growth factor; Epidermal growth factor; Signal transduction; INS-1 cells; Phosphorylation
Affiliations: Pacific Northwest Research Institute, Seattle, Washington 98122, USA.

Abstract:  Transforming growth factor (TGF)-alpha- and epidermal growth factor (EGF)-induced signal transduction was directly compared with that of glucose and insulin-like growth factor-1 (IGF-1) in INS-1 cells. TGF-alpha/EGF transiently (&lt;20 min) induced phosphorylation of extracellular-regulated kinase (Erk)-1/2 (&gt;20-fold), glycogen synthase kinase (GSK)-3 (&gt;10-fold), and protein kinase B (PKB) (Ser(473) and Thr(308)), but did not increase [(3)H]thymidine incorporation. In contrast, phosphorylation of Erk1/2, GSK-3, and PKB in response to glucose and IGF-1 was more prolonged (&gt;24 h) and, though not as robust as TGF-alpha/EGF, did increase beta-cell proliferation. Phosphorylation of p70(S6K) was also increased by IGF-1/glucose, but not by TGF-alpha/EGF, despite upstream PKB activation. It was found that IGF-1 induced phosphatidylinositol 3-kinase (PI3K) association with insulin receptor substrate (IRS)-1 and -2 in a glucose-dependent manner, whereas TGF-alpha/EGF did not. The importance of specific IRS-2-mediated signaling events was emphasized in that adenoviral-mediated overexpression of IRS-2 further increased glucose/IGF-1-induced beta-cell proliferation (more than twofold; P &lt; 0.05) compared with control or adenoviral-mediated IRS-1 overexpressing INS-1 cells. Neither IRS-1 nor IRS-2 overexpression induced a beta-cell proliferative response to TGF-alpha/EGF. Thus, a prolonged activation of Erk1/2 and PI3K signaling pathways is important in committing a beta-cell to a mitogenic event, and it is likely that this sustained activation is instigated by signal transduction occurring specifically through IRS-2. 

Retracted: No

PubPeer comments:
 Fig. 4A u2013 More similar than expected ![file] ,
miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN
Authors: X L Liu
Y P Shi
S Li
G L Liu
Journal: Neoplasma (2020)
Discipline: CLINICAL MEDICINE
Keywords: Thyroid cancer; miR-17-5p; PTEN; cell proliferation; apoptosis
Affiliations: Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, China.

Abstract:  Thyroid cancer is one common endocrine malignancy with various pathological types. MicroRNAs (miRNAs) play essential roles in development, prognosis and treatment of thyroid cancer. However, the role of miR-17-5p in thyroid cancer progression and its mechanism remain poorly understood. The expressions of miR-17-5p and phosphatase and tensin homolog (PTEN) were measured in thyroid cancer tissues and cells by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. The protein levels of biomarkers in autophagy or protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway were analyzed by western blot. The interaction between miR-17-5p and PTEN was probed by luciferase activity assay. We found that miR-17-5p expression was elevated and PTEN level was reduced in thyroid cancer tissues and cells compared with their corresponding controls. Knockdown of miR-17-5p or overexpression of PTEN suppressed cell proliferation and autophagy but promoted apoptosis in thyroid cancer cells. PTEN was indicated as a target of miR-17-5p and its interference reversed abrogation of miR-17-5p-mediated inhibition of proliferation and autophagy and increase of apoptosis. Moreover, downregulation of miR-17-5p impeded the activation of AKT/mTOR pathway in thyroid cancer cells, which was attenuated by silencing PTEN. Our data supported that knockdown of miR-17-5p upregulated PTEN expression, therefore leading to suppression of the malignancy of thyroid cancer and inactivation of AKT/mTOR pathway, providing a novel avenue for treatment of thyroid cancer. 

Retracted: No

PubPeer comments:
 Similarities between this paper and  Long non-coding RNA HOTAIR promotes cell viability, migration and invasion in thyroid cancer by sponging miR-17-5p See especially fig 5C D in this paper vs fig 2B C in the other, along with many more similarities. Many authors in common also, along with nonsense email addresses. ,
Expression of microtubule-associated protein TPX2 in human gastric carcinoma and its prognostic significance
Authors: Deqiang Wang
Jiani Wang
Dan Jin
Yong Gao
Cuijie Shao
Changsheng Duan
Shunlian Luan
Yuming Li
Lihua Xu
Journal: Cancer cell international (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Gastric carcinoma; Prognostic marker; TPX2.
Affiliations: Department of Pain, Affiliated Hospital of Binzhou Medical College, Binzhou, 256600 China., Department of Gastrointestinal Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, 256600 China., Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Department of Oncology, Affiliated Hospital of Binzhou Medical College, Binzhou, 256600 China., Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230 China., Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong China.

Abstract:  Background: The molecular mechanisms underlying the development and progression of gastric carcinoma remain poorly understood. The main objective of this study was to investigate the expression level of targeting protein for Xenopus kinesin-like protein 2 (TPX2) and its clinical significance in human gastric carcinoma. Methods: Real-time quantitative polymerase chain reaction (RT-PCR) and western blotting were used to determine the mRNA and protein levels of TPX2 in 20 paired gastric carcinoma tissues and the adjacent normal tissues, and the expression of TPX2 protein in 106 specimens of a gastric carcinoma tissue microarray was determined by immunohistochemistry. The associations of TPX2 expression with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evaluated. Results: The results showed that the expression of TPX2 mRNA was significantly higher in gastric carcinoma than in the adjacent normal tissues in 20 paired samples. Western blotting analysis revealed that TPX2 protein was differentially increased in 17 of 20 specimens from primary human gastric carcinoma tissues compared with those from adjacent non-tumor tissues. Immunohistochemical staining showed that TPX2 over-expression was significantly associated with advanced age (P = 0.001) and tumor T stage (P = 0.003). In addition, TPX2 was an independent prognostic factor for overall survival (OS) in the multivariate analysis [hazard ratio (HR) 0.001; 95 % confidence interval (CI) 2.626-7.198; P = 0.001]. Conclusions: TPX2 is up-regulated in gastric carcinoma and is associated with old age and tumor T stage. TPX2 may serve as a good prognostic indicator in patients with gastric carcinoma. 

Retracted: No

PubPeer comments:
 Two bands in Figure 3a may show splicing in one band but not in the respective control bands. Could the authors provide the uncropped original scans? *** ![file] ,
Expression of NAG-1, a transforming growth factor-beta superfamily member, by troglitazone requires the early growth response gene EGR-1
Authors: Jennifer B Nixon
Jong-Sik Kim
Richard P DiAugustine
Thomas E Eling
Seung Joon Baek
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Troglitazone; 15-deoxy-Delta(12,14)-prostaglandin J2; PPARgamma; apoptosis; EGR-1

Abstract:  Troglitazone (TGZ) and 15-deoxy-Delta(12,14)-prostaglandin J2 (PGJ2) are peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands that have been shown to possess pro-apoptotic activity in human colon cancer. Although these compounds bind to PPARgamma transcription factors as agonists, emerging evidence suggests that TGZ acts independently of PPARgamma in many functions, including apoptosis. We previously reported that TGZ induces an early growth response transcription factor (EGR-1) by the ERK phosphorylation pathway rather than by the PPARgamma pathway (Baek, S. J., Wilson, L. C., Hsi, L. C., and Eling, T. E. (2003) J. Biol. Chem. 278, 5845-5853). In this report, we show that the expression of the antitumorigenic and/or pro-apoptotic gene NAG-1 (nonsteroidal anti-inflammatory drug-activated gene-1) is induced by TGZ and correlates with EGR-1 induction. In cotransfection and gel shift assays, we show that EGR-1-binding sites are located within region -73 to -51 of the NAG-1 promoter and have an important role in the transactivation of TGZ-induced NAG-1 expression. In contrast, PGJ2 induced NAG-1 protein expression, but PGJ2 may not affect the same region that TGZ does in the NAG-1 promoter. The effect of PGJ2 is probably PPARgamma-dependent because a PPARgamma antagonist inhibited the PGJ2-induced expression of NAG-1. TGZ-induced NAG-1 expression was not inhibited by the PPARgamma antagonist. The fact that TGZ-induced NAG-1 expression was accompanied by the biosynthesis of EGR-1 also suggests that EGR-1 plays a pivotal role in TGZ-induced NAG-1 expression. Our results suggest that EGR-1 induction is a unique property of TGZ, but is independent of PPARgamma activation. The up-regulation of NAG-1 may provide a novel explanation for the antitumorigenic property of TGZ. 

Retracted: No

PubPeer comments:
 Undeclared splicing site. ![file] ,
Methanol and Butanol Extracts of Paeonia lutea Leaves Repress Metastasis of Squamous Cell Carcinoma
Authors: Hideyuki Shigemori
Tatsuo Shirota
Meilin Zhang
Sunao Shiogama
Chihiro Ito
Kazunaga Yazawa
Kosuke Kato
Satoru Shintani
Seiji Kondo
Yoshiki Mukudai
Miharu Fujii
Hiromi Motohashi
Journal: Evidence-based Complementary and Alternative Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: Squamous cell carcinoma; Paeoniaceae family; chemotherapeutics; anticancer agent; apoptosis
Affiliations: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan., Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan., Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan., Division of Health Food Science, Institute for Nanoscience and Nanotechnology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-0041, Japan.

Abstract:  Squamous cell carcinoma (SCC) is one of the most common cancers of the head and neck region worldwide and is generally treated surgically in combination with radiotherapy and/or chemotherapy. However, anticancer agents have numerous serious side effects, and alternative, less toxic agents that are effective as chemotherapeutics for SCC are required. The Paeoniaceae family is widely used in traditional Chinese medicine. We examined methanol and butanol extracts of Paeonia lutea (P. lutea) leaves for their potential as an anticancer agent. Both extracts decreased the proliferation of SCC cells, induced apoptotic cell death, and modulated migration, adhesion, chemotaxis, and haptotaxis in an extracellular matrix- (ECM-) dependent manner due to altered expression of several integrin subunits. Subsequently, SCC cells were subcutaneously transplanted into athymic nude mice; the extracts reduced the metastasis of SCC cells but had little effect on the volume of the primary tumor or survival or body weight of the mice. The results suggest that the extracts may hold promise for preventing cancer metastasis. 

Retracted: No

PubPeer comments:
 Figure 3, there are two image duplications (red and blue boxes). Could the authors please check? ![file] ,